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Sample records for depressive disorder mdd

  1. Emotional modulation of pain and spinal nociception in persons with major depressive disorder (MDD)

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    Terry, Ellen L.; DelVentura, Jennifer L.; Bartley, Emily J.; Vincent, Ashley; Rhudy, Jamie L.

    2013-01-01

    Major depressive disorder (MDD) is associated with risk for chronic pain, but the mechanisms contributing to the MDD and pain relationship are unclear. To examine whether disrupted emotional modulation of pain might contribute, this study assessed emotional processing and emotional modulation of pain in healthy controls and unmedicated persons with MDD (14 MDD, 14 controls). Emotionally-charged pictures (erotica, neutral, mutilation) were presented in four blocks. Two blocks assessed physiolo...

  2. MK4MDD: a multi-level knowledge base and analysis platform for major depressive disorder.

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    Liyuan Guo

    Full Text Available BACKGROUND: Major depressive disorder (MDD is a complex neuropsychiatric syndrome with high heterogeneity. There are different levels of biological components that underlie MDD and interact with each other. To uncover the disease mechanism, large numbers of studies at different levels have been conducted. There is a growing need to integrate data from multiple levels of research into a database to provide a systematic review of current research results. The cross level integration will also help bridge gaps of different research levels for further understanding on MDD. So far, there has been no such effort for MDD. DESCRIPTIONS: We offer researchers a Multi-level Knowledge base for MDD (MK4MDD to study the interesting interplay of components in the pathophysiological cascade of MDD from genetic variations to diagnostic syndrome. MK4MDD contains 2,341 components and 5,206 relationships between components based on reported experimental results obtained by diligent literature reading with manual curation. All components were well classified with careful curation and supplementary annotation. The powerful search and visualization tools make all data in MK4MDD form a cross-linked network to be applied to a broad range of both basic and applied research. CONCLUSIONS: MK4MDD aims to provide researchers with a central knowledge base and analysis platform for MDD etiological and pathophysiological mechanisms research. MK4MDD is freely available at http://mdd.psych.ac.cn.

  3. Emotional modulation of pain and spinal nociception in persons with major depressive disorder (MDD).

    Science.gov (United States)

    Terry, Ellen L; DelVentura, Jennifer L; Bartley, Emily J; Vincent, Ashley L; Rhudy, Jamie L

    2013-12-01

    Major depressive disorder (MDD) is associated with risk for chronic pain, but the mechanisms contributing to the MDD and pain relationship are unclear. To examine whether disrupted emotional modulation of pain might contribute, this study assessed emotional processing and emotional modulation of pain in healthy controls and unmedicated persons with MDD (14 MDD, 14 controls). Emotionally charged pictures (erotica, neutral, mutilation) were presented in 4 blocks. Two blocks assessed physiological-emotional reactions (pleasure/arousal ratings, corrugator electromyography (EMG), startle modulation, skin conductance) in the absence of pain and 2 blocks assessed emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations. Results indicated pictures generally evoked the intended emotional responses; erotic pictures elicited pleasure, subjective arousal, and smaller startle magnitudes, whereas mutilation pictures elicited displeasure, corrugator EMG activation, and subjective/physiological arousal. However, emotional processing was partially disrupted in MDD, as evidenced by a blunted pleasure response to erotica and a failure to modulate startle according to a valence linear trend. Furthermore, emotional modulation of pain was observed in controls but not MDD, even though there were no group differences in NFR threshold or emotional modulation of NFR. Together, these results suggest supraspinal processes associated with emotion processing and emotional modulation of pain may be disrupted in MDD, but brain to spinal cord processes that modulate spinal nociception are intact. Thus, emotional modulation of pain deficits may be a phenotypic marker for future pain risk in MDD.

  4. CREB1 gene polymorphisms combined with environmental risk factors increase susceptibility to major depressive disorder (MDD).

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    Wang, Peng; Yang, Yanjie; Yang, Xiuxian; Qiu, Xiaohui; Qiao, Zhengxue; Wang, Lin; Zhu, Xiongzhao; Sui, Hong; Ma, Jingsong

    2015-01-01

    Major depressive disorder (MDD) is one of the most severe psychiatric disorders. The objective of this study was to explore the effects of CREB1 gene polymorphisms on risk of developing MDD and the joint effects of gene-environment interactions. Genotyping was performed by Taqman allelic discrimination assay among 586 patients and 586 healthy controls. A significant impact on rs6740584 genotype distribution was found for childhood trauma (P = 0.015). We did not find an association of CREB1 polymorphisms with MDD susceptibility. However, we found a significantly increased risk associated with the interactions of CREB1 polymorphisms and drinking (OR = 11.67, 95% CI = 2.52-54.18; OR = 11.52, 95% CI = 2.55-51.95 for rs11904814; OR = 4.18, 95% CI = 1.87-9.38; OR = 5.02, 95% CI = 2.27-11.14 for rs6740584; OR = 7.58, 95% CI = 2.05-27.98; OR = 7.59, 95% CI = 2.12-27.14 for rs2553206; OR = 8.37, 95% CI = 3.02-23.23; OR = 7.84, 95% CI = 2.93-20.98 for rs2551941). We also noted that CREB polymorphisms combined with family harmony and childhood trauma conferred increased susceptibility for MDD. In conclusion, polymorphisms in the CREB gene may not be independently associated with MDD risk, but they are likely to confer increased susceptibility by interacting with environmental risk factors in the Chinese population.

  5. Serotonin transporter polymorphism in major depressive disorder (MDD), psychiatric disorders, and in MDD in response to stressful life events: causes and treatment with antidepressant.

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    Daniele, Antonella; Divella, Rosa; Paradiso, Angelo; Mattioli, Vittorio; Romito, Francesca; Giotta, Francesco; Casamassima, Porzia; Quaranta, Michele

    2011-01-01

    A functional polymorphism in the promoter region of the 5-hidroxytryptamine transporter gene (5-HTTLPR), alters its transcription. Short allele (SS) variation decreases the transcriptional efficacy of serotonin, causing psychiatric disorders, major depressive disorder (MDD) and major depression in response to stressful life events. The aim of this study was to determine the current understanding of the role of 5-HTTLPR polymorphism in the development of depressive episodes and its response to treatment. Twenty-five articles were identified from PubMed, utilizing the following keyword, 5-HTT transporter gene, polymorphism, depression, stressful condition, psychiatric disorder. All articles were read and notes were made regarding study participant, measures, data analysis and results, and were used to write this review. The distribution of the SS allele in patients is associated with an increased risk of MDD following exposure to stressful events of life. Additionally, this genetic variant is closely associated with several psychiatric conditions such as suicidal behaviour, psychoses, personality disorders, and aggressive-impulsive traits.

  6. PHQ-8 Days: a measurement option for DSM-5 Major Depressive Disorder (MDD severity

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    Balluz Lina S

    2011-04-01

    Full Text Available Abstract Background Proposed draft diagnostic criteria for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5 suggest that dimensional assessments can supplement dichotomous diagnoses by incorporating measures of severity, frequency, and duration, providing the ability to monitor changes in symptoms over time and to guide appropriate treatment. Methods This report is based on data from the Behavioral Risk Factor Surveillance System 2006 from 198,678 survey participants who responded to all eight Patient Health Questionnaire (PHQ-8 items. We evaluated use of the days version of the PHQ-8 to determine an optimal cut-point for identifying respondents with depression and to evaluate the performance characteristics of the PHQ-8 at this cut-point. Results A PHQ-8 score of 55 or more days was determined to be the optimal cut-point when compared to the DSM-derived PHQ-8 algorithm for a major depressive episode (five or more symptoms present "more than half the days," at least one of which must be anhedonia or depression. In the full sample, the sensitivity and the specificity of this cut-point were 0.91 (0.90-0.93 and 0.99 (0.99-0.99, respectively. Conclusion The days version of the PHQ-8 may be a valuable dimensional alternative to the traditional PHQ-8 by offering finer granularity of dimensionality (a score of 0 to 112.

  7. Suicide risk and prevalence of major depressive disorder (MDD) among individuals infected with HIV-1 subtype C versus B in Southern Brazil.

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    de Almeida, Sergio Monteiro; Barbosa, Francisco Jaime; Kamat, Rujvi; de Pereira, Ana Paula; Raboni, Sonia Mara; Rotta, Indianara; Ribeiro, Clea Elisa; Cherner, Mariana; Ellis, Ronald J; Atkinson, Joseph Hampton

    2016-12-01

    Major depressive disorder (MDD) is among the most prevalent neuropsychiatric disorders associated with HIV infection; however, its risks and neurobiologic correlates in diverse cultures are poorly understood. This study aimed to examine the frequency of MDD among HIV+ participants in southern Brazil. We hypothesized that the frequency and severity of MDD would be higher among individuals with HIV+ compared with HIV- and higher in HIV subtype B compared with C. Individuals with HIV (n = 39) as well as seronegative controls (n = 22) were enrolled in a cross-sectional, prospective, observational study. Current and lifetime history of MDD was diagnosed by MINI-Plus; symptom severity was assessed by Beck Depression Inventory-II (BDI-II). Current and past episodes of MDD were significantly more frequent in the HIV+ versus HIV- group: current MDD, 15 (38.5 %) vs. 0 (0 %), p = 0.0004; past MDD, 24 (61.5 %) vs. 3 (13.6 %), p = 0.0004. The median BDI-II score in the HIV+ group was significantly higher than that in the HIV- (13 (8-27.5) vs. 2.5 (1-5.5); p < 0.0001). Current suicide risk, defined as during the last month, was found in 18 % of participants in the HIV-positive and none in the HIV-negative group. Neither current MDD frequency (8 (57.1 %) vs. 6 (40 %), p = 0.47) nor BDI-II score differed across subtypes B and C. HIV+ group may be more likely to experience current MDD than HIV-. This was the first study to compare the frequency and severity of MDD in HIV subtypes B and C; we found no difference between HIV subtypes B and C.

  8. A preliminary analysis of association between plasma microRNA expression alteration and symptomatology improvement in Major Depressive Disorder (MDD patients before and after antidepressant treatment

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    Zhang Qiao-li

    2014-12-01

    Full Text Available Background and Objectives: Currently, there is a serious need to find practical biomarker(s for Major Depressive Disorder (MDD therapeutic target(s. This study aimed to investigate the association between microRNA (miRNA, miR expression level in Peripheral Blood Mononuclear Cells (PBMCs and symptomatology improvement in MDD patients before and after six-week antidepressant treatment. Methods: By using an Affymetrix array that covers 723 human miRNAs, 26 miRNAs were identified with significantly altered expression in PBMCs in MDD patients, of which 10 miRNAs were selected for quantitative real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR study. Twenty out of all the 81 MDD patients were selected for miRNA expression levels testing and symptomatology assessments before and after six-week treatment. Results: Compared with the control group, the expression levels of miR-26b, miR-4743, miR-4498, miR-4485 and miR-1972 of the MDD group were significantly higher (P < 0.05; the changes of expression levels of miR-4743, miR-4498, miR-4485 and miR-1972 were positively related to retardation improvement (P < 0.05, and the change of expression level of miR-26b negatively to the improvement of day and night change (P < 0.05; regression analysis result demonstrated that the alteration of miR-4485 expression accounted for 28.8% of retardation improvement (P < 0.05. Conclusions: These five miRNAs (miR-4743, miR-4498, miR-4485, miR-1972 and miR-26b may serve as biomarker for MDD diagnosis and therapeutic targets for MDD treatment.

  9. Common variants in FKBP5 gene and major depressive disorder (MDD) susceptibility: a comprehensive meta-analysis

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    Rao, Shuquan; Yao, Yao; Ryan, Joanne; Li, Tao; Wang, Duan; Zheng, Chuan; Xu, Yong; Xu, Qi

    2016-09-01

    Previous studies have investigated the association between common variants in FKBP5 and MDD; however, the results remain inconsistent. In order to conduct a comprehensive meta-analysis of the association between FKBP5 variants and MDD risk, seven studies involving 26582 subjects, including 12491 cases with MDD and 14091 controls, were enrolled totally. Four common SNPs (rs1360780, rs4713916, rs3800373 and rs755658) with complete data from two or more studies were analyzed. In the total sample, there was no evidence of a significant association between MDD and any of the four SNPs using a random-effects model. However, after removing one heterogeneous German study, as indicated by sensitivity analysis, both the rs1360780 T-allele (Z = 2.95, P = 0.003, OR = 1.06, 95% CI = 1.02-1.11) and the rs3800373 C-allele (Z = 3.05, P = 0.002, OR = 1.07, 95% CI 1.02-1.12) were significantly associated with MDD in a fixed-effect model. Our study thus provides support for an association between specific FKBP5 genetic variants and MDD risk. Rs4713916 was not significantly associated with MDD; However, this analysis had limited statistical power and larger sample sizes are required to further validate this result. Future research should also investigate possible gender- and ethnicity-specific differences in the association between FKBP5 and MDD.

  10. Efficacy, safety and tolerability of escitalopram in doses up to 50 mg in Major Depressive Disorder (MDD: an open-label, pilot study

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    Crawford Gordon M

    2011-03-01

    Full Text Available Abstract Background Escitalopram is licensed for use at doses up to 20 mg but is used clinically at higher doses. There is limited published data at higher doses and none in the treatment of Major Depressive Disorder (MDD. Methods This open-label, pilot study was designed to investigate the efficacy, safety and tolerability of escitalopram in doses up to 50 mg in MDD. It was conducted in 60 primary care patients with MDD who had not responded to adequate treatment with citalopram. Patients were treated with escalating doses of escitalopram up to 50 mg for up to 32 weeks until they achieved remission (Montgomery-Asberg Depression Rating Scale [MADRS] ≤8 or failed to tolerate the dose. Results Forty-two patients (70% completed the study. Twenty-one patients (35% achieved remission with 8 of the 21 patients (38% needing the 50 mg dose to achieve remission. Median time to remission was 24 weeks and median dose in remission was 30 mg. No significant safety issues were identified although tolerability appeared to decline above a dose of 40 mg with 26% of patients unable to tolerate 50 mg. Twelve (20% patients had adverse events leading to discontinuation. The most common adverse events were headache (35%, nausea, diarrhoea and nasopharyngitis (all 25%. Minor mean weight gain was found during the study, which did not appear to be dose-related. Half of the patients who completed the study chose to continue treatment with escitalopram rather than taper down the dose at 32 weeks. Conclusions Dose escalation with escitalopram above 20 mg may have a useful role in the management of patients with MDD, although further studies are needed to confirm this finding. Trial Registration ClinicalTrials.gov: NCT00785434

  11. Efficacy, Safety and Tolerability of Augmentative rTMS in Treatment of Major Depressive Disorder (MDD): A Prospective Cohort Study in Croatia.

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    Filipcic, Igor; Milovac, Zeljko; Sucic, Strahimir; Gajsak, Tomislav; Filipcic, Ivona Simunovic; Ivezic, Ena; Aljinovic, Vjekoslav; Orgulan, Ivana; Penic, Sandra Zecevic; Bajic, Zarko

    2017-03-01

    An increasing body of research suggest that repetitive Transcranial Magnetic Stimulation (rTMS) is effective and safe treatment option for patients with major depressive disorder (MDD). The Psychiatric Hospital "Sveti Ivan" has the first TMS laboratory with rTMS and deep TMS (dTMS) in Croatia. The objective of this study was to assess the efficacy, safety and tolerability of augmentative rTMS treatment vs standard treatment in Croatian patients with major depressive disorder (MDD). Total of 93 MDD patients were enrolled; 41 of them were treated by augmentative rTMS and 52 were treated by standard (psychopharmacotherapy and psychotherapy) therapy only. We delivered rTMS to the left dorsolateral prefrontal cortex at 120% motor threshold (10 Hz, 4-second train duration), 3000 pulses per session using a figure-eight coil, minimum of 20 sessions during four weeks. Our key outcome was the change in Hamilton Depression Scale (HAM-D17) result from baseline to 4(th) week. Our secondary outcomes were changes in Hamilton Anxiety (HAM-A) and WHOQOL-BREF scales. After four weeks the changes of HAM-D17 and HAM-A results were significantly different between the group of patients treated by augmentative rTMS (48% and 53% decrease, respectively) and the group of patients treated by the standard therapy alone (24% and 30% decrease) (P=0.004, P=0.007). Absolute benefit increase defined as the difference between rates of remission (HAM-D17 ≤7) in rTMS and control group was 33% (P=0.001). Number of patients needed to treat with rTMS in order to achieve remission in one patient was NNT=3. In a group of patients treated with augmentative rTMS 21/41 (51%), and in control group 17/52 (33%) were responders (P=0.071). It seems that augmentative treatment with rTMS is more effective on depression and anxiety symptoms than standard therapy in MDD with equal safety and tolerability. Randomized, controlled studies are required to verify this finding.

  12. Investigating the (cost-) effectiveness of attention bias modification (ABM) for outpatients with major depressive disorder (MDD): a randomized controlled trial protocol.

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    Ferrari, Gina R A; Becker, Eni S; Smit, Filip; Rinck, Mike; Spijker, Jan

    2016-11-03

    Despite the range of available, evidence-based treatment options for Major Depressive Disorder (MDD), the rather low response and remission rates suggest that treatment is not optimal, yet. Computerized attention bias modification (ABM) trainings may have the potential to be provided as cost-effective intervention as adjunct to usual care (UC), by speeding up recovery and bringing more patients into remission. Research suggests, that a selective attention for negative information contributes to development and maintenance of depression and that reducing this negative bias might be of therapeutic value. Previous ABM studies in depression, however, have been limited by small sample sizes, lack of long-term follow-up measures or focus on sub-clinical samples. This study aims at evaluating the long-term (cost-) effectiveness of internet-based ABM, as add-on treatment to UC in adult outpatients with MDD, in a specialized mental health care setting. This study presents a double-blind randomized controlled trial in two parallel groups with follow-ups at 1, 6, and 12 months, combined with an economic evaluation. One hundred twenty six patients, diagnosed with MDD, who are registered for specialized outpatient services at a mental health care organization in the Netherlands, are randomized into either a positive training (towards positive and away from negative stimuli) or a sham training, as control condition (continuous attentional bias assessment). Patients complete eight training sessions (seven at home) during a period of two weeks (four weekly sessions). Primary outcome measures are change in attentional bias (pre- to post-test), mood response to stress (at post-test) and long-term effects on depressive symptoms (up to 1-year follow-up). Secondary outcome measures include rumination, resilience, positive and negative affect, and transfer to other cognitive measures (i.e., attentional bias for verbal stimuli, cognitive control, positive mental imagery), as well as

  13. Infant sleep and feeding patterns are associated with maternal sleep, stress, and depressed mood in women with a history of major depressive disorder (MDD).

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    Sharkey, Katherine M; Iko, Ijeoma N; Machan, Jason T; Thompson-Westra, Johanna; Pearlstein, Teri B

    2016-04-01

    Our goal was to examine associations of infant sleep and feeding patterns with maternal sleep and mood among women at risk for postpartum depression. Participants were 30 women (age ± SD = 28.3 ± 5.1 years) with a history of MDD (but not in a mood episode at enrollment) who completed daily sleep diaries, wore wrist actigraphs to estimate sleep, and had their mood assessed with the Hamilton Depression Rating Scale (HAM-D-17) during four separate weeks of the perinatal period (33 weeks pregnancy and weeks 2, 6, and 16 postpartum). They logged their infants' sleep and feeding behaviors daily and reported postnatal stress on the Childcare Stress Inventory (CSI) at week 16. Mothers' actigraphically estimated sleep showed associations with infant sleep and feeding patterns only at postpartum week 2. Shorter duration of the longest infant-sleep bout was associated with shorter maternal sleep duration (p = .02) and lower sleep efficiency (p = .04), and maternal sleep efficiency was negatively associated with the number of infant-sleep bouts (p = .008) and duration of infant feeding (p = .008). Neither infant sleep nor feeding was associated with maternal sleep at 6 or 16 weeks, but more disturbed infant sleep and more frequent feeding at 6 weeks were associated with higher HAM-D scores at 6 and 16 weeks and higher CSI scores. Sleep in the mother-infant dyad is most tightly linked in the early postpartum weeks, but mothers continue to experience disturbed sleep and infant sleep and feeding behaviors continue to be associated with mothers' depressive symptoms and stress ratings as long as 16 weeks postpartum. These data imply that interventions designed to improve maternal sleep and postpartum mood should include both mothers and infants because improving infant sleep alone is not likely to improve maternal sleep, and poor infant sleep is linked to postpartum depression and stress.

  14. A possible common basis for MDD, bipolar disorder and schizophrenia: Lessons from electrophysiology

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    Goded eShahaf

    2016-06-01

    Full Text Available There is ample electrophysiological evidence of attention dysfunction in the EEG/ERP signal of various psychopathologies such as major depressive disorder (MDD, bipolar disorder, and schizophrenia. The reduced attention-related ERP waves show much similarity between MDD, bipolar disorder, and schizophrenia, raising the question whether there are similarities in the neurophysiologic process that underlies attention dysfunction in these pathologies. The present work suggests that there is such a unified underlying neurophysiologic process, which results in reduced attention in the three pathologies. Naturally, as these pathologies involve different clinical manifestations, we expect differences in their underlying neurophysiology. These differences and their subtle manifestation in the ERP marker for attention are also discussed.MDD, bipolar disorder and schizophrenia are just three of multiple neuropsychiatric disorders, which involve changes in the EEG/ERP manifestations of attention. Further work should expand the basic model presented here to offer comprehensive modeling of these multiple disorders and to emphasize similarities and dissimilarities of the underlying neurophysiologic processes.

  15. Familiality of major depressive disorder and gender differences in comorbidity

    NARCIS (Netherlands)

    Verhagen, M.; Meij, A. van der; Franke, B.; Vollebergh, W.A.M.; Graaf, R. de; Buitelaar, J.K.; Janzing, J.G.E.

    2008-01-01

    Objective: Gender differences exist in the prevalence and psychiatric comorbidity of major depressive disorder (MDD). This study investigates whether familiality of MDD contributes to observed gender differences in comorbidity. Method: Familial (f-MDD) and non-familial (nf-MDD) MDD cases from a popu

  16. Depression and major depressive disorder in patients with Parkinson's disease.

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    Inoue, Takeshi; Kitagawa, Mayumi; Tanaka, Teruaki; Nakagawa, Shin; Koyama, Tsukasa

    2010-01-15

    The prevalence of depression in Parkinson's disease (PD) varies greatly. In this study, we investigated major depressive disorder (MDD) and depressive symptoms without MDD in patients with PD. The psychopathological characteristics of depressive symptoms were assessed by a psychiatric interview. A total of 105 Japanese patients with PD without dementia were included. The Japanese version of the Beck Depression Inventory-II (BDI-II) with a cutoff score of 13/14 was used to screen for depression. Using a structured interview, a comprehensive psychiatric evaluation of patients with BDI-II scores >13 (high BDI patients) was completed using the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR. Forty patients (38%) had a BDI-II >13, but 29 did not show any depressed mood. Five cases met the criteria for MDD (three current, two past) and one patient was diagnosed with minor depressive disorder. A slight depressed mood that was associated with worrying about PD was seen in 6 of 34 patients without any depressive disorder and fluctuated with aggravation of PD symptoms in two of these patients. For the diagnosis of MDD, the number of positive items from the DSM-IV-TR definition of MDD is most important and useful for differentiating MDD and non-MDD. The low-prevalence rate of MDD in our patient population suggests that PD may be a psychological stressor for MDD, but does not necessarily induce MDD.

  17. Disorder-specific cognitive profiles in major depressive disorder and generalized anxiety disorder

    OpenAIRE

    Hendriks, S.M.; Licht, C.M.M.; Spijker, J; Beekman, A T F; Hardeveld, F.; de Graaf, R.; Penninx, B.W.J.H.

    2014-01-01

    Background: This investigation examines differences in cognitive profiles in subjects with major depressive disorder (MDD) and generalized anxiety disorder (GAD). Methods: Data were used from subjects with current MDD (n = 655), GAD (n = 107) and comorbid MDD/GAD (n = 266) diagnosis from the Netherlands Study of Depression and Anxiety (NESDA). The Composite Interview Diagnostic Instrument was used to diagnose MDD and GAD. Cognitive profiles were measured using the Leiden Index of Depression S...

  18. Course trajectories of unipolar depressive disorders identified by latent class growth analysis

    NARCIS (Netherlands)

    Rhebergen, D.; Lamers, F.; Spijker, J.; Graaf, R. de; Beekman, A.T.; Penninx, B.W.J.H.

    2012-01-01

    BACKGROUND: Current classification of unipolar depression reflects the idea that prognosis is essential. However, do DSM categories of major depressive disorder (MDD), dysthymic disorder (Dysth) and double depression (DD=MDD+Dysth) indeed adequately represent clinically relevant course trajectories

  19. Course trajectories of unipolar depressive disorders identified by latent class growth analysis

    NARCIS (Netherlands)

    Rhebergen, D.; Lamers, F.; Spijker, J.; Graaf, R. de; Beekman, A.T.F.; Penninx, B.W.J.H.

    2012-01-01

    Background. Current classification of unipolar depression reflects the idea that prognosis is essential. However, do DSM categories of major depressive disorder (MDD), dysthymic disorder (Dysth) and double depression (DD=MDD+Dysth) indeed adequately represent clinically relevant course trajectories

  20. Disorder-specific cognitive profiles in major depressive disorder and generalized anxiety disorder

    NARCIS (Netherlands)

    Hendriks, S.M.; Licht, C.M.; Spijker, J.; Beekman, A.T.; Hardeveld, F.; Graaf, R. de; Penninx, B.W.J.H.

    2014-01-01

    BACKGROUND: This investigation examines differences in cognitive profiles in subjects with major depressive disorder (MDD) and generalized anxiety disorder (GAD). METHODS: Data were used from subjects with current MDD (n = 655), GAD (n = 107) and comorbid MDD/GAD (n = 266) diagnosis from the

  1. Disorder-specific cognitive profiles in major depressive disorder and generalized anxiety disorder

    NARCIS (Netherlands)

    Hendriks, Sanne M.; Licht, Carmilla M. M.; Spijker, Jan; Beekman, Aartjan T. F.; Hardeveld, Florian; de Graaf, Ron; Penninx, Brenda W. J. H.

    2014-01-01

    Background: This investigation examines differences in cognitive profiles in subjects with major depressive disorder (MDD) and generalized anxiety disorder (GAD). Methods: Data were used from subjects with current MDD (n = 655), GAD (n = 107) and comorbid MDD/GAD (n = 266) diagnosis from the Netherl

  2. Disorder-specific cognitive profiles in major depressive disorder and generalized anxiety disorder

    NARCIS (Netherlands)

    Hendriks, Sanne M.; Licht, Carmilla M. M.; Spijker, Jan; Beekman, Aartjan T. F.; Hardeveld, Florian; de Graaf, Ron; Penninx, Brenda W. J. H.

    2014-01-01

    Background: This investigation examines differences in cognitive profiles in subjects with major depressive disorder (MDD) and generalized anxiety disorder (GAD). Methods: Data were used from subjects with current MDD (n = 655), GAD (n = 107) and comorbid MDD/GAD (n = 266) diagnosis from the

  3. Migraine symptomatology and major depressive disorder

    NARCIS (Netherlands)

    Ligthart, Lannie; Penninx, Brenda; Nyholt, Dale R.; Distel, Marijn A.; de Geus, Eco J. C.; Willemsen, Gonneke; Smit, Johannes H.; Boomsma, Dorret I.

    2010-01-01

    Introduction and objective: Migraine and major depressive disorder (MDD) frequently co-occur, but it is unclear whether depression is associated with a specific subtype of migraine. The objective of this study was to investigate whether migraine is qualitatively different in MDD patients (N = 1816)

  4. Serum proteomic profiling of major depressive disorder.

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    Bot, M; Chan, M K; Jansen, R; Lamers, F; Vogelzangs, N; Steiner, J; Leweke, F M; Rothermundt, M; Cooper, J; Bahn, S; Penninx, B W J H

    2015-07-14

    Much has still to be learned about the molecular mechanisms of depression. This study aims to gain insight into contributing mechanisms by identifying serum proteins related to major depressive disorder (MDD) in a large psychiatric cohort study. Our sample consisted of 1589 participants of the Netherlands Study of Depression and Anxiety, comprising 687 individuals with current MDD (cMDD), 482 individuals with remitted MDD (rMDD) and 420 controls. We studied the relationship between MDD status and the levels of 171 serum proteins detected on a multi-analyte profiling platform using adjusted linear regression models. Pooled analyses of two independent validation cohorts (totaling 78 MDD cases and 156 controls) was carried out to validate our top markers. Twenty-eight analytes differed significantly between cMDD cases and controls (P depression. Changes were more prominent in cMDD, suggesting that molecular alterations in serum are associated with acute depression symptomatology. These findings may help to establish serum-based biomarkers of depression and could improve our understanding of its pathophysiology.

  5. Maternal Depressive Symptoms in Pediatric Major Depressive Disorder: Relationship to Acute Treatment Outcome

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    Kennard, Betsy D.; Hughes, Jennifer L.; Stewart, Sunita M.; Mayes, Taryn; Nightingale-Teresi, Jeanne; Tao, Rongrong; Carmody, Thomas; Emslie, Graham J.

    2008-01-01

    A study examined maternal depressive symptoms at the beginning and end of acute pediatric treatment of children with major depressive disorder (MDD). Results suggested a direct and possible reciprocal association between maternal and child depression severity.

  6. Subcortical brain alterations in major depressive disorder : findings from the ENIGMA Major Depressive Disorder working group

    NARCIS (Netherlands)

    Schmaal, L.; Veltman, D. J.; van Erp, T. G. M.; Saemann, P. G.; Frodl, T.; Jahanshad, N.; Loehrer, E.; Tiemeier, H.; Hofman, A.; Niessen, W. J.; Vernooij, M. W.; Ikram, M. A.; Wittfeld, K.; Grabe, H. J.; Block, A.; Hegenscheid, K.; Voelzke, H.; Hoehn, D.; Czisch, M.; Lagopoulos, J.; Hatton, S. N.; Hickie, I. B.; Goya-Maldonado, R.; Kraemer, B.; Gruber, O.; Couvy-Duchesne, B.; Renteria, M. E.; Strike, L. T.; Mills, N. T.; de Zubicaray, G. I.; McMahon, K. L.; Medland, S. E.; Martin, N. G.; Gillespie, N. A.; Wright, M. J.; Hall, G.B.; MacQueen, G. M.; Frey, E. M.; Carballedo, A.; van Velzen, L. S.; van Tol, M. J.; van der Wee, N. J.; Veer, I. M.; Walter, H.; Schnell, K.; Schramm, E.; Normann, C.; Schoepf, D.; Konrad, C.; Zurowski, B.; Nickson, T.; McIntosh, A. M.; Papmeyer, M.; Whalley, H. C.; Sussmann, J. E.; Godlewska, B. R.; Cowen, P. J.; Fischer, F. H.; Rose, M.; Penninx, B. W. J. H.; Thompson, P. M.; Hibar, D. P.

    2016-01-01

    The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristic

  7. Gender differences in major depressive disorder : Results from the Netherlands study of depression and anxiety

    NARCIS (Netherlands)

    Schuch, Jerome J. J.; Roest, Annelieke M.; Nolen, Willem A.; Penninx, Brenda W. J. H.; de Jonge, Peter

    2014-01-01

    Background: Although an overall gender difference in prevalence of major depressive disorder (MDD) has been well established, several questions concerning gender differences in the clinical manifestation of depression remain. This study aims to identify gender differences in psychopathology, treatme

  8. The impact of perfectionism and anxiety traits on action monitoring in major depressive disorder

    NARCIS (Netherlands)

    Schrijvers, D.L.; Bruijn, E.R.A. de; Destoop, M.; Hulstijn, W.; Sabbe, B.G.C.C.

    2010-01-01

    Perfectionism and anxiety features are involved in the clinical presentation and neurobiology of major depressive disorder (MDD). In MDD, cognitive control mechanisms such as action monitoring can adequately be investigated applying electrophysiological registrations of the error-related negativity

  9. The impact of perfectionism and anxiety traits on action monitoring in major depressive disorder

    NARCIS (Netherlands)

    Schrijvers, D.L.; Bruijn, E.R.A. de; Destoop, M.; Hulstijn, W.; Sabbe, B.G.C.C.

    2010-01-01

    Perfectionism and anxiety features are involved in the clinical presentation and neurobiology of major depressive disorder (MDD). In MDD, cognitive control mechanisms such as action monitoring can adequately be investigated applying electrophysiological registrations of the error-related negativity

  10. Altered fecal microbiota composition in patients with major depressive disorder.

    Science.gov (United States)

    Jiang, Haiyin; Ling, Zongxin; Zhang, Yonghua; Mao, Hongjin; Ma, Zhanping; Yin, Yan; Wang, Weihong; Tang, Wenxin; Tan, Zhonglin; Shi, Jianfei; Li, Lanjuan; Ruan, Bing

    2015-08-01

    Studies using animal models have shown that depression affects the stability of the microbiota, but the actual structure and composition in patients with major depressive disorder (MDD) are not well understood. Here, we analyzed fecal samples from 46 patients with depression (29 active-MDD and 17 responded-MDD) and 30 healthy controls (HCs). High-throughput pyrosequencing showed that, according to the Shannon index, increased fecal bacterial α-diversity was found in the active-MDD (A-MDD) vs. the HC group but not in the responded-MDD (R-MDD) vs. the HC group. Bacteroidetes, Proteobacteria, and Actinobacteria strongly increased in level, whereas that of Firmicutes was significantly reduced in the A-MDD and R-MDD groups compared with the HC group. Despite profound interindividual variability, levels of several predominant genera were significantly different between the MDD and HC groups. Most notably, the MDD groups had increased levels of Enterobacteriaceae and Alistipes but reduced levels of Faecalibacterium. A negative correlation was observed between Faecalibacterium and the severity of depressive symptoms. These findings enable a better understanding of changes in the fecal microbiota composition in such patients, showing either a predominance of some potentially harmful bacterial groups or a reduction in beneficial bacterial genera. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and depression and to evaluate the suitability of the microbiome as a biomarker.

  11. Does major depressive disorder in parents predict specific fears and phobias in offspring?

    Science.gov (United States)

    Biel, Matthew G; Klein, Rachel G; Mannuzza, Salvatore; Roizen, Erica R; Truong, Nhan L; Roberson-Nay, Roxann; Pine, Daniel S

    2008-01-01

    Evidence suggests a relationship between parental depression and phobias in offspring as well as links between childhood fears and risk for major depression. This study examines the relationship between major depressive disorder (MDD) and anxiety disorders in parents and specific fears and phobias in offspring. Three hundred and eighteen children of parents with lifetime MDD, anxiety disorder, MDD+anxiety disorder, or neither were psychiatrically assessed via parent interview. Rates of specific phobias in offspring did not differ significantly across parental groups. Specific fears were significantly elevated in offspring of parents with MDD+anxiety disorder relative to the other groups (MDD, anxiety disorder, and controls, which did not differ). We failed to find increased phobias in offspring of parents with MDD without anxiety disorder. Elevated rates of specific fears in offspring of parents with MDD+anxiety disorder may be a function of more severe parental psychopathology, increased genetic loading, or unmeasured environmental influences. (c) 2007 Wiley-Liss, Inc.

  12. Recurrence of major depressive disorder across different treatment settings : Results from the NESDA study

    NARCIS (Netherlands)

    Hardeveld, Florian; Spijker, Jan; De Graaf, Ron; Hendriks, Sanne M.; Licht, Carmilla M. M.; Nolen, Willem A.; Penninx, Brenda W. J. H.; Beekman, Aartjan T. F.

    Objective: Examine time to recurrence of major depressive disorder (MDD) across different treatment settings and assess predictors of time to recurrence of MDD. Methods: Data were from 375 subjects with a MDD diagnosis from the Netherlands Study of Depression and Anxiety (NESDA). The study sample

  13. Replacement of Homologous Mouse DNA Sequence With Pathogenic 6-Base Human CREB1 Promoter Sequence Creates Murine Model of Major Depressive Disorder

    OpenAIRE

    Zubenko, George S.; Hughes, Hugh B.

    2011-01-01

    Major Depressive Disorder (MDD) is a leading cause of disability worldwide. Families with Recurrent, Early-Onset MDD (RE-MDD), a severe, familial form of MDD, have provided an important resource for identifying and characterizing genetic variants that confer susceptibility to MDD and related disorders. Previous studies identified a rare, highly penetrant A(-115)G transition within the human CREB1 promoter that reduced promoter activity in vitro and was associated with depressive disorders in ...

  14. Epigenetic Modifications of Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Kathleen Saavedra

    2016-08-01

    Full Text Available Major depressive disorder (MDD is a chronic disease whose neurological basis and pathophysiology remain poorly understood. Initially, it was proposed that genetic variations were responsible for the development of this disease. Nevertheless, several studies within the last decade have provided evidence suggesting that environmental factors play an important role in MDD pathophysiology. Alterations in epigenetics mechanism, such as DNA methylation, histone modification and microRNA expression could favor MDD advance in response to stressful experiences and environmental factors. The aim of this review is to describe genetic alterations, and particularly altered epigenetic mechanisms, that could be determinants for MDD progress, and how these alterations may arise as useful screening, diagnosis and treatment monitoring biomarkers of depressive disorders.

  15. Epigenetic Modifications of Major Depressive Disorder.

    Science.gov (United States)

    Saavedra, Kathleen; Molina-Márquez, Ana María; Saavedra, Nicolás; Zambrano, Tomás; Salazar, Luis A

    2016-08-05

    Major depressive disorder (MDD) is a chronic disease whose neurological basis and pathophysiology remain poorly understood. Initially, it was proposed that genetic variations were responsible for the development of this disease. Nevertheless, several studies within the last decade have provided evidence suggesting that environmental factors play an important role in MDD pathophysiology. Alterations in epigenetics mechanism, such as DNA methylation, histone modification and microRNA expression could favor MDD advance in response to stressful experiences and environmental factors. The aim of this review is to describe genetic alterations, and particularly altered epigenetic mechanisms, that could be determinants for MDD progress, and how these alterations may arise as useful screening, diagnosis and treatment monitoring biomarkers of depressive disorders.

  16. Subcortical volumes differentiate Major Depressive Disorder, Bipolar Disorder, and remitted Major Depressive Disorder.

    Science.gov (United States)

    Sacchet, Matthew D; Livermore, Emily E; Iglesias, Juan Eugenio; Glover, Gary H; Gotlib, Ian H

    2015-09-01

    Subcortical gray matter regions have been implicated in mood disorders, including Major Depressive Disorder (MDD) and Bipolar Disorder (BD). It is unclear, however, whether or how these regions differ among mood disorders and whether such abnormalities are state- or trait-like. In this study, we examined differences in subcortical gray matter volumes among euthymic BD, MDD, remitted MDD (RMD), and healthy (CTL) individuals. Using automated gray matter segmentation of T1-weighted MRI images, we estimated volumes of 16 major subcortical gray matter structures in 40 BD, 57 MDD, 35 RMD, and 61 CTL individuals. We used multivariate analysis of variance to examine group differences in these structures, and support vector machines (SVMs) to assess individual-by-individual classification. Analyses yielded significant group differences for caudate (p = 0.029) and ventral diencephalon (VD) volumes (p = 0.003). For the caudate, both the BD (p = 0.004) and the MDD (p = 0.037) participants had smaller volumes than did the CTL participants. For the VD, the MDD participants had larger volumes than did the BD and CTL participants (ps disorders are characterized by anomalies in subcortical gray matter volumes and that the caudate and VD contribute uniquely to differential affective pathology. Identifying abnormalities in subcortical gray matter may prove useful for the prevention, diagnosis, and treatment of mood disorders.

  17. 'Hot' cognition in major depressive disorder

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla W; Carvalho, Andre F

    2014-01-01

    Major depressive disorder (MDD) is associated with significant cognitive dysfunction in both 'hot' (i.e. emotion-laden) and 'cold' (non-emotional) domains. Here we review evidence pertaining to 'hot' cognitive changes in MDD. This systematic review searched the PubMed and PsycInfo computerized...... in a fronto-limbic network with hyper-activity in limbic and ventral prefrontal regions paired with hypo-activity of dorsal prefrontal regions subserve these abnormalities. A cross-talk of 'hot' and 'cold' cognition disturbances in MDD occurs. Disturbances in 'hot cognition' may also contribute...... to the perpetuation of negative emotional states in MDD. Limited success in the identification of susceptibility genes in MDD has led to great research interest in identifying vulnerability biomarkers or endophenotypes. Emerging evidence points to the persistence of 'hot' cognition dysfunction during remission...

  18. Advances in biomarkers of major depressive disorder.

    Science.gov (United States)

    Huang, Tiao-Lai; Lin, Chin-Chuen

    2015-01-01

    Major depressive disorder (MDD) is characterized by mood, vegetative, cognitive, and even psychotic symptoms and signs that can cause substantial impairments in quality of life and functioning. Biomarkers are measurable indicators that could help diagnosing MDD or predicting treatment response. In this chapter, lipid profiles, immune/inflammation, and neurotrophic factor pathways that have long been implicated in the pathogenesis of MDD are discussed. Then, pharmacogenetics and epigenetics of serotonin transport and its metabolism pathway, brain-derived neurotrophic factor, and abnormality of hypothalamo-pituitary-adrenocortical axis also revealed new biomarkers. Lastly, new techniques, such as proteomics and metabolomics, which allow researchers to approach the studying of MDD with new directions and make new discoveries are addressed. In the future, more data are needed regarding pathophysiology of MDD, including protein levels, single nucleotide polymorphism, epigenetic regulation, and clinical data in order to better identify reliable and consistent biomarkers for diagnosis, treatment choice, and outcome prediction.

  19. Prospective mental imagery in patients with major depressive disorder or anxiety disorders

    NARCIS (Netherlands)

    Morina, N.; Deeprose, C.; Pusowski, C.; Schmid, M.; Holmes, E.A.

    2011-01-01

    Prospective negative cognitions are suggested to play an important role in maintaining anxiety disorders and major depressive disorder (MDD). However, little is known about positive prospective mental imagery. This study investigated differences in prospective mental imagery among 27 patients with

  20. Behavioral Activation in the Treatment of Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder

    Science.gov (United States)

    Mulick, Patrick S.; Naugle, Amy E.

    2009-01-01

    This study investigated the efficacy of 10-weeks of Behavioral Activation (BA) in the treatment of comorbid Post-traumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD) in four adults using a nonconcurrent multiple baseline across participants design. All participants met full "DSM-IV" criteria for both MDD and PTSD at the…

  1. Review: Magnetic Resonance Spectroscopy Studies of Pediatric Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Douglas G. Kondo

    2011-01-01

    Full Text Available Introduction. This paper focuses on the application of Magnetic Resonance Spectroscopy (MRS to the study of Major Depressive Disorder (MDD in children and adolescents. Method. A literature search using the National Institutes of Health's PubMed database was conducted to identify indexed peer-reviewed MRS studies in pediatric patients with MDD. Results. The literature search yielded 18 articles reporting original MRS data in pediatric MDD. Neurochemical alterations in Choline, Glutamate, and N-Acetyl Aspartate are associated with pediatric MDD, suggesting pathophysiologic continuity with adult MDD. Conclusions. The MRS literature in pediatric MDD is modest but growing. In studies that are methodologically comparable, the results have been consistent. Because it offers a noninvasive and repeatable measurement of relevant in vivo brain chemistry, MRS has the potential to provide insights into the pathophysiology of MDD as well as the mediators and moderators of treatment response.

  2. Unique and related predictors of major depressive disorder, posttraumatic stress disorder, and their comorbidity after Hurricane Katrina.

    Science.gov (United States)

    Nillni, Yael I; Nosen, Elizabeth; Williams, Patrick A; Tracy, Melissa; Coffey, Scott F; Galea, Sandro

    2013-10-01

    The current study examined demographic and psychosocial factors that predict major depressive disorder (MDD) and comorbid MDD/posttraumatic stress disorder (MDD/PTSD) diagnostic status after Hurricane Katrina, one of the deadliest and costliest hurricanes in the history of the United States. This study expanded on the findings published in the article by Galea, Tracy, Norris, and Coffey (J Trauma Stress 21:357-368, 2008), which examined the same predictors for PTSD, to better understand related and unique predictors of MDD, PTSD, and MDD/PTSD comorbidity. A total of 810 individuals representative of adult residents living in the 23 southernmost counties of Mississippi before Hurricane Katrina were interviewed. Ongoing hurricane-related stressors, low social support, and hurricane-related financial loss were common predictors of MDD, PTSD, and MDD/PTSD, whereas educational and marital status emerged as unique predictors of MDD. Implications for postdisaster relief efforts that address the risk for both MDD and PTSD are discussed.

  3. A mega-analysis of genome-wide association studies for major depressive disorder

    NARCIS (Netherlands)

    Sullivan, Patrick F.; Daly, Mark J.; Ripke, Stephan; Lewis, Cathryn M.; Lin, Dan-Yu; Wray, Naomi R.; Neale, Benjamin; Levinson, Douglas F.; Breen, Gerome; Byrne, Enda M.; Wray, Naomi R.; Levinson, Douglas F.; Rietschel, Marcella; Hoogendijk, Witte; Ripke, Stephan; Sullivan, Patrick F.; Hamilton, Steven P.; Levinson, Douglas F.; Lewis, Cathryn M.; Ripke, Stephan; Weissman, Myrna M.; Wray, Naomi R.; Breuer, Rene; Cichon, Sven; Degenhardt, Franziska; Frank, Josef; Gross, Magdalena; Herms, Stefan; Hoefels, Susanne; Maier, Wolfgang; Mattheisen, Manuel; Noeethen, Markus M.; Rietschel, Marcella; Schulze, Thomas G.; Steffens, Michael; Treutlein, Jens; Boomsma, Dorret I.; De Geus, Eco J.; Hoogendijk, Witte; Hottenga, Jouke Jan; Jung-Ying, Tzeng; Lin, Dan-Yu; Middeldorp, Christel M.; Nolen, Willem A.; Penninx, Brenda P.; Smit, Johannes H.; Sullivan, Patrick F.; van Grootheest, Gerard; Willemsen, Gonneke; Zitman, Frans G.; Coryell, William H.; Knowles, James A.; Lawson, William B.; Levinson, Douglas F.; Potash, James B.; Scheftner, William A.; Shi, Jianxin; Weissman, Myrna M.; Holsboer, Florian; Muglia, Pierandrea; Tozzi, Federica; Blackwood, Douglas H. R.; Boomsma, Dorret I.; De Geus, Eco J.; Hottenga, Jouke Jan; MacIntyre, Donald J.; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M.; Penninx, Brenda P.; Ripke, Stephan; Smit, Johannes H.; Sullivan, Patrick F.; van Grootheest, Gerard; Willemsen, Gonneke; Zitman, Frans G.; van den Oord, Edwin J. C. G.; Holsboer, Florian; Lucae, Susanne; Binder, Elisabeth; Mueller-Myhsok, Bertram; Ripke, Stephan; Czamara, Darina; Kohli, Martin A.; Ising, Marcus; Uhr, Manfred; Bettecken, Thomas; Barnes, Michael R.; Breen, Gerome; Craig, Ian W.; Farmer, Anne E.; Lewis, Cathryn M.; McGuffin, Peter; Muglia, Pierandrea; Byrne, Enda; Gordon, Scott D.; Heath, Andrew C.; Henders, Anjali K.; Hickie, Ian B.; Madden, Pamela A. F.; Martin, Nicholas G.; Montgomery, Grant M.; Nyholt, Dale R.; Pergadia, Michele L.; Wray, Naomi R.; Hamilton, Steven P.; McGrath, Patrick J.; Shyn, Stanley I.; Slager, Susan L.; Oskarsson, Hoegni; Sigurdsson, Engilbert; Stefansson, Hreinn; Stefansson, Kari; Steinberg, Stacy; Thorgeirsson, Thorgeir; Levinson, Douglas F.; Potash, James B.; Shi, Jianxin; Weissman, Myrna M.; Guipponi, Michel; Lewis, Glyn; O'Donovan, Michael; Tansey, Katherine E.; Uher, Rudolf; Coryell, William H.; Knowles, James A.; Lawson, William B.; Levinson, Douglas F.; Potash, James B.; Scheftner, William A.; Shi, Jianxin; Weissman, Myrna M.; Castro, Victor M.; Churchill, Susanne E.; Fava, Maurizio; Gainer, Vivian S.; Gallagher, Patience J.; Goryachev, Sergey; Iosifescu, Dan V.; Kohane, Isaac S.; Murphy, Shawn N.; Perlis, Roy H.; Smoller, Jordan W.; Weilburg, Jeffrey B.; Kutalik, Zoltan; Preisig, Martin; Grabe, Hans J.; Nauck, Matthias; Schulz, Andrea; Teumer, Alexander; Voelzke, Henry; Landen, Mikael; Lichtenstein, Paul; Magnusson, Patrik; Pedersen, Nancy; Viktorin, Alexander

    Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X

  4. A mega-analysis of genome-wide association studies for major depressive disorder

    NARCIS (Netherlands)

    Sullivan, Patrick F.; Daly, Mark J.; Ripke, Stephan; Lewis, Cathryn M.; Lin, Dan-Yu; Wray, Naomi R.; Neale, Benjamin; Levinson, Douglas F.; Breen, Gerome; Byrne, Enda M.; Wray, Naomi R.; Levinson, Douglas F.; Rietschel, Marcella; Hoogendijk, Witte; Ripke, Stephan; Sullivan, Patrick F.; Hamilton, Steven P.; Levinson, Douglas F.; Lewis, Cathryn M.; Ripke, Stephan; Weissman, Myrna M.; Wray, Naomi R.; Breuer, Rene; Cichon, Sven; Degenhardt, Franziska; Frank, Josef; Gross, Magdalena; Herms, Stefan; Hoefels, Susanne; Maier, Wolfgang; Mattheisen, Manuel; Noeethen, Markus M.; Rietschel, Marcella; Schulze, Thomas G.; Steffens, Michael; Treutlein, Jens; Boomsma, Dorret I.; De Geus, Eco J.; Hoogendijk, Witte; Hottenga, Jouke Jan; Jung-Ying, Tzeng; Lin, Dan-Yu; Middeldorp, Christel M.; Nolen, Willem A.; Penninx, Brenda P.; Smit, Johannes H.; Sullivan, Patrick F.; van Grootheest, Gerard; Willemsen, Gonneke; Zitman, Frans G.; Coryell, William H.; Knowles, James A.; Lawson, William B.; Levinson, Douglas F.; Potash, James B.; Scheftner, William A.; Shi, Jianxin; Weissman, Myrna M.; Holsboer, Florian; Muglia, Pierandrea; Tozzi, Federica; Blackwood, Douglas H. R.; Boomsma, Dorret I.; De Geus, Eco J.; Hottenga, Jouke Jan; MacIntyre, Donald J.; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M.; Penninx, Brenda P.; Ripke, Stephan; Smit, Johannes H.; Sullivan, Patrick F.; van Grootheest, Gerard; Willemsen, Gonneke; Zitman, Frans G.; van den Oord, Edwin J. C. G.; Holsboer, Florian; Lucae, Susanne; Binder, Elisabeth; Mueller-Myhsok, Bertram; Ripke, Stephan; Czamara, Darina; Kohli, Martin A.; Ising, Marcus; Uhr, Manfred; Bettecken, Thomas; Barnes, Michael R.; Breen, Gerome; Craig, Ian W.; Farmer, Anne E.; Lewis, Cathryn M.; McGuffin, Peter; Muglia, Pierandrea; Byrne, Enda; Gordon, Scott D.; Heath, Andrew C.; Henders, Anjali K.; Hickie, Ian B.; Madden, Pamela A. F.; Martin, Nicholas G.; Montgomery, Grant M.; Nyholt, Dale R.; Pergadia, Michele L.; Wray, Naomi R.; Hamilton, Steven P.; McGrath, Patrick J.; Shyn, Stanley I.; Slager, Susan L.; Oskarsson, Hoegni; Sigurdsson, Engilbert; Stefansson, Hreinn; Stefansson, Kari; Steinberg, Stacy; Thorgeirsson, Thorgeir; Levinson, Douglas F.; Potash, James B.; Shi, Jianxin; Weissman, Myrna M.; Guipponi, Michel; Lewis, Glyn; O'Donovan, Michael; Tansey, Katherine E.; Uher, Rudolf; Coryell, William H.; Knowles, James A.; Lawson, William B.; Levinson, Douglas F.; Potash, James B.; Scheftner, William A.; Shi, Jianxin; Weissman, Myrna M.; Castro, Victor M.; Churchill, Susanne E.; Fava, Maurizio; Gainer, Vivian S.; Gallagher, Patience J.; Goryachev, Sergey; Iosifescu, Dan V.; Kohane, Isaac S.; Murphy, Shawn N.; Perlis, Roy H.; Smoller, Jordan W.; Weilburg, Jeffrey B.; Kutalik, Zoltan; Preisig, Martin; Grabe, Hans J.; Nauck, Matthias; Schulz, Andrea; Teumer, Alexander; Voelzke, Henry; Landen, Mikael; Lichtenstein, Paul; Magnusson, Patrik; Pedersen, Nancy; Viktorin, Alexander

    2013-01-01

    Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chro

  5. A mega-analysis of genome-wide association studies for major depressive disorder

    NARCIS (Netherlands)

    Sullivan, Patrick F.; Daly, Mark J.; Ripke, Stephan; Lewis, Cathryn M.; Lin, Dan-Yu; Wray, Naomi R.; Neale, Benjamin; Levinson, Douglas F.; Breen, Gerome; Byrne, Enda M.; Wray, Naomi R.; Levinson, Douglas F.; Rietschel, Marcella; Hoogendijk, Witte; Ripke, Stephan; Sullivan, Patrick F.; Hamilton, Steven P.; Levinson, Douglas F.; Lewis, Cathryn M.; Ripke, Stephan; Weissman, Myrna M.; Wray, Naomi R.; Breuer, Rene; Cichon, Sven; Degenhardt, Franziska; Frank, Josef; Gross, Magdalena; Herms, Stefan; Hoefels, Susanne; Maier, Wolfgang; Mattheisen, Manuel; Noeethen, Markus M.; Rietschel, Marcella; Schulze, Thomas G.; Steffens, Michael; Treutlein, Jens; Boomsma, Dorret I.; De Geus, Eco J.; Hoogendijk, Witte; Hottenga, Jouke Jan; Jung-Ying, Tzeng; Lin, Dan-Yu; Middeldorp, Christel M.; Nolen, Willem A.; Penninx, Brenda P.; Smit, Johannes H.; Sullivan, Patrick F.; van Grootheest, Gerard; Willemsen, Gonneke; Zitman, Frans G.; Coryell, William H.; Knowles, James A.; Lawson, William B.; Levinson, Douglas F.; Potash, James B.; Scheftner, William A.; Shi, Jianxin; Weissman, Myrna M.; Holsboer, Florian; Muglia, Pierandrea; Tozzi, Federica; Blackwood, Douglas H. R.; Boomsma, Dorret I.; De Geus, Eco J.; Hottenga, Jouke Jan; MacIntyre, Donald J.; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M.; Penninx, Brenda P.; Ripke, Stephan; Smit, Johannes H.; Sullivan, Patrick F.; van Grootheest, Gerard; Willemsen, Gonneke; Zitman, Frans G.; van den Oord, Edwin J. C. G.; Holsboer, Florian; Lucae, Susanne; Binder, Elisabeth; Mueller-Myhsok, Bertram; Ripke, Stephan; Czamara, Darina; Kohli, Martin A.; Ising, Marcus; Uhr, Manfred; Bettecken, Thomas; Barnes, Michael R.; Breen, Gerome; Craig, Ian W.; Farmer, Anne E.; Lewis, Cathryn M.; McGuffin, Peter; Muglia, Pierandrea; Byrne, Enda; Gordon, Scott D.; Heath, Andrew C.; Henders, Anjali K.; Hickie, Ian B.; Madden, Pamela A. F.; Martin, Nicholas G.; Montgomery, Grant M.; Nyholt, Dale R.; Pergadia, Michele L.; Wray, Naomi R.; Hamilton, Steven P.; McGrath, Patrick J.; Shyn, Stanley I.; Slager, Susan L.; Oskarsson, Hoegni; Sigurdsson, Engilbert; Stefansson, Hreinn; Stefansson, Kari; Steinberg, Stacy; Thorgeirsson, Thorgeir; Levinson, Douglas F.; Potash, James B.; Shi, Jianxin; Weissman, Myrna M.; Guipponi, Michel; Lewis, Glyn; O'Donovan, Michael; Tansey, Katherine E.; Uher, Rudolf; Coryell, William H.; Knowles, James A.; Lawson, William B.; Levinson, Douglas F.; Potash, James B.; Scheftner, William A.; Shi, Jianxin; Weissman, Myrna M.; Castro, Victor M.; Churchill, Susanne E.; Fava, Maurizio; Gainer, Vivian S.; Gallagher, Patience J.; Goryachev, Sergey; Iosifescu, Dan V.; Kohane, Isaac S.; Murphy, Shawn N.; Perlis, Roy H.; Smoller, Jordan W.; Weilburg, Jeffrey B.; Kutalik, Zoltan; Preisig, Martin; Grabe, Hans J.; Nauck, Matthias; Schulz, Andrea; Teumer, Alexander; Voelzke, Henry; Landen, Mikael; Lichtenstein, Paul; Magnusson, Patrik; Pedersen, Nancy; Viktorin, Alexander

    2013-01-01

    Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chro

  6. Psychiatric comorbidities in patients with major depressive disorder

    Directory of Open Access Journals (Sweden)

    Thaipisuttikul P

    2014-11-01

    Full Text Available Papan Thaipisuttikul, Pichai Ittasakul, Punjaporn Waleeprakhon, Pattarabhorn Wisajun, Sudawan Jullagate Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Background: Psychiatric comorbidities are common in major depressive disorder (MDD. They may worsen outcome and cause economic burden. The primary objective was to examine the prevalence of psychiatric comorbidities in MDD. The secondary objectives were to compare the presence of comorbidities between currently active and past MDD, and between patients with and without suicidal risk.Methods: This was a cross-sectional study. A total of 250 patients with lifetime MDD and age ≥18 years were enrolled. The Mini International Neuropsychiatric Interview (MINI, Thai version, was used to confirm MDD diagnosis and classify comorbidities. MDD diagnosis was confirmed in 190, and 60 patients were excluded due to diagnosis of bipolar disorder.Results: Of the 190 MDD patients, 25.8% had current MDD and 74.2% had past MDD. Eighty percent were women. The mean age at enrollment was 50 years, and at MDD onset was 41 years. Most patients were married (53.2%, employed (54.8%, and had ≥12 years of education (66.9%. There were 67 patients (35.3% with one or more psychiatric comorbidities. Comorbidities included dysthymia (19.5%, any anxiety disorders (21.1% (panic disorder [6.8%], agoraphobia [5.8%], social phobia [3.7%], obsessive–compulsive disorder [OCD] [4.7%], generalized anxiety disorder [5.3%], and post-traumatic stress disorder [4.2%], alcohol dependence (0.5%, psychotic disorder (1.6%, antisocial personality (1.1%, and eating disorders (0%. Compared with past MDD, the current MDD group had significantly higher OCD (P<0.001, psychotic disorder (P=0.048, past panic disorder (P=0.017, and suicidal risk (P<0.001. Suicidal risk was found in 32.1% of patients. Patients with suicidal risk had more comorbid anxiety disorder of any type (P=0.019 and

  7. Smoking and major depressive disorder in Chinese women.

    Directory of Open Access Journals (Sweden)

    Qiang He

    Full Text Available OBJECTIVE: To investigate the risk factors that contribute to smoking in female patients with major depressive disorder (MDD and the clinical features in depressed smokers. METHODS: We examined the smoking status and clinical features in 6120 Han Chinese women with MDD (DSM-IV between 30 and 60 years of age across China. Logistic regression was used to determine the association between clinical features of MDD and smoking status and between risk factors for MDD and smoking status. RESULTS: Among the recurrent MDD patients there were 216(3.6% current smokers, 117 (2.0% former smokers and 333(5.6% lifetime smokers. Lifetime smokers had a slightly more severe illness, characterized by more episodes, longer duration, more comorbid illness (panic and phobias, with more DSM-IV A criteria and reported more symptoms of fatigue and suicidal ideation or attempts than never smokers. Some known risk factors for MDD were also differentially represented among smokers compared to non-smokers. Smokers reported more stressful life events, were more likely to report childhood sexual abuse, had higher levels of neuroticism and an increased rate of familial MDD. Only neuroticism was significantly related to nicotine dependence. CONCLUSIONS: Although depressed women smokers experience more severe illness, smoking rates remain low in MDD patients. Family history of MDD and environmental factors contribute to lifetime smoking in Chinese women, consistent with the hypothesis that the association of smoking and depression may be caused by common underlying factors.

  8. Functional versus syndromal recovery in patients with major depressive disorder and bipolar disorder.

    Science.gov (United States)

    van der Voort, Trijntje Y G; Seldenrijk, Adrie; van Meijel, Berno; Goossens, Peter J J; Beekman, Aartjan T F; Penninx, Brenda W J H; Kupka, Ralph W

    2015-06-01

    Many patients with major depressive disorder (MDD) or bipolar disorder (BD) experience impairments in daily life. We investigated whether patients with single-episode MDD (MDD-s), recurrent MDD (MDD-r), and BD differ in functional impairments, whether time since last episode (syndromal state, in 4 categories) contributes to impairment, whether this association is moderated by diagnosis, and the role of depressive symptoms. Data were derived from 1,664 participants in the Netherlands Study of Depression and Anxiety (MDD-s, n = 483; MDD-r, n = 1,063; BD, n = 118), from 2006 into 2009. In additional analyses, 530 healthy controls were included. DSM-IV-TR diagnosis and information about syndromal state were based on the Composite International Diagnostic Interview. Psychosocial impairment was assessed with the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Adjusted associations between diagnosis, syndromal state, impairment, and depression severity were investigated. Syndromal state not being taken into account, patients with BD experienced more functional impairment than patients with MDD-s or with MDD-r, and in all diagnostic groups, impairments decreased with increasing time since last episode. However, impact of syndromal state on functioning showed a different course between diagnostic groups (mean [SD] WHODAS score: current: MDD-s 30.8 [2.8], MDD-r 32.7 [0.9], BD 37.7 [2.1], P = .07; recently remitted: MDD-s 21.7 [3.5], MDD-r 24.0 [1.2], BD 22.1[3.2], P = .7; remitted: MDD-s 10.6 [3.7], MDD-r 21.6 [1.4], BD 19.2 [4.4], P = .02; remitted > 1 year: MDD-s 13.3 [0.6], MDD-r 14.7 [0.5], BD 17.1 [2.2], P = .8). Depression severity accounted for these differences. Moreover, functioning in all remitted patients remained impaired when compared to that in healthy controls. Functional recovery may take up to 1 year after syndromal remission in recurrent depressive and bipolar disorder, mainly due to residual depressive symptoms, emphasizing the

  9. Disrupted reward circuits is associated with cognitive deficits and depression severity in major depressive disorder.

    Science.gov (United States)

    Gong, Liang; Yin, Yingying; He, Cancan; Ye, Qing; Bai, Feng; Yuan, Yonggui; Zhang, Haisan; Lv, Luxian; Zhang, Hongxing; Xie, Chunming; Zhang, Zhijun

    2017-01-01

    Neuroimaging studies have demonstrated that major depressive disorder (MDD) patients show blunted activity responses to reward-related tasks. However, whether abnormal reward circuits affect cognition and depression in MDD patients remains unclear. Seventy-five drug-naive MDD patients and 42 cognitively normal (CN) subjects underwent a resting-state functional magnetic resonance imaging scan. The bilateral nucleus accumbens (NAc) were selected as seeds to construct reward circuits across all subjects. A multivariate linear regression analysis was employed to investigate the neural substrates of cognitive function and depression severity on the reward circuits in MDD patients. The common pathway underlying cognitive deficits and depression was identified with conjunction analysis. Compared with CN subjects, MDD patients showed decreased reward network connectivity that was primarily located in the prefrontal-striatal regions. Importantly, distinct and common neural pathways underlying cognition and depression were identified, implying the independent and synergistic effects of cognitive deficits and depression severity on reward circuits. This study demonstrated that disrupted topological organization within reward circuits was significantly associated with cognitive deficits and depression severity in MDD patients. These findings suggest that in addition to antidepressant treatment, normalized reward circuits should be a focus and a target for improving depression and cognitive deficits in MDD patients.

  10. Collaborative care for sick-listed workers with major depressive disorder : a randomised controlled trial from the Netherlands Depression Initiative aimed at return to work and depressive symptoms

    NARCIS (Netherlands)

    Vlasveld, Moniek C.; van der Feltz-Cornelis, Christina M.; Ader, Herman J.; Anema, Johannes R.; Hoedeman, Rob; van Mechelen, Willem; Beekman, Aartjan T. F.

    Objectives Major depressive disorder (MDD) is associated with absenteeism. In this study, the effectiveness of collaborative care, with a focus on return to work (RTW), was evaluated in its effect on depressive symptoms and the duration until RTW in sick-listed workers with MDD in the occupational

  11. Collaborative care for sick-listed workers with major depressive disorder : a randomised controlled trial from the Netherlands Depression Initiative aimed at return to work and depressive symptoms

    NARCIS (Netherlands)

    Vlasveld, Moniek C.; van der Feltz-Cornelis, Christina M.; Ader, Herman J.; Anema, Johannes R.; Hoedeman, Rob; van Mechelen, Willem; Beekman, Aartjan T. F.

    2013-01-01

    Objectives Major depressive disorder (MDD) is associated with absenteeism. In this study, the effectiveness of collaborative care, with a focus on return to work (RTW), was evaluated in its effect on depressive symptoms and the duration until RTW in sick-listed workers with MDD in the occupational h

  12. Major Depressive Disorder in Adolescence: The Role of Subthreshold Symptoms

    Science.gov (United States)

    Georgiades, Katholiki; Lewinsohn, Peter M.; Monroe, Scott M.; Seeley, John R.

    2006-01-01

    Objective: To examine the longitudinal association between individual subthreshold symptoms and onset of major depressive disorder (MDD) in adolescence. Method: Data for analysis come from the Oregon Adolescent Depression Project, a prospective epidemiological study of psychological disorders among adolescents, ages 14 to 18 years, from the…

  13. Depression (Major Depressive Disorder)

    Science.gov (United States)

    ... generally miserable or unhappy without really knowing why. Depression symptoms in children and teens Common signs and ... in normal activities, and avoidance of social interaction. Depression symptoms in older adults Depression is not a ...

  14. Patterns of co-morbidity with anxiety disorders in Chinese women with recurrent major depression

    OpenAIRE

    Li, Y; Shi, S; Yang, F.; Gao, J.; Li,Youhui; M. Tao; Wang, G.; Zhang, K; Gao, C.; Liu, L.; Li, Kan; Li, Keqing; Liu, Y.; Wang, Xumei; Zhang, J.

    2011-01-01

    Background Studies conducted in Europe and the USA have shown that co-morbidity between major depressive disorder (MDD) and anxiety disorders is associated with various MDD-related features, including clinical symptoms, degree of familial aggregation and socio-economic status. However, few studies have investigated whether these patterns of association vary across different co-morbid anxiety disorders. Here, using a large cohort of Chinese women with recurrent MDD, we examine the prevalence a...

  15. [Cognition - the core of major depressive disorder].

    Science.gov (United States)

    Polosan, M; Lemogne, C; Jardri, R; Fossati, P

    2016-02-01

    Cognitive deficits have been only recently recognized as a major phenotype determinant of major depressive disorder, although they are an integral part of the definition of the depressive state. Congruent evidence suggest that these cognitive deficits persist beyond the acute phase and may be identified at all ages. The aim of the current study was to review the main meta-analyses on cognition and depression, which encompasses a large range of cognitive domains. Therefore, we discuss the "cold" (attention, memory, executive functions) and "hot" (emotional bias) cognitive impairments in MDD, as well as those of social cognition domains (empathy, theory of mind). Several factors interfere with cognition in MDD such as clinical (melancholic, psychotic...) features, age, age of onset, illness severity, medication and comorbid condition. As still debated in the literature, the type of relationship between the severity of cognitive symptoms and functioning in depression is detailed, thus highlighting their predictive value of functional outcome, independently of the affective symptoms. A better identification of the cognitive deficits in MDD and a monitoring of the effects of different treatments require appropriate instruments, which may be developed by taking advantage of the increasing success of computing tools. Overall, current data suggest a core role for different cognitive deficits in MDD, therefore opening new perspectives for optimizing the treatment of depression. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. The role of oxidative and nitrosative stress in accelerated aging and major depressive disorder.

    Science.gov (United States)

    Maurya, Pawan Kumar; Noto, Cristiano; Rizzo, Lucas B; Rios, Adiel C; Nunes, Sandra O V; Barbosa, Décio Sabbatini; Sethi, Sumit; Zeni, Maiara; Mansur, Rodrigo B; Maes, Michael; Brietzke, Elisa

    2016-02-01

    Major depressive disorder (MDD) affects millions of individuals and is highly comorbid with many age associated diseases such as diabetes mellitus, immune-inflammatory dysregulation and cardiovascular diseases. Oxidative/nitrosative stress plays a fundamental role in aging, as well as in the pathogenesis of neurodegenerative/neuropsychiatric disorders including MDD. In this review, we critically review the evidence for an involvement of oxidative/nitrosative stress in acceleration of aging process in MDD. There are evidence of the association between MDD and changes in molecular mechanisms involved in aging. There is a significant association between telomere length, enzymatic antioxidant activities (SOD, CAT, GPx), glutathione (GSH), lipid peroxidation (MDA), nuclear factor κB, inflammatory cytokines with MDD. Major depression also is characterized by significantly lower concentration of antioxidants (zinc, coenzyme Q10, PON1). Since, aging and MDD share a common biological base in their pathophysiology, the potential therapeutic use of antioxidants and anti-aging molecules in MDD could be promising.

  17. Structural MRI correlates for vulnerability and resilience to major depressive disorder.

    LENUS (Irish Health Repository)

    Amico, Francesco

    2011-01-01

    In major depressive disorder (MDD), it is unclear to what extent structural brain changes are associated with depressive episodes or represent part of the mechanism by which the risk for illness is mediated. The aim of this study was to investigate whether structural abnormalities are related to risk for the development of MDD.

  18. Deficits of magnetoencephalography regional power in patients with major depressive disorder:an individual spectral analysis

    Institute of Scientific and Technical Information of China (English)

    汤浩

    2014-01-01

    Objective To explore the discrepancies of individualized frequency and band power between major depressive disorder(MDD)and controls in resting state,and the association of abnormal spectral power with clinical severity of MDD.Methods Whole-head MEG recordings were collected in 19 patients with MDD and 19 non-depressed controls in eye-closed resting state.Individual spectral power of each subject was calculated based on

  19. Mixed features in major depressive disorder: diagnoses and treatments.

    Science.gov (United States)

    Suppes, Trisha; Ostacher, Michael

    2017-04-01

    For the first time in 20 years, the American Psychiatric Association (APA) updated the psychiatric diagnostic system for mood disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Perhaps one of the most notable changes in the DSM-5 was the recognition of the possibility of mixed symptoms in major depression and related disorders (MDD). While MDD and bipolar and related disorders are now represented by 2 distinct chapters, the addition of a mixed features specifier to MDD represents a structural bridge between bipolar and major depression disorders, and formally recognizes the possibility of a mix of hypomania and depressive symptoms in someone who has never experienced discrete episodes of hypomania or mania. This article reviews historical perspectives on "mixed states" and the recent literature, which proposes a range of approaches to understanding "mixity." We discuss which symptoms were considered for inclusion in the mixed features specifier and which symptoms were excluded. The assumption that mixed symptoms in MDD necessarily predict a future bipolar course in patients with MDD is reviewed. Treatment for patients in a MDD episode with mixed features is critically considered, as are suggestions for future study. Finally, the premise that mood disorders are necessarily a spectrum or a gradient of severity progressing in a linear manner is argued.

  20. Quality of Life and Functioning in Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder After Treatment With Citalopram Monotherapy.

    Science.gov (United States)

    Steiner, Alexander J; Boulos, Nathalie; Mirocha, James; Wright, Stephanie M; Collison, Katherine L; IsHak, Waguih W

    Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) often have high comorbidity, consequently influencing patient-reported outcomes of depressive symptom severity, quality of life (QOL), and functioning. We hypothesized that the combined effects of concurrent PTSD and MDD would result in worse treatment outcomes, whereas individuals who achieved MDD remission would have better treatment outcomes. We analyzed 2280 adult participants who received level 1 treatment (citalopram monotherapy) in the Sequenced Treatment Alternatives to Relieve Depression study, including 2158 participants with MDD without comorbid PTSD and 122 participants with MDD with comorbid PTSD (MDD + PTSD). Post hoc analysis examined the proportion of participants whose scores were within normal or severely impaired for functioning and QOL. Remission status at exit from MDD was also determined. At entry, participants with MDD + PTSD experienced significantly worse QOL, functioning, and depressive symptom severity compared with participants with MDD without comorbid PTSD. Although both groups had significant improvements in functioning and QOL posttreatment, the participants with MDD + PTSD were less likely to achieve remission from MDD. Findings suggested that participants with MDD + PTSD are at a greater risk for severe impairment across all domains and less likely to achieve remission from MDD after treatment with citalopram monotherapy. As such, the use of patient-reported measures of QOL and functioning may inform practicing clinicians' and clinical trial researchers' abilities to develop appropriate interventions and monitor treatment efficacy. More importantly, we encourage clinicians and health care providers to routinely screen for PTSD in patients with MDD because this at-risk group requires tailored and specific pharmacotherapy and psychotherapy interventions beyond traditionally standard treatments for depression.

  1. Influence of Parental and Grandparental Major Depressive Disorder on Behavior Problems in Early Childhood: A Three-Generation Study

    Science.gov (United States)

    Olino, Thomas M.; Pettit, Jeremy W.; Klein, Daniel N.; Allen, Nicholas B.; Seeley, John R.; Lewinsohn, Peter M.

    2008-01-01

    The study examines the influence of parental and grandparental major depressive disorder (MDD) on behavior problems in children. The results conclude that MDD in parents and grandparents may result in high levels of incorporation problems of MDD in children but don't indicate additional risk.

  2. Vulnerability for new episodes in recurrent major depressive disorder : Protocol for the longitudinal DELTA-neuroimaging cohort study

    NARCIS (Netherlands)

    Mocking, R. J. T.; Bockting, C. L. H.; Figueroa, C. A.; Rive, M. M.; Geugies, H.; Servaas, M. N.; Assies, J.; Koeter, M. W. J.; Vaz, F.M.; Wichers, M.; Van Straalen, J. P.; De Raedt, R.; Harmer, C. J.; Schene, A. H.; Ruhé, H. G.

    2016-01-01

    Abstract Introduction Major depressive disorder (MDD) is widely prevalent and severely disabling, mainly due to its recurrent nature. A better understanding of the mechanisms underlying MDD-recurrence may help to identify high-risk patients and to improve the preventive treatment they need. MDD-recu

  3. Vulnerability for new episodes in recurrent major depressive disorder : protocol for the longitudinal DELTA-neuroimaging cohort study

    NARCIS (Netherlands)

    Mocking, Roel J T; Figueroa, Caroline A; Rive, Maria M; Geugies, Hanneke; Servaas, Michelle N; Assies, Johanna; Koeter, Maarten W J; Vaz, Frédéric M; Wichers, Marieke; van Straalen, Jan P; de Raedt, Rudi; Bockting, Claudi L H; Harmer, Catherine J; Schene, Aart H; Ruhe, Eric

    2016-01-01

    INTRODUCTION: Major depressive disorder (MDD) is widely prevalent and severely disabling, mainly due to its recurrent nature. A better understanding of the mechanisms underlying MDD-recurrence may help to identify high-risk patients and to improve the preventive treatment they need. MDD-recurrence h

  4. Personality traits in the differentiation of major depressive disorder and bipolar disorder during a depressive episode.

    Science.gov (United States)

    Araujo, Jaciana Marlova Gonçalves; dos Passos, Miguel Bezerra; Molina, Mariane Lopez; da Silva, Ricardo Azevedo; Souza, Luciano Dias de Mattos

    2016-02-28

    The aim of this study was to determine the differences in personality traits between individuals with Major Depressive Disorder (MDD) and Bipolar Disorder (BD) during a depressive episode, when it can be hard to differentiate them. Data on personality traits (NEO-FFI), mental disorders (Mini International Neuropsychiatric Interview Plus) and socioeconomic variables were collected from 245 respondents who were in a depressive episode. Individuals with MDD (183) and BD (62) diagnosis were compared concerning personality traits, clinical aspects and socioeconomic variables through bivariate analyses (chi-square and ANOVA) and multivariate analysis (logistic regression). There were no differences in the prevalence of the disorders between socioeconomic and clinical variables. As for the personality traits, only the difference in Agreeableness was statistically significant. Considering the control of suicide risk, gender and anxiety comorbidity in the multivariate analysis, the only variable that remained associated was Agreeableness, with an increase in MDD cases. The brief version of the NEO inventories (NEO-FFI) does not allow for the analysis of personality facets. During a depressive episode, high levels of Agreeableness can indicate that MDD is a more likely diagnosis than BD.

  5. The role of major depression in neurocognitive functioning in patients with posttraumatic stress disorder

    OpenAIRE

    Nijdam, Mirjam J.; Gersons, Berthold P R; Olff, Miranda

    2013-01-01

    Background: Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) frequently co-occur after traumatic experiences and share neurocognitive disturbances in verbal memory and executive functioning. However, few attempts have been made to systematically assess the role of a comorbid MDD diagnosis in neuropsychological studies in PTSD.Objective: The purpose of the current study is to investigate neurocognitive deficits in PTSD patients with and without MDD. We hypothesized that...

  6. Stimulated Gene Expression Profiles as a Blood Marker of Major Depressive Disorder

    NARCIS (Netherlands)

    Spijker, Sabine; Van Zanten, Jeroen S.; De Jong, Simone; Penninx, Brenda; van Dyck, Richard; Zitman, Frans G.; Smit, Jan H.; Ylstra, Bauke; Smit, August B.; Hoogendijk, Witte J. G.

    2010-01-01

    Background: Major depressive disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of unmedicated subje

  7. Comorbidity between post-traumatic stress disorder and major depressive disorder: alternative explanations and treatment considerations.

    Science.gov (United States)

    Flory, Janine D; Yehuda, Rachel

    2015-06-01

    Approximately half of people with post-traumatic stress disorder (PTSD) also suffer from Major Depressive Disorder (MDD). The current paper examines evidence for two explanations of this comorbidity. First, that the comorbidity reflects overlapping symptoms in the two disorders. Second, that the co-occurrence of PTSD and MDD is not an artifact, but represents a trauma-related phenotype, possibly a subtype of PTSD. Support for the latter explanation is inferred from literature that examines risk and biological correlates of PTSD and MDD, including molecular processes. Treatment implications of the comorbidity are considered.

  8. Anhedonia and cognitive function in adults with MDD

    DEFF Research Database (Denmark)

    McIntyre, Roger S; Woldeyohannes, Hanna O; Soczynska, Joanna K

    2015-01-01

    BACKGROUND: Cognitive dysfunction is common in major depressive disorder (MDD) and a critical determinant of health outcome. Anhedonia is a criterion item toward the diagnosis of a major depressive episode (MDE) and a well-characterized domain in MDD. We sought to determine the extent to which...... measure of anhedonia (r=0.131, p=0.012). Moreover, total depression symptom severity, as measured by the total Montgomery-Åsberg Depression Rating Scale (MADRS) score, was also significantly correlated with self-rated measures of cognitive dysfunction (r=0.147, p=0.005). The association between anhedonia...... variability in self-reported cognitive function correlates with anhedonia. METHOD: A post hoc analysis was conducted using data from (N=369) participants with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR)-defined diagnosis of MDD who were enrolled...

  9. Automaticity in Anxiety Disorders and Major Depressive Disorder

    Science.gov (United States)

    Teachman, Bethany A.; Joormann, Jutta; Steinman, Shari; Gotlib, Ian H.

    2012-01-01

    In this paper we examine the nature of automatic cognitive processing in anxiety disorders and Major Depressive Disorder (MDD). Rather than viewing automaticity as a unitary construct, we follow a social cognition perspective (Bargh, 1994) that argues for four theoretically independent features of automaticity: unconscious (processing of emotional stimuli occurs outside awareness), efficient (processing emotional meaning uses minimal attentional resources), unintentional (no goal is needed to engage in processing emotional meaning), and uncontrollable (limited ability to avoid, alter or terminate processing emotional stimuli). Our review of the literature suggests that most anxiety disorders are characterized by uncontrollable, and likely also unconscious and unintentional, biased processing of threat-relevant information. In contrast, MDD is most clearly typified by uncontrollable, but not unconscious or unintentional, processing of negative information. For the anxiety disorders and for MDD, there is not sufficient evidence to draw firm conclusions about efficiency of processing, though early indications are that neither anxiety disorders nor MDD are characterized by this feature. Clinical and theoretical implications of these findings are discussed and directions for future research are offered. In particular, it is clear that paradigms that more directly delineate the different features of automaticity are required to gain a more comprehensive and systematic understanding of the importance of automatic processing in emotion dysregulation. PMID:22858684

  10. Psychosocial Functioning in Depressive Patients: A Comparative Study between Major Depressive Disorder and Bipolar Affective Disorder

    Directory of Open Access Journals (Sweden)

    Shubham Mehta

    2014-01-01

    Full Text Available Introduction. Major depressive disorder (MDD and bipolar affective disorder (BAD are among the leading causes of disability. These are often associated with widespread impairments in all domains of functioning including relational, occupational, and social. The main aim of the study was to examine and compare nature and extent of psychosocial impairment of patients with MDD and BAD during depressive phase. Methodology. 96 patients (48 in MDD group and 48 in BAD group were included in the study. Patients were recruited in depressive phase (moderate to severe depression. Patients having age outside 18–45 years, psychotic symptoms, mental retardation, and current comorbid medical or axis-1 psychiatric disorder were excluded. Psychosocial functioning was assessed using Range of Impaired Functioning Tool (LIFE-RIFT. Results. Domains of work, interpersonal relationship, life satisfaction, and recreation were all affected in both groups, but the groups showed significant difference in global psychosocial functioning score only (P=0.031 with BAD group showing more severe impairment. Conclusion. Bipolar depression causes higher global psychosocial impairment than unipolar depression.

  11. Increased amygdala response to shame in remitted major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Erdem Pulcu

    Full Text Available Proneness to self-blaming moral emotions such as shame and guilt is increased in major depressive disorder (MDD, and may play an important role in vulnerability even after symptoms have subsided. Social psychologists have argued that shame-proneness is relevant for depression vulnerability and is distinct from guilt. Shame depends on the imagined critical perception of others, whereas guilt results from one's own judgement. The neuroanatomy of shame in MDD is unknown. Using fMRI, we compared 21 participants with MDD remitted from symptoms with no current co-morbid axis-I disorders, and 18 control participants with no personal or family history of MDD. The MDD group exhibited higher activation of the right amygdala and posterior insula for shame relative to guilt (SPM8. This neural difference was observed despite equal levels of rated negative emotional valence and frequencies of induced shame and guilt experience across groups. These same results were found in the medication-free MDD subgroup (N = 15. Increased amygdala and posterior insula activations, known to be related to sensory perception of emotional stimuli, distinguish shame from guilt responses in remitted MDD. People with MDD thus exhibit changes in the neural response to shame after symptoms have subsided. This supports the hypothesis that shame and guilt play at least partly distinct roles in vulnerability to MDD. Shame-induction may be a more sensitive probe of residual amygdala hypersensitivity in MDD compared with facial emotion-evoked responses previously found to normalize on remission.

  12. Comorbidity of anxiety disorders in major depressive disorder: A clinical trial to evaluate neuropsychological deficit

    Directory of Open Access Journals (Sweden)

    Ixchel Herrera-Guzmán

    2009-03-01

    Full Text Available Background and objectives: Various clinical aspects of Major Depressive Disorder (MDD are related to the neuropsychological impairments characteristic of this illness. The aim of this study was to determine the relation between certain clinical variables of MDD - in particular the presence of comorbid anxiety disorders - and the neuropsychological performance of patients with MDD selected for a clinical trial. Methods: Using cluster analyses, we generated two groups of patients: one group with Major Depressive Disorder and a Comorbid Anxiety Disorder (MDDAD, and the other with Pure Major Depressive Disorder (PMDD. Both groups were assessed clinically and neuropsychologically before and after 24 weeks of pharmacological treatment. Neuropsychological performance prior to treatment was comparable in the two groups. Results: After treatment, both groups showed cognitive improvement in attention tasks, memory, and executive functions Conclusions: The PMDD group obtained greater neurocognitive benefits from the antidepressive treatment than the MDDAD group.

  13. Hippocampal neuroplasticity in major depressive disorder.

    Science.gov (United States)

    Malykhin, N V; Coupland, N J

    2015-11-19

    One of the most replicated findings has been that hippocampus volume is decreased in patients with major depressive disorder (MDD). Recent volumetric magnetic resonance imaging (MRI) studies suggest that localized differences in hippocampal volume may be more prominent than global differences. Preclinical and post-mortem studies in MDD indicated that different subfields of the hippocampus may respond differently to stress and may also have differential levels of plasticity in response to antidepressant treatment. Advances in high-field MRI allowed researchers to visualize and measure hippocampal subfield volumes in MDD patients in vivo. The results of these studies provide the first in vivo evidence that hippocampal volume reductions in MDD are specific to the cornu ammonis and dentate gyrus hippocampal subfields, findings that appear, on the surface, consistent with preclinical evidence for localized mechanisms of hippocampal neuroplasticity. In this review we discuss how recent advances in neuroimaging allow researchers to further understand hippocampal neuroplasticity in MDD and how it is related to antidepressant treatment, memory function, and disease progression.

  14. Health functioning impairments associated with posttraumatic stress disorder, anxiety disorders, and depression.

    Science.gov (United States)

    Zayfert, Claudia; Dums, Aricca R; Ferguson, Robert J; Hegel, Mark T

    2002-04-01

    Although anxiety disorders have been associated with impairments in self-reported health functioning, the relative effect of various anxiety disorders has not been studied. We compared health functioning of patients with a principal diagnosis of posttraumatic stress disorder (PTSD), panic disorder (PD), generalized anxiety disorder (GAD), and major depressive disorder (MDD). Patients with PTSD and MDD were equally impaired on overall mental health functioning, and both were significantly worse than patients with PD and GAD. PTSD was associated with significantly worse physical health functioning relative to PD, GAD, and MDD. Hierarchical regression showed that the association of PTSD with physical health functioning was unique and was not caused by the effects of age, depression, or comorbid anxiety disorders. Both PTSD and comorbid anxiety accounted for unique variance in mental functioning. These results highlight the association of PTSD with impaired physical and mental functioning and suggest that effective treatment of PTSD may affect overall health.

  15. Defense mechanisms in patients with fibromyalgia and major depressive disorder

    Directory of Open Access Journals (Sweden)

    Tormod Landmark

    2008-12-01

    Full Text Available Background and objectives: Fibromyalgia (FM and depression has been suggested to share a common underlying etiology. Few studies have investigated the role of emotional regulation processes in FM compared to depressive disorders.The purpose of the current study was to explore the use of defense mechanisms in FM patients with and without comorbid lifetime depressive disorder (LDD, and to compare their use of defenses to healthy control subjects and patients with Major Depressive Disorder (MDD. Methods: A total of 91 participants were included (17 with FM and LDD, 25 with FM but not LDD, 24 with MDD, and 25 healthy controls. Depressive disorders were identified by using the Structured Clinical Interview for DSM Axis I disorders (SCID-I. All diagnosis of FM were confirmed to meet the American College of Rheumatology's criteria for FM. The Life Style Index (LSI was used to measure defense mechanisms. Results and Conclusions: Group comparisons indicated that MDD patients and FM patients with LDD made significantly more use of defenses than healthy controls, whereas FM patients without LDD made significantly less use of defenses than both MDD patients and FM patients with LDD, but did not differ from healthy controls. Follow up analyses indicated significant main effects for the defense mechanisms of regression, compensation and displacement. This study suggests that FM and depression do not share common risk factors in terms of restricted affects or avoidance of conflicted feelings.

  16. Altered functional connectivity in posttraumatic stress disorder with versus without comorbid major depressive disorder: a resting state fMRI study.

    Science.gov (United States)

    Kennis, Mitzy; Rademaker, Arthur R; van Rooij, Sanne J H; Kahn, René S; Geuze, Elbert

    2013-01-01

    Posttraumatic stress disorder (PTSD) is an anxiety disorder that is often diagnosed with comorbid depressive disorder. Therefore, neuroimaging studies investigating PTSD typically include both patients with and without comorbid depression. Differences in activity of the anterior cingulate cortex (ACC) and insula have been shown to differentiate PTSD patients with and without major depressive disorder (MDD). Whether or not comorbid MDD affects resting state functional connectivity of PTSD patients has not been investigated to our knowledge. Here, resting state functional connectivity of PTSD patients with (PTSD+MDD; n=27) and without (PTSD-MDD; n=23) comorbid MDD was investigated. The subgenual ACC and insula were investigated as seed regions. Connectivity between the subgenual ACC and perigenual parts of the ACC was increased in PTSD+MDD versus PTSD-MDD, which may reflect the presence of depressive specific symptoms such as rumination. Functional connectivity of the subgenual ACC with the thalamus was reduced, potentially related to more severe deficits in executive functioning in the PTSD+MDD group versus the PTSD-MDD group. In addition, the PTSD+MDD group showed reduced functional connectivity of the insula with the hippocampus compared to the PTSD-MDD group. However, this cluster was no longer significantly different when PTSD patients that were using medication were excluded from analyses. Thus, resting state functional connectivity of the subgenual ACC can distinguish PTSD+MDD from PTSD-MDD, and this may therefore be used as a neurobiological marker for comorbid MDD in the presence of PTSD. As PTSD+MDD are more treatment resistant, these findings can also guide treatment development, for example by targeting the subgenual ACC network with treatment.

  17. Major depressive disorder induced by prolactinoma--a case report.

    Science.gov (United States)

    Liao, Wei-Ting; Bai, Ya-Mei

    2014-01-01

    Prolactinomas, the most common type of pituitary tumor, can induce hyperprolactinemia and cause some psychiatric symptoms, such as anxiety, depression and even psychotic symptoms. However, in previous case reports, no information about estrogen levels was mentioned. Here, we present a 48-year-old female patient who had a recurrent episode of major depressive disorder (MDD) and amenorrhea. Hyperprolactinemia (167 ng/ml), low estrogen (15.31 pg/ml) and a pituitary prolactinoma were found by MRI. After a dopamine agonist (Dostinex) and aripiprazole were prescribed, the patient's depressed mood remitted and her menstruation normalized. The possible mechanism of MDD induced by prolactinoma is discussed.

  18. Disorder-specific volumetric brain difference in adolescent major depressive disorder and bipolar depression.

    Science.gov (United States)

    MacMaster, Frank P; Carrey, Normand; Langevin, Lisa Marie; Jaworska, Natalia; Crawford, Susan

    2014-03-01

    Structural abnormalities in frontal, limbic and subcortical regions have been noted in adults with both major depressive disorder (MDD) and bipolar disorder (BD). In the current study, we examined regional brain morphology in youth with MDD and BD as compared to controls. Regional brain volumes were measured in 32 MDD subjects (15.7 ± 2.1 years), 14 BD subjects (16.0 ± 2.4 years) and 22 healthy controls (16.0 ± 2.8 years) using magnetic resonance imaging (MRI). Regions of interest included the hippocampus, dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), caudate, putamen and thalamus. Volumetric differences between groups were significant (F26,80 = 1.80, p = 0.02). Post-hoc analyses indicated that individuals with MDD showed reduced left hippocampus volumes (p = 0.048) as well as right ACC white and gray matter volumes (p = 0.003; p = 0.01) compared to controls. BD participants also displayed reduced left hippocampal and right/left putamen volumes compared to controls (p < 0.001; p = 0.015; p = 0.046 respectively). Interestingly, right and left ACC white matter volumes were smaller in MDD than in BD participants (p = 0.019; p = 0.045 respectively). No volumetric group differences were observed for the DLPFC and thalamus. Discriminant analysis was able to correctly classify 81.0 % of subjects as having BD or as MDD based on imaging data. Confirmation and extension of our findings requires larger sample sizes. Our findings provide new evidence of distinct, specific regional brain volumetric differences between MDD and BD that may be used to distinguish the two disorders.

  19. Cognitive Deficits as a Mediator of Poor Occupational Function in Remitted Major Depressive Disorder Patients

    OpenAIRE

    Woo, Young Sup; Rosenblat, Joshua D.; Kakar, Ron; Bahk, Won-Myong; McIntyre, Roger S.

    2016-01-01

    Cognitive deficits in major depressive disorder (MDD) patients have been described in numerous studies. However, few reports have aimed to describe cognitive deficits in the remitted state of MDD and the mediational effect of cognitive deficits on occupational outcome. The aim of the current review is to synthesize the literature on the mediating and moderating effects of specific domains of cognition on occupational impairment among people with remitted MDD. In addition, predictors of cognit...

  20. Biomarkers for Major Depressive Disorder: Economic Considerations.

    Science.gov (United States)

    Bogavac-Stanojevic, Natasa; Lakic, Dragana

    2016-11-01

    Preclinical Research Major depressive disorder (MDD) is a major psychiatric illness and it is predicted to be the second leading cause of disability by 2020 with a lifetime prevalence of about 13%. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used therapeutic class for MDD. However, response to SSRI treatment varies considerably between patients. Biomarkers of treatment response may enable clinicians to target the appropriate drug for each patient. Biomarkers need to have accuracy in real life, sensitivity, specificity, and relevance to depression. Introduction of MDD biomarkers into the health care system can increase the overall cost of clinical diagnosis of patients. Because of that, decisions to allocate health research funding must be based on drug effectiveness and cost-effectiveness. The assessment of MDD biomarkers should include reliable evidence of associated drug effectiveness, adverse events and consequences (reduced productivity and quality of life, disability) and effectiveness of alternative approaches, other drug classes or behavioral or alternative therapies. In addition, all the variables included in an economic model (probabilities, outcomes, and costs) should be based on reliable evidence gained from the literature-ideally meta-analyses-and the evidence should also be determined by informed and specific expert opinion. Early assessment can guide decisions about whether or not to continue test development, and ideally to optimize the process. Drug Dev Res 77 : 374-378, 2016. © 2016 Wiley Periodicals, Inc.

  1. DNA modification study of major depressive disorder: Beyond locus-by-locus comparisons

    NARCIS (Netherlands)

    Oh, G.; Wang, S.C.; Pal, M.; Chen, Z.F.; Khare, T.; Tochigi, M.; Ng, C.; Yang, Y.A.; Kwan, A.; Kaminsky, Z.A.; Mill, J.; Gunasinghe, C.; Tackett, J.L.; Gottesman, I.I.; Willemsen, G.; Geus, E.J.C. de; Vink, J.M.; Slagboom, P.E.; Wray, N.R.; Heath, A.C.; Montgomery, G.W.; Turecki, G.; Martin, N.G.; Boomsma, D.I.; McGuffin, P.; Kustra, R.; Petronis, A.

    2015-01-01

    Background: Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined.

  2. DNA modification study of major depressive disorder: Beyond locus-by-locus comparisons

    NARCIS (Netherlands)

    Oh, G.; Wang, S.C.; Pal, M.; Chen, Z.F.; Khare, T.; Tochigi, M.; Ng, C.; Yang, Y.A.; Kwan, A.; Kaminsky, Z.A.; Mill, J.; Gunasinghe, C.; Tackett, J.L.; Gottesman, I.I.; Willemsen, G.; Geus, E.J.C. de; Vink, J.M.; Slagboom, P.E.; Wray, N.R.; Heath, A.C.; Montgomery, G.W.; Turecki, G.; Martin, N.G.; Boomsma, D.I.; McGuffin, P.; Kustra, R.; Petronis, A.

    2015-01-01

    Background: Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined. Methods

  3. Safety and Tolerability of Desvenlafaxine in Children and Adolescents with Major Depressive Disorder

    OpenAIRE

    Findling, Robert L; Groark, James; Chiles, Deborah; Ramaker, Sara; Yang, Lingfeng; Tourian, Karen A

    2014-01-01

    Objective: The purpose of this study was to assess long-term safety and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) in children and adolescents with major depressive disorder (MDD).

  4. Vascular Pathology and Trajectories of Late-Life Major Depressive Disorder in Secondary Psychiatric Care

    DEFF Research Database (Denmark)

    Musliner, Katherine L; Zandi, Peter P; Liu, Xiaoqin

    2017-01-01

    OBJECTIVE: To examine 5-year trajectories of psychiatrist-treated late-life major depressive disorder (MDD), and evaluate whether previous vascular pathology is associated with more severe trajectories of late-life MDD. METHODS: Data were obtained from nationally representative civil, psychiatric...

  5. The impact of somatic symptoms on the course of major depressive disorder

    NARCIS (Netherlands)

    Bekhuis, Ella; Boschloo, Lynn; Rosmalen, Judith G. M.; de Boer, Marrit K.; Schoevers, Robert A.

    2016-01-01

    Objective: Somatic symptoms have been suggested to negatively affect the course of major depressive disorder (MDD). Mechanisms behind this association, however, remain elusive. This study examines the impact of somatic symptoms on MDD prognosis and aims to determine whether this effect can be explai

  6. Major depressive disorder alters perception of emotional body movements

    Directory of Open Access Journals (Sweden)

    Morten eKaletsch

    2014-01-01

    Full Text Available Much recent research has shown an association between mood disorders and an altered emotion perception. However, these studies were conducted mainly with stimuli such as faces. This is the first study to examine possible differences in how people with major depressive disorder (MDD and healthy controls perceive emotions expressed via body movements. 30 patients with MDD and 30 healthy controls observed video scenes of human interactions conveyed by point–light displays (PLDs. They rated the depicted emotions and judged their confidence in their rating. Results showed that patients with MDD rated the depicted interactions more negatively than healthy controls. They also rated interactions with negative emotionality as being more intense and were more confident in their ratings. It is concluded that patients with MDD exhibit an altered emotion perception compared to healthy controls when rating emotions expressed via body movements depicted in PLDs.

  7. Major Depressive Disorder Is Associated with Broad Impairments on Neuropsychological Measures of Executive Function: A Meta-Analysis and Review

    Science.gov (United States)

    Snyder, Hannah R.

    2013-01-01

    Cognitive impairments are now widely acknowledged as an important aspect of major depressive disorder (MDD), and it has been proposed that executive function (EF) may be particularly impaired in patients with MDD. However, the existence and nature of EF impairments associated with depression remain strongly debated. Although many studies have…

  8. The oft-neglected role of parietal EEG asymmetry and risk for major depressive disorder.

    Science.gov (United States)

    Stewart, Jennifer L; Towers, David N; Coan, James A; Allen, John J B

    2011-01-01

    Relatively less right parietal activity may reflect reduced arousal and signify risk for major depressive disorder (MDD). Inconsistent findings with parietal electroencephalographic (EEG) asymmetry, however, suggest issues such as anxiety comorbidity and sex differences have yet to be resolved. Resting parietal EEG asymmetry was assessed in 306 individuals (31% male) with (n=143) and without (n=163) a DSM-IV diagnosis of lifetime MDD and no comorbid anxiety disorders. Past MDD+ women displayed relatively less right parietal activity than current MDD+ and MDD- women, replicating prior work. Recent caffeine intake, an index of arousal, moderated the relationship between depression and EEG asymmetry for women and men. Findings suggest that sex differences and arousal should be examined in studies of depression and regional brain activity.

  9. A Study of the Predictive Validity of the Children's Depression Inventory for Major Depression Disorder in Puerto Rican Adolescents

    Science.gov (United States)

    Rivera-Medina, Carmen L.; Bernal, Guillermo; Rossello, Jeannette; Cumba-Aviles, Eduardo

    2010-01-01

    This study aims to evaluate the predictive validity of the Children's Depression Inventory items for major depression disorder (MDD) in an outpatient clinic sample of Puerto Rican adolescents. The sample consisted of 130 adolescents, 13 to 18 years old. The five most frequent symptoms of the Children's Depression Inventory that best predict the…

  10. Neurobiology of Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Rosa Villanueva

    2013-01-01

    Full Text Available We survey studies which relate abnormal neurogenesis to major depressive disorder. Clinically, descriptive gene and protein expression analysis and genetic and functional studies revised here show that individual alterations of a complex signaling network, which includes the hypothalamic-pituitary-adrenal axis; the production of neurotrophins and growth factors; the expression of miRNAs; the production of proinflammatory cytokines; and, even, the abnormal delivery of gastrointestinal signaling peptides, are able to induce major mood alterations. Furthermore, all of these factors modulate neurogenesis in brain regions involved in MDD, and are functionally interconnected in such a fashion that initial alteration in one of them results in abnormalities in the others. We highlight data of potential diagnostic significance and the relevance of this information to develop new therapeutic approaches. Controversial issues, such as whether neurogenesis is the basis of the disease or whether it is a response induced by antidepressant treatments, are also discussed.

  11. The Relationship between Major Depressive Disorder and Personality Traits.

    Directory of Open Access Journals (Sweden)

    Sara Bensaeed

    2014-03-01

    Full Text Available The aim of this study was to compare the clinical temperaments and characters of Iranian patients with Major Depressive Disorder (MDD with healthy controls.The study participants included 47 outpatients with Major Depressive Disorder (MDD and 120 normal controls with no psychiatric disorders. Sampling method was convenience. The MDD patients were diagnosed as MDD by a psychiatrist using the Persian structured clinical interview for axis I disorders (SCID-I, and they completed at least 8 weeks of antidepressant treatment. All the patients filled out the Persian version of the Temperament and Character Inventory (TCI. Data were analyzed using SPSS version 17, Chi square, T test and Multiple Regression. The level of significance was set at 5%.The present study demonstrates a link between depression and lower persistence (p≤0.001, self-directedness (p≤0.001 and cooperativeness (p≤0.001 scores. A negative correlation between age and Harm Avoidance (p≤0.001 was observed in both groups.Lower scores of persistence (P, self-directedness (SD and cooperativeness (CO were observed in patients with depression more than controls even in the remission phase which could indicate a relationship between these traits and depression.

  12. Differential urinary metabolites related with the severity of major depressive disorder.

    Science.gov (United States)

    Chen, Jian-Jun; Zhou, Chan-Juan; Zheng, Peng; Cheng, Ke; Wang, Hai-Yang; Li, Juan; Zeng, Li; Xie, Peng

    2017-08-14

    Major depressive disorder (MDD) is a common mental disorder that affects a person's general health. However, there is still no objective laboratory test for diagnosing MDD. Here, an integrated analysis of data from our previous studies was performed to identify the differential metabolites in the urine of moderate and severe MDD patients. A dual platform approach (NMR spectroscopy and GC-MS) was used. Consequently, 14 and 22 differential metabolites responsible for separating moderate and severe MDD patients, respectively, from their respective healthy controls (HCs) were identified. Meanwhile, the moderate MDD-specific panel (N-Methylnicotinamide, Acetone, Choline, Citrate, vanillic acid and azelaic acid) and severe MDD-specific panel (indoxyl sulphate, Taurine, Citrate, 3-hydroxyphenylacetic acid, palmitic acid and Lactate) could discriminate moderate and severe MDD patients, respectively, from their respective HCs with high accuracy. Moreover, the differential metabolites in severe MDD were significantly involved in three metabolic pathways and some biofunctions. These results showed that there were divergent urinary metabolic phenotypes in moderate and severe MDD patients, and the identified potential urinary biomarkers might be useful for future developing objective diagnostic tests for MDD diagnosis. Our results could also be helpful for researchers to study the pathogenesis of MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Spatial affect learning restricted in major depression relative to anxiety disorders and healthy controls.

    Science.gov (United States)

    Gollan, Jackie K; Norris, Catherine J; Hoxha, Denada; Irick, John Stockton; Hawkley, Louise C; Cacioppo, John T

    2014-01-01

    Detecting and learning the location of unpleasant or pleasant scenarios, or spatial affect learning, is an essential skill that safeguards well-being (Crawford & Cacioppo, 2002). Potentially altered by psychiatric illness, this skill has yet to be measured in adults with and without major depressive disorder (MDD) and anxiety disorders (AD). This study enrolled 199 adults diagnosed with MDD and AD (n=53), MDD (n=47), AD (n=54), and no disorders (n=45). Measures included clinical interviews, self-reports, and a validated spatial affect task using affective pictures (IAPS; Lang, Bradley, & Cuthbert, 2005). Participants with MDD showed impaired spatial affect learning of negative stimuli and irrelevant learning of pleasant pictures compared with non-depressed adults. Adults with MDD may use a "GOOD is UP" heuristic reflected by their impaired learning of the opposite correlation (i.e., "BAD is UP") and performance in the pleasant version of the task.

  14. Biomarkers in major depressive disorder: the role of mass spectrometry.

    Science.gov (United States)

    Woods, Alisa G; Iosifescu, Dan V; Darie, Costel C

    2014-01-01

    Major depressive disorder (MDD) is common. Despite numerous available treatments, many individuals fail to improve clinically. MDD continues to be diagnosed exclusively via behavioral rather than biological methods. Biomarkers-which include measurements of genes, proteins, and patterns of brain activity-may provide an important objective tool for the diagnosis of MDD or in the rational selection of treatments. Proteomic analysis and validation of its results as biomarkers is less explored than other areas of biomarker research in MDD. Mass spectrometry (MS) is a comprehensive, unbiased means of proteomic analysis, which can be complemented by directed protein measurements, such as Western Blotting. Prior studies have focused on MS analysis of several human biomaterials in MDD, including human post-mortem brain, cerebrospinal fluid (CSF), blood components, and urine. Further studies utilizing MS and proteomic analysis in MDD may help solidify and establish biomarkers for use in diagnosis, identification of new treatment targets, and understanding of the disorder. The ultimate goal is the validation of a biomarker or a biomarker signature that facilitates a convenient and inexpensive predictive test for depression treatment response and helps clinicians in the rational selection of next-step treatments.

  15. The significance of routine biochemical markers in patients with major depressive disorder

    Science.gov (United States)

    Peng, You-Fan; Xiang, Yang; Wei, Ye-Sheng

    2016-01-01

    The aim of our study is to examine the levels of routine biochemical markers in patients with major depressive disorder (MDD), and combine multiple biochemical parameters to assess the discriminative power for patients with MDD. We used the Hamilton Depression (HAMD) score to evaluate the severity of depressive symptoms in 228 patients with MDD. The phase of depression severity was between moderate and severe in MDD patients. There were significant differences between MDD patients and healthy controls in alanine transaminase (ALT), urea nitrogen (UN), lactate dehydrogenase (LDH), uric acid (UA), total protein (TP), total bile acid (TBA), creatinine (Cr), total bilirubin (Tbil), direct bilirubin (Dbil) and indirect bilirubin (Ibil), high density lipoprotein-cholesterol (HDL-C), fasting blood-glucose (FBG) and fructosamine (SF). Multivariate analysis showed that UN, FBG, HDL-C, SF, TP, Cr and Tbil remained independently association with MDD. Further, a logit equation was established to identify patients with MDD. The composite markers exhibited an area under the curve of 0.810 with cut-off values of 0.410. Our results suggest the associations between UN, FBG, HDL-C, TP, Cr, Tbil, SF and MDD, use of these routine biochemical markers in combination may contribute to improve the complete management for patients with MDD. PMID:27683078

  16. Pericardial adipose tissue and the metabolic syndrome is increased in patients with chronic major depressive disorder compared to acute depression and controls.

    Science.gov (United States)

    Kahl, K G; Herrmann, J; Stubbs, B; Krüger, T H C; Cordes, J; Deuschle, M; Schweiger, U; Hüper, K; Helm, S; Birkenstock, A; Hartung, D

    2017-01-04

    Major depressive disorder (MDD) is associated with an estimated fourfold risk for premature death, largely attributed to cardiovascular disorders. Pericardial adipose tissue (PAT), a fat compartment surrounding the heart, has been implicated in the development of coronary artery disease. An unanswered question is whether people with chronic MDD are more likely to have elevated PAT volumes versus acute MDD and controls (CTRL). The study group consists of sixteen patients with chronic MDD, thirty-four patients with acute MDD, and twenty-five CTRL. PAT and adrenal gland volume were measured by magnetic resonance tomography. Additional measures comprised factors of the metabolic syndrome, cortisol, relative insulin resistance, and pro-inflammatory cytokines (interleukin-6; IL-6 and tumor necrosis factor-α, TNF-α). PAT volumes were significantly increased in patients with chronic MDD>patients with acute MDD>CTRL. Adrenal gland volume was slightly enlarged in patients with chronic MDD>acute MDD>CTRL, although this difference failed to reach significance. The PAT volume was correlated with adrenal gland volume, and cortisol concentrations were correlated with depression severity, measured by BDI-2 and MADRS. Group differences were found concerning the rate of the metabolic syndrome, being most frequent in chronic MDD>acute MDD>CTRL. Further findings comprised increased fasting cortisol, increased TNF-α concentration, and decreased physical activity level in MDD compared to CTRL. Our results extend the existing literature in demonstrating that patients with chronic MDD have the highest risk for developing cardiovascular disorders, indicated by the highest PAT volume and prevalence of metabolic syndrome. The correlation of PAT with adrenal gland volume underscores the role of the hypothalamus-pituitary-adrenal system as mediator for body-composition changes. Metabolic monitoring, health advices and motivation for the improvement of physical fitness may be recommended in

  17. Personality disorders, but not cancer severity or treatment type, are risk factors for later generalised anxiety disorder and major depressive disorder in non metastatic breast cancer patients.

    Science.gov (United States)

    Champagne, Anne-Laure; Brunault, Paul; Huguet, Grégoire; Suzanne, Isabelle; Senon, Jean-Louis; Body, Gilles; Rusch, Emmanuel; Magnin, Guillaume; Voyer, Mélanie; Réveillère, Christian; Camus, Vincent

    2016-02-28

    This study aimed to determine whether personality disorders were associated with later Major Depressive Disorder (MDD) or Generalised Anxiety Disorder (GAD) in breast cancer patients. This longitudinal and multicentric study included 120 French non-metastatic breast cancer patients. After cancer diagnosis (T1) and 7 months after diagnosis (T3), we assessed MDD and GAD (Mini International Neuropsychiatric Interview 5.0). We assessed personality disorders 3 months after diagnosis (VKP). We used multiple logistic regression analysis to determine what were the factors associated with GAD and MDD at T3. At T3, prevalence rate was 10.8% for MDD and 19.2% for GAD. GAD at T3 was significantly and independently associated with GAD at T1 and with existence of a personality disorder, no matter the cluster type. MDD at T3 was significantly and independently associated with MDD at T1 and with the existence of a cluster C personality disorder. Initial cancer severity and the type of treatment used were not associated with GAD or MDD at T3. Breast cancer patients with personality disorders are at higher risk for GAD and MDD at the end of treatment. Patients with GAD should be screened for personality disorders. Specific interventions for patients with personality disorders could prevent psychiatric disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. The network structure of major depressive disorder, generalized anxiety disorder and somatic symptomatology

    NARCIS (Netherlands)

    Bekhuis, E.; Schoevers, R. A.; van Borkulo, C. D.; Rosmalen, J. G. M.; Boschloo, L.

    2016-01-01

    Background Major depressive disorder (MDD) and generalized anxiety disorder (GAD) often co-occur with somatic symptomatology. Little is known about the contributions of individual symptoms to this association and more insight into their relationships could help to identify symptoms that are central

  19. Common Genetic and Environmental Influences on Major Depressive Disorder and Conduct Disorder

    Science.gov (United States)

    Subbarao, Anjali; Rhee, Soo Hyun; Young, Susan E.; Ehringer, Marissa A.; Corley, Robin P.; Hewitt, John K.

    2008-01-01

    The evidence for common genetic and environmental influences on conduct disorder (CD) and major depressive disorder (MDD) in adolescents was examined. A sample of 570 monozygotic twin pairs, 592 dizygotic twin pairs, and 426 non-twin siblings, aged 12-18 years, was recruited from the Colorado Twin Registry. For the past year data, there was a…

  20. The network structure of major depressive disorder, generalized anxiety disorder and somatic symptomatology

    NARCIS (Netherlands)

    Bekhuis, E.; Schoevers, R. A.; van Borkulo, C. D.; Rosmalen, J. G. M.; Boschloo, L.

    2016-01-01

    Background Major depressive disorder (MDD) and generalized anxiety disorder (GAD) often co-occur with somatic symptomatology. Little is known about the contributions of individual symptoms to this association and more insight into their relationships could help to identify symptoms that are central

  1. The network structure of major depressive disorder, generalized anxiety disorder and somatic symptomatology

    NARCIS (Netherlands)

    Bekhuis, E.; Schoevers, R.A.; van Borkulo, C.D.; Rosmalen, J.G.M.; Boschloo, L.

    2016-01-01

    Major depressive disorder (MDD) and generalized anxiety disorder (GAD) often co-occur with somatic symptomatology. Little is known about the contributions of individual symptoms to this association and more insight into their relationships could help to identify symptoms that are central in the proc

  2. Prolidase activity in major depressive disorder

    Directory of Open Access Journals (Sweden)

    Süleyman Demir

    2015-09-01

    Full Text Available Objective: Prolidase enzyme, which exists in plasma, brain and various organs, is a cytosolic exopeptidase, that divisor the imidodipeptides with carboxyl terminal position of proline and hydroxyproline. The aim of the present study was to investigate serum prolidase activity level in major depressive disorder (MDD. Methods: This study included 22 patients with MDD as the study group, and 26 healthy subjects without any psychiatric disorders as the control group. Each patient underwent a detailed diagnostic evaluation by experienced psychiatrists. The sociodemographic information form given to both patients and the control subjects, while Hamilton Depression Scale Scoring (HDS, Hamilton Anxiety Scale Scoring (HAS, Clinical Global Impression Scoring (CGI applied to patients. Blood samples were obtained for biochemical analyses. Results: The mean age of the patient group was 31.3±10.1 years old, whereas the mean age of the control group was 32.3±8.8 years old. The mean duration of the education for the patient group was 8.1±6.2 years, whereas for the control group was 10.2±3.8 years. There was no significant differences in terms of the mean age of participants and the mean duration of the education between two groups (p>0.05. The level of prolidase activity of patient group was 510.3±480.8 U/L, whereas the level of prolidase activity of control group was 457.8±386.0 U/L. No significant difference was observed in serum prolidase activity between patient and the control groups (p>0.05. Conclusion: In our study similar level of prolidase activity was found in MDD and healthy subjects. We suggest that this finding may be an evidence indicating that MDD and bipolar depression may be different clinical entities. J Clin Exp Invest 2015; 6 (3: 296-300

  3. Additive genetic contribution to symptom dimensions in major depressive disorder.

    Science.gov (United States)

    Pearson, Rahel; Palmer, Rohan H C; Brick, Leslie A; McGeary, John E; Knopik, Valerie S; Beevers, Christopher G

    2016-05-01

    Major depressive disorder (MDD) is a phenotypically heterogeneous disorder with a complex genetic architecture. In this study, genomic-relatedness-matrix restricted maximum-likelihood analysis (GREML) was used to investigate the extent to which variance in depression symptoms/symptom dimensions can be explained by variation in common single nucleotide polymorphisms (SNPs) in a sample of individuals with MDD (N = 1,558) who participated in the National Institute of Mental Health Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. A principal components analysis of items from the Hamilton Rating Scale for Depression (HRSD) obtained prior to treatment revealed 4 depression symptom components: (a) appetite, (b) core depression symptoms (e.g., depressed mood, anhedonia), (c) insomnia, and (d) anxiety. These symptom dimensions were associated with SNP-based heritability (hSNP2) estimates of 30%, 14%, 30%, and 5%, respectively. Results indicated that the genetic contribution of common SNPs to depression symptom dimensions were not uniform. Appetite and insomnia symptoms in MDD had a relatively strong genetic contribution whereas the genetic contribution was relatively small for core depression and anxiety symptoms. While in need of replication, these results suggest that future gene discovery efforts may strongly benefit from parsing depression into its constituent parts. (PsycINFO Database Record

  4. Course of major depressive disorder and labor market outcome disruption.

    Science.gov (United States)

    Luo, Zhehui; Cowell, Alexander J; Musuda, Yuta J; Novak, Scott P; Johnson, Eric O

    2010-09-01

    Major depressive disorder (MDD) has been found to be negatively associated with labor market outcomes. However, MDD has many different courses that are chronic or persistent, relapsing and remitting, or limited to a single lifetime episode. Such heterogeneity has been ignored in most past analyses. We examine the impact of heterogeneity in course of MDD on labor market outcomes. Wave I (2001-2002) respondents of the National Epidemiological Survey on Alcohol and Related Conditions - a nationally representative panel survey - were interviewed on average 3 years later (2004-2005). We categorized changes in MDD before and after wave I and before wave II into six courses: incident, recent remission, persistent remission, relapse, persistent depression, and no history of MDD. Odds ratios (ORs) and marginal effects of MDD transitions in multivariable multinomial regressions of labor market outcomes (being out of the labor force, being unemployed, working part-time, and working full-time -- the reference outcome) are reported. Men and women who exhibited persistent remission (2 to 3 years) were equally likely to be in the labor force, employed, and working full-time, compared to those with no history of MDD (reference group). For men, recently remitted MDD (less than 1 year), compared to the reference group, increased the likelihood of being unemployed (3.2% higher probability of being unemployed conditional on being in the labor force; OR = 1.97, 95% confidence interval [CI] = 1.13--3.44) and working part-time (5.8% higher probability of working part-time conditional on being employed; OR = 1.75, 95% CI = 1.10-2.80). For women, no statistically significant effect for recent remission was found. The negative effects of incident onset, relapse, and persistence of MDD were found on some labor market outcomes for men and, to a lesser extent, for women. Clinical treatment for depression should be coordinated and/or integrated with work-related interventions that help

  5. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

    Science.gov (United States)

    Schmaal, L; Veltman, D J; van Erp, T G M; Sämann, P G; Frodl, T; Jahanshad, N; Loehrer, E; Tiemeier, H; Hofman, A; Niessen, W J; Vernooij, M W; Ikram, M A; Wittfeld, K; Grabe, H J; Block, A; Hegenscheid, K; Völzke, H; Hoehn, D; Czisch, M; Lagopoulos, J; Hatton, S N; Hickie, I B; Goya-Maldonado, R; Krämer, B; Gruber, O; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Wright, M J; Hall, G B; MacQueen, G M; Frey, E M; Carballedo, A; van Velzen, L S; van Tol, M J; van der Wee, N J; Veer, I M; Walter, H; Schnell, K; Schramm, E; Normann, C; Schoepf, D; Konrad, C; Zurowski, B; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Sussmann, J E; Godlewska, B R; Cowen, P J; Fischer, F H; Rose, M; Penninx, B W J H; Thompson, P M; Hibar, D P

    2016-06-01

    The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

  6. Consumers with Major Depressive Disorder: Factors Influencing Job Placement

    Science.gov (United States)

    Hergenrather, Kenneth C.; Haase, Eileen; Zeglin, Robert J.; Rhodes, Scott D.

    2013-01-01

    The theory of planned behavior (TPB) was applied to study the factors that influence the intention of public rehabilitation placement professionals to place consumers with major depressive disorder (MDD) in jobs. A sample of 108 public rehabilitation placement professionals in the Mid-Atlantic region of the United States completed the MDD…

  7. Consumers with Major Depressive Disorder: Factors Influencing Job Placement

    Science.gov (United States)

    Hergenrather, Kenneth C.; Haase, Eileen; Zeglin, Robert J.; Rhodes, Scott D.

    2013-01-01

    The theory of planned behavior (TPB) was applied to study the factors that influence the intention of public rehabilitation placement professionals to place consumers with major depressive disorder (MDD) in jobs. A sample of 108 public rehabilitation placement professionals in the Mid-Atlantic region of the United States completed the MDD…

  8. Cognitive inflexibility in obsessive-compulsive disorder and major depression is associated with distinct neural correlates.

    Directory of Open Access Journals (Sweden)

    Peter L Remijnse

    Full Text Available Obsessive-compulsive disorder (OCD and major depressive disorder (MDD are frequently co-morbid, and dysfunctional frontal-striatal circuits have been implicated in both disorders. Neurobiological distinctions between OCD and MDD are insufficiently clear, and comparative neuroimaging studies are extremely scarce. OCD and MDD may be characterized by cognitive rigidity at the phenotype level, and frontal-striatal brain circuits constitute the neural substrate of intact cognitive flexibility. In the present study, 18 non-medicated MDD-free patients with OCD, 19 non-medicated OCD-free patients with MDD, and 29 matched healthy controls underwent functional magnetic resonance imaging during performance of a self-paced letter/digit task switching paradigm. Results showed that both patient groups responded slower relative to controls during repeat events, but only in OCD patients slowing was associated with decreased error rates. During switching, patients with OCD showed increased activation of the putamen, anterior cingulate and insula, whereas MDD patients recruited inferior parietal cortex and precuneus to a lesser extent. Patients with OCD and MDD commonly failed to reveal anterior prefrontal cortex activation during switching. This study shows subtle behavioral abnormalities on a measure of cognitive flexibility in MDD and OCD, associated with differential frontal-striatal brain dysfunction in both disorders. These findings may add to the development of biological markers that more precisely characterize frequently co-morbid neuropsychiatric disorders such as OCD and MDD.

  9. Treat the brain and treat the periphery: toward a holistic approach to major depressive disorder.

    Science.gov (United States)

    Zheng, Xiao; Zhang, Xueli; Wang, Guangji; Hao, Haiping

    2015-05-01

    The limited medication for major depressive disorder (MDD) against an ever-rising disease burden presents an urgent need for therapeutic innovations. During recent years, studies looking at the systems regulation of mental health and disease have shown a remarkably powerful control of MDD by systemic signals. Meanwhile, the identification of a host of targets outside the brain opens the way to treat MDD by targeting systemic signals. We examine these emerging findings and consider the implications for current thinking regarding MDD pathogenesis and treatment. We highlight the opportunities and challenges of a periphery-targeting strategy and propose its incorporation into a holistic approach.

  10. Does intensity or youth affect the neurobiological effect of exercise on major depressive disorder?

    Science.gov (United States)

    Budde, Henning; Velasques, Bruna; Ribeiro, Pedro; Machado, Sergio; Emeljanovas, Arunas; Kamandulis, Sigitas; Skurvydas, Albertas; Wegner, Mirko

    2016-09-28

    The purpose of this commentary is to discuss the different neurobiological effects of exercise on major depressive disorder (MDD) in children and adolescents and to provide additional explanations to this well written systematic review. This commentary highlights the effects of exercise on the hypothalamic-pituitary-adrenal (HPA) axis, which plays a crucial role in MDD. We address the questions of whether age and different exercise intensities may provide additional information on the neurobiological effects of acute or chronic exercise on MDD. Previous findings clearly suggest that the etiology of MDD is complex and multifaceted, involving numerous neurobiological systems, which are additionally influenced by these two factors.

  11. Identification of IL6 as a susceptibility gene for major depressive disorder

    OpenAIRE

    2016-01-01

    Our previous work implied that interleukin 6 (IL6) may be a biological marker for major depressive disorder (MDD). In this study, we performed a comprehensive genetic study to determine the association between the gene encoding IL6 (IL6) and MDD in Han Chinese. There were 50 drug-naïve MDD patients and 50 healthy controls undergoing an mRNA expression study. A sample of 772 patients with MDD and 759 healthy controls were used for genetic analysis. Next, we performed an eQTL analysis to identi...

  12. Parental sexual abuse and suicidal behaviour among women with major depressive disorder

    OpenAIRE

    Çankaya, Banu; Talbot, Nancy L.; Ward, Erin A.; Duberstein, Paul R.

    2012-01-01

    Objective: Women with major depressive disorder (MDD) and childhood sexual abuse histories have an increased risk for suicidal behaviours, but it is unclear whether specific abuse characteristics contribute to risk. We aimed to examine the contributions of abuse characteristics to lifetime history of suicide attempts and multiple suicide attempts, independent of posttraumatic stress disorder and borderline personality disorder. Method: Women with MDD and sexual abuse histories (n = 106) w...

  13. Are Worry and Rumination Specific Pathways Linking Neuroticism and Symptoms of Anxiety and Depression in Patients with Generalized Anxiety Disorder, Major Depressive Disorder and Mixed Anxiety-Depressive Disorder?

    OpenAIRE

    Hipólito Merino; Carmen Senra; Fátima Ferreiro

    2016-01-01

    This study examines the relationships between neuroticism (higher-order vulnerability factor), the cognitive styles of worry, brooding and reflection (second-order vulnerability factors) and symptoms of anxiety and depression in three groups of patients: patients with Generalized Anxiety Disorder (GAD), with Major Depressive Disorder (MDD) and with Mixed Anxiety-Depressive Disorder (MADD). One hundred and thirty four patients completed a battery of questionnaires including measures of neuroti...

  14. Affective personality predictors of disrupted reward learning and pursuit in major depressive disorder.

    Science.gov (United States)

    DelDonno, Sophie R; Weldon, Anne L; Crane, Natania A; Passarotti, Alessandra M; Pruitt, Patrick J; Gabriel, Laura B; Yau, Wendy; Meyers, Kortni K; Hsu, David T; Taylor, Stephen F; Heitzeg, Mary M; Herbener, Ellen; Shankman, Stewart A; Mickey, Brian J; Zubieta, Jon-Kar; Langenecker, Scott A

    2015-11-30

    Anhedonia, the diminished anticipation and pursuit of reward, is a core symptom of major depressive disorder (MDD). Trait behavioral activation (BA), as a proxy for anhedonia, and behavioral inhibition (BI) may moderate the relationship between MDD and reward-seeking. The present studies probed for reward learning deficits, potentially due to aberrant BA and/or BI, in active or remitted MDD individuals compared to healthy controls (HC). Active MDD (Study 1) and remitted MDD (Study 2) participants completed the modified monetary incentive delay task (mMIDT), a behavioral reward-seeking task whose response window parameters were individually titrated to theoretically elicit equivalent accuracy between groups. Participants completed the BI Scale and BA Reward-Responsiveness and Drive Scales. Despite individual titration, active MDD participants won significantly less money than HCs. Higher Reward-Responsiveness scores predicted more won; Drive and BI were not predictive. Remitted MDD participants' performance did not differ from controls', and trait BA and BI measures did not predict r-MDD performance. These results suggest that diminished reward-responsiveness may contribute to decreased motivation and reward pursuit during active MDD, but that reward learning is intact in remission. Understanding individual reward processing deficits in MDD may inform personalized intervention addressing anhedonia and motivation deficits in select MDD patients.

  15. Changes in cognitive symptoms after a buspirone-melatonin combination treatment for Major Depressive Disorder.

    Science.gov (United States)

    Targum, Steven D; Wedel, Pamela C; Fava, Maurizio

    2015-09-01

    Cognitive deficits are often associated with acute depressive episodes and contribute to the functional impairment seen in patients with Major Depressive Disorder (MDD). Many patients sustain residual cognitive deficits after treatment that may be independent of the core MDD disorder. We tracked changes in cognitive deficits relative to antidepressant treatment response using the patient self-rated Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) during a 6-week, double-blind trial of a combination antidepressant treatment (buspirone 15 mg with melatonin-SR 3 mg) versus buspirone (15 mg) monotherapy versus placebo in MDD patients with acute depressive episodes. The CPFQ includes distinct cognitive and physical functioning dimension subscales. Treatment response was determined using the Inventory of Depressive Symptomatology (IDSc30). Treatment responders improved significantly more on the total CPFQ than non-responders (p symptoms and that some aspects of cognition may be specific targets for treatment within a population of patients with MDD.

  16. Italian neurologists' perception on cognitive symptoms in major depressive disorder.

    Science.gov (United States)

    Neri, G; Serrati, C; Zolo, P; Cataldo, N; Ripellino, C

    2016-09-01

    The assessment of cognition is an important part of major depressive disorder (MDD) evaluation and a crucial issue is the physicians' perception of cognitive dysfunction in MDD that remains nowadays a little known matter. The present study aims at investigating the understanding of neurologists' perception about cognitive dysfunction in MDD. An on-line survey addressed to 85 Italian neurologists in the period between May and June 2015 was performed. The questionnaire comprised three sections: the first section collecting information on neurologists' socio-demographic profile, the second investigating cognitive symptoms relevance in relation with different aspects and the third one explicitly focusing on cognitive symptoms in MDD. Cognitive symptoms are considered most significant among DSM-5 symptoms to define the presence of a Major Depressive Episode in a MDD, to improve antidepressant therapy adherence, patients' functionality and concurrent neurological condition, once resolved. Furthermore, an incongruity came to light from this survey: the neurologists considered cognitive symptoms a not relevant aspect to choose the antidepressant treatment in comparison with the other DSM-5 symptoms on one side, but they declared the opposite in the third part of the questionnaire focused on cognitive symptoms. Cognitive symptoms appeared to be a relevant aspect in MDD and neurologists have a clear understanding of this issue. Nevertheless, the discrepancy between neurologists' perception on cognitive symptoms and the antidepressant treatment highlights the feeling of an unmet need that could be filled increasing the awareness of existing drugs with pro-cognitive effects.

  17. Discrimination, arrest history, and major depressive disorder in the U.S. Black population.

    Science.gov (United States)

    Anglin, Deidre M; Lighty, Quenesha; Yang, Lawrence H; Greenspoon, Michelle; Miles, Rashun J; Slonim, Tzachi; Isaac, Kathleen; Brown, Monique J

    2014-09-30

    Everyday discrimination contributes negatively to depressive symptomatology among Blacks in the US and being arrested could add to this depression. Using data from the National Survey on American Life, the present study determined the association between an arrest history and major depressive disorder (MDD), while accounting for discrimination among African Americans, US-born Afro-Caribbeans and first-generation Black immigrants. Findings from logistic regression analyses adjusted for discrimination suggested an arrest history is associated with 12-month MDD (Adjusted OR=1.47; 95% CI=1.02-2.10) and lifetime MDD (Adjusted OR=1.56 CI=1.17-2.09). Accounting for drug and alcohol dependence attenuated the association between arrest history and 12-month MDD, but not lifetime MDD. The associations between arrest history and both 12-month and lifetime MDD, and discrimination and lifetime MDD varied by ethnic/immigrant group. Specifically, while the association between arrest history and MDD (both 12-month and lifetime) was strongest among US-born Afro-Caribbeans, evidence consistent with the immigrant paradox, the association between discrimination and lifetime MDD was particularly relevant for first-generation Black immigrants, suggesting discrimination may hinder the protection of first-generation status. Mental health prevention and treatment programs should target the stress associated with being arrested and experiencing discrimination among US Blacks. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Repetitive transcranial magnetic stimulation for treatment of major depressive disorder with comorbid generalized anxiety disorder.

    Science.gov (United States)

    White, Daniela; Tavakoli, Sason

    2015-08-01

    Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in treating individuals with behavioral disorders such as major depressive disorder (MDD), posttraumatic stress disorder, obsessive-compulsive disorder, and social anxiety disorder. A number of applications of rTMS to different regions of the left and right prefrontal cortex have been used to treat these disorders, but no study of treatment for MDD with generalized anxiety disorder (GAD) has been conducted with application of rTMS to both the left and right prefrontal cortex. We hypothesized that applying low-frequency rTMS to the right dorsolateral prefrontal cortex (DLPFC) before applying it to the left DLPFC for the treatment of depression would be anxiolytic in patients with MDD with GAD. Thirteen adult patients with comorbid MDD and GAD received treatment with rTMS in an outpatient setting. The number of treatments ranged from 24 to 36 over 5 to 6 weeks. Response was defined as a ≥ 50% reduction in symptoms from baseline, and remission was defined as a score of depressive symptoms on the 21-item Hamilton Rating Scale for Depression (HAM-D-21). At the end of the treatment period, for the GAD-7 scale, 11 out of 13 (84.6%) patients' anxiety symptoms were in remission, achieving a score of depressive symptoms. In this small pilot study of 13 patients with comorbid MDD and GAD, significant improvement in anxiety symptoms along with depressive symptoms was achieved in a majority of patients after bilateral rTMS application.

  19. Is plasminogen activator inhibitor-1 a physiological bottleneck bridging major depressive disorder and cardiovascular disease?

    Science.gov (United States)

    Savoy, C; Van Lieshout, R J; Steiner, M

    2016-06-01

    Major depressive disorder (MDD) is estimated to affect one in twenty people worldwide. MDD is highly comorbid with cardiovascular disease (CVD), itself one of the single largest causes of mortality worldwide. A number of pathological changes observed in MDD are believed to contribute to the development of cardiovascular disease, although no single mechanism has been identified. There are also no biological markers capable of predicting the future risk of developing heart disease in depressed individuals. Plasminogen activator inhibitor-1 (PAI-1) is a prothrombotic plasma protein secreted by endothelial tissue and has long been implicated in CVD. An expanding body of literature has recently implicated it in the pathogenesis of major depressive disorder as well. In this study, we review candidate pathways implicating MDD in CVD and consider how PAI-1 might act as a mediator by which MDD induces CVD development: chiefly through sleep disruption, adiposity, brain-derived neurotrophic factor (BDNF) metabolism, systemic inflammation and hypothalamic-pituitary-adrenal (HPA)-axis dysregulation. As both MDD and CVD are more prevalent in women than in men, and incidence of either condition is dramatically increased during reproductive milestones, we also explore hormonal and sex-specific associations between MDD, PAI-1 and CVD. Of special interest is the role PAI-1 plays in perinatal depression and in cardiovascular complications of pregnancy. Finally, we propose a theoretical model whereby PAI-1 might serve as a useful biomarker for CVD risk in those with depression, and as a potential target for future treatments.

  20. DEPRESSIVE DISORDERS IN EPILEPSY

    Directory of Open Access Journals (Sweden)

    Koralia Todorova

    2010-11-01

    Full Text Available Depressive disorders are the most frequent psychiatric comorbidity in epilepsy but very often remain unrecognized and untreated. We examined 103 epileptic patients, aged 18-60 years, 40 males and 63 females, for the presence of interictal depressive disorder. All subjects underwent clinical psychiatric examination, including evaluation on Hamilton Depression Rating Scale (HAM-D-17. A questionnaire for demographic and seizure-related variables was also completed. Concurrent depressive disorder (clinically presented according to ICD-10 diagnostic criteria affected 28.3% of all evaluated patients. Based on HAM-D-17 scores depression was defined as mild - 80% of all depressed patients, moderate - 17% and severe - 3%. Atypical presentation of interictal depressive disorder was frequent. Depression has a tremendous effect on one’s family, social and psychological functioning, even more than the actual seizure frequency and severity. Diagnostic difficulties come through the atypical mode of presentation of depressive disorders in epilepsy. Proper neuropsychiatric evaluation is essential for improving treatment and quality of life for patients with epilepsy.

  1. Blood-based gene expression profiles models for classification of subsyndromal symptomatic depression and major depressive disorder.

    Science.gov (United States)

    Yi, Zhenghui; Li, Zezhi; Yu, Shunying; Yuan, Chengmei; Hong, Wu; Wang, Zuowei; Cui, Jian; Shi, Tieliu; Fang, Yiru

    2012-01-01

    Subsyndromal symptomatic depression (SSD) is a subtype of subthreshold depressive and also lead to significant psychosocial functional impairment as same as major depressive disorder (MDD). Several studies have suggested that SSD is a transitory phenomena in the depression spectrum and is thus considered a subtype of depression. However, the pathophysioloy of depression remain largely obscure and studies on SSD are limited. The present study compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD, and matched controls (8 subjects in each group). Support vector machines (SVMs) were utilized for training and testing on candidate signature expression profiles from signature selection step. Firstly, we identified 63 differentially expressed SSD signatures in contrast to control (Pbiomarkers for SSD and MDD together, we selected top gene signatures from each group of pair-wise comparison results, and merged the signatures together to generate better profiles used for clearly classify SSD and MDD sets in the same time. In details, we tried different combination of signatures from the three pair-wise compartmental results and finally determined 48 gene expression signatures with 100% accuracy. Our finding suggested that SSD and MDD did not exhibit the same expressed genome signature with peripheral blood leukocyte, and blood cell-derived RNA of these 48 gene models may have significant value for performing diagnostic functions and classifying SSD, MDD, and healthy controls.

  2. Explaining heterogeneity in disability associated with current major depressive disorder: effects of illness characteristics and comorbid mental disorders.

    Science.gov (United States)

    van der Werff, E; Verboom, C E; Penninx, B W J H; Nolen, W A; Ormel, J

    2010-12-01

    Although major depressive disorder (MDD) is associated with disability, some persons do function well despite their illness. Aim of the present study was to examine the effect of illness characteristics and comorbid mental disorders on various aspects of disability among persons with a current MDD episode. Data were derived from 607 participants with a current MDD based on the Composite International Diagnostic Interview (CIDI). Severity was assessed via the Inventory of Depressive Symptoms self-report (IDS-SR). For disability three outcome measures were used: World Health Organization Disability Assessment Schedule II (WHODAS) disability and its 7 dimensions, days out of role, and work absence. Using multiple regression analysis the effects of MDD characteristics and comorbid mental disorders were estimated. The IDS-SR score was the best predictor of all disability outcomes. Of the comorbid mental disorders, agoraphobia was significantly associated with overall disability. Collectively, all illness characteristics accounted for 43% of variance in WHODAS disability, 13% in days out of role and 10% in work absence, suggesting substantial unexplained variance. Only self-report measures of disability were used. There were no assessments of other diagnoses than depressive, anxiety and alcohol use disorders. Although heterogeneity in disability of persons with current MDD is partially explained by illness characteristics of MDD (especially symptom severity) and comorbid mental disorders, most of the variance is not accounted for. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. 'Hot' cognition in major depressive disorder: a systematic review.

    Science.gov (United States)

    Miskowiak, Kamilla W; Carvalho, Andre F

    2014-01-01

    Major depressive disorder (MDD) is associated with significant cognitive dysfunction in both 'hot' (i.e. emotion-laden) and 'cold' (non-emotional) domains. Here we review evidence pertaining to 'hot' cognitive changes in MDD. This systematic review searched the PubMed and PsycInfo computerized databases in May 2014 augmented by hand searches of reference lists. We included original articles in which MDD participants (or their healthy first-degree relatives) and a healthy control group were compared on standard measures of emotional processing or reward/ punishment processing as well as systematic reviews and meta-analyses. A total of 116 articles met the inclusion criteria of which 97 were original studies. Negative biases in perception, attention and memory for emotional information, and aberrant reward/punishment processing occur in MDD. Imbalanced responses to negative stimuli in a fronto-limbic network with hyper-activity in limbic and ventral prefrontal regions paired with hypo-activity of dorsal prefrontal regions subserve these abnormalities. A cross-talk of 'hot' and 'cold' cognition disturbances in MDD occurs. Disturbances in 'hot cognition' may also contribute to the perpetuation of negative emotional states in MDD. Limited success in the identification of susceptibility genes in MDD has led to great research interest in identifying vulnerability biomarkers or endophenotypes. Emerging evidence points to the persistence of 'hot' cognition dysfunction during remission and to subtle 'hot' cognition deficits in healthy relatives of patients with MDD. Taken together, these findings suggest that abnormalities in 'hot' cognition may constitute a candidate neurocognitive endophenotype for depression.

  4. Functional Magnetic Resonance Imaging Correlates of Emotional Word Encoding and Recognition in Depression and Anxiety Disorders

    NARCIS (Netherlands)

    van Tol, Marie-Jose; Demenescu, Liliana R.; van der Wee, Nic J. A.; Kortekaas, Rudle; Nielen, Marjan M. A.; Den Boer, J. A.; Renken, Remco J.; van Buchem, Mark A.; Zitman, Frans G.; Aleman, Andre; Veltman, Dick J.

    2012-01-01

    Background: Major depressive disorder (MDD), panic disorder, and social anxiety disorder are among the most prevalent and frequently co-occurring psychiatric disorders in adults and may be characterized by a common deficiency in processing of emotional information. Methods: We used functional magnet

  5. Gene expression-based biological test for major depressive disorder: an advanced study

    Science.gov (United States)

    Watanabe, Shin-ya; Numata, Shusuke; Iga, Jun-ichi; Kinoshita, Makoto; Umehara, Hidehiro; Ishii, Kazuo; Ohmori, Tetsuro

    2017-01-01

    Purpose Recently, we could distinguished patients with major depressive disorder (MDD) from nonpsychiatric controls with high accuracy using a panel of five gene expression markers (ARHGAP24, HDAC5, PDGFC, PRNP, and SLC6A4) in leukocyte. In the present study, we examined whether this biological test is able to discriminate patients with MDD from those without MDD, including those with schizophrenia and bipolar disorder. Patients and methods We measured messenger ribonucleic acid expression levels of the aforementioned five genes in peripheral leukocytes in 17 patients with schizophrenia and 36 patients with bipolar disorder using quantitative real-time polymerase chain reaction (PCR), and we combined these expression data with our previous expression data of 25 patients with MDD and 25 controls. Subsequently, a linear discriminant function was developed for use in discriminating between patients with MDD and without MDD. Results This expression panel was able to segregate patients with MDD from those without MDD with a sensitivity and specificity of 64% and 67.9%, respectively. Conclusion Further research to identify MDD-specific markers is needed to improve the performance of this biological test. PMID:28260899

  6. The Impact of a Single Nucleotide Polymorphism in SIGMAR1 on Depressive Symptoms in Major Depressive Disorder and Bipolar Disorder.

    Science.gov (United States)

    Mandelli, Laura; Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Patkar, Ashwin A; Masand, Prakash S; Pae, Chi-Un; Serretti, Alessandro

    2017-03-01

    Ample evidence suggested a role of sigma-1 receptor in affective disorders since the interaction of numerous antidepressants with sigma receptors was discovered. A recent study on Japanese subjects found a genetic variant within the encoding gene SIGMAR1 (rs1800866A>C) associated with major depressive disorder (MDD). We aimed to evaluate the same polymorphism in both MDD and bipolar disorder (BD) as well as its relationship to response to treatment with antidepressants and mood stabilizers. A total of 238 MDD patients treated for an acute episode of depression, 132 BD patients in treatment with mood stabilizers for a manic or mixed episode, and 324 controls were genotyped for rs1800866. At discharge, response to treatments was evaluated in MDD and BD patients by the Hamilton Rating Scale for Depression (HRSD) and the Young Mania Rating Score (YMRS), respectively. In our Korean sample, allele frequencies were different from those reported in other Asian and non-Asian populations. The CC genotype was associated with BD and, as a trend, with MDD. No significant effect was observed on response to antidepressants in MDD or mood stabilizers in BD, although the CC genotype was more frequent among BD patients experiencing a mixed episode. The present findings are the first to propose the putative role of genetic variants within SIGMAR1 and sigma-1 receptor in BD. Sigma-1 receptor can modulate a number of central neurotransmitter systems as well as some other signaling pathways (e.g., neurotrophin and growth factor signaling) which are seemingly involved in BD and other mood disorders.

  7. Altered choroid plexus gene expression in major depressive disorder

    Directory of Open Access Journals (Sweden)

    Cortney Ann Turner

    2014-04-01

    Full Text Available Given the emergent interest in biomarkers for mood disorders, we assessed gene expression in the choroid plexus, the region that produces cerebrospinal fluid (CSF, in individuals with major depressive disorder (MDD. Genes that are expressed in the choroid plexus (CP can be secreted into the CSF and may be potential biomarker candidates. Given that we have previously shown that fibroblast growth factor family members are differentially expressed in post-mortem brain of subjects with MDD and the CP is a known source of growth factors in the brain, we posed the question whether growth factor dysregulation would be found in the CP of subjects with MDD. We performed laser capture microscopy of the choroid plexus at the level of the hippocampus in subjects with MDD and psychiatrically normal controls. We then extracted, amplified, labeled and hybridized the cRNA to Illumina BeadChips to assess gene expression. In controls, the most highly abundant known transcript was transthyretin. Moreover, half of the 14 most highly expressed transcripts in controls encode ribosomal proteins. Using BeadStudio software, we identified 169 transcripts differentially expressed (p< 0.05 between control and MDD samples. Using pathway analysis we noted that the top network altered in subjects with MDD included multiple members of the transforming growth factor-beta (TGFβ pathway. Quantitative real-time PCR (qRT-PCR confirmed downregulation of several transcripts that interact with the extracellular matrix in subjects with MDD. These results suggest that there may be an altered cytoskeleton in the choroid plexus in MDD subjects that may lead to a disrupted blood-CSF-brain barrier.

  8. Differential co-expression and regulation analyses reveal different mechanisms underlying major depressive disorder and subsyndromal symptomatic depression.

    Science.gov (United States)

    Xu, Fan; Yang, Jing; Chen, Jin; Wu, Qingyuan; Gong, Wei; Zhang, Jianguo; Shao, Weihua; Mu, Jun; Yang, Deyu; Yang, Yongtao; Li, Zhiwei; Xie, Peng

    2015-04-03

    Recent depression research has revealed a growing awareness of how to best classify depression into depressive subtypes. Appropriately subtyping depression can lead to identification of subtypes that are more responsive to current pharmacological treatment and aid in separating out depressed patients in which current antidepressants are not particularly effective. Differential co-expression analysis (DCEA) and differential regulation analysis (DRA) were applied to compare the transcriptomic profiles of peripheral blood lymphocytes from patients with two depressive subtypes: major depressive disorder (MDD) and subsyndromal symptomatic depression (SSD). Six differentially regulated genes (DRGs) (FOSL1, SRF, JUN, TFAP4, SOX9, and HLF) and 16 transcription factor-to-target differentially co-expressed gene links or pairs (TF2target DCLs) appear to be the key differential factors in MDD; in contrast, one DRG (PATZ1) and eight TF2target DCLs appear to be the key differential factors in SSD. There was no overlap between the MDD target genes and SSD target genes. Venlafaxine (Efexor™, Effexor™) appears to have a significant effect on the gene expression profile of MDD patients but no significant effect on the gene expression profile of SSD patients. DCEA and DRA revealed no apparent similarities between the differential regulatory processes underlying MDD and SSD. This bioinformatic analysis may provide novel insights that can support future antidepressant R&D efforts.

  9. The role of obsessive beliefs in patients with major depressive disorder.

    Science.gov (United States)

    Bahceci, Bulent; Bagcioglu, Erman; Celik, Fatmagül Helvacı; Polat, Selim; Koroglu, Ayşe; Kandemir, Gökhan; Hocaoglu, Cicek

    2014-01-01

    The aim of this study is to evaluate the differences in obsessional beliefs between patients with major depressive disorder (MDD) and matched healthy controls using the obsessive-beliefs questionnaire (OBQ). The study sample included 74 outpatients with MDD and 74 healthy subjects. The two groups were matched for age, gender, and education level. The diagnoses were based on the Diagnostic and Statistical Manual of Mental Disorder (DSM-IV). The severity of depression was measured with the Hamilton Depression Rating Scale (HAM-D). All participants filled out the 44-item OBQ. The total and subscale OBQ scores [Responsibility/Threat Estimation (RT), Perfectionism/Certainly (PC), and Importance/Control of Thoughts (ICT)], were significantly higher in patients with MDD than those of the control group. There was a positive correlation between HAM-D scores and the OBQ subscale scores (RT, PC, and ICT) in the patients. Obsessional beliefs appear to be related to MDD.

  10. Premorbid risk factors for major depressive disorder: are they associated with early onset and recurrent course?

    Science.gov (United States)

    Wilson, Sylia; Vaidyanathan, Uma; Miller, Michael B; McGue, Matt; Iacono, William G

    2014-11-01

    Premorbid risk for major depressive disorder (MDD) and predictors of an earlier onset and recurrent course were examined in two studies in a large, community-based sample of parents and offspring, prospectively assessed from late childhood into adulthood. In Study 1 (N = 2,764 offspring and their parents), parental psychiatric status, offspring personality at age 11, and age 11 offspring internalizing and externalizing symptoms predicted the subsequent development of MDD, as did poor quality parent-child relationships, poor academic functioning, early pubertal development, and childhood maltreatment by age 11. Parental MDD and adult antisocial behavior, offspring negative emotionality and disconstraint, externalizing symptoms, and childhood maltreatment predicted an earlier onset of MDD, after accounting for course; lower positive emotionality, trait anxiety, and childhood maltreatment predicted recurrent MDD, after accounting for age of onset. In Study 2 (N = 7,146), we examined molecular genetic risk for MDD by extending recent reports of associations with glutamatergic system genes. We failed to confirm associations with MDD using either individual single nucleotide polymorphism based tests or gene-based analyses. Overall, results speak to the pervasiveness of risk for MDD, as well as specific risk for early onset MDD; risk for recurrent MDD appears to be largely a function of its often earlier onset.

  11. Affective Priming in Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Joelle eLeMoult

    2012-10-01

    Full Text Available Research on cognitive biases in depression has provided considerable evidence for the impact of emotion on cognition. Individuals with depression tend to preferentially process mood-congruent material and to show deficits in the processing of positive material leading to biases in attention, memory, and judgments. More research is needed, however, to fully understand which cognitive processes are affected. The current study further examines the impact of emotion on cognition using a priming design with facial expressions of emotion. Specifically, this study tested whether the presentation of facial expressions of emotion affects subsequent processing of affective material in participants with major depressive disorder (MDD and healthy controls (CTL. Facial expressions displaying happy, sad, angry, disgusted, or neutral expressions were presented as primes for 500ms, and participants’ speed to identify a subsequent target’s emotional expression was assessed. All participants displayed greater interference from emotional versus neutral primes, marked by slower response times to judge the emotion of the target face when it was preceded by an emotional prime. Importantly, the CTL group showed the strongest interference when happy emotional expressions served as primes whereas the MDD group failed to show this bias. These results add to a growing literature that shows that depression is associated with difficulties in the processing of positive material.

  12. Discrimination in the workplace, reported by people with major depressive disorder : A cross-sectional study in 35 countries

    NARCIS (Netherlands)

    Brouwers, E.P.M.; Mathijssen, J.J.P.; van Boxtel, T.; Knifton, L.; Wahlbeck, K.; Van Audenhove, C.; Kadri, N.; Chang, Ch.; Goud, B.R.; Ballester, D.; Tófoli, L.F.; Bello, R.; Jorge-Monteiro, M.F.; Zäske, H.; Milacic, I.; Uçok, A.; Lasalvia, A.; Thornicroft, G.; van Weeghel, J.

    2016-01-01

    Objective: Whereas employment has been shown to be beneficial for people with Major Depressive Disorder (MDD) across different cultures, employers’ attitudes have been shown to be negative towards workers with MDD. This may form an important barrier to work participation. Today, little is known abou

  13. Successful emotion regulation skills application predicts subsequent reduction of symptom severity during treatment of major depressive disorder

    NARCIS (Netherlands)

    Radkovsky, Anna; McArdle, John J; Bockting, Claudi L H; Berking, Matthias

    2014-01-01

    OBJECTIVE: Deficits in emotion regulation (ER) skills are considered a putative maintaining factor for major depressive disorder (MDD) and hence a promising target in the treatment of MDD. However, to date, the association between the successful application of arguably adaptive ER skills and changes

  14. Mindfulness, Quality of Life, and Severity of Depressive Symptoms Among Patients With Schizophrenia and Patients With Major Depressive Disorder.

    Science.gov (United States)

    Rayan, Ahmad Hussien Rateb

    2017-05-01

    The current study used a descriptive correlational design to examine the relationship between mindfulness and quality of life (QOL) among patients with schizophrenia (n = 160) and patients with major depressive disorder (MDD) (n = 161), controlling for demographic and clinical variables. Participants completed self-reported questionnaires regarding demographic variables, severity of depression, QOL, and mindfulness. Patients diagnosed with MDD had higher mindfulness scores than patients diagnosed with schizophrenia. Mindfulness scores were significantly associated with the severity of depression among participants. After controlling for the demographic variables and severity of depressive symptoms, mindfulness had a unique variance in QOL among patients with schizophrenia, but not among patients with MDD. The current study provides preliminary evidence regarding the role of mindfulness in improving depressive symptoms and the overall QOL among patients diagnosed with mental illness. [Journal of Psychosocial Nursing and Mental Health Services, 55(5), 40-50.]. Copyright 2017, SLACK Incorporated.

  15. Desvenlafaxine succinate for the treatment of major depressive disorder.

    Science.gov (United States)

    Lohoff, Falk W; Rickels, Karl

    2008-08-01

    Major depressive disorder (MDD) remains one of the most common psychiatric disorders with high morbidity and mortality. Effective treatment is limited and response/remission to antidepressant pharmacotherapy remains poor and unpredictable. The development of new antidepressants is thus of great importance to the field. Desvenlafaxine succinate (DVS) is the active metabolite of the serotonin and noradrenaline re-uptake inhibitor venlafaxine and was recently FDA approved for the treatment of MDD. DVS showed efficacy in clinical trials in MDD with doses ranging from 50 - 400 mg. Advantages compared to other antidepressants include once daily dosing at effective doses, no CYP450 metabolism and low drug-drug interactions. Concerns include side effect profile and moderate efficacy. DVS might be a useful addition to the arsenal of antidepressants available to the clinician. Additional studies, in particular head-to-head comparison to other antidepressants and long-term treatment studies, will be necessary to comprehensively evaluate DVS safety and efficacy for clinical practice.

  16. Brief report: Overgeneral autobiographical memory in adolescent major depressive disorder.

    Science.gov (United States)

    Champagne, Katelynn; Burkhouse, Katie L; Woody, Mary L; Feurer, Cope; Sosoo, Effua; Gibb, Brandon E

    2016-10-01

    The current study examined whether overgeneral autobiographical memory (OGM) bias serves as a state-like marker of major depressive disorder (MDD) in adolescence or whether it would also be observed in currently nondepressed adolescents with a history of MDD. We examined differences in OGM to positive and negative cue words between adolescents (aged 11-18 years) with current MDD (n = 15), remitted MDD (n = 25), and no history of any depressive disorder (n = 25). Youth and their parents were administered a structured diagnostic interview and adolescents completed the autobiographical memory test. Compared to never depressed adolescents, adolescents with current or remitted MDD recalled less specific memories in response to positive and negative cue words. The difference between the two MDD groups was small and nonsignificant. These findings suggest that OGM is not simply a state-like marker in currently depressed adolescents, but is also evident in adolescents with remitted MDD, indicating that it may represent a trait-like vulnerability that increases risk for relapse.

  17. Effectiveness and cost-effectiveness of transmural collaborative care with consultation letter (TCCCL) and duloxetine for major depressive disorder (MDD) and (sub)chronic pain in collaboration with primary care: design of a randomized placebo-controlled multi-Centre trial: TCC:PAINDIP

    NARCIS (Netherlands)

    E. de Heer (Eric); J.J.M. Dekker (Jack); J.F. van Eck van der Sluijs (Jonna); A.T.F. Beekman (Aartjan); H.W. van Marwijk (Harm); T. Holwerda (Tjalling); P.M. Bet (Pierre); J. Roth (Joost); L. van Hakkaart-van Roijen (Leona); L. Ringoir (Lianne); F. Kat (Fiona); C.M. van der Feltz-Cornelis (Christina)

    2013-01-01

    markdownabstract__Abstract__ Background: The comorbidity of pain and depression is associated with high disease burden for patients in terms of disability, wellbeing, and use of medical care. Patients with major and minor depression often present themselves with pain to a general practitioner and r

  18. Misdiagnosis of bipolar disorder in children and adolescents: a comparison with ADHD and major depressive disorder.

    Science.gov (United States)

    Chilakamarri, Jagan K; Filkowski, Megan M; Ghaemi, S Nassir

    2011-02-01

    Controversy surrounds the frequency of underdiagnosis vs overdiagnosis of bipolar disorder (BD) in children and adolescents compared with diagnoses of attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD). Sixty-four children and adolescents (age 7 to 18) treated in a community setting were systematically assessed for diagnostic and treatment histories. Best estimate consensus diagnosis was made using DSM-IV criteria. ADHD was overdiagnosed (all patients with ADHD had received the diagnosis, as did 38% of patients with MDD and 29% of patients with BD, respectively), while MDD was partially underdiagnosed and partially overdiagnosed (57% of MDD patients received the diagnosis, 43% did not; 33% of patients with BD were incorrectly diagnosed with MDD). BD was underdiagnosed, not overdiagnosed (38% received the diagnosis, 62% did not; BD was not diagnosed in the ADHD sample, and in only 5% of the patients with MDD). The absence of a positive family history predicted misdiagnosis of BD (relative risk = 2.48, 95% confidence interval 1.10 to 5.56). Observational treatment response to stimulants was equally high in all groups (75% to 82%). In the first controlled study on this topic, BD was not over-diagnosed in children and adolescents, as it is often claimed, and ADHD was. Stimulant response was nonspecific and diagnostically uninformative. Studies with larger samples are needed to replicate or refute these results.

  19. Disorder-specific characteristics of borderline personality disorder with co-occurring depression and its comparison with major depression: An fMRI study with emotional interference task

    Directory of Open Access Journals (Sweden)

    Natalia Chechko

    2016-01-01

    Thus, our data indicate dysfunctionality in the neural circuitry responsible for emotional conflict control in both disorders. The enhanced visual cortex activation in BPD + MDD suggests the visual system's hyperresponsiveness to faces at an early perceptual level. Not being associated with co-occurring depression, this effect in BPD + MDD appears to represent specific personality traits such as disturbed reactivity toward emotionally expressive facial stimuli.

  20. Mania and depression in the perinatal period among women with a history of major depressive disorders

    Science.gov (United States)

    Inglis, Angela J; Hippman, Catriona L; Carrion, Prescilla B; Honer, William G; Austin, Jehannine C

    2014-01-01

    Background Women with a history of major depressive disorder (MDD) have increased risks for postpartum depression, but less is known about postpartum mania in this population. Objectives To prospectively determine the frequency with which mania occurs in the postpartum among women who have a history of MDD, and to explore temporal relationships between onset of mania/hypomania and depression. Methods We administered the Structured Clinical Interview for DSM IV disorders (SCID) to pregnant women with a self-reported history of MDD to confirm diagnosis and exclude women with any history of mania/hypomania. Participants completed the Edinburgh Postnatal Depression Scale (EPDS) and Altman Self-Rated Mania scale (ASRM): once during the pregnancy (~26 weeks), and one week, one month, and three months postpartum. Results Among women (N=107) with a SCID-confirmed diagnosis of MDD, 34.6% (n=37) experienced mania/hypomania (defined by an ASRM score of ≥6) at ≥1 timepoint during the postpartum: and for just over half (20/37, 54%), onset was during the postpartum. The highest frequency of mania/hypomania (26.4%, n=26) was at one week postpartum. Women who experienced mania/hypomania at one week postpartum had significantly more symptoms of mania/hypomania later in the postpartum. Conclusion A substantive proportion of women with a history of MDD may experience first onset of mania/hypomania symptoms in the early postpartum, others may experience first onset during pregnancy. Taken with other recent data, these findings suggest a possible rationale for screening women with a history of MDD for mania/hypomania during the early postpartum period, but issues with screening instruments are discussed. PMID:24402681

  1. Molecular and Genetic Characterization of Depression: Overlap with other Psychiatric Disorders and Aging.

    Science.gov (United States)

    Ding, Ying; Chang, Lun-Ching; Wang, Xingbin; Guilloux, Jean-Philippe; Parrish, Jenna; Oh, Hyunjung; French, Beverly J; Lewis, David A; Tseng, George C; Sibille, Etienne

    2015-05-01

    Genome-wide expression and genotyping technologies have uncovered the genetic bases of complex diseases at unprecedented rates; However despite its heavy burden and high prevalence, the molecular characterization of major depressive disorder (MDD) has lagged behind. Transcriptome studies report multiple brain disturbances but are limited by small sample sizes. Genome-wide association studies (GWAS) report weak results but suggest overlapping genetic risk with other neuropsychiatric disorders. We performed systematic molecular characterization of altered brain function in MDD, using meta-analysis of differential expression in eight gene array studies in three corticolimbic brain regions in 101 subjects. The identified "metaA-MDD" genes suggest altered neurotrophic support, brain plasticity and neuronal signaling in MDD. Notably, metaA-MDD genes display low connectivity and hubness in coexpression networks, and uniform genomic distribution, consistent with diffuse polygenic mechanisms. We next integrated these findings with results from over 1800 published GWAS and show that genetic variations nearby metaA-MDD genes predict greater risk for neuropsychiatric disorders and notably for age-related phenotypes, but not for other medical illnesses, including those frequently co-morbid with depression, or body characteristics. Collectively, the intersection of unbiased investigations of gene function (transcriptome) and structure (GWAS) provides novel leads to investigate molecular mechanisms of MDD and suggest common biological pathways between depression, other neuropsychiatric diseases, and brain aging.

  2. Number needed to treat to harm for discontinuation due to adverse events in the treatment of bipolar depression, major depressive disorder, and generalized anxiety disorder with atypical antipsychotics.

    Science.gov (United States)

    Gao, Keming; Kemp, David E; Fein, Elizabeth; Wang, Zuowei; Fang, Yiru; Ganocy, Stephen J; Calabrese, Joseph R

    2011-08-01

    To estimate the number needed to treat to harm (NNTH) for discontinuation due to adverse events with atypical antipsychotics relative to placebo during the treatment of bipolar depression, major depressive disorder (MDD), and generalized anxiety disorder (GAD). English-language literature published and cited in MEDLINE from January 1966 to May 2009 was searched with the terms antipsychotic, atypical antipsychotic, generic and brand names of atypical antipsychotics, safety, tolerability, discontinuation due to adverse events, somnolence, sedation, weight gain, akathisia, or extrapyramidal side effect; and bipolar depression, major depressive disorder, or generalized anxiety disorder; and randomized, placebo-controlled clinical trial. This search was augmented with a manual search. Studies with a cumulative sample of ≥ 100 patients were included. The NNTHs for discontinuation due to adverse events, somnolence, sedation, ≥ 7% weight gain, and akathisia relative to placebo were estimated with 95% confidence intervals to reflect the magnitude of variance. Five studies in bipolar depression, 10 studies in MDD, and 4 studies in GAD were identified. Aripiprazole and olanzapine have been studied in bipolar depression and refractory MDD. Only quetiapine extended release (quetiapine-XR) has been studied in 3 psychiatric conditions with different fixed dosing schedules. For aripiprazole, the mean NNTH for discontinuation due to adverse events was 14 in bipolar depression, but was not significantly different from placebo in MDD. For olanzapine, the mean NNTHs were 24 in bipolar depression and 9 in MDD. The risk for discontinuation due to adverse events during quetiapine-XR treatment appeared to be associated with dose. For quetiapine-XR 300 mg/d, the NNTHs for discontinuation due to adverse events were 9 for bipolar depression, 8 for refractory MDD, 9 for MDD, and 5 for GAD. At the same dose of quetiapine-XR, patients with GAD appeared to have a lower tolerability than

  3. Blood-based gene expression profiles models for classification of subsyndromal symptomatic depression and major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Zhenghui Yi

    Full Text Available Subsyndromal symptomatic depression (SSD is a subtype of subthreshold depressive and also lead to significant psychosocial functional impairment as same as major depressive disorder (MDD. Several studies have suggested that SSD is a transitory phenomena in the depression spectrum and is thus considered a subtype of depression. However, the pathophysioloy of depression remain largely obscure and studies on SSD are limited. The present study compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD, and matched controls (8 subjects in each group. Support vector machines (SVMs were utilized for training and testing on candidate signature expression profiles from signature selection step. Firstly, we identified 63 differentially expressed SSD signatures in contrast to control (P< = 5.0E-4 and 30 differentially expressed MDD signatures in contrast to control, respectively. Then, 123 gene signatures were identified with significantly differential expression level between SSD and MDD. Secondly, in order to conduct priority selection for biomarkers for SSD and MDD together, we selected top gene signatures from each group of pair-wise comparison results, and merged the signatures together to generate better profiles used for clearly classify SSD and MDD sets in the same time. In details, we tried different combination of signatures from the three pair-wise compartmental results and finally determined 48 gene expression signatures with 100% accuracy. Our finding suggested that SSD and MDD did not exhibit the same expressed genome signature with peripheral blood leukocyte, and blood cell-derived RNA of these 48 gene models may have significant value for performing diagnostic functions and classifying SSD, MDD, and healthy controls.

  4. Early Maladaptive Schemas: A Comparison Between Bipolar Disorder and Major Depressive Disorder.

    Science.gov (United States)

    Nilsson, Kristine Kahr; Nielsen Straarup, Krista; Halvorsen, Marianne

    2015-01-01

    It is still unclear how bipolar disorder (BD) differentiates from major depressive disorder (MDD) outside major mood episodes. To further elucidate this area, the present study compared the two mood disorders in terms of early maladaptive schemas (EMSs) during remission. The sample consisted of 49 participants with BD and 30 participants with MDD who were currently in remission. The participants completed the Young Schema Questionnaire. The BD group scored significantly higher than the MDD group on seven EMSs: abandonment, failure to achieve, insufficient self-control, subjugation, unrelenting standards, enmeshment and entitlement. By suggesting that EMSs are more severe in BD compared with MDD, the findings highlight potential vulnerabilities in BD, which merit further examination in terms of their underlying causes and potential treatment implications. Early maladaptive schemas are relevant psychological dimensions to consider in remitted phases of major mood disorders. Findings from the current study suggest that early maladaptive schemas are more prevalent in adults with bipolar disorder compared to adults with major depressive disorder when measured during remission. Interventions targeting early maladaptive schemas may be valuable in treatment of bipolar disorder. Copyright © 2014 John Wiley & Sons, Ltd.

  5. Learning from Negative Feedback in Patients with Major Depressive Disorder is Attenuated by SSRI Antidepressants

    Directory of Open Access Journals (Sweden)

    Mohammad M. Herzallah

    2013-09-01

    Full Text Available One barrier to interpreting past studies of cognition and Major Depressive Disorder (MDD has been the failure in many studies to adequately dissociate the effects of MDD from the potential cognitive side effects of Selective Serotonin Reuptake Inhibitors (SSRI use. To better understand how remediation of depressive symptoms affects cognitive function in MDD, we evaluated three groups of subjects: medication-naïve patients with MDD, medicated patients with MDD receiving the SSRI paroxetine and healthy control subjects. All were administered a category-learning task that allows for dissociation between learning from positive feedback (reward versus learning from negative feedback (punishment. Healthy subjects learned significantly better from positive feedback than medication-naïve and medicated MDD groups, whose learning accuracy did not differ significantly. In contrast, medicated patients with MDD learned significantly less from negative feedback than medication-naïve patients with MDD and healthy subjects, whose learning accuracy was comparable. A comparison of subject’s relative sensitivity to positive versus negative feedback showed that both the medicated MDD and healthy control groups conform to Kahneman and Tversky’s (1979 Prospect Theory, which expects losses (negative feedback to loom psychologically slightly larger than gains (positive feedback. However, medicated MDD and HC profiles are not similar, which indicates that the state of medicated MDD is not ‘normal’ when compared to HC, but rather balanced with less learning from both positive and negative feedback. On the other hand, medication-naïve patients with MDD violate Prospect Theory by having significantly exaggerated learning from negative feedback. This suggests that SSRI antidepressants impair learning from negative feedback, while having negligible effect on learning from positive feedback. Overall, these findings shed light on the importance of dissociating the

  6. Descriptive epidemiology of major depressive disorder in Canada in 2012.

    Science.gov (United States)

    Patten, Scott B; Williams, Jeanne V A; Lavorato, Dina H; Wang, Jian Li; McDonald, Keltie; Bulloch, Andrew G M

    2015-01-01

    The epidemiology of major depressive disorder (MDD) was first described in the Canadian national population in 2002. Updated information is now available from a 2012 survey: the Canadian Community Health Study-Mental Health (CCHS-MH). The CCHS-MH employed an adaptation of the World Health Organization World Mental Health Composite International Diagnostic Interview and had a sample of n=25 113. Demographic variables, treatment, comorbidities, suicidal ideation, and perceived stigma were assessed. The analysis estimated adjusted and unadjusted frequencies and prevalence ratios. All estimates incorporated analysis methods to account for complex survey design effects. The past-year prevalence of MDD was 3.9% (95% CI 3.5% to 4.2%). Prevalence was higher in women and in younger age groups. Among respondents with past-year MDD, 63.1% had sought treatment and 33.1% were taking an antidepressant (AD); 4.8% had past-year alcohol abuse and 4.5% had alcohol dependence. Among respondents with past-year MDD, the prevalence of cannabis abuse was 2.5% and that of dependence was 2.9%. For drugs other than cannabis, the prevalence of abuse was 2.3% and dependence was 2.9%. Generalized anxiety disorder was present in 24.9%. Suicide attempts were reported by 6.6% of respondents with past-year MDD. Among respondents accessing treatment, 37.5% perceived that others held negative opinions about them or treated them unfairly because of their disorder. MDD is a common, burdensome, and stigmatized condition in Canada. Seeking help from professionals was reported at a higher frequency than in prior Canadian studies, but there has been no increase in AD use among Canadians with MDD.

  7. Peripheral biomarkers in animal models of major depressive disorder.

    Science.gov (United States)

    Carboni, Lucia

    2013-01-01

    Investigations of preclinical biomarkers for major depressive disorder (MDD) encompass the quantification of proteins, peptides, mRNAs, or small molecules in blood or urine of animal models. Most studies aim at characterising the animal model by including the assessment of analytes or hormones affected in depressive patients. The ultimate objective is to validate the model to better understand the neurobiological basis of MDD. Stress hormones or inflammation-related analytes associated with MDD are frequently measured. In contrast, other investigators evaluate peripheral analytes in preclinical models to translate the results in clinical settings afterwards. Large-scale, hypothesis-free studies are performed in MDD models to identify candidate biomarkers. Other studies wish to propose new targets for drug discovery. Animal models endowed with predictive validity are investigated, and the assessment of peripheral analytes, such as stress hormones or immune molecules, is comprised to increase the confidence in the target. Finally, since the mechanism of action of antidepressants is incompletely understood, studies investigating molecular alterations associated with antidepressant treatment may include peripheral analyte levels. In conclusion, preclinical biomarker studies aid the identification of new candidate analytes to be tested in clinical trials. They also increase our understanding of MDD pathophysiology and help to identify new pharmacological targets.

  8. Onset of Alcohol or Substance Use Disorders Following Treatment for Adolescent Depression

    Science.gov (United States)

    Curry, John; Silva, Susan; Rohde, Paul; Ginsburg, Golda; Kennard, Betsy; Kratochvil, Christopher; Simons, Anne; Kirchner, Jerry; May, Diane; Mayes, Taryn; Feeny, Norah; Albano, Anne Marie; Lavanier, Sarah; Reinecke, Mark; Jacobs, Rachel; Becker-Weidman, Emily; Weller, Elizabeth; Emslie, Graham; Walkup, John; Kastelic, Elizabeth; Burns, Barbara; Wells, Karen; March, John

    2012-01-01

    Objective: This study tested whether positive response to short-term treatment for adolescent major depressive disorder (MDD) would have the secondary benefit of preventing subsequent alcohol use disorders (AUD) or substance use disorders (SUD). Method: For 5 years, we followed 192 adolescents (56.2% female; 20.8% minority) who had participated in…

  9. Onset of Alcohol or Substance Use Disorders Following Treatment for Adolescent Depression

    Science.gov (United States)

    Curry, John; Silva, Susan; Rohde, Paul; Ginsburg, Golda; Kennard, Betsy; Kratochvil, Christopher; Simons, Anne; Kirchner, Jerry; May, Diane; Mayes, Taryn; Feeny, Norah; Albano, Anne Marie; Lavanier, Sarah; Reinecke, Mark; Jacobs, Rachel; Becker-Weidman, Emily; Weller, Elizabeth; Emslie, Graham; Walkup, John; Kastelic, Elizabeth; Burns, Barbara; Wells, Karen; March, John

    2012-01-01

    Objective: This study tested whether positive response to short-term treatment for adolescent major depressive disorder (MDD) would have the secondary benefit of preventing subsequent alcohol use disorders (AUD) or substance use disorders (SUD). Method: For 5 years, we followed 192 adolescents (56.2% female; 20.8% minority) who had participated in…

  10. Atypical depressive symptoms as a predictor of treatment response to exercise in Major Depressive Disorder.

    Science.gov (United States)

    Rethorst, Chad D; Tu, Jian; Carmody, Thomas J; Greer, Tracy L; Trivedi, Madhukar H

    2016-08-01

    Effective treatment of Major Depressive Disorder (MDD) will require the development of alternative treatments and the ability for clinicians to match patients with the treatment likely to produce the greatest effect. We examined atypical depression subtype as a predictor of treatment response to aerobic exercise augmentation in persons with non-remitted MDD. Our results revealed a small-to-moderate effect, particularly in a group assigned to high-dose exercise (semi-partial eta-squared =0.0335, p=0.0735), indicating that those with atypical depression tended to have larger treatment response to exercise. Through this hypothesis-generating analysis, we indicate the need for research to examine depression subtype, along with other demographic, clinical and biological factors as predictors of treatment response to exercise.

  11. 个体和社会功能量表中文版在抑郁障碍患者中的信效度%The reliability and validity of Chinese version of Personal and Social Performance Scale (PSP) in patients with major depressive disorder (MDD)

    Institute of Scientific and Technical Information of China (English)

    司天梅; 张卫华; 党卫民; 张鸿燕; 舒良; 田成华; 苏允爱; 闫俊; 程嘉; 李雪霓; 刘琦; 马燕桃

    2010-01-01

    目的:考察个体和社会功能量表中文版(Chinese version of the Personal and Social Performance scale,PSP-CHN)在抑郁障碍患者中的信度和效度.方法:收集74例符合第四版(Diagnostic and Statistical Mannual of Mental Disorders,Fourth Edition,test revision,DSM-IV-TR)抑郁障碍诊断标准的门诊或住院患者,其中6例参加了研究者之间一致性培训,68例(急性期42例,稳定期26例)进行了大体功能量表(Global Assessment ofFunctioning Scale,GAF))、Hamilton抑郁量表17项(Hamilton Depression Rating Scale 17 items,HAMD-17)和PSP-CHN检查,分析PSP-CHN量表评估抑郁障碍患者的内部一致性、PSP-CHN与GAF的一致性(效标效度)以及与患者疾病严重度的相关性(关联效度),32例患者在首次PSP-CHN评估后的5~7天内,由另一名研究者对其进行第2次检查,评价PSP-CHN在抑郁障碍患者中的重测信度.26例HAMD17评分>17分的患者,接受标准化治疗8周后,评估HAMD17评分和PSP-CHN的评分变化.结果:PSP-CHN量表的内部一致性Cronbach α系数为0.71,PSP-CHN总分的研究者之间一致性Kappa值为0.82(ICC=0.94),重测一致性ICC=0.90.PSP-CHN总分与GAF总分呈i正相关(r=0.95,P<0.001),与HAMD-17总分负相关(r=-0.54),急性期和稳定期与PSP-CHN总分相关的抑郁因子不同.结论:个体和社会功能量表中文版可以评价抑郁症患者的个体和社会功能,但是总体信度低于在精神分裂症患者中的评估.

  12. The role of major depression in neurocognitive functioning in patients with posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Mirjam J. Nijdam

    2013-04-01

    Full Text Available Background: Posttraumatic stress disorder (PTSD and major depressive disorder (MDD frequently co-occur after traumatic experiences and share neurocognitive disturbances in verbal memory and executive functioning. However, few attempts have been made to systematically assess the role of a comorbid MDD diagnosis in neuropsychological studies in PTSD. Objective: The purpose of the current study is to investigate neurocognitive deficits in PTSD patients with and without MDD. We hypothesized that PTSD patients with comorbid MDD (PTSD+MDD would have significantly lower performance on measures of verbal memory and executive functioning than PTSD patients without MDD (PTSD–MDD. Method: Participants included in this study were 140 treatment-seeking outpatients who had a diagnosis of PTSD after various single traumatic events and participated in a randomized controlled trial comparing different treatment types. Baseline neuropsychological data were compared between patients with PTSD+MDD (n=84 and patients with PTSD–MDD (n=56. Results: The PTSD+MDD patients had more severe verbal memory deficits in learning and retrieving words than patients with PTSD alone. There were no differences between the groups in recall of a coherent paragraph, recognition, shifting of attention, and cognitive interference. Conclusions: The results of this study suggest that a more impaired neurocognitive profile may be associated with the presence of comorbid MDD, with medium-sized group differences for verbal memory but not for executive functioning. From a clinical standpoint, being aware that certain verbal memory functions are more restricted in patients with comorbid PTSD and MDD may be relevant for treatment outcome of trauma-focused psychotherapy.

  13. Attention-deficit/hyperactivity disorder in adolescence predicts onset of major depressive disorder through early adulthood.

    Science.gov (United States)

    Meinzer, Michael C; Lewinsohn, Peter M; Pettit, Jeremy W; Seeley, John R; Gau, Jeff M; Chronis-Tuscano, Andrea; Waxmonsky, James G

    2013-06-01

    The aim of this study was to examine the prospective relationship between a history of attention-deficit/hyperactivity disorder (ADHD) assessed in mid-adolescence and the onset of major depressive disorder (MDD) through early adulthood in a large school-based sample. A secondary aim was to examine whether this relationship was robust after accounting for comorbid psychopathology and psychosocial impairment. One thousand five hundred seven participants from the Oregon Adolescent Depression Project completed rating scales in adolescence and structured diagnostic interviews up to four times from adolescence to age 30. Adolescents with a lifetime history of ADHD were at significantly higher risk of MDD through early adulthood relative to those with no history of ADHD. ADHD remained a significant predictor of MDD after controlling for gender, lifetime history of other psychiatric disorders in adolescence, social and academic impairment in adolescence, stress and coping in adolescence, and new onset of other psychiatric disorders through early adulthood (hazard ratio, 1.81; 95% confidence interval, 1.04, 3.06). Additional significant, robust predictors of MDD included female gender, a lifetime history of an anxiety disorder, and poor coping skills in mid-adolescence, as well as the onset of anxiety, oppositional defiant disorder, and substance-use disorder after mid-adolescence. A history of ADHD in adolescence was associated with elevated risk of MDD through early adulthood and this relationship remained significant after controlling for psychosocial impairment in adolescence and co-occurring psychiatric disorders. Additional work is needed to identify the mechanisms of risk and to inform depression prevention programs for adolescents with ADHD. © 2013 Wiley Periodicals, Inc.

  14. Evaluation of the risk factors of depressive disorders comorbid with obstructive sleep apnea

    Science.gov (United States)

    Cai, Liqiang; Xu, Luoyi; Wei, Lili; Sun, Yi; Chen, Wei

    2017-01-01

    Objective Overlap of obstructive sleep apnea (OSA) complicates diagnosis of depressive disorder and renders antidepressant treatment challenging. Previous studies have reported that the incidence of OSA is higher in patients with depression than in the general population. The purpose of this article was to investigate clinical risk factors to predict OSA in depression disorders. Methods A total of 115 patients diagnosed with major depressive disorder (MDD) and bipolar disorder (in a major depressive episode), who underwent overnight polysomnography, were studied retrospectively. They were divided into two groups: non-OSA and OSA. The patients who had apnea–hypopnea index (AHI) <5 were defined as the non-OSA group, whereas the OSA group was defined as those with an AHI ≥5. Logistic regression was used to analyze the association among AHI and clinical factors, including sex, age, body mass index (BMI), Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale, Pittsburgh Sleep Quality Index (PSQI), and diagnosis (MDD or bipolar disorder [in a major depressive episode]). Results In 115 patients, 51.3% had OSA. Logistic regression analysis showed significant associations between AHI and diagnosis (MDD or bipolar disorder [in a major depressive episode]), BMI, HAMD, and PSQI (P<0.05). Conclusion The findings of our study suggested that the rate of depression being comorbid with OSA is remarkably high and revealed that there is a high rate of undetected OSA among depressive disorder patients and untreated OSA among mood disorder patients. The clinical risk factors (diagnosis [MDD or bipolar disorder {in a major depressive episode}], BMI, HAMD, and PSQI) could predict AHI or OSA diagnosis and contribute to OSA screening in depressive disorder patients. PMID:28144146

  15. Role of depression severity and impulsivity in the relationship between hopelessness and suicidal ideation in patients with major depressive disorder.

    Science.gov (United States)

    Wang, Yan-yu; Jiang, Neng-zhi; Cheung, Eric F C; Sun, Hong-wei; Chan, Raymond C K

    2015-09-01

    Hopelessness, depression and impulsivity all contribute to the development of suicidal ideation in patients with major depressive disorder, but the pathway of these factors to suicidal ideation is not clear. This study examined the meditating effect of depression severity on the relationship between hopelessness and suicidal ideation and explored how this mediating effect was moderated by impulsivity. A total of 162 patients with major depressive disorder (MDD) completed a structured clinical diagnostic interview and a battery of scales assessing depression severity, hopelessness, suicidal ideation, and impulsivity. Regression analyses with bootstrapping methods were used to examine the mediating and moderating effects of various risk factors. Mediation analysis revealed a significant indirect effect of hopelessness on suicidal ideation, and the effect was fully mediated through depression severity. On moderation analysis, the moderating effects of the relationship between depression severity and suicidal ideation were significant in both the medium and high impulsivity groups. The present study was limited by the assessment of trait impulsivity and observer-rated depression severity, which might not fully reflect momentary impulsivity and feeling of depression when suicidal ideation occurs. Depression severity plays a mediator role in the relationship between hopelessness and suicidal ideation and this mechanism is contingent on the levels of impulsivity. MDD patients with higher impulsivity appear to be more likely to have suicidal ideations even when they are less depressed. These findings highlight the importance of impulsivity assessment and alleviation of depressive symptoms to prevent suicidality in patients with MDD. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Clinical characteristics of inflammation-associated depression: Monocyte gene expression is age-related in major depressive disorder.

    Science.gov (United States)

    Grosse, Laura; Carvalho, Livia A; Wijkhuijs, Annemarie J M; Bellingrath, Silja; Ruland, Tillmann; Ambrée, Oliver; Alferink, Judith; Ehring, Thomas; Drexhage, Hemmo A; Arolt, Volker

    2015-02-01

    Increased inflammatory activation might only be present in a subgroup of depressed individuals in which immune processes are especially relevant to disease development. We aimed to analyze demographic, depression, and trauma characteristics of major depressive disorder (MDD) patients with regard to inflammatory monocyte gene expression. Fifty-six naturalistically treated MDD patients (32 ± 12 years) and 57 healthy controls (HC; 31 ± 11 years) were analyzed by the Inventory of Depressive Symptomatology (IDS) and by the Childhood Trauma Questionnaire (CTQ). We determined the expression of 38 inflammatory and immune activation genes including the glucocorticoid receptor (GR)α and GRβ genes in purified CD14(+) monocytes using quantitative-polymerase chain reaction (RT-qPCR). Monocyte gene expression was age-dependent, particularly in MDD patients. Increased monocyte gene expression and decreased GRα/β ratio were only present in MDD patients aged ⩾ 28 years. Post hoc analyses of monocyte immune activation in patients depression (recurrent type, onset depression, onset ⩾15 years) - additionally characterized by the absence of panic symptoms - that exhibited a strongly reduced inflammatory monocyte activation compared to HC. In conclusion, monocyte immune activation was not uniformly raised in MDD patients but was increased only in patients of 28 years and older.

  17. Discovering new genetic and psychosocial pathways in Major Depressive Disorder: the NewMood project.

    Science.gov (United States)

    Freeborough, Annabel; Kimpton, Jessica

    2011-09-01

    The World Health Organisation predicts that Major Depressive Disorder (MDD) will be the second greatest contributor to the global burden of disease by 2020, however, the neurobiological mechanisms behind the disease and the risk factors for it are yet unknown. NewMood (New Molecules for Mood Disorders) was a research project funded by the EU, collaborating work from 10 European countries with the aim of finding new molecular mechanisms behind MDD to develop more effective treatment options. This review explains the aims and objectives of NewMood and how it intends to achieve them with regards to the current literature. It also outlines two of its most recent projects: genome wide association replication study for single nucleotide polymorphisms (SNPs) increasing susceptibility to MDD and stress related pathways in depression using the cortisol awakening response (CAR). Both of these studies had significant results and could further contribute to our current understanding of MDD.

  18. Executive Attention Impairment in Adolescents With Major Depressive Disorder.

    Science.gov (United States)

    Sommerfeldt, Sasha L; Cullen, Kathryn R; Han, Georges; Fryza, Brandon J; Houri, Alaa K; Klimes-Dougan, Bonnie

    2016-01-01

    Neural network models that guide neuropsychological assessment practices are increasingly used to explicate depression, though a paucity of work has focused on regulatory systems that are under development in adolescence. The purpose of this study was to evaluate subsystems of attention related to executive functioning including alerting, orienting, and executive attention networks, as well as sustained attention with varying working memory load, in a sample of depressed and well adolescents. Neuropsychological functioning in 99 adolescents diagnosed with major depressive disorder (MDD) and 63 adolescent healthy controls (M = 16.6 years old) was assessed on the Attention Network Test (ANT) and the Continuous Performance Test, Identical Pairs. Adolescents with MDD, particularly those who were not medicated, were slower to process conflict (slower reaction time on the Executive Attention scale of the ANT) compared to controls, particularly for those who were not undergoing psychopharmacological treatment. Tentative evidence also suggests that within the MDD group, orienting performance was more impaired in those with a history of comorbid substance use disorder, and alerting was more impaired in those with a history of a suicide attempt. Adolescents with depression showed impaired executive attention, although cognitive performance varied across subgroups of patients. These findings highlight the importance of examining neurocognitive correlates associated with features of depression and suggest an avenue for future research to help guide the development of interventions.

  19. Effects of cigarette smoking on cortical thickness in major depressive disorder.

    Science.gov (United States)

    Zorlu, Nabi; Cropley, Vanessa Louise; Zorlu, Pelin Kurtgoz; Delibas, Dursun Hakan; Adibelli, Zehra Hilal; Baskin, Emel Pasa; Esen, Özgür Sipahi; Bora, Emre; Pantelis, Christos

    2017-01-01

    Findings of surface-based morphometry studies in major depressive disorder (MDD) are still inconsistent. Given that cigarette smoking is highly prevalent in MDD and has documented negative effects on the brain, it is possible that some of the inconsistencies may be partly explained by cigarette use. The aim of the current study was to examine the influence of cigarette smoking on brain structure in MDD. 50 MDD patients (25 smokers and 25 non-smokers) and 22 age, education, gender and BMI matched non-smoker healthy controls underwent structural magnetic resonance imaging. Thickness and area of the cortex were measured using surface-based morphometry implemented with Freesurfer (v5.3.0). The non-smoker MDD patients had significantly increased cortical thickness, including in the left temporal cortex (p smoked compared to non-smoking patients in regions that overlapped with the regions found to be increased in non-smoking patients in comparison to controls. Non-smoker MDD patients had increased surface area in the right lateral occipital cortex (p = 0.009). We did not find any region where cortical thickness or surface area significantly differed between controls and either smoker MDD patients or all MDD patients. The findings of the current study suggest that cigarette smoking is associated with cortical thinning in regions found to be increased in patients with MDD. However, these results should be considered preliminary due to methodological limitations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Association between latent toxoplasmosis and major depression, generalised anxiety disorder and panic disorder in human adults.

    Science.gov (United States)

    Gale, Shawn D; Brown, Bruce L; Berrett, Andrew; Erickson, Lance D; Hedges, Dawson W

    2014-08-01

    Latent infection with the apicomplexan Toxoplasma gondii (Nicolle et Manceaux, 1908) has been associated with schizophrenia, bipolar disorder and self-harm behaviour. However, the potential relationship between T. gondii immunoglobulin G antibody (IgG) seropositivity and generalised-anxiety disorder (GAD) and panic disorder (PD) has not been investigated. The associations between serum reactivity to T. gondii and major depressive disorder (MDD), GAD and PD were evaluated in a total sample of 1 846 adult participants between the ages of 20 and 39 years from the United States Center for Disease Control's National Health and Nutrition Examination Survey (NHANES). Approximately 16% of the overall sample was seropositive for T. gondii and 7% of the sample met criteria for MDD, 2% for GAD and 2% for PD. There were no significant associations between T. gondii IgG seroprevalence and MDD (OR = 0.484, 95% CI = 0.186-1.258), GAD (OR = 0.737, 95% CI = 0.218-2.490) or PD (OR = 0.683, 95% CI = 0.206-2.270) controlling for sex, ethnicity, poverty-to-income ratio and educational attainment. However, limited evidence suggested a possible association between absolute antibody titres for T. gondii and GAD and PD but not MDD. Toxoplasma gondii seroprevalence was not associated with MDD, GAD or PD within the context of the limitations of this study, although there may be an association of T. gondii serointensity with and GAD and PD, which requires further study.

  1. Associations of educational attainment, occupation, social class and major depressive disorder among Han Chinese women.

    Science.gov (United States)

    Shi, Jianguo; Zhang, Yan; Liu, Feihu; Li, Yajuan; Wang, Junhui; Flint, Jonathan; Gao, Jingfang; Li, Youhui; Tao, Ming; Zhang, Kerang; Wang, Xumei; Gao, Chengge; Yang, Lijun; Li, Kan; Shi, Shenxun; Wang, Gang; Liu, Lanfen; Zhang, Jinbei; Du, Bo; Jiang, Guoqing; Shen, Jianhua; Zhang, Zhen; Liang, Wei; Sun, Jing; Hu, Jian; Liu, Tiebang; Wang, Xueyi; Miao, Guodong; Meng, Huaqing; Li, Yi; Hu, Chunmei; Li, Yi; Huang, Guoping; Li, Gongying; Ha, Baowei; Deng, Hong; Mei, Qiyi; Zhong, Hui; Gao, Shugui; Sang, Hong; Zhang, Yutang; Fang, Xiang; Yu, Fengyu; Yang, Donglin; Liu, Tieqiao; Chen, Yunchun; Hong, Xiaohong; Wu, Wenyuan; Chen, Guibing; Cai, Min; Song, Yan; Pan, Jiyang; Dong, Jicheng; Pan, Runde; Zhang, Wei; Shen, Zhenming; Liu, Zhengrong; Gu, Danhua; Wang, Xiaoping; Liu, Xiaojuan; Zhang, Qiwen; Li, Yihan; Chen, Yiping; Kendler, Kenneth S

    2014-01-01

    The prevalence of major depressive disorder (MDD) is higher in those with low levels of educational attainment, the unemployed and those with low social status. However the extent to which these factors cause MDD is unclear. Most of the available data comes from studies in developed countries, and these findings may not extrapolate to developing countries. Examining the relationship between MDD and socio economic status in China is likely to add to the debate because of the radical economic and social changes occurring in China over the last 30 years. We report results from 3,639 Chinese women with recurrent MDD and 3,800 controls. Highly significant odds ratios (ORs) were observed between MDD and full time employment (OR = 0.36, 95% CI = 0.25-0.46, logP = 78), social status (OR = 0.83, 95% CI = 0.77-0.87, logP = 13.3) and education attainment (OR = 0.90, 95% CI = 0.86-0.90, logP = 6.8). We found a monotonic relationship between increasing age and increasing levels of educational attainment. Those with only primary school education have significantly more episodes of MDD (mean 6.5, P-value = 0.009) and have a clinically more severe disorder, while those with higher educational attainment are likely to manifest more comorbid anxiety disorders. In China lower socioeconomic position is associated with increased rates of MDD, as it is elsewhere in the world. Significantly more episodes of MDD occur among those with lower educational attainment (rather than longer episodes of disease), consistent with the hypothesis that the lower socioeconomic position increases the likelihood of developing MDD. The phenomenology of MDD varies according to the degree of educational attainment: higher educational attainment not only appears to protect against MDD but alters its presentation, to a more anxious phenotype.

  2. Escalation to Major Depressive Disorder among adolescents with subthreshold depressive symptoms: evidence of distinct subgroups at risk.

    Science.gov (United States)

    Hill, Ryan M; Pettit, Jeremy W; Lewinsohn, Peter M; Seeley, John R; Klein, Daniel N

    2014-04-01

    The presence of subthreshold depressive symptoms (SubD) in adolescence is associated with high prospective risk of developing Major Depressive Disorder (MDD). Little is known about variables that predict escalation from SubD to MDD. This study used a longitudinal prospective design in a community sample of adolescents to identify combinations of risk factors that predicted escalation from SubD to MDD. Classification tree analysis was used to identify combinations of risk factors that improved the sensitivity and specificity of prediction of MDD onset among 424 adolescents with a lifetime history of SubD. Of the 424, 144 developed MDD during the follow-up period. Evidence for multiple subgroups was found: among adolescents with poor friend support, the highest risk of escalation was among participants with lifetime histories of an anxiety or substance use disorder. Among adolescents with high friend support, those reporting multiple major life events in the past year or with a history of an anxiety disorder were at highest risk of escalation. Study findings may not inform prevention efforts for individuals who first develop SubD during adulthood. This study did not examine the temporal ordering of predictors involved in escalation from SubD to MDD. Adolescents with a history of SubD were at highest risk of escalation to MDD in the presence of poor friend support and an anxiety or substance use disorder, or in the presence of better friend support, multiple major life events, and an anxiety disorder. Findings may inform case identification approaches for adolescent depression prevention programs. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Functional anomalies in healthy individuals with a first degree family history of major depressive disorder

    Directory of Open Access Journals (Sweden)

    Amico Francesco

    2012-01-01

    Full Text Available Abstract Background Individuals with major depressive disorder (MDD process information with a bias towards negative stimuli. However, little is known on the link between vulnerability to MDD and brain functional anomalies associated with stimulus bias. Methods A cohort of 38 subjects, of which 14 were patients with acute MDD and 24 were healthy controls (HC, were recruited and compared. The HC group included 10 healthy participants with a first degree family history of depression (FHP and 14 volunteers with no family history of any psychiatric disease (FHN. Blood oxygen level dependence signals were acquired from functional magnetic resonance imaging (fMRI during performance in a dot-probe task using fearful and neutral stimuli. Reaction times and the number of errors were also obtained. Results Although MDD patients and HC showed no behavioral difference, the MDD group exhibited smaller activation in the left middle cingulum. The MDD group also showed smaller activation in the left insula when compared to the HC group or the FHN group. Finally, FHP participants exhibited higher activation in the right Heschl's gyrus compared to FHN participants. Conclusions The present study shows that family risk for MDD is associated with increased activation in the Heschl's gyrus. Our results also suggest that acute MDD is linked to reduced activation in the insula and anterior cingulate cortex during processing of subliminal, not recognizable, masked fearful stimuli. Further research should confirm these results in a larger cohort of participants.

  4. Correlates of Psychological Distress and Major Depressive Disorder among African American Men

    Science.gov (United States)

    Lincoln, Karen D.; Taylor, Robert Joseph; Watkins, Daphne C.; Chatters, Linda M.

    2011-01-01

    This study examines the demographic correlates of depressive symptoms, serious psychological distress (SPD), and major depressive disorder (MDD; 12-month and lifetime prevalence) among a national sample of African American men. Analysis of the National Survey of American Life (NSAL) data set provides first-time substantiation of important…

  5. The error processing system in major depressive disorder: cortical phenotypal marker hypothesis

    NARCIS (Netherlands)

    Schoenberg, P.L.

    2014-01-01

    Major depressive disorder (MDD) ensues reduced goal-directed cognition and behaviour. Cognitive and emotional flexibility to disengage and adapt future responses was examined in the error processing system (error-related negativity/ERN, error-positivity/Pe event-related potentials) of 58 depressed p

  6. Increased cortisol awakening response was associated with time to recurrence of major depressive disorder

    NARCIS (Netherlands)

    Hardeveld, Florian; Spijker, Jan; Vreeburg, Sophie A.; De Graaf, Ron; Hendriks, Sanne M.; Licht, Carmilla M. M.; Nolen, Willem A.; Penninx, Brenda W. J. H.; Beekman, Aartjan T. F.

    2014-01-01

    Introduction: Although HPA-axis activity has been studied extensively in relation to depression, there is no consensus whether HPA-axis parameters predicts major depressive disorder (MDD) recurrence. We investigated whether HPA-axis parameters (cortisol awakening response (CAR), the dexamethasone

  7. Gene expression-based biological test for major depressive disorder: an advanced study

    Directory of Open Access Journals (Sweden)

    Watanabe S

    2017-02-01

    Full Text Available Shin-ya Watanabe,1 Shusuke Numata,1 Jun-ichi Iga,2 Makoto Kinoshita,1 Hidehiro Umehara,1 Kazuo Ishii,3 Tetsuro Ohmori1 1Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 2Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Ehime, 3Department of Applied Biological Science, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan Purpose: Recently, we could distinguished patients with major depressive disorder (MDD from nonpsychiatric controls with high accuracy using a panel of five gene expression markers (ARHGAP24, HDAC5, PDGFC, PRNP, and SLC6A4 in leukocyte. In the present study, we examined whether this biological test is able to discriminate patients with MDD from those without MDD, including those with schizophrenia and bipolar disorder.Patients and methods: We measured messenger ribonucleic acid expression levels of the aforementioned five genes in peripheral leukocytes in 17 patients with schizophrenia and 36 patients with bipolar disorder using quantitative real-time polymerase chain reaction (PCR, and we combined these expression data with our previous expression data of 25 patients with MDD and 25 controls. Subsequently, a linear discriminant function was developed for use in discriminating between patients with MDD and without MDD.Results: This expression panel was able to segregate patients with MDD from those without MDD with a sensitivity and specificity of 64% and 67.9%, respectively.Conclusion: Further research to identify MDD-specific markers is needed to improve the performance of this biological test. Keywords: depressive disorder, biomarker, gene expression, schizophrenia, bipolar disorder

  8. Explaining heterogeneity in disability associated with current major depressive disorder : Effects of illness characteristics and comorbid mental disorders

    NARCIS (Netherlands)

    van der Werff, E.; Verboom, C.E.; Penninx, Brenda; Nolen, W.A.; Ormel, J.

    2010-01-01

    Background: Although major depressive disorder (MDD) is associated with disability, some persons do function well despite their illness. Aim of the present study was to examine the effect of illness characteristics and comorbid mental disorders on various aspects of disability among persons with a c

  9. Correlative study of peripheral ATP1A1 gene expression level to anxiety severity score on major depressive disorder patients.

    Science.gov (United States)

    Zhao, Jingjie; Guo, Xu; Du, Yi; Han, Yu; Wang, Yongzhi; Li, Li; Qian, Jialin; Li, Mingzhen; Wu, Huijuan; Golden, Teresa; Wu, Ning

    2016-11-01

    Major depressive disorder (MDD) frequently co-occurs with other psychiatric problems. Our previous study showed that ATP1A1 gene expression level was significantly decreased in MDD patients. This research explores the potential correlations between the ATP1A1 expression level reduction and MDD patients' clinical manifestation. All participant patients were diagnosed by Diagnostic and Statistical Manual of Mental Disorders - 4th edition (DSM-IV). Hamilton rating scale for depression (HAM-D) and anxiety (HAM-A) were applied to group patients into different categories. ATP1A1 expression level was measured by reverse transcript real-time polymerase chain reaction. ATP1A1 expression levels of all MDD subgroups showed significant reduction compared to the control group (p0.05). ATP1A1 expression level reduction is related to MDD anxiety score, which may be an explanation for the clinical manifestations and the underlining physiological mechanisms.

  10. Second Generation Antipsychotics in the Treatment of Major Depressive Disorder: An Update.

    Science.gov (United States)

    Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Jun, Tae-Youn; Patkar, Ashwin A; Masand, Prakash S; Pae, Chi-Un

    2016-09-01

    Less than one third of patients who suffer from major depressive disorder (MDD) report remission following antidepressant treatments requiring more diverse treatment approaches. Augmentation of second generation antipsychotics (SGAs) has been increasingly recognized as an important treatment option. The authors have previously provided a comprehensive review of SGAs for the treatment of MDD in 2013. Since then, numerous additional clinical trials have been conducted to investigate diverse issues regarding the utility of SGAs in MDD. Moreover, a new SGA, brexpiprazole, was recently approved by the Food and Drug Administration in July 2015 for the treatment of MDD as an augmentation agent to antidepressants. Thus, the aim of this study was to provide a concise update of all the available SGAs for the treatment of MDD, in particular on the additional clinical trials which have been published since 2013.

  11. Auditory Memory Decrements, Without Dissimulation, among Patients with Major Depressive Disorder

    Science.gov (United States)

    Considine, Ciaran M.; Weisenbach, Sara L.; Walker, Sara J.; McFadden, E. Michelle; Franti, Lindsay M.; Bieliauskas, Linas A.; Maixner, Daniel F.; Giordani, Bruno; Berent, Stanley; Langenecker, Scott A.

    2011-01-01

    Questions have been raised about whether poor performance on memory tasks by individuals with major depressive disorder (MDD) might be the result of poor or variable effort or disease-related disruption of neural circuits supporting memory functions. The present study examined performance on a measure of task engagement and on an auditory memory task among 45 patients with MDD (M age = 47.82, SD = 19.55) relative to 32 healthy controls (HC; M age = 51.03, SD = 22.09). One-hundred percent of HC and MDD volunteers performed above the threshold for adequate effort on a formal measure of task engagement. The MDD subjects performed significantly more poorly than the HC subjects on an auditory learning and memory test. The present results suggest that auditory memory difficulties do occur among those with MDD and that decrements in performance in this group may be related to factors other than lack of effort. PMID:21593060

  12. Differences in depressive symptoms between Korean and American outpatients with major depressive disorder.

    Science.gov (United States)

    Jeon, Hong Jin; Walker, Rosemary S; Inamori, Aya; Hong, Jin Pyo; Cho, Maeng Je; Baer, Lee; Clain, Alisabet; Fava, Maurizio; Mischoulon, David

    2014-05-01

    Previous epidemiologic studies have revealed that East-Asian populations experience fewer depressive symptoms than American populations do. However, it is unclear whether this difference applies to clinical patients with major depressive disorder (MDD). This present study included 1592 Korean and 3744 American outpatients who were 18 years of age or older and met the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. criteria for single or recurrent episodes of nonpsychotic MDD, and evaluated their symptoms of depression using the Hamilton Depression Rating Scale and the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form. Korean patients scored significantly lower for guilt and depressed mood items, and higher for hypochondriasis and suicidality items than American patients did, after adjusting for total Hamilton Depression Rating Scale scores. Conversely, no significant differences were found in quality and function of daily life between groups. Multivariate logistic regression analyses revealed that Korean patients experienced less frequent depressed mood and guilt, including verbal and nonverbal expression of depressed mood [adjusted odds ratio (AOR) = 0.14, 95% confidence interval (CI) 0.08-0.23] and feelings of punishment (AOR = 0.036, 95% CI 0.025-0.054) when compared with Americans after adjusting for age and sex. Conversely, Korean patients experienced more frequent suicidality and hypochondriasis, including suicidal ideas or gestures (AOR = 2.10, 95% CI 1.60-2.76) and self-absorption of hypochondriasis (AOR = 1.94, 95% CI 1.70-2.20). In conclusion, decreased expression of depressed mood and guilt may cause underdiagnosis of MDD in Korean patients. Early diagnosis of and intervention for depression and suicide may be delayed because of this specific cross-cultural difference in depression symptoms.

  13. Sex Differences in Serum Markers of Major Depressive Disorder in the Netherlands Study of Depression and Anxiety (NESDA)

    Science.gov (United States)

    Ramsey, Jordan M.; Cooper, Jason D.; Bot, Mariska; Guest, Paul C.; Lamers, Femke; Weickert, Cynthia S.

    2016-01-01

    Women have a consistently higher prevalence of major depressive disorder (MDD) than men. Hypotheses implicating hypothalamic-pituitary -adrenal, -gonadal, and -thyroid axes, immune response, genetic factors, and neurotransmitters have emerged to explain this difference. However, more evidence for these hypotheses is needed and new explanations must be explored. Here, we investigated sex differences in MDD markers using multiplex immunoassay measurements of 171 serum molecules in individuals enrolled in the Netherlands Study of Depression and Anxiety (NMDD = 231; Ncontrol = 365). We found 28 sex-dependent markers of MDD, as quantified by a significant interaction between sex and log2-transformed analyte concentration in a logistic regression with diagnosis (MDD/control) as the outcome variable (ptrefoil factor 3, cystatin-C, fetuin-A, β2-microglobulin, CD5L, FASLG receptor, and tumor necrosis factor receptor 2. Furthermore, only male MDD could be classified with an accuracy greater than chance using the measured serum analytes (area under the ROC curve = 0.63). These findings may have consequences for the generalization of inflammatory hypotheses of depression to males and females and have important implications for the development of diagnostic biomarker tests for MDD. More studies are needed to validate these results, investigate a broader range of biological pathways, and integrate this data with brain imaging, genetic, and other relevant data. PMID:27232630

  14. Stress-evoked opioid release inhibits pain in major depressive disorder.

    Science.gov (United States)

    Frew, Ashley K; Drummond, Peter D

    2008-10-15

    To determine whether stress-evoked release of endogenous opioids might account for hypoalgesia in major depressive disorder (MDD), the mu-opioid antagonist naltrexone (50mg) or placebo was administered double-blind to 24 participants with MDD and to 31 non-depressed controls. Eighty minutes later participants completed a painful foot cold pressor test and, after a 5-min interval, began a 25-min arithmetic task interspersed with painful electric shocks. Ten minutes later participants completed a second cold pressor test. Negative affect was greater in participants with MDD than in non-depressed controls throughout the experiment, and increased significantly in both groups during mental arithmetic. Before the math task, naltrexone unmasked direct linear relationships between severity of depression, negative affect while resting quietly, and cold-induced pain in participants with MDD. In contrast, facilitatory effects of naltrexone on cold- and shock-induced pain were greatest in controls with the lowest depression scores. Naltrexone strengthened the relationship between negative affect and shock-induced pain during the math task, particularly in the depressed group, and heightened anxiety in both groups toward the end of the task. Thus, mu-opioid activity apparently masked a positive association between negative affect and pain in the most distressed participants. These findings suggest that psychological distress inhibits pain via stress-evoked release of opioid peptides in severe cases of MDD. In addition, tonic endogenous opioid neurotransmission could inhibit depressive symptoms and pain in people with low depression scores.

  15. St. John’s Wort for Major Depressive Disorder: A Systematic Review

    Science.gov (United States)

    2015-01-01

    St. John’s Wort for Major Depressive Disorder A Systematic Review Alicia Ruelaz Maher, Susanne Hempel, Eric Apaydin, Roberta M. Shanman, Marika...effectiveness of St. John’s wort for major depressive disorder (MDD), conducted during year two of a two-year project on integrative medicine approaches for...the web page). v Abstract This systematic review synthesized evidence of St. John’s wort (SJW) for the treatment of major depressive

  16. Major depressive disorder following terrorist attacks: A systematic review of prevalence, course and correlates

    Science.gov (United States)

    2011-01-01

    Background Terrorist attacks are traumatic events that may result in a wide range of psychological disorders for people exposed. This review aimed to systematically assess the current evidence on major depressive disorder (MDD) after terrorist attacks. Methods A systematic review was performed. Studies included assessed the impact of human-made, intentional, terrorist attacks in direct victims and/or persons in general population and evaluated MDD based on diagnostic criteria. Results A total of 567 reports were identified, 11 of which were eligible for this review: 6 carried out with direct victims, 4 with persons in general population, and 1 with victims and general population. The reviewed literature suggests that the risk of MDD ranges between 20 and 30% in direct victims and between 4 and 10% in the general population in the first few months after terrorist attacks. Characteristics that tend to increase risk of MDD after a terrorist attack are female gender, having experienced more stressful situations before or after the attack, peritraumatic reactions during the attack, loss of psychosocial resources, and low social support. The course of MDD after terrorist attacks is less clear due to the scarcity of longitudinal studies. Conclusions Methodological limitations in the literature of this field are considered and potentially important areas for future research such as the assessment of the course of MDD, the study of correlates of MDD or the comorbidity between MDD and other mental health problems are discussed. PMID:21627850

  17. Structural Asymmetry of Dorsolateral Prefrontal Cortex Correlates with Depressive Symptoms: Evidence from Healthy Individuals and Patients with Major Depressive Disorder.

    Science.gov (United States)

    Liu, Wei; Mao, Yu; Wei, Dongtao; Yang, Junyi; Du, Xue; Xie, Peng; Qiu, Jiang

    2016-06-01

    In this study, we investigated the role of structural asymmetry of the dorsolateral prefrontal cortex (DLPFC) in the continuum of depression from healthy individuals to patients. Structural magnetic resonance imaging was performed in 70 patients with major depressive disorder (MDD), 49 matched controls, and 349 healthy university students to calculate structural asymmetry indexes of the DLPFC. First-episode, treatment-naive MDD patients showed a relatively lower asymmetry index than healthy controls, and their asymmetry index was negatively correlated with the depressive symptoms. This abnormality was normalized by antidepressants in medicated MDD patients. Furthermore, the asymmetry index was negatively correlated with the depressive symptoms in university students; this was replicated at two time points in a subgroup of students, suggesting good test-retest reliability. Our findings are consistent with previous studies that support the imbalance hypothesis of MDD and suggest a potential structural basis underlying the functional asymmetry of the DLPFC in depression. In future, the structural index of the DLPFC may become a potential biomarker to evaluate individuals' risk for the onset of MDD.

  18. Inpatients with major depressive disorder: Psychometric properties of the new Multidimensional Depression Scale.

    Science.gov (United States)

    Darharaj, Mohammad; Habibi, Mojtaba; Power, Michael J; Farzadian, Farzaneh; Rahimi, Maesoumeh; Kholghi, Habibeh; Kazemitabar, Maryam

    2016-12-01

    The New Multi-dimensional Depression Scale (NMDS) is one of the most comprehensive scales that measures depression symptoms in four domains, including emotional, cognitive, somatic, and interpersonal. This study aimed to evaluate the factor structure and psychometric properties of the NMDS in a group of Iranian inpatients with Major Depressive Disorder (MDD). At first, the scale was translated into Persian and used as part of a battery consisting of the Beck Depression Inventory-II (BDI-II), Oxford Happiness Inventory (OHI), Beck Anxiety Inventory (BAI), and Short Form Health Survey (SF-36). The battery was administered to 271 inpatients with MDD (90 men and 181 women) aged from 18 to 60 who had been referred to psychiatric hospitals in Tehran, Iran. Confirmatory factor analysis of the Persian version of the NMDS upheld its original four-factor structure. Moreover, the results showed its good internal consistency (Cronbach's alpha coefficient ranging from 0.70 for the emotional subscale to 0.83 for the interpersonal subscale). In addition, the NMDS scores were correlated with other constructs in empirically and theoretically expected ways, which provides evidence for the convergent (positive significant relationships with anxiety and cognitive and somatic-affective symptoms of depression) and divergent (negative significant relationships with happiness and mental health and physical health) validity of the scale. These findings supported the Persian version of the NMDS as a reliable and valid measure for the assessment of depression symptoms in patients with MDD.

  19. Cognitive Dysfunction in Major Depressive Disorder. A Translational Review in Animal Models of the Disease.

    Science.gov (United States)

    Darcet, Flavie; Gardier, Alain M; Gaillard, Raphael; David, Denis J; Guilloux, Jean-Philippe

    2016-02-17

    Major Depressive Disorder (MDD) is the most common psychiatric disease, affecting millions of people worldwide. In addition to the well-defined depressive symptoms, patients suffering from MDD consistently complain about cognitive disturbances, significantly exacerbating the burden of this illness. Among cognitive symptoms, impairments in attention, working memory, learning and memory or executive functions are often reported. However, available data about the heterogeneity of MDD patients and magnitude of cognitive symptoms through the different phases of MDD remain difficult to summarize. Thus, the first part of this review briefly overviewed clinical studies, focusing on the cognitive dysfunctions depending on the MDD type. As animal models are essential translational tools for underpinning the mechanisms of cognitive deficits in MDD, the second part of this review synthetized preclinical studies observing cognitive deficits in different rodent models of anxiety/depression. For each cognitive domain, we determined whether deficits could be shared across models. Particularly, we established whether specific stress-related procedures or unspecific criteria (such as species, sex or age) could segregate common cognitive alteration across models. Finally, the role of adult hippocampal neurogenesis in rodents in cognitive dysfunctions during MDD state was also discussed.

  20. DNA methylation in a Scottish family multiply affected by bipolar disorder and major depressive disorder

    OpenAIRE

    2016-01-01

    Background Bipolar disorder (BD) is a severe, familial psychiatric condition. Progress in understanding the aetiology of BD has been hampered by substantial phenotypic and genetic heterogeneity. We sought to mitigate these confounders by studying a multi-generational family multiply affected by BD and major depressive disorder (MDD), who carry an illness-linked haplotype on chromosome 4p. Within a family, aetiological heterogeneity is likely to be reduced, thus conferring greater power to det...

  1. Relapse prevention and residual symptoms: a closer analysis of placebo-controlled continuation studies with escitalopram in major depressive disorder, generalized anxiety disorder, social anxiety disorder, and obsessive-compulsive disorder

    DEFF Research Database (Denmark)

    Bech, Per; Lönn, Sara L; Overø, Kerstin F

    2010-01-01

    -Severity of Illness scores and relapse status in 4 studies published from 2005 to 2007, 1 each in major depressive disorder (MDD), generalized anxiety disorder, social anxiety disorder, and obsessive-compulsive disorder (OCD), were analyzed using mixed-effects model repeated measures as a function of Montgomery...

  2. Fat distribution and major depressive disorder in late adolescence.

    Science.gov (United States)

    Coryell, William H; Butcher, Brandon D; Burns, Trudy L; Dindo, Lilian N; Schlechte, Janet A; Calarge, Chadi A

    2016-01-01

    Substantial evidence exists to indicate bidirectional relationships between obesity and depressive disorders and the importance of fat distribution to this relationship. This analysis used a well-characterized sample of individuals in late adolescence to determine the association between depressive illness and fat distribution. Medically healthy 15- to 20-year-olds, one-half of whom had recently begun treatment with a selective serotonin reuptake inhibitor, underwent a comprehensive psychiatric evaluation that resulted in diagnostic classification and weekly psychiatric disorder ratings over the prior 4 months using the Longitudinal Interval Follow-Up Evaluation. A whole-body scan, using dual-energy x-ray absorptiometry, allowed estimations of total body less head (TBLH), total mass, fat mass, and visceral adipose tissue (VAT) mass. Assessments occurred between September 2010 and April 2014. Multivariable linear regression analyses, adjusted for relevant covariates, examined the association between DSM-IV-TR-diagnosed major depressive disorder (MDD) and VAT, the primary outcome of interest. These procedures also determined whether significant associations were confined to overweight/obese participants. The analysis included data from 200 participants (71% female; mean age = 19.0 ± 1.6 years), of whom 128 had current MDD. The presence of MDD was associated with increased fat mass among overweight/obese participants (Cohen d = 0.79, P adolescents, relationships between central adiposity and MDD may be confined to those who are overweight/obese. Despite the high comorbidity of GAD and depressive disorders, only the latter appeared to be significantly associated with central adiposity. © Copyright 2015 Physicians Postgraduate Press, Inc.

  3. Challenging Treatment-Resistant Major Depressive Disorder: A Roadmap for Improved Therapeutics.

    Science.gov (United States)

    de Sousa, Rafael T; Zanetti, Marcus V; Brunoni, Andre R; Machado-Vieira, Rodrigo

    2015-01-01

    Major depressive disorder (MDD) is associated with a significant burden and costs to the society. As remission of depressive symptoms is achieved in only one-third of the MDD patients after the first antidepressant trial, unsuccessful treatments contribute largely to the observed suffering and social costs of MDD. The present article provides a summary of the therapeutic strategies that have been tested for treatment-resistant depression (TRD). A computerized search on MedLine/PubMed database from 1975 to September 2014 was performed, using the keywords "treatment-resistant depression", "major depressive disorder", "adjunctive", "refractory" and "augmentation". From the 581 articles retrieved, two authors selected 79 papers. A manual searching further considered relevant articles of the reference lists. The evidence found supports adding or switching to another antidepressant from a different class is an effective strategy in more severe MDD after failure to an initial antidepressant trial. Also, in subjects resistant to two or more classes of antidepressants, some augmentation strategies and antidepressant combinations should be considered, although the overall response and remission rates are relatively low, except for fast acting glutamatergic modulators. The wide range of available treatments for TRD reflects the complexity of MDD, which does not underlie diverse key features of the disorder. Larger and well-designed studies applying dimensional approaches to measure efficacy and effectiveness are warranted.

  4. Urinary peptidomics identifies potential biomarkers for major depressive disorder.

    Science.gov (United States)

    Wang, Ying; Chen, Jianjun; Chen, Liang; Zheng, Peng; Xu, Hong-Bo; Lu, Jia; Zhong, Jiaju; Lei, Yang; Zhou, Chanjuan; Ma, Qingwei; Li, Yan; Xie, Peng

    2014-06-30

    Major depressive disorder (MDD) is a debilitating psychiatric illness with no available objective laboratory-based diagnostic test. In this study, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based peptidomics was applied to identify potential urinary diagnostic biomarkers for MDD. A training set of 42 first-episode drug-naive MDD patients and 28 age- and gender-matched healthy controls (HC) was used to develop a peptide diagnostic pattern. Then, the diagnostic efficacy of this pattern was assessed in an independent blinded test set consisting of 24 MDD patients and 13 age- and gender-matched HC. A combination of five potential biomarkers was identified, yielding a sensitivity of 91.7% and specificity of 84.6% in the test set. Moreover, the protein precursors of four of the five peptides were identified by tandem mass spectrometric analysis: serum albumin, apolipoprotein A-I, protein AMBP, and basement membrane-specific heparan sulfate proteoglycan core protein. Taken together, the peptide pattern may be valuable for establishing an objective laboratory-based diagnostic test for MDD.

  5. Desvenlafaxine for the treatment of major depressive disorder.

    Science.gov (United States)

    Kornstein, Susan G; McIntyre, Roger S; Thase, Michael E; Boucher, Matthieu

    2014-07-01

    Major depressive disorder (MDD) is a chronic and debilitating condition often characterized by inadequate treatment. Notwithstanding the availability of more than a dozen first-line agents across disparate classes (e.g., selective serotonin reuptake inhibitors), the majority of individuals with MDD do not achieve and sustain a recovered state. A substantial percentage of MDD patients require a treatment change due to poor efficacy or tolerability. This review focuses on recent (≤ 5 years) literature describing the pharmacokinetics, efficacy, and tolerability of desvenlafaxine , one of the more recently approved antidepressant drugs. Published papers identified via PubMed search and congress presentations were included. Results from short-term, placebo-controlled, MDD trials and randomized withdrawal trials, as well as post hoc analyses in patient subgroups, are reviewed. Desvenlafaxine has been shown to be an effective antidepressant with a favorable safety and tolerability profile in the general MDD population and in important patient subgroups. It has several notable differences from other serotonin-norepinephrine reuptake inhibitors, and those differences suggest populations in which it may have the most clinical benefit.

  6. Early adverse events, HPA activity and rostral anterior cingulate volume in MDD.

    Directory of Open Access Journals (Sweden)

    Michael T Treadway

    Full Text Available BACKGROUND: Prior studies have independently reported associations between major depressive disorder (MDD, elevated cortisol concentrations, early adverse events and region-specific decreases in grey matter volume, but the relationships among these variables are unclear. In the present study, we sought to evaluate the relationships between grey matter volume, early adverse events and cortisol levels in MDD. METHODS/RESULTS: Grey matter volume was compared between 19 controls and 19 individuals with MDD using voxel-based morphometry. A history of early adverse events was assessed using the Childhood Trauma Questionnaire. Subjects also provided salivary cortisol samples. Depressed patients showed decreased grey matter volume in the rostral ACC as compared to controls. Rostral ACC volume was inversely correlated with both cortisol and early adverse events. CONCLUSIONS: These findings suggest a key relationship between ACC morphology, a history of early adverse events and circulating cortisol in the pathophysiology of MDD.

  7. Mitochondrial variants in schizophrenia, bipolar disorder, and major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Brandi Rollins

    Full Text Available BACKGROUND: Mitochondria provide most of the energy for brain cells by the process of oxidative phosphorylation. Mitochondrial abnormalities and deficiencies in oxidative phosphorylation have been reported in individuals with schizophrenia (SZ, bipolar disorder (BD, and major depressive disorder (MDD in transcriptomic, proteomic, and metabolomic studies. Several mutations in mitochondrial DNA (mtDNA sequence have been reported in SZ and BD patients. METHODOLOGY/PRINCIPAL FINDINGS: Dorsolateral prefrontal cortex (DLPFC from a cohort of 77 SZ, BD, and MDD subjects and age-matched controls (C was studied for mtDNA sequence variations and heteroplasmy levels using Affymetrix mtDNA resequencing arrays. Heteroplasmy levels by microarray were compared to levels obtained with SNaPshot and allele specific real-time PCR. This study examined the association between brain pH and mtDNA alleles. The microarray resequencing of mtDNA was 100% concordant with conventional sequencing results for 103 mtDNA variants. The rate of synonymous base pair substitutions in the coding regions of the mtDNA genome was 22% higher (p = 0.0017 in DLPFC of individuals with SZ compared to controls. The association of brain pH and super haplogroup (U, K, UK was significant (p = 0.004 and independent of postmortem interval time. CONCLUSIONS: Focusing on haplogroup and individual susceptibility factors in psychiatric disorders by considering mtDNA variants may lead to innovative treatments to improve mitochondrial health and brain function.

  8. Qualitative changes in symptomatology as an effect of treatment with escitalopram in generalized anxiety disorder and major depressive disorder.

    Science.gov (United States)

    Lecrubier, Yves; Dolberg, Ornah T; Andersen, Henning F; Weiller, Emmauelle

    2008-04-01

    The purpose of this article is to examine the similarities and differences between patients with Major Depressive Disorder (MDD) versus Generalized Anxiety Disorder (GAD) versus MDD with anxiety symptoms. Data were analysed from all randomized double-blind clinical studies with escitalopram that measured symptoms using either Hamilton Anxiety Scale (HAMA) or Montgomery-Asberg Depression Rating Scale (MADRS). The contribution of each item of a scale to the total score was calculated before and after treatment, in remitters. Most single items of the HAMA contribute nearly equally in patients with GAD. In patients with MDD, four symptoms (i.e. anxious mood, tension, insomnia and concentration) contribute to most to the HAMA total score. In patients with GAD, three symptoms (tension, sleep and concentration) contribute two-thirds of the MADRS total score. In contrast, most MADRS items contribute equally to the total score in patients with MDD. After treatment to remission, the profile of residual symptoms MDD or GAD was similar to the symptom profile before treatment. Anxiety symptoms are very common in patients with MDD or GAD, and the symptomatic pattern is similar. In both disorders, the symptomatic pattern of residual symptoms is similar to the pattern of symptoms before treatment.

  9. A diagnosis of bipolar spectrum disorder predicts diagnostic conversion from unipolar depression to bipolar disorder: a 5-year retrospective study.

    Science.gov (United States)

    Woo, Young Sup; Shim, In Hee; Wang, Hee-Ryung; Song, Hoo Rim; Jun, Tae-Youn; Bahk, Won-Myong

    2015-03-15

    The major aims of this study were to identify factors that may predict the diagnostic conversion from major depressive disorder (MDD) to bipolar disorder (BP) and to evaluate the predictive performance of the bipolar spectrum disorder (BPSD) diagnostic criteria. The medical records of 250 patients with a diagnosis of MDD for at least 5 years were retrospectively reviewed for this study. The diagnostic conversion from MDD to BP was observed in 18.4% of 250 MDD patients, and the diagnostic criteria for BPSD predicted this conversion with high sensitivity (0.870) and specificity (0.917). A family history of BP, antidepressant-induced mania/hypomania, brief major depressive episodes, early age of onset, antidepressant wear-off, and antidepressant resistance were also independent predictors of this conversion. This study was conducted using a retrospective design and did not include structured diagnostic interviews. The diagnostic criteria for BPSD were highly predictive of the conversion from MDD to BP, and conversion was associated with several clinical features of BPSD. Thus, the BPSD diagnostic criteria may be useful for the prediction of bipolar diathesis in MDD patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Current understanding of the neurobiology of major depressive disorder.

    Science.gov (United States)

    Chiriţă, Anca Livia; Gheorman, Victor; Bondari, Dan; Rogoveanu, Ion

    2015-01-01

    Depression is highly prevalent worldwide and associated with significant morbidity and mortality. Approximately 340 million people worldwide suffer from depression at any given time. Based on estimates from the World Health Organization (WHO), depression is responsible for the greatest proportion of burden associated with non-fatal health outcomes and accounts for approximately 12% total years lived with disability. Probably no single risk factor can be completely isolated in major depressive disorder (MDD), as interactions between many sources of vulnerability are the most likely explanation. Buttressing the identification of grief, demoralization, hopelessness and styles of psychological coping of the depressed patient are vital, ongoing scientific developments that flow from an increased understanding of this interplay amongst the immune system, endocrine system and brain. The rapidly accumulating body of neurobiological knowledge has catalyzed fundamental changes in how we conceptualize depressive symptoms and has important implications regarding the treatment and even prevention of depressive symptoms in patients.

  11. Cognitive behavioral therapy for insomnia enhances depression outcome in patients with comorbid major depressive disorder and insomnia.

    Science.gov (United States)

    Manber, Rachel; Edinger, Jack D; Gress, Jenna L; San Pedro-Salcedo, Melanie G; Kuo, Tracy F; Kalista, Tasha

    2008-04-01

    Insomnia impacts the course of major depressive disorder (MDD), hinders response to treatment, and increases risk for depressive relapse. This study is an initial evaluation of adding cognitive behavioral therapy for insomnia (CBTI) to the antidepressant medication escitalopram (EsCIT) in individuals with both disorders. A randomized, controlled, pilot study in a single academic medical center. 30 individuals (61% female, mean age 35 +/- 18) with MDD and insomnia. EsCIT and 7 individual therapy sessions of CBTI or CTRL (quasi-desensitization). Depression was assessed with the HRSD17 and the depression portion of the SCID, administered by raters masked to treatment assignment, at baseline and after 2, 4, 6, 8, and 12 weeks of treatment. The primary outcome was remission of MDD at study exit, which required both an HRSD17 score depression (61.5%) than EsCIT + CTRL (33.3%). EsCIT + CBTI was also associated with a greater remission from insomnia (50.0%) than EsCIT + CTRL (7.7%) and larger improvement in all diary and actigraphy measures of sleep, except for total sleep time. This pilot study provides evidence that augmenting an antidepressant medication with a brief, symptom focused, cognitive-behavioral therapy for insomnia is promising for individuals with MDD and comorbid insomnia in terms of alleviating both depression and insomnia.

  12. Depression Reduces Accuracy While Parkinsonism Slows Response Time for Processing Positive Feedback in Patients with Parkinson’s Disease with Comorbid Major Depressive Disorder Tested on a Probabilistic Category-Learning Task

    Directory of Open Access Journals (Sweden)

    Mohammad M. Herzallah

    2017-06-01

    Full Text Available Major depressive disorder (MDD is the most common non-motor manifestation of Parkinson’s disease (PD affecting 50% of patients. However, little is known about the cognitive correlates of MDD in PD. Using a computer-based cognitive task that dissociates learning from positive and negative feedback, we tested four groups of subjects: (1 patients with PD with comorbid MDD, (2 patients with PD without comorbid MDD, (3 matched patients with MDD alone (without PD, and (4 matched healthy control subjects. Furthermore, we used a mathematical model of decision-making to fit both choice and response time data, allowing us to detect and characterize differences between the groups that are not revealed by cognitive results. The groups did not differ in learning accuracy from negative feedback, but the MDD groups (PD patients with MDD and patients with MDD alone exhibited a selective impairment in learning accuracy from positive feedback when compared to the non-MDD groups (PD patients without MDD and healthy subjects. However, response time in positive feedback trials in the PD groups (both with and without MDD was significantly slower than the non-PD groups (MDD and healthy groups. While faster response time usually correlates with poor learning accuracy, it was paradoxical in PD groups, with PD patients with MDD having impaired learning accuracy and PD patients without MDD having intact learning accuracy. Mathematical modeling showed that both MDD groups (PD with MDD and MDD alone were significantly slower than non-MDD groups in the rate of accumulation of information for stimuli trained by positive feedback, which can lead to lower response accuracy. Conversely, modeling revealed that both PD groups (PD with MDD and PD alone required more evidence than other groups to make responses, thus leading to slower response times. These results suggest that PD patients with MDD exhibit cognitive profiles with mixed traits characteristic of both MDD and PD

  13. Depression Reduces Accuracy While Parkinsonism Slows Response Time for Processing Positive Feedback in Patients with Parkinson's Disease with Comorbid Major Depressive Disorder Tested on a Probabilistic Category-Learning Task.

    Science.gov (United States)

    Herzallah, Mohammad M; Khdour, Hussain Y; Taha, Ahmad B; Elmashala, Amjad M; Mousa, Hamza N; Taha, Mohamad B; Ghanim, Zaid; Sehwail, Mahmud M; Misk, Adel J; Balsdon, Tarryn; Moustafa, Ahmed A; Myers, Catherine E; Gluck, Mark A

    2017-01-01

    Major depressive disorder (MDD) is the most common non-motor manifestation of Parkinson's disease (PD) affecting 50% of patients. However, little is known about the cognitive correlates of MDD in PD. Using a computer-based cognitive task that dissociates learning from positive and negative feedback, we tested four groups of subjects: (1) patients with PD with comorbid MDD, (2) patients with PD without comorbid MDD, (3) matched patients with MDD alone (without PD), and (4) matched healthy control subjects. Furthermore, we used a mathematical model of decision-making to fit both choice and response time data, allowing us to detect and characterize differences between the groups that are not revealed by cognitive results. The groups did not differ in learning accuracy from negative feedback, but the MDD groups (PD patients with MDD and patients with MDD alone) exhibited a selective impairment in learning accuracy from positive feedback when compared to the non-MDD groups (PD patients without MDD and healthy subjects). However, response time in positive feedback trials in the PD groups (both with and without MDD) was significantly slower than the non-PD groups (MDD and healthy groups). While faster response time usually correlates with poor learning accuracy, it was paradoxical in PD groups, with PD patients with MDD having impaired learning accuracy and PD patients without MDD having intact learning accuracy. Mathematical modeling showed that both MDD groups (PD with MDD and MDD alone) were significantly slower than non-MDD groups in the rate of accumulation of information for stimuli trained by positive feedback, which can lead to lower response accuracy. Conversely, modeling revealed that both PD groups (PD with MDD and PD alone) required more evidence than other groups to make responses, thus leading to slower response times. These results suggest that PD patients with MDD exhibit cognitive profiles with mixed traits characteristic of both MDD and PD, furthering

  14. The volumetric and shape changes of the putamen and thalamus in first episode, untreated major depressive disorder.

    Science.gov (United States)

    Lu, Yi; Liang, Hongmin; Han, Dan; Mo, Yin; Li, Zongfang; Cheng, Yuqi; Xu, Xiufeng; Shen, Zonglin; Tan, Chunyan; Zhao, Wei; Zhu, Yun; Sun, Xuejin

    2016-01-01

    Previous MRI studies confirmed abnormalities in the limbic-cortical-striatal-pallidal-thalamic (LCSPT) network or limbic-cortico-striatal-thalamic-cortical (LCSTC) circuits in patients with major depressive disorder (MDD), but few studies have investigated the subcortical structural abnormalities. Therefore, we sought to determine whether focal subcortical grey matter (GM) changes might be present in MDD at an early stage. We recruited 30 first episode, untreated patients with major depressive disorder (MDD) and 26 healthy control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetric and shape analyses were used to assess volume and shape changes of the subcortical GM structures, respectively. In addition, probabilistic tractography methods were used to demonstrate the relationship between the subcortical and the cortical GM. Compared to healthy controls, MDD patients had significant volume reductions in the bilateral putamen and left thalamus (FWE-corrected, p putamen, and on the dorsal and ventral aspects of left thalamus in MDD patients (FWE-corrected, p putamen and left thalamus have connections with the frontal and temporal lobes, which were found to be related to major depression. Our results suggested that structural abnormalities in the putamen and thalamus might be present in the early stages of MDD, which support the role of subcortical structure in the pathophysiology of MDD. Meanwhile, the present study showed that these subcortical structural abnormalities might be the potential trait markers of MDD.

  15. Genetic effects influencing risk for major depressive disorder in China and Europe

    NARCIS (Netherlands)

    Bigdeli, T. B.; Ripke, S.; Peterson, R. E.; Trzaskowski, M.; Bacanu, S-A; Abdellaoui, A.; Andlauer, T. F. M.; Beekman, A. T. F.; Berger, K.; Blackwood, D. H. R.; Boomsma, D. I.; Breen, G.; Buttenschon, H. N.; Byrne, E. M.; Cichon, S.; Clarke, T-K; Couvy-Duchesne, B.; Craddock, N.; de Geus, E. J. C.; Degenhardt, F.; Dunn, E. C.; Edwards, A. C.; Fanous, A. H.; Forstner, A. J.; Frank, J.; Gill, M.; Gordon, S. D.; Grabe, H. J.; Hamilton, S. P.; Hardiman, O.; Hayward, C.; Heath, A. C.; Henders, A. K.; Herms, S.; Hickie, I. B.; Hoffmann, P.; Homuth, G.; Hottenga, J-J; Ising, M.; Jansen, R.; Kloiber, S.; Knowles, J. A.; Lang, M.; Li, Q. S.; Lucae, S.; MacIntyre, D. J.; Madden, P. A. F.; Martin, N. G.; McGrath, P. J.; McGuffin, P.; McIntosh, A. M.; Medland, S. E.; Mehta, D.; Middeldorp, C. M.; Milaneschi, Y.; Montgomery, G. W.; Mors, O.; Mueller-Myhsok, B.; Nauck, M.; Nyholt, D. R.; Noethen, M. M.; Owen, M. J.; Penninx, B. W. J. H.; Pergadia, M. L.; Perlis, R. H.; Peyrot, W. J.; Porteous, D. J.; Potash, J. B.; Rice, J. P.; Rietschel, M.; Riley, B. P.; Rivera, M.; Schoevers, R.; Schulze, T. G.; Shi, J.; Shyn, S. I.; Smit, J. H.; Smoller, J. W.; Streit, F.; Strohmaier, J.; Teumer, A.; Treutlein, J.; Van der Auwera, S.; van Grootheest, G.; van Hemert, A. M.; Voelzke, H.; Webb, B. T.; Weissman, M. M.; Wellmann, J.; Willemsen, G.; Witt, S. H.; Levinson, D. F.; Lewis, C. M.; Wray, N. R.; Flint, J.; Sullivan, P. F.; Kendler, K. S.

    2017-01-01

    Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (similar to 30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated

  16. Treatment inadequacy in primary and specialized care patients with depressive and/or anxiety disorders

    NARCIS (Netherlands)

    Bet, Pierre M.; Hugtenburg, Jacqueline G.; Penninx, Brenda W. J. H.; van Balkom, Anton; Nolen, Willem A.; Hoogendijk, Witte J. G.

    2013-01-01

    All guidelines on major depressive disorder (MDD) and anxiety disorders recommend pharmacotherapy and/or psychological treatment for moderate to severe disease. The aim of this cross-sectional study was to investigate treatment inadequacy, both pharmacological and psychological, in a large naturalis

  17. Theory of mind in major depressive disorder: A meta-analysis.

    Science.gov (United States)

    Bora, Emre; Berk, Michael

    2016-02-01

    Social cognitive deficits can contribute to risk for depression and to psychosocial impairment during depression. However, available evidence suggests that emotion recognition is only marginally impaired in major depressive disorder (MDD). Recent studies have investigated theory of mind (ToM) abilities, a cognitively more demanding aspect of social cognition. We conducted a meta-analysis of studies comparing ToM abilities in MDD and healthy controls. 18 studies comparing 613 patients with MDD and 529 healthy controls were included. MDD patients significantly underperformed healthy controls in ToM (d=0.51-0.58). ToM impairment in MDD was evident in response to different types of ToM tasks (verbal/visual and cognitive/affective and reasoning/decoding). ToM impairment was significantly related to severity of depressive symptoms. Theory of mind abilities are impaired during depression and can potentially contribute to psychosocial difficulties during depression. There is a need to investigate ToM abilities in different subtypes and stages of depression, especially in remitted patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Anterior cingulate volume predicts response to cognitive behavioral therapy in major depressive disorder.

    Science.gov (United States)

    Fujino, Junya; Yamasaki, Nobuyuki; Miyata, Jun; Sasaki, Hitoshi; Matsukawa, Noriko; Takemura, Ariyoshi; Tei, Shisei; Sugihara, Genichi; Aso, Toshihiko; Fukuyama, Hidenao; Takahashi, Hidehiko; Inoue, Kazuomi; Murai, Toshiya

    2015-03-15

    Cognitive behavioral therapy (CBT) is widely used to treat major depressive disorder (MDD). Although improved response prediction could facilitate the development of individualized treatment plans, few studies have investigated whether underlying brain structure is related to CBT response in MDD. Ten MDD patients who received individual CBT were studied in this study. We investigated the relationship between the regional gray matter (GM) volume and subsequent responses to CBT using voxel-based morphometry. The degree of improvement in depressive symptoms was positively correlated with GM volume in the caudal portion of the anterior cingulate cortex. The sample size was small, and the effects of medication on the results could not be excluded. Our results, although preliminary, suggest that the anterior cingulate cortex is a key structure whose volume can be used to predict responses to CBT and is thus a potential prognostic marker in MDD. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Computer-assisted cognitive behavioral therapy for pregnant women with major depressive disorder.

    Science.gov (United States)

    Kim, Deborah R; Hantsoo, Liisa; Thase, Michael E; Sammel, Mary; Epperson, C Neill

    2014-10-01

    Pregnant women with major depressive disorder (MDD) report that psychotherapy is a more acceptable treatment than pharmacotherapy. However, although results of several studies suggest that psychotherapy is an effective treatment for pregnant women, logistical barriers-including cost and traveling for weekly visits-can limit real-world utility. We hypothesized that computer-assisted cognitive behavior therapy (CCBT) would be both acceptable and would significantly decrease depressive symptoms in pregnant women with MDD. As a preliminary test of this hypothesis, we treated 10 pregnant women with MDD using a standardized CCBT protocol. The pilot results were very promising, with 80% of participants showing treatment response and 60% showing remission after only eight sessions of CCBT. A larger, randomized controlled trial of CCBT in pregnant women with MDD is warranted.

  20. Prevalence of major depressive disorder and minor depressive disorder in an elderly Korean population: results from the Korean Longitudinal Study on Health and Aging (KLoSHA).

    Science.gov (United States)

    Park, Joon Hyuk; Lee, Jung Jae; Lee, Seok Bum; Huh, Yoonseok; Choi, Eun Ae; Youn, Jong Choul; Jhoo, Jin Hyeong; Kim, Jin Sun; Woo, Jong Inn; Kim, Ki Woong

    2010-09-01

    We investigated the prevalence, risk factors and impact of major depressive disorder (MDD) and minor depressive disorder (MnDD) in a randomly selected community-dwelling Korean elderly population. This study was conducted as a part of the Korean Longitudinal Study on Health and Aging (KLoSHA). A study population of 1118 Korean elders was randomly sampled from residents of Seongnam, Korea aged 65 years or older. Standardized face-to-face interviews and neurological and physical examinations were conducted on 714 respondents using the Korean version of Mini International Neuropsychiatric Interview. MDD was diagnosed according to the DSM-IV criteria, and MnDD according to research criteria proposed in Appendix B of the DSM-IV criteria. Age-, gender- and education-standardized prevalence rates in Korean elders aged 65 years or older were estimated as 5.37% (95% CI=3.72-7.03) for MDD, 5.52% (95% CI=3.84-7.19) for MnDD, and 10.89% (95% CI=8.60-13.17) for overall late-life depression (LLD). A prior MDD episode (OR=3.07, 95% CI=1.38-6.82 in MDD, OR=3.44, 95% CI=1.49-7.94 in MnDD), female gender (OR=3.55, 95% CI=1.53-8.24 in MDD, OR=2.68, 95% CI=1.19-6.04 in MnDD) and history of stroke or TIA (OR=3.45, 95% CI=1.62-7.35 in MDD, OR=2.95, 95% CI=1.34-6.52 in MnDD) were associated with the risks of both MDD and MnDD. Lack of formal education (OR=2.75, 95% CI=1.30-5.85) and low income (OR=2.83, 95% CI=1.02-7.88) were associated with the risk of MDD only. Quality of life (QOL) of the MDD and MnDD patients was worse than that of non-depressed elders (Pelders and impacted QOL as MDD did. MnDD patients may increase in the future with accelerated population aging and westernization of lifestyle in Korea. 2010 Elsevier B.V. All rights reserved.

  1. Affective temperaments play an important role in the relationship between childhood abuse and depressive symptoms in major depressive disorder.

    Science.gov (United States)

    Toda, Hiroyuki; Inoue, Takeshi; Tsunoda, Tomoya; Nakai, Yukiei; Tanichi, Masaaki; Tanaka, Teppei; Hashimoto, Naoki; Takaesu, Yoshikazu; Nakagawa, Shin; Kitaichi, Yuji; Boku, Shuken; Tanabe, Hajime; Nibuya, Masashi; Yoshino, Aihide; Kusumi, Ichiro

    2016-02-28

    Previous studies have shown that various factors, such as genetic and environmental factors, contribute to the development of major depressive disorder (MDD). The aim of this study is to clarify how multiple factors, including affective temperaments, childhood abuse and adult life events, are involved in the severity of depressive symptoms in MDD. A total of 98 participants with MDD were studied using the following self-administered questionnaire surveys: Patient Health Questionnaire-9 measuring the severity of depressive symptoms; Life Experiences Survey (LES) measuring negative and positive adult life events; Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego auto-questionnaire (TEMPS-A) measuring affective temperaments; and the Child Abuse and Trauma Scale (CATS) measuring childhood abuse. The data were analyzed using single and multiple regression analyses and structural equation modeling (SEM). The neglect score reported by CATS indirectly predicted the severity of depressive symptoms through affective temperaments measured by TEMPS-A in SEM. Four temperaments (depressive, cyclothymic, irritable, and anxious) directly predicted the severity of depressive symptoms. The negative change in the LES score also directly predicted severity. This study suggests that childhood abuse, especially neglect, indirectly increases the severity of depressive symptoms through increased scores of affective temperaments in MDD.

  2. Comparison of treated and untreated major depressive disorder in a nationwide sample of Korean adults.

    Science.gov (United States)

    Park, Subin; Cho, Maeng Je; Bae, Jae Nam; Chang, Sung Man; Jeon, Hong Jin; Hahm, Bong-Jin; Son, Jung-Woo; Kim, Shin Gyeom; Bae, Ahn; Hong, Jin Pyo

    2012-06-01

    We examined factors associated with lifetime treatment of major depressive disorder (MDD) in a nationwide sample of Korean adults. Of the 6,510 subjects aged 18-64 years who participated in the Korean Epidemiologic Catchment Area study, 362 (5.6%) with a lifetime diagnosis of MDD were analyzed. Diagnostic assessments were based on the Korean version of the Composite International Diagnostic Interview administered by lay interviewers. Of the 362 respondents with a lifetime diagnosis of MDD, 117 (32.3%) had been treated for psychiatric problems. Treated individuals with MDD were more likely to have chronic episode(s), more symptoms of depression, insomnia, and suicidal ideation, and were less likely to have feelings of guilt. In addition, treated individuals were more likely to have comorbid anxiety disorders, especially obsessive-compulsive disorder, post-traumatic stress disorder, and generalized anxiety disorder. Treatment-seeking by individuals with MDD is affected by socio-cultural factors such as misconception and stigma of mental illness, as well as severity of depression and comorbid conditions.

  3. A Korean validation study of the Clinically Useful Anxiety Outcome Scale: Comorbidity and differentiation of anxiety and depressive disorders.

    Science.gov (United States)

    Jeon, Sang Won; Han, Changsu; Ko, Young-Hoon; Yoon, Seoyoung; Pae, Chi-Un; Choi, Joonho; Kim, Jae-Min; Yoon, Ho-Kyoung; Lee, Hoseon; Patkar, Ashwin A; Zimmerman, Mark

    2017-01-01

    This study aimed to evaluate the psychometric properties of the Korean version of the Clinically Useful Anxiety Outcome Scale (CUXOS) and to examine the current diagnostic comorbidity and differential severity of anxiety symptoms between major depressive disorder (MDD) and anxiety disorders. In total, 838 psychiatric outpatients were analyzed at their intake appointment. Diagnostic characteristics were examined using the structured clinical interview from the DSM-IV because the DSM5 was not available at the start of the study. The CUXOS score was measured and compared with that of 3 clinician rating scales and 4 self-report scales. The CUXOS showed excellent results for internal consistency (Cronbach's α = 0.90), test-retest reliability (r = 0.74), and discriminant and convergent validity. The CUXOS significantly discriminated between different levels of anxiety severity, and the measure was sensitive to change after treatment. Approximately 45% of patients with MDD were additionally diagnosed with anxiety disorders while 55% of patients with anxiety disorders additionally reported an MDD. There was a significant difference in CUXOS scores between diagnostic categories (MDD only, anxiety only, both disorders, and no MDD or anxiety disorder). The CUXOS scores differed significantly between all categories of depression (major, minor, and non-depression) except for the comparison between minor depression and non-depression groups. The Korean version of the CUXOS is a reliable and valid measure of the severity of anxiety symptoms. The use of the CUXOS could broaden the understanding of coexisting and differentiating characteristics of anxiety and depression.

  4. Differential gene expression in patients with subsyndromal symptomatic depression and major depressive disorder.

    Science.gov (United States)

    Yang, Chengqing; Hu, Guoqin; Li, Zezhi; Wang, Qingzhong; Wang, Xuemei; Yuan, Chengmei; Wang, Zuowei; Hong, Wu; Lu, Weihong; Cao, Lan; Chen, Jun; Wang, Yong; Yu, Shunying; Zhou, Yimin; Yi, Zhenghui; Fang, Yiru

    2017-01-01

    Subsyndromal symptomatic depression (SSD) is a subtype of subthreshold depressive and can lead to significant psychosocial functional impairment. Although the pathogenesis of major depressive disorder (MDD) and SSD still remains poorly understood, a set of studies have found that many same genetic factors play important roles in the etiology of these two disorders. Nowadays, the differential gene expression between MDD and SSD is still unknown. In our previous study, we compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD and matched healthy controls (8 subjects in each group), and finally determined 48 gene expression signatures. Based on these findings, we further clarify whether these genes mRNA was different expressed in peripheral blood in patients with SSD, MDD and healthy controls (60 subjects respectively). With the help of the quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR), we gained gene relative expression levels among the three groups. We found that there are three of the forty eight co-regulated genes had differential expression in peripheral blood among the three groups, which are CD84, STRN, CTNS gene (F = 3.528, p = 0.034; F = 3.382, p = 0.039; F = 3.801, p = 0.026, respectively) while there were no significant differences for other genes. CD84, STRN, CTNS gene may have significant value for performing diagnostic functions and classifying SSD, MDD and healthy controls.

  5. Differences of biased recall memory for emotional information among children and adolescents of mothers with MDD, children and adolescents with MDD, and normal controls.

    Science.gov (United States)

    Fattahi Asl, Abouzar; Ghanizadeh, Ahmad; Mollazade, Javad; Aflakseir, Abdolaziz

    2015-08-15

    This study examines explicit memory bias for emotional information in children and adolescents with major depressive disorder (MDD). Participants were a convenient sample of 28 children and adolescents of mothers with MDD, 28 children and adolescents with MDD, and 29 healthy controls. Their age range was 11-17 years old. The groups were matched for gender ratio, mean age, and the years of educational level. They were assessed by the Recall Task. Emotional stimuli consisted of three sets of words namely sad, happy, and neutral words. Children and adolescents of mothers with MDD similar to children and adolescents with MDD recalled more sadness stimuli in comparison with the controls. In other words, they showed an explicit memory bias towards sad stimuli. Also, healthy children significantly recalled more happy words than the other two groups. There was no significant difference among the three groups for the recall of neutral stimuli. Current findings support that there is a recall memory bias for emotional information in children with MDD. These children more than healthy children recall sad words. Moreover, healthy children recall happy words more than children with MDD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Comparing neural correlates of REM sleep in posttraumatic stress disorder and depression: a neuroimaging study.

    Science.gov (United States)

    Ebdlahad, Sommer; Nofzinger, Eric A; James, Jeffrey A; Buysse, Daniel J; Price, Julie C; Germain, Anne

    2013-12-30

    Rapid eye movement (REM) sleep disturbances predict poor clinical outcomes in posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). In MDD, REM sleep is characterized by activation of limbic and paralimbic brain regions compared to wakefulness. The neural correlates of PTSD during REM sleep remain scarcely explored, and comparisons of PTSD and MDD have not been conducted. The present study sought to compare brain activity patterns during wakefulness and REM sleep in 13 adults with PTSD and 12 adults with MDD using [¹⁸F]-fluoro-2-deoxy-D-glucose positron emission tomography (PET). PTSD was associated with greater increase in relative regional cerebral metabolic rate of glucose (rCMRglc) in limbic and paralimbic structures in REM sleep compared to wakefulness. Post-hoc comparisons indicated that MDD was associated with greater limbic and paralimbic rCMRglc during wakefulness but not REM sleep compared to PTSD. Our findings suggest that PTSD is associated with increased REM sleep limbic and paralimbic metabolism, whereas MDD is associated with wake and REM hypermetabolism in these areas. These observations suggest that PTSD and MDD disrupt REM sleep through different neurobiological processes. Optimal sleep treatments between the two disorders may differ: REM-specific therapy may be more effective in PTSD.

  7. The effect of comorbid major depressive disorder or bipolar disorder on cognitive behavioral therapy for social anxiety disorder.

    Science.gov (United States)

    Fracalanza, Katie; McCabe, Randi E; Taylor, Valerie H; Antony, Martin M

    2014-06-01

    Major depressive disorder (MDD) and bipolar disorder (BD) commonly co-occur in individuals with social anxiety disorder (SAD), yet whether these comorbidities influence the outcomes of cognitive behavioral therapy (CBT) for SAD is unclear. The present study examined the degree to which individuals with SAD and comorbid MDD (SAD+MDD; n=76), comorbid BD (SAD+BD; n=19), a comorbid anxiety disorder (SAD+ANX; n=27), or no comorbid diagnoses (SAD+NCO; n=41) benefitted from CBT for SAD. Individuals were screened using the Structured Clinical Interview for DSM-IV and then completed the Social Phobia Inventory and the Depression Anxiety Stress Scales before and after 12-weeks of group CBT for SAD. At pretreatment the SAD+MDD and SAD+BD groups reported higher social anxiety symptoms than the SAD+ANX and SAD+NCO groups. All groups reported large and significant improvement in social anxiety with CBT. However, at posttreatment the SAD+MDD and SAD+BD groups continued to have higher social anxiety symptoms than the SAD+NCO group, and the SAD+ANX group did not differ in social anxiety symptoms from any group. The sample also showed small and statistically significant improvement in depressive symptoms with CBT for SAD. Information about medication was not collected in the present study, and we did not assess the long-term effects of CBT. Our results suggest that CBT for SAD is an effective treatment even in the presence of comorbid mood disorders in the short-term, although extending the course of treatment may be helpful for this population and should be investigated in future research. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Blood diagnostic biomarkers for major depressive disorder using multiplex DNA methylation profiles: discovery and validation.

    Science.gov (United States)

    Numata, Shusuke; Ishii, Kazuo; Tajima, Atsushi; Iga, Jun-ichi; Kinoshita, Makoto; Watanabe, Shinya; Umehara, Hidehiro; Fuchikami, Manabu; Okada, Satoshi; Boku, Shuken; Hishimoto, Akitoyo; Shimodera, Shinji; Imoto, Issei; Morinobu, Shigeru; Ohmori, Tetsuro

    2015-01-01

    Aberrant DNA methylation in the blood of patients with major depressive disorder (MDD) has been reported in several previous studies. However, no comprehensive studies using medication-free subjects with MDD have been conducted. Furthermore, the majority of these previous studies has been limited to the analysis of the CpG sites in CpG islands (CGIs) in the gene promoter regions. The main aim of the present study is to identify DNA methylation markers that distinguish patients with MDD from non-psychiatric controls. Genome-wide DNA methylation profiling of peripheral leukocytes was conducted in two set of samples, a discovery set (20 medication-free patients with MDD and 19 controls) and a replication set (12 medication-free patients with MDD and 12 controls), using Infinium HumanMethylation450 BeadChips. Significant diagnostic differences in DNA methylation were observed at 363 CpG sites in the discovery set. All of these loci demonstrated lower DNA methylation in patients with MDD than in the controls, and most of them (85.7%) were located in the CGIs in the gene promoter regions. We were able to distinguish patients with MDD from the control subjects with high accuracy in the discriminant analysis using the top DNA methylation markers. We also validated these selected DNA methylation markers in the replication set. Our results indicate that multiplex DNA methylation markers may be useful for distinguishing patients with MDD from non-psychiatric controls.

  9. Effectiveness of meta-cognitive and cognitive-behavioral therapy in patients with major depressive disorder.

    Science.gov (United States)

    Ashouri, Ahmad; Atef Vahid, Mohammad Kazem; Gharaee, Banafsheh; Rasoulian, Maryam

    2013-01-01

    The present study aimed to compare the effectiveness of metacognitive therapy (MCT) and cognitive-behavior therapy (CBT) in treating Iranian patients with major depressive disorder (MDD). Thirty three outpatients meeting DSM-IV-TR criteria for MDD without any other axis I and II disorders were randomly assigned to one of three treatment conditions, i.e. MCT, CBT and pharmacotherapy. The Beck Depression Inventory-II-Second Edition (BDI-II), Beck Anxiety Inventory (BAI), Ruminative Response Scale (RRS) and Dysfunctional Attitude Scale (DAS) were administered for pre-treatment, post-treatment and follow-up. Data were analyzed by repeated measures analysis of variance (ANOVA). Based on repeated measures ANOVA, all the participants demonstrated improvement in depression, anxiety, dysfunctional attitude and ruminative response. Based on percentage results, all the patients in MCT and CBT groups showed significant improvement at post-treatment phase. MCT and CBT were more effective than pharmacotherapy alone In treatment of MDD. None.

  10. Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

    Science.gov (United States)

    Power, Robert A; Tansey, Katherine E; Buttenschøn, Henriette Nørmølle; Cohen-Woods, Sarah; Bigdeli, Tim; Hall, Lynsey S; Kutalik, Zoltán; Lee, S Hong; Ripke, Stephan; Steinberg, Stacy; Teumer, Alexander; Viktorin, Alexander; Wray, Naomi R; Arolt, Volker; Baune, Bernard T; Boomsma, Dorret I; Børglum, Anders D; Byrne, Enda M; Castelao, Enrique; Craddock, Nick; Craig, Ian W; Dannlowski, Udo; Deary, Ian J; Degenhardt, Franziska; Forstner, Andreas J; Gordon, Scott D; Grabe, Hans J; Grove, Jakob; Hamilton, Steven P; Hayward, Caroline; Heath, Andrew C; Hocking, Lynne J; Homuth, Georg; Hottenga, Jouke J; Kloiber, Stefan; Krogh, Jesper; Landén, Mikael; Lang, Maren; Levinson, Douglas F; Lichtenstein, Paul; Lucae, Susanne; MacIntyre, Donald J; Madden, Pamela; Magnusson, Patrik K E; Martin, Nicholas G; McIntosh, Andrew M; Middeldorp, Christel M; Milaneschi, Yuri; Montgomery, Grant W; Mors, Ole; Müller-Myhsok, Bertram; Nyholt, Dale R; Oskarsson, Hogni; Owen, Michael J; Padmanabhan, Sandosh; Penninx, Brenda W J H; Pergadia, Michele L; Porteous, David J; Potash, James B; Preisig, Martin; Rivera, Margarita; Shi, Jianxin; Shyn, Stanley I; Sigurdsson, Engilbert; Smit, Johannes H; Smith, Blair H; Stefansson, Hreinn; Stefansson, Kari; Strohmaier, Jana; Sullivan, Patrick F; Thomson, Pippa; Thorgeirsson, Thorgeir E; Van der Auwera, Sandra; Weissman, Myrna M; Breen, Gerome; Lewis, Cathryn M

    2017-02-15

    Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset. Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer's disease, and coronary artery disease. We identified one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11-1.21, p = 5.2 × 10(-11)). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD. We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. A systematic review of mechanisms of change in mindfulness-based cognitive therapy in the treatment of recurrent major depressive disorder

    DEFF Research Database (Denmark)

    van der Velden, Anne Maj; Kuyken, Willem; Wattar, Ulla

    2015-01-01

    Background The investigation of treatment mechanisms in randomized controlled trials has considerable clinical and theoretical relevance. Despite the empirical support for the effect of mindfulness-based cognitive therapy (MBCT) in the treatment of recurrent major depressive disorder (MDD...

  12. Multidisciplinary Collaborative Care for Depressive Disorder in the Occupational Health Setting: Design of a randomised controlled trial and cost-effectiveness study

    NARCIS (Netherlands)

    M.C. Zijlstra-Vlasveld (Moniek); J.R. Anema (Han); A.T.F. Beekman (Aartjan); W. van Mechelen (Willem); R. Hoedeman (Rob); H.W. van Marwijk (Harm); F.F.H. Rutten (Frans); L. van Hakkaart-van Roijen (Leona); C.M. van der Feltz-Cornelis (Christina)

    2008-01-01

    textabstractBackground. Major depressive disorder (MDD) has major consequences for both patients and society, particularly in terms of needlessly long sick leave and reduced functioning. Although evidence-based treatments for MDD are available, they show disappointing results when implemented in

  13. Multidisciplinary Collaborative Care for Depressive Disorder in the Occupational Health Setting : design of a randomised controlled trial and cost-effectiveness study

    NARCIS (Netherlands)

    Vlasveld, Moniek C.; Anema, Johannes R.; Beekman, Aartjan T. F.; van Mechelen, Willem; Hoedeman, Rob; van Marwijk, Harm W. J.; Rutten, Frans F.; Roijen, Leona Hakkaart-van; van der Feltz-Cornelis, Christina M.

    2008-01-01

    Background: Major depressive disorder (MDD) has major consequences for both patients and society, particularly in terms of needlessly long sick leave and reduced functioning. Although evidence-based treatments for MDD are available, they show disappointing results when implemented in daily practice.

  14. Pharmacological Treatment of Major Depressive Disorder in Adolescents

    Directory of Open Access Journals (Sweden)

    Rachel L. Farley

    2005-01-01

    Full Text Available Major depressive disorder (MDD affects a significant number of adolescents today. Its consequences (including social isolation, failure to achieve crucial developmental milestones, and suicide mandate close attention in clinical practice. While tricyclics and monoamine oxidase inhibitors (MAOIs have been used infrequently and with questionable efficacy, selective serotonin reuptake inhibitors (SSRIs, particularly fluoxetine, consistently have been shown to be of benefit in treating outpatient adolescents with MDD. Despite some success with other drugs in its class, fluoxetine remains the only SSRI that is FDA approved for treatment of children and adolescents with depression. A review of recent studies is presented, including the controversy regarding the relationship of antidepressants and suicidal behavior in this patient population.

  15. Symptoms of depression as possible markers of bipolar II disorder.

    Science.gov (United States)

    Benazzi, Franco

    2006-05-01

    Underdiagnosis and misdiagnosis of bipolar-II disorder (BP-II) as a major depressive disorder (MDD) are frequently reported. The study aim was to find which symptoms of depression could be possible cross-sectional markers of BP-II, in order to reduce underdiagnosing BP-II. Consecutive 379 BP-II and 271 MDD major depressive episode (MDE) outpatients were interviewed with the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the Family History Screen, by a senior psychiatrist in a private practice. Inside-MDE hypomanic symptoms (elevated mood and increased self-esteem always absent by definition) were systematically assessed. Mixed depression was defined as an MDE plus 3 or more inside-MDE hypomanic symptoms, a definition validated by Akiskal and Benazzi. The MDE symptoms significantly more common in BP-II versus MDD were weight gain, increased eating, hypersomnia, psychomotor agitation, worthlessness, and diminished ability to concentrate. The inside-MDE hypomanic symptoms significantly more common in BP-II were distractibility, racing/crowded thoughts, irritability, psychomotor agitation, more talkativeness, increased risky and goal-directed activities. Multiple logistic regression showed that hypersomnia, racing/crowded thoughts, irritability, and psychomotor agitation were independent predictors of BP-II. Irritability had the most balanced combination of sensitivity and specificity predicting BP-II. Psychomotor agitation had the highest specificity but the lowest sensitivity. Racing/crowded thoughts had the highest sensitivity but the lowest specificity. These symptoms had a similar positive predictive value (PPV) for BP-II, which was around 70% (PPV is more clinically useful than sensitivity and specificity), which in turn was similar to the PPV of mixed depression and atypical depression (two diagnostic clinical markers of BP-II). All possible combinations of these symptoms had a PPV similar to that of the individual symptoms. The

  16. Individual Variations in Nucleus Accumbens Responses Associated with Major Depressive Disorder Symptoms.

    Science.gov (United States)

    Misaki, Masaya; Suzuki, Hideo; Savitz, Jonathan; Drevets, Wayne C; Bodurka, Jerzy

    2016-02-16

    Abnormal reward-related responses in the nucleus accumbens (NAcc) have been reported for major depressive disorder (MDD) patients. However, variability exists in the reported results, which could be due to heterogeneity in neuropathology of depression. To parse the heterogeneity of MDD we investigated variation of NAcc responses to gain and loss anticipations using fMRI. We found NAcc responses to monetary gain and loss were significantly variable across subjects in both MDD and healthy control (HC) groups. The variations were seen as a hyperactive response subtype that showed elevated activation to the anticipation of both gain and loss, an intermediate response with greater activation to gain than loss, and a suppressed-activity with reduced activation to both gain and loss compared to a non-monetary condition. While these response variability were seen in both MDD and HC subjects, specific symptoms were significantly associated with the right NAcc variation in MDD. Both the hyper- and suppressed-activity subtypes of MDD patients had severe suicidal ideation and anhedonia symptoms. The intermediate subjects had less severity in these symptoms. These results suggest that differing propensities in reward responsiveness in the NAcc may affect the development of specific symptoms in MDD.

  17. Augmentation treatment in major depressive disorder: focus on aripiprazole

    Directory of Open Access Journals (Sweden)

    J Craig Nelson

    2008-08-01

    Full Text Available J Craig Nelson1, Andrei Pikalov2, Robert M Berman31University of California San Francisco, San Francisco, California, USA; 2Otsuka Pharmaceutical Inc., Rockville, MD, USA; 3Bristol-Myers Squibb, Wallingford, CT, USAAbstract: Major depressive disorder (MDD is a disabling psychiatric condition for which effective treatment remains an outstanding need. Antidepressants are currently the mainstay of treatment for depression; however, almost two-thirds of patients will fail to achieve remission with initial treatment. As a result, a range of augmentation and combination strategies have been used in order to improve outcomes for patients. Despite the popularity of these approaches, limited data from double-blind, randomized, placebo-controlled studies are available to allow clinicians to determine which are the most effective augmentation options or which patients are most likely to respond to which options. Recently, evidence has shown that adjunctive therapy with atypical antipsychotics has the potential for beneficial antidepressant effects in the absence of psychotic symptoms. In particular, aripiprazole has shown efficacy as an augmentation option with standard antidepressant therapy in two, large, randomized, double-blind studies. Based on these efficacy and safety data, aripiprazole was recently approved by the FDA as adjunctive therapy for MDD. The availability of this new treatment option should allow more patients with MDD to achieve remission and, ultimately, long-term, successful outcomes.Keywords: major depression, antipsychotic, mood disorder, aripiprazole

  18. Genetic effects influencing risk for major depressive disorder in China and Europe

    DEFF Research Database (Denmark)

    Bigdeli, Tim B; Ripke, S; Peterson, Roseann E

    2017-01-01

    Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic...... directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects...... between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta...

  19. Reduced Caudate and Nucleus Accumbens Response to Rewards in Unmedicated Subjects with Major Depressive Disorder

    Science.gov (United States)

    Pizzagalli, Diego A.; Holmes, Avram J.; Dillon, Daniel G.; Goetz, Elena L.; Birk, Jeffrey L.; Bogdan, Ryan; Dougherty, Darin D.; Iosifescu, Dan V.; Rauch, Scott L.; Fava, Maurizio

    2009-01-01

    Objective Major depressive disorder (MDD) is characterized by impaired reward processing, possibly due to dysfunction in the basal ganglia. However, few neuroimaging studies of depression have distinguished between anticipatory and consummatory phases of reward processing. Using functional magnetic resonance imaging (fMRI) and a task that dissociates anticipatory and consummatory phases of reward processing, the authors tested the hypothesis that MDD participants would show reduced reward-related responses in basal ganglia structures. Method A monetary incentive delay task was presented to 30 unmedicated MDD subjects and 31 healthy comparison subjects during fMRI scanning. Whole-brain analyses focused on neural responses to reward-predicting cues and rewarding outcomes (i.e., monetary gains). Secondary analyses focused on the relationship between anhedonic symptoms and basal ganglia volumes. Results Relative to comparison subjects, MDD participants showed significantly weaker responses to gains in the left nucleus accumbens and bilateral caudate. Group differences in these regions were specific to rewarding outcomes and did not generalize to neutral or negative outcomes, although relatively reduced responses to monetary penalties in MDD emerged in other caudate regions. By contrast, evidence for group differences during reward anticipation was weaker, although MDD subjects showed reduced activation to reward cues in a small sector of the left posterior putamen. Among MDD subjects, anhedonic symptoms and depression severity were associated with reduced bilateral caudate volume. Conclusions These results indicate that basal ganglia dysfunction in MDD may affect the consummatory phase of reward processing. Additionally, morphometric results suggest that anhedonia in MDD is related to caudate volume. PMID:19411368

  20. Clinical Significance of the Number of Depressive Symptoms in Major Depressive Disorder: Results from the CRESCEND Study.

    Science.gov (United States)

    Park, Seon-Cheol; Sakong, Jeongkyu; Koo, Bon Hoon; Kim, Jae-Min; Jun, Tae-Youn; Lee, Min-Soo; Kim, Jung-Bum; Yim, Hyeon-Woo; Park, Yong Chon

    2016-04-01

    Our study aimed to establish the relationship between the number of depressive symptoms and the clinical characteristics of major depressive disorder (MDD). This would enable us to predict the clinical significance of the number of depressive symptoms in MDD patients. Using data from the Clinical Research Center for Depression (CRESCEND) study in Korea, 853 patients with DSM-IV MDD were recruited. The baseline and clinical characteristics of groups with different numbers of depressive symptoms were compared using the χ(2) test for discrete variables and covariance (ANCOVA) for continuous variables. In addition, the scores of these groups on the measurement tools were compared by ANCOVA after adjusting the potential effects of confounding variables. After adjusting the effects of monthly income and history of depression, a larger number of depressive symptoms indicated higher overall severity of depression (F [4, 756] = 21.458, P depressive symptoms (F [4, 767] = 19.145, P symptoms (F [4, 765] = 12.890, P depressive symptoms can be used as an index of greater illness burden in clinical psychiatry.

  1. Elevated specific peripheral cytokines found in major depressive disorder patients with childhood trauma exposure: a cytokine antibody array analysis.

    Science.gov (United States)

    Lu, Shaojia; Peng, Hongjun; Wang, Lifeng; Vasish, Seewoobudul; Zhang, Yan; Gao, Weijia; Wu, Weiwei; Liao, Mei; Wang, Mi; Tang, Hao; Li, Wenping; Li, Weihui; Li, Zexuan; Zhou, Jiansong; Zhang, Zhijun; Li, Lingjiang

    2013-10-01

    Taking into consideration the previous evidence of revealing the relationship of early life adversity, major depressive disorder (MDD), and stress-linked immunological changes, we recruited 22 MDD patients with childhood trauma exposures (CTE), 21 MDD patients without CTE, and 22 healthy controls without CTE, and then utilized a novel cytokine antibody array methodology to detect potential biomarkers underlying MDD in 120 peripheral cytokines and to evaluate the effect of CTE on cytokine changes in MDD patients. Although 13 cytokines were identified with highly significant differences in expressions between MDD patients and normal controls, this relationship was significantly attenuated and no longer significant after consideration of the effect of CTE in MDD patients. Depressed individuals with CTE (TD patients) were more likely to have higher peripheral levels of those cytokines. Severity of depression was associated with plasma levels of certain increased cytokines; meanwhile, the increased cytokines led to a proper separation of TD patients from normal controls during clustering analyses. Our research outcomes add great strength to the relationship between depression and cytokine changes and suggest that childhood trauma may play a vital role in the co-appearance of cytokine changes and depression.

  2. Extended family and friendship support networks are both protective and risk factors for major depressive disorder and depressive symptoms among African-Americans and black Caribbeans.

    Science.gov (United States)

    Taylor, Robert Joseph; Chae, David H; Lincoln, Karen D; Chatters, Linda M

    2015-02-01

    This study explores relationships between lifetime and 12-month Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) major depressive disorder (MDD), depressive symptoms, and involvement with family and friends within a national sample of African-American and Black Caribbean adults (n = 5191). MDD was assessed using the DSM-IV World Mental Health Composite International Diagnostic Interview and depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression subscale and the K6. Findings indicated that among both populations, close supportive ties with family members and friends are associated with lower rates of depression and MDD. For African-Americans, closeness to family members was important for both 12-month and lifetime MDD, and both family and friend closeness were important for depressive symptoms. For Caribbean Blacks, family closeness had more limited associations with outcomes and was directly associated with psychological distress only. Negative interactions with family (conflict, criticisms), however, were associated with higher MDD and depressive symptoms among both African-Americans and Black Caribbeans.

  3. Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group

    NARCIS (Netherlands)

    Schmaal, L; Hibar, D P; Sämann, P G; Hall, G B; Baune, B T; Jahanshad, N; Cheung, J W; van Erp, T G M; Bos, D; Ikram, M A; Vernooij, M W; Niessen, W J; Tiemeier, H; Hofman, A.; Wittfeld, K; Grabe, H J; Janowitz, D; Bülow, R; Selonke, M; Völzke, H; Grotegerd, D; Dannlowski, U; Arolt, V; Opel, N; Heindel, W; Kugel, H; Hoehn, D; Czisch, M; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Wright, M J; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Goya-Maldonado, R; Gruber, O; Krämer, B; Hatton, S N; Lagopoulos, J; Hickie, I B; Frodl, T; Carballedo, A; Frey, E M; van Velzen, L S; Penninx, B W J H; van Tol, M-J; van der Wee, N J; Davey, C G; Harrison, B J; Mwangi, B; Cao, B; Soares, J C; Veer, I M; Walter, H; Schoepf, D; Zurowski, B; Konrad, C; Schramm, E; Normann, C; Schnell, K; Sacchet, M D; Gotlib, I H; MacQueen, G M; Godlewska, B R; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Hall, J; Sussmann, J E; Li, M; Walter, M; Aftanas, L; Brack, I; Bokhan, N A; Thompson, P M; Veltman, D J

    2016-01-01

    The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Diso

  4. The gender-specific association of rs334558 in GSK3β with major depressive disorder

    Science.gov (United States)

    Liu, Sha; Wang, Le; Sun, Ning; Yang, Chunxia; Liu, Zhifen; Li, Xinrong; Cao, Xiaohua; Xu, Yong; Zhang, Kerang

    2017-01-01

    Abstract Major depressive disorder (MDD) is one of the most prevalent psychiatric illnesses with a heritability ranging from 40% to 50%. The single nucleotide polymorphism (SNP) rs334558 on the glycogen synthase kinase-3β (GSK3β) gene has been identified as a genetic risk loci associated with schizophrenia and bipolar disorder. However, results from replication studies examining the association between rs334558 and MDD remain inconsistent. In the present study, first, we conducted a meta-analysis of the association between rs334558 and MDD by combining 5 available case-control samples totaling 2311 cases and 2535 controls. Second, genotyping data from patients with MDD at our institution, after further stratification by gender, were analyzed to determine the association between rs334558 and MDD. All studies retrieved and included in the meta-analysis were from Korea and China. The meta-analysis suggested that the functional polymorphism rs334558 within the GSK3β promoter region was associated with MDD risk (P < 0.05). The associations were observed both in the allelic and genetic models. Analysis of the genotyping data extracted from our hospital database revealed that rs334558 exhibited exclusive association with MDD in female patients (P=0.015). Our findings suggest that GSK3β rs334558 polymorphisms might be a potential risk for MDD, and females with GSK3β rs334558 polymorphisms might have higher penetrance of MDD. If validated in larger scale samples and in different ethnic populations, these findings might be of value as diagnostic references for MDD. PMID:28099358

  5. Mismatch negativity of sad syllables is absent in patients with major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Xiaomei Pang

    Full Text Available BACKGROUND: Major depressive disorder (MDD is an important and highly prevalent mental disorder characterized by anhedonia and a lack of interest in everyday activities. Additionally, patients with MDD appear to have deficits in various cognitive abilities. Although a number of studies investigating the central auditory processing of low-level sound features in patients with MDD have demonstrated that this population exhibits impairments in automatic processing, the influence of emotional voice processing has yet to be addressed. To explore the automatic processing of emotional prosodies in patients with MDD, we analyzed the ability to detect automatic changes using event-related potentials (ERPs. METHOD: This study included 18 patients with MDD and 22 age- and sex-matched healthy controls. Subjects were instructed to watch a silent movie but to ignore the afferent acoustic emotional prosodies presented to both ears while continuous electroencephalographic activity was synchronously recorded. Prosodies included meaningless syllables, such as "dada" spoken with happy, angry, sad, or neutral tones. The mean amplitudes of the ERPs elicited by emotional stimuli and the peak latency of the emotional differential waveforms were analyzed. RESULTS: The sad MMN was absent in patients with MDD, whereas the happy and angry MMN components were similar across groups. The abnormal sad emotional MMN component was not significantly correlated with the HRSD-17 and HAMA scores, respectively. CONCLUSION: The data indicate that patients with MDD are impaired in their ability to automatically process sad prosody, whereas their ability to process happy and angry prosodies remains normal. The dysfunctional sad emotion-related MMN in patients with MDD were not correlated with depression symptoms. The blunted MMN of sad prosodies could be considered a trait of MDD.

  6. Further evidence of emotional allodynia in unmedicated young adults with major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Alexander Ushinsky

    Full Text Available BACKGROUND: Recent evidence suggests that sensitivity to the emotional sequela of experimental thermal pain(measured by emotional unpleasantness is heightened in individuals with major depressive disorder(MDD, a phenomenon we termed "emotional allodynia". The aim of this study was to examine whether acute happy and sad mood induction alters emotional allodynia in MDD. We hypothesized that emotional allodynia will be a robust characteristic of individuals with MDD compared to healthy controls. Thus, it would remain following acute mood induction, independent of valence. METHODS: Twenty-one subjects with current MDD and 21 well-matched healthy subjects(HC received graded brief temperature stimuli following happy and sad mood inductions procedures(MIP. All subjects rated the intensity and affect(pleasantness/unpleasantness of each stimulus. Sensory(pain intensity and affective(pain unpleasantness thresholds were determined by methods of constant stimuli. RESULTS: The MIPs reliably induced happy and sad mood and the resulting induced mood and subjective arousal were not different between the groups at the time of temperature stimulation. Compared to HC, MDD individuals demonstrated emotional allodynia. We found significantly decreased affective pain thresholds whereby significantly lower temperatures became unpleasant in the MDD compared to the HC group. This was not observed for the sensory pain thresholds. Within the MDD, the affective pain thresholds were significantly lower than the corresponding pain intensity thresholds, whereby non-painful temperatures were already unpleasant for the MDD irrespective of the induced mood. This was not observed for the HC groups where the affective and pain intensity thresholds were comparable. CONCLUSIONS: These findings suggest that emotional allodynia may be a chronic characteristic of current MDD. Future studies should determine if emotional allodynia persists after psychological or pharmacological

  7. Preferences regarding targeted education and risk assessment in people with a family history of major depressive disorder.

    Science.gov (United States)

    Quinn, Veronica; Meiser, Bettina; Wilde, Alex; Cousins, Zoe; Barlow-Stewart, Kristine; Mitchell, Philip B; Schofield, Peter R

    2014-10-01

    Genetic testing for susceptibility to major depressive disorder (MDD) is not available for clinical use at present. Given this, family history remains the best predictor for development of MDD, and family-history-based risk assessment and information about familial aspects of MDD may be useful to clients at increased risk for MDD attending for genetic counseling. This study uses a mixed-methods design to assess the information needs and preferences of people at increased familial risk for MDD. Telephone interviews were conducted with 23 individuals, who had at least one first-degree relative with MDD and were recruited through advertisements placed on depression education websites. The most preferred way to access depression information was via the internet (87 % of participants), although this preference may have been due to the internet-based recruitment method. The second most preferred dissemination strategy (56 %) was face-to-face delivery through a health professional, including genetic counselors. Individuals reported a need for information about etiology and development of MDD, reproductive decision-making, early detection of symptoms and risk-reducing strategies. Nearly all participants expressed an interest in risk assessment. The present study found evidence of a high level of interest for information targeted to people at increased familial risk for MDD. Genetic counselors are likely to be called upon increasingly to provide supportive counseling to assist clients at increased familial risk in interpreting and contextualizing such information once it becomes available.

  8. Gray Matter Abnormalities in Non-comorbid Medication-naive Patients with Major Depressive Disorder or Social Anxiety Disorder.

    Science.gov (United States)

    Zhao, Youjin; Chen, Lizhou; Zhang, Wenjing; Xiao, Yuan; Shah, Chandan; Zhu, Hongru; Yuan, Minlan; Sun, Huaiqiang; Yue, Qiang; Jia, Zhiyun; Zhang, Wei; Kuang, Weihong; Gong, Qiyong; Lui, Su

    2017-07-01

    An overlap of clinical symptoms between major depressive disorder (MDD) and social anxiety disorder (SAD) suggests that the two disorders exhibit similar brain mechanisms. However, few studies have directly compared the brain structures of the two disorders. The aim of this study was to assess the gray matter volume (GMV) and cortical thickness alterations between non-comorbid medication-naive MDD patients and SAD patients. High-resolution T1-weighted images were acquired from 37 non-comorbid MDD patients, 24 non-comorbid SAD patients and 41 healthy controls (HCs). Voxel-based morphometry analysis of the GMV (corrected with a false discovery rate of psuperior parietal cortex; and cortical thinning in the left lateral OFC and bilateral rostral middle frontal cortex. In addition, MDD patients specifically showed a greater thickness in the left fusiform gyrus and right lateral occipital cortex and a thinner thickness in the bilateral lingual and left cuneus. SAD patients specifically showed a thinner cortical thickness in the right precentral cortex. Our results indicate that MDD and SAD share common patterns of gray matter abnormalities in the orbitofrontal-striatal-thalamic circuit, salience network and dorsal attention network. These consistent structural differences in the two patient groups may contribute to the broad spectrum of emotional, cognitive and behavioral disturbances observed in MDD patients and SAD patients. In addition, we found disorder-specific involvement of the visual processing regions in MDD and the precentral cortex in SAD. These findings provide new evidence regarding the shared and specific neuropathological mechanisms that underlie MDD and SAD. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. The epidemiology of major depressive disorder and subthreshold depression in Izmir, Turkey: Prevalence, socioeconomic differences, impairment and help-seeking.

    Science.gov (United States)

    Topuzoğlu, Ahmet; Binbay, Tolga; Ulaş, Halis; Elbi, Hayriye; Tanık, Feride Aksu; Zağlı, Nesli; Alptekin, Köksal

    2015-08-01

    Subclinical and clinical depression is common, widely distributed in the general population, and usually associated with role impairment and help-seeking. Reliable information at the population level is needed to estimate the disease burden of depression and associated care needs in Turkey. The cross-sectional study aimed to assess the prevalence of subthreshold (SubD) and clinical major depressive disorder (MDD) in Izmir, Turkey. In the 5242 eligible households, a total of 4011 individuals were successfully interviewed, yielding a response rate of 76.5%. Prevalence estimates of MDD and SubD depression were formed by using the responses to the questions of the CIDI section E. Short Form 36 (SF-36) to assess health status and functional impairments in eight scaled scores during the last four weeks. All respondents were questioned about receiving 12-month treatment for any psychological complaints, the route of help-seeking, as well as prescribed medicines and any hospitalization. The one year prevalence estimate for CIDI/DSM IV MDD was 8.2% (95% CI, 7.4-9.1). Less educated, low income, uninsured, low SES, unemployed/disabled and housewives, slum area residents had higher one year MDD prevalence. Determined prevalence of help seeking from mental health services of SubD and MDD cases were 23.6%, 30.6% respectively. Only 24.8% of clinically depressive patients received minimally adequate treatment. Cross sectional design. Higher MDD prevalence correlates with younger ages, female gender, unemployment, less education, lower monthly income, lower SES and uninsurance. Help seeking from mental health services were low. There are treatment gap and impairment in depressive group. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Learning from negative feedback in patients with major depressive disorder is attenuated by SSRI antidepressants.

    Science.gov (United States)

    Herzallah, Mohammad M; Moustafa, Ahmed A; Natsheh, Joman Y; Abdellatif, Salam M; Taha, Mohamad B; Tayem, Yasin I; Sehwail, Mahmud A; Amleh, Ivona; Petrides, Georgios; Myers, Catherine E; Gluck, Mark A

    2013-01-01

    One barrier to interpreting past studies of cognition and major depressive disorder (MDD) has been the failure in many studies to adequately dissociate the effects of MDD from the potential cognitive side effects of selective serotonin reuptake inhibitors (SSRIs) use. To better understand how remediation of depressive symptoms affects cognitive function in MDD, we evaluated three groups of subjects: medication-naïve patients with MDD, medicated patients with MDD receiving the SSRI paroxetine, and healthy control (HC) subjects. All were administered a category-learning task that allows for dissociation between learning from positive feedback (reward) vs. learning from negative feedback (punishment). Healthy subjects learned significantly better from positive feedback than medication-naïve and medicated MDD groups, whose learning accuracy did not differ significantly. In contrast, medicated patients with MDD learned significantly less from negative feedback than medication-naïve patients with MDD and healthy subjects, whose learning accuracy was comparable. A comparison of subject's relative sensitivity to positive vs. negative feedback showed that both the medicated MDD and HC groups conform to Kahneman and Tversky's (1979) Prospect Theory, which expects losses (negative feedback) to loom psychologically slightly larger than gains (positive feedback). However, medicated MDD and HC profiles are not similar, which indicates that the state of medicated MDD is not "normal" when compared to HC, but rather balanced with less learning from both positive and negative feedback. On the other hand, medication-naïve patients with MDD violate Prospect Theory by having significantly exaggerated learning from negative feedback. This suggests that SSRI antidepressants impair learning from negative feedback, while having negligible effect on learning from positive feedback. Overall, these findings shed light on the importance of dissociating the cognitive consequences of MDD

  11. Altered effective connectivity within default mode network in major depression disorder

    Science.gov (United States)

    Li, Liang; Li, Baojuan; Bai, Yuanhan; Wang, Huaning; Zhang, Linchuan; Cui, Longbiao; Lu, Hongbing

    2016-03-01

    Understanding the neural basis of Major Depressive Disorder (MDD) is important for the diagnosis and treatment of this mental disorder. The default mode network (DMN) is considered to be highly involved in the MDD. To find directed interaction between DMN regions associated with the development of MDD, the effective connectivity within the DMN of the MDD patients and matched healthy controls was estimated by using a recently developed spectral dynamic causal modeling. Sixteen patients with MDD and sixteen matched healthy control subjects were included in this study. While the control group underwent the resting state fMRI scan just once, all patients underwent resting state fMRI scans before and after two months' treatment. The spectral dynamic causal modeling was used to estimate directed connections between four DMN nodes. Statistical analysis on connection strengths indicated that efferent connections from the medial frontal cortex (MFC) to posterior cingulate cortex (PCC) and to right parietal cortex (RPC) were significant higher in pretreatment MDD patients than those of the control group. After two-month treatment, the efferent connections from the MFC decreased significantly, while those from the left parietal cortex (LPC) to MFC, PCC and RPC showed a significant increase. These findings suggest that the MFC may play an important role for inhibitory conditioning of the DMN, which was disrupted in MDD patients. It also indicates that disrupted suppressive function of the MFC could be effectively restored after two-month treatment.

  12. Coping strategies related to treatment in substance use disorder patients with and without comorbid depression.

    Science.gov (United States)

    Adan, Ana; Antúnez, Juan Manuel; Navarro, José Francisco

    2017-05-01

    Coping strategies exert an important influence in the development and course of both substance use disorder (SUD) and major depressive disorder (MDD) and its treatment outcomes. We examined the coping strategies related to treatment in SUD and SUD-MDD patients and their associations with clinical characteristics. Forty SUD and 40 SUD-MDD males, each group composed by 20 therapeutic community and 20 ambulatory treatment patients, were assessed through the Coping Strategies Inventory and clinical characteristics questionnaires. SUD-MDD patients scored higher in Disengagement strategies such as Social Withdrawal and lower in Engagement ones such as Problem Solving, Cognitive Restructuring and Social Support, as well as in self-perceived capacity for coping. No differences for treatment were found. SUD and, specially, SUD-MDD patients scored higher than norms in maladaptive strategies. Time of abstinence, age of onset and severity of SUD were related to maladaptive coping. SUD and SUD-MDD patients are prone to employ Disengagement coping strategies and SUD-MDD patients coping repertory is more maladaptive than the SUD ones. Likewise, clinical characteristics associated to maladaptive coping might differ by diagnosis and modality of treatment in male patients. These findings could be considered for the treatment design and to improve the recovery and prevent relapses.

  13. Moderators of the Effects of Indicated Group and Bibliotherapy Cognitive Behavioral Depression Prevention Programs on Adolescents’ Depressive Symptoms and Depressive Disorder Onset

    Science.gov (United States)

    Müller, Sina; Rohde, Paul; Gau, Jeff M.; Stice, Eric

    2015-01-01

    We investigated factors hypothesized to moderate the effects of cognitive behavioral group-based (CB group) and bibliotherapy depression prevention programs. Using data from two trials (N = 631) wherein adolescents (M age = 15.5, 62% female, 61% Caucasian) with depressive symptoms were randomized into CB group, CB bibliotherapy, or an educational brochure control condition, we evaluated the moderating effects of individual, demographic, and environmental factors on depressive symptom reductions and major depressive disorder (MDD) onset over 2-year follow-up. CB group and bibliotherapy participants had lower depressive symptoms than controls at posttest but these effects did not persist. No MDD prevention effects were present in the merged data. Relative to controls, elevated depressive symptoms and motivation to reduce depression amplified posttest depressive symptom reduction for CB group, and elevated baseline symptoms amplified posttest symptom reduction effects of CB bibliotherapy. Conversely, elevated substance use mitigated the effectiveness of CB group relative to controls on MDD onset over follow-up. Findings suggest that both CB prevention programs are more beneficial for youth with at least moderate depressive symptoms, and that CB group is more effective for youth motivated to reduce their symptoms. Results also imply that substance use reduces the effectiveness of CB group-based depression prevention. PMID:26480199

  14. Moderators of the effects of indicated group and bibliotherapy cognitive behavioral depression prevention programs on adolescents' depressive symptoms and depressive disorder onset.

    Science.gov (United States)

    Müller, Sina; Rohde, Paul; Gau, Jeff M; Stice, Eric

    2015-12-01

    We investigated factors hypothesized to moderate the effects of cognitive behavioral group-based (CB group) and bibliotherapy depression prevention programs. Using data from two trials (N = 631) wherein adolescents (M age = 15.5, 62% female, 61% Caucasian) with depressive symptoms were randomized into CB group, CB bibliotherapy, or an educational brochure control condition, we evaluated the moderating effects of individual, demographic, and environmental factors on depressive symptom reductions and major depressive disorder (MDD) onset over 2-year follow-up. CB group and bibliotherapy participants had lower depressive symptoms than controls at posttest but these effects did not persist. No MDD prevention effects were present in the merged data. Relative to controls, elevated depressive symptoms and motivation to reduce depression amplified posttest depressive symptom reduction for CB group, and elevated baseline symptoms amplified posttest symptom reduction effects of CB bibliotherapy. Conversely, elevated substance use mitigated the effectiveness of CB group relative to controls on MDD onset over follow-up. Findings suggest that both CB prevention programs are more beneficial for youth with at least moderate depressive symptoms, and that CB group is more effective for youth motivated to reduce their symptoms. Results also imply that substance use reduces the effectiveness of CB group-based depression prevention. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Increased activities of both superoxide dismutase and catalase were indicators of acute depressive episodes in patients with major depressive disorder.

    Science.gov (United States)

    Tsai, Meng-Chang; Huang, Tiao-Lai

    2016-01-30

    Oxidative stress may play an important role in the pathophysiology of major depressive disorder (MDD). The aim of this study was to investigate the serum levels of oxidative stress biomarkers and S100B in patients with MDD in an acute phase, and evaluate the changes in superoxide dismutase (SOD), protein carbonyl content (PCC), glutathione peroxidase (GPX), 8-hydroxy 2'-deoxyguanosine after treatment (8-OHdG), catalase (CAT), thiobarbituric acid reactive substances (TBARS) and S100B. We consecutively enrolled 21 MDD inpatients in an acute phase and 40 healthy subjects. Serum oxidative stress markers were measured with assay kits. Serum SOD and CAT activities in MDD patients in an acute phase were significantly higher than those of healthy subjects, and serum PCC levels were significantly lower. The HAM-D scores had a significantly positive association with S100B levels. Eighteen depressed patients were followed up, and there was no significant difference among all of the markers after treatment. In conclusion, our results suggest that increased activities of both SOD and CAT might be indicators of acute depressive episodes in MDD patients.

  16. Combined effects of major depression, pain and somatic disorders on general functioning in the general adult population.

    Science.gov (United States)

    Baune, Bernhard T; Caniato, Riccardo N; Garcia-Alcaraz, Miguel A; Berger, Klaus

    2008-08-31

    This study was carried out to assess the prevalence of major depressive disorder (MDD) in persons suffering from pain symptoms in various locations, both with and without comorbid somatic disorders and to analyze the single and combined effects of MDD, pain symptoms and somatic disorders on general functioning in the community. The 12-month prevalence of MDD, somatic disorders and pain symptoms, grouped according to location, were determined among 4181 participants from a community sample. Depression was assessed utilising the Composite International Diagnostic Interview. Pain symptoms were self-reported by participants whereas medical diagnoses were validated by medical examinations. General functioning was evaluated utilising the established MOS-SF-36 scale. The prevalence of MDD was significantly increased for persons with pain in any location. In the absence of a somatic disorder, MDD prevalence was highest in persons with abdominal/chest pain (9.3%) and arm or leg pain (7.9%) and lowest in persons with back pain (6.2%). Mental and physical well-being were lowest for persons with both MDD and a somatic disorder, irrespective of pain locations. Increasing numbers of pain locations impaired mental and physical well-being across all groups, but the effect on mental well-being was most marked in participants with MDD and comorbid somatic disorders. The presence of pain increases risk of associated MDD. The number of pain locations experienced, rather than the specific location of pain, has the greatest impact on general functioning. Not only chronic pain, but pain of any type may be an indicator of MDD and decreased general functioning.

  17. Treatment inadequacy in primary and specialized care patients with depressive and/or anxiety disorders.

    Science.gov (United States)

    Bet, Pierre M; Hugtenburg, Jacqueline G; Penninx, Brenda W J H; Balkom, Anton van; Nolen, Willem A; Hoogendijk, Witte J G

    2013-12-15

    All guidelines on major depressive disorder (MDD) and anxiety disorders recommend pharmacotherapy and/or psychological treatment for moderate to severe disease. The aim of this cross-sectional study was to investigate treatment inadequacy, both pharmacological and psychological, in a large naturalistic cohort of subjects with MDD and anxiety disorders from the Netherlands Study of Depression and Anxiety. All subjects with a current 6-month diagnosis were included (n=1662). Demographic data, clinical features and actual medication use were assessed in face-to-face interviews. In moderate to severe MDD, 43% of the subjects were not treated sufficiently with antidepressants or psychological treatment. In primary health care patients, this undertreatment was 70%. In moderate to severe anxiety disorders, 44% of the subjects were not treated sufficiently with antidepressants, benzodiazepines or psychological treatment. Among antidepressant users with moderate to severe MDD, 21% of the pharmacotherapy was inadequate with respect to drug choice, dose and every day use. Undertreatment and pharmacotherapeutic inadequacy are common in moderate to severe MDD and anxiety disorders. Both are more pronounced in primary care than in specialized care. This may be partly due to differences in disease recognition and help seeking behaviour. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Large-Scale Hypoconnectivity Between Resting-State Functional Networks in Unmedicated Adolescent Major Depressive Disorder.

    Science.gov (United States)

    Sacchet, Matthew D; Ho, Tiffany C; Connolly, Colm G; Tymofiyeva, Olga; Lewinn, Kaja Z; Han, Laura Km; Blom, Eva H; Tapert, Susan F; Max, Jeffrey E; Frank, Guido Kw; Paulus, Martin P; Simmons, Alan N; Gotlib, Ian H; Yang, Tony T

    2016-11-01

    Major depressive disorder (MDD) often emerges during adolescence, a critical period of brain development. Recent resting-state fMRI studies of adults suggest that MDD is associated with abnormalities within and between resting-state networks (RSNs). Here we tested whether adolescent MDD is characterized by abnormalities in interactions among RSNs. Participants were 55 unmedicated adolescents diagnosed with MDD and 56 matched healthy controls. Functional connectivity was mapped using resting-state fMRI. We used the network-based statistic (NBS) to compare large-scale connectivity between groups and also compared the groups on graph metrics. We further assessed whether group differences identified using nodes defined from functionally defined RSNs were also evident when using anatomically defined nodes. In addition, we examined relations between network abnormalities and depression severity and duration. Finally, we compared intranetwork connectivity between groups and assessed the replication of previously reported MDD-related abnormalities in connectivity. The NBS indicated that, compared with controls, depressed adolescents exhibited reduced connectivity (pdepression was significantly correlated with reduced connectivity in this set of network interactions (p=0.020, corrected), specifically with reduced connectivity between components of the dorsal attention network. The dorsal attention network was also characterized by reduced intranetwork connectivity in the MDD group. Finally, we replicated previously reported abnormal connectivity in individuals with MDD. In summary, adolescents with MDD show hypoconnectivity between large-scale brain networks compared with healthy controls. Given that connectivity among these networks typically increases during adolescent neurodevelopment, these results suggest that adolescent depression is associated with abnormalities in neural systems that are still developing during this critical period.

  19. Anxious and non-anxious major depressive disorder in the World Health Organization World Mental Health Surveys

    Science.gov (United States)

    Kessler, R.C.; Sampson, N.A.; Berglund, P.; Gruber, M.J.; Al-Hamzawi, A.; Andrade, L.; Bunting, B.; Demyttenaere, K.; Florescu, S.; de Girolamo, G.; Gureje, O.; He, Y.; Hu, C.; Huang, Y.; Karam, E.; Kovess-Masfety, V.; Lee, S; Levinson, D.; Mora, M.E. Medina; Moskalewicz, J.; Nakamura, Y.; Navarro-Mateu, F.; Oakley Browne, Mark A.; Piazza, M.; Posada-Villa, J.; Slade, T.; ten Have, M.; Torres, Y.; Vilagut, G.; Xavier, M.; Zarkov, Z.; Shahly, V.; Wilcox, M.A.

    2016-01-01

    AIMS To examine cross-national patterns and correlates of lifetime and 12-month comorbid DSM-IV anxiety disorders among people with lifetime and 12-month DSM-IV major depressive disorder (MDD). METHODS Nationally or regionally representative epidemiological interviews were administered to 74,045 adults in 27 surveys across 24 countries in the WHO World Mental Health (WMH) Surveys. DSM-IV MDD, a wide range of comorbid DSM-IV anxiety disorders, and a number of correlates were assessed with the WHO Composite International Diagnostic Interview (CIDI). RESULTS 45.7% of respondents with lifetime MDD (32.0–46.5% inter-quartile range [IQR] across surveys) had one of more lifetime anxiety disorders. A slightly higher proportion of respondents with 12-month MDD had lifetime anxiety disorders (51.7%, 37.8–54.0% IQR) and only slightly lower proportions of respondents with 12-month MDD had 12-month anxiety disorders (41.6%, 29.9–47.2% IQR). Two-thirds (68%) of respondents with lifetime comorbid anxiety disorders and MDD reported an earlier age-of-onset of their first anxiety disorder than their MDD, while 13.5% reported an earlier age-of-onset of MDD and the remaining 18.5% reported the same age-of-onset of both disorders. Women and previously married people had consistently elevated rates of lifetime and 12-month MDD as well as comorbid anxiety disorders. Consistently higher proportions of respondents with 12-month anxious than non-anxious MDD reported severe role impairment (64.4% vs. 46.0%; χ21=187.0, p<.001) and suicide ideation (19.5% vs. 8.9%; χ21=71.6, p<.001). Significantly more respondents with 12-month anxious than non-anxious MDD received treatment for their depression in the 12 months before interview, but this difference was more pronounced in high income countries (68.8% vs. 45.4%; χ21=108.8, p<.001) than low/middle income countries (30.3% vs. 20.6%; χ21=11.7, p<.001). CONCLUSIONS Patterns and correlates of comorbid DSM-IV anxiety disorders among people

  20. Identifying major depressive disorder using Hurst exponent of resting-state brain networks.

    Science.gov (United States)

    Wei, Maobin; Qin, Jiaolong; Yan, Rui; Li, Haoran; Yao, Zhijian; Lu, Qing

    2013-12-30

    Resting-state functional magnetic resonance imaging (fMRI) studies of major depressive disorder (MDD) have revealed abnormalities of functional connectivity within or among the resting-state networks. They provide valuable insight into the pathological mechanisms of depression. However, few reports were involved in the "long-term memory" of fMRI signals. This study was to investigate the "long-term memory" of resting-state networks by calculating their Hurst exponents for identifying depressed patients from healthy controls. Resting-state networks were extracted from fMRI data of 20 MDD and 20 matched healthy control subjects. The Hurst exponent of each network was estimated by Range Scale analysis for further discriminant analysis. 95% of depressed patients and 85% of healthy controls were correctly classified by Support Vector Machine with an accuracy of 90%. The right fronto-parietal and default mode network constructed a deficit network (lower memory and more irregularity in MDD), while the left fronto-parietal, ventromedial prefrontal and salience network belonged to an excess network (longer memory in MDD), suggesting these dysfunctional networks may be related to a portion of the complex of emotional and cognitive disturbances. The abnormal "long-term memory" of resting-state networks associated with depression may provide a new possibility towards the exploration of the pathophysiological mechanisms of MDD.

  1. Divergent Urinary Metabolic Phenotypes between Major Depressive Disorder and Bipolar Disorder Identified by a Combined GC-MS and NMR Spectroscopic Metabonomic Approach.

    Science.gov (United States)

    Chen, Jian-Jun; Zhou, Chan-Juan; Liu, Zhao; Fu, Yu-Ying; Zheng, Peng; Yang, De-Yu; Li, Qi; Mu, Jun; Wei, You-Dong; Zhou, Jing-Jing; Huang, Hua; Xie, Peng

    2015-08-07

    Bipolar disorder (BD) is a complex debilitating mental disorder that is often misdiagnosed as major depressive disorder (MDD). Therefore, a large percentage of BD subjects are incorrectly treated with antidepressants in clinical practice. To address this challenge, objective laboratory-based tests are needed to discriminate BD from MDD patients. Here, a combined gas chromatography-mass spectrometry (GC-MS)-based and nuclear magnetic resonance (NMR) spectroscopic-based metabonomic approach was performed to profile urine samples from 76 MDD and 43 BD subjects (training set) to identify the differential metabolites. Samples from 126 healthy controls were included as metabolic controls. A candidate biomarker panel was identified by further analyzing these differential metabolites. A testing set of, 50 MDD and 28 BD subjects was then used to independently validate the diagnostic efficacy of the identified panel using an area under the receiver operating characteristic curve (AUC). A total of 20 differential metabolites responsible for the discrimination between MDD and BD subjects were identified. A panel consisting of six candidate urinary metabolite biomarkers (propionate, formate, (R*,S*)2,3-dihydroxybutanoic acid, 2,4-dihydroxypyrimidine, phenylalanine, and β-alanine) was identified. This panel could distinguish BD from MDD subjects with an AUC of 0.913 and 0.896 in the training and testing sets, respectively. These results reveal divergent urinary metabolic phenotypes between MDD and BD. The identified urinary biomarkers can aid in the future development of an objective laboratory-based diagnostic test for distinguishing BD from MDD patients.

  2. Near-infrared spectroscopic study of frontopolar activation during face-to-face conversation in major depressive disorder and bipolar disorder.

    Science.gov (United States)

    Takei, Yuichi; Suda, Masashi; Aoyama, Yoshiyuki; Sakurai, Noriko; Tagawa, Minami; Motegi, Tomokazu; Yamaguchi, Miho; Narita, Kosuke; Fukuda, Masato

    2014-10-01

    Major depressive disorder (MDD) and bipolar disorder (BD) patients show speech characteristics that vary greatly according to mood state. In a previous study, we found impaired temporal and right inferior frontal gyrus (IFG) activation in schizophrenia during face-to-face conversation; no study had, however, previously investigated mood disorders during face-to-face conversation. Here, we investigated frontal and temporal lobe activation during conversation in patients with MDD and BD. Frontal and temporal lobe activation was measured using near-infrared spectroscopy (NIRS) in 29 patients with MDD, 31 patients with BD, and 31 normal controls (NC). We compared continuous activation and rapid change of activation with talk/listen phase changes during the conversation and analyzed the correlation between these indices and clinical variables. Both the MDD and BD groups showed decreased continuous activation in the left dorsolateral prefrontal (DLPFC) and left frontopolar cortices (FPCs); they also showed decreased rapid change in bilateral FPC activation. In the MDD group, the rapid change of activation was positively correlated with Global Assessment of Functioning (GAF) scores. In the BD group, continuous activation was negatively correlated with age of onset. These results indicate that frontal activation during conversation decreases in both MDD and BD. However, both continuous activation and rapid change may reflect the pathophysiological character of MDD and BD; in particular, the reduced amount of rapid change in the right FPC may be related to impaired adaptive ability in MDD.

  3. The role of the potassium channel gene KCNK2 in major depressive disorder.

    Science.gov (United States)

    Congiu, Chiara; Minelli, Alessandra; Bonvicini, Cristian; Bortolomasi, Marco; Sartori, Riccardo; Maj, Carlo; Scassellati, Catia; Maina, Giuseppe; Trabucchi, Luigi; Segala, Matilde; Gennarelli, Massimo

    2015-02-28

    Six single nucleotide polymorphisms (SNPs) of the KCNK2 gene were investigated for their association with major depressive disorder (MDD) and treatment efficacy in 590 MDD patients and 441 controls. The A homozygotes of rs10779646 were significantly more frequent in patients than controls whereas G allele of rs7549184 was associated with the presence of psychotic symptoms and the severity of disease. Evaluating the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) dataset, we confirmed our findings. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Stressful life events preceding the onset of depression in Asian patients with major depressive disorder.

    Science.gov (United States)

    Park, Subin; Hatim, Ahmad; Si, Tian-Mei; Jeon, Hong Jin; Srisurapanont, Manit; Bautista, Dianne; Liu, Shen-ing; Chua, Hong Choon; Hong, Jin Pyo

    2015-12-01

    Previous studies have identified the significant role of stressful life events in the onset of depressive episodes. However, there is a paucity of cross-national studies on stressful life events that precede depression. We aimed to compare types of stressful life events associated with the onset of depressive episodes in patients with major depressive disorder (MDD) in five Asian countries. A total of 507 outpatients with MDD were recruited in China (n = 114), South Korea (n = 101), Malaysia (n = 90), Thailand (n = 103) and Taiwan (n = 99). All patients were assessed with the Mini-International Neuropsychiatric Interview and the List of Threatening Experiences. The prevalence of each type of stressful life events was calculated and compared between each country. The type of stressful life event that preceded the onset of a depressive episode differed between patients in China and Taiwan and those in South Korea, Malaysia and Thailand. Patients in China and Taiwan were less likely to report interpersonal relationship problems and occupational/financial problems than patients in South Korea, Malaysia and Thailand. Understanding the nature and basis of culturally determined susceptibilities to specific stressful life events is critical for establishing a policy of depression prevention and providing effective counseling services for depressed patients. © The Author(s) 2015.

  5. Reduced frontal-subcortical white matter connectivity in association with suicidal ideation in major depressive disorder.

    Science.gov (United States)

    Myung, W; Han, C E; Fava, M; Mischoulon, D; Papakostas, G I; Heo, J-Y; Kim, K W; Kim, S T; Kim, D J H; Kim, D K; Seo, S W; Seong, J-K; Jeon, H J

    2016-06-07

    Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r=0.59, P=0.02) and BIS (r=0.59, P=0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal

  6. Ego-rotation and object-rotation in major depressive disorder.

    Science.gov (United States)

    Chen, Jiu; Yang, Laiqi; Ma, Wentao; Wu, Xingqu; Zhang, Yan; Wei, Dunhong; Liu, Guangxiong; Deng, Zihe; Hua, Zhen; Jia, Ting

    2013-08-30

    Mental rotation (MR) performance provides a direct insight into a prototypical higher-level visuo-spatial cognitive operation. Previous studies suggest that progressive slowing with an increasing angle of orientation indicates a specific wing of object-based mental transformations in the psychomotor retardation that occurs in major depressive disorder (MDD). It is still not known, however, whether the ability of object-rotation is associated with the ability of ego-rotation in MDD. The present study was designed to investigate the level of impairment of mental transformation abilities in MDD. For this purpose we tested 33 MDD (aged 18-52 years, 16 women) and 30 healthy control subjects (15 women, age and education matched) by evaluating the performance of MDD subjects with regard to ego-rotation and object-rotation tasks. First, MDD subjects were significantly slower and made more errors than controls in mentally rotating hands and letters. Second, MDD and control subjects displayed the same pattern of response times to stimuli at various orientations in the letter task but not the hand task. Third, in particular, MDD subjects were significantly slower and made more errors during the mental transformation of hands than letters relative to control subjects and were significantly slower and made more errors in physiologically impossible angles than physiologically possible angles in the mental rotation hand task. In conclusion, MDD subjects present with more serious mental rotation deficits specific to the hand than the letter task. Importantly, deficits were more present during the mental transformation in outward rotation angles, thus suggesting that the mental imagery for hands and letters relies on different processing mechanisms which suggest a module that is more complex for the processing of human hands than for letters during mental rotation tasks. Our study emphasises the necessity of distinguishing different levels of impairment of action in MDD subjects

  7. Kappa Opioids, Salvinorin A and Major Depressive Disorder.

    Science.gov (United States)

    Taylor, George T; Manzella, Francesca

    2016-01-01

    Opioids are traditionally associated with pain, analgesia and drug abuse. It is now clear, however, that the opioids are central players in mood. The implications for mood disorders, particularly clinical depression, suggest a paradigm shift from the monoamine neurotransmitters to the opioids either alone or in interaction with monoamine neurons. We have a special interest in dynorphin, the last of the major endogenous opioids to be isolated and identified. Dynorphin is derived from the Greek word for power, dynamis, which hints at the expectation that the neuropeptide held for its discoverers. Yet, dynorphin and its opioid receptor subtype, kappa, has always taken a backseat to the endogenous b-endorphin and the exogenous morphine that both bind the mu opioid receptor subtype. That may be changing as the dynorphin/ kappa system has been shown to have different, often opposite, neurophysiological and behavioral influences. This includes major depressive disorder (MDD). Here, we have undertaken a review of dynorphin/ kappa neurobiology as related to behaviors, especially MDD. Highlights include the unique features of dynorphin and kappa receptors and the special relation of a plant-based agonist of the kappa receptor salvinorin A. In addition to acting as a kappa opioid agonist, we conclude that salvinorin A has a complex pharmacologic profile, with potential additional mechanisms of action. Its unique neurophysiological effects make Salvinorina A an ideal candidate for MDD treatment research.

  8. Acute stress disorder and major depressive disorder in flood victims from Tingo Maria: prevlence and the effect of relocating

    OpenAIRE

    2008-01-01

    Objectives. To determine the prevalence of acute stress disorder (ASD) and comorbidity with major depressive disorder (ASD+MDD) in flood victims from Tingo María, Huánuco (Peruvian central jungle), 20 days after the traumatic event. Material and methods: One hundred and twenty injured (people relocated after disaster) and 110 affected (people living in their own homes) were surveyed and compared. Was applied to structured clinical interview for disorders axis I from DSM-IV, clinical versi...

  9. Implicit and Explicit Self-Esteem in Current, Remitted, Recovered, and Comorbid Depression and Anxiety Disorders: The NESDA Study

    Science.gov (United States)

    van Tuijl, Lonneke A.; Glashouwer, Klaske A.; Bockting, Claudi L. H.; Tendeiro, Jorge N.; Penninx, Brenda W. J. H.; de Jong, Peter J.

    2016-01-01

    Background Dual processing models of psychopathology emphasize the relevance of differentiating between deliberative self-evaluative processes (explicit self-esteem; ESE) and automatically-elicited affective self-associations (implicit self-esteem; ISE). It has been proposed that both low ESE and ISE would be involved in major depressive disorder (MDD) and anxiety disorders (AD). Further, it has been hypothesized that MDD and AD may result in a low ISE “scar” that may contribute to recurrence after remission. However, the available evidence provides no straightforward support for the relevance of low ISE in MDD/AD, and studies testing the relevance of discrepant SE even showed that especially high ISE combined with low ESE is predictive of the development of internalizing symptoms. However, these earlier findings have been limited by small sample sizes, poorly defined groups in terms of comorbidity and phase of the disorders, and by using inadequate indices of discrepant SE. Therefore, this study tested further the proposed role of ISE and discrepant SE in a large-scale study allowing for stricter differentiation between groups and phase of disorder. Method In the context of the Netherlands Study of Depression and Anxiety (NESDA), we selected participants with current MDD (n = 60), AD (n = 111), and comorbid MDD/AD (n = 71), remitted MDD (n = 41), AD (n = 29), and comorbid MDD/AD (n = 14), recovered MDD (n = 136) and AD (n = 98), and never MDD or AD controls (n = 382). The Implicit Association Test was used to index ISE and the Rosenberg Self-Esteem Scale indexed ESE. Results Controls reported higher ESE than all other groups, and current comorbid MDD/AD had lower ESE than all other clinical groups. ISE was only lower than controls in current comorbid AD/MDD. Discrepant self-esteem (difference between ISE and ESE) was not associated with disorder status once controlling for ESE. Limitations Cross-sectional design limits causal inferences. Conclusion Findings

  10. Implicit and Explicit Self-Esteem in Current, Remitted, Recovered, and Comorbid Depression and Anxiety Disorders: The NESDA Study.

    Science.gov (United States)

    van Tuijl, Lonneke A; Glashouwer, Klaske A; Bockting, Claudi L H; Tendeiro, Jorge N; Penninx, Brenda W J H; de Jong, Peter J

    2016-01-01

    Dual processing models of psychopathology emphasize the relevance of differentiating between deliberative self-evaluative processes (explicit self-esteem; ESE) and automatically-elicited affective self-associations (implicit self-esteem; ISE). It has been proposed that both low ESE and ISE would be involved in major depressive disorder (MDD) and anxiety disorders (AD). Further, it has been hypothesized that MDD and AD may result in a low ISE "scar" that may contribute to recurrence after remission. However, the available evidence provides no straightforward support for the relevance of low ISE in MDD/AD, and studies testing the relevance of discrepant SE even showed that especially high ISE combined with low ESE is predictive of the development of internalizing symptoms. However, these earlier findings have been limited by small sample sizes, poorly defined groups in terms of comorbidity and phase of the disorders, and by using inadequate indices of discrepant SE. Therefore, this study tested further the proposed role of ISE and discrepant SE in a large-scale study allowing for stricter differentiation between groups and phase of disorder. In the context of the Netherlands Study of Depression and Anxiety (NESDA), we selected participants with current MDD (n = 60), AD (n = 111), and comorbid MDD/AD (n = 71), remitted MDD (n = 41), AD (n = 29), and comorbid MDD/AD (n = 14), recovered MDD (n = 136) and AD (n = 98), and never MDD or AD controls (n = 382). The Implicit Association Test was used to index ISE and the Rosenberg Self-Esteem Scale indexed ESE. Controls reported higher ESE than all other groups, and current comorbid MDD/AD had lower ESE than all other clinical groups. ISE was only lower than controls in current comorbid AD/MDD. Discrepant self-esteem (difference between ISE and ESE) was not associated with disorder status once controlling for ESE. Cross-sectional design limits causal inferences. Findings suggest a prominent role for ESE in MDD and AD, while

  11. Gene expression profiling in postmortem prefrontal cortex of major depressive disorder.

    Science.gov (United States)

    Kang, Hyo Jung; Adams, David H; Simen, Arthur; Simen, Birgitte B; Rajkowska, Grazyna; Stockmeier, Craig A; Overholser, James C; Meltzer, Herbert Y; Jurjus, George J; Konick, Lisa C; Newton, Samuel S; Duman, Ronald S

    2007-11-28

    Investigations of the molecular mechanisms underlying major depressive disorder (MDD) have been hampered by the complexity of brain tissue and sensitivity of gene expression profiling approaches. To address these issues, we used discrete microdissections of postmortem dorsolateral prefrontal cortex (DLPFC) (area 9) and an oligonucleotide (60mer) microarray hybridization procedure that increases sensitivity without RNA amplification. Mixed-effects statistical methods were used to rigorously control for medication usage in the subset of medicated depressed subjects. These analyses yielded a rich profile of dysregulated genes. Two of the most highly dysregulated genes of interest were stresscopin, a neuropeptide involved in stress responses, and Forkhead box D3 (FOXD3), a transcription factor. Secondary cell-based analysis demonstrated that stresscopin and FoxD3 are increased in neurons of DLPFC gray matter of MDD subjects. These findings identify abnormal gene expression in a discrete region of MDD subjects and contribute to further elucidation of the molecular alterations of this complex mood disorder.

  12. Game Theory Paradigm: A New Tool for Investigating Social Dysfunction in Major Depressive Disorders

    Science.gov (United States)

    Wang, Yun; Yang, Liu-Qing; Li, Shu; Zhou, Yuan

    2015-01-01

    Social dysfunction is a prominent source of distress and disability in patients with major depressive disorder (MDD) but is commonly omitted from current clinical studies, although some researchers propose an evolutionary strategy to understand these negative outcomes. Limited knowledge about the neural basis of social dysfunction in MDD results from traditional paradigms, which lack insights into social interactions. Game theoretical modeling offers a new tool for investigating social-interaction impairments in neuropsychiatric disorders. This review first introduces three widely used games from game theory and the major behavioral and neuroimaging findings obtained using these games in healthy populations. We also address the factors that modulate behaviors in games and their neural bases. We then summarize the current findings obtained by using these games in depressed patients and discuss the clinical implications of these abnormal game behaviors. Finally, we briefly discuss future prospects that may further elucidate the clinical use of a game theory paradigm in MDD. PMID:26441689

  13. Game Theory Paradigm: A New Tool for Investigating Social Dysfunction in Major Depressive Disorders.

    Science.gov (United States)

    Wang, Yun; Yang, Liu-Qing; Li, Shu; Zhou, Yuan

    2015-01-01

    Social dysfunction is a prominent source of distress and disability in patients with major depressive disorder (MDD) but is commonly omitted from current clinical studies, although some researchers propose an evolutionary strategy to understand these negative outcomes. Limited knowledge about the neural basis of social dysfunction in MDD results from traditional paradigms, which lack insights into social interactions. Game theoretical modeling offers a new tool for investigating social-interaction impairments in neuropsychiatric disorders. This review first introduces three widely used games from game theory and the major behavioral and neuroimaging findings obtained using these games in healthy populations. We also address the factors that modulate behaviors in games and their neural bases. We then summarize the current findings obtained by using these games in depressed patients and discuss the clinical implications of these abnormal game behaviors. Finally, we briefly discuss future prospects that may further elucidate the clinical use of a game theory paradigm in MDD.

  14. Optimizing the Use of Aripiprazole Augmentation in the Treatment of Major Depressive Disorder: From Clinical Trials to Clinical Practice

    Science.gov (United States)

    Han, Changsu; Wang, Sheng-Min; Lee, Soo-Jung; Jun, Tae-Youn

    2015-01-01

    Major depressive disorder (MDD) is a recurrent, chronic, and devastating disorder leading to serious impairment in functional capacity as well as increasing public health care costs. In the previous decade, switching therapy and dose adjustment of ongoing antidepressants was the most frequently chosen subsequent treatment option for MDD. However, such recommendations were not based on firmly proven efficacy data from well-designed, placebo-controlled, randomized clinical trials (RCTs) but on practical grounds and clinical reasoning. Aripiprazole augmentation has been dramatically increasing in clinical practice owing to its unique action mechanisms as well as proven efficacy and safety from adequately powered and well-controlled RCTs. Despite the increased use of aripiprazole in depression, limited clinical information and knowledge interfere with proper and efficient use of aripiprazole augmentation for MDD. The objective of the present review was to enhance clinicians' current understanding of aripiprazole augmentation and how to optimize the use of this therapy in the treatment of MDD. PMID:26306301

  15. Joint source based analysis of multiple brain structures in studying major depressive disorder

    Science.gov (United States)

    Ramezani, Mahdi; Rasoulian, Abtin; Hollenstein, Tom; Harkness, Kate; Johnsrude, Ingrid; Abolmaesumi, Purang

    2014-03-01

    We propose a joint Source-Based Analysis (jSBA) framework to identify brain structural variations in patients with Major Depressive Disorder (MDD). In this framework, features representing position, orientation and size (i.e. pose), shape, and local tissue composition are extracted. Subsequently, simultaneous analysis of these features within a joint analysis method is performed to generate the basis sources that show signi cant di erences between subjects with MDD and those in healthy control. Moreover, in a cross-validation leave- one-out experiment, we use a Fisher Linear Discriminant (FLD) classi er to identify individuals within the MDD group. Results show that we can classify the MDD subjects with an accuracy of 76% solely based on the information gathered from the joint analysis of pose, shape, and tissue composition in multiple brain structures.

  16. T helper 17 cells may drive neuroprogression in major depressive disorder: Proposal of an integrative model.

    Science.gov (United States)

    Slyepchenko, Anastasiya; Maes, Michael; Köhler, Cristiano A; Anderson, George; Quevedo, João; Alves, Gilberto S; Berk, Michael; Fernandes, Brisa S; Carvalho, André F

    2016-05-01

    The exact pathophysiology of major depressive disorder (MDD) remains elusive. The monoamine theory, which hypothesizes that MDD emerges as a result of dysfunctional serotonergic, dopaminergic and noradrenergic pathways, has guided the therapy of this illness for several decades. More recently, the involvement of activated immune, oxidative and nitrosative stress pathways and of decreased levels of neurotrophic factors has provided emerging insights regarding the pathophysiology of MDD, leading to integrated theories emphasizing the complex interplay of these mechanisms that could lead to neuroprogression. In this review, we propose an integrative model suggesting that T helper 17 (Th17) cells play a pivotal role in the pathophysiology of MDD through (i) microglial activation, (ii) interactions with oxidative and nitrosative stress, (iii) increases of autoantibody production and the propensity for autoimmunity, (iv) disruption of the blood-brain barrier, and (v) dysregulation of the gut mucosa and microbiota. The clinical and research implications of this model are discussed.

  17. Childhood traumatic stress and obesity in women: the intervening effects of PTSD and MDD.

    Science.gov (United States)

    Dedert, Eric A; Becker, Mary E; Fuemmeler, Bernard F; Braxton, Loretta E; Calhoun, Patrick S; Beckham, Jean C

    2010-12-01

    In this study, symptoms of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) were modeled as intervening variables in the relationship between childhood traumatic stress and weight outcomes in civilian women in the United States. Of the 148 participants, 72 had current PTSD, 64 had current MDD, and 32 had neither disorder. In separate single indirect effect models, there were significant indirect effects of both PTSD and depressive symptoms on body mass index and waist-hip ratio. When models included both PTSD and depressive symptoms, an indirect effect of PTSD symptoms was evident in the relationship between childhood traumatic stress and waist-hip ratio. Posttraumatic stress disorder may play a particularly important role in the development of central adiposity. Copyright © 2010 International Society for Traumatic Stress Studies.

  18. Local cortical thinning links to resting-state disconnectivity in major depressive disorder

    NARCIS (Netherlands)

    van Tol, M. -J.; Li, M.; Metzger, C. D.; Hailla, N.; Horn, D. I.; Li, W.; Heinze, H. J.; Bogerts, B.; Steiner, J.; He, H.; Walter, M.

    2014-01-01

    Background. Local structural and metabolic as well as inter-regional connectivity abnormalities have been implicated in the neuropathology of major depressive disorder (MDD). How local tissue properties affect intrinsic functional connectivity is, however, unclear. Using a cross-sectional, multi-mod

  19. Using patient self-reports to study heterogeneity of treatment effects in major depressive disorder

    NARCIS (Netherlands)

    Kessler, R C; van Loo, H. M.; Wardenaar, K J; Bossarte, R M; Brenner, L A; Ebert, D D; de Jonge, P; Nierenberg, A A; Rosellini, A J; Sampson, N A; Schoevers, R A; Wilcox, M A; Zaslavsky, A M

    2016-01-01

    BACKGROUNDS: Clinicians need guidance to address the heterogeneity of treatment responses of patients with major depressive disorder (MDD). While prediction schemes based on symptom clustering and biomarkers have so far not yielded results of sufficient strength to inform clinical decision-making, p

  20. Quantitative review of the efficacy of slow-frequency magnetic brain stimulation in major depressive disorder

    NARCIS (Netherlands)

    Schutter, D.J.L.G.

    2010-01-01

    Background Slow-frequency repetitive transcranial magnetic stimulation (rTMS) to the frontal cortex has been suggested as a safer and better tolerable alternative to fast-frequency rTMS in the treatment of major depressive disorder (MDD). The aim of the present study was to examine the efficacy of s

  1. Indicators of patients with major depressive disorder in need of highly specialized care: A systematic review

    NARCIS (Netherlands)

    F.C.W. van Krugten (Frédérique); M. Kaddouri (Meriam); M. Goorden (Maartje); A.J.L.M. van Balkom (Anton); C.L.H. Bockting (Claudi ); F.P.M.L. Peeters (Frenk ); L. van Hakkaart-van Roijen (Leona)

    2017-01-01

    textabstractObjectives Early identification of patients with major depressive disorder (MDD) that cannot be managed by secondary mental health services and who require highly specialized mental healthcare could enhance need-based patient stratification. This, in turn, may reduce the number of treatm

  2. Explaining heterogeneity in disability with major depressive disorder : Effects of personal and environmental characteristics

    NARCIS (Netherlands)

    Verboom, C.E.; Sentse, M.; Sijtsema, J.J.; Nolen, W.A.; Ormel, J.; Penninx, B.W.

    2011-01-01

    Background: Major depressive disorder (MDD) is associated with disability, yet some patients function surprisingly well. The reason for this heterogeneity between patients is unclear. Building on the International Classification of Functioning (ICE) model, this study aims to examine effects of perso

  3. Explaining heterogeneity in disability with major depressive disorder : Effects of personal and environmental characteristics

    NARCIS (Netherlands)

    Verboom, C.E.; Sentse, M.; Sijtsema, J.J.; Nolen, W.A.; Ormel, J.; Penninx, B.W.

    2011-01-01

    Background: Major depressive disorder (MDD) is associated with disability, yet some patients function surprisingly well. The reason for this heterogeneity between patients is unclear. Building on the International Classification of Functioning (ICE) model, this study aims to examine effects of perso

  4. Intergenerational Transmission of Internalizing Problems: Effects of Parental and Grandparental Major Depressive Disorder on Child Behavior

    Science.gov (United States)

    Pettit, Jeremy W.; Olino, Thomas M.; Roberts, Robert E.; Seeley, John R.; Lewinsohn, Peter M.

    2008-01-01

    Effects of lifetime histories of grandparental (G1) and parental (G2) major depressive disorder (MDD) on children's (G3) internalizing problems were investigated among 267 G3 children (ages 2-18 years) who received Child Behavior Checklist (CBCL) ratings and had diagnostic data available on 267 biological G2 parents and 527 biological G1…

  5. Childhood Maltreatment and Differential Treatment Response and Recurrence in Adult Major Depressive Disorder

    Science.gov (United States)

    Harkness, Kate L.; Bagby, R. Michael; Kennedy, Sidney H.

    2012-01-01

    Objective: A substantial number of patients with major depressive disorder (MDD) do not respond to treatment, and recurrence rates remain high. The purpose of this study was to examine a history of severe childhood abuse as a moderator of response following a 16-week acute treatment trial, and of recurrence over a 12-month follow-up. Method:…

  6. Psychotherapy, Pharmacotherapy, and Their Combination for Adolescents with Major Depressive Disorder: A Meta-Analysis

    Science.gov (United States)

    Singh, Nikita; Reece, John

    2014-01-01

    This meta-analysis aims to inform clinical practice of treatment strategies for adolescents with major depressive disorder (MDD). The efficacy of three empirically validated treatments was compared to determine the most effective treatment. These were: cognitive-behavioural therapy (CBT), selective serotonin reuptake inhibitor (SSRI)…

  7. Aberrant Global and Regional Topological Organization of the Fractional Anisotropy-weighted Brain Structural Networks in Major Depressive Disorder

    Institute of Scientific and Technical Information of China (English)

    Jian-Huai Chen; Zhi-Jian Yao; Jiao-Long Qin; Rui Yan; Ling-Ling Hua; Qing Lu

    2016-01-01

    Background:Most previous neuroimaging studies have focused on the structural and functional abnormalities of local brain regions in major depressive disorder (MDD).Moreover,the exactly topological organization of networks underlying MDD remains unclear.This study examined the aberrant global and regional topological patterns of the brain white matter networks in MDD patients.Methods:The diffusion tensor imaging data were obtained from 27 patients with MDD and 40 healthy controls.The brain fractional anisotropy-weighted structural networks were constructed,and the global network and regional nodal metrics of the networks were explored by the complex network theory.Results:Compared with the healthy controls,the brain structural network of MDD patients showed an intact small-world topology,but significantly abnormal global network topological organization and regional nodal characteristic of the network in MDD were found.Our findings also indicated that the brain structural networks in MDD patients become a less strongly integrated network with a reduced central role of some key brain regions.Conclusions:All these resulted in a less optimal topological organization of networks underlying MDD patients,including an impaired capability of local information processing,reduced centrality of some brain regions and limited capacity to integrate information across different regions.Thus,these global network and regional node-level aberrations might contribute to understanding the pathogenesis of MDD from the view of the brain network.

  8. Treatment with escitalopram improves the attentional bias toward negative facial expressions in patients with major depressive disorders.

    Science.gov (United States)

    Zhou, Zhenhe; Cao, Suxia; Li, Hengfen; Li, Youhui

    2015-10-01

    We hypothesized that treatment with escitalopram would improve cognitive bias and contribute to the recovery process for patients with major depressive disorder (MDD). Many previous studies have established that patients with MDD tend to pay selective attention to negative stimuli. The assessment of the level of cognitive bias is regarded as a crucial dimension of treatment outcomes for MDD. To our knowledge, no prior studies have been reported on the effects of treatment with escitalopram on attentional bias in MDD, employing a dot probe task of facial expression. We studied 25 patients with MDD and 25 controls, and used a dot probe task of facial expression to measure cognitive bias. The patients' psychopathologies were rated using the Hamilton Depression Scale (HAMD) at baseline and after 8 weeks of treatment with escitalopram. All participants performed the facial expression dot probe task. The results revealed that the 8 week escitalopram treatment decreased the HAMD scores. The patients with MDD at baseline exhibited an attentional bias towards negative faces, however, no significant bias toward either negative or happy faces were observed in the controls. After the 8 week escitalopram treatment, no significant bias toward negative faces was observed in the patient group. In conclusion, patients with MDD pay more attention to negative facial expressions, and treatment with escitalopram improves this attentional bias toward negative facial expressions. This is the first study, to our knowledge, on the effects of treatment with escitalopram on attentional bias in patients with MDD that has employed a dot probe task of facial expression.

  9. The status of sleep abnormalities as a diagnostic test for major depressive disorder.

    Science.gov (United States)

    Arfken, C L; Joseph, A; Sandhu, G R; Roehrs, T; Douglass, A B; Boutros, N N

    2014-03-01

    Psychiatry lags other fields in development of diagnostic tests. A literature review and meta-analysis was conducted to ascertain if polysomnographic abnormalities (REM density, REM latency, sleep efficiency, slow wave sleep, stage 1 and stage 2 sleep) warrant additional effort to develop them into a clinical diagnostic test for major depressive disorder (MDD). The 31 publications meeting inclusion criteria were then classified into one of three progressive steps using guidelines for evaluating the clinical usefulness of a diagnostic test. Most of the abnormalities found in MDD patients, when compared to healthy controls, occurred in the expected direction with moderate effect sizes but with substantial publication bias and heterogeneity. Eleven studies compared abnormalities in MDD to other psychiatric disorders (step 2a), and four studies provided data on the sensitivity or specificity of the findings in differentiating among the psychiatric disorders that frequently appear on the same differential diagnostic list as MDD (step 2b). No multicenter trial has been conducted prospectively to test the clinical utility of the diagnostic test (step 3). Only published articles in the English language were used. Sleep studies for the detection of MDD appear replicable with a moderate effect size. However, additional step 1 studies are needed to define the sensitivity and specificity. The heterogeneity of sleep recording, scoring techniques, and MDD must also be addressed. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. A pattern of cerebral perfusion anomalies between Major Depressive Disorder and Hashimoto Thyroiditis

    Directory of Open Access Journals (Sweden)

    Altoé Gianmarco

    2011-09-01

    Full Text Available Abstract Background This study aims to evaluate relationship between three different clinical conditions: Major Depressive Disorders (MDD, Hashimoto Thyroiditis (HT and reduction in regional Cerebral Blood Flow (rCBF in order to explore the possibility that patients with HT and MDD have specific pattern(s of cerebral perfusion. Methods Design: Analysis of data derived from two separate data banks. Sample: 54 subjects, 32 with HT (29 women, mean age 38.8 ± 13.9; 22 without HT (19 women, mean age 36.5 ± 12.25. Assessment: Psychiatric diagnosis was carried out by Simplified Composite International Diagnostic Interview (CIDIS using DSM-IV categories; cerebral perfusion was measured by 99 mTc-ECD SPECT. Statistical analysis was done through logistic regression. Results MDD appears to be associated with left frontal hypoperfusion, left temporal hypoperfusion, diffuse hypoperfusion and parietal perfusion asymmetry. A statistically significant association between parietal perfusion asymmetry and MDD was found only in the HT group. Conclusion In HT, MDD is characterized by a parietal flow asymmetry. However, the specificity of rCBF in MDD with HT should be confirmed in a control sample with consideration for other health conditions. Moreover, this should be investigated with a longitudinally designed study in order to determine a possible pathogenic cause. Future studies with a much larger sample size should clarify whether a particular perfusion pattern is associated with a specific course or symptom cluster of MDD.

  11. Identification of IL6 as a susceptibility gene for major depressive disorder.

    Science.gov (United States)

    Zhang, Chen; Wu, Zhiguo; Zhao, Guoqing; Wang, Fan; Fang, Yiru

    2016-08-09

    Our previous work implied that interleukin 6 (IL6) may be a biological marker for major depressive disorder (MDD). In this study, we performed a comprehensive genetic study to determine the association between the gene encoding IL6 (IL6) and MDD in Han Chinese. There were 50 drug-naïve MDD patients and 50 healthy controls undergoing an mRNA expression study. A sample of 772 patients with MDD and 759 healthy controls were used for genetic analysis. Next, we performed an eQTL analysis to identify whether risk SNP(s) is associated with IL6 expression in brain. Our results showed that patients with MDD have higher levels of IL6 than healthy controls (P = 0.008). The SNP rs1800797 has a significant association with MDD (P = 0.01) in a dominant model. The eQTL analysis showed a marginally significant association between the rs1800797 and IL6 expression in the frontal cortex (P = 0.087). Our preliminary findings are suggestive of an association between rs1800797 and the risk of MDD. Further investigations are required to evaluate this association in larger samples to increase statistical power, and to examine the correlation between rs1800797 and IL6 methylation patterns.

  12. Selection and implementation of emotion regulation strategies in major depressive disorder: An integrative review.

    Science.gov (United States)

    Liu, Daphne Y; Thompson, Renee J

    2017-07-13

    Emotion regulation (ER), broadly defined, has been implicated in mental health, including major depressive disorder (MDD). We review empirical studies examining selection and implementation of ER strategies in adults with current or past MDD. We focus on eight strategies (rumination, distraction, cognitive reappraisal, suppression, acceptance, savoring, positive rumination, dampening), organizing the review by research design: (1) self-reported habitual use (i.e., trait) of ER strategies, (2) spontaneous use of ER strategies in laboratory settings, (3) experimentally instructed ER strategies, and (4) use of ER strategies in naturalistic settings. Reviewed findings suggest that MDD is associated with unskillful selection of ER strategies-indexed by self-reported habitual use of ER strategies-but not impaired abilities to implement them; in fact, those with current MDD and MDD in remission show intact abilities to implement many ER strategies when instructed to do so. Additionally, the vast majority of research examines trait ER, while there is a dearth of laboratory and naturalistic studies using MDD samples. There are also discrepant findings on habitual use of ER strategies assessed by self-reports and spontaneous use of ER strategies in the lab. We discuss implications of reviewed findings and five areas for future research in emotion dysregulation in MDD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Melancholic features in inpatients with major depressive disorder associate with differential clinical characteristics and treatment outcomes.

    Science.gov (United States)

    Lin, Ching-Hua; Huang, Chun-Jen; Liu, Shi-Kai

    2016-04-30

    To determine whether the presence of melancholic features in hospitalized patients with major depressive disorder (MDD) was associated with specific clinical characteristics and treatment outcomes, supporting melancholic depression as a distinct subtype within MDD. 126 acutely ill inpatients with MDD were enrolled in an open, 6-week trial with fixed-dose fluoxetine 20mg daily. Symptom severity was assessed regularly, using the 17-item Hamilton Depression Rating Scale (HAMD-17) and Clinical Global Impression of Severity (CGI-S). Melancholic features were defined according to the DSM-IV criteria. Clinical variables were compared between patients with and without melancholic features. Generalized estimating equations method was used to explore the differences in HAMD-17 and CGI-S scores between the 2 groups over time. Clinical response was defined as having a 50% or greater reduction in HAMD-17 scores. 96 (76.2%) of the 126 patients with at least one post-baseline assessment met the criteria for melancholic depression. Melancholic depression differed from non-melancholic depression in clinical characteristics and predicted a better response to fluoxetine treatment. The differentiation between melancholic and non-melancholic depression within MDD hence is clinically significant and valid. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Comorbid generalized anxiety disorder and its association with quality of life in patients with major depressive disorder

    Science.gov (United States)

    Zhou, Yongjie; Cao, Zhongqiang; Yang, Mei; Xi, Xiaoyan; Guo, Yiyang; Fang, Maosheng; Cheng, Lijuan; Du, Yukai

    2017-01-01

    The comorbidity of major depressive disorder (MDD) and generalized anxiety disorder (GAD) is common and often predicts poorer outcomes than either disorder alone. This study aimed to examine the prevalence of comorbid GAD and its association with quality of life (QOL) among MDD patients. A total of 1225 psychiatric outpatients were screened using the Hospital Anxiety and Depression Scale (HADS). Those who scored ≥8 on the HADS were interviewed using DSM-IV criteria by two senior psychiatrists. Patients diagnosed with MDD were further assessed using the 9-item Patient Health Questionnaire, Social Support Rating Scale, Pittsburgh Sleep Quality Index, and World Health Organization QOL Scale, brief version (WHOQOL-BREF). Ultimately, 667 patients were diagnosed with MDD, of 71.7% of whom had GAD. Compared to those with MDD alone, comorbid patients had lower scores on the physical (38.64 ± 10.35 vs.36.54 ± 12.32, P = 0.026) and psychological (35.54 ± 12.98 vs. 30.61 ± 14.66, P WHOQOL-BREF. The association between comorbid GAD and poor QOL on the two domains remained statistically significant in the multiple linear regression (unstandardized coefficients: −1.97 and −4.65, P < 0.001). In conclusion, the prevalence of comorbid GAD in MDD patients is high, and co-occurring GAD may exacerbate impaired physical and psychological QOL in Chinese MDD patients. PMID:28098176

  15. Sexual dysfunction during treatment of major depressive disorder with vilazodone, citalopram, or placebo: results from a phase IV clinical trial

    OpenAIRE

    Clayton, Anita H.; Gommoll, Carl; Chen, Dalei; Nunez, Rene; Mathews, Maju

    2015-01-01

    Sexual dysfunction commonly occurs with major depressive disorder (MDD). Vilazodone, a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist antidepressant approved for the treatment of MDD in adults, was evaluated to determine its effects on sexual function. The primary study was a double-blind, randomized, controlled trial comparing vilazodone 20 and 40 mg/day with placebo; citalopram 40 mg/day was an active control (NCT01473381; http://www.clinicaltrials.gov). Post-hoc...

  16. Brain activation before and after cognitivebehavior therapy in first-episode patients with mildto-moderate major depressive disorder

    Institute of Scientific and Technical Information of China (English)

    谭雅容

    2014-01-01

    Objective To explore the neurobiological mechanisms underlying cognitive-behavior therapy(CBT)for major depressive disorder(MDD)by detecting the neural changes of patients following CBT.Methods Thirteen first-episode treatment-naive patients with MDD and 13 matched healthy volunteers underwent fM RI scan.All the patients were treated with 6-week CBT only and scanned again after treatment.A gender recognition task

  17. Electroencephalographic findings in patients with major depressive disorder during cognitive or emotional tasks: a systematic review

    Directory of Open Access Journals (Sweden)

    Sabrina B. de Freitas

    Full Text Available Objective: Major depressive disorder (MDD is a prevalent psychiatric condition characterized by multiple symptoms that cause great distress. Uncovering the brain areas involved in MDD is essential for improving therapeutic strategies and predicting response to interventions. This systematic review discusses recent findings regarding cortical alterations in depressed patients during emotional or cognitive tasks, as measured by electroencephalography (EEG. Methods: A search of the MEDLINE/PubMed and Cochrane databases was carried out using the keywords EEG and depression, confined to article title. Results: The studies identified reveal the frontal cortex as an important brain structure involved in the complex neural processes associated with MDD. Findings point to disorganization of right-hemisphere activity and deficient cognitive processing in MDD. Depressed individuals tend to ruminate on negative information and respond with a pattern of relatively higher right frontal activity to emotional stimuli associated with withdrawal and isolation. Conclusion: Patients with MDD may have altered dynamic patterns of activity in several neuroanatomical structures, especially in prefrontal and limbic areas involved in affective regulation. Identification of these alterations might help predict the response of patients to different interventions more effectively and thus maximize the effects both of pharmacotherapeutic and of psychotherapeutic strategies.

  18. Decreased Total Antioxidant Activity in Major Depressive Disorder Patients Non-Responsive to Antidepressant Treatment

    Science.gov (United States)

    Baek, Song-Eun; Lee, Gyoung-Ja; Rhee, Chang-Kyu; Rho, Dae-Young; Kim, Do-Hoon; Huh, Sun

    2016-01-01

    Objective This study aimed to evaluate the total antioxidant activity (TAA) in patients with major depressive disorder (MDD) and the effect of antidepressants on TAA using a novel potentiometric method. Methods Twenty-eight patients with MDD and thirty-one healthy controls were enrolled in this study. The control group comprised 31 healthy individuals matched for gender, drinking and smoking status. We assessed symptoms of depression using the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI). We measured TAA using potentiometry. All measurements were made at baseline and four and eight weeks later. Results There was a significant negative correlation between BDI scores and TAA. TAA was significantly lower in the MDD group than in controls. When the MDD group was subdivided into those who showed clinical response to antidepressant therapy (response group) and those who did not (non-response group), only the non-response group showed lower TAA, while the response group showed no significant difference to controls at baseline. After eight weeks of antidepressant treatment, TAA in both the response and non-response groups was similar, and there was no significant difference among the three groups. Conclusion These results suggest that the response to antidepressant treatment in MDD patients might be predicted by measuring TAA. PMID:27081384

  19. Prevalence and characteristics of depressive disorders in early adolescents in central Norway

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    Larsson Bo

    2011-08-01

    Full Text Available Abstract Background Prevalence of depressive disorders among adolescents has varied across studies. The present study aims to assess current and lifetime prevalence and characteristics of adolescent Major Depressive Disorder (MDD, Dysthymia and Depression NOS among adolescents in Central Norway in addition to socio-demographics and use of mental health care. Method In the Youth and Mental Health Study a representative sample of 2432 junior high school students (mean age 14.9 years, SD = 0.6 from two counties in Central Norway were screened with the Mood and Feelings Questionnaire (MFQ. A subset of 345 of these adolescents (72.5% girls, 220 high scorers (MFQ = > 26, 74 middle scorers (MFQ 7-25, and 50 low scorers (MFQ Results Almost one in four subjects (23% had life-time depression. Prevalences of current Major Depressive Disorder (MDD, Dysthymia and "Double depression" were 2.6%, 1.0% and 0.6%, respectively, and for Depression NOS 6.3%. All depressive disorders were characterized by long duration of episodes with large variations, and for any depressive disorder onset before 12 years of age. In multivariate analyses MDD and Dysthymia were most strongly associated with gender and not living with both biological parents. There was no gender difference for Depression NOS. Although a considerable number of depressed subjects had received mental health care, the reason for contact with services was seldom due to affective symptoms. Less than 20% had been in contact with specialist mental health services. Conclusion High rates of Depression NOS, early onset of depressive episodes, long duration, and low use of specialized services point to the need for improved diagnostic assessment and treatment for young individuals.

  20. Accuracy of automated classification of major depressive disorder as a function of symptom severity.

    Science.gov (United States)

    Ramasubbu, Rajamannar; Brown, Matthew R G; Cortese, Filmeno; Gaxiola, Ismael; Goodyear, Bradley; Greenshaw, Andrew J; Dursun, Serdar M; Greiner, Russell

    2016-01-01

    Growing evidence documents the potential of machine learning for developing brain based diagnostic methods for major depressive disorder (MDD). As symptom severity may influence brain activity, we investigated whether the severity of MDD affected the accuracies of machine learned MDD-vs-Control diagnostic classifiers. Forty-five medication-free patients with DSM-IV defined MDD and 19 healthy controls participated in the study. Based on depression severity as determined by the Hamilton Rating Scale for Depression (HRSD), MDD patients were sorted into three groups: mild to moderate depression (HRSD 14-19), severe depression (HRSD 20-23), and very severe depression (HRSD ≥ 24). We collected functional magnetic resonance imaging (fMRI) data during both resting-state and an emotional-face matching task. Patients in each of the three severity groups were compared against controls in separate analyses, using either the resting-state or task-based fMRI data. We use each of these six datasets with linear support vector machine (SVM) binary classifiers for identifying individuals as patients or controls. The resting-state fMRI data showed statistically significant classification accuracy only for the very severe depression group (accuracy 66%, p = 0.012 corrected), while mild to moderate (accuracy 58%, p = 1.0 corrected) and severe depression (accuracy 52%, p = 1.0 corrected) were only at chance. With task-based fMRI data, the automated classifier performed at chance in all three severity groups. Binary linear SVM classifiers achieved significant classification of very severe depression with resting-state fMRI, but the contribution of brain measurements may have limited potential in differentiating patients with less severe depression from healthy controls.

  1. Predictors, moderators, and mediators (correlates) of treatment outcome in major depressive disorder.

    Science.gov (United States)

    Papakostas, George I; Fava, Maurizio

    2008-01-01

    Major Depressive Disorder (MDD) is a prevalent illness that is frequently associated with significant disability, morbidity and mortality Despite the development and availability of numerous treatment options for MDD, studies have shown that antidepressant monotherapy yields only modest rates of response and remission. Clearly, there is an urgent need to develop more effective treatment strategies for patients with MDD. One possible approach towards the development of novel pharmacotherapeutic strategies for MDD involves identifying subpopulations of depressed patients who are more likely to experience the benefits of a given (existing) treatment versus placebo, or versus a second treatment. Attempts have been made to identify such "subpopulations", specifically by testing whether a given biological or clinical marker also serves as a moderator, mediator (correlate), or predictor of clinical improvement following the treatment of MDD with standard, first-line antidepressants. In the following article, we will attempt to summarize the literature focusing on several major areas ("leads") where preliminary evidence exists regarding clinical and biologic moderators, mediators, and predictors of symptom improvement in MDD. Such clinical leads will include the presence of hopelessness, anxious symptoms, or medical comorbidity. Biologic leads will include gene polymorphisms, brain metabolism, quantitative electroencephalography, loudness dependence of auditory evoked potentials, and functional brain asymmetry.

  2. A meta-analysis of the risk of major affective disorder in relatives of individuals affected by major depressive disorder or bipolar disorder.

    Science.gov (United States)

    Wilde, A; Chan, H-N; Rahman, B; Meiser, B; Mitchell, P B; Schofield, P R; Green, M J

    2014-04-01

    To conduct a meta-analysis to estimate the incidence of major depressive disorder (MDD) and bipolar disorder (BD) in first-degree relatives (FDRs) of probands affected by MDD or BD. The risk for MDD in FDR of BD probands and vice versa is also investigated. A systematic review of case-control and cohort studies, which were published between 1977 and 2012; reported relative risks (RR) or odd ratios (OR) or equivalent raw data; made an explicit distinction between MDD and BD; used operational diagnostic criteria; and reported systematic proband recruitment and ascertainment of relatives. Studies were obtained by electronic MEDLINE and EMBASE searches and hand-searching. Estimates were derived from pooled data using random effects methods. Of an initial sample of 241 articles, 22 were eligible for inclusion. For FDRs of one proband with MDD compared to healthy control probands, estimates for MDD were OR=2.14 (95% CI 1.72-2.67), increasing to OR=3.23 (95% CI 2.11-4.94) for two MDD probands. For FDRs of one BD proband compared to healthy control probands, estimates for BD were OR=7.92 (95% CI 2.45-25.61), and OR=6.58 (95% CI 2.64-16.43) for FDRs of two BD probands. These findings support previously published data indicating strong familiality for both MDD and BD. Data will be useful in providing individuals with a family history of MDD or BPD with tailored risk estimates. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Substance Use and the Treatment of Resistant Depression in Adolescents

    Science.gov (United States)

    Goldstein, Benjamin I.; Shamseddeen, Wael; Spirito, Anthony; Emslie, Graham; Clarke, Greg; Wagner, Karen Dineen; Asarnow, Joan Rosenbaum; Vitiello, Benedetto; Ryan, Neal; Birmaher, Boris; Mayes, Taryn; Onorato, Matthew; Zelazny, Jamie; Brent, David A.

    2009-01-01

    Objective: Despite the known association between substance use disorders and major depressive disorder (MDD) among adolescents, little is known regarding substance use among adolescents with MDD. Method: Youths with MDD who had not improved after an adequate selective serotonin reuptake inhibitor trial (N = 334) were enrolled in the Treatment of…

  4. Membrane Omega-3 Fatty Acid Deficiency as a Preventable Risk Factor for Comorbid Coronary Heart Disease in Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Robert K. McNamara

    2009-01-01

    Full Text Available Major depression disorder (MDD significantly increases the risk for coronary heart disease (CHD which is a leading cause of mortality in patients with MDD. Moreover, depression is frequently observed in a subset of patients following acute coronary syndrome (ACS and increases risk for mortality. Here evidence implicating omega-3 (n-3 fatty acid deficiency in the pathoaetiology of CHD and MDD is reviewed, and the hypothesis that n-3 fatty acid deficiency is a preventable risk factor for CHD comorbidity in MDD patients is evaluated. This hypothesis is supported by cross-national and cross-sectional epidemiological surveys finding an inverse correlation between n-3 fatty acid status and prevalence rates of both CHD and MDD, prospective studies finding that lower dietary or membrane EPA+DHA levels increase risk for both MDD and CHD, case-control studies finding that the n-3 fatty acid status of MDD patients places them at high risk for emergent CHD morbidity and mortality, meta-analyses of controlled n-3 fatty acid intervention studies finding significant advantage over placebo for reducing depression symptom severity in MDD patients, and for secondary prevention of cardiac events in CHD patients, findings that n-3 fatty acid status is inversely correlated with other documented CHD risk factors, and patients diagnosed with MDD after ACS exhibit significantly lower n-3 fatty acid status compared with nondepressed ACS patients. This body of evidence provides strong support for future studies to evaluate the effects of increasing dietary n-3 fatty acid status on CHD comorbidity and mortality in MDD patients.

  5. Age and gender modulate the neural circuitry supporting facial emotion processing in adults with major depressive disorder.

    Science.gov (United States)

    Briceño, Emily M; Rapport, Lisa J; Kassel, Michelle T; Bieliauskas, Linas A; Zubieta, Jon-Kar; Weisenbach, Sara L; Langenecker, Scott A

    2015-03-01

    Emotion processing, supported by frontolimbic circuitry known to be sensitive to the effects of aging, is a relatively understudied cognitive-emotional domain in geriatric depression. Some evidence suggests that the neurophysiological disruption observed in emotion processing among adults with major depressive disorder (MDD) may be modulated by both gender and age. Therefore, the present study investigated the effects of gender and age on the neural circuitry supporting emotion processing in MDD. Cross-sectional comparison of fMRI signal during performance of an emotion processing task. Outpatient university setting. One hundred adults recruited by MDD status, gender, and age. Participants underwent fMRI while completing the Facial Emotion Perception Test. They viewed photographs of faces and categorized the emotion perceived. Contrast for fMRI was of face perception minus animal identification blocks. Effects of depression were observed in precuneus and effects of age in a number of frontolimbic regions. Three-way interactions were present between MDD status, gender, and age in regions pertinent to emotion processing, including frontal, limbic, and basal ganglia. Young women with MDD and older men with MDD exhibited hyperactivation in these regions compared with their respective same-gender healthy comparison (HC) counterparts. In contrast, older women and younger men with MDD exhibited hypoactivation compared to their respective same-gender HC counterparts. This the first study to report gender- and age-specific differences in emotion processing circuitry in MDD. Gender-differential mechanisms may underlie cognitive-emotional disruption in older adults with MDD. The present findings have implications for improved probes into the heterogeneity of the MDD syndrome. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  6. Oxytocin and Major Depressive Disorder: Experimental and Clinical Evidence for Links to Aetiology and Possible Treatment

    Directory of Open Access Journals (Sweden)

    Inga D. Neumann

    2010-03-01

    Full Text Available Affective disorders represent the most common psychiatric diseases, with substantial co-morbidity existing between major depressive disorders (MDD and anxiety disorders. The lack of truly novel acting compounds has led to non-monoaminergic based research and hypotheses in recent years. The large number of brain neuropeptides, characterized by discrete synthesis sites and multiple receptors, represent likely research candidates for novel therapeutic targets. The present review summarises the available preclinical and human evidence regarding the neuropeptide, oxytocin, and its implications in the aetiology and treatment of MDD. While the evidence is not conclusive at present additional studies are warranted to determine whether OXT may be of therapeutic benefit in subsets of MDD patients such as those with comorbid anxiety symptoms and low levels of social attachment.

  7. Distinct proteomic profiles in post-mortem pituitary glands from bipolar disorder and major depressive disorder patients.

    Science.gov (United States)

    Stelzhammer, Viktoria; Alsaif, Murtada; Chan, Man K; Rahmoune, Hassan; Steeb, Hannah; Guest, Paul C; Bahn, Sabine

    2015-01-01

    Disturbances of the hypothalamic-pituitary-adrenal axis have been implicated in the pathophysiology of bipolar disorder (BD) and major depressive disorder (MDD). To examine this further, we carried out proteomic profiling of post-mortem pituitaries from 13 BD and 14 MDD patients, in comparison to 15 controls. Liquid chromatography-mass spectrometry (LC-MS(E)) analysis showed that BD patients had significantly increased levels of the major pituitary hormones pro-opiomelanocortin (POMC) and galanin. BD patients also showed changes in proteins associated with gene transcription, stress response, lipid metabolism and growth signalling. In contrast, LC-MS(E) profiling revealed that MDD patients had significantly decreased levels of the prohormone-converting enzyme carboxypeptidease E and follow-up enzymatic analysis showed decreased activity of prolyl-oligopeptidase convertase. This suggested that altered prohormone processing may occur in pituitaries of MDD patients. In addition, MDD patients had significant changes in proteins involved in intracellular transport and cytoskeletal signalling. Finally, we carried out selective reaction monitoring (SRM) mass spectrometry profiling for validation of protein changes in key biological pathways. This confirmed increased POMC levels in BD patients with no change in the levels of this prohormone in MDD. This study demonstrates that proteomic profiling analysis of the pituitary can lead to new insights into the pathophysiology of BD and MDD. Also, given that the pituitary directly releases a variety of bioactive molecules into the bloodstream, many of the proteins identified here could serve as focal points in the search for peripheral biomarkers in clinical or drug treatment studies of BD and MDD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Analyzing prefrontal cortex hemoglobin concentration exchange spectrum in patients with major depressive disorder combined with anxiety and obsession through near-infrared spectroscopy

    Institute of Scientific and Technical Information of China (English)

    刘晓敏

    2014-01-01

    Objective Exploring the characteristics of prefrontal cortex activation in patients of major depressive disorder(MDD)combined with anxiety and obsession through functional near-infrared spectroscopy(fN IRS).Methods Prefrontal cortex hemoglobin concentration exchange of30 MDD patients combined with anxiety and obsession was detected by fN IRS under voice fluency task(VFT),then psychological assessment was made using Hanmilton Depression Scale(HAMD),Hamilton Anxiety Scale

  9. IRRITABLE MOOD IN ADULT MAJOR DEPRESSIVE DISORDER: RESULTS FROM THE WORLD MENTAL HEALTH SURVEYS

    Science.gov (United States)

    Kovess-Masfety, Viviane; Alonso, Jordi; Angermeyer, Matthias; Bromet, Evelyn; de Girolamo, Giovanni; de Jonge, Peter; Demyttenaere, Koen; Florescu, Silvia E.; Gruber, Michael J.; Gureje, Oye; Hu, Chiyi; Huang, Yueqin; Karam, Elie G.; Jin, Robert; Lépine, Jean-Pierre; Levinson, Daphna; McLaughlin, Katie A.; Medina-Mora, María E.; O’Neill, Siobhan; Ono, Yutaka; Posada-Villa, José A.; Sampson, Nancy A.; Scott, Kate M.; Shahly, Victoria; Stein, Dan J.; Viana, Maria C.; Zarkov, Zahari; Kessler, Ronald C.

    2014-01-01

    Background Although irritability is a core symptom of DSM-IV major depressive disorder (MDD) for youth but not adults, clinical studies find comparable rates of irritability between nonbipolar depressed adults and youth. Including irritability as a core symptom of adult MDD would allow detection of depression-equivalent syndromes with primary irritability hypothesized to be more common among males than females. We carried out a preliminary examination of this issue using cross-national community-based survey data from 21 countries in the World Mental Health (WMH) Surveys (n = 110,729). Methods The assessment of MDD in the WHO Composite International Diagnostic Interview includes one question about persistent irritability. We examined two expansions of the definition of MDD involving this question: (1) cases with dysphoria and/or anhedonia and exactly four of nine Criterion A symptoms plus irritability; and (2) cases with two or more weeks of irritability plus four or more other Criterion A MDD symptoms in the absence of dysphoria or anhedonia. Results Adding irritability as a tenth Criterion A symptom increased lifetime prevalence by 0.4% (from 11.2 to 11.6%). Adding episodes of persistent irritability increased prevalence by an additional 0.2%. Proportional prevalence increases were significantly higher, but nonetheless small, among males compared to females. Rates of severe role impairment were significantly lower among respondents with this irritable depression who did not meet conventional DSM-IV criteria than those with DSM-IV MDD. Conclusion Although limited by the superficial assessment in this single question on irritability, results do not support expanding adult MDD criteria to include irritable mood. PMID:23364997

  10. Diagnosing major depressive disorder III: can some symptoms be eliminated from the diagnostic criteria?

    Science.gov (United States)

    Zimmerman, Mark; McGlinchey, Joseph B; Young, Diane; Chelminski, Iwona

    2006-05-01

    All criteria used to diagnose a psychiatric disorder should contribute to distinguishing cases from noncases. The principal of parsimony argues for defining a disorder with as few criteria as possible. Thus, criteria that do not contribute to the case-noncase distinction should be eliminated from the list of defining features because they unnecessarily increase the complexity of the definition of the disorder. In polythetically defined disorders such as major depressive disorder (MDD), diagnosis is based on the presence of a minimum number of features from a list. For a criterion to be retained on such a list, it should contribute to distinguishing between individuals with and without MDD. Simply demonstrating that a criterion is significantly more common in individuals with MDD than individuals without MDD is not a sufficient demonstration of its necessity. Rather, to demonstrate an impact on diagnosis, it should be shown that eliminating the criterion from the list results in individuals being reclassified from a case to a noncase. A criterion does not contribute to determining caseness if its elimination does not result in diagnostic reclassification. The goal of this report from the Rhode Island Hospital Methods to Improve Diagnostic Assessment and Services project was to determine if any of the criteria of MDD are candidates for elimination because of their lack of impact on diagnosis. The results indicated that the symptoms of increased weight, decreased weight, and indecisiveness rarely influenced diagnostic classification and thus are candidates for elimination.

  11. High-dose desvenlafaxine in outpatients with major depressive disorder.

    Science.gov (United States)

    Ferguson, James M; Tourian, Karen A; Rosas, Gregory R

    2012-09-01

    This study investigated the safety and efficacy of long-term treatment with high-dose desvenlafaxine (administered as desvenlafaxine succinate) in major depressive disorder (MDD). In this multicenter, open-label study, adult outpatients with MDD aged 18-75 were treated with flexible doses of desvenlafaxine (200-400 mg/d) for ≤ 1 year. Safety assessments included monitoring of treatment-emergent adverse events (TEAEs), patient discontinuations due to adverse events, electrocardiograms, vital signs, and laboratory determinations. The primary efficacy measure was mean change from baseline in the 17-item Hamilton Rating Scale for Depression [HAM-D(17)] total score. The mean daily desvenlafaxine dose range over the duration of the trial was 267-356 mg (after titration). The most frequent TEAEs in the safety population (n = 104) were nausea (52%) and headache (41%), dizziness (31%), insomnia (29%), and dry mouth (27%). All TEAEs were mild or moderate in severity. Thirty-four (33%) patients discontinued from the study because of TEAEs; nausea (12%) and dizziness (9%) were the most frequently cited reasons. The mean change in HAM-D(17) total score for the intent-to-treat population (n = 99) was -9.9 at the last on-therapy visit in the last-observation-carried-forward analysis and -14.0 at month 12 in the observed cases analysis. Conclusion High-dose desvenlafaxine (200-400 mg/d) was generally safe and effective in the long-term treatment of MDD.

  12. Evaluation of the risk factors of depressive disorders comorbid with obstructive sleep apnea

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    Cai LQ

    2017-01-01

    Full Text Available Liqiang Cai,1 Luoyi Xu,1 Lili Wei,1 Yi Sun,2 Wei Chen1,3 1Department of Psychiatry, Sir Run Run Shaw Hospital, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, 2Department of Electroencephalogram, Sir Run Run Shaw Hospital, 3Key Laboratory of Medical Neurobiology, Chinese Ministry of Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China Objective: Overlap of obstructive sleep apnea (OSA complicates diagnosis of depressive disorder and renders antidepressant treatment challenging. Previous studies have reported that the incidence of OSA is higher in patients with depression than in the general population. The purpose of this article was to investigate clinical risk factors to predict OSA in depression disorders.Methods: A total of 115 patients diagnosed with major depressive disorder (MDD and bipolar disorder (in a major depressive episode, who underwent overnight polysomnography, were studied retrospectively. They were divided into two groups: non-OSA and OSA. The patients who had apnea–hypopnea index (AHI <5 were defined as the non-OSA group, whereas the OSA group was defined as those with an AHI ≥5. Logistic regression was used to analyze the association among AHI and clinical factors, including sex, age, body mass index (BMI, Hamilton Depression Rating Scale (HAMD, Hamilton Anxiety Rating Scale, Pittsburgh Sleep Quality Index (PSQI, and diagnosis (MDD or bipolar disorder [in a major depressive episode].Results: In 115 patients, 51.3% had OSA. Logistic regression analysis showed significant associations between AHI and diagnosis (MDD or bipolar disorder [in a major depressive episode], BMI, HAMD, and PSQI (P<0.05.Conclusion: The findings of our study suggested that the rate of depression being comorbid with OSA is remarkably high and revealed that there is a high rate of undetected OSA among depressive disorder patients and untreated OSA among mood

  13. G Protein-Linked Signaling Pathways in Bipolar and Major Depressive Disorders

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    Hiroaki eTomita

    2013-12-01

    Full Text Available The G-protein linked signaling system (GPLS comprises a large number of G-proteins, G protein-coupled receptors (GPCRs, GPCR ligands, and downstream effector molecules. G-proteins interact with both GPCRs and downstream effectors such as cyclic adenosine monophosphate (cAMP, phosphatidylinositols, and ion channels. The GPLS is implicated in the pathophysiology and pharmacology of both major depressive disorder (MDD and bipolar disorder (BPD. This study evaluated whether GPLS is altered at the transcript level. The gene expression in the dorsolateral prefrontal (DLPFC and anterior cingulate (ACC were compared from MDD, BPD, and control subjects using Affymetrix Gene Chips and real time quantitative PCR. High quality brain tissue was used in the study to control for confounding effects of agonal events, tissue pH, RNA integrity, gender, and age. GPLS signaling transcripts were altered especially in the ACC of BPD and MDD subjects. Transcript levels of molecules which repress cAMP activity were increased in BPD and decreased in MDD. Two orphan GPCRs, GPRC5B and GPR37, showed significantly decreased expression levels in MDD, and significantly increased expression levels in BPD. Our results suggest opposite changes in BPD and MDD in the GPLS, ‘activated’ cAMP signaling activity in BPD and ‘blunted’ cAMP signaling activity in MDD. GPRC5B and GPR37 both appear to have behavioral effects, and are also candidate genes for neurodegenerative disorders. In the context of the opposite changes observed in BPD and MDD, these GPCRs warrant further study of their brain effects.

  14. The potential role of monocyte chemoattractant protein-1 for major depressive disorder.

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    Pae, Chi-Un

    2014-07-01

    The immune hypothesis of major depressive disorder (MDD) fits well with the supposed interaction between genetic and environmental factors in disorders with a complicated etiopathogenesis. It has been suggested that infectious diseases are associated with MDD in that cytokines may play a critical role as a key modulator in the transition between infection and the development of MDD. It has been also suggested that antidepressants have immunomodulatory effects on some cytokines and cytokine receptors, although the exact mechanism has not yet been fully elucidated. Among cytokines, monocyte chemoattractant protein-1 (MCP-1) is especially well known and has attracted considerable interest owing to its immunomodulatory functions. MCP-1 is expressed in highly regionalized neuronal areas in the brain, leading to kind of modulation of neuronal activity and neuroendocrine functions commonly seen in patients with MDD. Additionally, it is involved in the control of other cytokines that have been consistently proposed as associated with the development of MDD. It also has a possible role in the neurodegenerative process of a number of central nervous system (CNS) diseases. Hence, this paper draws from the perspective of immunology to offer several suggestions about the role of MPC-1 in the development of MDD.

  15. Altered slow wave activity in major depressive disorder with hypersomnia: a high density EEG pilot study.

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    Plante, David T; Landsness, Eric C; Peterson, Michael J; Goldstein, Michael R; Wanger, Tim; Guokas, Jeff J; Tononi, Giulio; Benca, Ruth M

    2012-03-31

    Hypersomnolence in major depressive disorder (MDD) plays an important role in the natural history of the disorder, but the basis of hypersomnia in MDD is poorly understood. Slow wave activity (SWA) has been associated with sleep homeostasis, as well as sleep restoration and maintenance, and may be altered in MDD. Therefore, we conducted a post-hoc study that utilized high density electroencephalography (hdEEG) to test the hypothesis that MDD subjects with hypersomnia (HYS+) would have decreased SWA relative to age- and sex-matched MDD subjects without hypersomnia (HYS-) and healthy controls (n=7 for each group). After correction for multiple comparisons using statistical non-parametric mapping, HYS+ subjects demonstrated significantly reduced parieto-occipital all-night SWA relative to HYS- subjects. Our results suggest hypersomnolence may be associated with topographic reductions in SWA in MDD. Further research using an adequately powered prospective design is indicated to confirm these findings. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Suicidal intent and the HPA-axis characteristics of suicide attempters with major depressive disorder and adjustment disorders.

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    Lindqvist, Daniel; Träskman-Bendz, Lil; Vang, Fredrik

    2008-01-01

    The main purpose of the study was to investigate Hypothalamic-Pituitary-Adrenal (HPA) axis characteristics in relation to suicidal intent among suicide attempters with Major Depressive Disorder (MDD) and Adjustment Disorders (AD). The relationship between suicidal intent, assessed by means of the Suicidal Intent Scale (SIS), and serum cortisol after a Dexamethasone Suppression Test (DST) was investigated in 78 suicide attempters, divided into diagnostic subgroups. There was a significant negative correlation between suicidal intent and post DST cortisol in patients with MDD. Our findings may be attributed to pathophysiological processes, where a high suicidal intent is revealed during a potential chronic course of MDD, which in turn results in a seemingly normal stress system.

  17. Early maladaptive schemas of emotional deprivation, social isolation, shame and abandonment are related to a history of suicide attempts among patients with major depressive disorders.

    Science.gov (United States)

    Ahmadpanah, Mohammad; Astinsadaf, Sommayyeh; Akhondi, Amineh; Haghighi, Mohammad; Sadeghi Bahmani, Dena; Nazaribadie, Marzieh; Jahangard, Leila; Holsboer-Trachsler, Edith; Brand, Serge

    2017-08-01

    Patients with psychiatric disorders have an exceptionally high risk of completed or attempted suicide. This holds particularly true for patients with major depressive disorders. The aim of the present study was to explore whether patients with major depressive disorders (MDD) and a history of suicide attempts differed in their early maladaptive schemas from patients with MDD but without such a history or from healthy controls. Ninety participants took part in the study. Of these, 30 were patients with MDD who had made a recent suicide attempt; 30 were patients with MDD but no suicide attempts, and 30 were gender- and age-matched healthy controls. Participants completed questionnaires covering socio-demographic characteristics and the Young Schema Questionnaire (YSQ- RE2R) to assess early maladaptive schemas. Experts rated patients' MDD with the Montgomery-Asberg Depression Rating Scale. Patients did not differ in experts' ratings of symptoms of depression. Compared to healthy controls, patients with MDD recorded higher scores on maladaptive schemas such as recognition seeking, negativity/pessimism, and insufficient self-control. Compared to patients without suicide attempts and healthy controls, those who had made a suicide attempt had higher scores on dimensions such as failure, mistrust, emotional inhibition, social isolation, and abandonment/instability. Compared to healthy controls, patients with MDD had more pronounced maladaptive schemas, but this was more marked in patients with a history of suicide attempts. The results suggest that suicide attempts and poorer psychological functioning are related. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Recollection deficiencies in patients with major depressive disorder.

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    Drakeford, Justine L; Edelstyn, Nicola M J; Oyebode, Femi; Srivastava, Shrikant; Calthorpe, William R; Mukherjee, Tirthankar

    2010-02-28

    Neuropsychological research suggests that recognition memory (RM) and recall memory are impaired in patients with a major depressive disorder or a dysphoric mood state. This study examines the proposal that abnormalities in recollection (a form of recall) result from a breakdown in frontal strategic memory processes involved in encoding and retrieval, and executive functions linked to reality monitoring, planning, problem-solving, reasoning and decision-making. We investigated two predictions arising from this theory. Firstly, patients diagnosed with a major depressive disorder (MDD) will display a dissociation between (deficient) recollection and (preserved) familiarity. Secondly, if recollection impairments are indicative of a breakdown in prefrontal strategic memory processes which are dependent, at least in part, on executive processes, then an explicit correlational approach predicts that recollection will be positively associated with the severity of executive dysfunction in MDD patients. The remember/know paradigm was used to investigate RM for words and neutral faces in 16 MDD patients and 16 healthy volunteers, matched for age, gender and estimates of premorbid IQ. Measures of executive function included working memory, reasoning and decision-making. Applying the Dual Process Signal Detection interpretation of the remember/know data, the MDD group displayed significant impairments in RM and recollection rates for both verbal and neutral facial memoranda. In contrast, familiarity-aware rates were preserved. There was no evidence of executive dysfunction in the patient group, and little evidence that recollection rates correlated with executive function. Furthermore, a single process signal detection approach suggested that the MDD patients displayed a reduction in sensitivity for RM and remember rates but not know responses. The criteria for detecting studied from unstudied items, and remembering from knowing, were the same in both patient and healthy

  19. Differences in the Prevalence, Severity and Symptom Profiles of Depression in Boys and Adolescents with an Autism Spectrum Disorder versus Normally Developing Controls

    Science.gov (United States)

    Bitsika, Vicki; Sharpley, Christopher F.

    2015-01-01

    The prevalence, severity and symptom profiles for major depressive disorder (MDD) were compared in samples of boys and adolescents with and without an autism spectrum disorder (ASD). Self-reports were obtained on the Depression subscale of the Child and Adolescent Symptoms Inventory (CASI-D) with 70 ASD and 50 non-ASD male participants between the…

  20. Reorganization of Anatomical Connectome following Electroconvulsive Therapy in Major Depressive Disorder

    OpenAIRE

    Jinkun Zeng; Qinghua Luo; Lian Du; Wei Liao; Yongmei Li; Haixia Liu; Dan Liu; Yixiao Fu; Haitang Qiu; Xirong Li; Tian Qiu; Huaqing Meng

    2015-01-01

    Objective. Electroconvulsive therapy (ECT) is considered one of the most effective and fast-acting treatment options for depressive episodes. Little is known, however, about ECT's enabling brain (neuro)plasticity effects, particular for plasticity of white matter pathway. Materials and Methods. We collected longitudinal diffusion tensor imaging in the first-episode, drug-naïve major depressive disorder (MDD) patients (n = 24) before and after a predefined time window ECT treatment. We constru...

  1. Measuring the Quality of Care for Psychological Health Conditions in the Military Health System: Candidate Quality Measures for Posttraumatic Stress Disorder and Major Depressive Disorder

    Science.gov (United States)

    2015-01-01

    and Statistical Manual of Mental Disorders, 4th ed., Axis I Disorders SDS Sheehan Disability Scale SI suicide ideation SIT Stress Inoculation Training...depression, behavioral health, mental health, MDD, PTSD, suicide , post-traumatic stress disorder, post- traumatic stress disorder, trauma, traumatic...gender, family history of suicide , same-sex orientation) and modifiable risk factors (e.g., unstable housing, financial problems, psychiatric disorders

  2. Comparison of Clinical Features and Personality Dimensions between Patients with Major Depressive Disorder and Normal Control.

    Science.gov (United States)

    Hur, Ji-Won; Kim, Yong-Ku

    2009-09-01

    Personality dimension is considered as a risk factor of depression. This study was to compare aggression, impulsivity, hopelessness, and TCI (temperament and character dimensions) between patients with major depressive disorder (MDD) and normal controls. A total of 56 MDD patients and the same number of normal controls who were matched for age, gender, and education were recruited. All subjects completed the following questionnaires; Aggression Questionnaire (AQ), Beck Hopelessness Scale (BHS), Barratt Impulsiveness Scale, 11th Version (BIS-11), and Temperament and Character Inventory (TCI). MDD patients were significantly higher scores in anger, hostility of AQ, BHS, motor impulsivity of BIS-11, and Harm Avoidances (HA) of TCI with all subscales of HA than normal controls, whereas novelty seeking 1 (NS1) (Exploratory of NS), Reward Dependence (RD) with RD3 (Attachment) . RD4 (Dependence), Self-Directedness (SD) with most subscales of SD, Cooperativeness (CO), and ST3 (Spiritual Acceptance) showed lower scores than normal controls. Moreover, BHS and HA, BIS and NS showed moderate positive correlation in MDD patients, while BHS and SD, HA and SD were negatively correlated. The present study showed unique clinical features, especially personality dimensions of patients with MDD. Our results could be applicable to suggest treatment process and to predict one's prognosis for depression in that psychological properties are important for drug compliance and treatment response.

  3. Neurobiological effects of exercise on major depressive disorder: A systematic review.

    Science.gov (United States)

    Schuch, Felipe Barreto; Deslandes, Andrea Camaz; Stubbs, Brendon; Gosmann, Natan Pereira; Silva, Cristiano Tschiedel Belem da; Fleck, Marcelo Pio de Almeida

    2016-02-01

    Exercise displays promise as an efficacious treatment for people with depression. However, no systematic review has evaluated the neurobiological effects of exercise among people with major depressive disorder (MDD). The aim of this article was to systematically review the acute and chronic biological responses to exercise in people with MDD. Two authors conducted searches using Medline (PubMed), EMBASE and PsycINFO. From the searches, twenty studies were included within the review, representing 1353 people with MDD. The results demonstrate that a single bout of exercise increases atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), copepetin and growth hormone among people with MDD. Exercise also potentially promotes long-term adaptations of copeptin, thiobarbituric acid reactive species (TBARS) and total mean frequency (TMF). However, there is limited evidence that exercise promotes adaptations on neurogenesis, inflammation biomarkers and brain structure. Associations between depressive symptoms improvement and hippocampus volume and IL-1β were found. Nevertheless, the paucity of studies and limitations presented within, precludes a more definitive conclusion of the underlying neurobiological explanation for the antidepressant effect of exercise in people with MDD. Further trials should utilize appropriate assessments of neurobiological markers in order to build upon the results of our review and further clarify the potential mechanisms associated with the antidepressant effects of exercise.

  4. Inverse changes in L1 retrotransposons between blood and brain in major depressive disorder.

    Science.gov (United States)

    Liu, Shu; Du, Tingfu; Liu, Zeyue; Shen, Yan; Xiu, Jianbo; Xu, Qi

    2016-11-22

    Long interspersed nuclear element-1 (LINE-1 or L1) is a type of retrotransposons comprising 17% of the human and mouse genome, and has been found to be associated with several types of neurological disorders. Previous post-mortem brain studies reveal increased L1 copy number in the prefrontal cortex from schizophrenia patients. However, whether L1 retrotransposition occurs similarly in major depressive disorder (MDD) is unknown. Here, L1 copy number was measured by quantitative PCR analysis in peripheral blood of MDD patients (n = 105) and healthy controls (n = 105). The results showed that L1 copy number was increased in MDD patients possibly due to its hypomethylation. Furthermore, L1 copy number in peripheral blood and five brain regions (prefrontal cortex, hippocampus, amygdala, nucleus accumbens and paraventricular hypothalamic nucleus) was measured in the chronic unpredictable mild stress (CUMS) model of depression in mice. Intriguingly, increased L1 copy number in blood and the decreased L1 copy number in the prefrontal cortex were observed in stressed mice, while no change was found in other brain regions. Our results suggest that the changes of L1 may be associated with the pathophysiology of MDD, but the biological mechanism behind dysfunction of L1 retrotransposition in MDD remains to be further investigated.

  5. Anxiety and depressive disorders are associated with delusional-like experiences: a replication study based on a National Survey of Mental Health and Wellbeing

    Science.gov (United States)

    Scott, James; Varghese, Daniel; McGrath, John

    2012-01-01

    Objectives There is growing evidence that delusional-like experiences (DLE) are associated with common mental disorders. In particular, a National Mental Health Survey conducted in Australia during 2007 reported an association between DLE and both anxiety disorder and major depressive disorder (MDD). However, the previous study did not examine this association with respect to subtypes of anxiety disorder nor with severity of MDD. The aim of this study was to examine the associations between DLE and both anxiety disorder and MDD in more detail based on an independent population sample. Design Cross-sectional study. Setting Subjects were drawn from the Australian Survey of Mental Health and Wellbeing 1997 using a stratified multistage area sampling of persons living in private dwellings in all States and Territories of Australia. Participants Approximately 13 600 private dwellings were initially selected with one person aged 18 years or older from each dwelling invited to participate. In total, 10 641 individuals participated in the survey. Primary and secondary outcome measures The Composite International Diagnostic Interview was used to identify individuals with DLE and Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM IV) lifetime diagnoses of anxiety disorders and MDD. The influence of various anxiety disorders and MDD on DLE was assessed with logistic regression. Results Having a lifetime diagnosis of either any anxiety disorder or MDD was significantly associated with the endorsement of DLE. The association was found for each of the main anxiety disorders when examined separately. There was a dose–response relationship between increasing severity of MDD and higher odds of DLE endorsement. Conclusions DLE are associated with a wide range of anxiety disorders and are more prevalent in those with MDD. Understanding the relationship between DLE, anxiety disorders and depression may provide insights into shared pathways that underpin

  6. Adapting Mindfulness-Based Cognitive Therapy for Treatment-Resistant Depression

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    Eisendrath, Stuart; Chartier, Maggie; McLane, Maura

    2011-01-01

    Major depressive disorder (MDD) is currently ranked the third leading cause of disability in the world. Treatment-resistant depression (TRD) causes the majority of MDD disability. Strikingly, 50% of individuals with MDD will fail to remit with 2 adequate trials of antidepressant medications, thus qualifying as treatment resistant. Current…

  7. Adapting Mindfulness-Based Cognitive Therapy for Treatment-Resistant Depression

    Science.gov (United States)

    Eisendrath, Stuart; Chartier, Maggie; McLane, Maura

    2011-01-01

    Major depressive disorder (MDD) is currently ranked the third leading cause of disability in the world. Treatment-resistant depression (TRD) causes the majority of MDD disability. Strikingly, 50% of individuals with MDD will fail to remit with 2 adequate trials of antidepressant medications, thus qualifying as treatment resistant. Current…

  8. Neutrophil–lymphocyte ratio in patients with major depressive disorder undergoing no pharmacological therapy

    Directory of Open Access Journals (Sweden)

    Demir S

    2015-08-01

    Full Text Available Süleyman Demir,1 Abdullah Atli,1 Mahmut Bulut,1 Aslihan Okan İbiloğlu,1 Mehmet Güneş,1 Mehmet Cemal Kaya,1 Özlem Demirpençe,2 Aytekin Sir1 1Department of Psychiatry, Dicle University, Diyarbakir, 2Department of Biochemistry, Cumhuriyet University, Sivas, Turkey Abstract: Studies attempting to clarify the relationship between major depressive disorder (MDD and the immune system have been increasing in recent years. It was reported that increased production of the main proinflammatory cytokines, such as interleukin-1, interleukin-6, and tumor necrosis factor-alpha, and that of acute phase reactants may play a role in the etiopathogenesis of depression. Stress and depression were reported to increase leukocyte and neutrophil counts and to decrease lymphocyte count. Biological determinants affecting the diagnosis, therapy, and prognosis of depression are quite limited. Therefore, new etiological models are needed to explain the pathophysiology of depression. In recent years, neutrophil–lymphocyte ratio (NLR was determined to be a good indicator of inflammatory status. There is no study in the literature investigating NLR in MDD. This study aims to examine the role of inflammation in the etiology of depression based on the NLR in MDD patients who are undergoing no pharmacological therapy. A total of 41 patients diagnosed with MDD, who received no antidepressant therapy within the past 1 month, were included in the study, which took place between January and March 2015. The control group consisted of 47 healthy subjects with no psychiatric disorders. A sociodemographic information form and a Beck Depression Scale were administered, and the blood was taken for biochemical analysis. Significant differences were identified in the NLR, neutrophil count, lymphocyte percentage, and leukocyte values of the patient group when compared with the control group (P<0.05. Our study is the first in which NLR was investigated in MDD. The findings of the

  9. Prevalence and relationship between major depressive disorder and lung cancer: a cross-sectional study

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    Maneeton B

    2014-05-01

    Full Text Available Benchalak Maneeton,1 Narong Maneeton,1 Jirayu Reungyos,1 Suthi Intaprasert,1 Samornsri Leelarphat,1 Sumitra Thongprasert21Department of Psychiatry, 2Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, ThailandObjective: The aims of this study were to estimate the prevalence and examine the factors associated with major depressive disorder (MDD in lung cancer patients.Materials and methods: This cross-sectional study was carried out in the oncology clinic of the University Hospital, Chiang Mai University, Thailand. Patients with all stages of lung cancer were included in this study. Demographic data of eligible patients were gathered. The Mini-International Neuropsychiatric Interview, Thai version 5.0.0 was used to identify MDD. The Thai version of the Personal Health Questionnaire Depression Scale was used to assess depression severity.Results: A total of 146 lung cancer patients from the outpatient clinic from July to December 2012 were approached. The 104 patients were included and analyzed in this study. Based on the Mini-International Neuropsychiatric Interview, 14.4% of them were defined as having MDD. Multiple linear regression analysis revealed that Chalder Fatigue Scale, Functional Assessment of Cancer Therapy – Lung, and Pittsburgh Sleep Quality Index scores were significantly correlated with MDD in lung cancer patients.Conclusion: The results suggest that MDD is more prevalent in lung cancer patients. In addition, fatigue, poor quality of life, and sleep disturbance may increase associated MDD. Because of the small sample size, further studies should be conducted to confirm these results.Keywords: lung cancer, major depressive disorder, prevalence

  10. Discovery and validation of plasma biomarkers for major depressive disorder classification based on liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Liu, Xinyu; Zheng, Peng; Zhao, Xinjie; Zhang, Yuqing; Hu, Chunxiu; Li, Jia; Zhao, Jieyu; Zhou, Jingjing; Xie, Peng; Xu, Guowang

    2015-05-01

    Major depressive disorder (MDD) is a debilitating mental disease with a pronounced impact on the quality of life of many people; however, it is still difficult to diagnose MDD accurately. In this study, a nontargeted metabolomics approach based on ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to find the differential metabolites in plasma samples from patients with MDD and healthy controls. Furthermore, a validation analysis focusing on the differential metabolites was performed in another batch of samples using a targeted approach based on the dynamic multiple reactions monitoring method. Levels of acyl carnitines, ether lipids, and tryptophan pronouncedly decreased, whereas LPCs, LPEs, and PEs markedly increased in MDD subjects as compared with the healthy controls. Disturbed pathways, mainly located in acyl carnitine metabolism, lipid metabolism, and tryptophan metabolism, were clearly brought to light in MDD subjects. The binary logistic regression result showed that carnitine C10:1, PE-O 36:5, LPE 18:1 sn-2, and tryptophan can be used as a combinational biomarker to distinguish not only moderate but also severe MDD from healthy control with good sensitivity and specificity. Our findings, on one hand, provide critical insight into the pathological mechanism of MDD and, on the other hand, supply a combinational biomarker to aid the diagnosis of MDD in clinical usage.

  11. A Preliminary Study of the Influence of Age of Onset and Childhood Trauma on Cortical Thickness in Major Depressive Disorder

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    Natalia Jaworska

    2014-01-01

    Full Text Available Background. Major depressive disorder (MDD neural underpinnings may differ based on onset age and childhood trauma. We assessed cortical thickness in patients who differed in age of MDD onset and examined trauma history influence. Methods. Adults with MDD (N=36 and controls (HC; N=18 underwent magnetic resonance imaging. Twenty patients had MDD onset 25 years of age (adult onset. The MDD group was also subdivided into those with (N=12 and without (N=19 physical and/or sexual abuse as assessed by the Childhood Trauma Questionnaire (CTQ. Cortical thickness was analyzed with FreeSurfer software. Results. Thicker frontal pole and a tendency for thinner transverse temporal cortices existed in MDD. The former was driven by the pediatric onset group and abuse history (independently, particularly in the right frontal pole. Inverse correlations existed between CTQ scores and frontal pole cortex thickness. A similar inverse relation existed with left inferior and right superior parietal cortex thickness. The superior temporal cortex tended to be thinner in pediatric versus adult onset groups with childhood abuse. Conclusions. This preliminary work suggests neural differences between pediatric and adult MDD onset. Trauma history also contributes to cytoarchitectural modulation. Thickened frontal pole cortices as a compensatory mechanism in MDD warrant evaluation.

  12. The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders.

    Science.gov (United States)

    Smoller, Jordan W

    2016-01-01

    Research into the causes of psychopathology has largely focused on two broad etiologic factors: genetic vulnerability and environmental stressors. An important role for familial/heritable factors in the etiology of a broad range of psychiatric disorders was established well before the modern era of genomic research. This review focuses on the genetic basis of three disorder categories-posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and the anxiety disorders-for which environmental stressors and stress responses are understood to be central to pathogenesis. Each of these disorders aggregates in families and is moderately heritable. More recently, molecular genetic approaches, including genome-wide studies of genetic variation, have been applied to identify specific risk variants. In this review, I summarize evidence for genetic contributions to PTSD, MDD, and the anxiety disorders including genetic epidemiology, the role of common genetic variation, the role of rare and structural variation, and the role of gene-environment interaction. Available data suggest that stress-related disorders are highly complex and polygenic and, despite substantial progress in other areas of psychiatric genetics, few risk loci have been identified for these disorders. Progress in this area will likely require analysis of much larger sample sizes than have been reported to date. The phenotypic complexity and genetic overlap among these disorders present further challenges. The review concludes with a discussion of prospects for clinical translation of genetic findings and future directions for research.

  13. Depression Case Control (DeCC) Study fails to support involvement of the muscarinic acetylcholine receptor M2 (CHRM2) gene in recurrent major depressive disorder.

    Science.gov (United States)

    Cohen-Woods, Sarah; Gaysina, Daria; Craddock, Nick; Farmer, Anne; Gray, Joanna; Gunasinghe, Cerisse; Hoda, Farzana; Jones, Lisa; Knight, Jo; Korszun, Ania; Owen, Michael J; Sterne, Abram; Craig, Ian W; McGuffin, Peter

    2009-04-15

    It has been suggested that alteration in the muscarinic-cholinergic system is involved in modulation of mood. Three studies have reported linkage on chromosome 7 with major depressive disorder (MDD) in or close to a region containing the muscarinic receptor CHRM2 gene. A haplotype of SNPs located in CHRM2 (rs1824024-rs2061174-rs324650) has been significantly associated with MDD in a previous study. We report the first study investigating this gene in a large, adequately powered, clinical depression case-control sample (n = 1420 cases, 1624 controls). Our data fail to support association with the CHRM2 polymorphisms previously implicated in the genetic aetiology of depression. It is possible our failure to replicate may be a consequence of differences in definition of the MDD phenotype and/or ethnic differences.

  14. Cerebral and cerebellar gray matter reduction in first-episode patients with major depressive disorder: A voxel-based morphometry study

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    Peng Jing, E-mail: ppengjjing@sina.com.cn [Department of Radiology, Xuanwu Hospital of Capital Medical University, No. 45, Chang-Chun St, Xuanwu District, Beijing 100053 (China); Liu Jiangtao, E-mail: Liujiangtao813@sina.com [Department of Radiology, Xuanwu Hospital of Capital Medical University, No. 45, Chang-Chun St, Xuanwu District, Beijing 100053 (China); Nie Binbin, E-mail: niebb@ihep.ac.cn [Institute of High Energy Physics, Chinese Academy of Sciences, PO Box 918, Yu-Quan St, Shijingshan District, Beijing 100049 (China); Li Yang, E-mail: Liyang2007428@hotmail.com [Department of Psychiatry, Anding Hospital of Capital Medical University, No. 5, An Kang Hutong, Deshengmen wai, Xicheng District, Beijing 100088 (China); Shan Baoci, E-mail: shanbc@ihep.ac.cn [Institute of High Energy Physics, Chinese Academy of Sciences, PO Box 918, Yu-Quan St, Shijingshan District, Beijing 100049 (China); Wang Gang, E-mail: gangwang@gmail.com [Department of Psychiatry, Anding Hospital of Capital Medical University, No. 5, An Kang Hutong, Deshengmen wai, Xicheng District, Beijing 100088 (China); Li Kuncheng, E-mail: likuncheng1955@yahoo.com.cn [Department of Radiology, Xuanwu Hospital of Capital Medical University, No. 45, Chang-Chun St, Xuanwu District, Beijing 100053 (China)

    2011-11-15

    Purpose: To investigate cerebral and cerebellar gray matter abnormalities in patients with first-episode major depressive disorder (MDD). Materials and methods: We examined the structural difference in regional gray matter density (GMD) between 22 first-episode MDD patients and 30 age-, gender- and education-matched healthy controls by optimized voxel-based morphometry (VBM) based on magnetic resonance imaging. Results: Compared with healthy controls, MDD patients showed decreased GMD in the right medial and left lateral orbitofrontal cortex, right dorsolateral prefrontal cortex (DLPFC), bilateral temporal pole, right superior temporal gyrus, bilateral anterior insular cortex, left parahippocampal gyrus, and left cerebellum. In addition, in MDD patients, there was a negative correlation between GMD values of the right DLPFC and the score of the depression rating scale. Conclusions: Our findings provided additional support for the involvement of limbic-cortical circuits in the pathophysiology of MDD and preliminary evidence that a defect involving the cerebellum may also be implicated.

  15. Symptoms of major depressive disorder subsequent to child maltreatment: Examining change across multiple levels of analysis to identify transdiagnostic risk pathways.

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    Shenk, Chad E; Griffin, Amanda M; O'Donnell, Kieran J

    2015-11-01

    Major depressive disorder (MDD) is a prevalent psychiatric condition in the child maltreatment population. However, not all children who have been maltreated will develop MDD or MDD symptoms, suggesting the presence of unique risk pathways that explain how certain children develop MDD symptoms when others do not. The current study tested several candidate risk pathways to MDD symptoms following child maltreatment: neuroendocrine, autonomic, affective, and emotion regulation. Female adolescents (N = 110; age range = 14-19) were recruited into a substantiated child maltreatment or comparison condition and completed a laboratory stressor, saliva samples, and measures of emotion regulation, negative affect, and MDD symptoms. MDD symptoms were reassessed 18 months later. Mediational modeling revealed that emotion regulation was the only significant indirect effect of the relationship between child maltreatment and subsequent MDD symptoms, demonstrating that children exposed to maltreatment had greater difficulties managing affective states that in turn led to more severe MDD symptoms. These results highlight the importance of emotion dysregulation as a central risk pathway to MDD following child maltreatment. Areas of future research and implications for optimizing prevention and clinical intervention through the direct targeting of transdiagnostic risk pathways are discussed.

  16. Exploring culture-specific differences in beliefs about causes, kinship and the heritability of major depressive disorder: the views of Anglo-Celtic and Chinese-Australians.

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    Xu, Mimi; Zou, Lilian; Wilde, Alex; Meiser, Bettina; Barlow-Stewart, Kristine; Chan, Bibiana; Mitchell, Philip B; Sousa, Mariana S; Schofield, Peter R

    2013-10-01

    The aim of this study was to explore cultural differences in causal attributions and beliefs about heritability of major depressive disorder (MDD). Face-to-face interviews with Anglo-Celtic- and Chinese-Australians community members with a family history of MDD were conducted and subjected to a rigorous qualitative analysis, using the computer software NVivo. Sixteen Anglo-Celtic-Australians and 16 Chinese-Australians were interviewed. Both groups believed that a combination of genetic and environmental factors contributed to MDD, that stress was an important cause of MDD, and that coping factors were significant moderators of the impact of stress on MDD. Both cultural groups believed that the causes of MDD affecting multiple family members included a shared family environment and a "contagion effect", in addition to genetics. Unique to the Chinese-Australian group was the beliefs that parental pressures to exceed academically contributed to MDD; this cultural group also reported beliefs that depression was due to God's will or alternatively fate, which in turn was related to attributions to feng shui and auspicious dates. This study documented key culture-specific differences in beliefs about causes and inheritance of MDD; such differences have major implications for clinician-patient communication about genetic risk associated with having a family history of MDD.

  17. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010.

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    Alize J Ferrari

    2013-11-01

    Full Text Available Depressive disorders were a leading cause of burden in the Global Burden of Disease (GBD 1990 and 2000 studies. Here, we analyze the burden of depressive disorders in GBD 2010 and present severity proportions, burden by country, region, age, sex, and year, as well as burden of depressive disorders as a risk factor for suicide and ischemic heart disease.Burden was calculated for major depressive disorder (MDD and dysthymia. A systematic review of epidemiological data was conducted. The data were pooled using a Bayesian meta-regression. Disability weights from population survey data quantified the severity of health loss from depressive disorders. These weights were used to calculate years lived with disability (YLDs and disability adjusted life years (DALYs. Separate DALYs were estimated for suicide and ischemic heart disease attributable to depressive disorders. Depressive disorders were the second leading cause of YLDs in 2010. MDD accounted for 8.2% (5.9%-10.8% of global YLDs and dysthymia for 1.4% (0.9%-2.0%. Depressive disorders were a leading cause of DALYs even though no mortality was attributed to them as the underlying cause. MDD accounted for 2.5% (1.9%-3.2% of global DALYs and dysthymia for 0.5% (0.3%-0.6%. There was more regional variation in burden for MDD than for dysthymia; with higher estimates in females, and adults of working age. Whilst burden increased by 37.5% between 1990 and 2010, this was due to population growth and ageing. MDD explained 16 million suicide DALYs and almost 4 million ischemic heart disease DALYs. This attributable burden would increase the overall burden of depressive disorders from 3.0% (2.2%-3.8% to 3.8% (3.0%-4.7% of global DALYs.GBD 2010 identified depressive disorders as a leading cause of burden. MDD was also a contributor of burden allocated to suicide and ischemic heart disease. These findings emphasize the importance of including depressive disorders as a public-health priority and implementing

  18. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010.

    Science.gov (United States)

    Ferrari, Alize J; Charlson, Fiona J; Norman, Rosana E; Patten, Scott B; Freedman, Greg; Murray, Christopher J L; Vos, Theo; Whiteford, Harvey A

    2013-11-01

    Depressive disorders were a leading cause of burden in the Global Burden of Disease (GBD) 1990 and 2000 studies. Here, we analyze the burden of depressive disorders in GBD 2010 and present severity proportions, burden by country, region, age, sex, and year, as well as burden of depressive disorders as a risk factor for suicide and ischemic heart disease. Burden was calculated for major depressive disorder (MDD) and dysthymia. A systematic review of epidemiological data was conducted. The data were pooled using a Bayesian meta-regression. Disability weights from population survey data quantified the severity of health loss from depressive disorders. These weights were used to calculate years lived with disability (YLDs) and disability adjusted life years (DALYs). Separate DALYs were estimated for suicide and ischemic heart disease attributable to depressive disorders. Depressive disorders were the second leading cause of YLDs in 2010. MDD accounted for 8.2% (5.9%-10.8%) of global YLDs and dysthymia for 1.4% (0.9%-2.0%). Depressive disorders were a leading cause of DALYs even though no mortality was attributed to them as the underlying cause. MDD accounted for 2.5% (1.9%-3.2%) of global DALYs and dysthymia for 0.5% (0.3%-0.6%). There was more regional variation in burden for MDD than for dysthymia; with higher estimates in females, and adults of working age. Whilst burden increased by 37.5% between 1990 and 2010, this was due to population growth and ageing. MDD explained 16 million suicide DALYs and almost 4 million ischemic heart disease DALYs. This attributable burden would increase the overall burden of depressive disorders from 3.0% (2.2%-3.8%) to 3.8% (3.0%-4.7%) of global DALYs. GBD 2010 identified depressive disorders as a leading cause of burden. MDD was also a contributor of burden allocated to suicide and ischemic heart disease. These findings emphasize the importance of including depressive disorders as a public-health priority and implementing cost

  19. Is there Progress? An Overview of Select Biomarker Candidates for Major Depressive Disorder

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    Juan Joseph Young

    2016-04-01

    Full Text Available Major Depressive Disorder (MDD contributes to a significant worldwide disease burden, expected to be second only to heart disease by 2050. However, accurate diagnosis has been a historical weakness in clinical psychiatry. As a result, there is a demand for diagnostic modalities with greater objectivity that could improve on current psychiatric practice that relies mainly on self-reporting of symptoms and clinical interviews. Over the past two decades, literature on a growing number of putative biomarkers for MDD increasingly suggests that MDD patients have significantly different biological profiles compared to healthy controls. However, difficulty in elucidating their exact relationships within depression pathology renders individual markers inconsistent diagnostic tools. Consequently, further biomarker research could potentially improve our understanding of MDD pathophysiology as well as aid in interpreting response to treatment, narrow differential diagnoses, and help refine current MDD criteria. Representative of this, multiplex assays using multiple sources of biomarkers are reported to be more accurate options in comparison to individual markers that exhibit lower specificity and sensitivity, and are more prone to confounding factors. In the future, more sophisticated multiplex assays may hold promise for use in screening and diagnosing depression and determining clinical severity as an advance over relying solely on current subjective diagnostic criteria. A pervasive limitation in existing research is heterogeneity inherent in MDD studies, which impacts the validity of biomarker data. Additionally, small sample sizes of most studies limit statistical power. Yet, as the RDoC project evolves to decrease these limitations, and stronger studies with more generalizable data are developed, significant advances in the next decade are expected to yield important information in the development of MDD biomarkers for use in clinical settings.

  20. Diagnosing major depressive disorder VIII: are some symptoms better than others?

    Science.gov (United States)

    McGlinchey, Joseph B; Zimmerman, Mark; Young, Diane; Chelminski, Iwona

    2006-10-01

    The present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project examined whether symptoms that are not part of the DSM-IV definition of major depressive disorder (MDD) are better at discriminating depressed from nondepressed patients than the current criteria. Symptoms assessed included diminished drive, helplessness, hopelessness, nonreactive mood, psychic anxiety, somatic anxiety, subjective anger, and overtly expressed anger. A total of 1538 psychiatric outpatients were administered a semistructured diagnostic interview. We inquired about all of the symptoms of depression for all patients. Diminished drive exhibited stronger performance in differentiating MDD from non-MDD relative to all DSM-IV criteria except depressed mood, reduced interest/pleasure, and impaired concentration/indecisiveness. A compound criterion combining diminished drive with loss of energy was endorsed by nearly all MDD patients. Helplessness and hopelessness, when combined into a single criterion, performed more strongly than some of the DSM-IV criteria. Lack of reactivity, anxiety, and anger symptoms failed to differentiate more strongly than current DSM-IV criteria. The implications of these results for revising the diagnostic criteria for major depression are discussed.

  1. Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy.

    Science.gov (United States)

    Redei, E E; Andrus, B M; Kwasny, M J; Seok, J; Cai, X; Ho, J; Mohr, D C

    2014-09-16

    An objective, laboratory-based diagnostic tool could increase the diagnostic accuracy of major depressive disorders (MDDs), identify factors that characterize patients and promote individualized therapy. The goal of this study was to assess a blood-based biomarker panel, which showed promise in adolescents with MDD, in adult primary care patients with MDD and age-, gender- and race-matched nondepressed (ND) controls. Patients with MDD received cognitive behavioral therapy (CBT) and clinical assessment using self-reported depression with the Patient Health Questionnaire-9 (PHQ-9). The measures, including blood RNA collection, were obtained before and after 18 weeks of CBT. Blood transcript levels of nine markers of ADCY3, DGKA, FAM46A, IGSF4A/CADM1, KIAA1539, MARCKS, PSME1, RAPH1 and TLR7, differed significantly between participants with MDD (N=32) and ND controls (N=32) at baseline (qdepressed. Thus, blood levels of different transcript panels may identify the depressed from the nondepressed among primary care patients, during a depressive episode or in remission, or follow and predict response to CBT in depressed individuals.

  2. Bupropion in the treatment of problematic online game play in patients with major depressive disorder.

    Science.gov (United States)

    Han, Doug Hyun; Renshaw, Perry F

    2012-05-01

    As one of the problematic behaviors in patients with major depressive disorder (MDD), excessive online game play (EOP) has been reported in a number of recent studies. Bupropion has been evaluated as a potential treatment for MDD and substance dependence. We hypothesized that bupropion treatment would reduce the severity of EOP as well as depressive symptoms. Fifty male subjects with comorbid EOP and MDD were randomly assigned to bupropion + education for internet use (EDU) or placebo + EDU groups. The current study consisted in a 12-week, prospective, randomized, double-blind clinical trial, including an eight-week active treatment phase and a four-week post treatment follow-up period. During the active treatment period, Young Internet Addiction Scale (YIAS) scores and the mean time of online game playing in the bupropion group were greatly reduced compared with those of the placebo group. The Beck Depression Inventory (BDI) scores in the bupropion group were also greatly reduced compared with those of the placebo group. During the four-week post-treatment follow-up period, bupropion-associated reductions in online game play persisted, while depressive symptoms recurred. Conclusively, bupropion may improve depressive mood as well as reduce the severity of EOP in patients with comorbid MDD and online game addiction.

  3. Interhemispheric functional connectivity and its relationships with clinical characteristics in major depressive disorder: a resting state fMRI study.

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    Li Wang

    Full Text Available BACKGROUND: Abnormalities in large-scale, structural and functional brain connectivity have been increasingly reported in patients with major depressive disorder (MDD. However, MDD-related alterations in functional interaction between the cerebral hemispheres are still not well understood. Resting state fMRI, which reveals spontaneous neural fluctuations in blood oxygen level dependent signals, provides a means to detect interhemispheric functional coherence. We examined the resting state functional connectivity (RSFC between the two hemispheres and its relationships with clinical characteristics in MDD patients using a recently proposed measurement named "voxel-mirrored homotopic connectivity (VMHC". METHODOLOGY/PRINCIPAL FINDINGS: We compared the interhemispheric RSFC, computed using the VMHC approach, of seventeen first-episode drug-naive patients with MDD and seventeen healthy controls. Compared to the controls, MDD patients showed significant VMHC decreases in the medial orbitofrontal gyrus, parahippocampal gyrus, fusiform gyrus, and occipital regions including the middle occipital gyrus and cuneus. In MDD patients, a negative correlation was found between VMHC of the fusiform gyrus and illness duration. Moreover, there were several regions whose VMHC showed significant negative correlations with the severity of cognitive disturbance, including the prefrontal regions, such as middle and inferior frontal gyri, and two regions in the cereballar crus. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the functional coordination between homotopic brain regions is impaired in MDD patients, thereby providing new evidence supporting the interhemispheric connectivity deficits of MDD. The significant correlations between the VMHC and clinical characteristics in MDD patients suggest potential clinical implication of VMHC measures for MDD. Interhemispheric RSFC may serve as a useful screening method for evaluating MDD where neural connectivity is

  4. Are Worry and Rumination Specific Pathways Linking Neuroticism and Symptoms of Anxiety and Depression in Patients with Generalized Anxiety Disorder, Major Depressive Disorder and Mixed Anxiety-Depressive Disorder?

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    Merino, Hipólito; Senra, Carmen; Ferreiro, Fátima

    2016-01-01

    This study examines the relationships between neuroticism (higher-order vulnerability factor), the cognitive styles of worry, brooding and reflection (second-order vulnerability factors) and symptoms of anxiety and depression in three groups of patients: patients with Generalized Anxiety Disorder (GAD), with Major Depressive Disorder (MDD) and with Mixed Anxiety-Depressive Disorder (MADD). One hundred and thirty four patients completed a battery of questionnaires including measures of neuroticism, worry, rumination (brooding and reflection), anxiety and depression. Multiple mediation analyses indicate that worry may act as a mediating mechanism linking neuroticism and anxiety symptoms in the three diagnostic groups, whereas brooding-rumination may play a mediating role between neuroticism and depressive symptoms in patients with MDD and MADD and, with less certainty, in patients with GAD. Overall, our findings suggest that neuroticism may increase the risk of anxious and depressive symptoms via specific links involving either worry or brooding, respectively, and that both worry and brooding may operate in the three groups examined, irrespectively of whether anxiety or depression are the main emotions or whether they coexist without any clear predominance; consequently, we hypothesize the existence of "specific transdiagnostic" mechanisms.

  5. Are Worry and Rumination Specific Pathways Linking Neuroticism and Symptoms of Anxiety and Depression in Patients with Generalized Anxiety Disorder, Major Depressive Disorder and Mixed Anxiety-Depressive Disorder?

    Directory of Open Access Journals (Sweden)

    Hipólito Merino

    Full Text Available This study examines the relationships between neuroticism (higher-order vulnerability factor, the cognitive styles of worry, brooding and reflection (second-order vulnerability factors and symptoms of anxiety and depression in three groups of patients: patients with Generalized Anxiety Disorder (GAD, with Major Depressive Disorder (MDD and with Mixed Anxiety-Depressive Disorder (MADD. One hundred and thirty four patients completed a battery of questionnaires including measures of neuroticism, worry, rumination (brooding and reflection, anxiety and depression. Multiple mediation analyses indicate that worry may act as a mediating mechanism linking neuroticism and anxiety symptoms in the three diagnostic groups, whereas brooding-rumination may play a mediating role between neuroticism and depressive symptoms in patients with MDD and MADD and, with less certainty, in patients with GAD. Overall, our findings suggest that neuroticism may increase the risk of anxious and depressive symptoms via specific links involving either worry or brooding, respectively, and that both worry and brooding may operate in the three groups examined, irrespectively of whether anxiety or depression are the main emotions or whether they coexist without any clear predominance; consequently, we hypothesize the existence of "specific transdiagnostic" mechanisms.

  6. Are Worry and Rumination Specific Pathways Linking Neuroticism and Symptoms of Anxiety and Depression in Patients with Generalized Anxiety Disorder, Major Depressive Disorder and Mixed Anxiety-Depressive Disorder?

    Science.gov (United States)

    Merino, Hipólito; Ferreiro, Fátima

    2016-01-01

    This study examines the relationships between neuroticism (higher-order vulnerability factor), the cognitive styles of worry, brooding and reflection (second-order vulnerability factors) and symptoms of anxiety and depression in three groups of patients: patients with Generalized Anxiety Disorder (GAD), with Major Depressive Disorder (MDD) and with Mixed Anxiety-Depressive Disorder (MADD). One hundred and thirty four patients completed a battery of questionnaires including measures of neuroticism, worry, rumination (brooding and reflection), anxiety and depression. Multiple mediation analyses indicate that worry may act as a mediating mechanism linking neuroticism and anxiety symptoms in the three diagnostic groups, whereas brooding-rumination may play a mediating role between neuroticism and depressive symptoms in patients with MDD and MADD and, with less certainty, in patients with GAD. Overall, our findings suggest that neuroticism may increase the risk of anxious and depressive symptoms via specific links involving either worry or brooding, respectively, and that both worry and brooding may operate in the three groups examined, irrespectively of whether anxiety or depression are the main emotions or whether they coexist without any clear predominance; consequently, we hypothesize the existence of "specific transdiagnostic" mechanisms. PMID:27243462

  7. Associations of educational attainment, occupation, social class and major depressive disorder among Han Chinese women.

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    Jianguo Shi

    Full Text Available BACKGROUND: The prevalence of major depressive disorder (MDD is higher in those with low levels of educational attainment, the unemployed and those with low social status. However the extent to which these factors cause MDD is unclear. Most of the available data comes from studies in developed countries, and these findings may not extrapolate to developing countries. Examining the relationship between MDD and socio economic status in China is likely to add to the debate because of the radical economic and social changes occurring in China over the last 30 years. PRINCIPAL FINDINGS: We report results from 3,639 Chinese women with recurrent MDD and 3,800 controls. Highly significant odds ratios (ORs were observed between MDD and full time employment (OR = 0.36, 95% CI = 0.25-0.46, logP = 78, social status (OR = 0.83, 95% CI = 0.77-0.87, logP = 13.3 and education attainment (OR = 0.90, 95% CI = 0.86-0.90, logP = 6.8. We found a monotonic relationship between increasing age and increasing levels of educational attainment. Those with only primary school education have significantly more episodes of MDD (mean 6.5, P-value = 0.009 and have a clinically more severe disorder, while those with higher educational attainment are likely to manifest more comorbid anxiety disorders. CONCLUSIONS: In China lower socioeconomic position is associated with increased rates of MDD, as it is elsewhere in the world. Significantly more episodes of MDD occur among those with lower educational attainment (rather than longer episodes of disease, consistent with the hypothesis that the lower socioeconomic position increases the likelihood of developing MDD. The phenomenology of MDD varies according to the degree of educational attainment: higher educational attainment not only appears to protect against MDD but alters its presentation, to a more anxious phenotype.

  8. A cross-sectional survey to investigate the prevalence of pain in Japanese patients with major depressive disorder and schizophrenia.

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    Kishi, Taro; Matsuda, Yuki; Mukai, Tomohiko; Matsunaga, Shinji; Yasue, Ichiro; Fujita, Kiyoshi; Okochi, Tomo; Hirano, Shigeki; Kajio, Yusuke; Funahashi, Toshihiko; Akamatsu, Kaku; Ino, Kei; Okuda, Momoko; Tabuse, Hideaki; Iwata, Nakao

    2015-05-01

    We conducted a cross-sectional survey to assess the prevalence of physical pain in Japanese major depressive disorder (MDD) and schizophrenia (SZ) patients as well as in healthy controls (HCs). We also examined the association between their psychopathology and characteristics of pain according to a face-to-face survey by an experienced psychiatrist and psychologist. We analyzed 233 HCs, 94 MDD patients, and 75 SZ patients using the McGill Pain Questionnaire (MPQ) and SF-8 (all participants), the Hamilton Depression Rating Scale 21 items (MDD patients), and the Positive and Negative Symptom Scale (SZ patients). Although MDD patients experienced more pain than HCs, there was no difference in the prevalence of pain between SZ patients and HCs. Moreover, HCs with pain did not have higher SF-8 total scores than those without pain, whereas both MDD and SZ patients with pain had higher SF-8 total scores than those without pain. The severity of psychopathology in MDD and SZ patients was also positively associated with both the prevalence of pain and MPQ scores. MPQ scores were also associated with positive symptoms in SZ patients. Considering these results, physicians need to query MDD patients about physical pain during examination if they are to ensure a favorable and quick response to treatment. The severity of positive symptoms (i.e., clinical status) in SZ patients might also be associated with pain sensitivity, and warrants further investigation.

  9. Is blunted cardiovascular reactivity in depression mood-state dependent? A comparison of major depressive disorder remitted depression and healthy controls.

    Science.gov (United States)

    Salomon, Kristen; Bylsma, Lauren M; White, Kristi E; Panaite, Vanessa; Rottenberg, Jonathan

    2013-10-01

    Prior work has repeatedly demonstrated that people who have current major depression exhibit blunted cardiovascular reactivity to acute stressors (e.g., Salomon et al., 2009). A key question regards the psychobiological basis for these deficits, including whether such deficits are depressed mood-state dependent or whether these effects are trait-like and are observed outside of depression episodes in vulnerable individuals. To examine this issue, we assessed cardiovascular reactivity to a speech stressor task and a forehead cold pressor in 50 individuals with current major depressive disorder (MDD), 25 with remitted major depression (RMD), and 45 healthy controls. Heart rate (HR), blood pressure and impedance cardiography were assessed and analyses controlled for BMI and sex. Significant group effects were found for SBP, HR, and PEP for the speech preparation period and HR, CO, and PEP during the speech. For each of these parameters, only the MDD group exhibited attenuated reactivity as well as impaired SBP recovery. Reactivity and recovery in the RMD group more closely resembled the healthy controls. Speeches given by the MDD group were rated as less persuasive than the RMD or healthy controls' speeches. No significant differences were found for the cold pressor. Blunted cardiovascular reactivity and impaired recovery in current major depression may be mood-state dependent phenomena and may be more reflective of motivational deficits than deficits in the physiological integrity of the cardiovascular system.

  10. The biochemistry of dysfunctional emotions: proton MR spectroscopic findings in major depressive disorder.

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    Ende, Gabriele; Demirakca, Traute; Tost, Heike

    2006-01-01

    Key neural systems involved in the processing and communication of emotions are impaired in patients with major depressive disorder (MDD). Emotional and behavioral symptoms are thought to be caused by damage or dysfunction in specific areas of the brain that are responsible for directing attention, motivating behavior, and learning the significance of environmental stimuli. Functional brain studies with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) give support for functional abnormalities in MDD that are predominantly located in areas known to play an important role in the communication and processing of emotions. Disturbances in emotional processing as they are observed in MDD, if any, have very subtle morphometrical brain correlates. With proton magnetic resonance spectroscopy (1H MRS), brain metabolites can be measured noninvasively in vivo, thus furthering the understanding of the effects of changes in neurotransmitters within the brain. The current literature on 1H MRS studies in MDD is small with a large diversity of MRS methods applied, brain regions studied, and metabolite changes found. Nevertheless, there is strong evidence that changes in neurometabolite concentrations in MDD occur within brain regions, which are involved in the processing and communication of emotions that can be monitored by 1H MRS. This review summarizes the literature about biochemical changes quantified via 1H MRS in MDD patients in brain regions that play an important role for the communication and processing of emotions.

  11. Major depressive disorder during teenage pregnancy: socio-demographic, obstetric and psychosocial correlates

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    Fábio Monteiro da Cunha Coelho

    2013-03-01

    Full Text Available OBJECTIVES: To describe the prevalence of Major Depressive Disorder (MDD during pregnancy in teenage mothers and to assess its association with socio-demographic characteristics, obstetric history and psychosocial variables. METHODS: A cross-sectional study was conducted with a sample of pregnant teenagers enrolled in the national public health system in the urban area of Pelotas, southern Brazil. MDD was assessed with the Mini International Neuropsychiatric Interview, the Abuse Assessment Screen was used to identify physical abuse within the last 12 months and during pregnancy, and social support was assessed with the Medical Outcomes Survey Social Support Scale. RESULTS: Forty-three (4.94% potential subjects refused to participate, resulting in 828 total participants. The prevalence of MDD was 17.8%, 9.2% reported they had been subjected to violence within the last 12 months, while 5.8% had suffered violence during pregnancy, and the mean (SD overall social support score was 87.40 (11.75. After adjustment, we found the highest incidence of MDD in adolescents with less than 8 years of education, followed by those with previous episodes of MDD and those with lower overall social support. CONCLUSIONS: MDD is a relatively common condition in pregnant teenagers and appears to be more prevalent in young mothers who are both socioeconomically and psychosocially underprivileged.

  12. AMYGDALA AND HIPPOCAMPAL VOLUMES IN FAMILIAL EARLY ONSET MAJOR DEPRESSIVE DISORDER

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    MacMaster, Frank P.; Mirza, Yousha; Szeszko, Philip R.; Kmiecik, Lauren E.; Easter, Phillip C.; Taormina, S. Preeya; Lynch, Michelle; Rose, Michelle; Moore, Gregory J.; Rosenberg, David R.

    2008-01-01

    Background Abnormalities in the amygdala and hippocampus have been implicated in the pathogenesis of major depressive disorder (MDD). To our knowledge, no prior study has examined amygdala-hippocampus anatomy in pediatric patients with familial MDD (at least one first degree relative with MDD). Methods 32 psychotropic-naïve patients with familial MDD, aged 8 − 21 years (12 males and 20 females), and 35 group-matched healthy participants (13 males and 22 females) underwent volumetric magnetic resonance imaging (MRI) in order to evaluate hippocampal and amygdala volumes. Results Patients with familial MDD had significantly smaller left hippocampal (p = 0.007, d = 0.44) and right hippocampal volumes (p = 0.025, d = 0.33) than controls. No differences were noted in amygdala volumes between groups (right: p > 0.05, left: p > 0.05). No correlations between hippocampal or amygdala volumes and demographic or clinical variables were noted. Conclusions Reduced hippocampal volume may be suggestive of a risk factor for developing MDD. PMID:17640621

  13. Predictors of persistence of comorbid generalized anxiety disorder among veterans with major depressive disorder.

    Science.gov (United States)

    Mittal, Dinesh; Fortney, John C; Pyne, Jeffrey M; Wetherell, Julie L

    2011-11-01

    A limited number of randomized clinical trials show that efficacious pharmacologic treatments exist for comorbid major depressive disorder (MDD) and generalized anxiety disorder (GAD). The aims of this effectiveness study were to describe the impact of a depression care management intervention on the persistence of comorbid GAD symptoms in a sample of primary care patients with MDD and to identify risk factors for persistent GAD. Data were collected from April 2003 to September 2005 for the Telemedicine-Enhanced Antidepressant Management (TEAM) study, a multisite, randomized effectiveness trial targeting US Department of Veterans Affairs (VA) primary care patients with depression. Veterans aged 26.59-88.36 years received either the TEAM intervention or usual care in small VA community-based outpatient clinics. The TEAM care management intervention focused on optimizing antidepressant therapy through patient education and activation, symptom monitoring, adherence promotion, and side-effect management. Veterans who screened positive for MDD using the Patient Health Questionnaire-9 (based on DSM-IV criteria) and who met the Mini-International Neuropsychiatric Interview criteria (maintaining consistency with DSM-IV-TR) for comorbid GAD at baseline were selected for the present study (N = 168). The primary outcome was persistence of GAD at 6 months and 12 months. All predictors available in the TEAM study data that were described in the literature to be associated with influencing GAD outcomes were examined. Persistence of depression was the strongest predictor of persistence of comorbid GAD at both 6 months (OR = 5.75; 95% CI, 2.38-13.86; P < .05) and 12 months (OR = 15.56; 95% CI, 6.10-39.68; P < .05). Although the TEAM intervention significantly reduced depression symptom severity, it was not significantly associated with GAD persistence. Insomnia was a significant protective factor for persistence of GAD at 6 months (OR = 0.66; 95% CI, 0.44-0.99; P < .05). Early

  14. TRAUMATIC EVENTS ASSOCIATED WITH POSTTRAUMATIC STRESS DISORDER: THE ROLE OF RACE/ETHNICITY AND DEPRESSION

    OpenAIRE

    Lipsky, Sherry; Kernic, Mary A.; Qiu, Qian; Hasin, Deborah S.

    2015-01-01

    This study sought to examine specific types of potentially traumatic experiences as predictors of posttraumatic stress disorder (PTSD) and the moderating effect of race/ethnicity and major depressive disorder (MDD) among non-Hispanic White, non-Hispanic Black, and Hispanic U.S. women. The study sample was drawn from two waves of the National Epidemiologic Surveys of Alcohol and Related Conditions. Sexual assault, intimate partner violence, and childhood trauma were the strongest predictors of...

  15. A case study in treating chronic comorbid obsessive-compulsive disorder and depression with behavioral activation and pharmacotherapy.

    Science.gov (United States)

    Arco, Lucius

    2015-06-01

    Obsessive-compulsive disorder (OCD) is difficult to treat, and more so when comorbid with major depressive disorder (MDD). The aim of the present case study was to examine effects of behavioral activation (BA) and pharmacotherapy with an adult with chronic comorbid OCD and MDD. BA aimed at increasing approach behaviors in life activities and decreasing avoidant and inactive behaviors. After 21 months of treatment at a community mental health clinic, OCD and MDD symptoms, including compulsive checking behaviors, were no longer at clinical levels. Symptom alleviation and psychological health improved in line with increases in activities of living such as self-care, domestic, social, and studying, and decreases in medications from a regimen of mood stabilizers and anxiolytics to a sole antidepressant. The participant was satisfied with treatment procedures and outcome. The results add to growing evidence of effective BA treatments for comorbid disorders that include depression.

  16. Relief of depression and pain improves daily functioning and quality of life in patients with major depressive disorder.

    Science.gov (United States)

    Lin, Ching-Hua; Yen, Yung-Chieh; Chen, Ming-Chao; Chen, Cheng-Chung

    2013-12-02

    The objective of this study was to investigate the effects of depression relief and pain relief on the improvement in daily functioning and quality of life (QOL) for depressed patients receiving a 6-week treatment of fluoxetine. A total of 131 acutely ill inpatients with major depressive disorder (MDD) were enrolled to receive 20mg of fluoxetine daily for 6 weeks. Depression severity, pain severity, daily functioning, and health-related QOL were assessed at baseline and again at week 6. Depression severity, pain severity, and daily functioning were assessed using the 17-item Hamilton Depression Rating Scale, the Short-Form 36 (SF-36) Body Pain Index, and the Work and Social Adjustment Scale. Health-related QOL was assessed by three primary domains of the SF-36, including social functioning, vitality, and general health perceptions. Pearson's correlation and structural equation modeling were used to examine relationships among the study variables. Five models were proposed. In model 1, depression relief alone improved daily functioning and QOL. In model 2, pain relief alone improved daily functioning and QOL. In model 3, depression relief, mediated by pain relief, improved daily functioning and QOL. In model 4, pain relief, mediated by depression relief, improved daily functioning and QOL. In model 5, both depression relief and pain relief improved daily functioning and QOL. One hundred and six patients completed all the measures at baseline and at week 6. Model 5 was the most fitted structural equation model (χ(2) = 8.62, df = 8, p = 0.376, GFI = 0.975, AGFI = 0.935, TLI = 0.992, CFI = 0.996, RMSEA = 0.027). Interventions which relieve depression and pain improve daily functioning and QOL among patients with MDD. The proposed model can provide quantitative estimates of improvement in treating patients with MDD. © 2013 Elsevier Inc. All rights reserved.

  17. Relationships between GAT1 and PTSD, Depression, and Substance Use Disorder

    Science.gov (United States)

    Bountress, Kaitlin E.; Wei, Wei; Sheerin, Christina; Chung, Dongjun; Amstadter, Ananda B.; Mandel, Howard; Wang, Zhewu

    2017-01-01

    Post-traumatic stress disorder (PTSD), Major Depressive Disorder (MDD), and Substance Use Disorder (SUD) have large public health impacts. Therefore, researchers have attempted to identify those at greatest risk for these phenotypes. PTSD, MDD, and SUD are in part genetically influenced. Additionally, genes in the glutamate and gamma-aminobutyric acid (GABA) system are implicated in the encoding of emotional and fear memories, and thus may impact these phenotypes. The current study examined the associations of single nucleotide polymorphisms in GAT1 individually, and at the gene level, using a principal components (PC) approach, with PTSD, PTSD comorbid with MDD, and PTSD comorbid with SUD in 486 combat-exposed veterans.  Findings indicate that several GAT1 SNPs, as well as one of the GAT1 PCs, was associated with PTSD, with and without MDD and SUD comorbidity. The present study findings provide initial insights into one pathway by which shared genetic risk influences PTSD-MDD and PTSD-SUD comorbidities, and thus identify a high-risk group (based on genotype) on whom prevention and intervention efforts should be focused. PMID:28067785

  18. Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group

    Science.gov (United States)

    Schmaal, L; Hibar, D P; Sämann, P G; Hall, G B; Baune, B T; Jahanshad, N; Cheung, J W; van Erp, T G M; Bos, D; Ikram, M A; Vernooij, M W; Niessen, W J; Tiemeier, H; Hofman, A; Wittfeld, K; Grabe, H J; Janowitz, D; Bülow, R; Selonke, M; Völzke, H; Grotegerd, D; Dannlowski, U; Arolt, V; Opel, N; Heindel, W; Kugel, H; Hoehn, D; Czisch, M; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Wright, M J; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Goya-Maldonado, R; Gruber, O; Krämer, B; Hatton, S N; Lagopoulos, J; Hickie, I B; Frodl, T; Carballedo, A; Frey, E M; van Velzen, L S; Penninx, B W J H; van Tol, M-J; van der Wee, N J; Davey, C G; Harrison, B J; Mwangi, B; Cao, B; Soares, J C; Veer, I M; Walter, H; Schoepf, D; Zurowski, B; Konrad, C; Schramm, E; Normann, C; Schnell, K; Sacchet, M D; Gotlib, I H; MacQueen, G M; Godlewska, B R; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Hall, J; Sussmann, J E; Li, M; Walter, M; Aftanas, L; Brack, I; Bokhan, N A; Thompson, P M; Veltman, D J

    2017-01-01

    The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: −0.10 to −0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: −0.26 to −0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life. PMID:27137745

  19. Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group.

    Science.gov (United States)

    Schmaal, L; Hibar, D P; Sämann, P G; Hall, G B; Baune, B T; Jahanshad, N; Cheung, J W; van Erp, T G M; Bos, D; Ikram, M A; Vernooij, M W; Niessen, W J; Tiemeier, H; Hofman, A; Wittfeld, K; Grabe, H J; Janowitz, D; Bülow, R; Selonke, M; Völzke, H; Grotegerd, D; Dannlowski, U; Arolt, V; Opel, N; Heindel, W; Kugel, H; Hoehn, D; Czisch, M; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Wright, M J; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Goya-Maldonado, R; Gruber, O; Krämer, B; Hatton, S N; Lagopoulos, J; Hickie, I B; Frodl, T; Carballedo, A; Frey, E M; van Velzen, L S; Penninx, B W J H; van Tol, M-J; van der Wee, N J; Davey, C G; Harrison, B J; Mwangi, B; Cao, B; Soares, J C; Veer, I M; Walter, H; Schoepf, D; Zurowski, B; Konrad, C; Schramm, E; Normann, C; Schnell, K; Sacchet, M D; Gotlib, I H; MacQueen, G M; Godlewska, B R; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Hall, J; Sussmann, J E; Li, M; Walter, M; Aftanas, L; Brack, I; Bokhan, N A; Thompson, P M; Veltman, D J

    2016-05-03

    The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.Molecular Psychiatry advance online publication, 3 May 2016; doi:10.1038/mp.2016.60.

  20. Prevalence and risk factors of major depressive disorder in HIV/AIDS as seen in semi-urban Entebbe district, Uganda

    Directory of Open Access Journals (Sweden)

    Kinyanda Eugene

    2011-12-01

    Full Text Available Abstract Background Not much is known about the risk factors of major depressive disorder (MDD in HIV/AIDS in the African socio-cultural context. Therefore a study was undertaken to examine the prevalence and risk factors of MDD in HIV/AIDS in semi-urban Uganda. Methods A cross-sectional study was undertaken among 618 respondents attending two HIV clinics in Uganda. Results Prevalence of MDD was 8.1%. Factors associated with MDD at univariate analysis only were female gender, family history of mental illness, negative coping style, alcohol dependency disorder, food insecurity and stress; not associated with MDD were social support, neurocognitive impairment, CD4 counts and BMI. Factors independently associated with MDD were psychosocial impairment, adverse life events, post traumatic stress disorder, generalised anxiety disorder and life-time attempted suicide. Conclusion Psychological and social factors were the main risk factors of MDD among ambulatory HIV positive persons with no evidence for the role of the neurotoxic effects of HIV. Treatment approaches for MDD in this patient group should be modeled on those used among non-HIV groups.

  1. Correlates of Psychological Distress and Major Depressive Disorder Among African American Men.

    Science.gov (United States)

    Lincoln, Karen D; Taylor, Robert Joseph; Watkins, Daphne C; Chatters, Linda M

    2011-05-01

    This study examines the demographic correlates of depressive symptoms, serious psychological distress (SPD), and major depressive disorder (MDD; 12-month and lifetime prevalence) among a national sample of African American men. Analysis of the National Survey of American Life (NSAL) data set provides first-time substantiation of important demographic differences in depressive symptoms (measured by the Center for Epidemiological Studies Depression scale [CES-D]), SPD (measured by the K6), and 12-month and lifetime MDD among African American men. Findings illuminate the heterogeneity within the African American male population. Findings also demonstrate the need for additional research focusing on within-group differences and a comprehensive research and mental health promotion agenda that recognizes the importance of improving access to education and employment and promoting healthy coping behaviors, while acknowledging the larger social context in which African American men live.

  2. Disorder-specific versus transdiagnostic and clinician-guided versus self-guided treatment for major depressive disorder and comorbid anxiety disorders: A randomized controlled trial.

    Science.gov (United States)

    Titov, N; Dear, B F; Staples, L G; Terides, M D; Karin, E; Sheehan, J; Johnston, L; Gandy, M; Fogliati, V J; Wootton, B M; McEvoy, P M

    2015-10-01

    Disorder-specific cognitive behavior therapy (DS-CBT) is effective at treating major depressive disorder (MDD) while transdiagnostic CBT (TD-CBT) addresses both principal and comorbid disorders by targeting underlying and common symptoms. The relative benefits of these two models of therapy have not been determined. Participants with MDD (n=290) were randomly allocated to receive an internet delivered TD-CBT or DS-CBT intervention delivered in either clinician-guided (CG-CBT) or self-guided (SG-CBT) formats. Large reductions in symptoms of MDD (Cohen's d≥1.44; avg. reduction≥45%) and moderate-to-large reductions in symptoms of comorbid generalised anxiety disorder (Cohen's d≥1.08; avg. reduction≥43%), social anxiety disorder (Cohen's d≥0.65; avg. reduction≥29%) and panic disorder (Cohen's d≥0.45; avg. reduction≥31%) were found. No marked or consistent differences were observed across the four conditions, highlighting the efficacy of different forms of CBT at treating MDD and comorbid disorders.

  3. Visuospatial and mathematical dysfunction in major depressive disorder and/or panic disorder: A study of parietal functioning.

    Science.gov (United States)

    Nelson, Brady D; Shankman, Stewart A

    2016-01-01

    The parietal cortex is critical for several different cognitive functions, including visuospatial processing and mathematical abilities. There is strong evidence indicating parietal dysfunction in depression. However, it is less clear whether anxiety is associated with parietal dysfunction and whether comorbid depression and anxiety are associated with greater impairment. The present study compared participants with major depression (MDD), panic disorder (PD), comorbid MDD/PD and controls on neuropsychological measures of visuospatial processing, Judgement of Line Orientation (JLO), and mathematical abilities, Wide Range Achievement Test (WRAT) Arithmetic. Only comorbid MDD/PD was associated with decreased performance on JLO, whereas all psychopathological groups exhibited comparably decreased performance on WRAT Arithmetic. Furthermore, the results were not accounted for by other comorbid disorders, medication use or psychopathology severity. The present study suggests comorbid depression and anxious arousal are associated with impairment in visuospatial processing and provides novel evidence indicating mathematical deficits across depression and/or anxiety. Implications for understanding parietal dysfunction in internalising psychopathology are discussed.

  4. Desvenlafaxine in the treatment of major depressive disorder

    Science.gov (United States)

    Lourenco, Maria Teresa C; Kennedy, Sidney H

    2009-01-01

    Major depressive disorder (MDD) is among the most incapacitating conditions in the world. The emergence of the selective serotonin reuptake inhibitor (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRI) antidepressants has improved the treatment of MDD. Desvenlafaxine succinate (DVS) is the succinate salt of the isolated major active metabolite of venlafaxine, O-desmethylvenlafaxine: it is the third SNRI to become available in the United States, and was approved in 2008 by the US Food and Drug Administration (FDA) for the treatment of MDD. Early investigations showed therapeutic efficacy for doses between 50 and 400 mg/day; however in doses above 100 mg/day there were incremental increases in side effects. Nausea was the most frequent adverse effect. Hence the recommended dosing for DVS is in the 50 to 100 mg range. Desvenlafaxine is excreted in urine, it is minimally metabolized via the CYP450 pathway, and is a weak inhibitor of CYP2D6. A reduced risk for pharmacokinetic drug interactions is a potential advantage over other SNRI. Further head-to-head trials involving comparisons of DVS in the 50 to 100 mg dose range with currently available SSRI and SNRI antidepressants are required. Evidence for relapse prevention is available in the 200 to 400 mg dose range, but this needs to be demonstrated in the 50 to 100 mg dose range, as well as health economic measures and quality of life evaluations. PMID:19557107

  5. The bidirectional relationships between alcohol, cannabis, co-occurring alcohol and cannabis use disorders with major depressive disorder: results from a national sample.

    Science.gov (United States)

    Pacek, Lauren R; Martins, Silvia S; Crum, Rosa M

    2013-06-01

    Alcohol use disorders (AUD) and cannabis use disorders (CUD) are common in the United States (US), and are associated with major depressive disorder (MDD). Co-occurring alcohol and cannabis use/use disorders (AUD+CUD), though understudied, have been found to be associated with greater adverse outcomes than alcohol or cannabis use/use disorders alone. There is a paucity of research on the co-occurring relationships of the two disorders with depression. Data came from Waves 1 and 2 of the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), a population-based longitudinal survey of the adult non-institutionalized, civilian population in the US. Logistic regression analyses were used to assess the associations between: 1) baseline AUD, CUD, and co-occurring AUD+CUD with incident MDD at follow-up and 2) baseline MDD with incident AUD, CUD, and co-occurring AUD+CUD at follow-up, adjusted for potential confounding variables. For Aim 1, most of the AUD and CUD were positively associated with MDD. The strongest associations with incident MDD were observed for cannabis dependence (OR=6.61, CI=1.67-26.21) and co-occurring alcohol and cannabis dependence (OR=2.34, CI=1.23-4.48). For Aim 2, baseline MDD was significantly associated with comparatively fewer cases of incident AUD and CUD but the strongest association was observed for new onset co-occurring alcohol and cannabis dependence (OR=4.51, CI=1.31-15.60). The present study is limited by the potential for social desirability and recall biases. Positive associations between AUD, CUD and MDD were observed bidirectionally. Findings have implications for preventive and treatment programs and initiatives. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. The volumetric and shape changes of the putamen and thalamus in first episode, untreated major depressive disorder

    Directory of Open Access Journals (Sweden)

    Yi Lu

    2016-01-01

    Full Text Available Previous MRI studies confirmed abnormalities in the limbic-cortical-striatal-pallidal-thalamic (LCSPT network or limbic-cortico-striatal-thalamic-cortical (LCSTC circuits in patients with major depressive disorder (MDD, but few studies have investigated the subcortical structural abnormalities. Therefore, we sought to determine whether focal subcortical grey matter (GM changes might be present in MDD at an early stage. We recruited 30 first episode, untreated patients with major depressive disorder (MDD and 26 healthy control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetric and shape analyses were used to assess volume and shape changes of the subcortical GM structures, respectively. In addition, probabilistic tractography methods were used to demonstrate the relationship between the subcortical and the cortical GM. Compared to healthy controls, MDD patients had significant volume reductions in the bilateral putamen and left thalamus (FWE-corrected, p < 0.05. Meanwhile, the vertex-based shape analysis showed regionally contracted areas on the dorsolateral and ventromedial aspects of the bilateral putamen, and on the dorsal and ventral aspects of left thalamus in MDD patients (FWE-corrected, p < 0.05. Additionally, a negative correlation was found between local atrophy in the dorsal aspects of the left thalamus and clinical variables representing severity. Furthermore, probabilistic tractography demonstrated that the area of shape deformation of the bilateral putamen and left thalamus have connections with the frontal and temporal lobes, which were found to be related to major depression. Our results suggested that structural abnormalities in the putamen and thalamus might be present in the early stages of MDD, which support the role of subcortical structure in the pathophysiology of MDD. Meanwhile, the present study showed that these subcortical structural abnormalities might be

  7. The Involvement of TNF-α in Cognitive Dysfunction Associated with Major Depressive Disorder: An Opportunity for Domain Specific Treatments.

    Science.gov (United States)

    Bortolato, Beatrice; Carvalho, Andre F; Soczynska, Joanna K; Perini, Giulia I; McIntyre, Roger S

    2015-01-01

    Major depressive disorder is a highly prevalent, chronic and recurring disorder, associated with substantial impairment in cognitive and interpersonal functions. Accumulating evidence suggests that inflammatory processes play an important role in the etio-pathogenesis, phenomenology, comorbidity and treatment of MDD. Suboptimal remission rates and the persistence of cognitive deficits contribute to functional impairment in MDD inviting the need for the development of mechanistically novel and domain specific treatment approaches. The MEDLINE/ Pubmed database was searched from inception to February, 9th, 2014 with combinations of the following search terms: 'TNF-alpha', 'depression', 'infliximab', 'etanercept', 'adalimumab', 'golimumab' and 'certolizumab'. Preclinical and clinical evidence linking TNF-α to MDD pathophysiology were reviewed as well as the current status of TNF-α modulators as novel agents for the treatment of MDD. Experimental models and clinical studies provide encouraging preliminary evidence for the efficacy of TNF- α antagonists in mitigating depressive symptoms and improving cognitive deficits. Further studies are warranted to confirm these data in larger randomized controlled trials in primary psychiatric populations. Translational research provides a promising perspective that may aid the development and/or repurposing of mechanism-based treatments for depressive symptoms and cognitive impairment in MDD.

  8. Cardiovascular Reactivity in Patients With Major Depressive Disorder With High- or Low-Level Depressive Symptoms: A Cross-Sectional Comparison of Cardiovascular Reactivity to Laboratory-Induced Mental Stress.

    Science.gov (United States)

    Wang, Mei-Yeh; Chiu, Chen-Huan; Lee, Hsin-Chien; Su, Chien-Tien; Tsai, Pei-Shan

    2016-03-01

    Depression increases the risk of adverse cardiac events. Cardiovascular reactivity is defined as the pattern of cardiovascular responses to mental stress. An altered pattern of cardiovascular reactivity is an indicator of subsequent cardiovascular disease. Because depression and adverse cardiac events may have a dose-dependent association, this study examined the differences in cardiovascular reactivity to mental stress between patients with major depressive disorder (MDD) with high depression levels and those with low depression levels. Moreover, autonomic nervous system regulation is a highly plausible biological mechanism for the pattern of cardiovascular reactivity to mental stress. The association between cardiovascular reactivity and parameters of heart rate variability (HRV), an index for quantifying autonomic nervous system activity modulation, was thus examined. This study included 88 patients with MDD. HRV was measured before stress induction. The Stroop Color and Word Test and mirror star-tracing task were used to induce mental stress. We observed no significant association between depressive symptom level and any of the cardiovascular reactivity parameters. Cardiovascular reactivity to mental stress was comparable between patients with MDD with high-level depressive symptoms and those with low-level depressive symptoms. After adjusting for confounding variables, the high-frequency domain of HRV was found to be an independent predictor of the magnitude of heart rate reactivity (β = -.33, p = .002). In conclusion, the magnitude of cardiovascular reactivity may be independent of depression severity in patients with MDD. The autonomic regulation of cardiovascular responses to mental stress primarily influences heart rate reactivity in patients with MDD.

  9. Anatomical and functional brain abnormalities in unmedicated major depressive disorder

    Directory of Open Access Journals (Sweden)

    Yang X

    2015-09-01

    Full Text Available Xiao Yang,1,2,* Xiaojuan Ma,3,* Mingli Li,1,2 Ye Liu,1 Jian Zhang,1 Bin Huang,4 Liansheng Zhao,1,2 Wei Deng,1,2 Tao Li,1,2 Xiaohong Ma1,2 1Psychiatric Laboratory and Department of Psychiatry, 2National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 3Chengdu First People’s Hospital, Chengdu, 4Dong Feng Mao Jian Hospital, Shiyan, People’s Republic of China *These authors contributed equally to this work Background: Using magnetic resonance imaging (MRI and resting-state functional magnetic resonance imaging (rsfMRI to explore the mechanism of brain structure and function in unmedicated patients with major depressive disorder (MDD. Patients and methods: Fifty patients with MDD and 50 matched healthy control participants free of psychotropic medication underwent high-resolution structural and rsfMRI scanning. Optimized diffeomorphic anatomical registration through exponentiated lie algebra and the Data Processing Assistant for rsfMRI were used to find potential differences in gray-matter volume (GMV and regional homogeneity (ReHo between the two groups. A Pearson correlation model was used to analyze associations of morphometric and functional changes with clinical symptoms. Results: Compared to healthy controls, patients with MDD showed significant GMV increase in the left posterior cingulate gyrus and GMV decrease in the left lingual gyrus (P<0.001, uncorrected. In ReHo analysis, values were significantly increased in the left precuneus and decreased in the left putamen (P<0.001, uncorrected in patients with MDD compared to healthy controls. There was no overlap between anatomical and functional changes. Linear correlation suggested no significant correlation between mean GMV values within regions with anatomical abnormality and ReHo values in regions with functional abnormality in the patient group. These changes were not significantly correlated with symptom severity. Conclusion: Our study suggests a dissociation

  10. Acupuncture treatment modulates the corticostriatal reward circuitry in major depressive disorder.

    Science.gov (United States)

    Wang, Zengjian; Wang, Xiaoyun; Liu, Jian; Chen, Jun; Liu, Xian; Nie, Guangning; Jorgenson, Kristen; Sohn, Ki Cheul; Huang, Ruiwang; Liu, Ming; Liu, Bo; Kong, Jian

    2017-01-01

    Major depressive disorder (MDD) is a common disorder with a high prevalence and significant social and economic impacts. Nevertheless, the treatment of MDD is far from satisfactory. Acupuncture treatment has emerged as a promising method for treating MDD. However, the neural mechanism by which acupuncture reduces depressive symptoms is not fully understood. Studies have shown that the corticostriatal reward circuitry is associated with the pathophysiology of MDD; thus, we investigated the corticostriatal resting-state functional connectivity (rsFC) before and after real and sham acupuncture treatments combined with the antidepressant fluoxetine. Forty-six female major depressive patients were assigned to either verum acupuncture plus fluoxetine (n = 22) or sham acupuncture plus fluoxetine (n = 24) treatment for 8 weeks, and resting state functional magnetic resonance imaging (fMRI) data were collected before the first and after the last treatment sessions. The results showed that compared with sham acupuncture, the verum acupuncture group showed: (1) significantly increased rsFC between inferior ventral striatum and medial prefrontal cortex, ventral rostral putamen and amygdala/parahippocampus, as well as dorsal caudate and middle temporal gyrus; (2) significantly decreased rsFC between right ventral rostral putamen and right dorsolateral prefrontal cortex, and right dorsal caudate and bilateral cerebellar tonsil. The increased rsFC between the inferior ventral striatum and medial prefrontal cortex, ventral rostral putamen and amygdala/parahippocampus were significantly positively associated with decreased clinical scores (Montgomery-Åsberg Depression Rating Scale and Self-Rating Depression Scale scores) at the end of the eight-week treatment. Our findings suggest that acupuncture may achieve treatment effects by modulating the corticostriatal reward/motivation circuitry in MDD patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Novel neurotherapeutics in psychiatry: use and rationale of transcranial direct current stimulation in major depressive disorder

    Directory of Open Access Journals (Sweden)

    Adriano H. Moffa

    2014-04-01

    Full Text Available Background : Transcranial direct current stimulation (tDCS is a novel non-pharmacological intervention being investigated for the treatment of major depressive disorder (MDD. Objective : To perform an updated review of tDCS for MDD. Method : Systematic review in Medline/PubMed and other databases of all clinical studies evaluating the clinical efficacy of tDCS in MDD, from the first date available to December/2013. Results : Out of 55 articles, 24 were included, being 6 open-label studies; 8 randomized, double-blind, sham-controlled trials; 2 follow-up studies; 2 meta-analyses and 6 case reports. We observed an improvement of 20-40% in depressive symptoms, being slightly better in open studies. Five randomized clinical trials displayed positive results. The meta-analyses presented mixed results; although none included the study of Brunoni et al. (2013 that represents almost 50% of the evaluated sample. Open-label studies and case reports also investigated tDCS in bipolar depression, post-stroke depression and employed different parameters of stimulation. Discussion : TDCS is a novel, promising treatment for MDD. Definite evidence from large, ongoing clinical trials will be available in the next years.

  12. Self-stigma in borderline personality disorder - cross-sectional comparison with schizophrenia spectrum disorder, major depressive disorder, and anxiety disorders.

    Science.gov (United States)

    Grambal, Ales; Prasko, Jan; Kamaradova, Dana; Latalova, Klara; Holubova, Michaela; Marackova, Marketa; Ociskova, Marie; Slepecky, Milos

    2016-01-01

    Self-stigma arises from one's acceptance of societal prejudices and is common in psychiatric patients. This investigation compares the self-stigma of a sample of patients with borderline personality disorder (BPD), schizophrenia spectrum disorder (SCH), major depressive disorder (MDD), bipolar affective disorder (BAD), and anxiety disorders (AD) and explores of the self-stigma with the subjective and objective measures of the severity of the disorder and demographic factors. The total of 184 inpatients admitted to the psychotherapeutic department diagnosed with BPD, SCH, MDD, BAP, and AD were compared on the internalized stigma of mental illness (ISMI) scale. The ISMI-total score was correlated with the subjective and objective evaluation of the disorder severity (clinical global impression), and clinical and demographic factors. The self-stigma levels were statistically significantly different among the diagnostic groups (BPD 71.15±14.74; SCH 63.2±13.27; MDD 64.09±12.2; BAD 62.0±14.21; AD 57.62±15.85; one-way analysis of variance: F=8.698, df=183; Pmultiple comparison test, the only significant difference was between the BPD patients and the patients with AD (Pdisorder. The BPD patients suffer from a higher level of self-stigma compared to patients with AD. In practice, it is necessary to address the reduction of self-stigma by using specific treatment strategies, such as cognitive therapy.

  13. Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder

    Directory of Open Access Journals (Sweden)

    Tzeng Dong-Sheng

    2011-05-01

    Full Text Available Abstract Background The MAOA uVNTR polymorphism has been documented to affect the MAOA gene at the transcriptional level and is associated with aggressive impulsive behaviors, depression associated with suicide (depressed suicide, and major depressive disorder (MDD. We hypothesized that the uVNTR polymorphism confers vulnerability to MDD, suicide or both. The aim of this study was to explore the association between the MAOA uVNTR and depressed suicide, using multiple controls. Methods Four different groups were included: 432 community controls, 385 patients with MDD who had not attempted suicide, 96 community subjects without mental disorders who had attempted suicide, and 109 patients with MDD who had attempted suicide. The MAOA uVNTR polymorphism was genotyped by a PCR technique. The symptom profiles and personal characteristics in each group were also compared. Results The MAOA 4R allele was more frequent in males with MDD than in male community controls (χ2 = 4.182, p = 0.041. Logistic regression analysis showed that, among the depressed subjects, those younger in age, more neurotic or who smoked had an increased risk of suicide (β = -0.04, p = 0.002; β = 0.15, p = 0.017; β = 0.79, p = 0.031, respectively. Moreover, among those who had attempted suicide, those younger in age, with more paternal overprotection, and more somatic symptoms were more likely to be in the MDD group than in the community group (β = -0.11, p Conclusion The MAOA 4R allele is associated with enhanced vulnerability to suicide in depressed males, but not in community subjects. The MAOA 4R allele affects vulnerability to suicide through the mediating factor of depressive symptoms. Further large-scale studies are needed to verify the psychopathology of the relationships among MAOA uVNTR polymorphism, symptom profiles, and suicidal behavior.

  14. Childhood maltreatment modifies the relationship of depression with hippocampal volume

    NARCIS (Netherlands)

    Gerritsen, L.; van Velzen, L.; Schmaal, L.; van der Graaf, Y.; van der Wee, N.; van Tol, M. -J.; Penninx, B.; Geerlings, M.

    2015-01-01

    Background. Childhood maltreatment (CM) may modify the relationship between major depressive disorder (MDD) and hippocampal volume reduction. To disentangle the impact of MDD and CM on hippocampal volume we investigated the association between MDD and hippocampal volume in persons with and without a

  15. Indicators of patients with major depressive disorder in need of highly specialized care: A systematic review

    Science.gov (United States)

    Kaddouri, Meriam; Goorden, Maartje; van Balkom, Anton J. L. M.; Bockting, Claudi L. H.; Peeters, Frenk P. M. L.; Hakkaart-van Roijen, Leona

    2017-01-01

    Objectives Early identification of patients with major depressive disorder (MDD) that cannot be managed by secondary mental health services and who require highly specialized mental healthcare could enhance need-based patient stratification. This, in turn, may reduce the number of treatment steps needed to achieve and sustain an adequate treatment response. The development of a valid tool to identify patients with MDD in need of highly specialized care is hampered by the lack of a comprehensive understanding of indicators that distinguish patients with and without a need for highly specialized MDD care. The aim of this study, therefore, was to systematically review studies on indicators of patients with MDD likely in need of highly specialized care. Methods A structured literature search was performed on the PubMed and PsycINFO databases following PRISMA guidelines. Two reviewers independently assessed study eligibility and determined the quality of the identified studies. Three reviewers independently executed data extraction by using a pre-piloted, standardized extraction form. The resulting indicators were grouped by topical similarity, creating a concise summary of the findings. Results The systematic search of all databases yielded a total of 7,360 references, of which sixteen were eligible for inclusion. The sixteen papers yielded a total of 48 unique indicators. Overall, a more pronounced depression severity, a younger age of onset, a history of prior poor treatment response, psychiatric comorbidity, somatic comorbidity, childhood trauma, psychosocial impairment, older age, and a socioeconomically disadvantaged status were found to be associated with proxies of need for highly specialized MDD care. Conclusions Several indicators are associated with the need for highly specialized MDD care. These indicators provide easily measurable factors that may serve as a starting point for the development of a valid tool to identify patients with MDD in need of highly

  16. Alterations in leukocyte transcriptional control pathway activity associated with major depressive disorder and antidepressant treatment

    Science.gov (United States)

    Mellon, S H; Wolkowitz, O M; Schonemann, M D; Epel, E S; Rosser, R; Burke, H B; Mahan, L; Reus, V I; Stamatiou, D; Liew, C -C; Cole, S W

    2016-01-01

    Major depressive disorder (MDD) is associated with a significantly elevated risk of developing serious medical illnesses such as cardiovascular disease, immune impairments, infection, dementia and premature death. Previous work has demonstrated immune dysregulation in subjects with MDD. Using genome-wide transcriptional profiling and promoter-based bioinformatic strategies, we assessed leukocyte transcription factor (TF) activity in leukocytes from 20 unmedicated MDD subjects versus 20 age-, sex- and ethnicity-matched healthy controls, before initiation of antidepressant therapy, and in 17 of the MDD subjects after 8 weeks of sertraline treatment. In leukocytes from unmedicated MDD subjects, bioinformatic analysis of transcription control pathway activity indicated an increased transcriptional activity of cAMP response element-binding/activating TF (CREB/ATF) and increased activity of TFs associated with cellular responses to oxidative stress (nuclear factor erythroid-derived 2-like 2, NFE2l2 or NRF2). Eight weeks of antidepressant therapy was associated with significant reductions in Hamilton Depression Rating Scale scores and reduced activity of NRF2, but not in CREB/ATF activity. Several other transcriptional regulation pathways, including the glucocorticoid receptor (GR), nuclear factor kappa-B cells (NF-κB), early growth response proteins 1–4 (EGR1–4) and interferon-responsive TFs, showed either no significant differences as a function of disease or treatment, or activities that were opposite to those previously hypothesized to be involved in the etiology of MDD or effective treatment. Our results suggest that CREB/ATF and NRF2 signaling may contribute to MDD by activating immune cell transcriptome dynamics that ultimately influence central nervous system (CNS) motivational and affective processes via circulating mediators. PMID:27187237

  17. Alterations in leukocyte transcriptional control pathway activity associated with major depressive disorder and antidepressant treatment.

    Science.gov (United States)

    Mellon, S H; Wolkowitz, O M; Schonemann, M D; Epel, E S; Rosser, R; Burke, H B; Mahan, L; Reus, V I; Stamatiou, D; Liew, C-C; Cole, S W

    2016-05-24

    Major depressive disorder (MDD) is associated with a significantly elevated risk of developing serious medical illnesses such as cardiovascular disease, immune impairments, infection, dementia and premature death. Previous work has demonstrated immune dysregulation in subjects with MDD. Using genome-wide transcriptional profiling and promoter-based bioinformatic strategies, we assessed leukocyte transcription factor (TF) activity in leukocytes from 20 unmedicated MDD subjects versus 20 age-, sex- and ethnicity-matched healthy controls, before initiation of antidepressant therapy, and in 17 of the MDD subjects after 8 weeks of sertraline treatment. In leukocytes from unmedicated MDD subjects, bioinformatic analysis of transcription control pathway activity indicated an increased transcriptional activity of cAMP response element-binding/activating TF (CREB/ATF) and increased activity of TFs associated with cellular responses to oxidative stress (nuclear factor erythroid-derived 2-like 2, NFE2l2 or NRF2). Eight weeks of antidepressant therapy was associated with significant reductions in Hamilton Depression Rating Scale scores and reduced activity of NRF2, but not in CREB/ATF activity. Several other transcriptional regulation pathways, including the glucocorticoid receptor (GR), nuclear factor kappa-B cells (NF-κB), early growth response proteins 1-4 (EGR1-4) and interferon-responsive TFs, showed either no significant differences as a function of disease or treatment, or activities that were opposite to those previously hypothesized to be involved in the etiology of MDD or effective treatment. Our results suggest that CREB/ATF and NRF2 signaling may contribute to MDD by activating immune cell transcriptome dynamics that ultimately influence central nervous system (CNS) motivational and affective processes via circulating mediators.

  18. Indicators of patients with major depressive disorder in need of highly specialized care: A systematic review.

    Science.gov (United States)

    van Krugten, Frédérique C W; Kaddouri, Meriam; Goorden, Maartje; van Balkom, Anton J L M; Bockting, Claudi L H; Peeters, Frenk P M L; Hakkaart-van Roijen, Leona

    2017-01-01

    Early identification of patients with major depressive disorder (MDD) that cannot be managed by secondary mental health services and who require highly specialized mental healthcare could enhance need-based patient stratification. This, in turn, may reduce the number of treatment steps needed to achieve and sustain an adequate treatment response. The development of a valid tool to identify patients with MDD in need of highly specialized care is hampered by the lack of a comprehensive understanding of indicators that distinguish patients with and without a need for highly specialized MDD care. The aim of this study, therefore, was to systematically review studies on indicators of patients with MDD likely in need of highly specialized care. A structured literature search was performed on the PubMed and PsycINFO databases following PRISMA guidelines. Two reviewers independently assessed study eligibility and determined the quality of the identified studies. Three reviewers independently executed data extraction by using a pre-piloted, standardized extraction form. The resulting indicators were grouped by topical similarity, creating a concise summary of the findings. The systematic search of all databases yielded a total of 7,360 references, of which sixteen were eligible for inclusion. The sixteen papers yielded a total of 48 unique indicators. Overall, a more pronounced depression severity, a younger age of onset, a history of prior poor treatment response, psychiatric comorbidity, somatic comorbidity, childhood trauma, psychosocial impairment, older age, and a socioeconomically disadvantaged status were found to be associated with proxies of need for highly specialized MDD care. Several indicators are associated with the need for highly specialized MDD care. These indicators provide easily measurable factors that may serve as a starting point for the development of a valid tool to identify patients with MDD in need of highly specialized care.

  19. Vision in depressive disorder

    DEFF Research Database (Denmark)

    Bubl, E.; Tebartz Van Elst, L.; Ebert, D.

    2009-01-01

    Background. Reduced dopaminergic transmission has been implicated in the pathophysiology of major depression. Furthermore, dopaminergic neurotransmission plays an important role in the physiology of visual contrast sensitivity (CS). To test the hypothesis that altered dopaminergic neurotransmissi...

  20. Dimensional psychiatry: reward dysfunction and depressive mood across psychiatric disorders.

    Science.gov (United States)

    Hägele, Claudia; Schlagenhauf, Florian; Rapp, Michael; Sterzer, Philipp; Beck, Anne; Bermpohl, Felix; Stoy, Meline; Ströhle, Andreas; Wittchen, Hans-Ulrich; Dolan, Raymond J; Heinz, Andreas

    2015-01-01

    A dimensional approach in psychiatry aims to identify core mechanisms of mental disorders across nosological boundaries. We compared anticipation of reward between major psychiatric disorders, and investigated whether reward anticipation is impaired in several mental disorders and whether there is a common psychopathological correlate (negative mood) of such an impairment. We used functional magnetic resonance imaging (fMRI) and a monetary incentive delay (MID) task to study the functional correlates of reward anticipation across major psychiatric disorders in 184 subjects, with the diagnoses of alcohol dependence (n = 26), schizophrenia (n = 44), major depressive disorder (MDD, n = 24), bipolar disorder (acute manic episode, n = 13), attention deficit/hyperactivity disorder (ADHD, n = 23), and healthy controls (n = 54). Subjects' individual Beck Depression Inventory-and State-Trait Anxiety Inventory-scores were correlated with clusters showing significant activation during reward anticipation. During reward anticipation, we observed significant group differences in ventral striatal (VS) activation: patients with schizophrenia, alcohol dependence, and major depression showed significantly less ventral striatal activation compared to healthy controls. Depressive symptoms correlated with dysfunction in reward anticipation regardless of diagnostic entity. There was no significant correlation between anxiety symptoms and VS functional activation. Our findings demonstrate a neurobiological dysfunction related to reward prediction that transcended disorder categories and was related to measures of depressed mood. The findings underline the potential of a dimensional approach in psychiatry and strengthen the hypothesis that neurobiological research in psychiatric disorders can be targeted at core mechanisms that are likely to be implicated in a range of clinical entities.

  1. Low plasma eicosapentaenoic acid levels are associated with elevated trait aggression and impulsivity in major depressive disorder with a history of comorbid substance use disorder

    DEFF Research Database (Denmark)

    Beier, Anne Mette; Lauritzen, Lotte; Galfalvy, Hanga C

    2014-01-01

    Major depressive disorder (MDD) is associated with low levels of omega-3 polyunsaturated fatty acids (PUFAs), holding promise for new perspectives on disease etiology and treatment targets. As aggressive and impulsive behaviors are associated with low omega-3 PUFA levels in some clinical contexts......, we investigated plasma PUFA relationships with trait aggression and impulsivity in patients with MDD. Medication-free MDD patients (n = 48) and healthy volunteers (HV, n = 35) were assessed with the Brown-Goodwin Aggression Inventory. A subset (MDD, n = 39; HV, n = 33) completed the Barratt...... Impulsiveness Scale. Plasma PUFAs eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and arachidonic acid (AA, 20:4n-6) were quantified and ln-transformed to mitigate distributional skew. Ln-transformed PUFA (lnPUFA) levels were predictors in regression models, with aggression...

  2. Cannabis use and the course and outcome of major depressive disorder: A population based longitudinal study.

    Science.gov (United States)

    Feingold, Daniel; Rehm, Jürgen; Lev-Ran, Shaul

    2017-05-01

    Cannabis use has been reported to affect the course of various psychiatric disorders, however its effect on the course of major depressive disorder (MDD) is not yet clear. We used data from Wave 1 and Wave 2 of the National Epidemiologic survey on Alcohol and Related Conditions (NESARC). Individuals with baseline MDD (N=2,348) were included in the study. Cannabis users without a Cannabis Use Disorder (CUDs) and individuals with a CUD were compared to nonusers using linear and logistic regression analyses controlling for sociodemographics, psychiatric disorders and substance use disorders at baseline. No differences were found in rates of remission between the groups. Level of cannabis use was associated with significantly more depressive symptoms at follow-up, particularly anhedonia, changes in body weight, insomnia or hypersomnia and psychomotor problems. After adjusting for baseline confounding factors, no associations were found between cannabis use and suicidality, functionality and quality of life. We conclude that many of the associations between cannabis use and a more severe course of MDD do not seem to be attributed to cannabis use itself but to associated sociodemographic and clinical factors. Further longitudinal studies using depression severity indices are required. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  3. The genetic association between personality and major depression or bipolar disorder. A polygenic score analysis using genome-wide association data.

    Science.gov (United States)

    Middeldorp, C M; de Moor, M H M; McGrath, L M; Gordon, S D; Blackwood, D H; Costa, P T; Terracciano, A; Krueger, R F; de Geus, E J C; Nyholt, D R; Tanaka, T; Esko, T; Madden, P A F; Derringer, J; Amin, N; Willemsen, G; Hottenga, J-J; Distel, M A; Uda, M; Sanna, S; Spinhoven, P; Hartman, C A; Ripke, S; Sullivan, P F; Realo, A; Allik, J; Heath, A C; Pergadia, M L; Agrawal, A; Lin, P; Grucza, R A; Widen, E; Cousminer, D L; Eriksson, J G; Palotie, A; Barnett, J H; Lee, P H; Luciano, M; Tenesa, A; Davies, G; Lopez, L M; Hansell, N K; Medland, S E; Ferrucci, L; Schlessinger, D; Montgomery, G W; Wright, M J; Aulchenko, Y S; Janssens, A C J W; Oostra, B A; Metspalu, A; Abecasis, G R; Deary, I J; Räikkönen, K; Bierut, L J; Martin, N G; Wray, N R; van Duijn, C M; Smoller, J W; Penninx, B W J H; Boomsma, D I

    2011-10-18

    The relationship between major depressive disorder (MDD) and bipolar disorder (BD) remains controversial. Previous research has reported differences and similarities in risk factors for MDD and BD, such as predisposing personality traits. For example, high neuroticism is related to both disorders, whereas openness to experience is specific for BD. This study examined the genetic association between personality and MDD and BD by applying polygenic scores for neuroticism, extraversion, openness to experience, agreeableness and conscientiousness to both disorders. Polygenic scores reflect the weighted sum of multiple single-nucleotide polymorphism alleles associated with the trait for an individual and were based on a meta-analysis of genome-wide association studies for personality traits including 13,835 subjects. Polygenic scores were tested for MDD in the combined Genetic Association Information Network (GAIN-MDD) and MDD2000+ samples (N=8921) and for BD in the combined Systematic Treatment Enhancement Program for Bipolar Disorder and Wellcome Trust Case-Control Consortium samples (N=6329) using logistic regression analyses. At the phenotypic level, personality dimensions were associated with MDD and BD. Polygenic neuroticism scores were significantly positively associated with MDD, whereas polygenic extraversion scores were significantly positively associated with BD. The explained variance of MDD and BD, ∼0.1%, was highly comparable to the variance explained by the polygenic personality scores in the corresponding personality traits themselves (between 0.1 and 0.4%). This indicates that the proportions of variance explained in mood disorders are at the upper limit of what could have been expected. This study suggests shared genetic risk factors for neuroticism and MDD on the one hand and for extraversion and BD on the other.

  4. Personalized medicine in major depressive disorder -- opportunities and pitfalls.

    Science.gov (United States)

    Miller, Diane B; O'Callaghan, James P

    2013-01-01

    The sequencing of the human genome in the early days of this millennium was greeted with great fanfare as this accomplishment was expected to revolutionize medicine and result in individualized treatments based on the genetic make-up of the patient. The ultimate promise of personalized medicine would be fulfilled with the identification of disease biomarkers that would be widely available for use in diagnosis and treatment. Progress, however, has been slow in providing disease biomarkers or approved diagnostic tests. This is true for major depressive disorder (MDD), despite its prevalence in the general population and the widespread acceptance of its biological basis. Studies using strategies like genome-wide association and candidate gene analyses have identified a number of possible biomarkers of MDD, including serum levels of neurotrophic factors, inflammatory cytokines and HPA axis hormones, but none have proven sufficiently powerful for clinical use. The lack of biologically based tests available for use in identifying patients with MDD is a significant impediment to personalized and more effective treatment, because it means diagnosis continues to be driven by subjective symptoms. While genetic studies of MDD have not yet led to diagnostic and treatment biomarkers, progress in determining the role of the genome in drug metabolism heralds the first effort in personalized prescribing for the antidepressants. The FDA suggested and approved genotyping tests for common variants of drug metabolism genes, such as the cytochrome p450s. By using these tests a physician can select an appropriate antidepressant for a given patient, as differences in clearance, half-life, and peak blood concentrations are controlled by genetic variability in drug metabolism. Personalization in drug choice can be achieved because these tests: (1) identify responders and non-responders; (2) provide alerts to possible adverse drug events; and (3) help optimize dose. Improved ways of

  5. Dynamic functional connectivity reveals altered variability in functional connectivity among patients with major depressive disorder

    Science.gov (United States)

    Tornador, Cristian; Falcón, Carles; López‐Solà, Marina; Hernández‐Ribas, Rosa; Pujol, Jesús; Menchón, José M.; Ritter, Petra; Cardoner, Narcis; Soriano‐Mas, Carles; Deco, Gustavo

    2016-01-01

    Abstract Resting‐state fMRI (RS‐fMRI) has become a useful tool to investigate the connectivity structure of mental health disorders. In the case of major depressive disorder (MDD), recent studies regarding the RS‐fMRI have found abnormal connectivity in several regions of the brain, particularly in the default mode network (DMN). Thus, the relevance of the DMN to self‐referential thoughts and ruminations has made the use of the resting‐state approach particularly important for MDD. The majority of such research has relied on the grand averaged functional connectivity measures based on the temporal correlations between the BOLD time series of various brain regions. We, in our study, investigated the variations in the functional connectivity over time at global and local level using RS‐fMRI BOLD time series of 27 MDD patients and 27 healthy control subjects. We found that global synchronization and temporal stability were significantly increased in the MDD patients. Furthermore, the participants with MDD showed significantly increased overall average (static) functional connectivity (sFC) but decreased variability of functional connectivity (vFC) within specific networks. Static FC increased to predominance among the regions pertaining to the default mode network (DMN), while the decreased variability of FC was observed in the connections between the DMN and the frontoparietal network. Hum Brain Mapp 37:2918–2930, 2016. © 2016 Wiley Periodicals, Inc. PMID:27120982

  6. Desvenlafaxine in the treatment of major depressive disorder

    Directory of Open Access Journals (Sweden)

    Maria Teresa C Lourenco1

    2009-02-01

    Full Text Available Maria Teresa C Lourenco1, Sidney H Kennedy1,21Department of Psychiatry, University Health Network, Toronto; 2Department of Psychiatry, University of Toronto, Toronto, CanadaAbstract: Major depressive disorder (MDD is among the most incapacitating conditions in the world. The emergence of the selective serotonin reuptake inhibitor (SSRI and serotonin norepinephrine reuptake inhibitors (SNRI antidepressants has improved the treatment of MDD. Desvenlafaxine succinate (DVS is the succinate salt of the isolated major active metabolite of venlafaxine, O-desmethylvenlafaxine: it is the third SNRI to become available in the United States, and was approved in 2008 by the US Food and Drug Administration (FDA for the treatment of MDD. Early investigations showed therapeutic efficacy for doses between 50 and 400 mg/day; however in doses above 100 mg/day there were incremental increases in side effects. Nausea was the most frequent adverse effect. Hence the recommended dosing for DVS is in the 50 to 100 mg range. Desvenlafaxine is excreted in urine, it is minimally metabolized via the CYP450 pathway, and is a weak inhibitor of CYP2D6. A reduced risk for pharmacokinetic drug interactions is a potential advantage over other SNRI. Further head-to-head trials involving comparisons of DVS in the 50 to 100 mg dose range with currently available SSRI and SNRI antidepressants are required. Evidence for relapse prevention is available in the 200 to 400 mg dose range, but this needs to be demonstrated in the 50 to 100 mg dose range, as well as health economic measures and quality of life evaluations.Keywords: desvenlafaxine, O-desmethylvenlafaxine, Pristiq®, SNRIs, MDD

  7. Hair cortisol as a marker of hypothalamic-pituitary-adrenal Axis activity in female patients with major depressive disorder.

    Science.gov (United States)

    Pochigaeva, Ksenia; Druzhkova, Tatiana; Yakovlev, Alexander; Onufriev, Mikhail; Grishkina, Maria; Chepelev, Aleksey; Guekht, Alla; Gulyaeva, Natalia

    2017-04-01

    Hair cortisol is regarded as a promising marker of hypothalamic-pituitary-adrenal axis (HPAA) activity alterations due to stress, somatic and mental health conditions. Hair cortisol was previously reported to be elevated in patients with depression, however the data related to remission and recurrent depressive episodes are different. In this study, levels of hair cortisol were assessed in female patients with major depressive disorder (MDD) and the validity of hair cortisol as a marker of HPAA activity in this condition was evaluated. Hair cortisol was measured in 1 cm hair segments of 21 female patients with MDD and 22 female age-matched controls using enzyme-immunoassay analysis. Concurrently, serum cortisol was assessed and psychological status was evaluated using 17-item Hamilton Depression Rating Scale (HAMD-17), Beck Depression Inventory (BDI) and the Spielberger state trait anxiety inventory (STAI). The levels of hair cortisol were significantly lower in the MDD group, while serum cortisol levels were significantly higher in patients, as compared with controls. A significant negative correlation was found between HAMD-17 scores and hair cortisol. Decreased hair cortisol found in female patients with MDD as compared to controls suggests downregulation of HPAA activity during the preceding month. Further studies are needed to investigate the profiles of hair cortisol at different stages of depressive disorder to establish this parameter as a handy clinical tool.

  8. Methylation of the SLC6a2 gene promoter in major depression and panic disorder.

    Directory of Open Access Journals (Sweden)

    Richard Bayles

    Full Text Available Reduced function of the noradrenaline transporter (NET has been demonstrated in patients with major depressive disorder (MDD and panic disorder. Attempts to explain NET dysfunction in MDD and panic disorder by genetic variation in the NET gene SLC6a2 have been inconclusive. Transcriptional silencing of the SLC6a2 gene may be an alternative mechanism which can lead to NET dysfunction independent of DNA sequence. The objective of this study was to characterise the DNA methylation state of the SLC6a2 gene promoter in patients with MDD and panic disorder. SLC6a2 promoter methylation was also analysed before and after antidepressant treatment. This study was performed with DNA from blood, using bisulphite sequencing and EpiTYPER methylation analyses. Patients with MDD or panic disorder were not found to differ significantly from healthy controls in the pattern of methylation of the SLC6a2 gene promotor. While significant correlations between methylation levels at some CpG sites and physiological measures were identified, overall the variation in DNA methylation between patients was small, and the significance of this variation remains equivocal. No significant changes in SLC6a2 promoter methylation were observed in response to antidepressant treatment. Further in-depth analysis of alternative mechanisms of transcriptional regulation of the SLC6a2 gene in human health and disease would be of value.

  9. Dissociation in Rating Negative Facial Emotions between Behavioral Variant Frontotemporal Dementia and Major Depressive Disorder.

    Science.gov (United States)

    Chiu, Isabelle; Piguet, Olivier; Diehl-Schmid, Janine; Riedl, Lina; Beck, Johannes; Leyhe, Thomas; Holsboer-Trachsler, Edith; Berres, Manfred; Monsch, Andreas U; Sollberger, Marc

    2016-11-01

    Features of behavioral variant frontotemporal dementia (bvFTD) such as executive dysfunction, apathy, and impaired empathic abilities are also observed in major depressive disorder (MDD). This may contribute to the reason why early stage bvFTD is often misdiagnosed as MDD. New assessment tools are thus needed to improve early diagnosis of bvFTD. Although emotion processing is affected in bvFTD and MDD, growing evidence indicates that the pattern of emotion processing deficits varies between the two disorders. As such, emotion processing paradigms have substantial potentials to distinguish bvFTD from MDD. The current study compared 25 patients with bvFTD, 21 patients with MDD, 21 patients with Alzheimer disease (AD) dementia, and 31 healthy participants on a novel facial emotion intensity rating task. Stimuli comprised morphed faces from the Ekman and Friesen stimulus set containing faces of each sex with two different degrees of emotion intensity for each of the six basic emotions. Analyses of covariance uncovered a significant dissociation between bvFTD and MDD patients in rating the intensity of negative emotions overall (i.e., bvFTD patients underrated negative emotions overall, whereas MDD patients overrated negative emotions overall compared with healthy participants). In contrast, AD dementia patients rated negative emotions similarly to healthy participants, suggesting no impact of cognitive deficits on rating facial emotions. By strongly differentiating bvFTD and MDDpatients through negative facial emotions, this sensitive and short rating task might help improve the early diagnosis of bvFTD. Copyright © 2016 American Association for Geriatric Psychiatry. All rights reserved.

  10. Proteomics, metabolomics, and protein interactomics in the characterization of the molecular features of major depressive disorder.

    Science.gov (United States)

    Martins-de-Souza, Daniel

    2014-03-01

    Omics technologies emerged as complementary strategies to genomics in the attempt to understand human illnesses. In general, proteomics technologies emerged earlier than those of metabolomics for major depressive disorder (MDD) research, but both are driven by the identification of proteins and/or metabolites that can delineate a comprehensive characterization of MDD's molecular mechanisms, as well as lead to the identification of biomarker candidates of all types-prognosis, diagnosis, treatment, and patient stratification. Also, one can explore protein and metabolite interactomes in order to pinpoint additional molecules associated with the disease that had not been picked up initially. Here, results and methodological aspects of MDD research using proteomics, metabolomics, and protein interactomics are reviewed, focusing on human samples.

  11. Use of benzodiazepines, hypnotics, and anxiolytics in major depressive disorder: association with chronic pain diseases.

    Science.gov (United States)

    Liu, Xianchen; Ye, Wenyu; Watson, Peter; Tepper, Ping

    2010-08-01

    We examined the use of benzodiazepines (BZD), hypnotics, and anxiolytics and their associations with chronic pain diseases (CPD) in patients with major depressive disorder (MDD). A retrospective analysis of 153,913 MDD patients (18-64 years) in a large administrative insured claims database during the year 2006 was performed. Results showed that during the study year, 33.1% of the patients had been prescribed BZD; 16.9%, hypnotics; and 6.1%, anxiolytics. The use of BZD and hypnotics increased with age. Patients with CPD were more likely than those without CPD to use BZD (41.2% vs. 27.0%, p hypnotics (21.7% vs. 13.3%, p hypnotics (OR = 1.49), and anxiolytics (OR = 1.51). Further research is needed to examine the long-term benefits and risks of BZD and hypnotics in the treatment of MDD and CPD.

  12. Evidence-based recommendations for the prescription of exercise for major depressive disorder.

    Science.gov (United States)

    Rethorst, Chad D; Trivedi, Madhukar H

    2013-05-01

    Major depressive disorder (MDD) is a source of great disease burden, due in part to the limited accessibility and effectiveness of current treatments. Although current treatments are efficacious in a segment of the population with MDD, there is a clear need for alternative and augmentation treatment strategies. Exercise is one such alternative treatment option. Research has shown exercise to be efficacious as both a stand-alone and an augmentation therapy. As a result, exercise is now included in the American Psychiatric Association's treatment recommendations. The purpose of this article is to provide clinicians with a knowledge base to prescribe exercise to their patients. The authors describe the evidence supporting the use of exercise in the treatment of MDD, provide evidence-based recommendations for prescribing exercise, and address practical considerations related to prescribing exercise in real-world treatment settings.

  13. Magnetic resonance spectroscopy in the evaluation of treatment efficacy in unipolar major depressive disorder: a review of the literature.

    Science.gov (United States)

    Caverzasi, Eduardo; Pichiecchio, Anna; Poloni, Guy Umberto; Calligaro, Alessandro; Pasin, Moreno; Palesi, Fulvia; Castellazzi, Gloria; Pasquini, Massimo; Biondi, Massimo; Barale, Francesco; Bastianello, Stefano

    2012-01-01

    More and more neuroimaging studies are using in vivo proton magnetic resonance spectroscopy (1H-MRS) to explore correlates of response to therapy in major depressive disorder (MDD). Their aim is to further understanding of the effects of neurotransmitter changes in areas involved in MDD and the mechanisms underlying a good treatment response. We set out to summarise the literature from the past fifteen years on biochemical correlates of treatment response in MDD patients, reflected in pre- and post-therapy changes in 1H-MRS measurements. Our literature search identified fifteen articles reporting 1H-MRS studies in MDD treatment; no study used 1P-MRS. Despite the wide diversity of 1H-MRS methods applied, brain regions studied, and metabolite changes found, there emerged strong evidence of a correlation between changes in neurometabolite concentrations, in particular glutamate, N-acetylaspartate and choline, and a good treatment response to pharmacotherapy or antidepressant stimulation techniques.

  14. In pursuit of neuroimaging biomarkers to guide treatment selection in major depressive disorder: a review of the literature.

    Science.gov (United States)

    Lener, Marc S; Iosifescu, Dan V

    2015-05-01

    Over the last few decades, neuroimaging techniques have advanced the identification of structural, functional, and neurochemical brain abnormalities that are associated with the increased risk, clinical course, and treatment outcomes of major depressive disorder (MDD). This paper reviews specific neuroimaging abnormalities that, on the basis of early studies, may discriminate between MDD patients who do or do not respond to current therapeutic modalities, such as antidepressants, cognitive behavioral therapy, or novel therapies. Differences in gray matter volume, white matter coherence, brain activity via structural and functional magnetic resonance imaging techniques, and concentrations of specific brain metabolites (as measured with magnetic resonance spectroscopy), are potential biomarkers discussed in this review. Given the heterogeneity of MDD, larger, multisite studies with increased statistical power will be needed to identify more precise imaging biomarkers of treatment response in MDD.

  15. Dissociation of glutamate and cortical thickness is restricted to regions subserving trait but not state markers in major depressive disorder

    NARCIS (Netherlands)

    Li, Meng; Metzger, Coraline D.; Li, Wenjing; Safron, Adam; van Tol, Marie-Jose; Lord, Anton; Krause, Anna Linda; Borchardt, Viola; Dou, Weiqiang; Genz, Axel; Heinze, Hans-Jochen; He, Huiguang; Walter, Martin

    2014-01-01

    Background: The anterior cingulate cortex (ACC) plays an important role in the neuropathology of major depressive disorder (MDD). So far, the effect of local cortical alteration on metabolites in multiple subdivisions of ACC has not been studied. We aimed to investigate structural and biochemical ch

  16. How do you feel? Detection of recurrent Major Depressive Disorder using a single-item screening tool

    NARCIS (Netherlands)

    Van Rijsbergen, G. D.; Burger, H.; Hollon, S. D.; Elgersma, H. J.; Kok, G. D.; Dekker, J.; de Jong, P. J.; Bockting, Claudi L. H.

    2014-01-01

    Mood is a key element of Major Depressive Disorder (MDD), and is perceived as a highly dynamic construct. The aim of the current study was to examine whether a single-item mood scale can be used for mood monitoring. One hundred thirty remitted out-patients were assessed using the Structured Clinical

  17. Aberrant Intrinsic Connectivity of Hippocampus and Amygdala Overlap in the Fronto-Insular and Dorsomedial-Prefrontal Cortex in Major Depressive Disorder

    Science.gov (United States)

    Tahmasian, Masoud; Knight, David C.; Manoliu, Andrei; Schwerthöffer, Dirk; Scherr, Martin; Meng, Chun; Shao, Junming; Peters, Henning; Doll, Anselm; Khazaie, Habibolah; Drzezga, Alexander; Bäuml, Josef; Zimmer, Claus; Förstl, Hans; Wohlschläger, Afra M.; Riedl, Valentin; Sorg, Christian

    2013-01-01

    Neuroimaging studies of major depressive disorder (MDD) have consistently observed functional and structural changes of the hippocampus (HP) and amygdale (AY). Thus, these brain regions appear to be critical elements of the pathophysiology of MDD. The HP and AY directly interact and show broad and overlapping intrinsic functional connectivity (iFC) to other brain regions. Therefore, we hypothesized the HP and AY would show a corresponding pattern of aberrant intrinsic connectivity in MDD. Resting-state functional MRI was acquired from 21 patients with MDD and 20 healthy controls. ß-Maps of region-of-interest-based FC for bilateral body of the HP and basolateral AY were used as surrogates for iFC of the HP and AY. Analysis of variance was used to compare ß-maps between MDD and healthy control groups, and included covariates for age and gender as well as gray matter volume of the HP and AY. The HP and AY of MDD patient’s showed an overlapping pattern of reduced FC to the dorsomedial-prefrontal cortex and fronto-insular operculum. Both of these regions are known to regulate the interactions among intrinsic networks (i.e., default mode, central executive, and salience networks) that are disrupted in MDD. These results provide the first evidence of overlapping aberrant HP and AY intrinsic connectivity in MDD. Our findings suggest that aberrant HP and AY connectivity may interact with dysfunctional intrinsic network activity in MDD. PMID:24101900

  18. Neurocognitive impairment of mental rotation in major depressive disorder: evidence from event-related brain potentials.

    Science.gov (United States)

    Chen, Jiu; Ma, Wentao; Zhang, Yan; Yang, Lai-Qi; Zhang, Zhijun; Wu, Xingqu; Deng, Zihe

    2014-08-01

    Mental rotation performance may be used as an index of mental slowing or bradyphrenia and may reflect speed of motor preparation. Previous studies suggest that major depressive disorder (MDD) presents correlates of impaired behavioral performance for mental rotation and psychomotor disturbance. Very little is known about the electrophysiological mechanism underlying this deficit. The present study was the first to investigate the event-related brain potential (ERP) correlates of mental rotation and their mental slowing or bradyphrenia in MDD. ERPs were recorded while we tested 25 MDD patients and 26 healthy controls by evaluating the performance of MDD patients on hand and letter rotation tasks at different orientations, and their 400-to-600-msec time window was measured and analyzed for latencies and peak amplitudes over the electrodes. First, individuals with MDD were slower and made more errors in mentally rotating hands and letters than healthy controls did, and individuals with MDD exhibited a greater difference in response times and errors than controls did between hands and letters. Second, the mean peak amplitude was significantly lower and the mean latency was significantly longer in the 400-to-600-msec time window at the parietal site in the hand tasks in MDD patients than in controls, but this was not seen in the letter task, with only lower mean peak amplitude. MDD patients present the absence of a typical mental rotation function for the amplitude of the rotation-related negativity in the hand and letter tasks. Third, the scalp activity maps in MDD patients exhibited the absence of activation in the left parietal site for the mental rotation of hands, as shown in healthy participants. In contrast, their brain activation for the letter task was similar to those of healthy participants. These data suggest that mental imagery of hands and letters relies on different cognitive and neural mechanisms and indicate that the left posterior parietal lobe is a

  19. Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis.

    Science.gov (United States)

    Cassano, Paolo; Petrie, Samuel R; Hamblin, Michael R; Henderson, Theodore A; Iosifescu, Dan V

    2016-07-01

    We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low-cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclinical studies via PubMed search (2015), using the following keywords: "near-infrared radiation," "NIR," "low-level light therapy," "low-level laser therapy," or "LLLT" plus "depression." We chose clinically focused studies and excluded studies involving near-infrared spectroscopy. In addition, we used PubMed to find articles that examine the link between PBM and relevant biological processes including metabolism, inflammation, oxidative stress, and neurogenesis. Studies suggest the processes aforementioned are potentially effective targets for PBM to treat depression. There is also clinical preliminary evidence suggesting the efficacy of PBM in treating MDD, and comorbid anxiety disorders, suicidal ideation, and traumatic brain injury. Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and well-tolerated. However, large randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD.

  20. Identification and validation of urinary metabolite biomarkers for major depressive disorder.

    Science.gov (United States)

    Zheng, Peng; Wang, Ying; Chen, Liang; Yang, Deyu; Meng, Huaqing; Zhou, Dezhi; Zhong, Jiaju; Lei, Yang; Melgiri, N D; Xie, Peng

    2013-01-01

    Major depressive disorder (MDD) is a widespread and debilitating mental disorder. However, there are no biomarkers available to aid in the diagnosis of this disorder. In this study, a nuclear magnetic resonance spectroscopy-based metabonomic approach was employed to profile urine samples from 82 first-episode drug-naïve depressed subjects and 82 healthy controls (the training set) in order to identify urinary metabolite biomarkers for MDD. Then, 44 unselected depressed subjects and 52 healthy controls (the test set) were used to independently validate the diagnostic generalizability of these biomarkers. A panel of five urinary metabolite biomarkers-malonate, formate, N-methylnicotinamide, m-hydroxyphenylacetate, and alanine-was identified. This panel was capable of distinguishing depressed subjects from healthy controls with an area under the receiver operating characteristic curve (AUC) of 0.81 in the training set. Moreover, this panel could classify blinded samples from the test set with an AUC of 0.89. These findings demonstrate that this urinary metabolite biomarker panel can aid in the future development of a urine-based diagnostic test for MDD.

  1. Modulation of induced frontocentral theta (Fm-theta) event-related (de-)synchronisation dynamics following mindfulness-based cognitive therapy in Major Depressive Disorder

    NARCIS (Netherlands)

    Schoenberg, P.L.; Speckens, A.E.M.

    2014-01-01

    Depressive severity has been associated with attenuated neocortical frontal midline theta (Fm-theta) power/evoked activity. Mindfulness-Based Cognitive Therapy (MBCT) has shown to be a successful novel intervention for Major Depressive Disorder (MDD), albeit precise working mechanisms remain elusive

  2. First-episode medication-naive major depressive disorder is associated with altered resting brain function in the affective network.

    Directory of Open Access Journals (Sweden)

    Xiaocui Zhang

    Full Text Available BACKGROUND: Major depressive disorder (MDD has been associated with abnormal structure and function of the brain's affective network, including the amygdala and orbitofrontal cortex (OFC. However, it is unclear if alterations of resting-state function in this affective network are present at the initial onset of MDD. AIMS: To examine resting-state function of the brain's affective network in first-episode, medication-naive patients with MDD compared to healthy controls (HCs. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI was performed on 32 first-episode, medication-naive young adult patients with MDD and 35 matched HCs. The amplitude of low-frequency fluctuations (ALFF of the blood oxygen level-dependent (BOLD signal and amygdala-seeded functional connectivity (FC were investigated. RESULTS: Compared to HC, MDD patients showed reduced ALFF in the bilateral OFC and increased ALFF in the bilateral temporal lobe extending to the insular and left fusiform cortices. Enhanced anti-correlation of activity between the left amygdala seed and the left OFC was found in MDD patients but not in HCs. CONCLUSIONS: Reduced ALFF in the OFC suggests hypo-functioning of emotion regulation in the affective network. Enhanced anti-correlation of activity between the amygdala and OFC may reflect dysfunction of the amygdala-OFC network and additionally represent a pathological process of MDD.

  3. Antecedents of New-Onset Major Depressive Disorder in Children and Adolescents at High Familial Risk.

    Science.gov (United States)

    Rice, Frances; Sellers, Ruth; Hammerton, Gemma; Eyre, Olga; Bevan-Jones, Rhys; Thapar, Ajay K; Collishaw, Stephan; Harold, Gordon T; Thapar, Anita

    2017-02-01

    Early-onset major depressive disorder (MDD) is common in individuals at high familial risk of depression and is associated with poor long-term mental health, social, and educational outcomes. To examine the developmental pathways that lead to first-episode adolescent-onset MDD (incident cases) in those at high familial risk and to postulate a theoretically informed model that enables simultaneous testing of different pathways to incident adolescent-onset MDD composed of contributions from familial/genetic and social risk factors, as well as effects via specific clinical antecedents. This investigation was a 4-year longitudinal study (April 2007 to March 2011) among offspring of depressed parents in the general community. Analyses were conducted between September 1, 2015, and May 27, 2016. Participants were 337 families in whom the index parent (315 mothers and 22 fathers) had experienced at least 2 episodes of MDD (recruited through primary care) and among whom there was a biologically related child in the age range of 9 to 17 years living with the index parent (197 girls and 140 boys with a mean [SD] age of 12.4 [2.0] years) at baseline. Offspring with MDD before the study or at baseline (n = 27), offspring with an episode of MDD that had remitted by follow-up (n = 4), and offspring with missing baseline MDD data (n = 2) were excluded. Ninety-two percent (279 of 304) of families completed the follow-up. The primary outcome was new-onset offspring MDD, and the secondary outcome was the total DSM-IV MDD symptom score. On average, children and adolescents had a mean (SD) of 1.85 (1.74) (range, 0-8.5) DSM-IV symptoms of MDD at follow-up. Twenty (6 males and 14 females) had new-onset MDD, with a mean (SD) age at onset of 14.4 (2.0) years (range, 10-18 years). Irritability (β = 0.12, P = .03) and fear and/or anxiety (β = 0.38, P adolescent-onset MDD, but disruptive behavior (β = -0.08, P = .14) and low mood (β = -0.03, P

  4. Dimensional approach to symptom factors of major depressive disorder in Koreans, using the Brief Psychiatric Rating Scale: the Clinical Research Center for Depression of South Korea study.

    Science.gov (United States)

    Park, Seon-Cheol; Jang, Eun Young; Kim, Daeho; Jun, Tae-Youn; Lee, Min-Soo; Kim, Jae-Min; Kim, Jung-Bum; Jo, Sun-Jin; Park, Yong Chon

    2015-01-01

    Although major depressive disorder (MDD) has a variety of symptoms beyond the affective dimensions, the factor structure and contents of comprehensive psychiatric symptoms of this disorder have rarely been explored using the 18-item Brief Psychiatric Rating Scale (BPRS). We aimed to identify the factor structure of the 18-item BPRS in Korean MDD patients. A total of 258 MDD patients were recruited from a multicenter sample of the Clinical Research Center for Depression of South Korea study. Psychometric scales were used to assess overall psychiatric symptoms (BPRS), depression (Hamilton Depression Rating Scale), anxiety (Hamilton Anxiety Rating Scale), global severity (Clinical Global Impression of Severity Scale), suicidal ideation (Scale for Suicide Ideation), functioning (Social and Occupational Functioning Assessment Scale), and quality of life (World Health Organization Quality of Life Assessment-abbreviated version). Common factor analysis with oblique rotation was used to yield factor structure. A four-factor structure was designed and interpreted by the symptom dimensions to reflect mood disturbance, positive symptoms/apathy, bipolarity, and thought distortion/mannerism. These individual factors were also significantly correlated with clinical variables. The findings of this study support the view that the BPRS may be a promising measuring tool for the initial assessment of MDD patients. In addition, the four-factor structure of the BPRS may be useful in understanding the mood and psychotic characteristics of these patients.

  5. Dimensional approach to symptom factors of major depressive disorder in Koreans, using the Brief Psychiatric Rating Scale: The Clinical Research Center for Depression of South Korea Study

    Directory of Open Access Journals (Sweden)

    Seon-Cheol Park

    2015-01-01

    Full Text Available Although major depressive disorder (MDD has a variety of symptoms beyond the affective dimensions, the factor structure and contents of comprehensive psychiatric symptoms of this disorder have rarely been explored using the 18-item Brief Psychiatric Rating Scale (BPRS. We aimed to identify the factor structure of the 18-item BPRS in Korean MDD patients. A total of 258 MDD patients were recruited from a multicenter sample of the Clinical Research Center for Depression of South Korea study. Psychometric scales were used to assess overall psychiatric symptoms (BPRS, depression (Hamilton Depression Rating Scale, anxiety (Hamilton Anxiety Rating Scale, global severity (Clinical Global Impression of Severity Scale, suicidal ideation (Scale for Suicide Ideation, functioning (Social and Occupational Functioning Assessment Scale, and quality of life (World Health Organization Quality of Life Assessment-abbreviated version. Common factor analysis with oblique rotation was used to yield factor structure. A four-factor structure was designed and interpreted by the symptom dimensions to reflect mood disturbance, positive symptoms/apathy, bipolarity, and thought distortion/mannerism. These individual factors were also significantly correlated with clinical variables. The findings of this study support the view that the BPRS may be a promising measuring tool for the initial assessment of MDD patients. In addition, the four-factor structure of the BPRS may be useful in understanding the mood and psychotic characteristics of these patients.

  6. Heart rate variability in major depressive disorder and after antidepressant treatment with agomelatine and paroxetine: Findings from the Taiwan Study of Depression and Anxiety (TAISDA).

    Science.gov (United States)

    Yeh, Ta-Chuan; Kao, Lien-Cheng; Tzeng, Nian-Sheng; Kuo, Terry B J; Huang, San-Yuan; Chang, Chuan-Chia; Chang, Hsin-An

    2016-01-04

    Evidence from previous studies suggests that heart rate variability (HRV) is reduced in major depressive disorder (MDD). However, whether this reduction is attributable to the disorder per se or to medication, since antidepressants may also affect HRV, is still debated. There is a dearth of information regarding the effects of agomelatine, a novel antidepressant, on HRV. Here, we investigated whether HRV is reduced in MDD and compared the effects of agomelatine and paroxetine on HRV. We recruited 618 physically healthy unmedicated patients with MDD and 506 healthy volunteers aged 20-65 years. Frequency-domain measures of resting HRV were obtained at the time of enrollment for all participants. For patients with MDD, these measures were obtained again after 6 weeks of either agomelatine or paroxetine monotherapy. Compared with healthy subjects, unmedicated patients with MDD exhibited significantly lower variance (total HRV), low frequency (LF), and high frequency (HF) HRV, and a higher LF/HF ratio. Depression severity independently contributed to decreased HRV and vagal tone. Fifty-six patients completed the open-label trial (n=29 for agomelatine, n=27 for paroxetine). Between-group analyses showed a significant group-by-time interaction for LF-HRV and HF-HRV, driven by increases in LF-HRV and HF-HRV only after agomelatine treatment. Within the paroxetine-treated group, there were no significant changes in mean R-R intervals or any HRV indices. We therefore concluded that MDD is associated with reduced HRV, which is inversely related to depression severity. Compared with paroxetine, agomelatine has a more vagotonic effect, suggesting greater cardiovascular safety. Clinicians should consider HRV effects while selecting antidepressants especially for depressed patients who already have decreased cardiac vagal tone. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Hopelessness as a predictor of non-response to fluoxetine in major depressive disorder.

    Science.gov (United States)

    Papakostas, George I; Petersen, Timothy; Homberger, Caitlin H; Green, Cassandra H; Smith, Juliana; Alpert, Jonathan E; Fava, Maurizio

    2007-01-01

    The purpose of this study was to study hopelessness as a predictor of response to fluoxetine in outpatients with Major Depressive Disorder (MDD). The degree of hopelessness was assessed during the baseline visit with the use of the Beck Hopelessness Scale (BHS) in 312 patients with MDD (56.1% women; 39.8 +/- 10.3 years of age) who entered an 8-week, 20-mg, fixed-dose, open trial of fluoxetine. With the use of a logistic regression we tested whether BHS scores at baseline predicted clinical response, controlling for the severity of depression as reflected by the total score on the 17-item Hamilton Depression Rating Scale (HAM-D-17). With the use of a multiple regression we also tested whether BHS scores at baseline predicted HAM-D-17 scores at endpoint, controlling for HAM-D-17 scores at baseline. After controlling for depression severity at baseline, a greater degree of hopelessness was found to significantly increase the risk of non-response to fluoxetine (p = 0.0413), as well as the risk of greater endpoint depression severity (p = 0.0305). Hopelessness appeared to be associated with poorer response to treatment with fluoxetine in MDD, and this was independent of depression severity. Similar studies involving treatment with higher doses of fluoxetine and for greater duration as well as a placebo comparator arm are needed to further explore the relationship between hopelessness, placebo response and drug response.

  8. Neural correlates of rumination in adolescents with remitted major depressive disorder and healthy controls.

    Science.gov (United States)

    Burkhouse, Katie L; Jacobs, Rachel H; Peters, Amy T; Ajilore, Olu; Watkins, Edward R; Langenecker, Scott A

    2017-04-01

    The aim of the present study was to use fMRI to examine the neural correlates of engaging in rumination among a sample of remitted depressed adolescents, a population at high risk for future depressive relapse. A rumination induction task was used to assess differences in the patterns of neural activation during rumination versus a distraction condition among 26 adolescents in remission from major depressive disorder (rMDD) and in 15 healthy control adolescents. Self-report depression and rumination, as well as clinician-rated depression, were also assessed among all participants. All of the participants recruited regions in the default mode network (DMN), including the posterior cingulate cortex, medial prefrontal cortex, inferior parietal lobe, and medial temporal gyrus, during rumination. Increased activation in these regions during rumination was correlated with increased self-report rumination and symptoms of depression across all participants. Adolescents with rMDD also exhibited greater activation in regions involved in visual, somatosensory, and emotion processing than did healthy peers. The present findings suggest that during ruminative thought, adolescents with rMDD are characterized by increased recruitment of regions within the DMN and in areas involved in visual, somatosensory, and emotion processing.

  9. Predictors of functional improvement in employed adults with major depressive disorder treated with desvenlafaxine.

    Science.gov (United States)

    Lam, Raymond W; Endicott, Jean; Hsu, Ming-Ann; Fayyad, Rana; Guico-Pabia, Christine; Boucher, Matthieu

    2014-09-01

    We carried out a secondary analysis of a double-blind, placebo-controlled trial of desvenlafaxine for major depressive disorder (MDD) to explore the associations between depressive symptoms and subtypes, and functional outcomes, including work functioning. Employed outpatients with MDD were assigned randomly in a 2 : 1 ratio to receive desvenlafaxine 50 mg/day or placebo for 12 weeks. Analyses were carried out post-hoc with the intent-to-treat (ITT) sample (N=427) and a prospectively defined modified ITT sample (N=310), composed of patients with baseline 17-item Hamilton Rating Scale for Depression score of at least 20. Functional outcomes at week 12 included items and factors from the Montgomery-Åsberg Depression Rating Scale, Sheehan Disability Scale, and the Work Productivity and Activity Impairment questionnaire. In the modified ITT sample, but not in the ITT sample, desvenlafaxine-treated patients showed significantly greater improvement in several functional outcomes in the responder, nonanxious, and normal-energy patient subgroups. Improvement in the 17-item Hamilton Rating Scale for Depression total score at week 2 predicted change at week 12 in several functional outcomes. Functional improvement at 12 weeks was greater in subgroups of patients and was also significantly predicted by early improvement in depressive symptoms in employed patients with MDD treated with desvenlafaxine.

  10. Major depressive disorder with subthreshold hypomania (mixed features): Clinical characteristics of patients entered in a multiregional, placebo-controlled study.

    Science.gov (United States)

    Targum, Steven D; Suppes, Trisha; Pendergrass, J Cara; Lee, Sang; Silva, Robert; Cucchiaro, Josephine; Loebel, Antony

    2016-07-04

    Major depressive disorder (MDD) associated with subthreshold hypomanic symptoms (mixed features), has been identified as a distinct nosological entity in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). We identified the predominant manic symptoms present at baseline in a multiregional, placebo-controlled trial involving 211 patients with MDD with mixed features (Clinicaltrials.govNCT01421134). Patients with 2 or 3 DSM-5 criteria defined manic symptoms were eligible for the study. At study baseline, increased talkativeness (pressure to keep talking) and flight of ideas (racing thoughts) were endorsed by approximately 65% of patients and a decreased need for sleep was endorsed by 40% of patients. Approximately 60% of patients also endorsed irritability and distractibility at baseline although these symptoms are not generally counted as part of the "mixed" depression diagnosis as they may overlap with criteria for MDD. Thus, five clinical symptoms characterized the manic presentation in the majority of patients diagnosed as having MDD with "mixed" features in this first placebo-controlled trial examining the use of a psychotropic medication (lurasidone) in this population. Our findings support the designation of MDD with mixed features specifier and suggest that this subpopulation of depressed patients may warrant additional medication beyond antidepressants.

  11. Systematic review of appropriate cognitive assessment instruments used in clinical trials of schizophrenia, major depressive disorder and bipolar disorder.

    Science.gov (United States)

    Bakkour, Nadia; Samp, Jennifer; Akhras, Kasem; El Hammi, Emna; Soussi, Imen; Zahra, Fatma; Duru, Gérard; Kooli, Amna; Toumi, Mondher

    2014-05-30

    Cognitive dysfunction is increasingly recognized as a symptom in mental conditions including schizophrenia, major depressive disorder (MDD), and bipolar disorder (BPD). Despite the many available cognitive assessment instruments, consensus is lacking on their appropriate use in clinical trials. We conducted a systematic literature review in Embase, PubMed/Medline and PsychINFO to identify appropriate cognitive function instruments for use in clinical trials of schizophrenia, MDD, and BPD. Instruments were identified from the articles. Instruments and articles were excluded if they did not address schizophrenia, MDD, or BPD. Instrument appropriateness was further assessed by the criteria of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative: test-retest reliability, utility, relationship to functional status, potential changeability to pharmacological agents, and tolerability and practicality for clinical trials. The database search yielded 173 articles describing 150 instruments used to assess cognitive function. Seventeen additional instruments were identified through Google and clinicaltrials.gov. Among all these, only 30 (18%) were deemed appropriate for use in the diseases of interest. Of these, 27 were studied in schizophrenia, one in MDD and two in BPD. These findings suggest the need for careful selection of appropriate cognitive assessment instruments, as not all may be valid in these disorders.

  12. The Antidepressant Treatment Response Index as a Predictor of Reboxetine Treatment Outcome in Major Depressive Disorder.

    Science.gov (United States)

    Caudill, Marissa M; Hunter, Aimee M; Cook, Ian A; Leuchter, Andrew F

    2015-10-01

    Biomarkers to predict clinical outcomes early during the treatment of major depressive disorder (MDD) could reduce suffering and improve outcomes. A quantitative electroencephalogram (qEEG) biomarker, the Antidepressant Treatment Response (ATR) index, has been associated with outcomes of treatment with selective serotonin reuptake inhibitor antidepressants in patients with MDD. Here, we report the results of a post hoc analysis initiated to evaluate whether the ATR index may also be associated with reboxetine treatment outcome, given that its putative mechanism of action is via norepinephrine reuptake inhibition (NRI). Twenty-five adults with MDD underwent qEEG studies during open-label treatment with reboxetine at doses of 8 to 10 mg daily for 8 weeks. The ATR index calculated after 1 week of reboxetine treatment was significantly associated with overall Hamilton Depression Rating Scale (HAM-D) improvement at week 8 (r=0.605, P=.001), even after controlling for baseline depression severity (P=.002). The ATR index predicted response (≥50% reduction in HAM-D) with 70.6% sensitivity and 87.5% specificity, and remission (final HAM-D≤7) with 87.5% sensitivity and 64.7% specificity. These results suggest that the ATR index may be a useful biomarker of clinical response during NRI treatment of adults with MDD. Future studies are warranted to investigate further the potential utility of the ATR index as a predictor of noradrenergic antidepressant treatment response.

  13. The course of major depressive disorder from childhood to young adulthood: Recovery and recurrence in a longitudinal observational study.

    Science.gov (United States)

    Kovacs, Maria; Obrosky, Scott; George, Charles

    2016-10-01

    The episodic nature of major depressive disorder (MDD) in clinically referred adults has been well-characterized, particularly by the NIMH Collaborative Depression Study. Previous work has established that MDD also is episodic prior to adulthood, but no study has yet provided comprehensive information on the actual course of MDD in clinically referred juveniles. Thus, the present investigation sought to characterize recovery, recurrence, and their predictors across multiple episodes of MDD in initially 8- to 13-year-old outpatients (N=102), and to estimate freedom from morbidity ("well-time") across the years. Clinically referred youngsters with MDD were repeatedly assessed in an observational study across two decades (median follow up length: 15 years). Survival analytic techniques served to model recovery from the 1st, 2nd and 3rd lifetime episodes of MDD, the risk of developing the 2nd, 3rd, and 4th episodes, and the effects of traditional psychosocial and clinical predictors of outcomes. "Well-time" across the follow-up and its predictors also were examined. Recovery rates ranged from 96% to 100% across MDD episodes; episode lengths ranged from 6 to 7 months. Up to 72% of those recovered from the first episode of MDD had a further episode; median inter-episode intervals were about 3-5 years. No single demographic, social, or clinical variable, nor treatment, consistently predicted recovery/recurrence. Psychiatric morbidity over time derived mostly from non-affective disorders, which, however, did not alter the course of MDD. The sample was relatively small and power to detect small effects further declined with each MDD episode recurrence. Echoing findings on adults, the course of pediatric-onset MDD in this clinical sample was unequivocally episodic. Traditional course predictors had limited temporal stability, highlighting the need to examine novel predictor variables. The ongoing risk of depression episodes into the second and third decades of life suggests

  14. Electroconvulsive therapy and aerobic exercise training increased BDNF and ameliorated depressive symptoms in patients suffering from treatment-resistant major depressive disorder.

    Science.gov (United States)

    Salehi, Iraj; Hosseini, Seyed Mohammad; Haghighi, Mohammad; Jahangard, Leila; Bajoghli, Hafez; Gerber, Markus; Pühse, Uwe; Kirov, Roumen; Holsboer-Trachsler, Edith; Brand, Serge

    2014-10-01

    To treat patients suffering from treatment-resistant major depressive disorder (TR-MDD), research has focused on electroconvulsive therapy (ECT) and aerobic exercise training (AET). Brain derived neurotrophic factor (BDNF) seems to be key in MDD. The aims of the present study were therefore two-fold, to investigate in a three-arm interventional study the differential effects of ECT, ECT plus AET, and AET alone in patients suffering from TR-MDD on 1. depressive symptoms and 2. 60 patients with TR-MDD (mean age: 31 years; 31.6% female patients) were randomly assigned either to the ECT, ECT + AET, or AET condition. The AET condition consisted of treadmill exercise for 30 min, three times a week. Both depression severity and BDNF levels were assessed at baseline and 4 weeks later. All patients were further treated with an SSRI standard medication. BDNF levels increased over time in all three study conditions. After completion of the intervention program, the ECT group showed significantly higher BDNF levels compared to the ECT + AET and the AET conditions. Depressive symptoms decreased in all three conditions over time. The combination of ECT + AET led to a significantly greater decrease than in either the ECT or AET alone conditions. BDNF levels were not associated with symptoms of depression. The pattern of results suggests that ECT, AET and particularly their combination are promising directions for treatment patients suffering from TR-MDD, and that it remains unclear to what extent BDNF is key and a reliable biomarker for TR-MDD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Electroconvulsive therapy (ECT) and aerobic exercise training (AET) increased plasma BDNF and ameliorated depressive symptoms in patients suffering from major depressive disorder.

    Science.gov (United States)

    Salehi, Iraj; Hosseini, Seyed Mohammad; Haghighi, Mohammad; Jahangard, Leila; Bajoghli, Hafez; Gerber, Markus; Pühse, Uwe; Holsboer-Trachsler, Edith; Brand, Serge

    2016-05-01

    To treat patients suffering from major depressive disorder (MDD), research has focused on electroconvulsive therapy (ECT) and aerobic exercise training (AET). Brain derived neurotrophic factor (BDNF) seems to be key in MDD. The aims of the present study were therefore two-fold, to investigate in a three-arm interventional study the differential effects of ECT, ECT plus AET, and AET alone in patients suffering from TR-MDD on 1. depressive symptoms and 2. plasma BDNF (pBDNF). 60 patients with MDD (mean age: 31 years; 31.6% female patients) were randomly assigned either to the ECT, ECT + AET, or AET condition. The AET condition consisted of treadmill exercise for 45 min, three times a week. Both depression severity and pBDNF levels were assessed at baseline and 4 weeks later. All patients were further treated with an SSRI standard medication. pBDNF levels increased over time in all three study conditions, though, highest increase was observed in the ECT + EAT condition, and lowest increase was observed in the AET condition. Depressive symptoms decreased in all three conditions over time, though, strongest decrease was observed in the ECT + AET condition. The combination of ECT + AET led to significantly greater remission rates than in either the ECT or AET alone conditions. BDNF levels were not associated with symptoms of depression. The pattern of results suggests that ECT, AET and particularly their combination are promising directions for the treatment of patients suffering from MDD, and that it remains unclear to what extent pBDNF is key and a reliable biomarker for MDD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Unexplained Painful Physical Symptoms in Patients with Major Depressive Disorder: Prevalence, Pathophysiology and Management.

    Science.gov (United States)

    Jaracz, Jan; Gattner, Karolina; Jaracz, Krystyna; Górna, Krystyna

    2016-04-01

    Patients with major depression often report pain. In this article, we review the current literature regarding the prevalence and consequences, as well as the pathophysiology, of unexplained painful physical symptoms (UPPS) in patients with major depressive disorder (MDD). UPPS are experienced by approximately two-thirds of depressed patients. The presence of UPPS makes a correct diagnosis of depression more difficult. Moreover, UPPS are a predictor of a poor response to treatment and a more chronic course of depression. Pain, in the course of depression, also has a negative impact on functioning and quality of life. Frequent comorbidity of depression and UPPS has inspired the formulation of an hypothesis regarding a shared neurobiological mechanism of both conditions. Evidence from neuroimaging studies has shown that frontal-limbic dysfunction in depression may explain abnormal pain processing, leading to the presence of UPPS. Increased levels of proinflamatory cytokines and substance P in patients with MDD may also clarify the pathophysiology of UPPS. Finally, dysfunction of the descending serotonergic and noradrenergic pathways that normally suppress ascending sensations has been proposed as a core mechanism of UPPS. Psychological factors such as catastrophizing also play a role in both depression and chronic pain. Therefore, pharmacological treatment and/or cognitive therapy are recommended in the treatment of depression with UPPS. Some data suggest that serotonin and noradrenaline reuptake inhibitors (SNRIs) are more effective than selective serotonin reuptake inhibitors (SSRIs) in the alleviation of depression and UPPS. However, the pooled analysis of eight randomised clinical trials showed similar efficacy of duloxetine (an SNRI) and paroxetine (an SSRI) in reducing UPPS in depression. Further integrative studies examining genetic factors (e.g. polymorphisms of genes for interleukins, serotonin transporter and receptors), molecular factors (e.g. cytokines

  17. Comparison of clinical characteristics of bipolar and depressive disorders in Korean clinical sample of youth: a retrospective chart review.

    Science.gov (United States)

    Shon, Seung-Hyun; Joo, Yeonho; Park, Jangho; Youngstrom, Eric A; Kim, Hyo-Won

    2014-05-01

    The purpose of this study was to compare the clinical characteristics of bipolar disorder I, II (BD I and II) and not otherwise specified (BD NOS) to those of major depressive disorder (MDD) in a clinical sample of Korean children and adolescents. This study was a cross-sectional review of longitudinal observational data. Two psychiatrists retrospectively reviewed the medical records of 198 children and adolescents (age 6-18) that were diagnosed as having bipolar or depressive disorders from March 2010 to February 2012 at Department of Psychiatry of Asan Medical Center, Seoul, Korea. Every subject's diagnoses were reviewed and confirmed. BD I, II and MDD were assessed according to the Diagnostic and Statistical Manual-IV criteria. BD NOS was defined based on the criteria for the Course and Outcome of Bipolar Youth study. Comparisons were made in demographic information, clinical characteristics, family history, and psychiatric comorbidities at baseline and during observation. Among 198 subjects, 20 (10.1 %) subjects were diagnosed as having BD I, 10 (5.1 %) as BD II, 25 (12.6 %) as BD NOS and 143 (73.7 %) as MDD. BD depression was associated with mood change while taking an antidepressant, familial bipolarity, aggressive behaviors, and atypical features. Comorbid obsessive-compulsive disorder tended to be higher in BD NOS than in MDD. Presence of psychosocial stressors was more common in MDD than in BD depression. In children and adolescents, bipolar depression is distinct from unipolar depression in family history, comorbidity, and clinical characteristics.

  18. The prevalence, measurement, and treatment of the cognitive dimension/domain in major depressive disorder.

    Science.gov (United States)

    McIntyre, Roger S; Xiao, Holly X; Syeda, Kahlood; Vinberg, Maj; Carvalho, Andre F; Mansur, Rodrigo B; Maruschak, Nadia; Cha, Danielle S

    2015-07-01

    Insufficient outcomes amongst adults with major depressive disorder (MDD) provide the impetus to identify and refine therapeutic targets that are most critical to outcome from patient, provider, and societal perspectives. Towards this aim, a pivotal shift towards the transnosological domain, cognition, is occurring in the study of MDD and other brain disorders. This paper aims to provide a framework for conceptualizing and prioritizing cognitive function amongst adults with MDD with a particular view to provide a conceptual framework for research and clinical priorities. We also summarize extant data pertaining to psychotropic effects, notably antidepressants, on the cognitive dimension/domain. This narrative review was based on articles identified through a PubMed/MEDLINE search of all English-language articles published between January 1966 and October 2014. The search words were major depressive disorder, depression, unipolar depression, cognition, cognitive dysfunction, cognitive deficit, and cognitive function. The search was supplemented with a manual review of relevant references. The selection of articles for inclusion in this review was based on overall methodological quality as well as on their pertinence to informing the framework described herein. Cognitive dysfunction in MDD is a discrete domain subserved by discrete yet overlapping substrates. There is a need to provide a glossary of terms commonly employed in the cognition literature for consensus as to the appropriate screening, measurement, and monitoring tools. The guiding principle of measurement-based care should include systematic assessment and measurement of cognition in subpopulations with MDD, as a tactic to improve outcome. Relatively few treatment strategies have demonstrated efficacy specifically for the cognitive domain in MDD. The antidepressant vortioxetine has replicated evidence of specific pro-cognitive effects in adults with MDD across multiple subdomains of cognitive function

  19. Comparison of venlafaxine alone versus venlafaxine plus bright light therapy combination for severe major depressive disorder.

    Science.gov (United States)

    Güzel Özdemir, Pınar; Boysan, Murat; Smolensky, Michael H; Selvi, Yavuz; Aydin, Adem; Yilmaz, Ekrem

    2015-05-01

    Phototherapy, ie, bright light therapy, is an effective and safe treatment of major depressive disorder (MDD). It exerts rapid mood-elevating activity, similar to antidepressant medications, most likely mediated through both monoaminergic and circadian system melatonergic mechanisms. We assessed the efficiency of bright light therapy as an adjuvant treatment to antidepressant pharmacotherapy in patients with severe MDD randomized by Hamilton Depression Rating Scale (HDRS) score to either (1) 150 mg venlafaxine hydrochloride daily at 7:00 AM or (2) 150 mg venlafaxine plus 60-minute light of 7000 lux the initial week of clinical management (venlafaxine + bright light therapy) daily at 7:00 AM. 50 inpatients with severe MDD at the Psychiatry Clinic of Yüzüncü Yıl University Training and Education Hospital participated. The study, which was conducted from January 2013 through June 2014, entailed patients diagnosed with severe MDD based on DSM-IV-TR for the first time. Mood states were assessed by the HDRS, Profile of Mood States (POMS), and Beck Depression Inventory (BDI) before treatment and at 1, 2, 4, and 8 weeks of treatment. On the basis of the HDRS score as the primary outcome variable, both strategies significantly improved depression and negative mood states already at the first treatment week (P treatment strategy were remarkable at the second and fourth weeks of clinical management (P = .018 and P = .011, respectively), with beneficial effects continuing until trial conclusion. Those treated with venlafaxine + bright light therapy evidenced significantly lower HDRS depression scores (P depression-dejection, tension-anxiety, anger-hostility, fatigue-inertia, and confusion-bewilderment subscales; all P treatment, a HDRS score ≤ 13, indicative of mild depression, and, although not statistically significant in our small sample study (P = .36), at week 8, 76% of venlafaxine + bright light therapy patients (n = 19) versus just 64% of the venlafaxine patients

  20. Putative transcriptomic biomarkers in the inflammatory cytokine pathway differentiate major depressive disorder patients from control subjects and bipolar disorder patients.

    Science.gov (United States)

    Powell, Timothy R; McGuffin, Peter; D'Souza, Ursula M; Cohen-Woods, Sarah; Hosang, Georgina M; Martin, Charlotte; Matthews, Keith; Day, Richard K; Farmer, Anne E; Tansey, Katherine E; Schalkwyk, Leonard C

    2014-01-01

    Mood disorders consist of two etiologically related, but distinctly treated illnesses, major depressive disorder (MDD) and bipolar disorder (BPD). These disorders share similarities in their clinical presentation, and thus show high rates of misdiagnosis. Recent research has revealed significant transcriptional differences within the inflammatory cytokine pathway between MDD patients and controls, and between BPD patients and controls, suggesting this pathway may possess important biomarker properties. This exploratory study attempts to identify disorder-specific transcriptional biomarkers within the inflammatory cytokine pathway, which can distinguish between control subjects, MDD patients and BPD patients. This is achieved using RNA extracted from subject blood and applying synthesized complementary DNA to quantitative PCR arrays containing primers for 87 inflammation-related genes. Initially, we use ANOVA to test for transcriptional differences in a 'discovery cohort' (total n = 90) and then we use t-tests to assess the reliability of any identified transcriptional differences in a 'validation cohort' (total n = 35). The two most robust and reliable biomarkers identified across both the discovery and validation cohort were Chemokine (C-C motif) ligand 24 (CCL24) which was consistently transcribed higher amongst MDD patients relative to controls and BPD patients, and C-C chemokine receptor type 6 (CCR6) which was consistently more lowly transcribed amongst MDD patients relative to controls. Results detailed here provide preliminary evidence that transcriptional measures within inflammation-related genes might be useful in aiding clinical diagnostic decision-making processes. Future research should aim to replicate findings detailed in this exploratory study in a larger medication-free sample and examine whether identified biomarkers could be used prospectively to aid clinical diagnosis.

  1. Putative transcriptomic biomarkers in the inflammatory cytokine pathway differentiate major depressive disorder patients from control subjects and bipolar disorder patients.

    Directory of Open Access Journals (Sweden)

    Timothy R Powell

    Full Text Available Mood disorders consist of two etiologically related, but distinctly treated illnesses, major depressive disorder (MDD and bipolar disorder (BPD. These disorders share similarities in their clinical presentation, and thus show high rates of misdiagnosis. Recent research has revealed significant transcriptional differences within the inflammatory cytokine pathway between MDD patients and controls, and between BPD patients and controls, suggesting this pathway may possess important biomarker properties. This exploratory study attempts to identify disorder-specific transcriptional biomarkers within the inflammatory cytokine pathway, which can distinguish between control subjects, MDD patients and BPD patients. This is achieved using RNA extracted from subject blood and applying synthesized complementary DNA to quantitative PCR arrays containing primers for 87 inflammation-related genes. Initially, we use ANOVA to test for transcriptional differences in a 'discovery cohort' (total n = 90 and then we use t-tests to assess the reliability of any identified transcriptional differences in a 'validation cohort' (total n = 35. The two most robust and reliable biomarkers identified across both the discovery and validation cohort were Chemokine (C-C motif ligand 24 (CCL24 which was consistently transcribed higher amongst MDD patients relative to controls and BPD patients, and C-C chemokine receptor type 6 (CCR6 which was consistently more lowly transcribed amongst MDD patients relative to controls. Results detailed here provide preliminary evidence that transcriptional measures within inflammation-related genes might be useful in aiding clinical diagnostic decision-making processes. Future research should aim to replicate findings detailed in this exploratory study in a larger medication-free sample and examine whether identified biomarkers could be used prospectively to aid clinical diagnosis.

  2. Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α in Major Depressive Disorder: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Ke Ma

    2016-05-01

    Full Text Available Major depressive disorder (MDD is characterized by mood, vegetative, cognitive, and even psychotic symptoms and signs that can cause substantial impairments in quality of life and functioning. Up to now, the exact pathogenesis of MDD remains poorly understood. Recent research has begun to reveal that the pro-inflammatory cytokines, particularly, tumor necrosis factor-α (TNF-α, play an integral role in the pathophysiology of depressive disorders and the mechanism of antidepressant treatment. On the base of several observations: it is found that subsets of MDD patients have enhanced plasma levels TNF-α; antidepressant treatments had linked with the decline of TNF-α; central administration of TNF-α gives rise to sickness behavior which shares features with depression; and a blockade of it can ameliorate depressive symptomatology in animal models and clinical trials. In this review article, we focus on recent evidence linking TNF-α and MDD looking at data from animal and clinical studies, illustrating the pathophysiological role, susceptibility and its therapeutic application in depression. We conclude by discussing future directions for research, in particular the opportunities for the development of novel therapeutics that target TNF-α. This will be very important for designing preventative strategies and for the identification of new drug targets and preventative strategies.

  3. Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α) in Major Depressive Disorder: A Systematic Review.

    Science.gov (United States)

    Ma, Ke; Zhang, Hongxiu; Baloch, Zulqarnain

    2016-05-14

    Major depressive disorder (MDD) is characterized by mood, vegetative, cognitive, and even psychotic symptoms and signs that can cause substantial impairments in quality of life and functioning. Up to now, the exact pathogenesis of MDD remains poorly understood. Recent research has begun to reveal that the pro-inflammatory cytokines, particularly, tumor necrosis factor-α (TNF-α), play an integral role in the pathophysiology of depressive disorders and the mechanism of antidepressant treatment. On the base of several observations: it is found that subsets of MDD patients have enhanced plasma levels TNF-α; antidepressant treatments had linked with the decline of TNF-α; central administration of TNF-α gives rise to sickness behavior which shares features with depression; and a blockade of it can ameliorate depressive symptomatology in animal models and clinical trials. In this review article, we focus on recent evidence linking TNF-α and MDD looking at data from animal and clinical studies, illustrating the pathophysiological role, susceptibility and its therapeutic application in depression. We conclude by discussing future directions for research, in particular the opportunities for the development of novel therapeutics that target TNF-α. This will be very important for designing preventative strategies and for the identification of new drug targets and preventative strategies.

  4. Selegiline transdermal system: in the treatment of major depressive disorder.

    Science.gov (United States)

    Frampton, James E; Plosker, Greg L

    2007-01-01

    The monamine oxidase (MAO) inhibitor selegiline is selective for MAO-B at the low oral dosages used in the treatment of Parkinson's disease. However, MAO-A is also inhibited at the high oral dosages needed to effectively treat depression (not an approved indication), necessitating a tyramine-restricted diet. The selegiline transdermal system was designed to deliver antidepressant drug concentrations to the CNS, without substantially impairing small intestine MAO-A activity. At the target dose of 6 mg/24 hours, tyramine dietary restrictions are not needed. Short-term treatment with fixed (6 mg/24 hours) or flexible (6, 9 or 12 mg/24 hours) doses of selegiline transdermal system was superior to placebo on most measures of antidepressant activity in 6- or 8-week, randomised, double-blind, multicentre studies in adult outpatients with major depressive disorder (MDD). Likewise, long-term treatment with a fixed dose of selegiline transdermal system 6 mg/24 hours was superior to placebo as maintenance therapy in a 52-week, randomised, double-blind, multicentre, relapse-prevention trial in patients with MDD. Selegiline transdermal system therapy was generally well tolerated in placebo-controlled studies; application site reactions, mostly of mild to moderate severity, were the most commonly reported adverse events. The incidence of sexual adverse effects and weight gain was low and similar to that with placebo.

  5. Enhanced Negative Feedback Responses in Remitted Depression

    OpenAIRE

    Pizzagalli, Diego; Meites, Tiffany M.; Deveney, Christen M; Holmes, Avram J.; Bogdan, Ryan; Steele, Katherine T.; Santesso, Diane L.

    2008-01-01

    Major depressive disorder (MDD)is characterized by hypersensitivity to negative feedback that might involve frontocingulate dysfunction. MDD patients exhibit enhanced electrophysiological responses to negative internal (errors) and external (feedback) cues. Whether this dysfunction extends to remitted depressed (RD) individuals with a history of MDD is currently unknown. To address this issue, we examined the feedback-related negativity in RD and control participants using a probabilistic pun...

  6. Affective and cognitive theory of mind abilities in youth with borderline personality disorder or major depressive disorder.

    Science.gov (United States)

    Tay, Sarah-Ann; Hulbert, Carol A; Jackson, Henry J; Chanen, Andrew M

    2017-09-01

    Theory of mind (ToM) is an important social cognitive ability that has been investigated in BPD, with inconsistent findings indicating impaired, comparable, and enhanced ToM in BPD. This study aimed to clarify and extend previous findings by investigating affective and cognitive ToM abilities in youth early in the course of BPD, by including a clinical comparison group of youth with major depressive disorder (MDD). Female participants aged 15-24 years diagnosed with BPD (n = 41) or MDD (n = 37) completed the Reading the Mind in the Eyes Test (RMET) and Happé's Cartoon Task, measures of affective and cognitive dimensions of ToM, respectively. The BPD group performed significantly worse than the MDD group on the affective ToM task, even after controlling for age, intelligence and depressive symptoms. Results for cognitive ToM were not significantly different. Finding of poorer performance on a measure of affective ToM, in BPD youth, relative to youth with MDD early in the course of BPD suggest a developmental failure of sociocognitive abilities needed for mentalising and which are theorised as giving rise to core features of BPD. Future research should employ more naturalistic paradigms to study social cognition and should assess individuals even earlier in the course of BPD. Copyright © 2017. Published by Elsevier B.V.

  7. The systematic activation method as a nursing intervention in depressed elderly : a protocol for a multi - centre cluster randomized trial

    NARCIS (Netherlands)

    Clignet, Frans; Meijel, Berno van; Straten, Annemiek van; Cuijpers, Pim

    2012-01-01

    BACKGROUND: Depression in later life is a common mental disorder with a prevalence rate of between 3% and 35% for minor depression and approximately 2% for Major Depressive Disorder (MDD). The most common treatment modalities for MDD are antidepressant medication and psychological interventions. Rec

  8. Prospective prediction of major depressive disorder from cortisol awakening responses in adolescence

    OpenAIRE

    Adam, Emma K.; Doane, Leah D.; Zinbarg, Richard E.; Mineka, Susan; Craske, Michelle G.; Griffith, James W.

    2010-01-01

    Levels of the stress-sensitive hormone cortisol increase dramatically in the first 30-40 minutes after waking, an effect known as the cortisol awakening response (CAR). There is considerable cross-sectional evidence that psychosocial stress is associated with an increased CAR, and the CAR has been found to be altered in the presence of stress-related diseases, including Major Depressive Disorder (MDD). To date, no prospective longitudinal studies have examined whether individual differences i...

  9. Psychosocial Interventions in Depressive Disorders

    Directory of Open Access Journals (Sweden)

    Ceyda Basogul

    2015-03-01

    Full Text Available In the last ten years, improvements in effective psychosocial interventions in the prevention and treatment of depression are remarkable. The World Health Organization stated that major depression affects children, adults and the elderly and is the leading cause of approximately 12% of all disabilities around the World. Medical expenses, loss of workforce, suicide risk, the risk of relapse or recurrence are taken into account, depression is an issue that needs to be handled with utmost care for health care workers especially psychiatric nurses. The purpose of this literature review is to examine psychosocial interventions and effectiveness of these interventions for depressive disorders shows a gradual increase in prevalence in worlwide. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(1: 1-15

  10. A neuropeptide Y variant (rs16139 associated with major depressive disorder in replicate samples from Chinese Han population.

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    Yongjun Wang

    Full Text Available OBJECTIVE: This study aimed to investigate the single nucleotide polymorphisms (SNPs of neuropeptide Y (NPY and major depressive disorder (MDD in Chinese Han population. DESIGN: Prospective and randomized studies were carried out. PATIENTS: A total of 700 patients (324 male and 376 female; mean age = 40±14.9 years with depression who met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV and 673 healthy controls (313 male and 360 female; mean age = 41.9±17.2 years were used to investigate the relationship between SNPs of NPY and the pathogenesis of MDD. A total of 417 patients (195 male and 202 female; mean age = 36±14.2 years diagnosed with MDD and 314 healthy controls (153 male and 161 female; mean age = 37.9±14.2 years from Chinese Han population were used to verify the relationship between SNPs of NPY and the pathogenesis of MDD. INTERVENTION AND OUTCOME: Ligase detection reactions were performed to detect the SNP sites of NPY. A series of statistical methods was carried out to investigate the correlation between the NPY gene SNP and MDD. RESULTS: Statistical analysis showed a significant correlation between the SNP sites rs16139 in NPY and the morbidity of depression. Patients with MDD have a lower frequency of A-allele in rs16139 in replicate samples from Chinese Han population. However, the frequency varied between male and female patients. CONCLUSION: The gene polymorphism loci rs16139 was closely related to MDD in Chinese Han population.

  11. Nice or effective? Social problem solving strategies in patients with major depressive disorder.

    Science.gov (United States)

    Thoma, Patrizia; Schmidt, Tobias; Juckel, Georg; Norra, Christine; Suchan, Boris

    2015-08-30

    Our study addressed distinct aspects of social problem solving in 28 hospitalized patients with Major Depressive Disorder (MDD) and 28 matched healthy controls. Three scenario-based tests assessed the ability to infer the mental states of story characters in difficult interpersonal situations, the capacity to freely generate good strategies for dealing with such situations and the ability to identify the best solutions among less optimal alternatives. Also, standard tests assessing attention, memory, executive function and trait empathy were administered. Compared to controls, MDD patients showed impaired interpretation of other peoples' sarcastic remarks but not of the mental states underlying other peoples' actions. Furthermore, MDD patients generated fewer strategies that were socially sensitive and practically effective at the same time or at least only socially sensitive. Overall, while the free generation of adequate strategies for difficult social situations was impaired, recognition of optimal solutions among alternatives was spared in MDD patients. Higher generation scores were associated with higher trait empathy and cognitive flexibility scores. We suggest that this specific pattern of impairments ought to be considered in the development of therapies addressing impaired social skills in MDD.

  12. Deficits of cognitive restructuring in major depressive disorder: Measured by textual micro-counseling dialogues.

    Science.gov (United States)

    Jiang, Nengzhi; Yu, Fei; Zhang, Wencai; Zhang, Jianxin

    2016-04-30

    Cognitive restructuring is an important strategy in cognitive behavioral therapy (CBT). The present study aimed to observe cognitive restructuring in major depressive disorder (MDD) patients using textual micro-counseling dialogue situations. A set of textual micro-counseling dialogues was used to trigger cognitive restructuring in 25 MDD patients and 27 healthy adults. The participants read descriptions ("problems") and explanations ("solutions") for psychologically distressing situations. High-, low-, and zero-restructuring solutions were randomly matched to the problems. The participants evaluated the adaptability and emotional valence of the problems and the insightfulness, adaptability, novelty, and emotional valence of the solutions. Insightfulness ratings for high-restructuring solutions were significantly higher relative to those of low-restructuring solutions in healthy adults, while adaptability ratings for low-restructuring solutions were significantly higher relative to those of high-restructuring solutions in MDD patients. Insightfulness ratings for the solutions were significantly predicted by novelty and adaptability in healthy adults and emotional valence in MDD patients. Lower insightfulness in high-restructuring solutions and higher adaptability in low-restructuring solutions in MDD patients may reflect deficits in cognitive control.

  13. Auditory evoked potentials in patients with major depressive disorder measured by Emotiv system.

    Science.gov (United States)

    Wang, Dongcui; Mo, Fongming; Zhang, Yangde; Yang, Chao; Liu, Jun; Chen, Zhencheng; Zhao, Jinfeng

    2015-01-01

    In a previous study (unpublished), Emotiv headset was validated for capturing event-related potentials (ERPs) from normal subjects. In the present follow-up study, the signal quality of Emotiv headset was tested by the accuracy rate of discriminating Major Depressive Disorder (MDD) patients from the normal subjects. ERPs of 22 MDD patients and 15 normal subjects were induced by an auditory oddball task and the amplitude of N1, N2 and P3 of ERP components were specifically analyzed. The features of ERPs were statistically investigated. It is found that Emotiv headset is capable of discriminating the abnormal N1, N2 and P3 components in MDD patients. Relief-F algorithm was applied to all features for feature selection. The selected features were then input to a linear discriminant analysis (LDA) classifier with leave-one-out cross-validation to characterize the ERP features of MDD. 127 possible combinations out of the selected 7 ERP features were classified using LDA. The best classification accuracy was achieved to be 89.66%. These results suggest that MDD patients are identifiable from normal subjects by ERPs measured by Emotiv headset.

  14. Using patient self-reports to study heterogeneity of treatment effects in major depressive disorder

    Science.gov (United States)

    Kessler, R.C.; van Loo, H.M.; Wardenaar, K.J.; Bossarte, R.M.; Brenner, L.A.; Ebert, D.D; de Jonge, P.; Nierenberg, A.A.; Rosellini, A.J.; Sampson, N.A.; Schoevers, R.A.; Wilcox, M.A.; Zaslavsky, A.M.

    2016-01-01

    Aims Clinicians need guidance to address the heterogeneity of treatment responses of patients with major depressive disorder (MDD). While prediction schemes based on symptom clustering and biomarkers have so far not yielded results of sufficient strength to inform clinical decision-making, prediction schemes based on big data predictive analytic models might be more practically useful. Methods We review evidence suggesting that prediction equations based on symptoms and other easily-assessed clinical features found in previous research to predict MDD treatment outcomes might provide a foundation for developing predictive analytic clinical decision support models that could help clinicians select optimal (personalized) MDD treatments. These methods could also be useful in targeting patient subsamples for more expensive biomarker assessments. Results Approximately two dozen baseline variables obtained from medical records or patient reports have been found repeatedly in MDD treatment trials to predict overall treatment outcomes (i.e., intervention versus control) or differential treatment outcomes (i.e., intervention A versus intervention B). Similar evidence has been found in observational studies of MDD persistence-severity. However, no treatment studies have yet attempted to develop treatment outcome equations using the full set of these predictors. Promising preliminary empirical results coupled with recent developments in statistical methodology suggest that models could be developed to provide useful clinical decision support in personalized treatment selection. These tools could also provide a strong foundation to increase statistical power in focused studies of biomarkers and MDD heterogeneity of treatment response in subsequent controlled trials. Conclusions Coordinated efforts are needed to develop a protocol for systematically collecting information about established predictors of heterogeneity of MDD treatment response in large observational treatment

  15. Neurobiological Alterations Induced by Exercise and Their Impact on Depressive Disorders

    Science.gov (United States)

    Helmich, Ingo; Latini, Alexandra; Sigwalt, Andre; Carta, Mauro Giovanni; Machado, Sergio; Velasques, Bruna; Ribeiro, Pedro; Budde, Henning

    2010-01-01

    Background: The impact of physical activity on brain metabolic functions has been investigated in different studies and there is growing evidence that exercise can be used as a preventive and rehabilitative intervention in the treatment of depressive disorders. However, the exact neuronal mechanisms underlying the latter phenomenon have not been clearly elucidated. The present article summarises key results derived from studies that focussed on the neurobiological impact of exercise on brain metabolic functions associated with depressive disorders. Since major depressive disorder (MDD) is a life threatening disease it is of great significance to find reliable strategies to prevent or to cure this illness. Therefore, the aim of this paper is to review (1) the physiological relationship between physical activity and depressive disorders and (2) the potential neurobiological alterations induced by exercise that might lead to the relief of mental disorders like depression. Methods: We searched electronic databases for literature concerning the relationship between exercise and depression from 1963 until 2009. Results: The data suggests an association between physical inactivity and higher levels of depressive symptoms. Properly designed studies could show that exercise training can be as effective as antidepressive medications. Conclusion: The exact mechanisms how exercise affects the brain are not fully understood and the literature lacks of well designed studies concerning the effects of exercise training on depressive disorders. But the observed antidepressant actions of exercise are strong enough that it already can be used as an alternative to current medications in the treatment of depressive disorders. PMID:21283646

  16. Sleep architecture variation: a mediator of metabolic disturbance in individuals with major depressive disorder.

    Science.gov (United States)

    Kudlow, P A; Cha, D S; Lam, R W; McIntyre, R S

    2013-10-01

    Remarkable proportions of individuals diagnosed with major depressive disorder (MDD) have comorbid metabolic disturbances (i.e., obesity, type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia), and vice versa. Accumulating evidence suggests that common pathophysiologic pathways such as a chronic, low-grade, proinflammatory state mediate this frequent co-occurrence. However, it remains unclear what traits precede the onset and increase the risk for these pathologic states. The aim of our review was to evaluate the evidentiary base supporting the hypothesis that the increased hazard for metabolic disturbance in MDD subpopulations (and vice versa) is mediated in part by endophenotypic variations in sleep architecture. We conducted a PubMed search of all English-language literature with the following search terms: sleep disturbance, circadian rhythm, inflammation, metabolic syndrome, obesity, MDD, mood disorder, prodrome, T2DM, cytokine, interleukin, hypertension, dyslipidemia, and hypercholesterolemia. Longitudinal and meta-analysis data indicate that specific variations in sleep architecture (i.e., decreased slow-wave sleep [SWS], increased rapid eye movement [REM] density) precede the onset of depressive symptomatology for a subpopulation of individuals. The same sleep architecture variations also are associated with obesity, T2DM, and hypertension. Decreased SWS and increased REM density is correlated with an increase in proinflammatory cytokines (e.g., IL-6, tumor necrosis factor, etc.). This proinflammatory state has been independently shown to be associated with MDD and metabolic disturbances. Taken together, our review suggests that sleep architecture variation of increased REM density and decreased SWS may be an endophenotypic trait, which serves to identify a subpopulation at increased risk for depressive symptoms and metabolic disturbances. Future research is needed to discern the predictive value, sensitivity, and specificity of using sleep

  17. The Impacts of Migraine among Outpatients with Major Depressive Disorder at a Two-Year Follow-Up.

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    Hung, Ching-I; Liu, Chia-Yih; Yang, Ching-Hui; Wang, Shuu-Jiun

    2015-01-01

    No study has investigated the impacts of migraine on depression, anxiety, and somatic symptoms and remission at the two-year follow-up point among patients with major depressive disorder (MDD). This study aimed to investigate the above issues. Psychiatric outpatients with MDD recruited at baseline were investigated at a two-year follow-up (N = 106). The Hamilton Depression Rating Scale, Hospital Anxiety and Depression Scale, and Depression and Somatic Symptoms Scale were used. Migraine was diagnosed according to the International Classification of Headache Disorders, 2nd edition. The patients were divided into no migraine, inactive migraine, and active migraine subgroups. Multiple logistic regressions were used to investigate the significant factors related to full remission of depression. Among patients without pharmacotherapy at the follow-up, patients with active migraine had significantly greater severities of anxiety and somatic symptoms as compared with patients without migraine; moreover, patients with active migraine had the lowest improvement percentage and full remission rate. There were no significant differences in depression, anxiety, and somatic symptoms between patients with inactive migraine and those without migraine. Active headache at follow-up was a significant factor related to a lower full remission rate. Active headache at follow-up was associated with a lower rate of full remission and more residual anxiety and somatic symptoms at follow-up among patients with migraine. Physicians should integrate a treatment plan for depression and migraine for the treatment of patients with MDD.

  18. Support vector machine classification of Major Depressive Disorder using diffusion-weighted neuroimaging and graph theory

    Directory of Open Access Journals (Sweden)

    Matthew D Sacchet

    2015-02-01

    Full Text Available Recently there has been considerable interest in understanding brain networks in Major Depressive Disorder (MDD. Neural pathways can be tracked in the living brain using diffusion weighted imaging (DWI; graph theory can then be used to study properties of the resulting fiber networks. To date, global abnormalities have not been reported in tractography-based graph metrics in MDD, so we used a machine learning approach based on ‘support vector machines’ to differentiate depressed from healthy individuals based on multiple brain network properties. We also assessed how important specific graph metrics were for this differentiation. Finally, we conducted a local graph analysis to identify abnormal connectivity at specific nodes of the network. We were able to classify depression using whole-brain graph metrics. Small-worldness was the most useful graph metric for classification. The right pars orbitalis, right inferior parietal cortex, and left rostral anterior cingulate all showed abnormal network connectivity in MDD. This is the first use of structural global graph metrics to classify depressed individuals. These findings highlight the importance of future research to understand network properties in depression across imaging modalities, improve classification results, and relate network alterations to psychiatric symptoms, medication, and co-morbidities.

  19. Parallels between major depressive disorder and Alzheimer's disease: role of oxidative stress and genetic vulnerability.

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    Rodrigues, Roberto; Petersen, Robert B; Perry, George

    2014-10-01

    The thesis of this review is that oxidative stress is the central factor in major depressive disorder (MDD) and Alzheimer's disease (AD). The major elements involved are inflammatory cytokines, the hypothalamic-pituitary axis, the hypothalamic-pituitary gonadal, and arginine vasopressin systems, which induce glucocorticoid and "oxidopamatergic" cascades when triggered by psychosocial stress, severe life-threatening events, and mental-affective and somatic diseases. In individuals with a genomic vulnerability to depression, these cascades may result in chronic depression-anxiety-stress spectra, resulting in MDD and other known depressive syndromes. In contrast, in subjects with genomic vulnerability to AD, oxidative stress-induced brain damage triggers specific antioxidant defenses, i.e., increased levels of amyloid-β (Aβ) and aggregation of hyper-phosphorylated tau, resulting in paired helical filaments and impaired functions related to the ApoEε4 isoform, leading to complex pathological cascades culminating in AD. Surprisingly, all the AD-associated molecular pathways mentioned in this review have been shown to be similar or analogous to those found in depression, including structural damage, i.e., hippocampal and frontal cortex atrophy. Other interacting molecular signals, i.e., GSK-3β, convergent survival factors (brain-derived neurotrophic factor and heat shock proteins), and transition redox metals are also mentioned to emphasize the vast array of intermediates that could interact via comparable mechanisms in both MDD and AD.

  20. Desvenlafaxine and Weight Change in Major Depressive Disorder

    Science.gov (United States)

    Leurent, Claire; Graepel, Jay; Ninan, Philip T.

    2010-01-01

    Objective: To characterize weight change during short- and longer-term treatment with desvenlafaxine (administered as desvenlafaxine succinate) for major depressive disorder (MDD). Method: Data from 9 short-term, double-blind, placebo-controlled studies and 1 longer-term relapse-prevention trial conducted between September 2002 and January 2007 were analyzed. Adult outpatients with a primary diagnosis of MDD using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition received fixed- or flexible-dose desvenlafaxine or placebo for 8 weeks in the short-term studies. In the longer-term study, responders to 12 weeks of open-label desvenlafaxine treatment were randomly assigned to double-blind treatment with desvenlafaxine or placebo for 6 months. Mean weight changes and incidence of potentially clinically important changes were evaluated. Results: In the short-term studies (desvenlafaxine: n = 1,834; placebo: n = 1,116), mean decreases in weight associated with desvenlafaxine were small but statistically significant compared with baseline (P desvenlafaxine vs + 0.05 kg placebo; P desvenlafaxine (n = 190) and placebo (n = 185) throughout the relapse-prevention phase, with no statistical difference between desvenlafaxine- and placebo-treated patients at the final evaluation. Less than 1% of desvenlafaxine-treated patients experienced a clinically meaningful weight change. Conclusions: Desvenlafaxine was not associated with clinically significant weight change during short- or longer-term treatment. PMID:20582292

  1. Major depressive disorder, suicidal ideation, and suicide attempt in twins discordant for cannabis dependence and early-onset cannabis use.

    Science.gov (United States)

    Lynskey, Michael T; Glowinski, Anne L; Todorov, Alexandre A; Bucholz, Kathleen K; Madden, Pamela A F; Nelson, Elliot C; Statham, Dixie J; Martin, Nicholas G; Heath, Andrew C

    2004-10-01

    Previous research has reported both a moderate degree of comorbidity between cannabis dependence and major depressive disorder (MDD) and that early-onset cannabis use is associated with increased risks for MDD. To examine whether associations between both lifetime cannabis dependence and early cannabis use and measures of MDD, suicidal ideation, and suicide attempt persist after controlling for genetic and/or shared environmental influences. Cross-sectional survey of twin pairs discordant for lifetime cannabis dependence and those discordant for early cannabis use. General population sample of twins (median age, 30 years). Two hundred seventy-seven same-sex twin pairs discordant for cannabis dependence and 311 pairs discordant for early-onset cannabis use (before age 17 years). Self-report measures of DSM-IV-defined lifetime MDD, suicidal ideation, and suicide attempt. Individuals who were cannabis dependent had odds of suicidal ideation and suicide attempt that were 2.5 to 2.9 times higher than those of their non-cannabis-dependent co-twin. Additionally, cannabis dependence was associated with elevated risks of MDD in dizygotic but not in monozygotic twins. Those who initiated cannabis use before age 17 years had elevated rates of subsequent suicide attempt (odds ratio, 3.5 [95% confidence interval, 1.4-8.6]) but not of MDD or suicidal ideation. Early MDD and suicidal ideation were significantly associated with subsequent risks of cannabis dependence in discordant dizygotic pairs but not in discordant monozygotic pairs. Comorbidity between cannabis dependence and MDD likely arises through shared genetic and environmental vulnerabilities predisposing to both outcomes. In contrast, associations between cannabis dependence and suicidal behaviors cannot be entirely explained by common predisposing genetic and/or shared environmental predispositions. Previously reported associations between early-onset cannabis use and subsequent MDD likely reflect shared genetic and

  2. Anhedonia and general distress show dissociable ventromedial prefrontal cortex connectivity in major depressive disorder.

    Science.gov (United States)

    Young, C B; Chen, T; Nusslock, R; Keller, J; Schatzberg, A F; Menon, V

    2016-05-17

    Anhedonia, the reduced ability to experience pleasure in response to otherwise rewarding stimuli, is a core symptom of major depressive disorder (MDD). Although the posterior ventromedial prefrontal cortex (pVMPFC) and its functional connections have been consistently implicated in MDD, their roles in anhedonia remain poorly understood. Furthermore, it is unknown whether anhedonia is primarily associated with intrinsic 'resting-state' pVMPFC functional connectivity or an inability to modulate connectivity in a context-specific manner. To address these gaps, a pVMPFC region of interest was first identified using activation likelihood estimation meta-analysis. pVMPFC connectivity was then examined in relation to anhedonia and general distress symptoms of depression, using both resting-state and task-based functional magnetic resonance imaging involving pleasant music, in current MDD and healthy control groups. In MDD, pVMPFC connectivity was negatively correlated with anhedonia but not general distress during music listening in key reward- and emotion-processing regions, including nucleus accumbens, ventral tegmental area/substantia nigra, orbitofrontal cortex and insula, as well as fronto-temporal regions involved in tracking complex sound sequences, including middle temporal gyrus and inferior frontal gyrus. No such dissociations were observed in the healthy controls, and resting-state pVMPFC connectivity did not dissociate anhedonia from general distress in either group. Our findings demonstrate that anhedonia in MDD is associated with context-specific deficits in pVMPFC connectivity with the mesolimbic reward system when encountering pleasurable stimuli, rather than a static deficit in intrinsic resting-state connectivity. Critically, identification of functional circuits associated with anhedonia better characterizes MDD heterogeneity and may help track of one of its core symptoms.

  3. Initial investigation of behavioral activation therapy for co-morbid major depressive disorder and obesity.

    Science.gov (United States)

    Pagoto, Sherry; Bodenlos, Jamie S; Schneider, Kristin L; Olendzki, Barbara; Spates, C Richard; Ma, Yunsheng

    2008-09-01

    More than one-third of treatment-seeking obese patients are clinically depressed. No evidence-based treatments exist for individuals with comorbid depression and obesity. Behavioral activation (BA), an effective treatment for depression, might also facilitate weight loss. The objective of this study is to evaluate the feasibility and efficacy of BA plus nutrition counseling for weight loss among individuals with comorbid major depressive disorder (MDD) and obesity. The BA intervention targeted both weight reduction and depression in 14 obese patients (79% female; 86% Caucasian) who met criteria for MDD. At baseline, mean Beck Depression Inventory (BDI-II) score was 26.71, and mean Hamilton Depression Rating Scale (HDRS) score was 16.00. Significant reductions at 12-weeks in both BDI-II and HDRS were observed with 10 participants reaching full remission at post treatment. Reductions in body weight, daily caloric intake, and physical activity were observed. BA with nutrition counseling appears to have potential as a weight loss treatment in the context of depression. Results support the need for a randomized controlled trial to evaluate the efficacy of BA for both weight loss and depression. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  4. Face-Memory and Emotion: Associations with Major Depression in Children and Adolescents

    Science.gov (United States)

    Pine, Daniel S.; Lissek, Shmuel; Klein, Rachel G.; Mannuzza, Salvatore; Moulton, John L., III; Guardino, Mary; Woldehawariat, Girma

    2004-01-01

    Background: Studies in adults with major depressive disorder (MDD) document abnormalities in both memory and face-emotion processing. The current study used a novel face-memory task to test the hypothesis that adolescent MDD is associated with a deficit in memory for face-emotions. The study also examines the relationship between parental MDD and…

  5. A Resting-State Brain Functional Network Study in MDD Based on Minimum Spanning Tree Analysis and the Hierarchical Clustering

    Directory of Open Access Journals (Sweden)

    Xiaowei Li

    2017-01-01

    Full Text Available A large number of studies demonstrated that major depressive disorder (MDD is characterized by the alterations in brain functional connections which is also identifiable during the brain’s “resting-state.” But, in the present study, the approach of constructing functional connectivity is often biased by the choice of the threshold. Besides, more attention was paid to the number and length of links in brain networks, and the clustering partitioning of nodes was unclear. Therefore, minimum spanning tree (MST analysis and the hierarchical clustering were first used for the depression disease in this study. Resting-state electroencephalogram (EEG sources were assessed from 15 healthy and 23 major depressive subjects. Then the coherence, MST, and the hierarchical clustering were obtained. In the theta band, coherence analysis showed that the EEG coherence of the MDD patients was significantly higher than that of the healthy controls especially in the left temporal region. The MST results indicated the higher leaf fraction in the depressed group. Compared with the normal group, the major depressive patients lost clustering in frontal regions. Our findings suggested that there was a stronger brain interaction in the MDD group and a left-right functional imbalance in the frontal regions for MDD controls.

  6. Activated depression: mixed bipolar disorder or agitated unipolar depression?

    Science.gov (United States)

    Swann, Alan C

    2013-08-01

    The combination of depression and activation presents clinical and diagnostic challenges. It can occur, in either bipolar disorder or major depressive disorder, as increased agitation as a dimension of depression. What is called agitation can consist of expressions of painful inner tension or as disinhibited goal-directed behavior and thought. In bipolar disorder, elements of depression can be combined with those of mania. In this case, the agitation, in addition to increased motor activity and painful inner tension, must include symptoms of mania that are related to goal-directed behavior or manic cognition. These diagnostic considerations are important, as activated depression potentially carries increased behavioral risk, especially for suicidal behavior, and optimal treatments for depressive episodes differ between bipolar disorder and major depressive disorder.

  7. The association between depressive disorders and health care utilization: results from the São Paulo ageing and health study (SPAH).

    Science.gov (United States)

    Huang, Hsiang; Menezes, Paulo R; da Silva, Simone A; Tabb, Karen; Barkil-Oteo, Andres; Scazufca, Marcia

    2014-01-01

    Although depressive disorders are associated with increased health care utilization in the elderly living in high-income countries, few studies have examined this relationship in Latin America. The present study is part of the São Paulo Ageing and Health Study, a population-based epidemiological study of mental disorders in 2072 low-income adults ≥ 65 years old living in São Paulo, Brazil. Depressive disorders defined as major depressive disorder (MDD) and clinically relevant depressive symptoms (CRDS) were assessed with the Geriatric Mental State and the Neuropsychiatric Inventory. We examined the association between depressive disorders/symptoms and health care utilization (outpatient visits, hospital admissions and medication use in the past 3 months) using count models. The prevalence of MDD and CRDS was 4.9% and 21.4%, respectively. In the fully adjusted model, older adults with MDD were 36% more likely to have one more outpatient visit (RM: 1.36, 95% CI: 1.11-1.67), while older adults with CRDS were 14% more likely to have one more outpatient visit (RM: 1.14, 95% CI: 1.02-1.28). Elderly individuals with MDD had a prevalence of hospital admissions in the previous 3 months that was twice that of those without depression (PR=2.02, 95% CI: 1.09-3.75). Significant differences were not found for medication use. Among low-income older adults living in Brazil, those with MDD are more likely to have a recent hospital admission and outpatient service use than those without depression. Future studies are needed to examine the effectiveness of depression treatments for this population in order to both decrease the burden of illness as well as to minimize health care utilization related to depression. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. A support vector machine model provides an accurate transcript-level-based diagnostic for major depressive disorder

    Science.gov (United States)

    Yu, J S; Xue, A Y; Redei, E E; Bagheri, N

    2016-01-01

    Major depressive disorder (MDD) is a critical cause of morbidity and disability with an economic cost of hundreds of billions of dollars each year, necessitating more effective treatment strategies and novel approaches to translational research. A notable barrier in addressing this public health threat involves reliable identification of the disorder, as many affected individuals remain undiagnosed or misdiagnosed. An objective blood-based diagnostic test using transcript levels of a panel of markers would provide an invaluable tool for MDD as the infrastructure—including equipment, trained personnel, billing, and governmental approval—for similar tests is well established in clinics worldwide. Here we present a supervised classification model utilizing support vector machines (SVMs) for the analysis of transcriptomic data readily obtained from a peripheral blood specimen. The model was trained on data from subjects with MDD (n=32) and age- and gender-matched controls (n=32). This SVM model provides a cross-validated sensitivity and specificity of 90.6% for the diagnosis of MDD using a panel of 10 transcripts. We applied a logistic equation on the SVM model and quantified a likelihood of depression score. This score gives the probability of a MDD diagnosis and allows the tuning of specificity and sensitivity for individual patients to bring personalized medicine closer in psychiatry. PMID:27779627

  9. Altered functional connectivity of the dorsolateral prefrontal cortex in first-episode patients with major depressive disorder

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    Ye, Ting, E-mail: yeting@ihep.ac.cn [Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, PO Box 918, Yu-Quan St, Shijingshan District, Beijing 100049 (China); Graduate School of Chinese Academy of Sciences, PO Box 918, Yu-Quan St, Shijingshan District, Beijing 100049 (China); Peng, Jing, E-mail: ppengjjing@sina.com.cn [Department of Radiology, Xuanwu Hospital of Capital Medical University, No. 45, Chang-Chun St, Xuanwu District, Beijing 100053 (China); Nie, Binbin, E-mail: niebb@ihep.ac.cn [Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, PO Box 918, Yu-Quan St, Shijingshan District, Beijing 100049 (China); Gao, Juan, E-mail: gaojuan@ihep.ac.cn [Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, PO Box 918, Yu-Quan St, Shijingshan District, Beijing 100049 (China); Graduate School of Chinese Academy of Sciences, PO Box 918, Yu-Quan St, Shijingshan District, Beijing 100049 (China); Liu, Jiangtao, E-mail: Liujiangtao813@sina.com [Department of Radiology, Xuanwu Hospital of Capital Medical University, No. 45, Chang-Chun St, Xuanwu District, Beijing 100053 (China); Li, Yang, E-mail: Liyang2007428@hotmail.com [Department of Psychiatry, Anding Hospital of Capital Medical University, No. 5, An Kang Hutong, Deshengmen wai, Xicheng District, Beijing 100088 (China); Wang, Gang, E-mail: gangwang@gmail.com [Department of Psychiatry, Anding Hospital of Capital Medical University, No. 5, An Kang Hutong, Deshengmen wai, Xicheng District, Beijing 100088 (China); Ma, Xin, E-mail: lijianshe@medmail.com.cn [Department of Psychiatry, Anding Hospital of Capital Medical University, No. 5, An Kang Hutong, Deshengmen wai, Xicheng District, Beijing 100088 (China); Li, Kuncheng [Department of Radiology, Xuanwu Hospital of Capital Medical University, No. 45, Chang-Chun St, Xuanwu District, Beijing 100053 (China); and others

    2012-12-15

    Background: The aim of this study was to investigate resting-state functional connectivity alteration of the right dorsolateral prefrontal cortex (DLPFC) in patients with first-episode major depressive disorder (MDD). Methods: Twenty-two first-episode MDD patients and thirty age-, gender- and education-matched healthy control subjects were enrolled. Rest state functional magnetic resonance images and structure magnetic resonance images were scanned. The functional connectivity analysis was done based on the result of voxel-based morphometry (VBM). And the right DLPFC was chosen as the seed region of interests (ROI), as its gray matter density (GMD) decreased in the MDD patients compared with controls and its GMD values were negative correlation with the Hamilton Depression Rating Scale (HDRS) scores. Results: Compared to healthy controls, the MDD patients showed increased functional connectivity with right the DLPFC in the left dorsal anterior cingulate cortex (ACC), left parahippocampal gyrus (PHG), thalamus and precentral gyrus. In contrast, there were decreased functional connectivity between the right DLPFC and right parietal lobe. Conclusions: By applying the VBM results to the functional connectivity analysis, the study suggested that abnormality of GMD in right DLPFC might be related to the functional connectivity alteration in the pathophysiology of MDD, which might be useful in further characterizing structure–function relations in this disorder.

  10. Endocrine and inflammatory profiles in type 2 diabetic patients with and without major depressive disorder.

    Science.gov (United States)

    Alvarez, Adriana; Faccioli, Jose; Guinzbourg, Mónica; Castex, María M; Bayón, Claudia; Masson, Walter; Bluro, Ignacio; Kozak, Andrea; Sorroche, Patricia; Capurro, Lina; Grosembacher, Luis; Proietti, Adrián; Finkelsztein, Carlos; Costa, Lucas; Fainstein Day, Patricia; Cagide, Arturo; Litwak, León E; Golden, Sherita H

    2013-02-14

    There is a high prevalence of depression in individuals with type 2 diabetes mellitus. Depressive disorders are associated with increased medical morbidity and mortality in individuals with diabetes. It has been demonstrated that there is a higher prevalence of diabetic complications among individuals with diabetes and depression compared to those without depression. Several biological alterations have been reported in individuals with depressive disorders, particularly abnormal levels of endocrine-inflammatory markers.This study aims to determine the prevalence of major depressive disorder (MDD) in type 2 diabetes patients, the prevalence of cardiovascular events in individuals with and without MDD and to compare the endocrine-inflammatory profile between groups. The study was approved by the "Comité de Etica de Protocolos de Investigación del Departamento de Docencia e Investigación del Hospital Italiano de Buenos Aires" with the number "1262" and included only patients who provided written informed consent. The study was conducted in accordance with the Declaration of Helsinki and the Habeas Data law on protection of personal data (Law Nª 25326, Argentina).Type 2 diabetes patients (n = 61) were included and they were classified as having MDD or not according to DSM-IV. Macrovascular disease was obtained from the medical history. Additionally, the intima-media thickness of the common carotid, carotid bifurcations and internal carotid arteries was measured non-invasively by two-dimensional ultrasound imaging. Fasting glucose, fasting lipid profile, inflammatory (CRP, TNF-α) and endocrine (urine free cortisol and saliva cortisol) markers. Student t tests were used to compare means for normally distributed variables and Mann-Whitney test for variables without normal distribution. Relative frequencies were calculated and a chi-square analysis was conducted. Data were expressed as mean ± standard deviation (SD) or median and interquartile range. Multivariable

  11. Efficacy of aripiprazole augmentation in Japanese patients with major depressive disorder: a subgroup analysis and Montgomery-Åsberg Depression Rating Scale and Hamilton Rating Scale for Depression item analyses of the Aripiprazole Depression Multicenter Efficacy study.

    Science.gov (United States)

    Ozaki, Norio; Otsubo, Tempei; Kato, Masaki; Higuchi, Teruhiko; Ono, Hiroaki; Kamijima, Kunitoshi

    2015-01-01

    Results from this randomized, placebo-controlled study of aripiprazole augmentation to antidepressant therapy (ADT) in Japanese patients with major depressive disorder (MDD) (the Aripiprazole Depression Multicenter Efficacy [ADMIRE] study) revealed that aripiprazole augmentation was superior to ADT alone and was well tolerated. In subgroup analyses, we investigated the influence of demographic- and disease-related factors on the observed responses. We also examined how individual symptom improvement was related to overall improvement in MDD. Data from the ADMIRE study were analyzed. Subgroup analyses were performed on the primary outcome measures: the mean change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from the end of selective serotonin reuptake inhibitor (SSRI)/serotonin norepinephrine reuptake inhibitor (SNRI) treatment to the end of the randomized treatment. Changes in the MADRS total scores were consistently greater with aripiprazole than placebo in each of the subgroups. Efficacy was not related to sex, age, number of adequate ADT trials in the current episode, MDD diagnosis, number of depressive episodes, duration of the current episode, age at first depressive episode, time since the first depressive episode, type of SSRI/SNRI, or severity at the end of SSRI/SNRI treatment phase. Compared to placebo, aripiprazole resulted in significant and rapid improvement on seven of the 10 MADRS items, including sadness. These post-hoc analyses indicated that aripiprazole was effective for a variety of Japanese patients with MDD who had exhibited inadequate responses to ADT. Additionally, we suggest that aripiprazole significantly and rapidly improved the core depressive symptoms. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

  12. Acculturation and other risk factors of depressive disorders in individuals with Turkish migration backgrounds.

    Science.gov (United States)

    Janssen-Kallenberg, Hanna; Schulz, Holger; Kluge, Ulrike; Strehle, Jens; Wittchen, Hans-Ulrich; Wolfradt, Uwe; Koch-Gromus, Uwe; Heinz, Andreas; Mösko, Mike; Dingoyan, Demet

    2017-07-19

    Acculturation is a long-term, multi-dimensional process occurring when subjects of different cultures stay in continuous contact. Previous studies have suggested that elevated rates of depression among different migrant groups might be due to patterns of acculturation and migration related risk factors. This paper focused on prevalence rates of depressive disorders and related risk factors among individuals with Turkish migration backgrounds. A population-based sample of 662 individuals with Turkish migration backgrounds were interviewed by bilingual interviewers using a standardised diagnostic interview for DSM-IV-TR and ICD-10 diagnoses (CIDI DIA-X Version 2.8). Associations between 12-month prevalence rates of depressive disorders with potential risk factors were assessed, including gender, age, socioeconomic status, acculturation status and migration status. 12-month prevalence rates of any depressive disorder were 29.0%, 14.4% of major depressive disorder (MDD) and 14.7% of dysthymia. Older age and low socioeconomic status were most consistently related to higher risks of depressive disorders. Acculturation status showed associations with subtypes of depressive disorder. Associations differed between men and women. Symptom severity of MDD was linked to gender, with females being more affected by severe symptoms. The prevalence of depressive disorders is high in individuals with Turkish migration backgrounds, which can be partly explained by older age, low socioeconomic status and acculturation pressures. Only a limited number of risk factors were assessed. Acculturation in particular is a complex process which might not be sufficiently represented by the applied measures. Further risk factors have to be identified in representative samples of this migrant group.

  13. Functional Recovery in Major Depressive Disorder: Focus on Early Optimized Treatment.

    Science.gov (United States)

    Habert, Jeffrey; Katzman, Martin A; Oluboka, Oloruntoba J; McIntyre, Roger S; McIntosh, Diane; MacQueen, Glenda M; Khullar, Atul; Milev, Roumen V; Kjernisted, Kevin D; Chokka, Pratap R; Kennedy, Sidney H

    2016-09-01

    This article presents the case that a more rapid, individualized approach to treating major depressive disorder (MDD) may increase the likelihood of achieving full symptomatic and functional recovery for individual patients and that studies show it is possible to make earlier decisions about appropriateness of treatment in order to rapidly optimize that treatment. A PubMed search was conducted using terms including major depressive disorder, early improvement, predictor, duration of untreated illness, and function. English-language articles published before September 2015 were included. Additional studies were found within identified research articles and reviews. Thirty antidepressant studies reporting predictor criteria and outcome measures are included in this review. Studies were reviewed to extract definitions of predictors, outcome measures, and results of the predictor analysis. Results were summarized separately for studies reporting effects of early improvement, baseline characteristics, and duration of untreated depression. Shorter duration of the current depressive episode and duration of untreated depression are associated with better symptomatic and functional outcomes in MDD. Early improvement of depressive symptoms predicts positive symptomatic outcomes (response and remission), and early functional improvement predicts an increased likelihood of functional remission. The approach to treatment of depression that exhibits the greatest potential for achieving full symptomatic and functional recovery is early optimized treatment: early diagnosis followed by rapid individualized treatment. Monitoring symptoms and function early in treatment is crucial to ensuring that patients do not remain on ineffective or poorly tolerated treatment, which may delay recovery and heighten the risk of residual functional deficits.

  14. Examination of the interrelations between the factors of PTSD, major depression, and generalized anxiety disorder in a heterogeneous trauma-exposed sample using DSM 5 criteria.

    Science.gov (United States)

    Price, Matthew; van Stolk-Cooke, Katherine

    2015-11-01

    Exposure to traumatic events places individuals at high risk for multiple psychiatric disorders, including posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and generalized anxiety disorder (GAD). The high rates of comorbidity among these conditions merit evaluation in order to improve diagnosis and treatment approaches. The current study evaluated the association between PTSD, MDD, and GAD factors as presented in the DSM 5. 602 trauma-exposed individuals who experienced an event that met Criterion A for the DSM 5 PTSD diagnosis were recruited through Amazon.com, Inc.'s Mechanical Turk (MTurk) to complete an assessment of the impact of stressful events on their lives. High interrelations were detected among the 4 PTSD factors, 2 MDD factors that corresponded to somatic and affective symptoms, and the single GAD factor. The affective factor of MDD was most strongly related to the emotional numbing factor of PTSD, whereas the somatic factor of MDD was most strongly related to the hyperarousal factor of PTSD. The GAD factor was most strongly related to the hyperarousal factor of PTSD, relative to the other PTSD factors. The strength of the interrelations between factors of the three disorders is largely a function of the overlap in symptoms and calls into question the uniqueness of negative affective symptoms of PTSD, MDD and GAD. Results suggest that improved understanding of the trauma reaction requires a focus on the unique presentation of each individual and assessment of multiple disorders.

  15. A new clinical rating scale for work absence and productivity: validation in patients with major depressive disorder

    Directory of Open Access Journals (Sweden)

    Yatham Lakshmi N

    2009-12-01

    Full Text Available Abstract Background The prevalence of major depressive disorder (MDD is highest in working age people and depression causes significant impairment in occupational functioning. Work productivity and work absence should be incorporated into clinical assessments but currently available scales may not be optimized for clinical use. This study seeks to validate the Lam Employment Absence and Productivity Scale (LEAPS, a 10-item self-report questionnaire that takes 3-5 minutes to complete. Methods The study sample consisted of consecutive patients attending a Mood Disorders outpatient clinic who were in full- or part-time paid work. All patients met DSM-IV criteria for MDD and completed during their intake assessment the LEAPS, the self-rated version of the Quick Inventory for Depressive Symptomatology (QIDS-SR, the Sheehan Disability Scale (SDS and the Health and Work Performance Questionnaire (HPQ. Standard psychometric analyses for validation were conducted. Results A total of 234 patients with MDD completed the assessments. The LEAPS displayed excellent internal consistency as assessed by Cronbach's alpha of 0.89. External validity was assessed by comparing the LEAPS to the other clinical and work functioning scales. The LEAPS total score was significantly correlated with the SDS work disability score (r = 0.63, p Conclusion The LEAPS displays good internal and external validity in a population of patients with MDD attending an outpatient clinic, which suggests that it may be a clinically useful tool to assess and monitor work functioning and productivity in depressed patients.