Tan, Huiying; Zou, Wei; Jiang, Jiamei; Tian, Ying; Xiao, Zhifang; Bi, Lili; Zeng, Haiying; Tang, Xiaoqing
The chronic unpredictable mild stress (CUMS) model is a widely used experimental model of depression. Exogenous stress-induced neuronal cell death in the hippocampus is closely associated with the pathogenesis of depression. Excessive and prolonged endoplasmic reticulum (ER) stress triggers cell death. Hydrogen sulfide (H2S), the third endogenous signaling gasotransmitter, plays an important role in brain functions as a neuromodulator and a neuroprotectant. We hypothesized that the disturbance of endogenous H2S generation and ER stress in the hippocampus might be involved in CUMS-induced depression-like behaviors. Thus, the present study focused on whether CUMS disturbs the generation of endogenous H2S and up-regulates ER stress in the hippocampus and whether exogenous H2S prevents CUMS-induced depressive-like behaviors. Results showed that CUMS-treated rats exhibit depression-like behavior and hippocampal ER stress responses including up-regulated levels of glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein, and cleaved caspase-12 expression, while the endogenous generation of H2S in the hippocampus is suppressed in CUMS-treated rats. Furthermore, exogenous H2S prevents CUMS-induced depression-like behavior. These data indicated that CUMS-induced depression-like behaviors are related to the disturbance of endogenous H2S generation and ER stress in the hippocampus and suggested that endogenous H2S and ER stress are novel treatment targets of depression. © The Author 2015. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
陈抗松; 廖华; 杨希林; 陈建新
Objective To study changes of auditory brainstem response (ABR) in a rat model of depression induced by chronic unpredictable mild stress (CUMS). Methods Sixteen rats were randomly divided into a control group (n=8) and a mod-el group (n=8). The model group was randomly treated with CUMS every day to keep animals in a depressive state for 28 days. Animal behaviors were recorded using an automatic tracking system at 1 day before experiment and on Days 14 and 28. In the present study, ABRs were tested using a TDT system on Day 28 for all animals. Results Compared with the control group, the basic indices of animal behavior of the model group were markedly different from the control group on Days 14 and 28 (p0.05). The latencies of waves I and V in the model group were significantly longer than the control group (P<0.05) and the amplitudes of waves II and V were markedly decreased compared to the control group (P<0.05 and P<0.01, respectively). Con-clusion Abnormal neuroelectric activities along the auditory pathway from the peripheral auditory organ to the brainstem may exist in rats with CUMS induced depression .% 目的探讨单纯抑郁症大鼠模型的听性脑干反应（ABR）的改变。方法16只大鼠随机分为对照组（8只）：正常喂养；模型组（8只）：每天随机给予多种低强度刺激，造成动物的抑郁状态，持续28天。记录各组大鼠实验前1天、第14、28天的行为学，并在造模完成后对两组大鼠行ABR检测。结果造模第14、28天，与对照组比较，模型组大鼠的旷场行为学、体重及摄食量的改变、糖水偏爱均有显著性差异（p<0.01）；第28天，在声强90dB SPL条件下，与对照组比较，模型组大鼠的Ⅰ波潜伏期明显延长(P<0.05)，Ⅱ波的波幅显著下降，差异有统计学意义(P<0.05)。结论抑郁症模型大鼠可能存在外周听觉神经至脑干通路存在神经电活动的异常。
Li, Hui; Linjuan-Li; Wang, Yaping
Neuronal plasticity in hippocampal neurons is closely related to memory, mood and behavior as well as in the development of depression. Granulocyte colony-stimulating factor (G-CSF) can promote neuronal plasticity and enhance motor skills. However, the function of G-CSF in depression remains poorly understood. In this study, we explored the biological role and potential molecular mechanism of G-CSF on depression-like behaviors. Our results showed that G-CSF was significantly downregulated in the hippocampus of chronic unexpected mild stress (CUMS) rats. Administration of G-CSF significantly reversed CUMS-induced depression-like behaviors in the open field test (OFT), sucrose preference test (SPT) and forced swimming test (FST). Moreover, G-CSF upregulated the expression of synaptic-associated proteins including polysialylated form of neural cell adhesion molecule (PSA-NCAM), synaptophysin (SYN), and postsynaptic density protein 95 (PSD-95) in the hippocampus and G-CSF significantly increased cell viability rate of hippocampal neurons in vitro. Further studies indicated that the renin-angiotensin system (Ras)/extracellular signal-regulated kinase (ERK)/p38 mitogen-activated protein kinase (MAPK) signaling pathways was involved in the regulation of G-CSF on depressive-like behaviors and neuronal plasticity in CUMS rats. Taken together, our results showed that G-CSF improves depression-like behaviors via inhibiting Ras/ERK/MAPK signaling pathways. Our study suggests that G-CSF may be a promising therapeutic strategy for the treatment of depression.
刘金鹏; 刘华; 高峻钰; 刘少君
目的：通过PET成像技术研究慢性不可预见性温和刺激（ CUMS）致抑郁症大鼠的全脑代谢特点。方法实验组大鼠给予CUMS 4周后，通过糖水偏嗜度、自发活动距离、体质量等指标分为刺激后抑郁大鼠（ D组）及刺激后非抑郁大鼠（ ND组），并与正常对照组大鼠（ CON组）一起行PET检查，比较不同组大鼠之间全脑的代谢变化。结果（1）D组大鼠的双侧S1、丘脑、苍白球、岛叶、M2、左屏状核较CON组代谢升高，右侧下丘、胼胝体压部、小脑则代谢降低；（2）D组大鼠双侧海马CA3区、M1、M2、纹状体、S1、嗅球等区较ND组代谢增高，左侧楔状核及海马则代谢降低；（3） ND组大鼠与CON组相比，无代谢升高的脑区，而外侧隔核、双侧纹状体、下丘脑室旁核、双侧S1、右侧苍白球则代谢降低。结论以前囟后4 mm处为界，抑郁大鼠脑代谢特点是前高后低，左右大致对称。抑郁症的发生可能与多个脑区功能的异常相互作用有关。%Objective To observe the metabolic changes in the whole brain of chronic unpredictable mild stimulations ( CUMS)-induced depressive rats using PET imaging technology.Methods After 4 weeks’ of CUMS, rats of experimental group were divided into two groups:Group D( depression) and Group ND( no depression) , according to the degree of sugar addiction, distance of spontaneous activity and relative body mass.Then metabolic changes in the whole brain of these rats and those in control group ( CON) were observed using PET technology, and the differences were companred between the threegroups.Results (1)ComparedwithGroupCON,metabolismofGroupDwaselevatedinbilateralS1,thalamus, globus pallidus, insula, M2 and left claustrum, but descended in right inferior colliculus, splenium of corpus callosum and cerebellum.(2) Metabolism of Group D increased in the bilateral CA3 region of hippocampus, M1, M2, striatum, S1 and olfactory bulb
Qiao, Hui; An, Shu-Cheng; Ren, Wei; Ma, Xin-Ming
Major depressive disorder is the most prevalent psychiatric condition, but the cellular and molecular mechanisms underlying this disorder are largely unknown, although multiple hypotheses have been proposed. The aim of this study was to characterize the progressive alteration of neuronal plasticity in the male rat hippocampus during depression induced by chronic unpredictable mild stress (CUMS), an established animal model of depression. The data in the hippocampus were collected on days 7, 14 and 21 after the onset of three-week CUMS. When analyzed on day 21, three-week CUMS induced typically depressive-like behaviors, impaired LTP induction, and decreased basal synaptic transmission at hippocampal CA3-CA1 synapses recorded in vivo, which was accompanied by decreased density of dendritic spines in CA1 and CA3 pyramidal neurons. The levels of both Kalirin-7 and brain-derived neurotrophic factor (BDNF) in the hippocampus were decreased at the same time. On day 14 (middle phase), some depressive-like behaviors were observed, which was accompanied by depressed basal synaptic transmission and enhanced LTP induction at the CA3-CA1 synapses. However, BDNF expression was decreased without alteration of Kalirin7 expression in comparison with no-stress control. Depressed basal synaptic transmission occurred in the middle phase of CUMS may contribute to decreased expression of BDNF. On day 7, depressive-like behaviors were not observed, and LTP induction, spine density, Kalirin-7 and BDNF expression were not altered by CUMS in comparison with no-stress control. These results showed that the functional changes at CA3-CA1synapses occurred earlier than the structural alteration during three-week CUMS as a strategy of neural adaptation, and rats required three weeks to develop depressive-like behaviors during CUMS. Our results suggest an important role of Kalirin-7 in CUMS-mediated alterations in spine density, synaptic function and overall depressive-like behaviors on day 21.
Wang, Q-S; Tian, J-S; Cui, Y-L; Gao, S
Genipin, an important bioactive component from Gardenia jasminoides Eills, was demonstrated to possess antidepressant-like effects in a previous study. However, the molecular mechanism of antidepressant-like effects on genipin was not clear. The present study aimed to investigate the possible mechanism of antidepressant-like effects on genipin with a chronic unpredictable mild stress (CUMS)-induced depression model in rats. In CUMS-induced depressive rats, bodyweight and 1% sucrose consumption decreased significantly compared with the normal control group. Furthermore, these changes could be significantly reversed by genipin application. The levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE) in the hippocampus decreased and the level of 5-hydroxyindole acetic acid (5-HIAA) increased in the CUMS-induced depressive rats. However, pre-treatments with genipin significantly increased the levels of 5-HT, NE and decreased the level of 5-HIAA in the hippocampus. The concentration of cAMP in the hippocampus was increased by genipin compared to the CUMS-exposed model group. The mRNA expressions of 5-hydroxytryptamine 1A receptor (5-HT1AR), cAMP response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in rats were decreased exposed to CUMS, which were reversed by genipin-treated rats exposed to CUMS. Compared to the CUMS-exposed model group, the mRNA expression of 5-hydroxytryptamine 2A receptor (5-HT(2A)R) was decreased significantly by genipin-treated rats. The mRNA and protein expression of CREB, BDNF were increased in genipin-treated rats compared to the CUMS-exposed model group. Moreover, the levels of corticosterone in serum were decreased by genipin-treated compared to the CUMS-exposed model group. These results suggest that the possible mechanism of antidepressant-like effects on genipin, at least in one part, resulted from monoaminergic neurotransmitter system and the potential dysfunctional regulation of the post-receptor signaling
Zhang, Yi; Su, Wen-Jun; Chen, Ying; Wu, Teng-Yun; Gong, Hong; Shen, Xiao-Liang; Wang, Yun-Xia; Sun, Xue-Jun; Jiang, Chun-Lei
Emerging evidence suggests that neuroinflammation and oxidative stress may be major contributors to major depressive disorder (MDD). Patients or animal models of depression show significant increase of proinflammatory cytokine interleukin-1β (IL-1β) and oxidative stress biomarkers in the periphery or central nervous system (CNS). Recent studies show that hydrogen selectively reduces cytotoxic oxygen radicals, and hydrogen-rich saline potentially suppresses the production of several proinflammatory mediators. Since current depression medications are accompanied by a wide spectrum of side effects, novel preventative or therapeutic measures with fewer side effects might have a promising future. We investigated the effects of drinking hydrogen-rich water on the depressive-like behavior in mice and its underlying mechanisms. Our study show that hydrogen-rich water treatment prevents chronic unpredictable mild stress (CUMS) induced depressive-like behavior. CUMS induced elevation in IL-1β protein levels in the hippocampus, and the cortex was significantly attenuated after 4 weeks of feeding the mice hydrogen-rich water. Over-expression of caspase-1 (the IL-1β converting enzyme) and excessive reactive oxygen species (ROS) production in the hippocampus and prefrontal cortex (PFC) was successfully suppressed by hydrogen-rich water treatment. Our data suggest that the beneficial effects of hydrogen-rich water on depressive-like behavior may be mediated by suppression of the inflammasome activation resulting in attenuated protein IL-1β and ROS production.
Deng, Xue-Yang; Li, Hong-Yan; Chen, Jun-Jun; Li, Rui-Peng; Qu, Rong; Fu, Qiang; Ma, Shi-Ping
Thymol, a bioactive monoterpene isolated from Thymus vulgaris, has displayed inspiring neuroprotective properties. The present study was designed to evaluate the antidepressant-like effects of thymol on a chronic unpredictable mild stress (CUMS) model of depression in mice and explore the underlying mechanisms. It was observed that thymol treatment (15 mg/kg and 30 mg/kg) significantly reversed the decrease of sucrose consumption, the loss of body weight, the reduction of immobile time in the tail suspension tests (TST) and forced swimming tests (FST) induced by CUMS paradigm. The levels of norepinephrine (NE) and serotonin (5-HT) in the hippocampus decreased in the CUMS-treated mice. Chronic treatments with thymol significantly restored the CUMS-induced alterations of monoamine neurotransmitters in the hippocampus. Our results further demonstrated that thymol administration negatively regulated the induction of proinflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in CUMS mice. Furthermore, thymol inhibited the activation of nod-like receptor protein 3 (NLRP3) inflammasome and its adaptor, and subsequently decreased the expression of caspase-1. In sum, our findings suggested that thymol played a potential antidepressant role in CUMS mice model through up-regulating the levels of central neurotransmitters and inhibiting the expressions of proinflammatory cytokines, which might provide potential for thymol in the light of opening up new therapeutic avenues for depression.
Qin, Tingting; Fang, Fang; Song, Meiting; Li, Ruipeng; Ma, Zhanqiang; Ma, Shiping
There is increasing evidence that major depressive disorder (MDD) is also a progressive neurodegeneration disorder and neuronal damage is the major pathology of MDD. Umbelliferone, a coumarin derivative, was found in a range of plants with proved anti-oxidative, anti-inflammatory and neuroprotective effects. The primary purpose of this investigation was to evaluate whether umbelliferone could confer an antidepressant-like effect on the depressive model in rats developed by chronic unpredictable mild stress (CUMS) and explore the possible mechanism involved in its neuroprotective effects. We found that treatments with umbelliferone (15mg/kg, 30mg/kg) significantly ameliorated CUMS-induced depressive-like behaviors, such as decreased sucrose consumption, reduced locomotor activity and prolonged immobility time. Rats under CUMS stimulation treated with umbelliferone (15mg/kg, 30mg/kg) showed reduced neuronal apoptosis, as well as inhibited inflammatory cytokines levels by down-regulating Rho-associated protein kinase (ROCK) signaling and up-regulating protein kinase B (Akt) signaling. In conclusion, umbelliferone showed neuroprotective effects on CUMS-induced model of depression, which was associated with the inhibition of neuronal apoptosis modulated by ROCK/Akt pathway.
Full Text Available Background. This study was to explore the pharmacokinetics of saxagliptin (Sax in Goto–Kakizaki (GK rats complicated with depression induced by chronic unpredicted mild stress (CUMS. The comorbidity of diabetic patients with depression is becoming more and more epidemic. Whether depression mental disorder alters the pharmacokinetics of hypoglycemic drugs in diabetes patients is not clear.Methods. Five-week-old male GK rats were kept in the cage for 7 weeks in a specific pathogen free (SPF-grade lab until the emergence of diabetes and were then divided into two groups: control group and depression model group. Rats in the CUMS-induced depression group were exposed to a series of stressors for 8 weeks. Plasma serotonin and dopamine levels and behavior of open-field test were used to confirm the establishment of the depression model. All rats were given 0.5 mg/kg Sax orally after 8 weeks and blood samples were collected at different time points. The Sax concentration was assayed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS. The CYP450 activity of the liver microsomes was determined by using cocktails of probe drugs in which the activities of CYP enzymes were assessed through the determination of the production of the probe drugs.Results. Statistically significant differences in Sax pharmacokinetics were observed for area under curve, clearance, peak concentration, peak time and mean residence time between the depression rats and the control rats, while no statistical differences were observed for half-time and distribution volume by HPLC-MS/MS analysis. The CYP450 activity had different changes in the depression group.Conclusions. These results indicated that CUMS-induced depression alters the drug metabolic process of Sax and CYP450 activity of the liver microsomal enzymes in GK rats.
Yan, Hua-Cheng; Cao, Xiong; Das, Manas; Zhu, Xin-Hong; Gao, Tian-Ming
Depression is a chronic, recurring and potentially life-threatening illness that affects up to 20% of the population across the world. Despite its prevalence and considerable impact on human, little is known about its pathogenesis. One of the major reasons is the restricted availability of validated animal models due to the absence of consensus on the pathology and etiology of depression. Besides, some core symptoms such as depressed mood, feeling of worthlessness, and recurring thoughts of death or suicide, are impossible to be modeled on laboratory animals. Currently, the criteria for identifying animal models of depression rely on either of the 2 principles: actions of known antidepressants and responses to stress. This review mainly focuses on the most widely used animal models of depression, including learned helplessness, chronic mild stress, and social defeat paradigms. Also, the behavioral tests for screening antidepressants, such as forced swimming test and tail suspension test, are also discussed. The advantages and major drawbacks of each model are evaluated. In prospective, new techniques that will be beneficial for developing novel animal models or detecting depression are discussed.
Kurhe, Yeshwant; Mahesh, Radhakrishnan
Pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ) agonist belonging to thiazolidinedione class, is mainly used in diabetes mellitus. Obese subjects are twice likely to become depressed than non-obese individuals. The biological mechanisms linking depression with obesity still remain poorly understood and there is immense need for better therapeutic intervention against such co-morbid disorders. The present study investigates the effect of pioglitazone on the chronic unpredictable mild stress (CUMS) induced depression in obese mice by using behavioral tests and biochemical estimations. Mice were fed with high fat diet (HFD) for 14 weeks and were further subjected to different stress procedures for 28 days to induce depressive behavior. Animals were administered orally with pioglitazone (30 mg/kg p.o.)/escitalopram (10 mg/kg p.o.)/vehicle (10 ml/kg p.o.) daily from day 15-28. Various behavioral paradigms such as sucrose preference test, forced swim test (FST), tail suspension test (TST) and elevated plus maze (EPM) were performed. Biochemical estimations including plasma glucose, total cholesterol, triglycerides, and total proteins were performed. The data obtained from behavioral assays and biochemical assessments indicated that obese animals exhibited severe depressive-like behavior compared to non-obese animals. Furthermore, obese animals subjected to CUMS worsen the depressive behavior compared to obese control animals. Repetitive treatment with pioglitazone reversed the CUMS induced behavioral and biochemical alterations in HFD fed obese mice which atleast in part may be mediated through improving altered plasma glucose. The study suggests that pioglitazone needs further attention with respect to molecular mechanisms that could provide a better therapeutic strategy against depression associated with obesity.
Full Text Available Pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ agonist belonging to thiazolidinedione class, is mainly used in diabetes mellitus. Obese subjects are twice likely to become depressed than non-obese individuals. The biological mechanisms linking depression with obesity still remain poorly understood and there is immense need for better therapeutic intervention against such co-morbid disorders. The present study investigates the effect of pioglitazone on the chronic unpredictable mild stress (CUMS induced depression in obese mice by using behavioral tests and biochemical estimations. Mice were fed with high fat diet (HFD for 14 weeks and were further subjected to different stress procedures for 28 days to induce depressive behavior. Animals were administered orally with pioglitazone (30 mg/kg p.o./escitalopram (10 mg/kg p.o./vehicle (10 ml/kg p.o. daily from day 15–28. Various behavioral paradigms such as sucrose preference test, forced swim test (FST, tail suspension test (TST and elevated plus maze (EPM were performed. Biochemical estimations including plasma glucose, total cholesterol, triglycerides, and total proteins were performed. The data obtained from behavioral assays and biochemical assessments indicated that obese animals exhibited severe depressive-like behavior compared to non-obese animals. Furthermore, obese animals subjected to CUMS worsen the depressive behavior compared to obese control animals. Repetitive treatment with pioglitazone reversed the CUMS induced behavioral and biochemical alterations in HFD fed obese mice which atleast in part may be mediated through improving altered plasma glucose. The study suggests that pioglitazone needs further attention with respect to molecular mechanisms that could provide a better therapeutic strategy against depression associated with obesity.
Kato, T; Kasahara, T; Kubota-Sakashita, M; Kato, T M; Nakajima, K
Animal models of mental disorders should ideally have construct, face, and predictive validity, but current animal models do not always satisfy these validity criteria. Additionally, animal models of depression rely mainly on stress-induced behavioral changes. These stress-induced models have limited validity, because stress is not a risk factor specific to depression, and the models do not recapitulate the recurrent and spontaneous nature of depressive episodes. Although animal models exhibiting recurrent depressive episodes or bipolar depression have not yet been established, several researchers are trying to generate such animals by modeling clinical risk factors as well as by manipulating a specific neural circuit using emerging techniques.
Lu, Jun; Shao, Run-Hui; Hu, Li; Tu, Ya; Guo, Jian-You
Accumulating evidence indicates that inflammation may contribute to the pathophysiology of depression. Acupuncture in traditional Chinese medicine has been considered an effective treatment for depression. However, whether the mechanisms that underlie the antidepressant effect of acupuncture are related to its antiinflammatory properties remains unclear. In the present study, rats were exposed to chronic unpredictable mild stress (CUMS) for 28 days to induce depressive-like behavior. Body weight, sucrose preference, and locomotor activity in the open field were measured. After the behavioral tests, reverse transcription polymerase chain reaction was used to determine the mRNA expression of proinflammatory cytokines (interleukin-1β [IL-1β], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]), and enzyme-linked immunosorbent assay was used to detect cytokine concentrations. CUMS rats exhibited decrease in body weight, sucrose preference, and locomotor activity in the open field test. Chronic acupuncture and fluoxetine treatment reversed CUMS-induced depressive-like behavior. Compared with control rats, the mRNA and protein expression of IL-1β, IL-6, and TNF-α in the hippocampus and prefrontal cortex and cytokine concentrations in serum significantly increased in CUMS rats. Acupuncture and fluoxetine treatment significantly decreased the levels of proinflammatory cytokines in the hippocampus, prefrontal cortex, and serum. These results suggest that acupuncture has antidepressant-like effects, and its mechanism of action appears to involve the inhibition of proinflammatory cytokines.
Garcia-Toro, Mauro; Aguirre, Iratxe
There are two fundamental etiological perspectives about mental disorders; biomedical and psychosocial. The biopsychosocial model has claimed to integrate these two perspectives in a scientific way, signalling their interconnection and interdependence. To that end, it used a systemic conceptual framework, taking advantage of the possibilities which it offers to establish general principles for diverse systems, independently of their physical, biological or sociological nature. In recent years, drawing on the theory of systems, theories have been developing of the dynamic non-linear systems, applicable to networks of a large quantity of densely interconnected elements (also called complex systems), like the mind or the brain. We believe that this revised systemic conceptual framework can bring integrative ideas to apply to Depression, such as the "binding dysfunction" concept we use in this article. According to this, vulnerability or predisposition to Depression would be associated with the imbalance between activating and inhibiting interactions (between some cognitions and emotions at a mental level, and between certain neuronal groups at a cerebral level). Precipitating factors would imply the increase of the activation level over this pattern of cognitions and emotions, or over those neuronal systems. When stress goes beyond the vulnerability threshold an excessive positive feedback between cognitions and emotions would appear (and between groups of neurons) with insufficient inhibitory control to mitigate it, which would imply a mental/cerebral dissociation in dominions of different level of activation. As a consequence, the generation and dissolution of patterns of cerebral and mental activation will no longer have the dynamism and flexibility that permits an optimal interaction with the environment ("binding dysfunction"). Therefore, our hypothesis is that the person with Depression will suffer at a cerebral level a functional dissociation in neural
Sadule-Rios, Nohemi; Tappen, Ruth; Williams, Christine L; Rosselli, Monica
Cultural variations in the perception of depression make it difficult to recognize the disorder resulting in older Hispanics not being diagnosed and not receiving appropriate treatment. This study used a mixed-method design to explore older Hispanics' explanatory model of depression. Depression was recognized as the result of life stressors and personal weaknesses. Terms used for depressed people included "crazy, worry, bored, and nerves." These culturally coded terms may confound diagnosis among many Hispanics who find depression a shameful condition. Findings can be used to inform the adaptation of culturally relevant approaches to better serve the Hispanic community in this country.
Madhu Devi* and Ramica Sharma
Full Text Available As described by the world health organization (WHO, depression is the most common and serious disorder leading to suicide. Numbers of synthetic drugs are available for the treatment of this fatal disease, but are associated with serious complications. A wide diversity of animal models has been used to examine antidepressant activity. These range from relatively simple models sensitive to acute treatment, to highly sophisticated models. The number of validated animal models for affective disorders is large and still growing. A basic understanding of the underlying disease processes in depression is lacking, and therefore, recreating the disease in animal models is not possible. For the animal model of depression, the relevance, reliability and reproducibility in laboratories need to be focused, currently used models of depression attempt to produce quantifiable correlates of human symptoms in experimental animals and the animal modeling remains a potentially important approach towards understanding neurochemical and neurobiological mechanisms in depression. Animal models of depression attempt to represent some aspect of the etiology, symptomatology and treatment of the disorders, in order to facilitate their scientific study. Hence, this review deals with animal models that are beneficial for evaluating the potential of antidepressants. The present review further discusses the ability of currently available animal models for depression to investigate the novel hypothesis.
Huiying Tan Wei Zou Jiamei Jiang Ying Tian Zhifang Xiao Lili Bi Haiying Zeng Xiaoqing Tang
.... Excessive and prolonged endoplasmic reticulum （ER） stress triggers cell death. Hydrogen sulfide （H2S）, the third endogenous signaling gasotransmitter, plays an import- ant role in brain functions as a neuromodulator and a neuroprotectant...
Mohsen Tahmasebi Nasab
Full Text Available Modeling hydrologic processes for depression-dominated areas such as the North American Prairie Pothole Region is complex and reliant on a clear understanding of dynamic filling-spilling-merging-splitting processes of numerous depressions over the surface. Puddles are spatially distributed over a watershed and their sizes, storages, and interactions vary over time. However, most hydrologic models fail to account for these dynamic processes. Like other traditional methods, depressions are filled as a required preprocessing step in the Soil and Water Assessment Tool (SWAT. The objective of this study was to facilitate hydrologic modeling for depression-dominated areas by coupling SWAT with a Puddle Delineation (PD algorithm. In the coupled PD-SWAT model, the PD algorithm was utilized to quantify topographic details, including the characteristics, distribution, and hierarchical relationships of depressions, which were incorporated into SWAT at the hydrologic response unit (HRU scale. The new PD-SWAT model was tested for a large watershed in North Dakota under real precipitation events. In addition, hydrologic modeling of a small watershed was conducted under two extreme high and low synthetic precipitation conditions. In particular, the PD-SWAT was compared against the regular SWAT based on depressionless DEMs. The impact of depressions on the hydrologic modeling of the large and small watersheds was evaluated. The simulation results for the large watershed indicated that SWAT systematically overestimated the outlet discharge, which can be attributed to the failure to account for the hydrologic effects of depressions. It was found from the PD-SWAT modeling results that at the HRU scale surface runoff initiation was significantly delayed due to the threshold control of depressions. Under the high precipitation scenario, depressions increased the surface runoff peak. However, the low precipitation scenario could not fully fill depressions to reach
Full Text Available Depression is a type of complex psychiatric disorder with long-term, recurrent bouts, and its etiology remains largely unknown. Here, an integrated approach utilizing (1H NMR and UPLC-Q-TOF/MS together was firstly used for a comprehensive urinary metabonomics study on chronic unpredictable mild stress (CUMS treated rats. More than twenty-nine metabolic pathways were disturbed after CUMS treatment and thirty-six potential biomarkers were identified by using two complementary analytical technologies. Among the identified biomarkers, nineteen (10, 11, 16, 17, 21-25, and 27-36 were firstly reported as potential biomarkers of CUMS-induced depression. Obviously, this paper presented a comprehensive map of the metabolic pathways perturbed by CUMS and expanded on the multitude of potential biomarkers that have been previously reported in the CUMS model. Four metabolic pathways, including valine, leucine and isoleucine biosynthesis; phenylalanine, tyrosine and tryptophan biosynthesis; tryptophan metabolism; synthesis and degradation of ketone bodies had the deepest influence in the pathophysiologic process of depression. Fifteen potential biomarkers (1-2, 4-6, 15, 18, 20-23, 27, 32, 35-36 involved in the above four metabolic pathways might become the screening criteria in clinical diagnosis and predict the development of depression. Moreover, the results of Western blot analysis of aromatic L-amino acid decarboxylase (DDC and indoleamine 2, 3-dioxygenase (IDO in the hippocampus of CUMS-treated rats indicated that depletion of 5-HT and tryptophan, production of 5-MT and altered expression of DDC and IDO together played a key role in the initiation and progression of depression. In addition, none of the potential biomarkers were detected by NMR and LC-MS simultaneously which indicated the complementary of the two kinds of detection technologies. Therefore, the integration of (1H NMR and UPLC-Q-TOF/MS in metabonomics study provided an approach to identify
Madhu Devi* and Ramica Sharma
As described by the world health organization (WHO), depression is the most common and serious disorder leading to suicide. Numbers of synthetic drugs are available for the treatment of this fatal disease, but are associated with serious complications. A wide diversity of animal models has been used to examine antidepressant activity. These range from relatively simple models sensitive to acute treatment, to highly sophisticated models. The number of validated animal models for affective diso...
Patten, S B
The aetiology of depression is not fully understood, which allows many different perspectives on aetiology to be adopted. Researchers and clinicians may be attracted to concepts of aetiology that parallel other diagnoses with which they are familiar. Such parallels may assume the role of informal models or metaphors for depressive disorders. They may even function as informal scientific theories of aetiology, energising research activities by guiding hypothesis generation and organising new knowledge. Parallels between different types of disease may ultimately prove valuable as frameworks supporting the emergence and maturation of new knowledge. However, such models may be counterproductive if their basis, which is likely to lay at least partially in analogy, is unacknowledged or overlooked. This could cause such models to appear more compelling than they really are. Listing examples of situations in which models of depression may arise from, or be strengthened by, parallels to other familiar conditions may increase the accessibility of such models either to criticism or support. However, such a list has not yet appeared in the literature. The present paper was written with the modest goal of stating several examples of models or metaphors for depression. This paper adopted narrative review methods. The intention was not to produce a comprehensive list of such ideas, but rather to identify prominent examples of ways of thinking about depression that may have been invigorated as a result parallels with other types of disease. Eight possible models are identified: depressive disorders as chemical imbalances (e.g., a presumed or theoretical imbalance of normally balanced neurotransmission in the brain), degenerative conditions (e.g., a brain disease characterised by atrophy of specified brain structures), toxicological syndromes (a result of exposure to a noxious psychological environment), injuries (e.g., externally induced brain damage related to stress), deficiency
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Ottesen, Johnny T.
Depression is a very common disease. Approximately 10% of people in the Western world experience severe depression during their lifetime and many more experience a mild form of depression. It is commonly believed that depression is caused by malfunctions in the biological system constituted...
Koolhaas, J.M.; Meerlo, P.; De Boer, S..; Strubbe, J.H.; Bohus, B.
Our current understanding of the physiological mechanisms underlying depressive disorders is not only based on behavioral, neuroendocrine and pharmacological studies in depressed humans, but also on experimental studies in a wide variety of animal models of depression. Ideally, the two approaches sh
Au, Raymond C. P.; Watkins, David; Hattie, John; Alexander, Patricia
This review explores developments in the construct of learned hopelessness, which originated in the clinical literature dealing with depression. In that context, the model developed by Abramson, Metalsky, and Alloy [Abramson, L. Y., Metalsky, G. I., & Alloy, L. B. (1989). "Hopelessness depression: A theory-based subtype of depression."…
Piven, Mary Lynn; Anderson, Ruth A.; Colón-Emeric, Cathleen S.; Sandelowski, Margarete
In this study, we explored how Certified Nursing Assistants (CNAs) understood resident depression. Interviews with 18 CNAs, working in two nursing homes were guided by Kleinman’s Explanatory Models of Illness framework. Interview data were content analyzed and CNAs’ descriptions of depression were compared to the MDS 2.0 Mood Screen and to DSM-IV-TR Depression Criteria. CNAs identified causes, signs, and symptoms of depression, but they were unsure about the duration and normalcy of depressio...
Nguyen, Michael; Stewart, Adam Michael; Kalueff, Allan V
Depression is a serious psychiatric condition affecting millions of patients worldwide. Unipolar depression is characterized by low mood, anhedonia, social withdrawal and other severely debilitating psychiatric symptoms. Bipolar disorder manifests in alternating depressed mood and 'hyperactive' manic/hypomanic states. Animal experimental models are an invaluable tool for research into the pathogenesis of bipolar/unipolar depression, and for the development of potential treatments. Due to their high throughput value, genetic tractability, low cost and quick reproductive cycle, zebrafish (Danio rerio) have emerged as a promising new model species for studying brain disorders. Here, we discuss the developing utility of zebrafish for studying depression disorders, and outline future areas of research in this field. We argue that zebrafish represent a useful model organism for studying depression and its behavioral, genetic and physiological mechanisms, as well as for anti-depressant drug discovery.
Hollis, Fiona; Kabbaj, Mohamed
Depression is one of the most disabling medical conditions in the world today, yet its etiologies remain unclear and current treatments are not wholly effective. Animal models are a powerful tool to investigate possible causes and treatments for human diseases. We describe an animal model of social defeat as a possible model for human depression. We discuss the paradigm, behavioral correlates to depression, and potential underlying neurobiological mechanisms with an eye toward possible future therapies.
Jiang, Ning; Fan, Lin-Xi; Yang, Yu-Jie; Liu, Xin-Min; Lin, Hai-Ying; Gao, Li; Wang, Qiong
To investigate whether the extract of Dendrobium nobile Lindl (DNL) has an antidepressant effect on chronic unpredictable mild stress (CUMS)-induced depressive mice, 72 BALB/c male mice were randomly divided into the control group, the CUMS model group, the extract of DNL groups (50, 100 and 200 mg/kg DNL, i.g.) and the paroxetine group (10 mg/kg, i.g.). The different doses of DNL or the paroxetine was administered orally once daily to CUMS mice for 8 weeks (containing two-week preventive medication before the modeling). The same volume of distilled water was given to the control group and the CUMS group. Except for the control group, the other mice were exposed to chronic stress for 35 days. Behavioral tests were performed by using the sucrose preference test (SPT), the novelty-suppressed feeding (NSF) test, the tail suspension test (TST), and the forced swim test (FST). The levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) were measured by the liquid chromatography-mass spectrometer (LC-MS)/MS. Compared with the control group, obvious behavioral changes were observed in the CUMS group after 5-week CUMS, including a decrease in the sucrose consumption, an increase in the latency to feeding in the NSF test and a prolongation of the immobility time in the TST. Compared with the CUMS group, the application of DNL resulted in a dose-dependent increase in sucrose consumption (P 0.05). In addition, in the hippocampus and cortex, the levels of 5-HT and DA were significantly decreased in the CUMS group compared with the control group (P < 0.05). In comparison with the CUMS group, paroxetine obviously increased the DA levels in the hippocampus and the cortex and the 5-HT level in the hippocampus (P < 0.05). DNL (50 and 200 mg/kg) significantly increased the DA level in cerebral cortex of the brain, and DNL (100 and 200 mg/kg) increased the DA level in the hippocampus. The 5-HT level in the 200 mg/kg DNL group was notably increased in both two brain regions (P < 0
Ottesen, Johnny T.
Depression is a very common disease. Approximately 10% of people in the Western world experience severe depression during their lifetime and many more experience a mild form of depression. It is commonly believed that depression is caused by malfunctions in the biological system constituted...... diagnoses more precise and to offer individual treatment plans and drug design. Efficient and reliable methods for parameter estimation are crucial. Presently we are investigating how well the Metropolis-Hastings Algorithm of the Bayesian Markov Chain Monte Carlo (MCMC) method for estimating the parameters...
K. M. Fassieh
Full Text Available Toshka Depression (TD, located about 250 km south west of the High Aswan Dam (HAD, consists of four deep-cut basins connected by natural sills. It is required to assess the contribution of TD as a spillway, in enhancing the effectiveness of Lake Nasser in flood control and water availability. However, most related previous works are descriptive and use qualitative methods. In order to provide the required assessment quantitatively, we developed a numerical model which computes TD mass balance and interbasin water movements. The model computes the variation of water volume, surface area, and water level in each one of the four basins (subdepressions, thus depicting their filling sequence, for the past 130 years. This TD response to realistic time series of water inflow gains and evaporation losses is analyzed to compute the TD overflow time series. This response helps assess water availability for agricultural use and effectiveness in alleviating flood risks. Furthermore, the developed model compares between three TD configurations to help the decision maker and recommends (i building a dam—height 10 m—at the end of the fourth subdepression near Kharga Oasis and/or (ii incorporating the third subdepression into TD by digging a canal through the hill that blocks it from the first subdepression.
Tang, Ming-Ming; Lin, Wen-Juan; Pan, Yu-Qin; Guan, Xi-Ting; Li, Ying-Cong
Our previous work found that triple central lipopolysaccharide (LPS) administration could induce depressive-like behaviors and increased central pro-inflammatory cytokines mRNA, hippocampal cytokine mRNA in particular. Since several neuroinflammation-associated conditions have been reported to impair neurogenesis, in this study, we further investigated whether the neuroinflammation induced depression would be associated with hippocampal neurogenesis dysfunction. An animal model of depression induced by triple central lipopolysaccharide (LPS) administration was used. In the hippocampus, the neuroinflammatory state evoked by LPS was marked by an increased production of pro-inflammatory cytokines, including interleukin-1β, interleukin-6, and tumor necrosis factor-α. It was found that rats in the neuroinflammatory state exhibited depressive-like behaviors, including reduced saccharin preference and locomotor activity as well as increased immobility time in the tail suspension test and latency to feed in the novelty suppressed feeding test. Adult hippocampal neurogenesis was concomitantly inhibited, including decreased cell proliferation and newborn cell survival. We also demonstrated that the decreased hippocampal neurogenesis in cell proliferation was significantly correlated with the depressive-like phenotypes of decreased saccharine preference and distance travelled, the core and characteristic symptoms of depression, under neuro inflammation state. These findings provide the first evidence that hippocampal neurogenesis dysfunction is correlated with neuroinflammation-induced depression, which suggests that hippocampal neurogenesis might be one of biological mechanisms underlying depression induced by neruoinflammation.
... overview URL of this page: //medlineplus.gov/ency/article/003213.htm Depression - overview To use the sharing features on this ... older adults Major depression Persistent depressive disorder Postpartum depression Premenstrual ... Review Date 1/4/2016 Updated by: Timothy Rogge, ...
Skoven, Christian; Sickman, Helle M.; Bastlund, Jesper Frank
Major depression is one of the most frequently occurring mental health disorders, but is characterized by diverse symptomatology. Sleep disturbances, however, are commonplace in depressive patients. These alterations include increased duration of Rapid Eye Movement Sleep (REMS) and increased sleep...... fragmentation. Stressful life events during the second trimester of human pregnancy increase the risk of depression in the offspring. Similarly, rodents exposed to prenatal stress (PNS) during gestation express depression- like behavioral changes. Accordingly, we investigated sleep changes in a rat PNS model...... of depression, to elucidate whether these are similar to those seen in clinical depression. Pregnant Sprague-Dawley rats were submitted to repeated variable stress during gestational days 13-21. The young adult offspring were surgically implanted with electrodes for subsequent electroencephalographic...
Klein, Daniel N.; Kotov, Roman; Bufferd, Sara J.
Understanding the association between personality and depression has implications for elucidating etiology and comorbidity, identifying at-risk individuals, and tailoring treatment. We discuss seven major models that have been proposed to explain the relation between personality and depression, and we review key methodological issues, including study design, the heterogeneity of mood disorders, and the assessment of personality. We then selectively review the extensive empirical literature on the role of personality traits in depression in adults and children. Current evidence suggests that depression is linked to traits such as neuroticism/negative emotionality, extraversion/positive emotionality, and conscientiousness. Moreover, personality characteristics appear to contribute to the onset and course of depression through a variety of pathways. Implications for prevention and prediction of treatment response are discussed, as well as specific considerations to guide future research on the relation between personality and depression. PMID:21166535
Wang, Jing; Zhou, Qi-Xin; Lv, Long-Bao; Xu, Lin; Yang, Yue-Xiong
Depression is a common neuropsychiatric disorder, marked by depressed mood for at least two weeks. The World Health Organization predicts that depression will be the number one leading cause of disease and injury burden by 2030. Clinical treatment faces at least three serious obstacles. First, the disease mechanism is not fully understood and thus there are no effective ways to predict and prevent depression and no biological method of diagnosis. Second, available antidepressants are based on monoamine mechanisms that commonly have a long delay of action and possibly cause a higher risk of suicide. Third, no other antidepressant mechanisms are available, with fast action and few side effects. Unfortunately, several decades of research based on rodent models of depression have not been successful in resolving these problems, at least partially due to the huge differences in brain function between rodents and people. Tree shrews are the closest sister to primates, and brain functions in these species are closer to those of humans. In this review, we discuss a tree shrew model of depression with social defeat etiology and aspects of construct, face and predicted validity of an animal model. Although a tree shrew model of depression has long been ignored and not fully established, its similarities to those aspects of depression in humans may open a new avenue to address this human condition.
In two randomized controlled studies it has been shown that Mindfulness-Based Cognitive Therapy (MBCT) has significantly decreased the relapse rate of depression. At the Unit for Studies of Integrative Health Care, Division of Nursing, Karolinska Institutet, a research study is taking place about mindfulness and its applicability for postpartum depression in Vietnam. This paper presents a second qualitative content analysis of interviews that were part of a pre-study where the aim was to map ...
Maria G. Puiu
Full Text Available Introduction: Major depressive disorder is one of the most prevalent psychiatric disorders and is associated with a severe impact on the personal functioning, thus with incurring significant direct and indirect costs. The presence of depression in patients with medical comorbidities increases the risks of myocardial infarction and decreases diabetes control, and adherence to treatment. The mechanism through which these effects are produced is still uncertain. Objectives of this study were to evaluate the metabolic alterations in female Wistar rats with induced depression, with and without administration of Agomelatine. The methods included two experiments. All data were analyzed by comparison with group I (control, and with each other. In the first experiment we induced depression by: exposure to chronic mild stress-group II; olfactory bulbectomy-group III; and exposure to chronic mild stress and hyperlipidic/ hyper caloric dietgroup IV. The second experiment was similar with the first but the rats received Agomelatine (0.16mg/ animal: group V (depression induced through exposure to chronic mild stress, VI (depression induced through olfactory bulbectomy and VII (depression induced through exposure to chronic mild stressing hyperlipidic/ hypercaloric diet. Weight, cholesterol, triglycerides and glycaemia were measured at day 0 and 28, and leptin value was measured at day 28. The results in the 1st experiment revealed significant differences (p<0.01 for weight and cholesterol in Group IV, for triglycerides in groups III and IV (p<0.001, and for glycaemia in group II. The 2nd experiment revealed significant differences (p<0.001 in group VII for weight and triglycerides, and in groups V and VI for triglycerides (p<0.01. In conclusion, significant correlations were found between high level of triglycerides and depression induced by chronic stress and olfactory bulbectomy. Agomelatine groups had a lower increase of triglycerides levels.
Pan, Ying; Chen, Xu-Yang; Zhang, Qing-Yu; Kong, Ling-Dong
Depression is an inflammatory disorder. Pro-inflammatory cytokine interleukin-1 beta (IL-1β) may play a pivotal role in the central nervous system (CNS) inflammation of depression. Here, we investigated IL-1β alteration in serum, cerebrospinal fluid (CSF) and prefrontal cortex (PFC) of chronic unpredictable mild stress (CUMS)-exposed rats, a well-documented model of depression, and further explored the molecular mechanism by which CUMS procedure induced IL-1β-related CNS inflammation. We showed that 12-week CUMS procedure remarkably increased PFC IL-1β mRNA and protein levels in depressive-like behavior of rats, without significant alteration of serum and CSF IL-1β levels. We found that CUMS procedure significantly caused PFC nuclear factor kappa B (NF-κB) inflammatory pathway activation in rats. The intriguing finding in this study was the induced activation of nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome with the increased IL-1β maturation in PFC of CUMS rats, suggesting a new grade of regulatory mechanism for IL-1β-related CNS inflammation. Moreover, microglial activation and astrocytic function impairment were observed in PFC of CUMS rats. The increased co-location of NLRP3 and ionized calcium binding adaptor molecule 1 (Iba1) protein expression supported that microglia in glial cells was the primary contributor for CUMS-induced PFC NLRP3 inflammasome activation in rats. These alterations in CUMS rats were restored by chronic treatment of the antidepressant fluoxetine, indicating that fluoxetine-mediated rat PFC IL-1β reduction involves both transcriptional and post-transcriptional regulatory mechanisms. These findings provide in vivo evidence that microglial NLRP3 inflammasome activation is a mediator of IL-1β-related CNS inflammation during chronic stress, and suggest a new therapeutic target for the prevention and treatment of depression.
Kessing, Lars Veddel; Bukh, Jens Otto Drachmann
The prevalence of depression is not clearly established, but estimated to 3-4% in a Danish questionnaire study. Lifetime's prevalences of 12-17% are reported in other community samples. In the current diagnostic system depression is defined categorically and operationally. It has been argued......, that these diagnostic criteria represent an oversimplification, which has blurred the concept of depression. We suggest a greater emphasis on the depressed mood as the core symptom of depression, which may increase the specificity of the diagnosis. Furthermore, basic principles for the treatment of depression...
Kessing, Lars Veddel; Bukh, Jens Drachmann
, that these diagnostic criteria represent an oversimplification, which has blurred the concept of depression. We suggest a greater emphasis on the depressed mood as the core symptom of depression, which may increase the specificity of the diagnosis. Furthermore, basic principles for the treatment of depression......The prevalence of depression is not clearly established, but estimated to 3-4% in a Danish questionnaire study. Lifetime's prevalences of 12-17% are reported in other community samples. In the current diagnostic system depression is defined categorically and operationally. It has been argued...
... judgment and mental functioning nausea and vomiting memory loss (depressants can cause users to have no memory of events that happened while they were under the influence) Long-Term Effects When people misuse depressants over a long ...
Xu Zhao, MD
Conclusions: Within certain dose ranges, xanthone derivatives 1101 and 1105 have similar effects to venlafaxine hydrochloride in the treatment of depression as suggested by behavioral despair animal models using rats and mice.
A new approach, namely, "defining protrusion-feature with depression-parameter" is advanced, which focuses on the shortcomings of protrusion-feature alteration method; The full depression-feature model is built up, and a basic converse reasoning iterative algorithm for machining process is given.The detailed examination has been implemented on the feature-based modeling system for light industry product (QJFMS) and the converse reasoning on fixture-based machining process is achieved.
Cizza, G; Ravn, Pernille; Chrousos, G P
Existing studies of the relationship between depression and osteoporosis have been heterogeneous in their design and use of diagnostic instruments for depression, which might have contributed to the different results on the comorbidity of these two conditions. Nevertheless, these studies reveal...... a strong association between depression and osteoporosis. Endocrine factors such as depression-induced hypersecretion of corticotropin-releasing hormone and hypercortisolism, hypogonadism, growth hormone deficiency and increased concentration of circulating interleukin 6, might play a crucial role...... in the bone loss observed in subjects suffering from major depression....
Full Text Available Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS, chronic unpredictable mild stress (CUMS, and chronic social defeat stress (CSDS, have been used to recapitulate depression-like behaviors in rodents and study the underlying mechanisms. In comparison with CRS, CUMS overcomes the stress habituation and has been widely used to model depression-like behaviors. CSDS is one of the most frequently used models for depression, but it is limited to the study of male mice. Generally, chronic stress causes dendritic atrophy and spine loss in the neurons of the hippocampus and prefrontal cortex. Meanwhile, neurons of the amygdala and nucleus accumbens exhibit an increase in spine density. These alterations induced by chronic stress are often accompanied by depression-like behaviors. However, the underlying mechanisms are poorly understood. This review summarizes our current understanding of the chronic stress-induced remodeling of dendritic spines in the hippocampus, prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens and also discusses the putative underlying mechanisms.
Demic, Selver; Cheng, Sen
Major depressive disorder (MDD) is a common and costly disorder associated with considerable morbidity, disability, and risk for suicide. The disorder is clinically and etiologically heterogeneous. Despite intense research efforts, the response rates of antidepressant treatments are relatively low and the etiology and progression of MDD remain poorly understood. Here we use computational modeling to advance our understanding of MDD. First, we propose a systematic and comprehensive definition of disease states, which is based on a type of mathematical model called a finite-state machine. Second, we propose a dynamical systems model for the progression, or dynamics, of MDD. The model is abstract and combines several major factors (mechanisms) that influence the dynamics of MDD. We study under what conditions the model can account for the occurrence and recurrence of depressive episodes and how we can model the effects of antidepressant treatments and cognitive behavioral therapy within the same dynamical systems model through changing a small subset of parameters. Our computational modeling suggests several predictions about MDD. Patients who suffer from depression can be divided into two sub-populations: a high-risk sub-population that has a high risk of developing chronic depression and a low-risk sub-population, in which patients develop depression stochastically with low probability. The success of antidepressant treatment is stochastic, leading to widely different times-to-remission in otherwise identical patients. While the specific details of our model might be subjected to criticism and revisions, our approach shows the potential power of computationally modeling depression and the need for different type of quantitative data for understanding depression.
Full Text Available Major depressive disorder (MDD is a common and costly disorder associated with considerable morbidity, disability, and risk for suicide. The disorder is clinically and etiologically heterogeneous. Despite intense research efforts, the response rates of antidepressant treatments are relatively low and the etiology and progression of MDD remain poorly understood. Here we use computational modeling to advance our understanding of MDD. First, we propose a systematic and comprehensive definition of disease states, which is based on a type of mathematical model called a finite-state machine. Second, we propose a dynamical systems model for the progression, or dynamics, of MDD. The model is abstract and combines several major factors (mechanisms that influence the dynamics of MDD. We study under what conditions the model can account for the occurrence and recurrence of depressive episodes and how we can model the effects of antidepressant treatments and cognitive behavioral therapy within the same dynamical systems model through changing a small subset of parameters. Our computational modeling suggests several predictions about MDD. Patients who suffer from depression can be divided into two sub-populations: a high-risk sub-population that has a high risk of developing chronic depression and a low-risk sub-population, in which patients develop depression stochastically with low probability. The success of antidepressant treatment is stochastic, leading to widely different times-to-remission in otherwise identical patients. While the specific details of our model might be subjected to criticism and revisions, our approach shows the potential power of computationally modeling depression and the need for different type of quantitative data for understanding depression.
Daniela de Sá Calçada
Full Text Available Depression is an extremely heterogeneous disorder. Diverse molecular mechanisms have been suggested to underlie its etiology. To understand the molecular mechanisms responsible for this complex disorder, researchers have been using animal models extensively, namely mice from various genetic backgrounds and harboring distinct genetic modifications. The use of numerous mouse models has contributed to enrich our knowledge on depression. However, accumulating data also revealed that the intrinsic characteristics of each mouse strain might influence the experimental outcomes, which may justify some conflicting evidence reported in the literature. To further understand the impact of the genetic background we performed a multimodal comparative study encompassing the most relevant parameters commonly addressed in depression in three of the most widely used mouse strains: Balb/c, C57BL/6 and CD-1. Moreover, female mice were selected for this study taken into account the higher prevalence of depression in woman and the fewer animal studies using this gender. Our results show that Balb/c mice have a more pronounced anxious-like behavior than CD-1 and C57BL/6 mice, whereas C57BL/6 animals present the strongest depressive-like trait. Furthermore, C57BL/6 mice display the highest rate of proliferating cells and brain-derived neurotrophic factor expression levels in the hippocampus, while hippocampal dentate granular neurons of Balb/c mice show smaller dendritic lengths and fewer ramifications. Of notice, the expression levels of inducible nitric oxide synthase (iNos predict 39,5% of the depressive-like behavior index, which suggests a key role of hippocampal iNOS in depression.Overall, this study reveals important interstrain differences in several behavioral dimensions and molecular and cellular parameters that should be considered when preparing and analyzing experiments addressing depression using mouse models. It further contributes to the literature by
Khadrawy, Yasser A; Sawie, Hussein G; Abdel-Salam, Omar M E; Hosny, Eman N
Cannabis sativa is one of the most widely recreational drugs and its use is more prevalent among depressed patients. Some studies reported that Cannabis has antidepressant effects while others showed increased depressive symptoms in Cannabis users. Therefore, the present study aims to investigate the effect of Cannabis extract on the depressive-like rats. Twenty four rats were divided into: control, rat model of depression induced by reserpine and depressive-like rats treated with Cannabis sativa extract (10mg/kg expressed as Δ9-tetrahydrocannabinol). The depressive-like rats showed a severe decrease in motor activity as assessed by open field test (OFT). This was accompanied by a decrease in monoamine levels and a significant increase in acetylcholinesterase activity in the cortex and hippocampus. Na(+),K(+)-ATPase activity increased in the cortex and decreased in the hippocampus of rat model. In addition, a state of oxidative stress was evident in the two brain regions. This was indicated from the significant increase in the levels of lipid peroxidation and nitric oxide. No signs of improvement were observed in the behavioral and neurochemical analyses in the depressive-like rats treated with Cannabis extract. Furthermore, Cannabis extract exacerbated the lipid peroxidation in the cortex and hippocampus. According to the present findings, it could be concluded that Cannabis sativa aggravates the motor deficits and neurochemical changes induced in the cortex and hippocampus of rat model of depression. Therefore, the obtained results could explain the reported increase in the depressive symptoms and memory impairment among Cannabis users. Copyright © 2017 Elsevier B.V. All rights reserved.
There is ample evidence that depression is000 a common comorbid health issue in people with type 1 or type 2 diabetes. Reviews have also concluded that depression in diabetes is associated with higher HbA1c levels, less optimal self-care behaviours, lower quality of life, incident vascular...... complications and higher mortality rates. However, longitudinal studies into the course of depression in people with type 1 diabetes remain scarce. In this issue of Diabetologia, Kampling and colleagues (doi: 10.1007/s00125-016-4123-0 ) report the 5 year trajectories of depression in adults with newly diagnosed...... type 1 diabetes (mean age, 28 years). Their baseline results showed that shortly after the diagnosis of type 1 diabetes a major depressive episode was diagnosed in approximately 6% of participants, while 8% suffered from an anxiety disorder. The longitudinal depression data showed that, in a 5 year...
Full Text Available Rodent models are an indispensable tool for studying etiology and progress of depression. Since interrelated systems of neurotrophic factors and cytokines comprise major regulatory mechanisms controlling normal brain plasticity, impairments of these systems form the basis for development of cerebral pathologies, including mental diseases. The present review focuses on the numerous experimental rodent models of depression induced by different stress factors (exteroceptive and interoceptive during early life (including prenatal period or adulthood, giving emphasis to the data on the changes of neurotrophic factors and neuroinflammatory indices in the brain. These parameters are closely related to behavioral depression-like symptoms and impairments of neuronal plasticity and are both gender- and genotype-dependent. Stress-related changes in expression of neurotrophins and cytokines in rodent brain are region-specific. Some contradictory data reported by different groups may be a consequence of differences of stress paradigms or their realization in different laboratories. Like all experimental models, stress-induced depression-like conditions are experimental simplification of clinical depression states; however, they are suitable for understanding the involvement of neurotrophic factors and cytokines in the pathogenesis of the disease—a goal unachievable in the clinical reality. These major regulatory systems may be important targets for therapeutic measures as well as for development of drugs for treatment of depression states.
Beseler, Cheryl L; Stallones, Lorann
The role of pesticide poisoning in risk of injuries may operate through a link between pesticide-induced depressive symptoms and reduced engagement in safety behaviors. The authors conducted structural equation modeling of cross-sectional data to examine the pattern of associations between pesticide poisoning, depressive symptoms, safety knowledge, safety behaviors, and injury. Interviews of 1637 Colorado farm operators and their spouses from 964 farms were conducted during 1993-1997. Pesticide poisoning was assessed based on a history of ever having been poisoned. The Center for Epidemiologic Studies-Depression scale was used to assess depressive symptoms. Safety knowledge and safety behaviors were assessed using ten items for each latent variable. Outcomes were safety behaviors and injuries. A total of 154 injuries occurred among 1604 individuals with complete data. Pesticide poisoning, financial problems, health, and age predicted negative affect/somatic depressive symptoms with similar effect sizes; sex did not. Depression was more strongly associated with safety behavior than was safety knowledge. Two safety behaviors were significantly associated with an increased risk of injury. This study emphasizes the importance of financial problems and health on depression, and provides further evidence for the link between neurological effects of past pesticide poisoning on risk-taking behaviors and injury.
Approximately ten percent of the population suffers from a depressive illness each year. Although the economic cost is high, the cost in human suffering is immeasurable. To help educate the population about this disorder, this paper presents a definition of depression and its common manifestations. The symptoms that people often experience are…
Johansen, Jon O. J.
Nyhederne er fulde af historier om depression. Overskrifter som: ’Danskerne propper sig med lykkepiller’ eller ‘depression er stadigvæk tabu’ går tit igen i dagspressen. Men hvor er nuancerne, og hvorfor gider vi læse de samme historier igen og igen? Måske er det fordi, vores egne forestillinger er...
Łakuta, Patryk; Marcinkiewicz, Kamil; Bergler-Czop, Beata; Brzezińska-Wcisło, Ligia
This study examined the relationship between psoriasis and depression, proposing a multiple mediation model to analyse the relationship. A total of 193 patients with psoriasis aged 20-67 years completed the Beck Depression Inventory, the Stigmatization Scale, the Appearance Schemas Inventory-Revised, and the Body Emotions Scale. The Body Surface Area index was used to assess severity of psoriasis. Serial multiple mediation analysis revealed that experiences of stigmatization, maladaptive beliefs about appearance and its salience to one's self-evaluation, and negative emotional attitudes towards the body, jointly, sequentially mediated the relationship between the presence of skin lesions of psoriasis and depressive symptoms. These results highlight the importance of the associations between stigmatization and cognitive and affective aspects of body image in relation to depression in patients with psoriasis. We suggest that prevention and intervention programs for psoriasis patients that target body image enhancement would be worthy of further research.
Buus, Niels; Johannessen, Helle; Stage, Kurt Bjerregaard
BACKGROUND: Adherence to antidepressant medication is a challenging clinical issue, which reduces treatment efficacy: 30-60% of all patients commencing treatment with antidepressants are estimated to stop taking the medication within the first 12 weeks. Patients' personal beliefs about depression...... analysed thematically with "explanatory models" as the starting point. RESULTS: Patients had ambiguous experiences of depression and antidepressants. Patients explained their illness and the medical treatment in experience-near terms. Explanations of the reasons for depression were psychosocial and biology...... and antidepressants are regarded as central influences on adherence. OBJECTIVES: The aim was to gain detailed insight into patients' personal accounts of depression and use of antidepressant medication and to relate these accounts to the patients' self-reported level of adherence. METHODS: In-depth, qualitative...
Full Text Available Angelica sinensis (AS, a traditional Chinese herbal medicine, has pharmaceutical effects on menstrual illness, cerebrovascular diseases, cardiovascular diseases, and cognitive impairments. However, until recently, few studies had explored its antidepressant effect. The current study attempts to investigate the effect of AS extracts on chronic unpredictable mild stress- (CUMS- induced depression in rats. Male SD rats were exposed to a CUMS-inducing procedure for 5 weeks, resulting in rodent depressive behaviors that included reduced sucrose consumption and lessened sucrose preference ratios in sucrose preference test, prolonged immobility times and decreased struggling time in force swim test, and decreased locomotor activity in open field test. Moreover, the expression of brain derived neurotrophic factor (BDNF and the phosphorylation of cAMP-response element binding protein (CREB and extracellular signal-regulated protein kinase (ERK 1/2 were markedly decreased in the hippocampus in depressed rats. However, chronically treating the depressed rats with AS (1 g/kg normalized their depression-related behaviors and molecular profiles. In conclusion, in the present study, we show that AS extracts exerted antidepressant effects that were mediated by the BDNF signaling pathway: in AS-treated depressed rats, the expression of the BDNF protein and the phosphorylation of its downstream targets (ERK 1/2, CREB were upregulated in the hippocampus.
... Different people have different symptoms. Some symptoms of depression include: Persistent sad, anxious, or “empty” mood Feelings of hopelessness or pessimism Feelings of guilt, worthlessness, or helplessness ...
... caring for children and aging parents, abuse, and poverty may trigger depression in some people. Medical illness – ... federal government website managed by the Office on Women’s Health in the Office of the Assistant Secretary ...
Epps, S Alisha; Weinshenker, David
Clinical evidence shows a strong, bidirectional comorbidity between depression and epilepsy that is associated with decreased quality of life and responsivity to pharmacotherapies. At present, the neurobiological underpinnings of this comorbidity remain hazy. To complicate matters, anticonvulsant drugs can cause mood disturbances, while antidepressant drugs can lower seizure threshold, making it difficult to treat patients suffering from both depression and epilepsy. Animal models have been created to untangle the mechanisms behind the relationship between these disorders and to serve as screening tools for new therapies targeted to treat both simultaneously. These animal models are based on chemical interventions (e.g. pentylenetetrazol, kainic acid, pilocarpine), electrical stimulations (e.g. kindling, electroshock), and genetic/selective breeding paradigms (e.g. genetically epilepsy-prone rats (GEPRs), genetic absence epilepsy rat from Strasbourg (GAERS), WAG/Rij rats, swim lo-active rats (SwLo)). Studies on these animal models point to some potential mechanisms that could explain epilepsy and depression comorbidity, such as various components of the dopaminergic, noradrenergic, serotonergic, and GABAergic systems, as well as key brain regions, like the amygdala and hippocampus. These models have also been used to screen possible therapies. The purpose of the present review is to highlight the importance of animal models in research on comorbid epilepsy and depression and to explore the contributions of these models to our understanding of the mechanisms and potential treatments for these disorders.
Clark and Watson's tripartite model of anxiety and depression symptoms is reinterpreted using their data. It is suggested that a parsimonious view of the factor loadings is a three-factor structure of "general psychological distress," "high positive affect," and "somatic anxiety."
Bech, P; Allerup, P; Gram, L F; Reisby, N; Rosenberg, R; Jacobsen, O; Nagy, A
The consistency of the Hamilton Depression Scale (HDS) as a measure of the severity of depressive states has been examined when the scale was used weekly during a trial when imipramine. By use of logistic models (Rasch) the consistency of the HDS has been considered across patient-variables as age, sex, plasma levels of imipramine, and diagnosis. The results showed that the original 17-item HDS was without adequate consistency, i.e. the total score of the sample of items was no one-dimensional measure of depressive states. However, a melancholia subscale of the HDS contained items the total of which can be used to compare patients quantitatively, although in some part of the analysis one of these items showed ceiling effect. It was concluded that the melancholia subscale (containing the items depressed mood, guilt, work and interests, retardation, psychic anxiety, and general somatic symptoms) can form the basis for further improvements in the field of quantitative rating scales for depressive states.
Czéh, Boldizsár; Fuchs, Eberhard; Wiborg, Ove; Simon, Mária
Major depressive disorder is a common, complex, and potentially life-threatening mental disorder that imposes a severe social and economic burden worldwide. Over the years, numerous animal models have been established to elucidate pathophysiology that underlies depression and to test novel antidepressant treatment strategies. Despite these substantial efforts, the animal models available currently are of limited utility for these purposes, probably because none of the models mimics this complex disorder fully. It is presumable that psychiatric illnesses, such as affective disorders, are related to the complexity of the human brain. Here, we summarize the animal models that are used most commonly for depression, and discuss their advantages and limitations. We discuss genetic models, including the recently developed optogenetic tools and the stress models, such as the social stress, chronic mild stress, learned helplessness, and early-life stress paradigms. Moreover, we summarize briefly the olfactory bulbectomy model, as well as models that are based on pharmacological manipulations and disruption of the circadian rhythm. Finally, we highlight common misinterpretations and often-neglected important issues in this field.
孙玉红; 任美萍; 张开莲; 刘明华; 肖顺汉
目的：观察积雪草提取物对抑郁大鼠、小鼠干预后行为学的改变。方法60只Wistar大鼠随机分为6组，每组10只，分别为对照组、模型组、氟西汀组、积雪草提取物高剂量组（成分10.08 mg+成分24.48 mg/kg），中剂量组（成分10.04 mg+成分22.24 mg/kg），低剂量组（成分10.02 mg+成分21.12 mg/kg）。采用慢性不可预知性温和应激刺激制备大鼠抑郁模型，糖水消耗量检测积雪草提取物抗抑郁效应。60只昆明小鼠，随机分为6组，分组情况同上。自主活动、强迫游泳、悬尾实验检测积雪草提取物对小鼠抑郁样行为的影响。结果积雪草提取物高、中、低剂量组能够明显增加大鼠糖水消耗量，与模型组比较(P<0.01)。积雪草提取物高、中、低剂量组能明显缩短悬尾实验和强迫游泳小鼠不动时间。结论积雪草提取物对大、小鼠抑郁样行为有一定的改善作用。%Objective To investigate the effect of the extracts of Centella asiatica(L.) Urban (ECA) on the depressive-like behavior alteration in rats and mice. Method 60 Wistar rats were randomly divided into 6 groups (10 rats each), the normal group, model group, Fluoxetine group, ECA high dose group (component 10.08 mg+component 24.48 mg/kg), ECA middle dose group (component 1 0.04 mg+component 2 2.24 mg/kg) and ECA low dose group component 1 0.02 mg+component 2 1.12 mg/kg. Chronic unpredictable mild stress (CUMS) induced depression in rats and sugar consumption to detect the antidepressant effect of ECU. 60 Kunming mice were randomly divided into six groups as above. Locomotor activity, forced swim, tail suspension test were used to detect the effect of ECA on the behavioral alteration in mice. Results Compared with model group, sugar consumption in ECA groups was significant increased (P<0.01). ECA treatments also decreased duration of immobility in the tail suspension test and forced swim. Conclusion ECA could improve the
McCarron, Robert M; Vanderlip, Erik R; Rado, Jeffrey
This issue provides a clinical overview of depression, focusing on screening, diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.
Salmeto, Amy L; Hymel, Kristen A; Carpenter, Erika C; Brilot, Ben O; Bateson, Melissa; Sufka, Kenneth J
Cognitive bias is a phenomenon that presents in clinical populations where anxious individuals tend to adopt a more pessimistic-like interpretation of ambiguous aversive stimuli whereas depressed individuals tend to adopt a less optimistic-like interpretation of ambiguous appetitive stimuli. To further validate the chick anxiety-depression model as a neuropsychiatric simulation we sought to quantify this cognitive endophenotype. Chicks exposed to an isolation stressor of 5m to induce an anxiety-like or 60 m to induce a depressive-like state were then tested in a straight alley maze to a series of morphed ambiguous appetitive (chick silhouette) to aversive (owl silhouette) cues. In non-isolated controls, runway start and goal latencies generally increased as a function of greater amounts of aversive characteristics in the cues. In chicks in the anxiety-like state, runway latencies were increased to aversive ambiguous cues, reflecting more pessimistic-like behavior. In chicks in the depression-like state, runway latencies were increased to both aversive and appetitive ambiguous cues, reflecting more pessimistic-like and less optimistic-like behavior, respectively.
Robert Charles Drugan
Full Text Available Experimental models of depression often entail exposing a rodent to a stressor and subsequently characterizing changes in learning and anhedonia, which may reflect symptoms of human depression. Importantly, not all people and not all laboratory rats exposed to stressors develop depressed behavior; these resilient individuals are the focus of our review. Herein we describe research from the learned helplessness and intermittent swim stress models of depression in which rats that were allowed to cope with the stressor appear to be behaviorally and neurochemically similar to rats that were not allowed to cope yet appeared resilient in behavioral tests. For example, rats exposed to inescapable tailshock, but do not develop learned helplessness, exhibit altered sensitivity to the behavioral effects of GABAA receptor antagonists and reduced in vitro benzodiazepine receptor ligand binding. This pattern suggested that resilience might involve activation of an endogenous benzodiazepine-like compound, possibly an allostatic modulator of the GABAA receptor like allopregnanolone. From the intermittent swim stress model, we have observed in resilient rats protection from stressor-induced glucocorticoid increases and immune activation. In order to identify the neural mediators of these correlates of resilience, non-invasive measures are needed to predict the resilient or vulnerable phenotype prior to analysis of neural endpoints. To this end, we found that ultrasonic vocalizations (USVs appear to predict the resilient phenotype in the intermittent swim stress paradigm. We propose that combining non-invasive predictive measures, such as USVs with biological endpoint measures, will facilitate future research into the neural correlates of resilience.
Bohon, Cara; Stice, Eric; Burton, Emily; Fudell, Molly; Nolen-Hoeksema, Susan
This study sought to provide a more rigorous prospective test of two cognitive vulnerability models of depression with longitudinal data from 496 adolescent girls. Results supported the cognitive vulnerability model in that stressors predicted future increases in depressive symptoms and onset of clinically significant major depression for…
Franceschelli, Anthony; Herchick, Samantha; Thelen, Connor; Papadopoulou-Daifoti, Zeta; Pitychoutis, Pothitos M
A large volume of clinical and experimental evidence documents sex differences in brain anatomy, chemistry, and function, as well as in stress and drug responses. The chronic mild stress model (CMS) is one of the most extensively investigated animal models of chronic stress. However, only a limited number of studies have been conducted in female rodents despite the markedly higher prevalence of major depression among women. Herein, we review CMS studies conducted in rats and mice of both sexes and further discuss intriguing sex-dependent behavioral and neurobiological findings. The PubMed literature search engine was used to find and collect all relevant articles analyzed in this review. Specifically, a multitermed search was performed with 'chronic mild stress', 'chronic unpredictable stress' and 'chronic variable stress' as base terms and 'sex', 'gender', 'females' and 'depression' as secondary terms in various combinations. Male and female rodents appear to be differentially affected by CMS application, depending on the behavioral, physiological, and neurobiological indices that are being measured. Importantly, the CMS paradigm, despite its limitations, has been successfully used to assess a constellation of interdisciplinary research questions in the sex differences field and has served as a 'silver bullet' in assessing the role of sex in the neurobiology of major depression.
Angelucci, F; Brenè, S; Mathé, A A
Understanding the etiology and pathogenesis schizophrenia and depression is a major challenge facing psychiatry. One hypothesis is that these disorders are secondary to a malfunction of neurotrophic factors. Inappropriate neurotrophic support during brain development could lead to structural disorganisation in which neuronal networks are established in a nonoptimal manner. Inadequate neurotrophic support in adult individuals could ultimately be an underlying mechanism leading to decreased capacity of brain to adaptive changes and increased vulnerability to neurotoxic damage. Brain-derived neurotrophic factor (BDNF) is a mediator involved in neuronal survival and plasticity of dopaminergic, cholinergic, and serotonergic neurons in the central nervous system (CNS). In this review, we summarize findings regarding altered BDNF in schizophrenia and depression and animal models, as well as the effects of antipsychotic and antidepressive treatments on the expression of BDNF.
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.
D'Ostilio, Kevin; Garraux, Gaëtan
The high prevalence of major depressive disorder in people with Parkinson's disease (PD), its negative impact on health-related quality of life and the low response rate to conventional pharmacological therapies call to seek innovative treatments. Here, we review the new approaches for treating major depressive disorder in patients with PD within the framework of the network model of depression. According to this model, major depressive disorder reflects maladaptive neuronal plasticity. Non-invasive brain stimulation (NIBS) using high frequency repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex has been proposed as a feasible and effective strategy with minimal risk. The neurobiological basis of its therapeutic effect may involve neuroplastic modifications in limbic and cognitive networks. However, the way this networks reorganize might be strongly influenced by the environment. To address this issue, we propose a combined strategy that includes NIBS together with cognitive and behavioral interventions.
Dia, David A; Harrington, Donna; Silverman, Wendy K
Anxiety and depressive disorders are the most common mental health problems for adolescents; understanding their etiology and course is necessary for developing effective prevention and treatment programs. The tripartite model of anxiety and depression was evaluated in a random, clinical sample of 185 adolescents, with an average age of 15.09 years (SD = 1.9), with 58.4% males (n = 108). Survey packets were mailed to participants (61% response rate). Two models were evaluated: (a) Model one fit adequately, however, modification indices and prior research and theory suggested adding paths between anxiety and depression. (b) Model two tested paths between anxiety and depression; this revised model fit the data well, suggesting a relationship from anxiety to depression. Further, physiological hyperarousal may be a distinct component for anxiety and negative affectivity may be a general risk factor for anxiety and depression in adolescents. The findings that different factors contribute to the cause of anxiety and depression have implications for practice.
Marshall, Grant N; Sherbourne, Cathy D; Meredith, Lisa S; Camp, Patti; Hays, Ron D
The structure of self-reported symptoms representative of the tripartite model was examined using data drawn from the Medical Outcomes Study (Tarlov et al., 1989). Participants were persons who had been diagnosed 48 months previously as suffering from either depression (N = 315) or hypertension (N = 403). Results of confirmatory factor analyses were broadly consistent with the tripartite model (L. A. Clark & Watson, 1991). Factors emerged corresponding to each of the 3 posited first-order dimensions of negative affect, positive affect, and physiologic arousal. Nonetheless, some discrepancies were found between the observed data and the hypothesized tripartite model. First, the obtained physiologic arousal factor was best viewed as reflecting nonspecific somatic distress rather than physiologic arousal. Finally, although differentiable in the strictest statistical sense, all three domains were significantly correlated (.36 to.86, absolute value). In particular, contrary to the tripartite model, positive and negative affect covaried markedly (-.81 to -.86). Findings raise issues concerning the utility of the tripartite model as a heuristic framework for enhancing understanding of individual differences in normal mood as well as mood disorders.
Needles, D J; Abramson, L Y
A model of a recovery process from depression that is compatible with the hopelessness theory of depressive onset is proposed. This model predicts that depressives who have an enhancing attributional style for positive events (i.e., make global, stable attributions for such events) will be more likely to regain hopefulness and, thereby, recover from depression, when positive events occur. This prediction was tested by following a group of depressed college students longitudinally for 6 weeks. Although neither positive events alone nor attributional style alone predicted reduction in hopelessness, depressives who both showed the enhancing attributional style for positive events and experienced more positive events showed dramatic reductions in hopelessness which were accompanied by remission of depressive symptoms. Thus, attributional style for positive events may be a factor that enables some depressives to recover when positive events occur in their lives.
Ng, Catalina S. M.; Hurry, Jane
Stress has an established association with depression. However, not all adolescents experiencing stressors become depressed and it is helpful to identify potential resilience factors. The current study tests a theoretical extension of a stress-diathesis model of depression in a Chinese context, with stress, coping, family relationships, and…
Sakr, H F; Abbas, A M; Elsamanoudy, A Z; Ghoneim, F M
Our objective was to investigate the effects of chronic unpredictable mild stress (CUMS) with or without selective serotonin reuptake inhibitor (fluoxetine) and anti-oxidant (resveratrol) on testicular functions and oxidative stress in rats. Fifty male rats were divided into 2 groups; control and CUMS. CUMS group was further subdivided into 4 subgroups administered water, fluoxetine, resveratrol and both. Sucrose intake, body weight gain, serum corticosterone, serotonin and testosterone levels, sperm count and motility, testicular malondialdehyde, superoxide dismutase (SOD), catalase, glutathione (GSH), and gene expression of steroidogenic acute-regulatory (StAR) protein and cytochrome P450 side chain cleavage (P450scc) enzyme were evaluated. CUMS decreased sucrose intake, weight gain, anti-oxidants (SOD, catalase, GSH), testosterone, serotonin, StAR and cytochrome P450scc gene expression, sperm count and motility and increased malondialdehyde and corticosterone. Fluoxetine increased malondialdehyde, sucrose intake, weight gain, serotonin and decreased anti-oxidants, StAR and cytochrome P450scc gene expression, sperm count and motility, testosterone, corticosterone in stressed rats. Administration of resveratrol increased anti-oxidants, sucrose intake, weight gain, serotonin, StAR and cytochrome P450scc gene expression, testosterone, sperm count and motility, and decreased malondialdehyde and corticosterone in stressed rats with or without fluoxetine. In conclusion, CUMS induces testicular dysfunctions and oxidative stress. While treatment of CUMS rats with fluoxetine decreases the depressive behavior, it causes further worsening of testicular dysfunctions and oxidative stress. Administration of resveratrol improves testicular dysfunctions and oxidative stress that are caused by CUMS and further worsened by fluoxetine treatment.
Full Text Available This paper develops multirelational data base for major depression costs. It lists how data are collected and stored into the fact base and dimension base. Uncertain data is described linguistically and modelled by fuzzy sets. Linguistic expressions are stored in dimension base. Models of major depression treatment costs are developed for each patient and all population. On the basis of this model and multirelational data base MD-OLAP a model for major depression treatment costs is developed.
Full Text Available BACKGROUND: The relationship between anxiety and depression in pain patients has not been clarified comprehensively. Previous research has identified a common factor in anxiety and depression, which may explain why depression and anxiety are strongly correlated. However, the specific clinical features of anxiety and depression seem to pull in opposite directions. OBJECTIVE: The purpose of this study is to develop a statistical model of depression and anxiety, based on data from pain patients using Hospital Anxiety and Depression Scale (HADS. This model should account for the positive correlation between depression and anxiety in terms of a general factor and also demonstrate a latent negative correlation between the specific factors underlying depression and anxiety. METHODS: The anxiety and depression symptoms of pain patients were evaluated using the HADS and the severity of their pain was assessed with the visual analogue scale (VAS. We developed a hierarchical model of the data using an IRT method called bifactor analysis. In addition, we tested this hierarchical model with model fit comparisons with unidimensional, bidimensional, and tridimensional models. The correlations among anxiety, depression, and pain severity were compared, based on both the bidimensional model and our hierarchical model. RESULTS: The bidimensional model analysis found that there was a large positive correlation between anxiety and depression (r = 0.638, and both scores were significantly positively correlated with pain severity. After extracting general factor of distress using bifactor analysis, the specific factors underlying anxiety and depression were weakly but significantly negatively correlated (r = -0.245 and only the general factor was significantly correlated with pain severity. Compared with the three first-order models, the bifactor hierarchical model had the best model fit. CONCLUSION: Our results support the hypothesis that apart from distress
Full Text Available BACKGROUND: The Flinders model is a validated genetic rat model of depression that exhibits a number of behavioural, neurochemical and pharmacological features consistent with those observed in human depression. PRINCIPAL FINDINGS: In this study we have used genome-wide microarray expression profiling of the hippocampus and prefrontal/frontal cortex of Flinders Depression Sensitive (FSL and control Flinders Depression Resistant (FRL lines to understand molecular basis for the differences between the two lines. We profiled two independent cohorts of Flinders animals derived from the same colony six months apart, each cohort statistically powered to allow independent as well as combined analysis. Using this approach, we were able to validate using real-time-PCR a core set of gene expression differences that showed statistical significance in each of the temporally distinct cohorts, representing consistently maintained features of the model. Small but statistically significant increases were confirmed for cholinergic (chrm2, chrna7 and serotonergic receptors (Htr1a, Htr2a in FSL rats consistent with known neurochemical changes in the model. Much larger gene changes were validated in a number of novel genes as exemplified by TMEM176A, which showed 35-fold enrichment in the cortex and 30-fold enrichment in hippocampus of FRL animals relative to FSL. CONCLUSIONS: These data provide significant insights into the molecular differences underlying the Flinders model, and have potential relevance to broader depression research.
Wang, Ying; Liu, Luofu; An, Fuli; Wang, Hongmei; Pang, Xiongqi
The Sufyan Depression is located in the northwest of Muglad Basin and is considered as a favorable exploration area by both previous studies and present oil shows. In this study, 16 wells are used or referred, the burial history model was built with new seismic, logging and well data, and the thermal maturity (Ro, %) of proved AG source rocks was predicted based on heat flow calculation and EASY %Ro modeling. The results show that the present heat flow range is 36 mW/m2˜50 mW/m2 (average 39 mW/m2) in 13 wells and 15 mW/m2˜55 mW/m2 in the whole depression. Accordingly, the geothermal gradient is 20 °C/km˜26 °C/km and 12 °C/km˜30 °C/km, respectively. The paleo-heat flow has three peaks, namely AG-3 period, lower Bentiu period and Early Paleogene, with the value decreases from the first to the last, which is corresponding to the tectonic evolution history. Corresponding to the heat flow distribution feature, the AG source rocks become mature earlier and have higher present marurity in the south area. For AG-2_down and AG-3_up source rocks that are proved to be good-excellent, most of them are mature with Ro as 0.5%-1.1%. But they can only generate plentiful oil and gas to charge reservoirs in the middle and south areas where their Ro is within 0.7%-1.1%, which is consistent with the present oil shows. Besides, the oil shows from AG-2_down reservoir in the middle area of the Sufyan Depression are believed to be contributed by the underlying AG-3_up source rock or the source rocks in the south area.
Piboon, Kanchana; Subgranon, Rarcharneeporn; Hengudomsub, Pornpat; Wongnam, Pairatana; Louise Callen, Bonnie
The purposes of this study are to develop and empirically test a theoretical model that examines the relationships between a set of predictors and depression among older adults. A biopsychosocial model was tested with 317 community dwelling older adults residing in Chon Buri Province, Thailand. A face-to-face interview was used in a cross-sectional community-based survey. A hypothesized model of depression was tested by using path analysis. It was found that the modified model fitted the data and the predictors accounted for 60% of the variance in depression. Female gender, activities of daily living, loneliness, stressful life events, and emotional-focused coping had a positive direct effect on depression. Social support and problem-focused coping had a negative direct effect on depression. Additionally, perceived stress, stressful life events, loneliness, and income had a negative indirect effect on depression through social support. Female gender, activities of daily living, and perceived stress also had a positive indirect effect on depression through emotional-focused coping. Stressful life events, perceived stress, and income had a negative indirect effect on depression through problem-focused coping. These findings contribute to a better understanding of the variables that predict depression in older adults. Thus, health care providers should consider the effects of these contributing factors on depression in the older adult person and can devise a program to prevent and promote health in older adults alleviating depression.
Yi, Zhenghui; Li, Zezhi; Yu, Shunying; Yuan, Chengmei; Hong, Wu; Wang, Zuowei; Cui, Jian; Shi, Tieliu; Fang, Yiru
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.
Jackson, Chris J; Izadikah, Zahra; Oei, Tian P S
Jackson's (2005, 2008a) hybrid model of learning identifies a number of learning mechanisms that lead to the emergence and maintenance of the balance between rationality and irrationality. We test a general hypothesis that Jackson's model will predict depressive symptoms, such that poor learning is related to depression. We draw comparisons between Jackson's model and Ellis' (2004) Rational Emotive Behavior Therapy and Theory (REBT) and thereby provide a set of testable learning mechanisms potentially underlying REBT. Results from 80 patients diagnosed with depression completed the learning styles profiler (LSP; Jackson, 2005) and two measures of depression. Results provide support for the proposed model of learning and further evidence that low rationality is a key predictor of depression. We conclude that the hybrid model of learning has the potential to explain some of the learning and cognitive processes related to the development and maintenance of irrational beliefs and depression. Copyright © 2011. Published by Elsevier B.V.
Christiansen, Sofie; Wiborg, Ove; Bouzinova, Elena
Aim: The focus of this project is to identify biomarkers related to circadian disturbances in major depressive disorder. Background: A large body of clinical data from depressed individuals showed that sleep, temperature, hormones, physiological states and moodchanges are consistent...... validated animal model of depression, the chronic mild stress model (CMS). Depression-like and control rats were killed by decapitation within 24 h. Trunk blood, brain and liver tissue were collected. The quantitative amount of plasma corticosterone and melatonin were measured using an ELISA and RIA kit...... that depression-like animals showed an abnormal circadian rhythm in the liver and in subregions of the rat brains related to depression. However, the SCN was partly protected against stress. We found an increased level of corticosteron and melatonin, in the depression-like animals as well as a shifted circadian...
Capron, Daniel W; Lamis, Dorian A; Schmidt, Norman B
Suicide is a leading cause of death among young adults and the rate of suicide has been increasing for decades. A depression distress amplification model posits that young adults with comorbid depression and anxiety have elevated suicide rates due to the intensification of their depressive symptoms by anxiety sensitivity cognitive concerns. The current study tested the effects of anxiety sensitivity subfactors as well as the depression distress amplification model in a very large sample of college students with elevated suicide risk. Participants were 721 college students who were at elevated risk of suicidality (scored>0 on the Beck Scale for Suicide Ideation). Consistent with prior work, anxiety sensitivity cognitive concerns, but not physical or social concerns, were associated with suicidal ideation. Consistent with the depression distress amplification model, in individuals high in depression, anxiety sensitivity cognitive concerns predicted elevated suicidal ideation but not among those with low depression. The results of this study corroborate the role of anxiety sensitivity cognitive concerns and the depression distress amplification model in suicidal ideation among a large potentially high-risk group of college students. The depression distress amplification model suggests a specific mechanism, anxiety sensitivity cognitive concerns, that may be responsible for increased suicide rates among those with comorbid anxiety and depression.
Love, Keisha M.; Murdock, Tamera B.
In an attempt to understand the cognitive mechanisms by which parental attachments predict depression among African American college students, the authors examined a mediational path model containing parental attachment, cognitive working models, and depression. The model demonstrated a close fit to the data, and several significant paths emerged.…
Byrne, S.; Ingersoll, A. P.
In an effort for explain the formation of the `Swiss-cheese' terrain visible on the southern residual cap of Mars (Thomas et al., Nature, 404,2000); we have developed a radiative model to follow the growth/decay of an initial depression due to sublimation/condensation of carbon dioxide. The pits making up this terrain have many distinctive features; they are shallow (~10m deep), with steep walls and flat floors and contain an interior moat that runs along the bottom of the walls. Their diameters range from a few 10's of meters to a kilometer. The model accounts for incident sunlight, emitted thermal radiation, and scattered short and long wave radiation. We have included the effects of a layer of water ice placed under the carbon dioxide at adjustable depth. The water ice layer is free to store heat during the summer (when the carbon dioxide has been removed) through subsurface diffusion of heat. Release of this heat at the end of the summer can inhibit frost formation. We have investigated many cases involving pure dry ice with constant albedo, albedo as a function of insolation, and differing albedo for fresh and residual frost (the latter has lower albedo). In most cases the initial depressions heal themselves and disappear into the surrounding terrain. Cases involving the layer of water ice provide a much closer approximation to the shape of the observed features (especially the flat bottoms). A problem arises of how much exposed water ice we can have during the summer season and still have temperatures averaged over the footprint of the Thermal Emission Spectrometer be close to the carbon dioxide sublimation temperatures. The depth to the water ice layer is a strong controlling factor of the evolution of depression shape and depth in our model. Matching this shape with observations yields important information regarding the depth to any putative water ice layer within the residual cap itself. It is known from laboratory measurements that carbon dioxide is too
Laurent, J; Ettelson, R
The ability to differentiate anxiety and depression has been a topic of discussion in the adult and youth literatures for several decades. The tripartite model of anxiety and depression proposed by L. A. Clark and D. Watson (1991) has helped focus the discussion. In the tripartite model, anxiety is characterized by elevated levels of physiological hyperarousal (PH), depression is characterized by low levels of positive affect (PA), and negative affect (NA) or generalized emotional distress is common to both. The advent of the model led to the development of measures of tripartite constructs and subsequent validity studies. The tripartite model and resultant activity concerning the model was largely devoted to adult samples. However. those interested in anxiety and depression among youth are now incorporating the tripartite model in their work. This paper examines the current influence of the tripartite model in the youth literature, especially with regard to measuring anxiety and depression.
Redfield, T. F.; Wheeler, W. H.; Often, M.
Few reconstructions of the Afar rift combine plate kinematics with analyses of the rift basin evolution. The Afar rift is a highly-extended region of continental to transitional oceanic crust lying at the junction of the Red Sea, Gulf of Aden and Ethiopian rifts. Here, we present a new Afar reconstruction taking into account plate kinematics, crustal thinning and magmatic construction. We use a regional plate reconstruction incorporating Nubia, Arabia, Somalia and Danakil to constrain the regional-scale extension and subsidence of the rift and relative movement of Danakil. The plate model is temporally and spatially well constrained at the onset of rifting (ca. 20 Ma) and from sea-floor spreading anomalies in the Red Sea (ca. 6 Ma-present) and Gulf of Aden (ca. 10 Ma-present). The Red Sea pre-rift fit is constrained by piercing points along the Red Sea margins (Sultan et al. 1993). We model the Late Oligocene to present-day evolution of the Afar crust by volume balance using a crustal model based on published topographic and depth-to-Moho interpretations as well as volume estimates of extrusive and sedimentary rocks. Errors stemming from plate boundary uncertainties are small in relation to the reconstructed volume. We partition Afar magmatism into pre-extensional and syn-extensional volumes. From thermal modeling and flexural considerations we infer that the regional-scale subsidence of the Afar depression was virtually complete by Mid Pliocene time. Our model supports the interpretation that the escarpments bounding the Afar Depression achieved nearly their present height (ca. 3 km) by the Late Miocene. Erosional considerations suggest the Late Miocene escarpments were steeper than they are today. Our model does not support the interpretation found in the paleo-anthropological literature that Late Miocene and Pliocene vertical movements were sufficiently large (ca. 2 km) to cause small fault blocks such as Hadar to migrate through climatic temperature zones
Tse, Wai S; Rochelle, Tina L; Cheung, Jacky C K
The relationship between personality, social functioning, and depression remains unclear. The present study employs structural equation modeling to examine the mediating role of social functioning between harm avoidance (HA), self-directedness (SD), and depression. A sample of 902 individuals completed a self-report questionnaire consisting of the following scales: HA and SD subscales of the Temperament and Character Inventory (TCI), Beck Depression Inventory (BDI), and Social Adaptation Self-Evaluation Scale (SASS). Structural equation modeling via analysis of moment structure was used to estimate the fit of nine related models. Results indicated that social functioning is a mediator between harm avoidance or self-directness and depression. Self-directedness was also shown to have direct effects on depression. The results support the social reinforcement theory of depression and provide a theoretical account of how the variables are related based on correlation methods. Suggestions are offered for future experimental and longitudinal research.
Ohaeri Jude U
Full Text Available Abstract Background An understanding of depressive symptomatology from the perspective of confirmatory factor analysis (CFA could facilitate valid and interpretable comparisons across cultures. The objectives of the study were: (i using the responses of a sample of Arab college students to the Beck Depression Inventory (BDI-II in CFA, to compare the "goodness of fit" indices of the original dimensional three-and two-factor first-order models, and their modifications, with the corresponding hierarchical models (i.e., higher - order and bifactor models; (ii to assess the psychometric characteristics of the BDI-II, including convergent/discriminant validity with the Hopkins Symptom Checklist (HSCL-25. Method Participants (N = 624 were Kuwaiti national college students, who completed the questionnaires in class. CFA was done by AMOS, version 16. Eleven models were compared using eight "fit" indices. Results In CFA, all the models met most "fit" criteria. While the higher-order model did not provide improved fit over the dimensional first - order factor models, the bifactor model (BFM had the best fit indices (CMNI/DF = 1.73; GFI = 0.96; RMSEA = 0.034. All regression weights of the dimensional models were significantly different from zero (P Conclusion The broadly adequate fit of the various models indicates that they have some merit and implies that the relationship between the domains of depression probably contains hierarchical and dimensional elements. The bifactor model is emerging as the best way to account for the clinical heterogeneity of depression. The psychometric characteristics of the BDI-II lend support to our CFA results.
In a six-wave longitudinal study with two cohorts (660 adolescents and 630 young adults), this study investigated the longitudinal stability of the Beck Depression Inventory II (BDI-II) using the Trait-State-Occasion (TSO) model. The results revealed that the full TSO model was the best fitting representation of the depression measured by the…
Mikrouli, Elli; Wörtwein, Gitta; Soylu, Rana
The Flinders Sensitive Line (FSL) rat is a genetic animal model of depression that displays characteristics similar to those of depressed patients including lower body weight, decreased appetite and reduced REM sleep latency. Hypothalamic neuropeptides such as orexin/hypocretin, melanin-concentra......The Flinders Sensitive Line (FSL) rat is a genetic animal model of depression that displays characteristics similar to those of depressed patients including lower body weight, decreased appetite and reduced REM sleep latency. Hypothalamic neuropeptides such as orexin/hypocretin, melanin...
Full Text Available Abstract Background Obesity and depression are two major diseases which are associated with many other health problems such as hypertension, dyslipidemia, diabetes mellitus, coronary heart disease, stroke, myocardial infarction, heart failure in patients with systolic hypertension, low bone mineral density and increased mortality. Both diseases share common health complications but there are inconsistent findings concerning the relationship between obesity and depression. In this work we used the structural equation modeling (SEM technique to examine the relation between body mass index (BMI, as a proxy for obesity, and depression using the Canadian Community Health Survey, Cycle 1.2. Methods In this SEM model we postulate that 1 BMI and depression are directly related, 2 BMI is directly affected by the physical activity and, 3depression is directly influenced by stress. SEM was also used to assess the relation between BMI and depression separately for males and females. Results The results indicate that higher BMI is associated with more severe form of depression. On the other hand, the more severe form of depression may result in less weight gain. However, the association between depression and BMI is gender dependent. In males, the higher BMI may result in a more severe form of depression while in females the relation may not be the same. Also, there was a negative relationship between physical activity and BMI. Conclusion In general, use of SEM method showed that the two major diseases, obesity and depression, are associated but the form of the relation is different among males and females. More research is necessary to further understand the complexity of the relationship between obesity and depression. It also demonstrated that SEM is a feasible technique for modeling the relation between obesity and depression.
James Nicholas Samsom
Full Text Available Patients with schizophrenia are at an increased risk for the development of depression. Overlap in the symptoms and genetic risk factors between the two disorders suggests a common etiological mechanism may underlie the presentation of comorbid depression in schizophrenia. Understanding these shared mechanisms will be important in informing the development of new treatments. Rodent models are powerful tools for understanding gene function as it relates to behavior. Examining rodent models relevant to both schizophrenia and depression reveals a number of common mechanisms. Current models which demonstrate endophenotypes of both schizophrenia and depression are reviewed here, including models of: CSMD1, PDLIM5, GluD1, diabetic db/db mice, NPY, DISC1 and its interacting partners, Reelin, maternal immune activation, and social isolation. Neurotransmission, brain connectivity, the immune system, the environment, and metabolism emerge as potential common mechanisms linking these models and potentially explaining comorbid depression in schizophrenia.
Depression will soon be the leading cause of disability in developing countries but effective treatments are not widely available. There is compelling evidence for the effectiveness and cost-effectiveness of the multicondition collaborative care (MCC) model for depression in developing and developed countries. In the MCC model integrated care for depression is provided along with care for different non-communicable disorders. MCC has been shown to reduce hyperglycaemia and hyperlipidaemia and can lead to depression-free days when integrated care for depression and diabetes is provided. However, due to limited resources, it is not possible to make this effective model of care available at the population level. It is suggested that a public health intervention based on the MCC model can lead to better care for depression in developing countries. A public health programme of MCC which provides treatment for depression, diabetes and hypertension in a collaborative care programme will be a cost-effective way of providing treatment for depression in developing countries. This will cater for the leading cause of disability (unipolar depression) and the leading projected causes of mortality (ischaemic heart disease and cerebrovascular disease) in low-income and middle-income countries.
Peterson, Kristina M; Smith, David A
Although perceived criticism is relational, most theory and research concerns only relatives' criticism toward patients and not the converse. With a sample of 33 depressed patients and their spouses, we take a fully relational approach to criticism by testing an actor-partner interdependence model (Kenny, Kashy, & Cook, 2006). Patient intended criticism was especially strongly associated with depressive symptoms for wives, whereas patient perceived criticism was especially negatively related to depressive symptoms for husbands. Nondepressed partner intended criticism was positively related to patient depressive symptoms, but nondepressed wife perceived criticism was negatively related to husband depressive symptoms. The importance of including patient intended and partner perceived criticism as well as examining sex differences in models of criticism and depression are discussed.
Mei, Lin; Mochizuki, Miyako; Hasegawa, Noboru
Oxidative stress is considered to be a mechanism of major depression. Pycnogenol (PYC) is a natural plant extract from the bark of Pinus pinaster Aiton and has potent antioxidant activities. We studied the ameliorative effect of PYC on depression-like behavior in chronic corticosterone- (CORT-) treated mice for 20 days. After the end of the CORT treatment period, PYC (0.2 mg/mL) was orally administered in normal drinking water. Depression-like behavior was investigated by the forced swimming test. Immobility time was significantly longer by CORT exposure. When the CORT-treated mice were supplemented with PYC, immobility time was significantly shortened. Our results indicate that orally administered PYC may serve to reduce CORT-induced stress by radical scavenging activity.
Full Text Available Oxidative stress is considered to be a mechanism of major depression. Pycnogenol (PYC is a natural plant extract from the bark of Pinus pinaster Aiton and has potent antioxidant activities. We studied the ameliorative effect of PYC on depression-like behavior in chronic corticosterone- (CORT- treated mice for 20 days. After the end of the CORT treatment period, PYC (0.2 mg/mL was orally administered in normal drinking water. Depression-like behavior was investigated by the forced swimming test. Immobility time was significantly longer by CORT exposure. When the CORT-treated mice were supplemented with PYC, immobility time was significantly shortened. Our results indicate that orally administered PYC may serve to reduce CORT-induced stress by radical scavenging activity.
The “hopelessness” theory is a recent cognitive model of depression, according to which maladaptive attributional patterns in interaction with stress lead to the development and aggravation of depressive symptoms. It also suggests that attributional patterns and their interaction with stress are closely related to the specific constellation of symptoms, called “hopelessness depression”, than to general depressive symptoms. The purpose of this study was to test the etiological predictions o...
Karlson, Cynthia W.; Stevens, Natalie R.; Olson, Christy A.; Hamilton, Nancy A.
Fatigue is a common and debilitating symptom of clinical depression; however, the causes are not well understood. The present study was designed to test the hypotheses that subjective sleep, objective sleep, and arousal in the pre-sleep state would mediate the relationship between depression status and fatigue. Sleep, pre-sleep arousal, and…
Habtewold, Tesfa; Islam, Atiqul; Radie, Yosef Tsige; Tegegne, Balewgizie
Background: Type 2 diabetes (T2D) is one of the most psychologically demanding chronic medical illness in adult. Comorbidity between diabetes and depression is quite common, but most studies were based on developed country sample. Limited data exists to document biopsychosocial predictors of depress
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.
Marinescu, Ileana P; Predescu, Anca; Udriştoiu, T; Marinescu, D
The neurobiological model of depressive disorder may be correlated with the animal model on rat, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, the increase of cortisol level being specific to the model of depression in women. The neurobiological model of depression in women presents vulnerabilities for some cerebral structures (hippocampus, frontal cortex, cerebral amygdala). A decrease of frontal cortex and hippocampus volumes are recognized in depressive disorder in women, depending on duration of disease and antidepressant therapy. Neurobiological vulnerability may be pronounced through cholinergic blockade. The purpose of the study was to highlight the cytoarchitectural changes in the frontal cortex and hippocampus by comparing two antidepressant substances: amitriptyline with a strong anticholinergic effect and trazodone, without anticholinergic effect. The superior neuroprotective qualities of trazodone for the frontal cortex, hippocampus and dentate gyrus are revealed. The particular neurobiological vulnerability of depression in women requires a differentiated therapeutic approach, avoiding the use of antidepressants with anticholinergic action.
Lim, Su-Min; Park, Soo-Hyun; Sharma, Naveen; Kim, Sung-Su; Lee, Jae-Ryeong; Jung, Jun-Sub; Suh, Hong-Won
Depression is more common among diabetes people than in the general population. In the present study, blood glucose change in depression animal model was characterized by various types of hyperglycemia models such as d-glucose-fed-, immobilization stress-, and drug-induced hyperglycemia models. First, the ICR mice were enforced into chronic restraint stress for 2h daily for 2 weeks to produce depression animal model. The animals were fed with d-glucose (2g/kg), forced into restraint stress for 30min, or administered with clonidine (5μg/5μl) supraspinally or spinally to produce hyperglycemia. The blood glucose level in depression group was down-regulated compared to that observed in the normal group in d-glucose-fed-, restraint stress-, and clonidine-induced hyperglycemia models. The up-regulated corticosterone level induced by d-glucose feeding or restraint stress was reduced in the depression group while the up-regulation of plasma corticosterone level is further elevated after i.t. or i.c.v. clonidine administration in the depression group. The up-regulated insulin level induced by d-glucose feeding or restraint stress was reduced in the depression group. On the other hand, blood corticosterone level in depression group was up-regulated compared to the normal group after i.t. or i.c.v. clonidine administration. Whereas the insulin level in depression group was not altered when mice were administered clonidine i.t. or i.c.v. Our results suggest that the blood glucose level in depression group is down-regulated compared to the normal group during d-glucose-fed-, immobilization stress-, and clonidine-induced hyperglycemia in mice. The down-regulation of the blood glucose level might be one of the important pathophysiologic changes in depression.
Adams, Richard E.; Boscarino, Joseph A.
Research suggests that perievent panic attacks – panic attacks in temporal proximity to traumatic events – are predictive of later mental health status, including the onset of depression. Using a community sample of New York City residents interviewed 1 year and 2 years after the World Trade Center Disaster, we estimated a structural equation model (SEM) using pre-disaster psychological status and post-disaster life events, together with psychosocial resources, to assess the relationship between perievent panic and later onset depression. Bivariate results revealed a significant association between perievent panic and both year-1 and year-2 depression. Results for the SEM, however, showed that perievent panic was predictive of year-1 depression, but not year-2 depression, once potential confounders were controlled. Year-2 stressors and year-2 psychosocial resources were the best predictors of year-2 depression onset. Pre-disaster psychological problems were directly implicated in year-1 depression, but not year-2 depression. We conclude that a conceptual model that includes pre- and post-disaster variables best explains the complex causal pathways between psychological status, stressor exposure, perievent panic attacks, and depression onset two years after the World Trade Center attacks. PMID:21957721
Andrus, B M; Blizinsky, K; Vedell, P T; Dennis, K; Shukla, P K; Schaffer, D J; Radulovic, J; Churchill, G A; Redei, E E
The etiology of depression is still poorly understood, but two major causative hypotheses have been put forth: the monoamine deficiency and the stress hypotheses of depression. We evaluate these hypotheses using animal models of endogenous depression and chronic stress. The endogenously depressed rat and its control strain were developed by bidirectional selective breeding from the Wistar-Kyoto (WKY) rat, an accepted model of major depressive disorder (MDD). The WKY More Immobile (WMI) substrain shows high immobility/despair-like behavior in the forced swim test (FST), while the control substrain, WKY Less Immobile (WLI), shows no depressive behavior in the FST. Chronic stress responses were investigated by using Brown Norway, Fischer 344, Lewis and WKY, genetically and behaviorally distinct strains of rats. Animals were either not stressed (NS) or exposed to chronic restraint stress (CRS). Genome-wide microarray analyses identified differentially expressed genes in hippocampi and amygdalae of the endogenous depression and the chronic stress models. No significant difference was observed in the expression of monoaminergic transmission-related genes in either model. Furthermore, very few genes showed overlapping changes in the WMI vs WLI and CRS vs NS comparisons, strongly suggesting divergence between endogenous depressive behavior- and chronic stress-related molecular mechanisms. Taken together, these results posit that although chronic stress may induce depressive behavior, its molecular underpinnings differ from those of endogenous depression in animals and possibly in humans, suggesting the need for different treatments. The identification of novel endogenous depression-related and chronic stress response genes suggests that unexplored molecular mechanisms could be targeted for the development of novel therapeutic agents.
Briggs, Michele Kielty; Shoffner, Marie F.
Overall spiritual wellness, as well as 4 individual components of spiritual wellness, has been theoretically and empirically linked with depression. Prior to this investigation, no study has examined the relationship between spiritual wellness and depression by using a 4-component measurement model of spiritual wellness. In this study of older…
Miura, Robert M.; Huang, Huaxiong; Wylie, Jonathan J.
Migraine with aura (MwA) is a debilitating disease that afflicts about 25%-30% of migraine sufferers. During MwA, a visual illusion propagates in the visual field, then disappears, and is followed by a sustained headache. MwA was conjectured by Lashley to be related to some neurological phenomenon. A few years later, Leão observed electrophysiological waves in the brain that are now known as cortical spreading depression (CSD). CSD waves were soon conjectured to be the neurological phenomenon underlying MwA that had been suggested by Lashley. However, the confirmation of the link between MwA and CSD was not made until 2001 by Hadjikhani et al. [Proc. Natl. Acad. Sci. U.S.A. 98, 4687-4692 (2001)] using functional MRI techniques. Despite the fact that CSD has been studied continuously since its discovery in 1944, our detailed understandings of the interactions between the mechanisms underlying CSD waves have remained elusive. The connection between MwA and CSD makes the understanding of CSD even more compelling and urgent. In addition to all of the information gleaned from the many experimental studies on CSD since its discovery, mathematical modeling studies provide a general and in some sense more precise alternative method for exploring a variety of mechanisms, which may be important to develop a comprehensive picture of the diverse mechanisms leading to CSD wave instigation and propagation. Some of the mechanisms that are believed to be important include ion diffusion, membrane ionic currents, osmotic effects, spatial buffering, neurotransmitter substances, gap junctions, metabolic pumps, and synaptic connections. Discrete and continuum models of CSD consist of coupled nonlinear differential equations for the ion concentrations. In this review of the current quantitative understanding of CSD, we focus on these modeling paradigms and various mechanisms that are felt to be important for CSD.
Feng, Zheng-Zhi; Yi, Hong
The diathesis-stress component hypothesis and the mediational role of hopelessness proposed by the hopelessness theory of depression were tested using data from a 16-week longitudinal study of Chinese...
Qing, Lu; Haiteng, Jiang; Haiyan, Liu; Gang, Liu; Gaojun, Teng; Zhijian, Yao
To develop a functional MRI (fMRI) signal based model that can evaluate depression severity in a numeric form; therefore, depressed patients can be identified during the course of illness, independent from symptoms. Data from 20 medication-free depressed patients and 16 healthy subjects were analyzed. The event-related fMRI scanning features under sad facial emotional stimuli were extracted as model inputs. Fuzzy logic and a genetic algorithm were used to provide suitable model outputs for numeric estimations of depression. The correlation value r between the model estimations and the professional Hamilton Depression Rating Scales (HAMD) was 0.7886 with P < 0.00016. A typical tracking history for a particular subject has also promised the possibility for early disease warning, when the clinal symptoms are ambiguous or recessive. A numeric and objective estimation for the course of illness can be provided. The model can be used by psychiatrists to track the recovery process. As a simple extended application, the proposed model can be applied to classify subjects into different patterns: major depression, moderate depression, or healthy. Copyright 2010 Wiley-Liss, Inc.
Scogin, Forrest R; Hanson, Ashley; Welsh, Douglas
Stepped behavioral health care models have begun to receive increased attention. Self-administered treatments deserve consideration as an element in these models for some disorders and for some consumers. Features suggesting inclusion include low cost, wide availability, and evidence-based status. We present a stepped-care model for depression inclusive of a self-administered treatment component. We also discuss cautions such as depression severity and consumer preference. Evaluation of the efficacy and cost effectiveness of this approach to depression treatment is necessary. Copyright 2003 Wiley Periodicals, Inc. J Clin Psychol 59: 341-349, 2003.
Mehta-Raghavan, N S; Wert, S L; Morley, C; Graf, E N; Redei, E E
In this study, we sought to learn whether adverse events such as chronic restraint stress (CRS), or 'nurture' in the form of environmental enrichment (EE), could modify depression-like behavior and blood biomarker transcript levels in a genetic rat model of depression. The Wistar Kyoto More Immobile (WMI) is a genetic model of depression that aided in the identification of blood transcriptomic markers, which successfully distinguished adolescent and adult subjects with major depressive disorders from their matched no-disorder controls. Here, we followed the effects of CRS and EE in adult male WMIs and their genetically similar control strain, the Wistar Kyoto Less Immobile (WLI), that does not show depression-like behavior, by measuring the levels of these transcripts in the blood and hippocampus. In WLIs, increased depression-like behavior and transcriptomic changes were present in response to CRS, but in WMIs no behavioral or additive transcriptomic changes occurred. Environmental enrichment decreased both the inherent depression-like behavior in the WMIs and the behavioral difference between WMIs and WLIs, but did not reverse basal transcript level differences between the strains. The inverse behavioral change induced by CRS and EE in the WLIs did not result in parallel inverse expression changes of the transcriptomic markers, suggesting that these behavioral responses to the environment work via separate molecular pathways. In contrast, 'trait' transcriptomic markers with expression differences inherent and unchanging between the strains regardless of the environment suggest that in our model, environmental and genetic etiologies of depression work through independent molecular mechanisms.
Meylan, E M
Recent studies implicate the arginine-decarboxylation product agmatine in mood regulation. Agmatine has antidepressant properties in rodent models of depression, and agmatinase (Agmat), the agmatine-degrading enzyme, is upregulated in the brains of mood disorder patients. We have previously shown that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) associate behavioral and molecular depressive-like endophenotypes, as well as blunted responses to classical antidepressants. Here, the molecular basis of the behavioral phenotype of Crtc1−/− mice was further examined using microarray gene expression profiling that revealed an upregulation of Agmat in the cortex of Crtc1−/− mice. Quantitative polymerase chain reaction and western blot analyses confirmed Agmat upregulation in the Crtc1−/− prefrontal cortex (PFC) and hippocampus, which were further demonstrated by confocal immunofluorescence microscopy to comprise an increased number of Agmat-expressing cells, notably parvalbumin- and somatostatin-positive interneurons. Acute agmatine and ketamine treatments comparably improved the depressive-like behavior of male and female Crtc1−/− mice in the forced swim test, suggesting that exogenous agmatine has a rapid antidepressant effect through the compensation of agmatine deficit because of upregulated Agmat. Agmatine rapidly increased brain-derived neurotrophic factor (BDNF) levels only in the PFC of wild-type (WT) females, and decreased eukaryotic elongation factor 2 (eEF2) phosphorylation in the PFC of male and female WT mice, indicating that agmatine might be a fast-acting antidepressant with N-methyl-D-aspartate (NMDA) receptor antagonist properties. Collectively, these findings implicate Agmat in the depressive-like phenotype of Crtc1−/− mice, refine current understanding of the agmatinergic system in the brain and highlight its putative role in major depression.
Meylan, E M; Breuillaud, L; Seredenina, T; Magistretti, P J; Halfon, O; Luthi-Carter, R; Cardinaux, J-R
Recent studies implicate the arginine-decarboxylation product agmatine in mood regulation. Agmatine has antidepressant properties in rodent models of depression, and agmatinase (Agmat), the agmatine-degrading enzyme, is upregulated in the brains of mood disorder patients. We have previously shown that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) associate behavioral and molecular depressive-like endophenotypes, as well as blunted responses to classical antidepressants. Here, the molecular basis of the behavioral phenotype of Crtc1(-/-) mice was further examined using microarray gene expression profiling that revealed an upregulation of Agmat in the cortex of Crtc1(-/-) mice. Quantitative polymerase chain reaction and western blot analyses confirmed Agmat upregulation in the Crtc1(-/-) prefrontal cortex (PFC) and hippocampus, which were further demonstrated by confocal immunofluorescence microscopy to comprise an increased number of Agmat-expressing cells, notably parvalbumin- and somatostatin-positive interneurons. Acute agmatine and ketamine treatments comparably improved the depressive-like behavior of male and female Crtc1(-/-) mice in the forced swim test, suggesting that exogenous agmatine has a rapid antidepressant effect through the compensation of agmatine deficit because of upregulated Agmat. Agmatine rapidly increased brain-derived neurotrophic factor (BDNF) levels only in the PFC of wild-type (WT) females, and decreased eukaryotic elongation factor 2 (eEF2) phosphorylation in the PFC of male and female WT mice, indicating that agmatine might be a fast-acting antidepressant with N-methyl-D-aspartate (NMDA) receptor antagonist properties. Collectively, these findings implicate Agmat in the depressive-like phenotype of Crtc1(-/-) mice, refine current understanding of the agmatinergic system in the brain and highlight its putative role in major depression.
Petersén, Asa; Wörtwein, Gitta; Gruber, Susanne H M
A prevailing hypothesis is that neurogenesis is reduced in depression and that the common mechanism for antidepressant treatments is to increase it in adult hippocampus. Reduced neurogenesis has been shown in healthy rats exposed to stress, but it has not yet been demonstrated in depressed patients....... Emerging studies now indicate that selective serotonin reuptake inhibitors can, exert behavioral effects without affecting neurogenesis in mice. Here we extend our previous findings demonstrating that the number of BrdU positive cells in hippocampus was significantly higher in a rat model of depression....... These results strengthen the arguments against hypothesis of neurogenesis being necessary in etiology of depression and as requisite for effects of antidepressants, and illustrate the importance of using a disease model and not healthy animals to assess effects of potential therapies for major depressive...
Francisco J. Ruiz
Full Text Available Beck's cognitive model of depression proposes that depressogenic schemas have an effect on depressive symptoms by increasing the frequency of negative automatic thoughts in response to negative life events. We aimed to test a moderated, serial mediation model where psychological inflexibility, a core concept of the Acceptance and Commitment Therapy (ACT model of psychopathology, both mediates and moderates the relationship between depressogenic schemas and the frequency of negative automatic thoughts. A cross-sectional design was used in which 210 undergraduates responded to questionnaires assessing the constructs of interest. Results supported the proposed moderated mediation model. Both psychological inflexibility and negative automatic thoughts were significant mediators of the relationship between depressogenic schemas and depressive symptoms, and psychological inflexibility also moderated the effect of depressogenic schemas on negative automatic thoughts. We conclude that the role of psychological inflexibility in the cognitive model of depression deserves more attention.
Fandiño-Losada, Andrés; Bangdiwala, Shrikant I; Lavebratt, Catharina; Forsell, Yvonne
Background Depressive disorder is recognized as recurrent or chronic in the majority of affected individuals; but literature is not consistent about determinants of the disorder course. Aims To analyse the relationships between familial, personal and environmental characteristics in different life phases and their effects on the chronicity of depression in a population-based sample. Methods It was a longitudinal panel study with three waves (W1-W3) for 651 adult men and women with diagnosis of minor/major depression or dysthymia at W1 of the Swedish PART (mental health, work and relations) study. Risk factors and co-morbidities were assessed with questionnaires. The main outcome was an episode of minor/major depression or dysthymia at 10-12 years of follow-up (W3). Liability for depressive episodes was determined using exploratory structural equation modelling (SEM), following a path approach with step-wise specification searches. Results Most of the risk factors determined, directly or indirectly, depression severity at W3. Somatic trait anxiety, partner loss and other negative life events at W1, depressive symptoms at W2, and life difficulties and other dependent life events at W3 had direct effects on the outcome. Conclusions SEM model revealed complex and intertwined psychopathological pathways leading to chronicity of depression, given previous episodes, which could be assembled in two main mechanisms: a depressive-internalizing path and an adversity path comprised of life events. Pathways are simpler than those of depression occurrence, emphasizing the relevance of personality factors as depression determinants, and excluding disability levels, co-morbidities and social support. These novel findings need to be replicated in future studies.
Full Text Available Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM and open field test (OFT in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST and forced swimming test (FST in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.
Full Text Available Objective: To identify the molecular mechanism of post-stroke depression (PSD, and observe the therapeutic effects of cerebellar fastigial nucleus electrical stimulation (FNS on the behaviors and regional cerebral blood flow (rCBF in a PSD rat model. Methods: Healthy SD rats were randomly divided into four groups (sham, stroke, post-stroke depress and FNS group. Sham group (n = 6 underwent sham operation. The other three groups (n = 6*3 underwent MCAO. Rats were examined twice a week in open filed test. Moreover, neuroprotective effect on cerebellar Purkinje cells and expression of cytokines in hippocampal tissue were examined. Results: The PSD group showed a significant weight loss, decreased consumption of sucrose water, reduced rearing and locomotor activities. The FNS significantly alleviates the body weight loss and sucrose preference, locomotor and rearing activities. The bilateral rCBF was also restored after FNS treatment. Moreover, FNS improved the neuroprotection via suppressing apoptosis of cerebellar Purkinje cells. And the inflammatory cytokines mRNA level in hippocampus was significantly decreased. Conclusion: FNS treatment alleviates depressive-like behaviors and rCBF in PSD rats model, which could be attributed to its ability to protect cerebellar Purkinje cells and decrease the mRNA level of inflammatory cytokines.
Oei, Tian P S; Kwon, Seok-Man
This study empirically tested the specificity of the integrated cognitive model (ICM) of depression, which postulates that negative life events interact with dysfunctional attitudes to increase the frequency and severity of automatic thoughts, subsequently affecting depressive symptoms. We also examined the three competing models: the linear mediation model, the alternative etiologies model, and the symptom model. We anticipated that we might examine these models more appropriately using data from a population at an increased risk of developing depressive symptoms. As such, two-wave panel data were obtained from a group of 107 Korean migrants who had been in Australia less than 1 year. Structural equation modeling revealed that the ICM provided an adequate and much better fit than the three competing models. The ICM was also found to support the cognitive specificity theory of depression and anxiety. These findings suggest that dysfunctional attitudes can be a common cognitive moderator of depression and anxiety, whereas automatic thoughts and anxious self-statements can be specific cognitive mediators of anxiety and depression, respectively.
Bouzinova, Elena; Bødtkjer, Donna Marie Briggs; Kudryavtseva, Olga
"anhedonia"), whereas others are stress resilient. METHODS: After 8 weeks of chronic mild stress, anhedonic rats reduced their sucrose intake by 55% (7%), whereas resilient rats did not. Acetylcholine-induced endothelium-dependent relaxation of norepinephrine-preconstricted mesenteric arteries was analyzed.......1% [11.65%]) groups (p activity revealed increased COX-2-dependent relaxation in the anhedonic group. In contrast, endothelial NO synthase- and COX-independent relaxation to acetylcholine (endothelium-dependent hyperpolarization......-like response) was reduced in anhedonic rats (p activated K channels. CONCLUSIONS: Our findings demonstrate that depression-like symptoms are associated with reduced endothelium-dependent relaxation due to suppressed...
Anderson, Emily R; Hope, Debra A
Although research from numerous investigations indicates that there is substantial overlap in anxiety and depressive symptoms and comorbid diagnoses in youth, these constructs can be adequately differentiated. Clark and Watson [Clark, L. A. & Watson, D., (1991). Tripartite model of anxiety and depression: Psychometric evidence and taxonomic implications. Journal of Abnormal Psychology, 100, 316-336] proposed a tripartite model to account for the symptom overlap and diagnostic comorbidity between anxiety and depression. This tripartite model posits that anxiety and depression share a common component of negative affect, but can be differentiated by low positive affect associated with depression and high physiological hyperarousal associated with anxiety. The present article reviews initial research which has supported the utility of the tripartite model for explaining the association between anxiety and depression in adult and youth samples. Following that review, more recent investigations which have called into question the applicability of the tripartite constructs for youth are presented. Finally, the paper reviews evidence suggesting that the tripartite factors may not function similarly across all anxiety and depressive disorders. This article concludes by suggesting that more research is necessary with children and adolescents in order to determine the functioning of tripartite constructs across anxiety disorders in youth.
Carnevali, Luca; Trombini, Mimosa; Rossi, Stefano; Graiani, Gallia; Manghi, Massimo; Koolhaas, Jaap M.; Quaini, Federico; Macchi, Emilio; Nalivaiko, Eugene; Sgoifo, Andrea
Objective: Despite a well-documented association between stress and depression with cardiac morbidity and mortality, there is no satisfactory explanation for the mechanisms linking affective and cardiac disorders. This study investigated cardiac electrophysiological properties in an animal model of
Chen, Sung-Wei; Wang, Po-Chuan; Hsin, Ping-Lung; Oates, Anthony; Sun, I-Wen; Liu, Shen-Ing
Microelectronic engineers are considered valuable human capital contributing significantly toward economic development, but they may encounter stressful work conditions in the context of a globalized industry. The study aims at identifying risk factors of depressive disorders primarily based on job stress models, the Demand-Control-Support and Effort-Reward Imbalance models, and at evaluating whether depressive disorders impair work performance in microelectronics engineers in Taiwan. The case-control study was conducted among 678 microelectronics engineers, 452 controls and 226 cases with depressive disorders which were defined by a score 17 or more on the Beck Depression Inventory and a psychiatrist's diagnosis. The self-administered questionnaires included the Job Content Questionnaire, Effort-Reward Imbalance Questionnaire, demography, psychosocial factors, health behaviors and work performance. Hierarchical logistic regression was applied to identify risk factors of depressive disorders. Multivariate linear regressions were used to determine factors affecting work performance. By hierarchical logistic regression, risk factors of depressive disorders are high demands, low work social support, high effort/reward ratio and low frequency of physical exercise. Combining the two job stress models may have better predictive power for depressive disorders than adopting either model alone. Three multivariate linear regressions provide similar results indicating that depressive disorders are associated with impaired work performance in terms of absence, role limitation and social functioning limitation. The results may provide insight into the applicability of job stress models in a globalized high-tech industry considerably focused in non-Western countries, and the design of workplace preventive strategies for depressive disorders in Asian electronics engineering population.
James Nicholas Samsom; Albert Hung Choy Wong
Patients with schizophrenia are at an increased risk for the development of depression. Overlap in the symptoms and genetic risk factors between the two disorders suggests a common etiological mechanism may underlie the presentation of comorbid depression in schizophrenia. Understanding these shared mechanisms will be important in informing the development of new treatments. Rodent models are powerful tools for understanding gene function as it relates to behavior. Examining rodent models rel...
Grover, Sandeep; Kumar, Vineet; Chakrabarti, Subho; Hollikatti, Prabhakar; Singh, Pritpal; Tyagi, Shikha; Kulhara, Parmanand; Avasthi, Ajit
The purpose of this work was to study the explanatory models of patients with first episode depression presenting to a tertiary care hospital located in North-western India. One hundred sixty four consecutive patients with diagnosis of first episode depression (except severe depression with psychotic symptoms) according to the International Classification of Diseases-10th Revision (ICD-10) and ≥18 years of age were evaluated for their explanatory models using the causal models section of Explanatory Model Interview Catalogue (EMIC). The most common explanations given were categorized into Karma-deed-heredity category (77.4%), followed by psychological explanations (62.2%), weakness (50%) and social causes (40.2%). Among the various specific causes the commonly reported explanations by at least one-fourth of the sample in decreasing order were: will of god (51.2%), fate/chance (40.9%), weakness of nerves (37.8%), general weakness (34.7%), bad deeds (26.2%), evil eye (24.4%) and family problems (21.9%). There was some influence of sociodemographic features on the explanations given by the patients. From the study, it can be concluded that patients with first episode depression have multiple explanatory models for their symptoms of depression which are slightly different than those reported in previous studies done from other parts of India. Understanding the multiple explanatory models for their symptoms of depression can have important treatment implications. Copyright © 2012 Elsevier B.V. All rights reserved.
Chu, Xun-Xun; Dominic Rizak, Joshua; Yang, Shang-Chuan; Wang, Jian-Hong; Ma, Yuan-Ye; Hu, Xin-Tian
Postpartum depression (PPD) is a modified form of major depressive disorders (MDD) that can exert profound negative effects on both mothers and infants than MDD. Within the postpartum period, both mothers and infants are susceptible; but because PPD typically occurs for short durations and has moderate symptoms, there exists challenges in exploring and addressing the underlying cause of the depression. This fact highlights the need for relevant animal models. In the present study, postpartum adult female cynomolgus monkeys (Macaca fascicularis) living in breeding groups were observed for typical depressive behavior. The huddle posture behavior was utilized as an indicator of behavioral depression postpartum (BDP) as it has been established as the core depressive-like behavior in primates. Monkeys were divided into two groups: A BDP group (n=6), which were found to spend more time huddling over the first two weeks postpartum than other individuals that formed a non-depression control group (n=4). The two groups were then further analyzed for locomotive activity, stressful events, hair cortisol levels and for maternal interactive behaviors. No differences were found between the BDP and control groups in locomotive activity, in the frequencies of stressful events experienced and in hair cortisol levels. These findings suggested that the postpartum depression witnessed in the monkeys was not related to external factors other than puerperium period. Interestingly, the BDP monkeys displayed an abnormal maternal relationship consisting of increased infant grooming. Taken together, these findings suggest that the adult female cynomolgus monkeys provide a natural model of behavioral postpartum depression that holds a number of advantages over commonly used rodent systems in PPD modeling. The cynomolgus monkeys have a highly-organized social hierarchy and reproductive characteristics without seasonal restriction-similar to humans-as well as much greater homology to humans
Habtewold, Tesfa; Islam, Atiqul; Radie, Yosef Tsige; Tegegne, Balewgizie
Background: Type 2 diabetes (T2D) is one of the most psychologically demanding chronic medical illness in adult. Comorbidity between diabetes and depression is quite common, but most studies were based on developed country sample. Limited data exists to document biopsychosocial predictors of
Lysaught, Eileen; Wodarski, John S.
Describes how adolescents are affected by depression and alcohol dependence and offers a treatment plan for a dual diagnosis. The plan consists of an adolescent group and family program to facilitate and maintain behavioral changes in treatment. The benefits of this treatment and rationale for its application are discussed. (LSR)
Kelley, George A; Kelley, Kristi S
Use a recently developed varying coefficient model to determine the effects of exercise in adults with depression. Data from a recent meta-analysis addressing the effects of exercise on depression in adults were used. Studies were limited to randomized controlled intervention trials of any type of chronic exercise (for example, walking and jogging) in adults greater than or equal to 18 years of age with a diagnosis of depression. For each study, the standardized mean difference (exercise minus control) effect size for depression, adjusted for small-sample bias, was calculated. Variance statistics for each effect size and pooling of results were calculated using the recently proposed varying coefficient (VC) model for standardized mean differences. Standardized effect-sizes of 0.20, 0.50 and 0.80 were considered to represent small, medium and large effects. Results were considered statistically significant if the 95% confidence intervals did not cross 0, with negative results indicative of reductions in depression. These findings were then compared with results using traditional random-effects (RE) models. A total of 23 studies representing 907 men and women (476 exercise, 431 control) were pooled for analysis. Both RE and VC models resulted in large, statistically significant improvements in depression as a result of exercise in adults. However, the VC model resulted in a larger overall effect size as well as confidence intervals that were narrower than previously reported using the RE model. The overall mean effect size for the RE model was -0.82 with a 95% confidence interval of -1.12 to -0.51. For the VC model, overall mean effect size was -0.88 with a 95% confidence interval of -1.08 to -0.68. The relative difference between the RE and VC approaches was 7.3%. The VC model, a potentially preferable model, confirms the positive effects of exercise on depression in adults.
王桂华; 栾海云; 杨丽娟; 王敏; 张慧
目的 探讨运动对慢性不可预见温和应激(CUMS)抑郁老年大鼠行为学及血清皮质醇和促肾上腺皮质激素(ACTH)浓度的影响.方法 50只雄性老年SD大鼠随机分为对照组、CUMS组、低强度跑台运动训练(LITT)组、中等强度跑台运动训练(MITT)组、高强度跑台运动训练(HITT)组.采用CUMS加孤养复制老年大鼠抑郁模型.采用旷场实验得分和强迫游泳实验评价各组大鼠行为学改变,分别采用ELISA和放射免疫方法检测血清皮质醇、ACTH浓度.结果 与对照组比较,CUMS组大鼠血清皮质醇和ACTH浓度增高(P＜0.01)；与CUMS组比较,LITT组、MITT组和HITT组大鼠水平运动和垂直运动增多、清理次数增加,中央格停留时间缩短,血清皮质醇和ACTH浓度降低(P＜0.05,P＜0.01).结论 CUMS可使老年大鼠行为及内分泌发生异常改变,引起抑郁；适度的运动可调节CUMS引起的下丘脑-垂体-肾上腺轴功能亢进,具有抗抑郁及降低抑郁程度的作用.%Objective To study the effect of exercise on chronic unpredictable mild stress(CUMS) induced abnormal behaviors and serum cortisol ( CORT) and adrenocorticotropic hormone (ACTH) levels in elderly depression-like rats. Methods Fifty elderly male SD rats were random ly divided into control group,model group,low intensity treadmill training(LITT)group,medium intensity treadmill training( MITT) group, and high intensity treadmill training(HITT)group(10 in each group). A rat depression model was induced by CUMS. Bahaviors of rats were assessed ac cording to the open field test and forced swimming test scores. Serum CORT and ACTH levels in different groups were measured by RIA and ELISA,respectively. Results The body weight gain was slower,the horizontal and vertical exercise scores and the modified scores were significantly lower,the central retention time was significantly longer,the serum CORT and ACTH levels were significantly higher in CUMS group than in control group
Full Text Available The purpose of this study was to test the validity of affective temperaments for predicting psychiatric morbidity and suicide risk, using a two-factor model to explain the relationships between temperament, anxiety, depression, and hopelessness. We investigated 210 high school students, 103 males and 107 females, 18-19 years old, who were administered self-report questionnaires to assess temperament (TEMPS-A, depression (BDI-II, anxiety (STAI and hopelessness (BHS. The final structural model had a good fit with the data, with two factors significantly correlated, the first labeled unstable cyclothymic temperament including Dysthymic/Cyclothymic/Anxious temperament, Irritable temperament and Depression, and the second labeled Demoralization including Anxiety (State/Trait and Hopelessness. Depression, anxiety and hopelessness are in a complex relationship partly mediated by temperament.
Beshai, Shadi; Dobson, Keith S; Adel, Ashraf; Hanna, Niveen
Introduction Models of depression that arise in the West need to be examined in other regions of the world. This study examined a set of foundational hypotheses generated by Beck’s cognitive model of depression among depressed individuals in Egypt and Canada. Method We recruited 29 depressed and 29 non-depressed Egyptians and compared their results with those of 35 depressed and 38 non-depressed Canadians. Depression status was ascertained using a structured interview, scores on the Beck Depression Inventory, and scores on the Psychiatric Diagnostic Screening Questionnaire. Participants completed questionnaires designed to measure the frequency of negative and positive automatic thoughts (ATQ–N, BHS, and ATQ–P), and dysfunctional attitudes (DAS). Results Depressed individuals in both countries had significantly more negative thoughts about self and future, greater frequency of dysfunctional attitudes, and diminished positive self-thoughts in comparison to non-depressed individuals. Egyptians generally showed significantly more dysfunctional attitudes than their Canadian counterparts. Discussion The four hypotheses that were tested were supported among the depressed Egyptian sample, which is consistent with the cognitive model. Implications for the cognitive-behavioral model and treatment for this group of sufferers are discussed. PMID:27010706
Paolo Iliceto; Maurizio Pompili; David Lester; Xenia Gonda; Cinzia Niolu; Nicoletta Girardi; Zoltán Rihmer; Gabriella Candilera; Paolo Girardi
The purpose of this study was to test the validity of affective temperaments for predicting psychiatric morbidity and suicide risk, using a two-factor model to explain the relationships between temperament, anxiety, depression, and hopelessness. We investigated 210 high school students, 103 males and 107 females, 18-19 years old, who were administered self-report questionnaires to assess temperament (TEMPS-A), depression (BDI-II), anxiety (STAI) and hopelessness (BHS). The final structural mo...
phase diagram that maps out when a retinal detachment is unstable, or is stable and will likely heal . We have begun to generalize this problem in two...Spreading Depression and W mmd Healing Sb. GRANT NUMBER Sc. PROGRAM ELEMENT NUMBER 611102 6. AUTHORS Sd. PROJECT NUMBER Tom Chou Se. TASK NUMBER...Spreading Depression and Wound Healing ." The research conducted under this grant represents advances made in image analysis, front tracking, modeling
Noh, Jin-Won; Kwon, Young Dae; Park, Jumin; Oh, In-Hwan; Kim, Jinseok
Background Depression in persons with physical disabilities may be more common than in the general population. The purpose of this study was to examine the relationship between physical disability and depression by gender among adults, using a large, nationally representative sample. Methods This study used data from the Korean Longitudinal Study of Aging, Wave one through four, and ran a series of random effect panel regression models to test the relationship between physical disability stat...
Thought processing and mood regulation are closely linked, but existing classifications of mood disorders fail to recognize the complex interplay between these two clinical dimensions. Furthermore, existing classifications fail to account for the possibility that depression might be associated with an increased frequency of self-referential thoughts that could in some circumstances be related to creativity processes. Based on recent evidence from clinical phenomenology, experimental psycholog...
Dilcio Dantas Guedes
Full Text Available Relatam-se casos clínicos de dois rapazes, que buscaram psicoterapia a partir de demandas afetivas e amorosas. Enfatizam-se a análise de seus modelos de apego e a queixa de depressão em relação a suas experiências homoafetivas. Partiu-se das suposições de que: (1 os modelos comportamentais de apego com os pais repetir-se-iam com os parceiros; e (2 o nível de segurança das relações amorosas mediaria inversamente o nível da depressão. Articularam-se dados da mensuração dos níveis de depressão pelo Inventário de Depressão Beck (BDI e da Attachment Security and Secondary Strategies Interview (ASSSI. Os resultados indicaram que os modelos de apego aos pais parecem ter influenciado as representações de apego e experiências amorosas, que pareceram mediar os níveis da depressão.Case studies of two young men are reported. Their reason for seeking psychotherapy lies in their affection and romantic love problems, what led us to an effort to understand their models of attachment and depression complaints in regard to their homo-affective experiences. Authors assumed that: (1 attachment models experienced with their parents would be repeated with love partners, and (2 the level of steadiness in the romantic relationship would inversely mediate the level of depression. Depression data obtained by means of Beck Depression Inventory (BDI were related to equivalent information generated by Attachment Security and Secondary Strategies Interview (ASSSI. Results showed that models of attachment to the parents seemed to have influenced the attachment representations' and love relationships, which seemed to have mediated the levels of depression.
Fuyou Liu; Shi Yang; Weiyin Chen; Jinyu Wang; Yi Tang; Guanxiang Zhu
BACKGROUND: Ideal model of poststroke depression (PSD) may be induced in rats guided by the theoretical evidence that "primary endogenous mechanism" and "reactivity mechanism" theories for PSD in human being.OBJECTIVE: To investigate the feasibility of comprehensive methods to induce PSD models in rats.DESrGN: A randomized controlled animal trial.SETTING: Department of Neurology, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine.MATERrALS: Male SD rats of SPF degree, weighing 350-500 g, were provided by the experimental animal center of Chengdu University of Traditional Chinese Medicine. The rats were raised for 1 week adaptively, then screened behaviorally by open-field test and passive avoidance test. Forty-five rats with close scores were randomly divided into normal control group (n =10), simple stroke group (n =10), stress group (n =10) and PSD group (n =15).METHODS: The experiments were carried out in the laboratory of Chengdu University of Traditional Chinese Medicine from July 2002 to February 2003. ① Rat models of focal cerebral ischemia were induced by thread embolization, then treated with separate raising and unpredictable stress to induce PSD models. ②The neurologic deficit was evaluated by Longa 5-grade standard (the higher the score, the severer the neurologic deficit) and horizontal round rod test (normal rat could stay on it for at least 3 minutes). ③ The behavioral changes of PSD rats were evaluated by the saccharin water test, open-field text and passive avoidance test,including the changes of interest, spontaneous and exploratory activities, etc. ④ The levels of monoamine neurotransmitters, including norepinephrine (NE), serotonin (5-HT) and dopamine, in brain were determined using fluorospectrophotometry.MAIN OUTCOME MEASURES: ① Score of Longa 5-grade standard; Stayed time in the horizontal round rod test;② Amount of saccharin water consumption; Open-field text: time stayed in the central square, times
Harrington, Marcus O; Pennington, Kyla; Durrant, Simon J
Since the 1960's polysomnographic sleep research has demonstrated that depressive episodes are associated with REM sleep alterations. Some of these alterations, such as increased REM sleep density, have also been observed in first-degree relatives of patients and remitted patients, suggesting that they may be vulnerability markers of major depressive disorder (MDD), rather than mere epiphenomena of the disorder. Neuroimaging studies have revealed that depression is also associated with heightened amygdala reactivity to negative emotional stimuli, which may also be a vulnerability marker for MDD. Several models have been developed to explain the respective roles of REM sleep alterations and negatively-biased amygdala activity in the pathology of MDD, however the possible interaction between these two potential risk-factors remains uncharted. This paper reviews the roles of the amygdala and REM sleep in the encoding and consolidation of negative emotional memories, respectively. We present our 'affect tagging and consolidation' (ATaC) model, which argues that increased REM sleep density and negatively-biased amygdala activity are two separate, genetically influenced risk-factors for depression which interact to promote the development of negative memory bias - a well-known cognitive vulnerability marker for depression. Predictions of the ATaC model may motivate research aimed at improving our understanding of sleep dependent memory consolidation in depression aetiology.
Noh, Jin-Won; Kwon, Young Dae; Park, Jumin; Oh, In-Hwan; Kim, Jinseok
Depression in persons with physical disabilities may be more common than in the general population. The purpose of this study was to examine the relationship between physical disability and depression by gender among adults, using a large, nationally representative sample. This study used data from the Korean Longitudinal Study of Aging, Wave one through four, and ran a series of random effect panel regression models to test the relationship between physical disability status and depression by gender. We tested the moderating effect of gender on the relationship between disability status and depression level by examining the significance of the cross-product term between disability status and gender. After controlling for self-rated health, marital status, employment status, education, and age, subjects who were female or diagnosed as having any disability presented higher levels of depression scores. Further, the difference in terms of their depression level measured by Center for Epidemiologic Studies Short Depression Scale (CES-D 10) scores between those who were diagnosed as having any disability and those who were not was greater for females than for their male counterparts. This study reaffirmed that disability is the risk factor of depression, using longitudinal data. In addition, female gender is the effect modifier rather than the risk factor. The effect of gender in the non-disability group, mostly composed of older persons, is limited. On the contrary, the female disability group showed more depressive symptoms than the male disability group. The gender difference in the disability group and the role of culture on these differences need further research.
The generalized Pareto distribution model is a kind of hydrocarbon pool size probability statistical method for resource assessment. By introducing the time variable, resource conversion rate and the geological variable, resource density, such model can describe not only different types of basins, but also any exploration samples at different phases of exploration, up to the parent population. It is a dynamic distribution model with profound geological significance and wide applicability. Its basic principle and the process of resource assessment are described in this paper. The petroleum accumulation system is an appropriate assessment unit for such method. The hydrocarbon resource structure of the Huanghua Depression in Bohai Bay Basin was predicted by using this model. The prediction results accord with the knowledge of exploration in the Huanghua Depression, and point out the remaining resources potential and structure of different petroleum accumulation systems, which are of great significance for guiding future exploration in the Huanghua Depression.
Jinhua Fu; Yingjin Zhang; Renrong Wu; Yingjun Zheng; Xianghui Zhang; Mei Yang; Jingping Zhao; Yong Liu
Shuganjieyu capsule has been approved for clinical treatment by the State Food and Drug Ad-ministration of China since 2008. In the clinic, Shuganjieyu capsule is often used to treat mild to moderate depression. In the rat model of depression established in this study, Shuganjieyu capsule was administered intragastrically daily before stress. Behavioral results conifrmed that depressive symptoms lessened after treatment with high-dose (150 mg/kg) Shuganjieyu capsule. Immunohistochemistry results showed that high-dose Shuganjieyu capsule signiifcantly increased phosphorylation levels of phosphorylation cyclic adenosine monophosphate response element binding protein and brain-derived neurotrophic factor expression in the medial prefrontal cortex and hippocampal CA3 area. Overall, our results suggest that in rats, Shuganjieyu capsule effec-tively reverses depressive-like behaviors by increasing expression levels of neurotrophic factors in the brain.
Full Text Available At present, the clinical diagnosis of depression is mainly through structured interviews by psychiatrists, which is lack of objective diagnostic methods, so it causes the higher rate of misdiagnosis. In this paper, a method of depression recognition based on SVM and particle swarm optimization algorithm mutation is proposed. To address on the problem that particle swarm optimization (PSO algorithm easily trap in local optima, we propose a feedback mutation PSO algorithm (FBPSO to balance the local search and global exploration ability, so that the parameters of the classification model is optimal. We compared different PSO mutation algorithms about classification accuracy for depression, and found the classification accuracy of support vector machine (SVM classifier based on feedback mutation PSO algorithm is the highest. Our study promotes important reference value for establishing auxiliary diagnostic used in depression recognition of clinical diagnosis.
González-Gutiérrez, María Victoria; Guerrero Velázquez, José; Morales García, Concepción; Casas Maldonado, Francisco; Gómez Jiménez, Francisco Javier; González Vargas, Francisco
The association between chronic obstructive pulmonary disease (COPD) and anxiety and depression is not yet completely characterized, and differences between countries may exist. We used a predictive model to assess this association in a Spanish population. Prospective transversal descriptive study of 204 patients with stable COPD. Concomitant anxiety or depression were diagnosed by psychiatric assessment, using the diagnostic criteria of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). Sociodemographic, clinical and lung function parameters were analyzed. In total, 36% of stable COPD patients had psychiatric comorbidities, but 76% were unaware of their diagnosis. Nineteen percent had a pure anxiety disorder, 9.8% had isolated depression, and 7.3% had a mixed anxiety-depression disorder. Predictive variables in the multivariate analysis were younger age, higher educational level, lack of home support, higher BODE index, and greater number of exacerbations. The ROC curve of the model had an AUC of 0.765 (P<0.001). In COPD, concomitant psychiatric disorders are significantly associated with sociodemographic factors. Anxiety disorders are more common than depression. Patients with more severe COPD, according to BODE, younger patients and those with a higher educational level have a greater risk of being diagnosed with anxiety or depression in a structured psychiatric interview. In our population, most patients with psychiatric comorbidities remain unidentified. Copyright © 2015 SEPAR. Published by Elsevier Espana. All rights reserved.
Desseilles, Martin; Chang, Trina; Piguet, Camille; Bertschy, Gilles; Dayer, Alexandre G
Thought processing and mood regulation are closely linked, but existing classifications of mood disorders fail to recognize the complex interplay between these two clinical dimensions. Furthermore, existing classifications fail to account for the possibility that depression might be associated with an increased frequency of self-referential thoughts that could in some circumstances be related to creativity processes. Based on recent evidence from clinical phenomenology, experimental psychology and affective neuroscience, we propose a novel comprehensive theoretical framework that incorporates thought processing and emotional valence. This new taxonomy provides insights into the clinical understanding of the spectrum of mood disorders and accounts for the possibility of increased creativity in altered mood states.
Hendrie, C A; Pickles, A R
Several authors have suggested that rather than being a disease state, depression is an evolutionary adaptation to human social organization. Adaptations are produced in response to selection pressures and similar adaptations may easily have evolved in a range of other species. The current paper seeks to identify the social pressures that may lead to a species developing depression as an adaptation and the potential benefits that this may confer. It also examines whether rats and mice, the species most commonly used to model depression in the laboratory, have social organizations in which selection pressures towards the development of depression as an adaptation are likely to exist. It is proposed that depression is a useful adaptation in group-living animals, where there is competition for a social rank that gives reproductive advantage over others. The cluster of symptoms associated with depression include altered activity patterns, reduced sociability and appetite, and increased submissiveness. This combination strongly suggests that the function of depression is to reduce the likelihood of an individual being subject to further attack once they have lost social status and so increase their chances of survival in the period immediately following this. Successful transition from high to low status may provide further opportunities to reproduce. Hence, animals that become depressed during this critical period gain a reproductive advantage over those that do not, as these are either killed or expelled from the group. Wild mice do not have social hierarchies and are highly territorial. Wild rats do have social hierarchies however these only compete for reproductive advantage at the level of the sperm, and social status does not translate into significantly greater access to mates. Therefore, there are no selection pressures in these species towards the development of depression and so it is most unlikely that rats and mice have this adaptation. It is concluded that
Joseph K. O. Amoah; Devendra M. Amatya; Soronnadi. Nnaji
Hydrologic models often require correct estimates of surface macro-depressional storage to accurately simulate rainfallârunoff processes. Traditionally, depression storage is determined through model calibration or lumped with soil storage components or on an ad hoc basis. This paper investigates a holistic approach for estimating surface depressional storage capacity...
Abreu, Paulo Roberto; Santos, Carlos E.
This paper provides a review of behavioral models of depression highlighting the problems associated with its historical emphasis on lowered frequencies of positive reinforcement. We analyzed the models of Ferster and Lewinsohn in their theoretical approach, methodology and application. We conducted a review of the suppressive characteristics…
Bookwala, Jamila; Lawson, Brendan
Purpose: This study tested the applicability of the activity restriction model of depressed affect to the context of poor vision in late life. This model hypothesizes that late-life stressors contribute to poorer mental health not only directly but also indirectly by restricting routine everyday functioning. Method: We used data from a national…
Keenan, Kate; Hipwell, Alison; Feng, Xin; Rischall, Michal; Henneberger, Angela; Klosterman, Susan
Purpose To apply a diathesis × stress model to testing the association between peer victimization and depression in a sample of preadolescent girls. Methods DSM-IV symptoms of depression symptoms were measured at ages 9 and 11, assertiveness and peer victimization were assessed by youth report at age 9. Results The interaction of low levels of assertiveness and high peer victimization at age 9 was predictive of depression symptoms at age 11, controlling for earlier depression symptoms. Conclusions The results extend the literature on peer relations and depression by identifying a group of girls who may be particularly vulnerable to the stress of negative peer interactions. PMID:20970089
Full Text Available Modeling depression in animals is based on the observation of behaviors interpreted as analogue to human symptoms. Typical tests used in experimental depression research are designed to evoke an either-or outcome. It is known that explorative and coping strategies are relevant for depression, however these aspects are generally not considered in animal behavioral testing. Here we investigate the Flinders Sensitive Line (FSL, a rat model of depression, compared to the Sprague-Dawley (SD rat in three independent tests where the animals are allowed to express a more extensive behavioral repertoire. The multivariate concentric square field™ (MCSF and the novel cage tests evoke exploratory behaviors in a novel environment and the home cage change test evokes social behaviors in the re-establishment of a social hierarchy. In the MCSF test, FSL rats exhibited less exploratory drive and more risk-assessment behavior compared to SD rats. When re-exposed to the arena, FSL, but not SD rats, increased their exploratory behavior compared to the first trial and displayed risk-assessment behavior to the same extent as SD rats. Thus, the behavior of FSL rats was more similar to that of SDs when the rats were familiar with the arena. In the novel cage test FSL rats exhibited a reactive coping style, consistent with the reduced exploration observed in the MCSF. Reactive coping is associated with less aggressive behavior. Accordingly, FSL rats displayed less aggressive behavior in the home cage change test. Taken together, our data show that FSL rats express altered explorative behavior and reactive coping style. Reduced interest is a core symptom of depression, and individuals with a reactive coping style are more vulnerable to the disease. Our results support the use of FSL rats as an animal model of depression and increase our understanding of the FSL rat beyond the behavioral dimensions targeted by the traditional depression-related tests.
Ruiz, Francisco J; Odriozola-González, Paula
This study analyzed the interrelationships between key constructs of cognitive therapy (CT; depressogenic schemas), metacognitive therapy (MCT; dysfunctional metacognitive beliefs), and acceptance and commitment therapy (ACT; psychological inflexibility) in the prediction of depressive symptoms. With a lapse of nine months, 106 nonclinical participants responded twice to an anonymous online survey containing the following questionnaires: the Depression subscale of the Depression Anxiety and Stress Scales (DASS), the Dysfunctional Attitude Scale Revised (DAS-R), the Positive beliefs, Negative beliefs and Need to control subscales of the Metacognitions Questionnaire-30 (MCQ-30), and the Acceptance and Action Questionnaire - II (AAQ-II). Results showed that when controlling for baseline levels of depressive symptoms and demographic variables, psychological inflexibility longitudinally mediated the effect of depressogenic schemas (path ab = .023, SE = .010; 95% BC CI [.008, .048]) and dysfunctional metacognitive beliefs on depressive symptoms (positive metacognitive beliefs: path ab = .052, SE = .031; 95% BC CI [.005, .134]; negative metacognitive beliefs: path ab = .087, SE = .049; 95% BC CI [.016, .214]; need to control: path ab = .087, SE = .051; 95% BC CI [.013, .220]). Results are discussed emphasizing the role of psychological inflexibility in the CT and MCT models of depression.
Hymel, Kristen A; Sufka, Kenneth J
Cognitive bias presents in clinical populations where anxious individuals adopt a more pessimistic interpretation of ambiguous aversive stimuli and depressed individuals adopt both a more pessimistic interpretation of ambiguous aversive stimuli and a less optimistic interpretation of ambiguous appetitive stimuli. These biases have been reversed by anxiolytics and antidepressants. In the current study, chicks exposed to an isolation stressor of 5-min to induce an anxiety-like state or 60-min to induce a depressive-like state were tested in a straight alley maze to a series of morphed ambiguous appetitive (chick silhouette) to aversive (owl silhouette) cues. Chicks in the depression-like state displayed more pessimistic-like and less optimistic-like approach behavior to ambiguous aversive and appetitive cues, respectively. Both forms of cognitive bias were reversed by 15.0 mg/kg imipramine. Chicks in anxiety-like state displayed more pessimistic-like approach behavior under the ambiguous aversive stimulus cues. However, 0.10 mg/kg clonidine produced modest sedation and thus, was ineffective at reversing this bias. The observation that cognitive biases of more pessimism and less optimism can be reversed in the depression-like phase by imipramine adds to the validity of the chick anxiety-depression model as a neuropsychiatric simulation. This article is part of a Special Issue entitled 'Anxiety and Depression'.
Huston, Joseph P; Silva, Maria A de Souza; Komorowski, Mara; Schulz, Daniela; Topic, Bianca
The absence or loss of rewards or reinforcers holds a major role in the development of depression in humans. In spite of the prevalence of extinction-induced depression (EID) in humans, few attempts have been made to establish animal models thereof. Here we present the concept of extinction-related depression and summarize the results of two sets of studies in our attempt to create animal models of EID, one set based on extinction after positive reinforcement in the Skinner-box, the other on extinction after negative reinforcement - escape from water. We found various behaviors emitted during the extinction trials that responded to treatment with antidepressant drugs: Accordingly, the important behavioral marker for EID during extinction of escape from the water was immobility. During extinction after positive reinforcement the important indices for extinction-induced depression are the withdrawal from the former site of reward, biting behavior and rearing up on the hind legs. Avoidance behavior and biting may model aspects of human depressive behavior, which may include withdrawal or avoidance as well as aggressive-like behaviors.
Gross, D; Conrad, B; Fogg, L; Wothke, W
The purpose of this study was to test a model of maternal self-efficacy during toddlerhood using a longitudinal sequential design. Participants were 126 mothers of 1-year olds (Cohort 1) and 126 mothers of 2-year olds (Cohort 2) who completed questionnaires measuring maternal self-efficacy, depression, and perceived difficult toddler temperament three times over 1 year. Data were analyzed using structural equation modeling and maximum likelihood estimation. Findings support a model whereby (a) the more depressed the mother feels, the more likely she is to rate her toddler's temperament as difficult, (b) the more difficult the child's temperament is perceived to be, the lower the mother's estimates of her parenting self-efficacy, (c) the lower the mother's self-efficacy, the greater her depression, and (d) the more depressed the mother feels at one point in time, the more likely she is to remain depressed 6 months later. Implications of the findings are discussed as they relate to self-efficacy theory and nursing intervention with parents of difficult toddlers.
Koschke, Konstantin; Jörg Limbach, Hans; Kremer, Kurt; Donadio, Davide
Crystallisation of liquid solutions is of uttermost importance in a wide variety of processes in materials, atmospheric and food science. Depending on the type and concentration of solutes the freezing point shifts, thus allowing control on the thermodynamics of complex fluids. Here we investigate the basic principles of solute-induced freezing point depression by computing the melting temperature of a Lennard-Jones fluid with low concentrations of solutes, by means of equilibrium molecular dynamics simulations. The effect of solvophilic and weakly solvophobic solutes at low concentrations is analysed, scanning systematically the size and the concentration. We identify the range of parameters that produce deviations from the linear dependence of the freezing point on the molal concentration of solutes, expected for ideal solutions. Our simulations allow us also to link the shifts in coexistence temperature to the microscopic structure of the solutions.
Mathe, A.; Sousa, V.; Fischer, C. W.
Background: Mood disorders are the major cause of 'Years of life lived with disability' and a major cause of 'Years of life lost because of premature death'. The problem is growing due to the increased life-span and higher depression frequency with increasing age. Methods to prevent the onset...... resistant patients diagnosed with major depressive disorder. In order to better understand the mechanisms of ketamine effects we decided to test it on animal models. Methods: All experiments were approved by the Karolinska Institutet's Committee for Animal Protection. Two rat models, bred at the Karolinska...
Ge, Lin; Zhu, Ming-Ming; Yang, Jing-Yu; Wang, Fang; Zhang, Rong; Zhang, Jing-Hai; Shen, Jing; Tian, Hui-Fang; Wu, Chun-Fu
Depression is a complex psychiatric disorder, and its etiology and pathophysiology are not completely understood. Depression involves changes in many biogenic amine, neuropeptide, and oxidative systems, as well as alterations in neuroendocrine function and immune-inflammatory pathways. Oleamide is a fatty amide which exhibits pharmacological effects leading to hypnosis, sedation, and anti-anxiety effects. In the present study, the chronic mild stress (CMS) model was used to investigate the antidepressant-like activity of oleamide. Rats were exposed to 10weeks of CMS or control conditions and were then subsequently treated with 2weeks of daily oleamide (5mg/kg, i.p.), fluoxetine (10mg/kg, i.p.), or vehicle. Protein extracts from the hippocampus were then collected, and hippocampal maps were generated by way of two-dimensional gel electrophoresis (2-DE). Altered proteins induced by CMS and oleamide were identified through mass spectrometry and database searches. Compared to the control group, the CMS rats exhibited significantly less body weight gain and decreased sucrose consumption. Treatment with oleamide caused a reversal of the CMS-induced deficit in sucrose consumption. In the proteomic analysis, 12 protein spots were selected and identified. CMS increased the levels of adenylate kinase isoenzyme 1 (AK1), nucleoside diphosphate kinase B (NDKB), histidine triad nucleotide-binding protein 1 (HINT1), acyl-protein thioesterase 2 (APT-2), and glutathione S-transferase A4 (GSTA4). Compared to the CMS samples, seven spots changed significantly following treatment with oleamide, including GSTA4, glutathione S-transferase A6 (GSTA6), GTP-binding nuclear protein Ran (Ran-GTP), ATP synthase subunit d, transgelin-3, small ubiquitin-related modifier 2 (SUMO2), and eukaryotic translation initiation factor 5A-1 (eIF5A1). Of these seven proteins, the level of eIF5A1 was up-regulated, whereas the remaining proteins were down-regulated. In conclusion, oleamide has antidepressant
Pryce, Christopher R; Seifritz, Erich
Depression presents as a disorder of feelings and thoughts that debilitate daily functioning and can be life threatening. Increased understanding of these specific emotional-cognitive pathological states and their underlying pathophysiologies and neuropathologies is fundamental to an increased understanding of the disorder and, therefore, to development of much-needed improved therapies. Despite this, there is a current lack of emphasis on development and application of translational (i.e. valid) neuropsychological measures in depression research. The appropriate strategy is neuropsychological research translated, bi-directionally, between epidemiological and clinical human research and in vivo - ex vivo preclinical research conducted, primarily, with mice. This paper presents a translational framework to stimulate and inform such research, in four inter-dependent sections. (1) A depression systems-model describes the pathway between human environment-gene (E-G) epidemiology, pathophysiology, psycho- and neuropathology, symptoms, and diagnosis. This model indicates that G→emotional-cognitive endophenotypes and E-G/endophenotype→emotional-cognitive state markers are central to experimental and translational depression research. (2) Human neuropsychological tests with (potential) translational value for the quantitative study of these endophenotypes and state markers are presented. (3) The analogous rodent behavioural tests are presented and their translational validity in terms of providing analogue emotional-cognitive endophenotypes and state markers are discussed. (4) The need for aetiological validity of mouse models in terms of G→endophenotypes and E-G→state markers is presented. We conclude that the informed application of the proposed neuropsychological translational framework will yield mouse models of high face, construct and aetiological validity with respect to emotional-cognitive dysfunction in depression. These models, together with the available
Full Text Available BACKGROUND: Recent reviews question current animal models of depression and emphasise the need for ethological models of mood disorders based on animals living under natural conditions. Domestic horses encounter chronic stress, including potential stress at work, which can induce behavioural disorders (e.g. "apathy". Our pioneering study evaluated the potential of domestic horses in their usual environment to become an ethological model of depression by testing this models' face validity (i.e. behavioural similarity with descriptions of human depressive states. METHODOLOGY/PRINCIPAL FINDINGS: We observed the spontaneous behaviour of 59 working horses in their home environment, focusing on immobility bouts of apparent unresponsiveness when horses displayed an atypical posture (termed withdrawn hereafter, evaluated their responsiveness to their environment and their anxiety levels, and analysed cortisol levels. Twenty-four percent of the horses presented the withdrawn posture, also characterized by gaze, head and ears fixity, a profile that suggests a spontaneous expression of "behavioural despair". When compared with control "non-withdrawn" horses from the same stable, withdrawn horses appeared more indifferent to environmental stimuli in their home environment but reacted more emotionally in more challenging situations. They exhibited lower plasma cortisol levels. Withdrawn horses all belonged to the same breed and females were over-represented. CONCLUSIONS/SIGNIFICANCE: Horse might be a useful potential candidate for an animal model of depression. Face validity of this model appeared good, and potential genetic input and high prevalence of these disorders in females add to the convergence. At a time when current animal models of depression are questioned and the need for novel models is expressed, this study suggests that novel models and biomarkers could emerge from ethological approaches in home environments.
Su, Chun-Lin; Su, Chun-Wei; Hsiao, Ya-Hsin; Gean, Po-Wu
Major depressive disorder (MDD), one of the most common mental disorders, is a significant risk factor for suicide and causes a low quality of life for many people. However, the causes and underlying mechanism of depression remain elusive. In the current work, we investigated epigenetic regulation of BDNF in the learned helplessness-induced animal model of depression. Mice were exposed to inescapable stress and divided into learned helplessness (LH) and resilient (LH-R) groups depending on the number they failed to escape. We found that the LH group had longer immobility duration in the forced swimming test (FST) and tail suspension tests (TST), which is consistent with a depression-related phenotype. Western blotting analysis and enzyme-linked immunosorbent assay (ELISA) revealed that the LH group had lower BDNF expression than that of the LH-R group. The LH group consistently had lower BDNF mRNA levels, as detected by qPCR assay. In addition, we found BDNF exon IV was down-regulated in the LH group. Intraperitoneal injection of imipramine or histone deacetylase inhibitors (HDACi) to the LH mice for 14 consecutive days ameliorated depression-like behaviors and reversed the decrease in BDNF. The expression of HDAC5 was up-regulated in the LH mice, and a ChIP assay revealed that the level of HDAC5 binding to the promoter region of BDNF exon IV was higher than that seen in other groups. Knockdown of HDAC5 reduced depression-like behaviors in the LH mice. Taken together, these results suggest that epigenetic regulation of BDNF by HDAC5 plays an important role in the learned helplessness model of depression. Copyright © 2016 Elsevier Ltd. All rights reserved.
Li, B.; Schulz, D.; Li, B; Piriz, J.; Mirrione, M.; Chung, C.H.; Proulx, C.D.; Schulz, D.; Henn, F.; Malinow, R.
The cellular basis of depressive disorders is poorly understood. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (that is, disappointment or anticipation of a negative outcome). LHb neurons project to, and modulate, dopamine-rich regions, such as the ventral tegmental area (VTA), that control reward-seeking behaviour and participate in depressive disorders. Here we show that in two learned helplessness models of depression, excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal's helplessness behaviour and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective for patients who are depressed, markedly suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behaviour in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression.
问黎敏; 安书成; 刘慧
sufficient validity. The most accepted one is the chronic unpredictable mild stress (CUMS) rodent model, in which rats are chronically and unpredictably subjected to a variety of stressors including immersion in cold water, tail pinch, day and night reversal, and so on. There are several theoretical mechanisms for depression, such as the monoamine neurotransmitter imbalance theory and the neural plasticity theory, but none of them can fully elucidate the formation of depression. Due to the weak and irregular anti-depressant effects of monoamines, glutamate (Glu) and its receptors, especially N-methyl-D-aspartic acid (NMDA) receptors and a-amino-3-hydroxy-5-methylisoxazole-4- propionic acid (AMPA) receptors, have gained more attention in recent years. As an important isoform of the 5-hydroxytryptamine (5-HT) receptor, the 1A receptor is highly expressed in the hippocampus. Numerous pharmacological and clinical studies show that the 1A receptor is correlated with the development and therapy of major depressive disorder, anxiety, and drug addiction. The present study investigates the expression and role of the 5-HT receptor 1A (5-HT1AR) and its relationship with NMDA and AMPA receptors in depression induced by CUMS.The CUMS induced depression model was done using Sprague-Dawley rats that were given intra-hippocampal microinjections of drugs. The location of injections was determined by rat brain stereotaxic coordinates. The behavioral observations were conducted by measurement of weight changes, sucrose preference test, open-field test, and tail suspension test. The expression of 5-HT1AR was detected by Western blot, and the expression and phosphorylation of the NMDA and AMPA receptor's subunits were detected by Western blot and ELISA, respectively.The results showed that CUMS rats had depressive-like behavior, lower expression of 5-HT1AR, lower expression and phosphorylation of AMPA receptor subunits (GluR2/3), and higher expression and phosphorylation of NMDA receptor
del Pino Pérez, Antonio; Ibáñez Fernández, Ignacio; Bosa Ojeda, Francisco; Dorta González, Ruth; Gaos Miezoso, María Teresa
The objective of this study was to validate in a sample of 205 coronary patients a factor model for the BDI-II, especially a model that would allow for modeling of depressive symptoms after explicitly removing bias related to somatic symptoms of depression that would overlap those of heart disease. Exploratory and confirmatory factor analyses for ordinal data were conducted. A one-factor model, six correlated two-factor models and, derivatives thereof, seven models with a single General Depression factor and two uncorrelated factors, were analyzed. Exploratory analysis extracted two factors, Somatic-affective and Cognitive. Confirmatory factor analyses showed the worst fit for the one-factor model. Two-factor models were surpassed in goodness of fit by the models of general-factor and group factors. Among these, the General, Somatic-affective and Cognitive (G-Sa-C) model of Beck with students is noteworthy. The reduced General, Somatic and Cognitive (G-S-C) model of Ward showed the worst goodness of fit. Our model surpasses the cutoff criteria of all fit indexes. We conclude that the inclusion of a general-factor and group factors in all the models surpasses the results of G-S-C model and, therefore, questions it. The G-Sa-C model is strengthened.
Wei Wang; Wenxun Li; Fang Fang; Hao Lei; Xiaoping Yin; Jianpin Qi; Baiseng Wang; Chengyuan Wang
Objective: To investigate findings and value of quantitative MR in depression model of rats. Methods: Twenty male SD rats were divided into model group and control group randomly (10 rats in each group). The depression model of rats was erected by separation and chronic unpredictable stress. The behavior of rat was detected by open-field test and sucrose consumption. The MR images of brain tissues were produced in vivo rats with T2-and diffusion-weighted imaging. The changes of body weight and behavior score and thevalues of T2 and ADC of ROIs were compared between the two groups. Histological verification of hippocampal neuron damage was alsoperformed under ultramicrosopy. Results: Compared with the control group, T2 values in hippocampus prolonged 5.5 % ( P ＜ 0.05),ADC values in hippocampus and in temporal lobe cortex decreased 11.7 % and 10.9% (P ＜ 0.01)respectively in the model group. Histo-logic data confirmed severe neuronal damage in the hippocampus of the model group. Conclusion: This study capitalized on diffusion-weighted imaging as a sensitive technique for the identification of neuronal damage in depression and it provides an experimental evidence ofMRI in depression investigation and clinical application.
Siddappa, Adarsh Lakkur; Raman, Rajesh; Hattur, Basavana Gowdappa
Introduction Conceptualization of depression may have bearing on treatment seeking. It may affect adherence behaviour of the patients. Aim To find out the explanatory models and their relationship with socio-demographic variables and medication adherence in patients with depression. Materials and Methods Fifty-eight consecutive patients with depression in remission were recruited as per selection criteria. Socio-demographic details were collected. Patients were assessed using Mental Distress Explanatory Model Questionnaire (MDEMQ) and Morisky Medication Adherence Scale (MMAS). Results Significant scores were observed in all dimensions of explanatory models. In the Mann-Whitney U test the patient’s marital status (MU=113.500, p=0.05, sig≤0.05, 2-tailed), and family history of mental illness (MU=165.5, p=0.03, sig≤0.05, 2-tailed) had a statistically significant group difference in the score of MDEMQ. In linear regression analysis, four predictors (MDEMQ subscales Stress, Western physiology, Non-Western physiology and Supernatural) had significantly predicted the value of MMAS (R2=0.937, f=153.558, p<0.001). Conclusion Findings of this study suggested that patients with depression harbor multidimensional explanatory model. The levels of explanatory models are inversely associated with levels of medication adherence. PMID:28274025
Blasco-Serra, Arantxa; Escrihuela-Vidal, Francesc; González-Soler, Eva M; Martínez-Expósito, Fernando; Blasco-Ausina, M Carmen; Martínez-Bellver, Sergio; Cervera-Ferri, Ana; Teruel-Martí, Vicent; Valverde-Navarro, Alfonso A
Since the pathogenesis of fibromyalgia is unknown, treatment options are limited, ineffective and in fact based on symptom relief. A recently proposed rat model of fibromyalgia is based on central depletion of monamines caused by reserpine administration. This model showed widespread musculoskeletal pain and depressive-like symptoms, but the methodology used to measure such symptoms has been criticized. Evidence relates the high prevalence of pain and depression in fibromyalgia to common pathogenic pathways, most probably focused on the monoaminergic system. The present study aims at a validation of the reserpine model of fibromyalgia. For this purpose, rats undergoing this model have been tested for depressive-like symptoms with a Novelty-Suppressed Feeding Test adaptation. Animals administered with reserpine and subjected to forced food deprivation performed a smaller number of incursions to the center of the open field, evidenced by a decrease in the per-minute rate of the rats' approaching, smelling or touching the food. They also took more time to eat from the central food than control rats. These NSFT findings suggest the presence of depressive-like disorders in this animal model of fibromyalgia.
Hu, Xiaofan; Dong, Yulin; Jin, Xiaohang; Zhang, Chunkui; Zhang, Ting; Zhao, Jie; Shi, Juan; Li, Jinlian
Chronic pain and depression frequently coexist in clinical setting, and current clinical treatments for this comorbidity have shown limited efficacy. Triptolide (T10), an active component of Tripterygium wilfordii Hook F., has been demonstrated to exert strong analgesic activities in experimental pain models, but whether it possesses anti-depressive actions remains unknown. Using a depression comorbidity of chronic pain rat model induced by spinal nerve ligation (SNL), we investigated the potency of T10 for the treatment of comorbid depression in comparison with a widely used antidepressant, fluoxetine (FLX). Concomitant neuroinflammation changes were also examined in the hippocampus. The results showed that prophylactic and reversal treatments with T10 dose-dependently (30, 100, 300μg/kg) inhibited the depression-like behaviors (DLB) assessed by the forced swim test, sucrose preference test and body weight measurement. The anti-depressive efficacy of T10 at 300μg/kg was significantly stronger than that of FLX at 18mg/kg. T10 at all three doses exhibited more efficient analgesic effects than FLX at 18mg/kg. The combined application of T10 with FLX markedly augmented the effects of T10 or FLX per se, with the facilitating effects of T10 at 30μg/kg being most prominent. In addition, nerve injury caused the activation of microglia and p38 MAPK, the upregulation of IL-1β and TNF-α as well as the downregulation of IL-10 in the hippocampus at postoperative week (POW) 3. These neuroinflammatory responses were reversed by subchronic treatment with T10. Taken together, these results demonstrate that T10 possesses potent anti-depressive function, which is correlated with its immunoregulation in the hippocampus. The combination of a low dose of T10 with FLX may become a more effective medication strategy for the treatment of comorbid depression and chronic pain.
Weitlauf, Amy S.; Cole, David A.
Attributional style models of depression in adults (Abramson et al. 1989, 1978) have been adapted for use with children; however, most applications do not consider that children's understanding of causal relations may be qualitatively different from that of adults. If children's causal attributions depend on children's level of cognitive…
Johnson, Jeffrey G.; Zhang, Baohui; Prigerson, Holly G.
Data from a community-based multi-wave investigation were used to examine a developmental model of risk for depression and suicidality following the death of a spouse. Measures of perceived parental affection and control during childhood were administered to 218 widowed adults 11 months after the death of the spouse. Self-esteem, spousal…
Weitlauf, Amy S.; Cole, David A.
Attributional style models of depression in adults (Abramson et al. 1989, 1978) have been adapted for use with children; however, most applications do not consider that children's understanding of causal relations may be qualitatively different from that of adults. If children's causal attributions depend on children's level of cognitive…
Bangsgaard, Elisabeth; Ottesen, Johnny T.
A novel model of the hypothalamic-pituitary-adrenal axis is presented. The axis is an endocrine system responsible for coping with stress and it is likely to be involved in depression. The dynamics of the system is studied and existence, uniqueness and positivity of the solution and the existence...
Depression is at the top position for "years lived with disability" (Smith, 2014). Its aetiology is unknown, but the pathogenesis implicates changes in glutamatergic neuronal plasticity. Glutamatergic plasticity likely mediates the effects of antidepressants acting through monoamines. Histamine is a monoaminergic neuromodulator able to regulate glutamatergic plasticity and synaptic transmission. The Flinders sensitive line (FSL) rat has face and predictive validity as model ...
Lambert, Sharon F.; McCreary, Beth T.; Joiner, Thomas E.; Schmidt, Norman B.; Ialongo, Nicolas S.
In this study, the authors examined the validity of the tripartite model of anxiety and depression (L. A. Clark & D. Watson, 1991) in a community epidemiological sample of 467 urban African American youth. Participants completed the Baltimore How I Feel (N. S. Ialongo, S. G. Kellam, & J. Poduska, 1999), a measure of anxiety and depressive…
Possel, Patrick; Seemann, Simone; Ahrens, Stefanie; Hautzinger, Martin
In Dodge's model of "social information processing" depression is the result of a linear sequence of five stages of information processing ("Annu Rev Psychol" 44: 559-584, 1993). These stages follow a person's reaction to situational stimuli, such that each stage of information processing mediates the relationship between earlier and later stages.…
Fransina J. de Jong
Full Text Available Background: In the Depression Initiative, a promising collaborative care model for depression that was developed in the US was adapted for implementation in the Netherlands. Aim: Description of a collaborative care model for major depressive disorder (MDD and of the factors influencing its implementation in the primary care setting in the Netherlands. Data sources: Data collected during the preparation phase of the CC:DIP trial of the Depression Initiative, literature, policy documents, information sheets from professional associations. Results: Factors facilitating the implementation of the collaborative care model are continuous supervision of the care managers by the consultant psychiatrist and the trainers, a supportive web-based tracking system and the new reimbursement system that allows for introduction of a mental health care-practice nurse (MHC-PN in the general practices and coverage of the treatment costs. Impeding factors might be the relatively high percentage of solo-primary care practices, the small percentage of professionals that are located in the same building, unfamiliarity with the concept of collaboration as required for collaborative care, the reimbursement system that demands regular negotiations between each health care provider and the insurance companies and the reluctance general practitioners might feel to expand their responsibility for their depressed patients. Conclusion: Implementation of the collaborative care model in the Netherlands requires extensive training and supervision on micro level, facilitation of reimbursement on meso- and macro level and structural effort to change the treatment culture for chronic mental disorders in the primary care setting.
Yu, Tao; Guo, Ming; Garza, Jacob; Rendon, Samantha; Sun, Xue-Li; Zhang, Wei; Lu, Xin-Yun
Human depression is associated with cognitive deficits. It is critical to have valid animal models in order to investigate mechanisms and treatment strategies for these associated conditions. The goal of this study was to determine the association of cognitive dysfunction with depression-like behaviour in an animal model of depression and investigate the neural circuits underlying the behaviour. Mice that were exposed to social defeat for 14 d developed depression-like behaviour, i.e. anhedonia and social avoidance as indicated by reduced sucrose preference and decreased social interaction. The assessment of cognitive performance of defeated mice demonstrated impaired working memory in the T-maze continuous alternation task and enhanced fear memory in the contextual and cued fear-conditioning tests. In contrast, reference learning and memory in the Morris water maze test were intact in defeated mice. Neuronal activation following chronic social defeat was investigated by c-fosin-situ hybridization. Defeated mice exhibited preferential neural activity in the prefrontal cortex, cingulate cortex, hippocampal formation, septum, amygdala, and hypothalamic nuclei. Taken together, our results suggest that the chronic social defeat mouse model could serve as a valid animal model to study depression with cognitive impairments. The patterns of neuronal activation provide a neural basis for social defeat-induced changes in behaviour.
Petersén, Asa; Wörtwein, Gitta; Gruber, Susanne H M
) reduced by escitalopram treatment in maternally separated animals to the level found in non-separated animals. These results argue against the prevailing hypothesis that adult cytogenesis is reduced in depression and that the common mechanism underlying antidepressant treatments is to increase adult...... cytogenesis. The results also point to the importance of using a disease model and not healthy animals for testing effects of potential treatments for human depression and suggest other cellular mechanisms of action than those that had previously been proposed for escitalopram....
Hamani, Clement; Nóbrega, José N
Deep brain stimulation (DBS) is currently being investigated as a therapy for the treatment of depression. Despite promising results of recent clinical trials, neural and chemical mechanisms responsible for the effects of stimulation are still unclear. In this article, we review clinical and laboratory findings on DBS for depression. Particular emphasis will be given to aspects involved in the translation of data from animal models to humans and in our findings on the potential substrates involved in the antidepressant effects of DBS in rats.
Fischer, C. W.; Elfving, B.; Lund, S.
(registered trademark) 2ML4, infusion rate 2.5l/day), which delivers LPS through a catheter into the abdomen. Depression-like behavior was assessed as increased time spent immobile in the forced swim test (FST). Peripheral markers of a low-grade inflammation was measured using a high sensitivity ELISA kit and central...... disturbances or sickness behavior. Thus, this model might help elucidating some of the mechanisms underlying inflammation-associated depression, in order to assist in developing more effective treatment strategies for this group of patients....
Hankin, Benjamin L.
Depression commonly co-occurs with anxiety and externalizing problems. Etiological factors from a central cognitive theory of depression, the Hopelessness Theory (Abramson et al. "Psychological Review," 96, 358-372, 1989), were examined to evaluate whether a negative inferential style about cause, consequence, and self interacted with stressors…
Cantazaro, Amy; Wei, Meifen
Attachment anxiety is expected to be positively associated with dependence and self-criticism. However, attachment avoidance is expected to be negatively associated with dependence but positively associated with self-criticism. Both dependence and self-criticism are expected to be related to depressive symptoms. Data were analyzed from 424 undergraduate participants at a large Midwestern university, using structural equation modeling. Results indicated that the relation between attachment anxiety and depressive symptoms was fully mediated by dependence and self-criticism, whereas the relation between attachment avoidance and depressive symptoms was partially mediated by dependence and self-criticism. Moreover, through a multiple-group comparison analysis, the results indicated that men with high levels of attachment avoidance are more likely than women to be self-critical.
Jianbin Zhang; Lingling Wang; Xinjun Wang; Jingfeng Jiang; Xiaoren Xiang; Tianjun Wang
Adrenergic receptor dysfunction is suggested as a potential cause of hippocampal vulnerability to stress-related pathology. We examined mRNA expression of adrenergic receptor (AR) subtypes α1-AR, α2-AR, and β1-AR in hippocampal subregions (CA1, CA3, dentate gyrus) using in situ hybridization in a depression model induced by chronic unpredictable mild stress and social isolation. α1-AR mRNA expression was significantly increased in the CA3 and dentate gyrus, β1-AR mRNA was significantly increased in the CA1, and α2-AR mRNA remained unchanged in all regions of depression rats compared with controls. Thus, different AR subtypes exhibit a differing pattern of mRNA expression in various hippocampal subregions following depression.
Hemanth Kumar, B S; Mishra, S K; Trivedi, R; Singh, S; Rana, P; Khushu, S
Depression is among the most debilitating diseases worldwide. Long-term exposure to stressors plays a major role in development of human depression. Chronic mild stress (CMS) seems to be a valid animal model for depression. Diffusion tensor imaging (DTI) is capable of inferring microstructural abnormalities of the white matter and has shown to serve as non-invasive marker of specific pathology. We developed a CMS rat model of depression and validated with behavioral experiments. We measured the diffusion indices (mean diffusivity (MD), fractional anisotropy (FA), axial (λ∥) and radial (λ⊥) diffusivity) to investigate the changes in CMS rat brain during depression onset. Diffusion indices have shown to be useful to discriminate myelin damage from axon loss. DTI was performed in both control and CMS rats (n=10, in each group) and maps of FA, MD, λ∥ and λ⊥ diffusivity values were generated using in-house built software. The diffusion indices were calculated by region of interest (ROI) analysis in different brain regions like the frontal cortex, hippocampus, hypothalamus, cingulum, thalamus, caudate putamen, corpus callosum, cerebral peduncle and sensory motor cortex. The results showed signs of demyelination, reflected by increased MD, decreased FA and increased λ⊥. The results also suggest a possible role of edema or inflammation concerning the brain morphology in CMS rats. The overall finding using DTI suggests there might be a major role of loss of myelin sheath, which leads to disrupted connectivity between the limbic area and the prefrontal cortex during the onset of depression. Our findings indicate that interpretation of these indices may provide crucial information about the type and severity of mood disorders.
Martin, Alison L; Brown, Richard E
Animal models of depression seldom test females, even though women are twice as likely as men to suffer from major depressive disorder. Since female mice are sensitive to social isolation, we tested a separation-based model of depression in three experiments. In experiment 1 female C57BL/6J mice were housed in three conditions: isolated (housed individually from 8 weeks of age), separated (housed in groups and then separated and housed individually at 23 weeks of age) and grouped (housed in groups from 8 weeks of age). At 24 weeks of age, there was a significant increase in weight and in immobility in individually housed mice in the forced swim test (FST) and tail suspension test (TST), a reduction in transitions in the L/D box, a reduced startle response and reduced prepulse inhibition, but no differences in cued or context fear conditioning. Experiment 2 showed that fluoxetine treatment administered via drinking water attenuated depressive-like behaviour in the FST and TST in individually housed female C57BL/6J mice, but had no effect on anxiety-like behaviour. Experiment 3 found that group-housed females had higher baseline corticosterone (CORT) levels than isolated females and fluoxetine had no effect on CORT levels. Thus, separation from group housing is a reliable and valid method for inducing depression-like behaviour in female mice. This procedure is both versatile, allowing for the study of genetic and environmental interactions, and accessible, making it useful for studying depression and testing new drugs for its treatment.
Zhen-Hua Chen; Ling Xiao; Ji-Hong Chen; He-Shen Luo; Gao-Hua Wang; Yong-Lan Huang; Xiao-Ping Wang
AIM: To investigate the effects of fluoxetine on depression-induced changes of mast cell morphology and protease-1 (rMCP-1) expression in rats.METHODS: A Sprague-Dawley rat model of chronic stress-induced depression was established. Fifty experimental rats were randomly divided into the following groups: normal control group, fluoxetine +normal control group, depressed model group, saline + depressed model group, and fluoxetine + depressed model group. Laser scanning confocal microscopy (LSCM) immunofluorecence and RT-PCR techniques were used to investigate rMCP-1 expression in gastric antrum. Mast cell morphology was observed under transmission electron microscopy. ANOVA was used for statistical analysis among groups.RESULTS: Morphologic observation indicated that depression induced mast cell proliferation, activation,and granule hyperplasia. Compared with the normal control group, the average immunofluorescence intensity of gastric antrum rMCP-1 significantly increased in depressed model group (37.4 4- 7.7 vs 24.5+ 5.6, P < 0.01) or saline + depressed model group (39.9 4- 5.0 vs 24.5 ± 5.6, P < 0.01), while there was no significant difference between fluoxetine + normal control group (23.1 4- 3.4) or fluoxetine + depressed model group (26.1 4- 3.6) and normal control group.The average level of rMCP-lmRNA of gastric antrum significantly increased in depressed model group (0.759 ± 0.357 vs 0.476 ± 0.029, P < 0.01) or saline + depressed model group (0.781 4- 0.451 vs 0.476 ±0.029, P < 0.01 ), while no significant difference was found between fluoxetine + normal control group (0.460 ± 0.027) or fluoxetine + depressed model group (0.488 ± 0.030) and normal control group. Fluoxetine showed partial inhibitive effects on mast cell ultrastructural alterations and de-regulated rMCP-1 expression in gastric antrum of the depressed rat model.CONCLUSION: Chronic stress can induce mast cell proliferation, activation, and granule hyperplasia in gastric antrum. Fluoxetine
Fowler, David; Hodgekins, Joanne; Garety, Philippa; Freeman, Daniel; Kuipers, Elizabeth; Dunn, Graham; Smith, Ben; Bebbington, Paul E.
The role of negative cognition and effect in maintaining psychotic symptoms is increasingly recognized but has yet to be substantiated though longitudinal analysis. Based on an a priori theoretical model, we hypothesized that negative cognition and depressed mood play a direct causal role in maintaining paranoia in people with psychosis and that the effect of mood is mediated by negative cognition. We used data from the 301 patients in the Prevention of Relapse in Psychosis Trial of cognitive behavior therapy. They were recruited from consecutive Community Mental Health Team clients presenting with a recent relapse of psychosis. The teams were located in inner and outer London and the rural county of Norfolk, England. The study followed a longitudinal cohort design, with initial measures repeated at 3 and 12 months. Structural equation modeling was used to investigate the direction of effect between negative cognition, depressed mood, and paranoia. Overall fit was ambiguous in some analyses and confounding by unidentified variables cannot be ruled out. Nevertheless, the most plausible models were those incorporating pathways from negative cognition and depressed mood to paranoid symptoms: There was no evidence whatsoever for pathways in the reverse direction. The link between depressed mood and paranoia appeared to be mediated by negative cognition. Our hypotheses were thus corroborated. This study provides evidence for the role of negative cognition in the maintenance of paranoia, a role of central relevance, both to the design of psychological interventions and to the conceptualizations of psychosis. PMID:21474550
Now 30 years old, the chronic mild stress (CMS) model of depression has been used in >1300 published studies, with a year-on-year increase rising to >200 papers in 2015. Data from a survey of users show that while a variety of names are in use (chronic mild/unpredictable/varied stress), these describe essentially the same procedure. This paper provides an update on the validity and reliability of the CMS model, and reviews recent data on the neurobiological basis of CMS effects and the mechanisms of antidepressant action: the volume of this research may be unique in providing a comprehensive account of antidepressant action within a single model. Also discussed is the use of CMS in drug discovery, with particular reference to hippocampal and extra-hippocampal targets. The high translational potential of the CMS model means that the neurobiological mechanisms described may be of particular relevance to human depression and mechanisms of clinical antidepressant action.
Avari, Jimmy N; Alexopoulos, George S
Depression worsens most treatment outcomes in medically ill older adults. Chronic medical illnesses weaken and demoralize patients and compromise their ability to adhere to treatments requiring consistency and effort. Acute medical illnesses create a psychosocial storm that finds patients and their ecosystem unprepared. We describe two intervention models that can be used to target and personalize treatment in depressed, chronically, or acutely medically ill older adults. The Personalized Adherence Intervention for Depression and COPD (PID-C) is a model intervention for depressed patients with chronic medical illnesses. It targets patient-specific barriers to treatment engagement and aims to shift the balance in favor of treatment participation. PID-C led to higher remission rates of depression, reduction in depressive symptoms, and reduction in dyspnea-related disability. The addition of problem-solving training enables patients to use resources available to them and hopefully improve their outcomes. Ecosystem-focused therapy (EFT) is a model intervention for depression developing in the context of an acute medical event. It was developed for patients with poststroke depression (PSD) and targets five areas, part of the "psychosocial storm" originating from the patient's sudden disability and the resulting change in the patient's needs and family's life. A preliminary study suggests that EFT is feasible and efficacious in reducing depressive symptoms and signs and disability in PSD.
Knowles, Sarah E; Chew-Graham, Carolyn; Adeyemi, Isabel; Coupe, Nia; Coventry, Peter A
Patients with comorbid depression and physical health problems have poorer outcomes compared with those with single long term conditions (LTCs), or multiple LTCs without depression. Primary care has traditionally struggled to provide integrated care for this group. Collaborative care can reduce depression in people with LTCs but evidence is largely based on trials conducted in the United States that adopted separate treat to target protocols for physical and mental health. Little is known about whether collaborative care that integrates depression care within the management of LTCs is implementable in UK primary care, and acceptable to patients and health care professionals. Nested interview study within the COINCIDE trial of collaborative care for patients with depression and diabetes/CHD (ISRCTN80309252). The study was conducted in primary care practices in North West England. Professionals delivering the interventions (nurses, GPs and psychological well-being practitioners) and patients in the intervention arm were invited to participate in semi-structured qualitative interviews. Based on combined thematic analysis of 59 transcripts, we identified two major themes: 1) Integration: patients and professionals valued collaborative ways of working because it enhanced co-ordination of mental and physical health care and provided a sense that patients' health was being more holistically managed. 2) Division: patients and professionals articulated a preference for therapeutic and spatial separation between mental and physical health. Patients especially valued a separate space outside of their LTC clinic to discuss their emotional health problems. The COINCIDE care model, that sought to integrate depression care within the context of LTC management, achieved service level integration but not therapeutic integration. Patients preferred a protected space to discuss mental health issues, and professionals maintained barriers around physical and mental health expertise
Tsai, Yi-Chen; Pai, Hsiang-Chu
This study proposes and evaluates a model of depression that concerns the role of burden and cognitive appraisal as mediators or moderators of outcomes among stroke survivor caregivers. A total of 105 informal caregivers of stroke survivor completed the self-report measures of Caregiver Burden Inventory, Center for Epidemiologic Studies Depression Scale, and Cognitive Impact of Appraisal Scale. The Glasgow Coma Scale and Barthel Index were used by the researcher to examine the physical functional status of the survivor. Partial least squares (PLS) path modeling was used to estimate the parameters of a depression model that included mediating or moderating effects. The model shows that burden and impact of cognitive appraisal have a significant direct and indirect impact on depression, while survivor physical functional status does not have a direct impact. The model also demonstrates that burden and impact of cognitive appraisal separately play a mediating role between survivor physical functional status and caregiver depression. In addition, cognitive appraisal has a moderating influence on the relationship between burden and depression. Overall, survivor physical functional status, burden, and cognitive appraisal were the predictors of caregiver depression, explaining 47.1% of the variance. This study has shown that burden and cognitive appraisal are mediators that more fully explain the relationship between patient severity and caregiver depression. Copyright © 2015 Elsevier Inc. All rights reserved.
Dinorah (Dina Martinez Tyson
Full Text Available The Surgeon General's report, “Culture, Race, and Ethnicity: A Supplement to Mental Health,” points to the need for subgroup specific mental health research that explores the cultural variation and heterogeneity of the Latino population. Guided by cognitive anthropological theories of culture, we utilized ethnographic interviewing techniques to explore cultural models of depression among foreign-born Mexican (n=30, Cuban (n=30, Columbian (n=30, and island-born Puerto Ricans (n=30, who represent the largest Latino groups in Florida. Results indicate that Colombian, Cuban, Mexican, and Puerto Rican immigrants showed strong intragroup consensus in their models of depression causality, symptoms, and treatment. We found more agreement than disagreement among all four groups regarding core descriptions of depression, which was largely unexpected but can potentially be explained by their common immigrant experiences. Findings expand our understanding about Latino subgroup similarities and differences in their conceptualization of depression and can be used to inform the adaptation of culturally relevant interventions in order to better serve Latino immigrant communities.
Arbabi, Leila; Baharuldin, Mohamad Taufik Hidayat; Moklas, Mohamad Aris Mohamad; Fakurazi, Sharida; Muhammad, Sani Ismaila
Postpartum depression (PPD) is a psychiatric disorder that occurs in 10-15% of childbearing women. It is hypothesized that omega-3 fatty acids, which are components of fish oil, may attenuate depression symptoms. In order to examine this hypothesis, the animal model of postpartum depression was established in the present study. Ovariectomized female rats underwent hormone-simulated pregnancy (HSP) regimen and received progesterone and estradiol benzoate or vehicle for 23 days, mimicking the actual rat's pregnancy. The days after hormone termination were considered as the postpartum period. Forced feeding of menhaden fish oil, as a source of omega-3, with three doses of 1, 3, and 9g/kg/d, fluoxetine 15mg/kg/d, and distilled water 2ml/d per rat started in five postpartum-induced and one vehicle group on postpartum day 1 and continued for 15 consecutive days. On postpartum day 15, all groups were tested in the forced swimming test (FST) and open field test (OFT), followed by a biochemical assay. Results showed that the postpartum-induced rats not treated with menhaden fish oil, exhibited an increase in immobility time seen in FST, hippocampal concentration of corticosterone and plasmatic level of corticosterone, and pro-inflammatory cytokines. These depression-related effects were attenuated by supplementation of menhaden fish oil with doses of 3 and 9g/kg. Moreover, results of rats supplemented with menhaden fish oil were comparable to rats treated with the clinically effective antidepressant, fluoxetine. Taken together, these results suggest that menhaden fish oil, rich in omega-3, exerts beneficial effect on postpartum depression and decreases the biomarkers related to depression such as corticosterone and pro-inflammatory cytokines. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
Bannach-Brown, Alexandra; Liao, Jing; Wegener, Gregers
The aim of this study is to systematically collect all published preclinical non-human animal literature on depression to provide an unbiased overview of existing knowledge. A systematic search will be carried out in PubMed and Embase. Studies will be included if they use non-human animal...... experimental model(s) to induce or mimic a depressive-like phenotype. Data that will be extracted include the model or method of induction; species and gender of the animals used; the behavioural, anatomical, electrophysiological, neurochemical or genetic outcome measure(s) used; risk of bias....../quality of reporting; and any intervention(s) tested. There were no exclusion criteria based on language or date of publication. Automation techniques will be used, where appropriate, to reduce the human reviewer time. Meta-analyses will be conducted if feasible. This broad systematic review aims to gain a better...
Bangsgaard, Elisabeth O; Ottesen, Johnny T
A novel model of the hypothalamic-pituitary-adrenal axis is presented. The axis is an endocrine system responsible for coping with stress and it is likely to be involved in depression. The dynamics of the system is studied and existence, uniqueness and positivity of the solution and the existence of an attracting trapping region are proved. The model is calibrated and compared to data for healthy and depressed subjects. A sensitivity analysis resulting in a set of identifiable physiological parameters is provided. A subset is selected for parameter estimation and a reduced version of the model is stated and an approximated version is discussed. The model is physiologically based, thus parameters are representative for gland functions or elimination processes. Hence the model may be used for pointing out pathologies by parameter estimation and hypothesis testing whereby it may be used as an objective and refined method for diagnosing depression and suggesting individual treatment protocols. Finally, the method may inspire pharmaceutical companies to develop target specific psychopharmaca for more effective and individual treatment.
周兰兰; 明亮; 马传庚; 樊美珍; 程燕; 江勤
Objective: To study the antidepressant effects and its mechanism of bioactive compounds (metabolite extract) from entomogenous fungi (BCEF) on experimental animal models of depression. Methods: The antidepressant effect of BCEF was examined on the acquired models of depression (rats and mice in forced swimming test) and unpredictable chronic stress mouse models. The behavior alterations were assayed by detecting the duration of immobility in forced swimming test. UV spectrophotometer analysis technique was used to detect the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) in mice brain mitochondria; and colorimetric method was used to detect the content of malondealdehyde (MDA), nitrogen oxide (NO) in rat brain cytoplasm and mitochondria. Results: BCEF (25, 50,100 mg/kg) could obviously shorten the immobility time in forced swimming mice and BCEF (50,100 mg/kg)could obviously shorten the immobility time in forced swimming rats. Both of them showed some extent of dose-effect relationship. BCEF (50, 100 mg/kg) could significantly inhibit the increase of MDA and NO content in brain mitochondria and cytoplasm in chronic unpredictable stress models. BCEF (25,50,100 mg/kg)could obviously enhance the activities of SOD and GSH-PX. BCEF (50 mg/kg) also enhances the activities of CAT. Conclusion: BCEF has antidepressant effects in depressed animal models. The anti-oxidation may be one of the important mechanisms.
van Veen, T.; Wardenaar, K. J.; Carlier, I. V. E.; Spinhoven, P.; Penninx, B. W. J. H.; Zitman, F. G.
Background: Different types of adverse events may have general or specific effects on depression and anxiety symptomatology. We examined the effects of adversities on the dimensions of the tripartite model: general distress, anhedonic depression and anxious arousal. Methods: Data were from 2615 indi
van Veen, T.; Wardenaar, K. J.; Carlier, I. V. E.; Spinhoven, P.; Penninx, B. W. J. H.; Zitman, F. G.
Background: Different types of adverse events may have general or specific effects on depression and anxiety symptomatology. We examined the effects of adversities on the dimensions of the tripartite model: general distress, anhedonic depression and anxious arousal. Methods: Data were from 2615
Jacques, Heather A. K.; Mash, Eric J.
The applicability of the tripartite model of emotion, which distinguishes the shared aspect of depression and anxiety, negative affect (NA), from their respective specific components of low positive affect (PA) and physiological hyperarousal (PH), was examined in 472 elementary and high school students. The relations among depression, anxiety, and…
董素平; 徐畅; 原婷婷; 安书成
theoretic mechanisms for depression, such as monoamine neurotransmitter imbalance theory, neural plasticity theory, but none of them can fully elucidate the formation of depression. Due to weakness of the antidepressant-like effect of monoamines, glutamate (Glu)and its receptors, especially N-methyl-D-aspartic acid (NMDA) receptor, and neuropeptides such as neuropeptide Y (NPY), substance P (SP), are drawing closer attention in recent years. Here, we are attempted to explore the interaction between Glu/NMDA receptor and SP/neurokinin 1 (NK1) receptor in chronic unpredictable mild stress (CUMS)-induced depression.CUMS-induced depression model was established in 250~300g weighted 90-day old Sprague-Dawley rats. Intrahippocampal microinjection of NK1 receptor antagonist CP-96345, NMDA receptor agonist NMDA or NMDA receptor antagonist MK-801 was performed under stereotaxic guide cannula. The body weight of rats was weighed on the 1st, 7th, 14th, and 21st days during the experiment. The behavioral conducts were observed by means of sucrose consumption test, open field test and tail suspension test. The substance P (SP) and glutamate (Glu) content in hippocampus were separately determined by High performance liquid chromatography (HPLC). One-way ANOVA, LSD and repeated measures in SPSS were used in datum analysis.Our data suggest that CUMS significantly induced the depressive-like behaviors in animals and the content of SP and Glu in hippocampus had increased significantly. Microinjection of NMDA into hippocampus resulted in similar animal depressive-like behaviors and an increased SP content compared to the CON/SAL group. Intrahippocampal injections of CP-96345 or MK-801 had effectively improved the depression-like behaviors induced by CUMS, and the elevation of SP level in hippocampus was attenuated in MK-801 injection, whereas Glu level remained unchanged in CP-96345 injection.Our results imply that hippocampal NMDA receptor may contribute to chronic stress induced depressive
Kokras, Nikolaos; Dalla, Christina; Sideris, Antonios C; Dendi, Artemis; Mikail, Hudu G; Antoniou, Katerina; Papadopoulou-Daifoti, Zeta
Anxiety and depression are considered as stress-related disorders, which present considerable sex differentiation. In animal models of anxiety and depression sex differences have been described and linked to the sexually dimorphic hypothalamus-pituitary-adrenals (HPA) axis. The present study aimed to adjust corticosterone, the main HPA axis stress hormone, in male and female adrenalectomized rats with oral (25 μg/ml) corticosterone replacement (ADXR). Subsequently we investigated the behavioral performance of ADXR rats in the open field, light/dark and forced swim test (FST). Male ADXR rats showed less anxiety-like behavior when compared to sham-operated controls, despite adequate corticosterone replacement. They further showed increased swimming and reduced climbing behavior in the FST, while immobility duration did not differ from sham-operated males. On the contrary, adrenalectomy and corticosterone replacement did not have significant effects on the female behavioral response. Females were generally more active and presented less anxiety-like behavior than males, while they exhibited higher depressive-like symptomatology in the FST. ADXR affected behavioral responses predominantly in males, which in turn modified sex differences in the behavioral profile. Females in proestrous and estrous did not differ from females in diestrous and methestrous in any measured behavioral response. Present results suggest that the male and not the female behavioral responses in models of anxiety and depression were mainly affected by ADXR. These findings may play a significant role in explaining the differential coping strategy of the two sexes in response to stressful experiences. This article is part of a Special Issue entitled 'Anxiety and Depression'.
Darcet, Flavie; Gardier, Alain M; Gaillard, Raphael; David, Denis J; Guilloux, Jean-Philippe
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.
Akindele, Abidemi J; Ajao, Mutiu Y; Aigbe, Flora R; Enumah, Uchenna S
Telfairia occidentalis (Cucurbitaceae) is a leafy vegetable used in soup and folk medicine in southern Nigeria. Ethnobotanical survey revealed that preparations of the plant are used in the treatment of central nervous system-related disorders including convulsion. This study was conducted to investigate the effect of the hydroethanolic leaf extract of T. occidentalis in mouse models of convulsion, muscle relaxation, and depression. The strychnine and isoniazid convulsion, traction and climbing muscle relaxation, and forced swim and tail suspension depression tests were used in this study. The extract was administered orally (p.o.) at dose range of 25-800 mg/kg while distilled water (10 mL/kg p.o.) served as negative control. Diazepam (5 mg/kg p.o.) was used as positive control in the convulsion and muscle relaxation models while imipramine (64 mg/kg p.o.) served the same purpose in the depression tests. T. occidentalis significantly increased the onset (Pconvulsion (P<.05, .01) in the strychnine test and increased the time to death (P<.05, .01, .001) in the isoniazid model. The extract insignificantly increased the reaction time in the traction test while it significantly increased the time in the climbing test (P<.001). In the forced swim and tail suspension models, T. occidentalis significantly (P<.001) and dose-dependently increased the duration of immobility. The results obtained in this study suggest that the hydroethanolic leaf extract of T. occidentalis possesses anticonvulsant and muscle relaxant properties, thus justifying its folkloric use.
Kronenberg, Golo; Kirste, Imke; Inta, Dragos; Chourbaji, Sabine; Heuser, Isabella; Endres, Matthias; Gass, Peter
Glucocorticoid receptor (GR) heterozygous mice (GR(+/- )) represent a valuable animal model for major depression. GR(+/- ) mice show a depression-related phenotype characterized by increased learned helplessness on the behavioral level and neuroendocrine alterations with hypothalamo-pituitary-adrenal (HPA) axis overdrive characteristic of depression. Hippocampal brain-derived neurotrophic factor (BDNF) levels have also been shown to be reduced in GR(+/- ) animals. Because adult hippocampal neurogenesis has been implicated in the pathophysiology of affective disorders, we studied here the effects of the GR(+/- ) genotype on neurogenesis in vivo. In a 2 x 2 design, GR(+/- ) mice and GR(+/+) littermate controls were either subjected to 1 h of restraint stress or left undisturbed in their home cages after intraperitoneal injection of BrdU. Stress exposure and BrdU injections were performed once daily for 7 days and neurogenesis analyzed 4 weeks later. BrdU cell counts were significantly reduced as an effect of GR(+/- ) genotype and as an effect of stress. Majority of the BrdU+ cells showed co-labeling with mature neuronal marker NeuN or astrocytic marker S100beta with no further significant effect of either experimental condition or of genotype. In sum, this results in reduced neurogenesis in GR(+/- ) mice which is further repressed by restraint stress. Our results, thus, reinforce the link between reduced neurogenesis, stress, neurotrophins, and behavioral symptoms of and susceptibility to depression.
Full Text Available Currently, antidepressants are the dominative treatment for depression, but they have limitations in efficacy and may even produce troublesome side effects. Electroacupuncture (EA has been reported to have therapeutic benefits in the treatment of depressive disorders. The present study was conducted to determine whether EA could enhance the antidepressant efficacy of a low dose of citalopram (an SSRI antidepressant in the chronic unpredictable stress-induced depression model rats. Here, we show that a combined treatment with 2 Hz EA and 5 mg/kg citalopram for three weeks induces a significant improvement in depressive-like symptoms as detected by sucrose preference test, open field test, and forced swimming test, whereas these effects were not observed with either of the treatments alone. Further investigations revealed that 2 Hz EA plus 5 mg/kg citalopram produced a remarkably increased expression of BDNF and its receptor TrkB in the hippocampus compared with those measured in the vehicle group. Our findings suggest that EA combined with a low dose of citalopram could produce greater therapeutic effects, thereby, predictive of a reduction in drug side effects.
Bámaca-Colbert, Mayra Y; Umaña-Taylor, Adriana J; Gayles, Jochebed G
The current study tested a developmental-contextual model of depressive symptomatology among Mexican-origin, female early and middle adolescents and their mothers. The final sample comprised 271 dyads. We examined the interrelations among cultural (i.e., acculturation dissonance), developmental (i.e., pubertal development and autonomy expectation discrepancies), and interpersonal (i.e., mother-daughter conflict and maternal supportive parenting) factors in predicting adolescents' depressive symptoms. For both early and middle adolescents, maternal support was negatively associated with mother-daughter conflict and depressive symptoms. Mother-daughter autonomy expectation discrepancies were positively associated with mother-daughter conflict, but this association was found only among early adolescents. Further, mother-daughter acculturation dissonance was positively associated with mother-daughter conflict but only among middle adolescents. Findings call for concurrently examining the interface of developmental, relational, and cultural factors in predicting female adolescents' depressive symptomatology and the potential differences by developmental stage (e.g., early vs. middle adolescence). PsycINFO Database Record (c) 2012 APA, all rights reserved.
Kellam, S G; Werthamer-Larsson, L; Dolan, L J; Brown, C H; Mayer, L S; Rebok, G W; Anthony, J C; Laudolff, J; Edelsohn, G
Describes a conceptual framework for identifying and targeting developmental antecedents in early childhood that have been shown in previous work to predict delinquency and violent behavior, heavy drug use, depression, and other psychiatric symptoms and possibly disorders in late adolescence and into adulthood. Criteria are described that guided choices of targets for two epidemiologically based, randomized preventive trials carried out in 19 elementary schools in the eastern half of Baltimore, involving more than 2,400 first-grade children over the course of first and second grades. Baseline models derived from the first of two cohorts show the evolving patterns of concurrence among the target antecedents. The central role of concentration problems emerged. From Fall to Spring in first grade, concentration problems led to shy and aggressive behavior and poor achievement in both genders and to depressive symptoms among girls. There was evidence for reciprocal relationships in girls. For example, depressive symptoms led to poor achievement in both girls and boys, whereas poor achievement led to depressive symptoms in girls but not boys, at least over the first-grade year. These results provide important epidemiological data relevant to the developmental paths leading to the problem outcomes and suggest preventive trials.
Depciuch, J.; Sowa-Kucma, M.; Nowak, G.; Papp, M.; Gruca, P.; Misztak, P.; Parlinska-Wojtan, M.
Depression becomes nowadays a high mortality civilization disease with one of the major causes being chronic stress. Raman, Fourier Transform Infra Red (FTIR) and Ultraviolet-Visible (UV-vis) spectroscopies were used to determine the changes in the quantity and structure of phospholipids and proteins in the blood serum of rats subjected to chronic mild stress, which is a common animal depression model. Moreover, the efficiency of the imipramine treatment was evaluated. It was found that chronic mild stress not only damages the structure of the phospholipids and proteins, but also decreases their level in the blood serum. A 5 weeks imipramine treatment did increase slightly the quantity of proteins, leaving the damaged phospholipids unchanged. Structural information from phospholipids and proteins was obtained by UV-vis spectroscopy combined with the second derivative of the FTIR spectra. Indeed, the structure of proteins in blood serum of stressed rats was normalized after imipramine therapy, while the impaired structure of phospholipids remained unaffected. These findings strongly suggest that the depression factor, which is chronic mild stress, may induce permanent (irreversible) damages into the phospholipid structure identified as shortened carbon chains. This study shows a possible new application of spectroscopic techniques in the diagnosis and therapy monitoring of depression.
Full Text Available Jinjun Liang,1,2 Xiaoran Yuan,1,2 Shaobo Shi,1,2 Fang Wang,1,2 Yingying Chen,1,2 Chuan Qu,1,2 Jingjing Chen,1,2 Dan Hu,1–3 Yang Bo1,2 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Cardiovascular Research Institute, Wuhan University, Wuhan, People’s Republic of China; 3Masonic Medical Research Laboratory, Utica, NY, USA Background: Major depression is diagnosed in 18% of patients following myocardial infarction (MI, and the antidepressant fluoxetine is shown to effectively decrease depressive symptoms and improve coronary heart disease prognosis. We observed the effect of fluoxetine on cardiac electrophysiology in vivo in a rat model of post-MI depression and the potential mechanism. Methods and results: Eighty adult male Sprague Dawley rats (200–250 g were randomly assigned to five groups: normal control (control group, MI (MI group, depression (depression group, post-MI depression (model group, and post-MI depression treated with intragastric administration of 10 mg/kg fluoxetine (fluoxetine group. MI was induced by left anterior descending coronary artery ligation. Depression was developed by 4-week chronic mild stress (CMS. Behavior measurement was done before and during the experiment. Electrophysiology study in vivo and Western blot analysis were carried on after 4 weeks of CMS. After 4 weeks of CMS, depression-like behaviors were observed in the MI, depression, and model groups, and chronic fluoxetine administration could significantly improve those behaviors (P<0.05 vs model group. Fluoxetine significantly increased the ventricular fibrillation threshold compared with the model group (20.20±9.32 V vs 14.67±1.85 V, P<0.05. Expression of Kv4.2 was significantly reduced by 29%±12%, 24%±6%, and 41%±15%, respectively, in the MI group, CMS group, and model group, which could be improved by fluoxetine (30%±9%. But fluoxetine showed no improvement on the MI-induced loss of Cx43
Yang, Jae-Won; Hong, Sungdo D.; Joung, Yoo Sook; Kim, Ji-Hae
Although the currently available literature has provided some empirical support for a tripartite model of child and adolescent anxiety and depression, one of the limitations of these studies was that they have been conducted in America, primarily with Caucasians. In order to make this model more applicable to diverse ethnic and cultural groups, this study used a tripartite model for child and adolescent anxiety and depression in Korea, using confirmatory factor analysis with logically selecte...
Sairam, K; Dorababu, M; Goel, R K; Bhattacharya, S K
Bacopa monniera Wettst. (syn. Herpestis monniera L.; Scrophulariaceae) is a commonly used Ayurvedic drug for mental disorders. The standardized extract was reported earlier to have significant anti-oxidant effect, anxiolytic activity and improve memory retention in Alzheimer's disease. Presently, the standardized methanolic extract of Bacopa monniera (bacoside A - 38.0+/-0.9) was investigated for potential antidepressant activity in rodent models of depression. The effect was compared with the standard antidepressant drug imipramine (15 mg/kg, ip). The extract when given in the dose of 20 and 40 mg/kg, orally once daily for 5 days was found to have significant antidepressant activity in forced swim and learned helplessness models of depression and was comparable to that of imipramine.
Kostowski, W; Dyr, W; Puciłowski, O
The effect of two calcium channel inhibitors, diltiazem and nifedipine in animal models of depression: a) behavioral despair test and b) behavioral deficit produced by uncontrollable footshock was investigated. Additionally, the influence of both drugs on mouse killing (muricide) behavior induced by chronic isolation was studied. Both drugs given in single doses increased the active behavior of rats in behavioral despair test. Nifedipine but not diltiazem was partially effective in the test when administered chronically (14 days). Both drugs also attenuated stress-induced behavioral depression in the open field and forced swim test. Diltiazem was markedly more active in the former whereas nifedipine in the latter test. Neither compound influenced killing behavior in muricidal rats. Our data support the notion that calcium channel inhibitors may possess antidepressant activity, although there appear to exist certain differences in their scope of action depending on the model applied.
Wegener, Gregers; Finger, Beate C; Elfving, Betina; Keller, Kirsten; Liebenberg, Nico; Fischer, Christina W; Singewald, Nicolas; Slattery, David A; Neumann, Inga D; Mathé, Aleksander A
Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behaviour in rodents. However, little knowledge is available regarding the NPS system in depression-related behaviours, and whether NPS also exerts anxiolytic effects in an animal model of psychopathology. Therefore, the aim of this work was to characterize the effects of NPS on depression- and anxiety-related parameters, using male and female rats in a well-validated animal model of depression: the Flinders Sensitive Line (FSL), their controls, the Flinders Resistant Line (FRL), and Sprague-Dawley (SD) rats. We found that FSL showed greater immobility in the forced swim test (FST) than FRL, confirming their phenotype. However, NPS did not affect depression-related behaviour in any rat line. No significant differences in baseline anxiety levels between the FSL and FRL strains were observed, but FSL and FRL rats displayed less anxiety-like behaviour compared to SD rats. NPS decreased anxiety-like behaviour on the elevated plus-maze in all strains. The expression of the NPSR in the amygdala, periventricular hypothalamic nucleus, and hippocampus was equal in all male strains, although a trend towards reduced expression within the amygdala was observed in FSL rats compared to SD rats. In conclusion, NPS had a marked anxiolytic effect in FSL, FRL and SD rats, but did not modify the depression-related behaviour in any strain, in spite of the significant differences in innate level between the strains. These findings suggest that NPS specifically modifies anxiety behaviour but cannot overcome/reverse a genetically mediated depression phenotype.
Mathe, A.; Wegener, Gregers; Finger, B.
of cannula, 0.25 or 1.0 nmol NPS, or vehicle/5 ml were infused into the lateral ventricle. 45 min after NPS infusion animals were tested on elevated plus maze (EPM). Five days later the animals were subjected to the two-day forced swim test (FST); NPS or vehicle were injected 45 min before the second day FST...... the effects of centrally administered NPS on depression- and anxiety-related behaviors, using a well validated animal model of depression, the Flinders Sensitive Line (FSL) rats and their controls the Flinders Resistant Line (FRL). Methods: Male and female were tested. Seven days following insertion...... while no difference in the anxiety-like behavior was observed. These findings confirm the utility of the FSL as a model of depression useful in exploration of neurobiological correlates both of depression and those discriminating between depression and anxiety endophenotypes. NPS had marked anxiolytic...
Tak, Yuli R; Brunwasser, Steven M; Lichtwarck-Aschoff, Anna; Engels, Rutger C M E
Over the course of adolescence, an increasing number of adolescents experience depression. In order to effectively target depression, identifying risk factors for depressive symptoms is pivotal. Since low levels of self-efficacy were associated with higher levels of depressive symptoms in previous studies, the current study investigated the bidirectional and prospective associations between depressive symptoms and academic, social and emotional self-efficacy from early to mid adolescence in a cross-lagged path model. The sample consisted of 1,341 adolescents (47 % girls) with a mean age of 14 years, SD = 0.56. Depressive symptoms and self-efficacy levels were assessed every 6 months over a period of 2.5 years. Depressive symptoms predicted subsequent levels of academic and emotional self-efficacy on all time points, and social self-efficacy on one time point. Self-efficacy did not predict subsequent levels of depressive symptoms. There was no evidence of sex differences in the cross-lagged associations between depressive symptoms and self-efficacy levels. Implications of the findings are discussed.
He, Zhi-Yong; Wang, Wen-Yue; Hu, Wei-Yan; Yang, Lu; Li, Yan; Zhang, Wei-Yuan; Yang, Ya-Shu; Liu, Si-Cheng; Zhang, Feng-Lan; Mei, Rong; Xing, Da; Xiao, Zhi-Cheng; Zhang, Ming
The PP2C family member Wild-type p53-induced phosphatase 1 (Wip1) critically regulates DNA damage response (DDR) under stressful situations. In the present study, we investigated whether Wip1 expression was involved in the regulation of DDR-induced and depression-related cellular senescence in mouse hippocampus. We found that Wip1 gene knockout (KO) mice showed aberrant elevation of hippocampal cellular senescence and of γ-H2AX activity, which is known as a biomarker of DDR and cellular senescence, indicating that the lack of Wip1-mediated γ-H2AX dephosphorylation facilitates cellular senescence in hippocampus. Administration of the antidepressant fluoxetine had no significant effects on the increased depression-like behaviors, enriched cellular senescence, and aberrantly upregulated hippocampal γ-H2AX activity in Wip1 KO mice. After wildtype C57BL/6 mice were exposed to the procedure of chronic unpredictable mild stress (CUMS), cellular senescence and γ-H2AX activity in hippocampus were also elevated, accompanied by the suppression of Wip1 expression in hippocampus when compared to the control group without CUMS experience. These CUMS-induced symptoms were effectively prevented following fluoxetine administration in wildtype C57BL/6 mice, with the normalization of depression-like behaviors. Our data demonstrate that Wip1-mediated γ-H2AX dephosphorylation may play an important role in the occurrence of depression-related cellular senescence. PMID:27686532
... 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 ...
Christiansen, Sofie; Wiborg, Ove; Bouzinova, Elena
with disturbances in circadian related processes. The suprachiasmatic nucleus (SCN) is well known for its function as the master clock and regulates several circadian systems by clock genes expression. In addition to central expression, peripheral clock genes have been found. Methods: The study is based on a highly...... rhythm. Conclusion: Abnormalities in circadian rhythms, both centrally and peripherally, are related to depression-like state in the CMS model. Research support: This study is supported by Aarhus University and Illum fondet...
Kalueff, Allan V.; Murphy, Dennis L.
Cognitive dysfunctions are commonly seen in many stress-related disorders, including anxiety and depression—the world's most common neuropsychiatric illnesses. Various genetic, pharmacological, and behavioral animal models have long been used to establish animal anxiety-like and depression-like phenotypes, as well as to assess their memory, learning, and other cognitive functions. Mounting clinical and animal evidences strongly supports the notion that disturbed cognitions represent an import...
Full Text Available Jie Yu Chu Fan capsule (JYCF is a new compounded Chinese herbal medicine for the treatment of depression. The present study was designed to explore the antidepressant effects and the possible mechanisms of JYCF by using chronic unpredictable mild stress (CUMS mouse model and comparing results to that of fluoxetine. Behavioral tests including an open field test, sucrose preference test and forced swim test were performed to evaluate the antidepressant effects of JYCF. The concentrations of monoamine neurotransmitters and metabolic products including norepinephrine (NE, 5-hydroxytryptamine (5-HT, dopamine (DA, 5-hydroxyindoleacetic acid (5-HIAA, homovanillic acid (HVA and 3,4-dihydroxyphenylacetic acid (DOPAC in the cerebral cortex and hippocampus of mice were determined by means of high performance liquid chromatography with electrochemical detection (HPLC-EC. The results show that a successful mouse CUMS model was established through 5 weeks of continuous unpredictable stimulation, as indicated by the significant decrease in sucrose preference and locomotor activity and increase in immobility time in the forced swim test. Chronic treatment of JYCF (1.25, 2.5 and 5 g/kg and fluoxetine (20 mg/kg significantly reversed the CUMS-induced behavioral abnormalities. JYCF (1.25, 2.5 and 5 g/kg significantly increased NE in CUMS mouse prefrontal cortex (P < 0.01, P < 0.01, P < 0.05 respectively and 5-HT in hippocampus (P < 0.05. In summary, our findings suggest that JYCF exerts comparable antidepressant-like effects to that of fluoxetine in CUMS mice. Besides, the antidepressant-like effect of JYCF is mediated by the increase of monoaminergic transmitters including 5-HT and NE.
Batool, Syeda Shahida; Nawaz, Samina
The objective of the present study was to determine the mediating role of self-efficacy between religiosity, social support, and depression in patients with lost limbs. We sampled 67 male and 33 female disabled patients who had lost limbs in accidents or amputations from four public hospitals in Lahore, Pakistan, and used Religiosity Index (Farooq and Imam, in The effect of religiosity on locus of control. Department of Psychology, Govt College University, Lahore, 1997), General Self-efficacy Scales (Tabassum et al., in Urdu adaptation of the general self-efficacy scale. Retrieved from http://userpage.fu-berlin.de/~health/urdu.htm , 2003), Berlin Social Support Scale (Schwarzer and Schulz, in Berlin Social Support Scales. Retrieved online from http://userpage.fuberlin.de/~gesund/skalen/Language_Selection/Turkish/BerlinSocialSupportScales/berlin_social_support_scales.htm , 2000), and Siddiqui-Shah Depression Scale (Siddiqui and Shah, in Pychol Dev Soc 9(2):245-262, 1997), and used a correlation matrix and mediational analyses along with other inferential statistics to develop a model that suggested self-efficacy mediated between religiosity, social support, and depression with negative correlations that partially mediated this relationship. The findings suggest that low level of religiosity, social support, and self-efficacy may play a role in the onset and continuation of depression or its symptoms. We found no significant differences in gender, education, and cause of disability in patients with lost limbs. Results have implications for clinical psychologists, counselors, and health psychologists to develop a treatment plan for such patients with depression focusing on the factors implicated above.
Dossat, Amanda M; Sanchez-Gonzalez, Marcos A; Koutnik, Andrew P; Leitner, Stefano; Ruiz, Edda L; Griffin, Brittany; Rosenberg, Jens T; Grant, Samuel C; Fincham, Francis D; Pinto, Jose R; Kabbaj, Mohamed
Cardiovascular dysfunction is highly comorbid with mood disorders, such as anxiety and depression. However, the mechanisms linking cardiovascular dysfunction with the core behavioral features of mood disorder remain poorly understood. In this study, we used mice bearing a knock-in sarcomeric mutation, which is exhibited in human hypertrophic cardiomyopathy (HCM), to investigate the influence of HCM over the development of anxiety and depression. We employed behavioral, MRI, and biochemical techniques in young (3-4 mo) and aged adult (7-8 mo) female mice to examine the effects of HCM on the development of anxiety- and depression-like behaviors. We focused on females because in both humans and rodents, they experience a 2-fold increase in mood disorder prevalence vs. males. Our results showed that young and aged HCM mice displayed echocardiographic characteristics of the heart disease condition, yet only aged HCM females displayed anxiety- and depression-like behaviors. Electrocardiographic parameters of sympathetic nervous system activation were increased in aged HCM females vs. controls and correlated with mood disorder-related symptoms. In addition, when compared with controls, aged HCM females exhibited adrenal gland hypertrophy, reduced volume in mood-related brain regions, and reduced hippocampal signaling proteins, such as brain-derived neurotrophic factor and its downstream targets vs. controls. In conclusion, prolonged systemic HCM stress can lead to development of mood disorders, possibly through inducing structural and functional brain changes, and thus, mood disorders in patients with heart disease should not be considered solely a psychologic or situational condition.-Dossat, A. M., Sanchez-Gonzalez, M. A., Koutnik, A. P., Leitner, S., Ruiz, E. L., Griffin, B., Rosenberg, J. T., Grant, S. C., Fincham, F. D., Pinto, J. R. Kabbaj, M. Pathogenesis of depression- and anxiety-like behavior in an animal model of hypertrophic cardiomyopathy. © FASEB.
Lee, Hung Sa; Kim, Chunmi
The purpose of this study was to find the relationship and conceptual model of discrimination, stress, support, and depression among the elderly in South Korea. This was a cross-sectional descriptive study involving 207 community-dwelling elders. Data were collected through questionnaires from May 5 to May 31, 2014 in community senior centers, and analyzed using descriptive statistics, t test, analysis of variance, Scheffé test, and structural equation modeling. There were significant effects of discrimination on stress, support on stress and stress on depression. Moreover, there were two significant indirect effects observed between discrimination and depression, and between support and depression. For each indirect effect, the mediating factor was stress. Additionally, there was no direct effect between discrimination and depression or support. This study found that social support and discrimination had indirect effects on depression through stress. More specifically, decreased stress led to a reduction of depression. Therefore, social support based on a thorough understanding of stress is very important for caring elderly who are depressive. Copyright © 2016. Published by Elsevier B.V.
Gudmand-Høyer, Johanne; Ottesen, Stine Timmermann; Ottesen, Johnny T.
In the Western world approximately 10% of the population experience severe depression at least once in their lifetime and many more experience a mild form of depression. Depression has been associated with malfunctions in the hypothalamus–pituitary–adrenal (HPA) axis. We suggest a novel mechanistic...... non-linear model capable of showing both circadian as well as ultradian oscillations of the hormone concentrations related to the HPA-axis. The fast ultradian rhythm is assumed to originate from the hippocampus whereas the slower circadian rhythm is assumed to be caused by the circadian clock....... The model is able to describe the oscillatory patterns in hormone concentration data from 29 patients and healthy controls. Using non-linear mixed effects modeling with statistical hypothesis testing, three of the model parameters are identified to be related to depression. These parameters represent...
Sah, A; Schmuckermair, C; Sartori, S B; Gaburro, S; Kandasamy, M; Irschick, R; Klimaschewski, L; Landgraf, R; Aigner, L; Singewald, N
Adult neurogenesis has been implicated in affective disorders and the action of antidepressants (ADs) although the functional significance of this association is still unclear. The use of animal models closely mimicking human comorbid affective and anxiety disorders seen in the majority of patients should provide relevant novel information. Here, we used a unique genetic mouse model displaying higher trait anxiety (HAB) and comorbid depression-like behavior. We demonstrate that HABs have a lower rate of hippocampal neurogenesis and impaired functional integration of newly born neurons as compared with their normal anxiety/depression-like behavior (NAB) controls. In HABs, chronic treatment with the AD fluoxetine alleviated their higher depression-like behavior and protected them from relapse for 3 but not 7 weeks after discontinuation of the treatment without affecting neurogenesis. Similar to what has been observed in depressed patients, fluoxetine treatment induced anxiogenic-like effects during the early treatment phase in NABs along with a reduction in neurogenesis. On the other hand, treatment with AD drugs with a particularly strong anxiolytic component, namely the neurokinin-1-receptor-antagonist L-822 429 or tianeptine, increased the reduced rate of neurogenesis in HABs up to NAB levels. In addition, challenge-induced hypoactivation of dentate gyrus (DG) neurons in HABs was normalized by all three drugs. Overall, these data suggest that AD-like effects in a psychopathological mouse model are commonly associated with modulation of DG hypoactivity but not neurogenesis, suggesting normalization of hippocampal hypoactivity as a neurobiological marker indicating successful remission. Finally, rather than to higher depression-related behavior, neurogenesis seems to be linked to pathological anxiety.
Lee Robert C
Full Text Available Abstract Background Most epidemiological studies of major depression report period prevalence estimates. These are of limited utility in characterizing the longitudinal epidemiology of this condition. Markov models provide a methodological framework for increasing the utility of epidemiological data. Markov models relating incidence and recovery to major depression prevalence have been described in a series of prior papers. In this paper, the models are extended to describe the longitudinal course of the disorder. Methods Data from three national surveys conducted by the Canadian national statistical agency (Statistics Canada were used in this analysis. These data were integrated using a Markov model. Incidence, recurrence and recovery were represented as weekly transition probabilities. Model parameters were calibrated to the survey estimates. Results The population was divided into three categories: low, moderate and high recurrence groups. The size of each category was approximated using lifetime data from a study using the WHO Mental Health Composite International Diagnostic Interview (WMH-CIDI. Consistent with previous work, transition probabilities reflecting recovery were high in the initial weeks of the episodes, and declined by a fixed proportion with each passing week. Conclusion Markov models provide a framework for integrating psychiatric epidemiological data. Previous studies have illustrated the utility of Markov models for decomposing prevalence into its various determinants: incidence, recovery and mortality. This study extends the Markov approach by distinguishing several recurrence categories.
Santiago, Ronise M; Barbiero, Janaína; Martynhak, Bruno J; Boschen, Suelen L; da Silva, Luisa M; Werner, Maria F P; Da Cunha, Claudio; Andreatini, Roberto; Lima, Marcelo M S; Vital, Maria A B F
Beyond the current hypothesis of depression, several new biological substrates have been proposed for this disorder. The present study investigated whether the anti-inflammatory drugs celecoxib and piroxicam have antidepressant activity in animal models of depression. After acute administration, we observed antidepressant-like effects of celecoxib (10 mg/kg) and piroxicam (10 mg/kg) in the modified forced swim test in rats. Piroxicam increased serotonin and norepinephrine levels in the hippocampus. Prolonged (21-day) treatment with celecoxib (10 mg/kg) and piroxicam (10 mg/kg) rescued sucrose preference in a chronic mild stress model of depression. Additionally, the chronic mild stress-induced reduction of hippocampal glutathione was prevented by treatment with celecoxib and piroxicam. Superoxide dismutase in the hippocampus was increased after chronic mild stress compared with the non-stressed saline group. The non-stressed celecoxib and piroxicam groups and stressed piroxicam group exhibited an increase in hippocampal superoxide dismutase activity compared with the stressed saline group. Lipid hydroperoxide was increased in the stressed group treated with vehicle and non-stressed group treated with imipramine but not in the stressed groups treated with celecoxib and piroxicam. These results suggest that the antidepressant-like effects of anti-inflammatory drugs might be attributable to enhanced antioxidant defenses and attenuated oxidative stress in the hippocampus.
Full Text Available Introduction: Interaction of several genes is responsible for psychiatric diseases such as depression. Despite the numerous microarray studies in this field, findings are controversial and hard to conclude. Methods: Male Wistar rats were randomly selected to receive Chronic Mild Stress model for 4 weeks. Different aspects of depression were measured by forced swimming test, open field trial and sucrose preference tests in the experience group and controls. Results: Sucrose was preferred by 40% of CMS group and 80% of controls (p=0.025. Twenty percent of CMS group and 80% of controls were “active” (p=0.001. Last escape was at minute 238 for CMS group and minute 245 for controls and controls had more escape efforts. Conclusion: This paper is a preliminary report of a genomic study on animal model of depression which tries to achieve reliable results by a joint of clinical view with recent techniques. Predicted challenges in this procedure and the solutions as well as the limitations may be helpful for future researches.
Henningsen, Kim; Palmfeldt, Johan; Christiansen, Sofie
Susceptibility to stress plays a crucial role in the development of psychiatric disorders such as unipolar depression and post-traumatic stress disorder. In the present study the chronic mild stress rat model of depression was used to reveal stress-susceptible and stress-resilient rats. Large......-scale proteomics was used to map hippocampal protein alterations in different stress states. Membrane proteins were successfully captured by two-phase separation and peptide based proteomics. Using iTRAQ labeling coupled with mass spectrometry, more than 2000 proteins were quantified and 73 proteins were found...... to be differentially expressed. Stress susceptibility was associated with increased expression of a sodium-channel protein (SCN9A) currently investigated as a potential antidepressant target. Differential protein profiling also indicated stress susceptibility to be associated with deficits in synaptic vesicle release...
Full Text Available Abstract Background There is still debate as to which features, types or components of primary care interventions are associated with improved depression outcomes. Previous reviews have focused on components of collaborative care models in general practice settings. This paper aims to determine the effective components of depression care in primary care through a systematic examination of both general practice and community based intervention trials. Methods Fifty five randomised and controlled research trials which focused on adults and contained depression outcome measures were identified through PubMed, PsycInfo and the Cochrane Central Register of Controlled Trials databases. Trials were classified according to the components involved in the delivery of treatment, the type of treatment, the primary focus or setting of the study, detailed features of delivery, and the discipline of the professional providing the treatment. The primary outcome measure was significant improvement on the key depression measure. Results Components which were found to significantly predict improvement were the revision of professional roles, the provision of a case manager who provided direct feedback and delivered a psychological therapy, and an intervention that incorporated patient preferences into care. Nurse, psychologist and psychiatrist delivered care were effective, but pharmacist delivery was not. Training directed to general practitioners was significantly less successful than interventions that did not have training as the most important intervention. Community interventions were effective. Conclusion Case management is important in the provision of care in general practice. Certain community models of care (education programs have potential while others are not successful in their current form (pharmacist monitoring.
Smaga, Irena; Jastrzębska, Joanna; Zaniewska, Magdalena; Bystrowska, Beata; Gawliński, Dawid; Faron-Górecka, Agata; Broniowska, Żaneta; Miszkiel, Joanna; Filip, Małgorzata
A growing body of evidence implicates the endocannabinoid (eCB) system in the pathophysiology of depression. The aim of this study was to investigate the influence of changes in the eCB system, such as levels of neuromodulators, eCB synthesizing and degrading enzymes, and cannabinoid (CB) receptors, in different brain structures in animal models of depression using behavioral and biochemical analyses. Both models used, i.e., bulbectomized (OBX) and Wistar Kyoto (WKY) rats, were characterized at the behavioral level by increased immobility time. In the OBX rats, anandamide (AEA) levels were decreased in the prefrontal cortex, hippocampus, and striatum and increased in the nucleus accumbens, while 2-arachidonoylglycerol (2-AG) levels were increased in the prefrontal cortex and decreased in the nucleus accumbens with parallel changes in the expression of eCB metabolizing enzymes in several structures. It was also observed that CB1 receptor expression decreased in the hippocampus, dorsal striatum, and nucleus accumbens, and CB2 receptor expression decreased in the prefrontal cortex and hippocampus. In WKY rats, the levels of eCBs were reduced in the prefrontal cortex (2-AG) and dorsal striatum (AEA) and increased in the prefrontal cortex (AEA) with different changes in the expression of eCB metabolizing enzymes, while the CB1 receptor density was increased in several brain regions. These findings suggest that dysregulation in the eCB system is implicated in the pathogenesis of depression, although neurochemical changes were linked to the particular brain structure and the factor inducing depression (surgical removal of the olfactory bulbs vs. genetic modulation).
Salehpour, Farzad; Rasta, Seyed Hossein; Mohaddes, Gisou; Sadigh-Eteghad, Saeed; Salarirad, Sima
Depression is a common psychiatric disorder that its prevalence has been reported to be 16% among adults. In recent years, transcranial near-infrared laser therapy (NILT) has gained considerable attention as a novel non-pharmaceutical method for depression. The present study was designed to compare the efficacy of two different treatment strategies in a rat model of depression. Forty male Wistar rats (180-200 g) divided into 4 groups: control, depressive, depressive-NILT, and depressive-Citalopram. All animals excepted control group was exposed to chronic mild stress (CMS) for 4 weeks. Rats in laser group received 10-Hz pulsed NILT (810 nm, energy density 1.2 J/cm2 per session) transcranially for a total of 12 sessions over a three-week period. Citalopram (10 mg/kg, Intraperitoneal) was administered for 21 consecutive days. Depressive-like behavior was tested in the forced swimming test (FST) model. Serum cortisol levels were also determined. The results of FST showed an increase in swimming and decrease in immobility period, for both NILT and Citalopram groups compared to the stress group. There was also no significant difference between the experimental groups in climbing behavior. The induction of CMS significantly increased serum cortisol levels and treatments with NILT and Citalopram decreased it. Our findings showed that NILT will be more beneficial to improve the depressive-like behaviors in the rat. Our data also showed that transcranial NILT was as effective as Citalopram in the treatment of depression. Therefore, these pieces of evidence may help improve NILT as an alternative non-pharmaceutical method for depression therapy.
Carrera, Stephanie G; Wei, Meifen
In his acculturative family distancing (AFD) theory, Hwang (2006b) argued that acculturation gaps among parents and youth may lead to psychological and emotional distancing. AFD includes 2 dimensions: incongruent cultural values and breakdowns in communication. This study examined whether bicultural competence (BC) served as a mediator and moderator for the relationship between AFD and depression using structural equation modeling. Two hundred and forty-one Latino/a college students attending predominantly White, midwestern universities completed an online survey at 2 time points. For mediation, results indicated that BC at Time 2 (T2) mediated the relationship between AFD at Time 1 (T1) and depression at T2 above and beyond the effects of depression, acculturation, and enculturation at T1. A bootstrap method estimated the significance of the indirect effect. Moreover, 16% of the variance in BC at T2 was explained by acculturation, enculturation, and AFD at T1; 30% of the variance in depression at T2 was explained by BC at T2 and depression at T1. Post hoc analyses of the AFD and BC dimensions suggested that (a) positive attitudes toward both groups, communication ability, and social groundedness were significant mediators for the incongruent cultural values-depression link and (b) communication ability and social groundedness were significant mediators for the communication breakdown-depression link. For moderation, the AFD × BC interaction did not significantly predict depression at T2. Limitations, future research directions, and counseling implications are discussed.
Full Text Available BACKGROUND: Several risk factors for depression during pregnancy have already been established. However, very few studies have conducted a multivariate analysis incorporating both the major predictors of depression in women, in accordance with comprehensive developmental models of depression, and specific stressors associated with the biological and psychosocial state of the mother-to-be. METHODOLOGY/PRINCIPAL FINDINGS: We used a cross-sectional cohort design to analyze the associations between prenatal depression and potential risk factors. 693 French-speaking women with singleton pregnancies at 20-28 weeks' gestation were consecutively recruited at Caen University Hospital. Fifty women with missing values were subsequently excluded from the analysis. Depressive symptoms were assessed on the Edinburgh Postnatal Depression Scale. Risk factors were either extracted from the computerized obstetric records or assessed by means of self-administered questionnaires. The associations between prenatal depression and the potential risk factors were assessed using log-binomial regression models to obtain a direct estimate of relative risk (RR. The following factors were found to be significant in the multivariate analysis: level of education (p<0.001, past psychiatric history (adjusted RR=1.8, 95% confidence interval (CI: 1.1;2.8, p=0.014, stress related to the health and viability of the fetus (adjusted RR=2.6, 95% CI: 1.6;4.1, p<0.001, and stress related to severe marital conflicts (adjusted RR=2.4, 95% CI: 1.5;3.9, p<0.001 or to serious difficulties at work (adjusted RR=1.6, 95% CI :1.04;2.4, p=0.031. An association was also found with the previous delivery of a child with a major or minor birth defect (adjusted RR=2.0, 95% CI: 1.04;4.0, p=0.038. Univariate analyses revealed a strong association with childhood adversity (parental rejection: RR=1.8, 95% CI: 1.2;2.8, p=0.0055 and family secrets: RR=2.0, 95% CI: 1.2;3.1, p=0.0046 and with lack of partner
Redei, Eva E; Mehta, Neha S
Depression is a heterogeneous disorder and, similar to other spectrum disorders, its manifestation varies by age of onset, severity, comorbidity, treatment responsiveness, and other factors. A laboratory blood test based on specific biomarkers for major depressive disorder (MDD) and its subgroups could increase diagnostic accuracy and expedite the initiation of treatment. We identified candidate blood biomarkers by examining genome-wide expression differences in the blood of animal models representing both the genetic and environmental/stress etiologies of depression. Human orthologs of the resulting transcript panel were tested in pilot studies. Transcript abundance of 11 blood markers differentiated adolescent subjects with early-onset MDD from adolescents with no disorder (ND). A set of partly overlapping transcripts distinguished adolescent patients who had comorbid anxiety disorders from those with only MDD. In adults, blood levels of nine transcripts discerned subjects with MDD from ND controls. Even though cognitive behavioral therapy (CBT) resulted in remission of some patients, the levels of three transcripts consistently signaled prior MDD status. A coexpression network of transcripts seems to predict responsiveness to CBT. Thus, our approach can be developed into clinically valid diagnostic panels of blood transcripts for different manifestations of MDD, potentially reducing diagnostic heterogeneity and advancing individualized treatment strategies.
Full Text Available Stress is a complicated condition that effects on person’s mental and physical health, and it is the precursor of other psychological disorders mainly depression. Serotonin (5-Hydroxytryptamine; 5-HT is well known to have hypofunction in unpredictable chronic mild stress whereas, unpredictable chronic mild stress (UCMS has produced the most steady and continuous results of anhedonia and learned helplessness particularly in rats. The stress-induced depressive like behavior can be reversed by many antidepressants such as SSRIs. Selective serotonin [5-hydroxytryptamine (5-HT] reuptake inhibitors (SSRIs is mostly prescribed antidepressant that can deplete neurochemical and behavioral deficits. The present study was designed to investigate whether repeated administration of dapoxetine at dose (1.0 mg/kg could reverse the behavioral deficits induced by UCMS in rat model of depression. UCMS induced behavioral deficits. Locomotor activity in familiar environment (home cage, novel (open field environment and anxiolytic behavior in light/dark activity box were greater in unstressed group than stressed group. The inhibition of serotonin reuptake at pre-synaptic receptors by repeated dapoxetine administration is mainly the mechanism involved and discussed. This particular study may assist in novel approach for understanding the interaction between stress and behavioral functions and extending the therapeutic use of dapoxetine.
Malick, M; Gilbert, K; Daniel, J; Arseneault-Breard, J; Tompkins, T A; Godbout, R; Rousseau, G
Myocardial infarction (MI) is associated with apoptosis in the amygdala and, ultimately, with clinical signs of depression. Different treatments have proven to be beneficial in preventing depression, including combination of the probiotics Lactobacillus helveticus and Bifidobacterium longum for prophylaxis. We have speculated previously that the benefit of these probiotics is due to their anti-inflammatory properties, and evidence suggests that an intact vagus nerve is important for this effect to occur. This study was designed to ascertain vagus nerve involvement in the beneficial influence of probiotics on caspase activities in our post-MI animal model of depression. Probiotics and/or vehicle were administered daily to male adult rats, 14 days before MI and until euthanasia. Vagotomy was performed in subgroups of rats 40 min before MI. They were sacrificed after 3 days of reperfusion, and MI size was assessed along with caspase-3 and -8 activities in the amygdala. Probiotics had no effect on infarct size but vagotomy increased it. Caspase-3 and caspase-8 activities in the amygdala were higher in MI than in sham-operated rats, and this outcome was reversed by probiotics. The beneficial influence of probiotics was abolished by vagotomy. Our data indicate that the effect of probiotics on caspase activities in the amygdala after MI depends on an intact vagus nerve. © 2015 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.
Full Text Available Current therapies for depression consist primarily of pharmacological agents, including antidepressants, and/or psychiatric counseling, such as psychotherapy. However, light therapy has recently begun to be considered as an effective tool for the treatment of the neuropsychiatric behaviors and symptoms of a variety of brain disorders or diseases, including depression. One methodology employed in light therapy involves flickering photic stimulation within a specific frequency range. The present study investigated whether flickering and flashing photic stimulation with light emitting diodes (LEDs could improve depression-like behaviors in a corticosterone (CORT-induced mouse model of depression. Additionally, the effects of the flickering and flashing lights on depressive behavior were compared with those of fluoxetine. Rhythmical flickering photic stimulation at alpha frequencies from 9-11 Hz clearly improved performance on behavioral tasks assessing anxiety, locomotor activity, social interaction, and despair. In contrast, fluoxetine treatment did not strongly improve behavioral performance during the same period compared with flickering photic stimulation. The present findings demonstrated that LED-derived flickering photic stimulation more rapidly improved behavioral outcomes in a CORT-induced mouse model of depression compared with fluoxetine. Thus, the present study suggests that rhythmical photic stimulation at alpha frequencies may aid in the improvement of the quality of life of patients with depression.
Maccari, S; Darnaudery, M; Van Reeth, O
Prenatal stress in rats can exert profound influence on the off spring's development, inducing abnormalities such as increased "anxiety", "emotionality" or "depression-like" behaviours.Prenatal stress has long-term effects on the development of the hypothalamo-pituitary-adrenal(HPA) axis and forebrain cholinergic systems. These long-term neuroendocrinological effects are mediated, at least in part, by stress-induced maternal corticosterone increase during pregnancy and stress-induced maternal anxiety during the postnatal period. We have shown a significant phase advance in the circadian rhythms of corticosterone secretion and locomotor activity in prenatally-stressed (PNS) rats. When subjected to an abrupt shift in the light-dark(LD) cycle, PNS rats resynchronized their activity rhythm more slowly than control rats. In view of the data suggesting abnormalities in the circadian timing system in these animals, we have investigated the effects of prenatal stress on the sleep-wake cycle in adult male rats. PNS rats exhibited various changes in sleep-wake parameters, including a dramatic increase in the amount of paradoxical sleep. Taken together, our results indicate that prenatal stress can induce increased responses to stress and abnormal circadian rhythms and sleep in adult rats.Various clinical observations in humans suggest a possible pathophysiological link between depression and disturbances in circadian rhythmicity. Circadian abnormalities in depression can be related to those found in PNS rats. Interestingly, we have recently shown that the increased immobility in the forced swimming test observed in PNS rats can be corrected by chronic treatment with the antidepressant tianeptine, or with melatonin or S23478, a melatonin agonist. Those results reinforce the idea of the usefulness of PNS rats as an appropriate animal model to study human depression and support a new antidepressant-like effect of melatonin and the melatonin agonist S23478.
Muñoz-Cobo, I; Belloch, F B; Díaz-Perdigón, T; Puerta, E; Tordera, R M
Some histone deacetylase (HDACs) enzymes have been proposed as epigenetic targets involved in the pathophysiology of depression and antidepressant-like action. Among them, we have recently identified SIRT2, a class III NAD(+)-dependent HDAC, as being oppositely regulated by stress and antidepressants. Moreover, SIRT2 inhibition has shown antianhedonic-like action in the chronic mild stress model of depression. Here we have extended the study using an alternative model of depression based in a genetic manipulation of glutamate function. Specifically, mice heterozygous for the vesicular glutamate transporter 1 (VGLUT1+/-) were used. Firstly, mRNA expression of the different members of the HDAC superfamily in the prefrontal cortex (PFC) of VGLUT1+/- mice and WT littermates were studied by RT-PCR. Secondly, the effect of repeated treatment with the selective SIRT2 inhibitor 33i and the antidepressant imipramine on anhedonic behaviour of VGLUT1+/- mice was studied by weekly monitoring of sucrose intake. Further, the interaction of 33i towards specific monoaminergic targets such as serotonin or noradrenaline transporters as well as the monoaminooxidase enzyme was studied. The mRNA occurance of the different members of HDAC superfamily was not altered in the PFC of VGLUT1+/- mice. While repeated imipramine showed an anti-anhedonic action in both VGLUT1+/- and WT, the selective SIRT2 inhibitor 33i fully reversed anhedonia of VGLUT1+/-. Further, 33i showed no interaction with the above mentioned monoaminergic molecular targets. These results confirm that SIRT2 inhibition is able to reverse anhedonia in different animal models and highlight the need to further investigate the role of SIRT2 inhibitors as new antidepressant agents. Copyright © 2017 Elsevier B.V. All rights reserved.
YU Shan Fa; NAKATA Akinori; GU Gui Zhen; SWANSON Naomi G; ZHOU Wen Hui; HE Li Hua; WANG Sheng
Objective To investigate the co-effect of Demand-control-support (DCS) model and Effort-reward Imbalance (ERI) model on the risk estimation of depression in humans in comparison with the effects when they are used respectively. Methods A total of 3 632 males and 1 706 females from 13 factories and companies in Henan province were recruited in this cross-sectional study. Perceived job stress was evaluated with the Job Content Questionnaire and Effort-Reward Imbalance Questionnaire (Chinese version). Depressive symptoms were assessed by using the Center for Epidemiological Studies Depression Scale (CES-D). Results DC (demands/job control ratio) and ERI were shown to be independently associated with depressive symptoms. The outcome of low social support and overcommitment were similar. High DC and low social support (SS), high ERI and high overcommitment, and high DC and high ERI posed greater risks of depressive symptoms than each of them did alone. ERI model and SS model seem to be effective in estimating the risk of depressive symptoms if they are used respectively. Conclusion The DC had better performance when it was used in combination with low SS. The effect on physical demands was better than on psychological demands. The combination of DCS and ERI models could improve the risk estimate of depressive symptoms in humans.
Resources - depression ... Depression is a medical condition. If you think you may be depressed, see a health care provider. ... following organizations are good sources of information on depression : American Psychological Association -- www.apa.org/topics/depress/ ...
Kelley, Michelle L; Lawrence, Hannah R; Milletich, Robert J; Hollis, Brittany F; Henson, James M
Children with substance abusing parents are at considerable risk for child maltreatment. The current study applied an actor-partner interdependence model to examine how father only (n=52) and dual couple (n=33) substance use disorder, as well as their depressive symptomology influenced parents' own (actor effects) and the partner's (partner effects) overreactivity in disciplinary interactions with their children, as well as their risk for child maltreatment. Parents completed the Center for Epidemiologic Studies Depression Scale (CES-D; Radloff, 1977), the overreactivity subscale from the Parenting Scale (Arnold, O'Leary, Wolff, & Acker, 1993), and the Brief Child Abuse Potential Inventory (Ondersma, Chaffin, Mullins, & LeBreton, 2005). Results of multigroup structural equation models revealed that a parent's own report of depressive symptoms predicted their risk for child maltreatment in both father SUD and dual SUD couples. Similarly, a parent's report of their own depressive symptoms predicted their overreactivity in disciplinary encounters both in father SUD and dual SUD couples. In all models, partners' depressive symptoms did not predict their partner's risk for child maltreatment or overreactivity. Findings underscore the importance of a parent's own level of depressive symptoms in their risk for child maltreatment and for engaging in overreactivity during disciplinary episodes. Copyright © 2015 Elsevier Ltd. All rights reserved.
Full Text Available Objective to develop a predictive model to evaluate the factors that modify the access to treatment for Postpartum Depression (PPD. Methods prospective study with mothers who participated in the monitoring of child health in primary care centers. For the initial assessment and during 3 months, it was considered: sociodemographic data, gyneco-obstetric data, data on the services provided, depressive symptoms according to the Edinburgh Postpartum Depression Scale (EPDS and quality of life according to the Short Form-36 Health Status Questionnaire (SF-36. The diagnosis of depression was made based on MINI. Mothers diagnosed with PPD in the initial evaluation, were followed-up. Results a statistical model was constructed to determine the factors that prevented access to treatment, which consisted of: item 2 of EPDS (OR 0.43, 95%CI: 0.20-0.93 and item 5 (OR 0.48, 95%CI: 0.21-1.09, and previous history of depression treatment (OR 0.26, 95%CI: 0.61-1.06. Area under the ROC curve for the model=0.79; p-value for the Hosmer-Lemershow=0.73. Conclusion it was elaborated a simple, well standardized and accurate profile, which advises that nurses should pay attention to those mothers diagnosed with PPD, presenting low/no anhedonia (item 2 of EPDS, scarce/no panic/fear (item 5 of EPDS, and no history of depression, as it is likely that these women do not initiate treatment.
Full Text Available This study explores the therapeutic effects of Xiangshao granules in a mouse depression model and examines the potential molecular mechanisms involved. After 21 consecutive days of chronic stress challenge, all mice were divided into three groups: control group, depression group, and Xiangshao granule treatment group. On the 22nd day, rats in the Xiangshao granule treatment group received Xiangshao granules via gastrogavage for 3 consecutive weeks. Depression group mice showed a significant reduction of crossings (P<0.01 but not rearings (P<0.05. Serum CRH, CORT, and ACTH levels were significantly increased in depression mice compared with control (P<0.05 and the expression levels of hippocampal BDNF and TrkB were reduced in the model group (P<0.05. However, Xiangshao granule treatment remarkably rescued the decrease in the body weight (P<0.05, increased crossings in the open field test (P<0.05, upregulated the expression of hippocampal BDNF and TrkB expression, and reduced the serum CRH, CORT, and ACTH concentrations compared with the depression group (P<0.05. Collectively, these results demonstrated that Xiangshao granule could effectively induce antidepressive effects in the depression mouse model by ameliorating the expression of hippocampal BDNF and TrkB.
Liu, K; Mazumdar, S; Stone, R A; Dew, M A; Houck, P R; Reynolds, C F
When a covariate measured with error is used as a predictor in a survival analysis using the Cox model, the parameter estimate is usually biased. In clinical research, covariates measured without error such as treatment procedure or sex are often used in conjunction with a covariate measured with error. In a randomized clinical trial of two types of treatments, we account for the measurement error in the covariate, log-transformed total rapid eye movement (REM) activity counts, in a Cox model analysis of the time to recurrence of major depression in an elderly population. Regression calibration and two variants of a likelihood-based approach are used to account for measurement error. The likelihood-based approach is extended to account for the correlation between replicate measures of the covariate. Using the replicate data decreases the standard error of the parameter estimate for log(total REM) counts while maintaining the bias reduction of the estimate. We conclude that covariate measurement error and the correlation between replicates can affect results in a Cox model analysis and should be accounted for. In the depression data, these methods render comparable results that have less bias than the results when measurement error is ignored.
Ewing, E Stephanie Krauthamer; Diamond, Guy; Levy, Suzanne
Attachment-Based Family Therapy (ABFT) is a manualized family-based intervention designed for working with depressed adolescents, including those at risk for suicide, and their families. It is an empirically informed and supported treatment. ABFT has its theoretical underpinnings in attachment theory and clinical roots in structural family therapy and emotion focused therapies. ABFT relies on a transactional model that aims to transform the quality of adolescent-parent attachment, as a means of providing the adolescent with a more secure relationship that can support them during challenging times generally, and the crises related to suicidal thinking and behavior, specifically. This article reviews: (1) the theoretical foundations of ABFT (attachment theory, models of emotional development); (2) the ABFT clinical model, including training and supervision factors; and (3) empirical support.
Seekatz, Bettina; Meng, Karin; Bengel, Juergen; Faller, Hermann
The fear-avoidance (FA) model has gained widespread acceptance as a conceptual framework for investigating psychological factors such as FA beliefs and avoidance behavior, which contribute to chronic back pain and reduced functioning. Depressive symptoms are supposed to be related to FA beliefs and to foster avoidance behavior. This study aims to investigate the multivariate assumptions of the FA model with a focus on the role of depressive symptoms. A total of N = 360 patients with chronic nonspecific low back pain at admission of inpatient orthopedic rehabilitation participated in the survey. Measures included a numeric pain rating scale, Fear-Avoidance Beliefs Questionnaire, Pain Anxiety Symptoms Scale, Hannover Functional Ability Questionnaire and Patient Health Questionnaire. Using structural equation modeling (SEM), we construed a basic FA model and subsequently extended it by adding symptoms of depression as a covariate. The results of SEM indicated a good model fit for a basic FA model (χ²(263) = 431.069, p < .001, RMSEA = .042, CFI = .964, WRMR = .986). They confirmed the hypothesized relations and supported single mediations of the relationship between pain and functioning by FA beliefs and avoidance behavior. A second model including symptoms of depression as additional covariate (χ²(511) = 722.761, p < .001, RMSEA = .034, CFI = .956, WRMR = .949) showed a high impact of depressive symptoms on all FA model variables leading to a decrease of the FA mediations. The findings provide empirical support for the multivariate FA model and underline the importance of considering depressive symptoms in a multiple-target approach to understand the mechanisms of chronic pain.
Strenn, Nina; Suchankova, Petra; Nilsson, Staffan; Fischer, Christina; Wegener, Gregers; Mathé, Aleksander A; Ekman, Agneta
The complex bidirectional communication between the central nervous system and the peripheral immune system is of possible relevance for both normal brain functions and the development of psychiatric disorders. The aim of this investigation was to study central expression of inflammatory markers in a genetic rat model of depression (the Flinders sensitive line (FSL) and its control, the Flinders resistant line (FRL)). A peripheral immune activation was induced by lipopolysaccharide (LPS) in order to investigate possible differences in immune reactions between the two rat lines. To confirm behavioural differences between the rat lines the forced swim test was performed, a test to assess depressive-like behaviour. Expression of candidate inflammatory genes was measured in amygdala, hippocampus, hypothalamus, prefrontal cortex and striatum using quantitative real time PCR. Our results show, for the first time, significantly lower central expression of the glial-specific protein S100B and complement factor C3 in several brain regions of the FSL rats compared to controls, both at baseline and after peripheral immune stimulation. No significant differences in immune responses to LPS were observed between the rats lines. Both S100B and C3 have been suggested to be of relevance for brain development and plasticity as well as brain disorders. These proteins may be of importance for the behavioural differences between the FSL and FRL rats, and this model may be useful in studies exploring the influence of the immune system on brain functions.
Mendez-David, Indira; Boursier, Céline; Domergue, Valérie; Colle, Romain; Falissard, Bruno; Corruble, Emmanuelle; Gardier, Alain M.; Guilloux, Jean-Philippe; David, Denis J.
The incorporation of peripheral biomarkers in the treatment of major depressive disorders (MDD) could improve the efficiency of treatments and increase remission rate. Peripheral blood mononuclear cells (PBMCs) represent an attractive biological substrate allowing the identification of a drug response signature. Using a proteomic approach with high-resolution mass spectrometry, the present study aimed to identify a biosignature of antidepressant response (fluoxetine, a Selective Serotonin Reuptake Inhibitor) in PBMCs in a mouse model of anxiety/depression. Following determination of an emotionality score, using complementary behavioral analysis of anxiety/depression across three different tests (Elevated Plus Maze, Novelty Suppressed Feeding, Splash Test), we showed that a 4-week corticosterone treatment (35 μg/ml, CORT model) in C57BL/6NTac male mice induced an anxiety/depressive-like behavior. Then, chronic fluoxetine treatment (18 mg/kg/day for 28 days in the drinking water) reduced corticosterone-induced increase in emotional behavior. However, among 46 fluoxetine-treated mice, only 30 of them presented a 50% decrease in emotionality score, defining fluoxetine responders (CORT/Flx-R). To determine a peripheral biological signature of fluoxetine response, proteomic analysis was performed from PBMCs isolated from the “most” affected corticosterone/vehicle (CORT/V), corticosterone/fluoxetine responders and non-responders (CORT/Flx-NR) animals. In comparison to CORT/V, a total of 263 proteins were differently expressed after fluoxetine exposure. Expression profile of these proteins showed a strong similarity between CORT/Flx-R and CORT/Flx-NR (R = 0.827, p < 1e-7). Direct comparison of CORT/Flx-R and CORT/Flx-NR groups revealed 100 differently expressed proteins, representing a combination of markers associated either with the maintenance of animals in a refractory state, or associated with behavioral improvement. Finally, 19 proteins showed a differential
Full Text Available The incorporation of peripheral biomarkers in the treatment of major depressive disorders (MDD could improve the efficiency of treatments and increase remission rate. Peripheral blood mononuclear cells (PBMCs represent an attractive biological substrate allowing the identification of a drug response signature. Using a proteomic approach with high-resolution mass spectrometry, the present study aimed to identify a biosignature of antidepressant response (fluoxetine, a Selective Serotonin Reuptake Inhibitor in PBMCs in a mouse model of anxiety/depression. Following determination of an emotionality score, using complementary behavioral analysis of anxiety/depression across three different tests (Elevated Plus Maze, Novelty Suppressed Feeding, Splash Test, we showed that a 4-week corticosterone treatment (35 μg/ml, CORT model in C57BL/6NTac male mice induced an anxiety/depressive-like behavior. Then, chronic fluoxetine treatment (18 mg/kg/day for 28 days in the drinking water reduced corticosterone-induced increase in emotional behavior. However, among 46 fluoxetine-treated mice, only 30 of them presented a 50% decrease in emotionality score, defining fluoxetine responders (CORT/Flx-R. To determine a peripheral biological signature of fluoxetine response, proteomic analysis was performed from PBMCs isolated from the “most” affected corticosterone/vehicle (CORT/V, corticosterone/fluoxetine responders and non-responders (CORT/Flx-NR animals. In comparison to CORT/V, a total of 263 proteins were differently expressed after fluoxetine exposure. Expression profile of these proteins showed a strong similarity between CORT/Flx-R and CORT/Flx-NR (R = 0.827, p < 1e-7. Direct comparison of CORT/Flx-R and CORT/Flx-NR groups revealed 100 differently expressed proteins, representing a combination of markers associated either with the maintenance of animals in a refractory state, or associated with behavioral improvement. Finally, 19 proteins showed a
Gao-Hua Wang; Hai-Yan Dong; Wei-Guo Dong; Xiao-Ping Wang; He-Sheng Luo; Jie-Ping Yu
AIM: To investigate the abnormity of rat colon caused by depression and the ameliorative effects of Radix Acanthopanacis Senticosi (RAS) capsule on colon and their mechanisms in rat depression model.METHODS: Chronic stress-induced model of depression of Wistar rats was produced. The experimental animals were randomly divided into model control, 5-aminosalicylic acid (5-ASA) therapy group and three RAS capsule therapy groups. These five groups were intracolonically treated daily (8:00 a.m.) for 2 wk with normal saline, 5-ASA(100 mg/ kg) and RAS capsule at the doses of 300, 600and 900 mg/kg, respectively. A normal control group of rats was also included in the study. Colonic activities of nitric oxide (NO) and superoxide dismutase (SOD), levels of malondialdehyde (MDA) and indudble nitric oxide synthase (iNOS) were determined by ultraviolet spectrophotometry.The expression of cyclooxygenase-2 (COX-2) in colonic tissue was detected by immunohistochemistry.RESULTS: Enhanced colon inflammatory response and oxidative stress were observed in the chronic stressinduced rat depression model, which manifested as the significant increase of MDA, iNOS and NO levels, as well as the expressions of COX-2 in the colon tissue, but the colonic SOD activity was significantly decreased compared with the normal control (MDA: 10.34±2.77 vs 2.55±0.70;iNOS: 1.11±0.44 vs0.25±0.16; COX2:53.26±8.16 vs4.87±1.65; NO: 11.28±5.66 vs 4.76±1.55; SOD: 53.39±11.15vs 84.45±22.31; P＜0.01). However, these parameters were significantly ameliorated in rats treated locally with RAS capsule at the doses of 300, 600 and 900 mg/kg(iNOS: 0.65±0.31, 0.58±0.22 and 0.64±0.33; NO: 5.99±2.73,6.87±1.96 and 6.50±1.58; MDA: 2.92±0.75, 3.19±1.08and 3.26±1.24; SOD: 70.81±12.36, 73.30±15.30 and69.09±11.03, respectively). The expressions of COX-2 in the colon were significantly ameliorated (28.83±9.48 and27.04±9.56, respectively) when RAS capsule was administered at the doses of 600 and 900 mg
Ormel, Johan; de Jonge, Peter
Background: Despite extensive research on the relationship between depression and coronary artery disease (CAD) after an acute coronary syndrome (ACS), causal interpretations are still difficult. This uncertainty has led to much confusion regarding screening and treatment for depression in CAD
Yankelevitch-Yahav, Roni; Franko, Motty; Huly, Avrham; Doron, Ravid
The goal of the present protocol is to describe the forced swim test (FST), which is one of the most commonly used assays for the study of depressive-like behavior in rodents. The FST is based on the assumption that when placing an animal in a container filled with water, it will first make efforts to escape but eventually will exhibit immobility that may be considered to reflect a measure of behavioral despair. This test has been extensively used because it involves the exposure of the animals to stress, which was shown to have a role in the tendency for major depression. Additionally, the FST has been shown to share some of the factors that are influenced or altered by depression in humans, including changes in food consumption, sleep abnormalities and drug-withdrawal-induced anhedonia. The main advantages of this procedure are that it is relatively easy to perform and that its results are easily and quickly analyzed. Moreover, its sensitivity to a broad range of antidepressant drugs that makes it a suitable screening test is one of the most important features leading to its high predictive validity. Despite its appeal, this model has a number of disadvantages. First, the issue of chronic augmentation is problematic in this test because in real life patients need to be treated for at least several weeks before they experience any relief from their symptoms. Last, due to the aversiveness of the FST, it is important to take into account possible influences it might have on brain structure/function if brain analyses are to be carried out following this procedure. PMID:25867960
Yankelevitch-Yahav, Roni; Franko, Motty; Huly, Avrham; Doron, Ravid
The goal of the present protocol is to describe the forced swim test (FST), which is one of the most commonly used assays for the study of depressive-like behavior in rodents. The FST is based on the assumption that when placing an animal in a container filled with water, it will first make efforts to escape but eventually will exhibit immobility that may be considered to reflect a measure of behavioral despair. This test has been extensively used because it involves the exposure of the animals to stress, which was shown to have a role in the tendency for major depression. Additionally, the FST has been shown to share some of the factors that are influenced or altered by depression in humans, including changes in food consumption, sleep abnormalities and drug-withdrawal-induced anhedonia. The main advantages of this procedure are that it is relatively easy to perform and that its results are easily and quickly analyzed. Moreover, its sensitivity to a broad range of antidepressant drugs that makes it a suitable screening test is one of the most important features leading to its high predictive validity. Despite its appeal, this model has a number of disadvantages. First, the issue of chronic augmentation is problematic in this test because in real life patients need to be treated for at least several weeks before they experience any relief from their symptoms. Last, due to the aversiveness of the FST, it is important to take into account possible influences it might have on brain structure/function if brain analyses are to be carried out following this procedure.
Thurstone's scaling based on judgments of 527 students and 37 clinical faculty members was applied to the Beck Depression Inventory, the Zung Depression Scale, and the Minnesota Multiphasic Personality Inventory and fitted the observed data well. A psychological continuum was derived for severity of depression. (SLD)
EunYoung Kim, PhD
Conclusion: The results suggest there are mediating effects of loneliness and depression in the relationship between attachment anxiety and smartphone addiction. The hypothesized model was found to be a suitable model for predicting smartphone addiction among university students. Future study is required to find a causal path to prevent smartphone addiction among university students.
Mathe, A.; Sousa, V.; Fischer, C. W.
pathophysiological factor and converging evidence indicates that other systems, such as the glutamatergic are of paramount importance. Indeed, work at the Yale University, NIMH, and Icahn School of Medicine at Mount Sinai demonstrated the marked antidepressant effects of intravenously infused ketamine to treatment...... resistant patients diagnosed with major depressive disorder. In order to better understand the mechanisms of ketamine effects we decided to test it on animal models. Methods: All experiments were approved by the Karolinska Institutet's Committee for Animal Protection. Two rat models, bred at the Karolinska...... Institutet, the Flinders Sensitive Line (FSL) and their controls, the Flinders Resistant Line (FRL), and the SERT KO (homozygous, heterozygous, and the wild type rats) were used. Male animals were injected 10 mg ketamine/kg body weight or vehicle and the Open Field Test (OF) and Forced Swim Test (FST...
Slyepchenko, Anastasiya; Maes, Michael; Köhler, Cristiano A; Anderson, George; Quevedo, João; Alves, Gilberto S; Berk, Michael; Fernandes, Brisa S; Carvalho, André F
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.
Yuanyuan Zhang; Jianjun Jia; Liping Chen; Zhitao Han; Yulan Zhao; Honghong Zhang; Yazhuo Hu
Shuyusan, a traditional Chinese medicine, was shown to improve depression symptoms and behavioral scores, as well as increase 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan levels, in a rat model of chronic stress-induced depression. However, dopamine, noradrenalin, and 3-methoxy-4-hydroxyphenylglycol expressions remained unchanged following Shuyusan treatment. Compared with the model group, the number of 5-HT-positive neurons in layers 4-5 of the frontal cortex, as well as hippocampal CA1 and CA3 regions, significantly increased following Shuyusan treatment. These results suggested that Shuyusan improved symptoms in a rat model of chronic stress-induced depression with mechanisms that involved 5-HT, 5-HT metabolite, 5-HT precursor expressions.
Berends, Constantijn J.; van de Wal, Roderik S. W.
Many processes govern the deglaciation of ice sheets. One of the processes that is usually ignored is the calving of ice in lakes that temporarily surround the ice sheet. In order to capture this process a "flood-fill algorithm" is needed. Here we present and evaluate several optimizations to a standard flood-fill algorithm in terms of computational efficiency. As an example, we determine the land-ocean mask for a 1 km resolution digital elevation model (DEM) of North America and Greenland, a geographical area of roughly 7000 by 5000 km (roughly 35 million elements), about half of which is covered by ocean. Determining the land-ocean mask with our improved flood-fill algorithm reduces computation time by 90 % relative to using a standard stack-based flood-fill algorithm. This implies that it is now feasible to include the calving of ice in lakes as a dynamical process inside an ice-sheet model. We demonstrate this by using bedrock elevation, ice thickness and geoid perturbation fields from the output of a coupled ice-sheet-sea-level equation model at 30 000 years before present and determine the extent of Lake Agassiz, using both the standard and improved versions of the flood-fill algorithm. We show that several optimizations to the flood-fill algorithm used for filling a depression up to a water level, which is not defined beforehand, decrease the computation time by up to 99 %. The resulting reduction in computation time allows determination of the extent and volume of depressions in a DEM over large geographical grids or repeatedly over long periods of time, where computation time might otherwise be a limiting factor. The algorithm can be used for all glaciological and hydrological models, which need to trace the evolution over time of lakes or drainage basins in general.
Gonzalez-Pena, Dianelys; Nixon, Scott E; O'Connor, Jason C; Southey, Bruce R; Lawson, Marcus A; McCusker, Robert H; Borras, Tania; Machuca, Debbie; Hernandez, Alvaro G; Dantzer, Robert; Kelley, Keith W; Rodriguez-Zas, Sandra L
Depression symptoms following immune response to a challenge have been reported after the recovery from sickness. A RNA-Seq study of the dysregulation of the microglia transcriptome in a model of inflammation-associated depressive behavior was undertaken. The transcriptome of microglia from mice at day 7 after Bacille Calmette Guérin (BCG) challenge was compared to that from unchallenged Control mice and to the transcriptome from peripheral macrophages from the same mice. Among the 562 and 3,851 genes differentially expressed between BCG-challenged and Control mice in microglia and macrophages respectively, 353 genes overlapped between these cells types. Among the most differentially expressed genes in the microglia, serum amyloid A3 (Saa3) and cell adhesion molecule 3 (Cadm3) were over-expressed and coiled-coil domain containing 162 (Ccdc162) and titin-cap (Tcap) were under-expressed in BCG-challenged relative to Control. Many of the differentially expressed genes between BCG-challenged and Control mice were associated with neurological disorders encompassing depression symptoms. Across cell types, S100 calcium binding protein A9 (S100A9), interleukin 1 beta (Il1b) and kynurenine 3-monooxygenase (Kmo) were differentially expressed between challenged and control mice. Immune response, chemotaxis, and chemokine activity were among the functional categories enriched by the differentially expressed genes. Functional categories enriched among the 9,117 genes differentially expressed between cell types included leukocyte regulation and activation, chemokine and cytokine activities, MAP kinase activity, and apoptosis. More than 200 genes exhibited alternative splicing events between cell types including WNK lysine deficient protein kinase 1 (Wnk1) and microtubule-actin crosslinking factor 1(Macf1). Network visualization revealed the capability of microglia to exhibit transcriptome dysregulation in response to immune challenge still after resolution of sickness symptoms
Full Text Available Depression symptoms following immune response to a challenge have been reported after the recovery from sickness. A RNA-Seq study of the dysregulation of the microglia transcriptome in a model of inflammation-associated depressive behavior was undertaken. The transcriptome of microglia from mice at day 7 after Bacille Calmette Guérin (BCG challenge was compared to that from unchallenged Control mice and to the transcriptome from peripheral macrophages from the same mice. Among the 562 and 3,851 genes differentially expressed between BCG-challenged and Control mice in microglia and macrophages respectively, 353 genes overlapped between these cells types. Among the most differentially expressed genes in the microglia, serum amyloid A3 (Saa3 and cell adhesion molecule 3 (Cadm3 were over-expressed and coiled-coil domain containing 162 (Ccdc162 and titin-cap (Tcap were under-expressed in BCG-challenged relative to Control. Many of the differentially expressed genes between BCG-challenged and Control mice were associated with neurological disorders encompassing depression symptoms. Across cell types, S100 calcium binding protein A9 (S100A9, interleukin 1 beta (Il1b and kynurenine 3-monooxygenase (Kmo were differentially expressed between challenged and control mice. Immune response, chemotaxis, and chemokine activity were among the functional categories enriched by the differentially expressed genes. Functional categories enriched among the 9,117 genes differentially expressed between cell types included leukocyte regulation and activation, chemokine and cytokine activities, MAP kinase activity, and apoptosis. More than 200 genes exhibited alternative splicing events between cell types including WNK lysine deficient protein kinase 1 (Wnk1 and microtubule-actin crosslinking factor 1(Macf1. Network visualization revealed the capability of microglia to exhibit transcriptome dysregulation in response to immune challenge still after resolution of sickness
Depression - postpartum; Postnatal depression; Postpartum psychological reactions ... behavioral therapy (CBT) and interpersonal therapy (IPT) are types of talk therapy that often help postpartum depression. ...
Demirtaş, Tuğçe; Utkan, Tijen; Karson, Ayşe; Yazır, Yusufhan; Bayramgürler, Dilek; Gacar, Nejat
Inflammation has been suggested to be associated with stress-induced depression and cardiovascular dysfunction. Tumor necrosis factor alpha (TNF-α) is a major cytokine in the activation of neuroendocrine, immune, and behavioral responses. In this study, we investigated the effects of infliximab (a TNF-α inhibitor) on endothelium-dependent vascular reactivity, systemic blood pressure, and endothelial nitric oxide synthase (eNOS) immunoreactivity in the unpredictable chronic mild stress (UCMS) model of depression in rats. There was no significant change between all groups in the systemic blood pressure. In UCMS, endothelium-dependent relaxation of the smooth muscle in response to carbachol was significantly decreased with 50 % maximal response (E max) and pD2 values compared with the controls. Infliximab was able to reverse this UCMS effect. Relaxation in response to the nitric oxide (NO) donor sodium nitroprusside and papaverine and KCl-induced contractile responses was similar between groups. In UCMS, decreased expression of eNOS was detected. Moreover, there was no significant change in UCMS + infliximab group with respect to control rats. Our results suggest that tumor necrosis factor-alpha (TNF-α) could be a major mediator of vascular dysfunction associated with UCMS, leading to decreased expression of eNOS.
Rania F. Ahmed
Full Text Available There are numerous herbal medicines that have been introduced into psychiatric practice because of greater compliance and milder side effects. Polygonum cuspidatum is a native Asian plant; known for its medicinal properties and traditionally used in the treatment of neuropsychiatric disorders, such as psychosocial stress, dementia and Parkinson’s disease. Resveratrol is the active ingredient of P. cuspidatum. Researchers have suggested that the trans-isomer of resveratrol demonstrates a variety of pharmacological activities including antioxidant, anti-inflammatory, hepatic and neuroprotective properties. In this study we examined the hepatoprotective and antidepressant effects of trans-resveratrol against fluoxetine in an acute reserpine model of depression in rats. Main methods: depression-like behaviors were induced by single reserpine intraperitoneal injection (6 mg/kg, i.p.. Trans-resveratrol (15, 30 and 60 mg/kg bwt and fluoxetine (24 mg/kg bwt were administered orally for the following 3 days. Behavioral effects namely open field test (OFT and forced swimming test (FST and biochemical parameters namely neurotransmitters levels and antioxidant contents were assessed. Liver histopathological examination was performed. Key findings: Results revealed that resveratrol (60 mg/kg bwt showed a potential hepatoprotective and an antidepressant-like effects compared to those of fluoxetine.
Vaccheri, A; Dall'Olio, R; Gaggi, R; Gandolfi, O; Montanaro, N
The atypical neuroleptic sulpiride is also prescribed for depression because of its activating effect. However, such an effect does not necessarily imply an action identical to that of classical antidepressants, and a laboratory comparison of the neuroleptic and antidepressant activities of sulpiride may contribute to a better definition of its psychotherapeutic profile. Sulpiride isomers were studied in the rat in four behavioural models of depression which are thought to be influenced by neuroleptics in different ways. Desipramine (imipramine) and haloperidol were employed in each test as a standard antidepressant and neuroleptic, respectively. The four tests were: 1) prevention of apomorphine-induced sedation: 2) antagonism of apomorphine-induced hypothermia; 3) behavioural despair (swim test); 4) learned helplessness ( FR2 lever pressing escape). Desipramine ameliorated behaviour in all tests; haloperidol ameliorated the response to test 1, influenced that to test 2 in a neuroleptic-like way and worsened the responses to tests 3 and 4. (-)-Sulpiride worked in a similar way to haloperidol in all tests. (+)-Sulpiride significantly and dose-dependently ameliorated the responses to test 3 and was inactive in the others. No conclusion was drawn from test 1 owing to its lack of specificity; the results of the remaining tests indicated a neuroleptic profile of (-)-sulpiride and suggested a potential "antidepressant" activity of (+)-sulpiride which merits further investigation.
Algorithms for extracting hydrologic features and properties from digital elevation models (DEMs) are challenged by large datasets, which often cannot fit within a computer's RAM. Depression filling is an important preconditioning step to many of these algorithms. Here, I present a new, linearly scaling algorithm which parallelizes the Priority-Flood depression-filling algorithm by subdividing a DEM into tiles. Using a single-producer, multi-consumer design, the new algorithm works equally well on one core, multiple cores, or multiple machines and can take advantage of large memories or cope with small ones. Unlike previous algorithms, the new algorithm guarantees a fixed number of memory access and communication events per subdivision of the DEM. In comparison testing, this results in the new algorithm running generally faster while using fewer resources than previous algorithms. For moderately sized tiles, the algorithm exhibits ∼60% strong and weak scaling efficiencies up to 48 cores, and linear time scaling across datasets ranging over three orders of magnitude. The largest dataset on which I run the algorithm has 2 trillion (2×1012) cells. With 48 cores, processing required 4.8 h wall-time (9.3 compute-days). This test is three orders of magnitude larger than any previously performed in the literature. Complete, well-commented source code and correctness tests are available for download from a repository.
Full Text Available Abstract Animal models of psychiatric disorders are usually discussed with regard to three criteria first elaborated by Willner; face, predictive and construct validity. Here, we draw the history of these concepts and then try to redraw and refine these criteria, using the framework of the diathesis model of depression that has been proposed by several authors. We thus propose a set of five major criteria (with sub-categories for some of them; homological validity (including species validity and strain validity, pathogenic validity (including ontopathogenic validity and triggering validity, mechanistic validity, face validity (including ethological and biomarker validity and predictive validity (including induction and remission validity. Homological validity requires that an adequate species and strain be chosen: considering species validity, primates will be considered to have a higher score than drosophila, and considering strains, a high stress reactivity in a strain scores higher than a low stress reactivity in another strain. Pathological validity corresponds to the fact that, in order to shape pathological characteristics, the organism has been manipulated both during the developmental period (for example, maternal separation: ontopathogenic validity and during adulthood (for example, stress: triggering validity. Mechanistic validity corresponds to the fact that the cognitive (for example, cognitive bias or biological mechanisms (such as dysfunction of the hormonal stress axis regulation underlying the disorder are identical in both humans and animals. Face validity corresponds to the observable behavioral (ethological validity or biological (biomarker validity outcomes: for example anhedonic behavior (ethological validity or elevated corticosterone (biomarker validity. Finally, predictive validity corresponds to the identity of the relationship between the triggering factor and the outcome (induction validity and between the effects of
Weng Yee Chin
Full Text Available The naturalistic course for patients suffering from depressive disorders can be quite varied. Whilst some remit with little or no intervention, others may suffer a more prolonged course of symptoms. The aim of this study was to identify trajectory patterns for depressive symptoms in a Chinese primary care cohort and their associated factors.A 12-month cohort study was conducted. Patients recruited from 59 primary care clinics across Hong Kong were screened for depressive symptoms using the Centre for Epidemiologic Studies Depression Scale (CES-D and monitored over 12 months using the Patient Health Questionnaire-9 items (PHQ-9 administered at 12, 26 and 52 weeks. 721 subjects were included for growth mixture modelling analysis. Using Akaike Information Criterion, Bayesian Information Criterion, Entropy and Lo-Mendell-Rubin adjusted likelihood ratio test, a seven-class trajectory path model was identified. Over 12 months, three trajectory groups showed improvement in depressive symptoms, three remained static, whilst one deteriorated. A mild severity of depressive symptoms with gradual improvement was the most prevalent trajectory identified. Multivariate, multinomial regression analysis was used to identify factors associated with each trajectory. Risk factors associated with chronicity included: female gender; not married; not in active employment; presence of multiple chronic disease co-morbidities; poor self-rated general health; and infrequent health service use.Whilst many primary care patients may initially present with a similar severity of depressive symptoms, their course over 12 months can be quite heterogeneous. Although most primary care patients improve naturalistically over 12 months, many do not remit and it is important for doctors to be able to identify those who are at risk of chronicity. Regular follow-up and greater treatment attention is recommended for patients at risk of chronicity.
Smolkina, M; Morley, K I; Rijsdijk, F; Agrawal, A; Bergin, J E; Nelson, E C; Statham, D; Martin, N G; Lynskey, M T
Cannabis use disorder (CUD) co-occurs with major depressive disorder (MDD) more frequently than would be expected by chance. However, studies to date have not produced a clear understanding of the mechanisms underlying this co-morbidity. Genetically informative studies can add valuable insight to this problem, as they allow the evaluation of competing models of co-morbidity. This study uses data from the Australian Twin Registry to compare 13 co-morbidity twin models initially proposed by Neale and Kendler (Am J Hum Genet 57:935-953, 1995). The analysis sample comprised 2410 male and female monozygotic and dizygotic twins (average age 32) who were assessed on CUD and MDD using the SSAGA-OZ interview. Data were analyzed in OpenMx. Of the 13 different co-morbidity models, two fit equally well: CUD causes MDD and Random Multiformity of CUD. Both fit substantially better than the Correlated Liabilities model. Although the current study cannot differentiate between them statistically, these models, in combination, suggest that CUD risk factors may causally influence the risk to develop MDD, but only when risk for CUD is high.
Andrew R Gallimore
Full Text Available The expression of long-term depression (LTD in cerebellar Purkinje cells results from the internalisation of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs from the postsynaptic membrane. This process is regulated by a complex signalling pathway involving sustained protein kinase C (PKC activation, inhibition of serine/threonine phosphatase, and an active protein tyrosine phosphatase, PTPMEG. In addition, two AMPAR-interacting proteins-glutamate receptor-interacting protein (GRIP and protein interacting with C kinase 1 (PICK1-regulate the availability of AMPARs for trafficking between the postsynaptic membrane and the endosome. Here we present a new computational model of these overlapping signalling pathways. The model reveals how PTPMEG cooperates with PKC to drive LTD expression by facilitating the effect of PKC on the dissociation of AMPARs from GRIP and thus their availability for trafficking. Model simulations show that LTD expression is increased by serine/threonine phosphatase inhibition, and negatively regulated by Src-family tyrosine kinase activity, which restricts the dissociation of AMPARs from GRIP under basal conditions. We use the model to expose the dynamic balance between AMPAR internalisation and reinsertion, and the phosphorylation switch responsible for the perturbation of this balance and for the rapid plasticity initiation and regulation. Our model advances the understanding of PF-PC LTD regulation and induction, and provides a validated extensible platform for more detailed studies of this fundamental synaptic process.
Watson, Fraser; Dalla, Silvia; Marshall, Stephen; 10.1007/s11207-009-9420-z
The distributions of sunspot longitude at first appearance and at disappearance display an east-west asymmetry that results from a reduction in visibility as one moves from disk centre to the limb. To first order, this is explicable in terms of simple geometrical foreshortening. However, the centre-to-limb visibility variation is much larger than that predicted by foreshortening. Sunspot visibility is also known to be affected by the Wilson effect: the apparent dish shape of the sunspot photosphere caused by the temperature-dependent variation of the geometrical position of the tau=1 layer. In this article we investigate the role of the Wilson effect on the sunspot appearance distributions, deducing a mean depth for the umbral tau=1 layer of 500 to 1500 km. This is based on the comparison of observations of sunspot longitude distribution and Monte Carlo simulations of sunspot appearance using different models for spot growth rate, growth time and depth of Wilson depression.
Watson, F.; Fletcher, L.; Dalla, S.; Marshall, S.
The distributions of sunspot longitude at first appearance and at disappearance display an east-west asymmetry that results from a reduction in visibility as one moves from disk centre to the limb. To first order, this is explicable in terms of simple geometrical foreshortening. However, the centre-to-limb visibility variation is much larger than that predicted by foreshortening. Sunspot visibility is also known to be affected by the Wilson effect: the apparent ‘dish’ shape of the sunspot photosphere caused by the temperature-dependent variation of the geometrical position of the τ=1 layer. In this article we investigate the role of the Wilson effect on the sunspot appearance distributions, deducing a mean depth for the umbral τ=1 layer of 500 - 1500 km. This is based on the comparison of observations of sunspot longitude distribution and Monte Carlo simulations of sunspot appearance using different models for spot growth rate, growth time and depth of Wilson depression.
Fischer, C. W.; Elfving, B.; Lund, S.
that elevated markers of inflammation predict a poor response to treatment. Furthermore, increasing evidences show that metabolic abnormalities such as obesity and diabetes mellitus type 2 are associated with a low-grade inflammation. Objectives: The aim of this study is to investigate the effects of a systemic...... levels of pro-inflammatory cytokines (TNF-alpha, IL-1, IL-6) together with the expression of enzymes involved in the tryptophan-kynurenine pathway, will be analyzed in specific brain regions using real-time qPCR. Body weight and food intake was measured once a week, while fasting glucose and insulin...... disturbances or sickness behavior. Thus, this model might help elucidating some of the mechanisms underlying inflammation-associated depression, in order to assist in developing more effective treatment strategies for this group of patients....
Airan, Raag D; Meltzer, Leslie A; Roy, Madhuri; Gong, Yuqing; Chen, Han; Deisseroth, Karl
The hippocampus is one of several brain areas thought to play a central role in affective behaviors, but the underlying local network dynamics are not understood. We used quantitative voltage-sensitive dye imaging to probe hippocampal dynamics with millisecond resolution in brain slices after bidirectional modulation of affective state in rat models of depression. We found that a simple measure of real-time activity-stimulus-evoked percolation of activity through the dentate gyrus relative to the hippocampal output subfield-accounted for induced changes in animal behavior independent of the underlying mechanism of action of the treatments. Our results define a circuit-level neurophysiological endophenotype for affective behavior and suggest an approach to understanding circuit-level substrates underlying psychiatric disease symptoms.
Full Text Available Advanced societies face increased health problems related to various stresses. Chronic psychological stress is a major risk factor for psychiatric disorders such as depression. Although therapeutic agents reduce several symptoms of depression, most have side effects in a broad range of the population. Furthermore, some victims of depression do not show significant improvement with any drugs, so alternative approaches are needed. Good dietary habits may potentially reduce depressive symptoms, but there is little scientific evidence thus far. Murine depression models are useful to test nutritional approaches in vivo. Our model mice subjected to a subchronic mild social defeat stress (sCSDS paradigm show several alterations in physiological parameters and social behavior. These stress-induced symptoms in sCSDS mice can be used as cues to identify antidepressant-like natural resources including foods and farm products. We previously discovered that sCSDS mice show more vulnerability to social stress by changing dietary condition. In addition, we developed a more objective system for analyzing mouse behavior using a 3D depth-sensing camera to understand relationships between diet and behavior. The combination of sCSDS mice with 3D behavioral analysis is a powerful method for screening ingredients in foods and farm products for antidepressant-like effects.
Kim, Kyoung-Shim; Kang, Young-Mi; Kang, Young; Park, Tae-Shin; Park, Hye-Yeon; Kim, Yoon-Jung; Han, Baek-Soo; Kim, Chun-Hyung; Lee, Chul-Ho; Ardayfio, Paul A; Han, Pyung-Lim; Jung, Bong-Hyun; Kim, Kwang-Soo
Approximately 40-50% of all patients with Parkinson׳s disease (PD) show symptoms and signs of depressive disorders, for which neither pathogenic understanding nor rational treatment are available. Using Pit3x-deficient mice, a model for selective nigrostriatal dopaminergic neurodegeneration, we tested depression-related behaviors and acute stress responses to better understand how a nigrostriatal dopaminergic deficit increases the prevalence of depressive disorders in PD patients. Pitx3-deficient mice showed decreased sucrose consumption and preference in the two-bottle free-choice test of anhedonia. Acute restraint stress increased c-Fos (known as a neuronal activity marker) expression levels in various brain regions, including the prefrontal cortex, striatum, nucleus accumbens, and paraventricular nucleus of the hypothalamus (PVN), in both Pitx3+/+ and -/- mice. However, the stress-induced increases in c-Fos levels in the cortex, dorsal striatum, and PVN were significantly greater in Pitx3-/- than +/+ mice, suggesting that signs of depressive disorders in parkinsonism are related to altered stress vulnerability. Based on these results, we propose that Pitx3-/- mice may serve as a useful genetic animal model for co-morbid depressive disorder and parkinsonism.
Rees, Gwyneth; Mellor, David; Holloway, Edith E; Sturrock, Bonnie A; Hegel, Mark T; Casten, Robin; Xie, Jing; Finkelstein, Eric; Lamoureux, Ecosse; Keeffe, Jill E
Depression is a common problem among people with visual impairment and contributes to functional decline. This article presents a study protocol to evaluate a new model of care for those patients with depressive symptoms in which psychological treatment is integrated into low vision rehabilitation services. Low vision staff will be trained to deliver "problem solving therapy for primary care" (PST-PC), an effective psychological treatment developed specifically for delivery by non-mental health care staff. PST-PC is delivered in 8 weekly telephone sessions of 30-45 minutes duration and 4 monthly maintenance sessions. We predict this new integrated model of care will significantly reduce depressive symptoms and improve the quality of life for people with visual impairment. A randomized controlled trial of PST-PC will be implemented nationally across low vision rehabilitation services provided by Vision Australia. Clients who screen positive for depressive symptoms and meet study criteria will be randomized to receive PST-PC or usual care, consisting of a referral to their general practitioner for more detailed assessment and treatment. Outcome measures include depressive symptoms and behaviors, quality of life, coping and psychological adjustment to visual impairment. Masked assessments will take place pre- and post-intervention as well as at 6- and 12-month follow-up. We anticipate that this innovative service delivery model will lead to sustained improvements in clients' quality of life in a cost effective manner and provide an innovative service delivery model suitable for other health care areas in which depression is co-morbid.
van Kampen, Marja; Kramer, Marian; Hiemke, Christoph; Flügge, Gabriele; Fuchs, Eberhard
To improve our knowledge of the causal mechanisms of stress-related disorders such as depression, we need animal models that mirror the situation in patients. One promising model is the chronic psychosocial stress paradigm in male tree shrews, which is based on the territorial behaviour of these animals that can be used to establish naturally occurring challenging situations under experimental control in the laboratory. Co-existence of two males in visual and olfactory contact leads to a stable dominant-subordinate relationship, with subordinates showing distinct stress-induced behavioural and neuroendocrine alterations that are comparable to the symptoms observed during episodes of depression in patients such as constantly elevated circulating glucocorticoid hormones due to a chronic hyperactivity of the hypothalamic-pituitary-adrenal axis. To elucidate whether the chronic psychosocial stress model in tree shrews besides its "face validity" for depression also has "predictive validity", we treated subordinate tree shrews with the tricyclic antidepressant clomipramine and found a time-dependent restoration of both endocrine and behavioural parameters. In contrast, the anxiolytic diazepam was ineffective. Although the chronic psychosocial stress model in tree shrews requires further validation, it has sufficient face, predictive, and construct validity to become an interesting non-rodent model for research on the etiology and pathophysiology of depression.
Verisokin, Andrey Y.; Verveyko, Darya V.; Postnov, Dmitry E.
In recent decades modelling studies on cortical spreading depression (CSD) and migraine waves successfully contributed to formation of modern view on these fundamental phenomena of brain physiology. However, due to the extreme complexity of object under study (brain cortex) and the diversity of involved physiological pathways, the development of new mathematical models of CSD is still a very relevant and challenging research problem. In our study we follow the functional modelling approach aimed to map the action of known physiological pathways to the specific nonlinear mechanisms that govern formation and evolution of CSD wave patterns. Specifically, we address the role of cerebral blood flow (CBF) redistribution that is caused by excessive neuronal activity by means of neurovascular coupling and mediates a spatial pattern of oxygen and glucose delivery. This in turn changes the local metabolic status of neural tissue. To build the model we simplify the web of known cell-to-cell interactions within a neurovascular unit by selecting the most relevant ones, such as local neuron-induced elevation of extracellular potassium concentration and biphasic response of arteriole radius. We propose the lumped description of distance-dependent hemodynamic coupling that fits the most recent experimental findings.
Clark, L A; Watson, D
We review psychometric and other evidence relevant to mixed anxiety-depression. Properties of anxiety and depression measures, including the convergent and discriminant validity of self- and clinical ratings, and interrater reliability, are examined in patient and normal samples. Results suggest that anxiety and depression can be reliably and validly assessed; moreover, although these disorders share a substantial component of general affective distress, they can be differentiated on the basis of factors specific to each syndrome. We also review evidence for these specific factors, examining the influence of context and scale content on ratings, factor analytic studies, and the role of low positive affect in depression. With these data, we argue for a tripartite structure consisting of general distress, physiological hyperarousal (specific anxiety), and anhedonia (specific depression), and we propose a diagnosis of mixed anxiety-depression.
Daniel M Iascone
Full Text Available Alzheimer's disease (AD, the most common cause of dementia, is also associated with depression. Although the precise mechanisms that lead to depression in AD are unknown, the impairments in adult hippocampal neurogenesis observed in AD may play a role. Adult-born neurons play a critical role in regulating both cognition and mood, and reduced hippocampal neurogenesis is associated with depression in other neurological disorders. To assess the relationship between Alzheimer's disease, neurogenesis, and depression, we studied human amyloid precursor protein (hAPP transgenic mice, a well-characterized model of AD. We report that reductions in hippocampal neurogenesis are evident early in disease progression in hAPP mice, but a mild depressive phenotype manifests only in later stages of disease. We found that hAPP mice exhibited a reduction in BrdU-positive cells in the subgranular zone of the dentate gyrus in the hippocampus, as well as a reduction in doublecortin-expressing cells, relative to nontransgenic controls at 5-7 months of age. These alterations in neurogenesis appeared to worsen with age, as the magnitude of reduction in doublecortin-expressing cells was greater in hAPP mice at 13-15 months of age. Only 13-15 month old hAPP mice exhibited depressive behavior in the tail suspension test. However, mice at both age groups exhibited deficits in spatial memory, which was observed in the Morris water maze test for hippocampus-dependent memory. These findings indicate that neurogenesis impairments are accompanied by cognitive deficits, but are not tightly linked to depressive behavior in hAPP mice.
Barnes, Richard; Lehman, Clarence; Mulla, David
Depressions (or pits) are areas within a digital elevation model that are surrounded by higher terrain, with no outlet to lower areas. Filling them so they are level, as fluid would fill them if the terrain was impermeable, is often necessary in preprocessing DEMs. The depression-filling algorithm presented here - called Priority-Flood - unifies and improves the work of a number of previous authors who have published similar algorithms. The algorithm operates by flooding DEMs inwards from their edges using a priority queue to determine the next cell to be flooded. The resultant DEM has no depressions or digital dams: every cell is guaranteed to drain. The algorithm is optimal for both integer and floating-point data, working in O(n) and O(n log2 n) time, respectively. It is shown that by using a plain queue to fill depressions once they have been found, an O(m log2 m) time-complexity can be achieved, where m does not exceed the number of cells n. This is the lowest time complexity of any known floating-point depression-filling algorithm. In testing, this improved variation of the algorithm performed up to 37% faster than the original. Additionally, a parallel version of an older, but widely used, depression-filling algorithm required six parallel processors to achieve a run-time on par with what the newer algorithm's improved variation took on a single processor. The Priority-Flood Algorithm is simple to understand and implement: the included pseudocode is only 20 lines and the included C++ reference implementation is under a hundred lines. The algorithm can work on irregular meshes as well as 4-, 6-, 8-, and n-connected grids. It can also be adapted to label watersheds and determine flow directions through either incremental elevation changes or depression carving. In the case of incremental elevation changes, the algorithm includes safety checks not present in prior works.
Mouton, Moné; Harvey, Brian H; Cockeran, Marike; Brink, Christiaan B
Methamphetamine (METH) is a psychostimulant and drug of abuse, commonly used early in life, including in childhood and adolescence. Adverse effects include psychosis, anxiety and mood disorders, as well as increased risk of developing a mental disorder later in life. The current study investigated the long-term effects of chronic METH exposure during pre-adolescence in stress-sensitive Flinders Sensitive Line (FSL) rats (genetic model of depression) and control Flinders Resistant Line (FRL) rats. METH or vehicle control was administered twice daily from post-natal day 19 (PostND19) to PostND34, followed by behavioural testing at either PostND35 (early effects) or long-lasting after withdrawal at PostND60 (early adulthood). Animals were evaluated for depressive-like behaviour, locomotor activity, social interaction and object recognition memory. METH reduced depressive-like behaviour in both FSL and FRL rats at PostND35, but enhanced this behaviour at PostND60. METH also reduced locomotor activity on PostND35 in both FSL and FRL rats, but without effect at PostND60. Furthermore, METH significantly lowered social interaction behaviour (staying together) in both FRL and FSL rats at PostND35 and PostND60, whereas self-grooming time was significantly reduced only at PostND35. METH treatment enhanced exploration of the familiar vs. novel object in the novel object recognition test (nORT) in FSL and FRL rats on PostND35 and PostND60, indicative of reduced cognitive performance. Thus, early-life METH exposure induce social and cognitive deficits. Lastly, early-life exposure to METH may result in acute antidepressant-like effects immediately after chronic exposure, whereas long-term effects after withdrawal are depressogenic. Data also supports a role for genetic predisposition as with FSL rats.
Wei, Y B; Liu, J J; Villaescusa, J C;
in the inflammation process and IL-6 was shown to be one of its targets. In the present study, we report elevation of Il6 in the prefrontal cortex (PFC) of a genetic rat model of depression, the Flinders Sensitive Line (FSL) compared to the control Flinders Resistant Line. This elevation was associated...
Hughes, Alicia A; Heimberg, Richard G; Coles, Meredith E; Gibb, Brandon E; Liebowitz, Michael R; Schneier, Franklin R
Our primary goal was to examine the relations of the specific components of the tripartite model of anxiety and depression [Clark, L. A., Watson, D. (1991). Tripartite model of anxiety and depression: Psychometric evidence and taxonomic implications. Journal of Abnormal Psychology, 100, 316-336] to two types of social anxiety (social interaction anxiety and performance anxiety) in 148 individuals with social phobia. In line with previous research, overall social anxiety was more closely related to the anhedonic depression (AD) or low positive affect factor of the tripartite model than to the physiological hyerarousal factor, controlling for general distress. However, as hypothesized, performance anxiety was more closely associated with the physiological hyerarousal factor, whereas social interaction anxiety was more closely associated with the AD or low positive affect factor. We also examined the convergent and discriminant validity of the Mood and Anxiety Symptom Questionnaire (MASQ; [Watson, D., Clark, L. A. (1991). The mood and anxiety symptom questionnaire. Unpublished manuscript, University of Iowa City]). Intercorrelations of the MASQ subscales were as expected, but correlations with measures of social anxiety, nonsocial anxiety, and depression provided only modest support for convergent and discriminant validity. Findings from this study provide a more detailed account of the specific components of the tripartite model that characterize the diversity of symptoms subsumed by social phobia.
Full Text Available Abstract Background The relationships between working conditions [job demand, job control and social support]; stress, anxiety, and depression; and perceived quality of life factors [physical health, psychological wellbeing, social relationships and environmental conditions] were assessed using a sample of 698 male automotive assembly workers in Malaysia. Methods The validated Malay version of the Job Content Questionnaire (JCQ, Depression Anxiety Stress Scales (DASS and the World Health Organization Quality of Life-Brief (WHOQOL-BREF were used. A structural equation modelling (SEM analysis was applied to test the structural relationships of the model using AMOS version 6.0, with the maximum likelihood ratio as the method of estimation. Results The results of the SEM supported the hypothesized structural model (χ2 = 22.801, df = 19, p = 0.246. The final model shows that social support (JCQ was directly related to all 4 factors of the WHOQOL-BREF and inversely related to depression and stress (DASS. Job demand (JCQ was directly related to stress (DASS and inversely related to the environmental conditions (WHOQOL-BREF. Job control (JCQ was directly related to social relationships (WHOQOL-BREF. Stress (DASS was directly related to anxiety and depression (DASS and inversely related to physical health, environment conditions and social relationships (WHOQOL-BREF. Anxiety (DASS was directly related to depression (DASS and inversely related to physical health (WHOQOL-BREF. Depression (DASS was inversely related to the psychological wellbeing (WHOQOL-BREF. Finally, stress, anxiety and depression (DASS mediate the relationships between job demand and social support (JCQ to the 4 factors of WHOQOL-BREF. Conclusion These findings suggest that higher social support increases the self-reported quality of life of these workers. Higher job control increases the social relationships, whilst higher job demand increases the self-perceived stress and decreases
Steer, R A; Clark, D A; Ranieri, W F
To determine the extent to which the SCL-90-R assesses general distress or specific dimensions of psychopathology, two principal components analyses were conducted based on 900 outpatients diagnosed with mixed psychiatric disorders. The first component explained 30.5% of the total variance and was interpreted as reflecting overall symptom distress. Partialling the first component out of the correlations among the symptoms in a second principal components analysis, we found four specific residual components reflecting somatic anxiety, depression, irritability, and attention problems. The results were discussed as partially supporting Clark and Watson's (1991) tripartite model of anxiety and depression.
Aditya J Reddy
Full Text Available Background: Musa sapientum, the banana plant, has shown to possess antioxidant activity in previous studies. Oxidative stress has been linked to the pathogenesis of major depressive disorder (MDD with evidence of increased serum levels of oxidative stress biomarkers in MDD patients. Objective: The present study aimed to evaluate the antidepressant activity of M. sapientum stem extract (MSSE in experimental models in mice. Materials and Methods: Forced swim test (FST and tail suspension test (TST were carried out in five different groups (n = 6/group of mice. The vehicle, standard drug, and the three test groups were orally administered distilled water (10 mL/kg, fluoxetine (25 mg/kg, and incremental doses of 25, 50, and 100 mg of MSSE, respectively, 45 min prior to the experiment. Results: On FST, the duration of immobility in control group, which was 161.5 ± 6.78 (in seconds, mean ± standard error of mean [SEM], decreased to 149.33 ± 2.70 (25 mg/kg MSSE, 120.17 ± 8.35 (50 mg/kg MSSE, and 45.17 ± 4.11 (100 mg/kg MSSE in the treated groups. On TST, the duration of immobility in control group, which was 173.83 ± 12.65 (mean ± SEM, decreased to 163.17 ± 6.91 (25 mg/kg MSSE, 139.0 ± 5.9 (50 mg/kg MSSE, and 124.0 ± 4.42 (100 mg/kg MSSE in the treated groups. The difference in the duration of immobility was statistically significant at middle and higher doses, i.e. 50 and 100 mg/kg MSSE (P < 0.05 respectively, when compared with the control group in both the tests. Conclusion: A significant antidepressant-like activity was found in MSSE, which could be a potential natural compound for use in depression.
Wróbel, Andrzej; Serefko, Anna; Wlaź, Piotr; Poleszak, Ewa
Relationship between the chronic and excessive exposure to glucocorticoids and the development of psychiatric disorders, including depression, has been described in the literature. We decided to investigate whether a combination of agents with antidepressant activity (i.e., imipramine, ketamine, and Zn(2+)) may influence/reverse the depressogenic effect of dexamethasone therapy. The antidepressant-like effect was assessed by the forced swim test in adult mice. The inhibitory activity of dexamethasone was dose-dependent: only the highest tested dose of the glucocorticoid (i.e., 64 μg/kg) given as a single injection increased immobility time, whereas 16 μg/kg/day of dexamethasone administered repeatedly (for 14 days) induced a significant alteration in animal behavior. Both the acute or sub-chronic administration of the active doses of imipramine (10 mg/kg), Zn(2+) (30 mg/kg), and ketamine (30 mg/kg), and the combinations of their per se inactive doses reversed the inhibitory activity of dexamethasone (16 μg/kg/day) administered for 14 consecutive days. Whereas a single injection of an inhibitory dose of dexamethasone (64 μg/kg) was not able to abolish the antidepressant effect of imipramine (5 mg/kg), Zn(2+) (10 mg/kg), and imipramine-Zn(2+) combination (2.5 and 5 mg/kg, respectively) given once a day for 14 consecutive days. Our findings indicate that the chronic dexamethasone injection procedure has some potential as an animal model of depression and they further support the theory of interplay between glutamatergic neurotransmission and the chronic or excessive exposition to glucocorticoids.
Kotsovolou, Olga; Ingelman-Sundberg, Magnus; Lang, Matti A; Marselos, Marios; Overstreet, David H; Papadopoulou-Daifoti, Zoi; Johanson, Inger; Fotopoulos, Andrew; Konstandi, Maria
The Flinders Sensitive Line (FSL) rat model of depression exhibits some behavioral, neurochemical, and pharmacological features that have been reported in depressed patients and has been very effective in screening antidepressants. Major factor that determines the effectiveness and toxicity of a drug is the drug metabolizing capacity of the liver. Therefore, in order to discriminate possible differentiation in the hepatic drug metabolism between FSL rats and Sprague-Dawley (SD) controls, their hepatic metabolic profile was investigated in this study. The data showed decreased glutathione (GSH) content and glutathione S-transferase (GST) activity and lower expression of certain major CYP enzymes, including the CYP2B1, CYP2C11 and CYP2D1 in FSL rats compared to SD controls. In contrast, p-nitrophenol hydroxylase (PNP), 7-ethoxyresorufin-O-dealkylase (EROD) and 16alpha-testosterone hydroxylase activities were higher in FSL rats. Interestingly, the wide spread environmental pollutant benzo(alpha)pyrene (B(alpha)P) induced CYP1A1, CYP1A2, CYP2B1/2 and ALDH3c at a lesser extend in FSL than in SD rats, whereas the antidepressant mirtazapine (MIRT) up-regulated CYP1A1/2, CYP2C11, CYP2D1, CYP2E1 and CYP3A1/2, mainly, in FSL rats. The drug also further increased ALDH3c whereas suppressed GSH content in B(alpha)P-exposed FSL rats. In conclusion, several key enzymes of the hepatic biotransformation machinery are differentially expressed in FSL than in SD rats, a condition that may influence the outcome of drug therapy. The MIRT-induced up-regulation of several drug-metabolizing enzymes indicates the critical role of antidepressant treatment that should be always taken into account in the designing of treatment and interpretation of insufficient pharmacotherapy or drug toxicity.
Bagdy, Gyorgy; Juhasz, Gabriella; Gonda, Xenia
In our current understanding of mood disorders, the role of genes is diverse including the mediation of the effects of provoking and protective factors. Different or partially overlapping gene sets play a major role in the development of personality traits including also affective temperaments, in the mediation of the effects of environmental factors, and in the interaction of these elements in the development of depression. Certain genes are associated with personality traits and temperaments including e.g., neuroticism, impulsivity, openness, rumination and extroversion. Environmental factors consist of external (early and provoking life events, seasonal changes, social support etc.) and internal factors (hormones, biological rhythm generators, comorbid disorders etc). Some of these environmental factors, such as early life events and some prenatal events directly influence the development of personality traits and temperaments. In the NEWMOOD cohort polymorphisms of the genes of the serotonin transporter, 5-HT1A, 5-HT1B and 5-HT2A and endocannabinoid CB1 receptors, tryptophan hydroxylase, CREB1, BDNF and GIRK provide evidence for the involvement of these genes in the development of depression. Based on their role in this process they could be assigned to different gene sets. The role of certain genes, such as promoter polymorphisms of the serotonin transporter (5-HTTLPR) and CB1 receptor has been shown in more than one of the above factors. Furthermore, gene-gene interactions of these promoters associated with anxiety suggest the application of these polymorphisms in personalized medicine. In this review we introduce a new model including environmental factors, genes, trait and temperament markers based on human genetic studies.
Tae, Young Sook; Heitkemper, Margaret; Kim, Mi Yea
To test a hypothetical model of depression in Korean women with breast cancer and to test the mediating effects of self-esteem and hope. Cross-sectional design. Participants were recruited from three general hospitals and one cancer hospital in Busan, South Korea. 214 Korean women diagnosed with breast cancer (stages I-III). All participants completed questionnaires (e.g., Zung Self-Rating Depression scale, Herth Hope Scale, Rosenberg Self-Esteem Scale, Health Self-Rating Scale in Health and Activity survey, Kang's Family Support Scale). Based on the literature, Mplus, version 3.0, was used to determine the best depression model with path analysis. Depression, self-esteem, hope, perceived health status, religious beliefs, family support, economic status, and fatigue. Self-esteem was directly affected by perceived health status, religious beliefs, family support, economic status, and fatigue. Hope was directly affected by family support, self-esteem, and how patients perceived their health status. Depression was directly affected by self-esteem and hope. The path analysis model explained 31% of the variance in depression in Korean women with breast cancer. A model of depression in Korean women with breast cancer was developed, and self-esteem and hope were mediating factors of depression. Self-esteem and hope must be considered when developing services to reduce depression in Korean women with breast cancer.
Dongmei Duan; Xiuyan Yang; Ya Tu; Liping Chen
Preliminary basic research and clinical ifndings have demonstrated that electroacupuncture ther-apy exhibits positive effects in ameliorating depression. However, most studies of the underlying mechanism are at the single gene level;there are few reports regarding the mechanism at the whole-genome level. Using a rat genomic gene-chip, we proifled hippocampal gene expression changes in rats after electroacupuncture therapy. Electroacupuncture therapy alleviated depres-sion-related manifestations in the model rats. Using gene-chip analysis, we demonstrated that electroacupuncture at Baihui (DU20) and Yintang (EX-HN3) regulates the expression of 21 genes. Real-time PCR showed that the genes Vg f, Ig f2, Tmp32, Loc500373, Hif1a, Folr1, Nmb, and Rtn were upregulated or downregulated in depression and that their expression tended to nor-malize after electroacupuncture therapy. These results indicate that electroacupuncture at Baihui and Yintang modulates depression by regulating the expression of particular genes.
Bouzinova, Elena; Wiborg, Ove; Aalkjær, Christian;
Major depression and cardiovascular diseases have strong co-morbidity but the reason for this is unknown. In CMS model of depression only some rats develop depression-like symptoms (i.e. anhedonia, measured by sucrose intake) while others are resilient to 8 weeks of CMS. Anhedonic rats have...... decreased cardiac output and unchanged blood pressure, suggesting increased total peripheral resistance. Small mesenteric and femoral arteries from CMS and non-stressed rats responded similarly to noradrenaline (NA) under control conditions but inhibition of neuronal reuptake with cocaine increased NA...... sensitivity stronger in anhedonic than in resilient and non-stressed groups. In contrast, corticosterone-sensitive extra-neuronal monoamine uptake was diminished in rats exposed to CMS. These changes in monoamine homeostasis were associated with upregulation neuronal NA transporter and reduced expression...
Chen, F.; Wegener, Gregers; Madsen, T. M.
Post-mortem, genetic, brain imaging, and peripheral cell studies showed that mitochondria may play an important role in the pathophysiology of depression and effects of antidepressant therapy. Here we investigated whether chronic antidepressant treatment on rats induce changes of the mitochondrial...... and SD-saline group. Impramine treatment can significantly increase the mitochondria numerical density and the number of mitochondria in FSL-imipramine group. Our results support the mitochondria plasticity hypothesis that depressive disorders may be related to impairments of mitochondria plasticity...... model of depression. The unbiased stereoloy methods were used to estimate the mitochondria numerical density, the number of mitochondria and the mean size and volume of mitochondria in CA1 stratum radiatum (CA1SR) of hippocampus. The results showed that the mitochondria numerical density and the number...
Full Text Available Abstract Background Neuronal mechanisms underlying affective disorders such as major depression (MD are still poorly understood. By selectively breeding mice for high (HR, intermediate (IR, or low (LR reactivity of the hypothalamic-pituitary-adrenocortical (HPA axis, we recently established a new genetic animal model of extremes in stress reactivity (SR. Studies characterizing this SR mouse model on the behavioral, endocrine, and neurobiological levels revealed several similarities with key endophenotypes observed in MD patients. HR mice were shown to have changes in rhythmicity and sleep measures such as rapid eye movement sleep (REMS and non-REM sleep (NREMS as well as in slow wave activity, indicative of reduced sleep efficacy and increased REMS. In the present study we were interested in how far a detailed spectral analysis of several electroencephalogram (EEG parameters, including relevant frequency bands, could reveal further alterations of sleep architecture in this animal model. Eight adult males of each of the three breeding lines were equipped with epidural EEG and intramuscular electromyogram (EMG electrodes. After recovery, EEG and EMG recordings were performed for two days. Results Differences in the amount of REMS and wakefulness and in the number of transitions between vigilance states were found in HR mice, when compared with IR and LR animals. Increased frequencies of transitions from NREMS to REMS and from REMS to wakefulness in HR animals were robust across the light-dark cycle. Detailed statistical analyses of spectral EEG parameters showed that especially during NREMS the power of the theta (6-9 Hz, alpha (10-15 Hz and eta (16-22.75 Hz bands was significantly different between the three breeding lines. Well defined distributions of significant power differences could be assigned to different times during the light and the dark phase. Especially during NREMS, group differences were robust and could be continuously monitored
Full Text Available Memories are believed to be represented in the synaptic pathways of vastly interconnected networks of neurons. The plasticity of synapses, that is, their strengthening and weakening depending on neuronal activity, is believed to be the basis of learning and establishing memories. An increasing number of studies indicate that endocannabinoids have a widespread action on brain function through modulation of synaptic transmission and plasticity. Recent experimental studies have characterised the role of endocannabinoids in mediating both short- and long-term synaptic plasticity in various brain regions including the hippocampus, a brain region strongly associated with cognitive functions, such as learning and memory. Here, we present a biophysically plausible model of cannabinoid retrograde signalling at the synaptic level and investigate how this signalling mediates depolarisation induced suppression of inhibition (DSI, a prominent form of short-term synaptic depression in inhibitory transmission in hippocampus. The model successfully captures many of the key characteristics of DSI in the hippocampus, as observed experimentally, with a minimal yet sufficient mathematical description of the major signalling molecules and cascades involved. More specifically, this model serves as a framework to test hypotheses on the factors determining the variability of DSI and investigate under which conditions it can be evoked. The model reveals the frequency and duration bands in which the post-synaptic cell can be sufficiently stimulated to elicit DSI. Moreover, the model provides key insights on how the state of the inhibitory cell modulates DSI according to its firing rate and relative timing to the post-synaptic activation. Thus, it provides concrete suggestions to further investigate experimentally how DSI modulates and is modulated by neuronal activity in the brain. Importantly, this model serves as a stepping stone for future deciphering of the role of
Full Text Available Objective. Refugees are at high risk for mental health problems due to trauma in their pasts and to acculturation stress as they settle in a new country. To develop efficient health services to meet the needs of refugees from various regions, an understanding of how they make sense of and prefer to cope with mental health problems is warranted. This study aims to investigate lay explanatory models of depression and preferred coping strategies among Somali refugees in Norway.Methods. The study used a mixed-method design with a vignette describing a moderately depressed person based on ICD-10 criteria. Firstly, a survey study was performed among Somali refugees (n = 101. Respondents were asked to provide advice to the vignette character, completing the Cross-Cultural Depression Coping Inventory and the General Help-Seeking Questionnaire. Secondly, focus group interviews (n = 10 were done separately with males and females to examine the relationship between the explanatory models of depression and preferred coping strategies.Results. The participants showed a strong preference for coping with depression by religious practices and reliance on family, friends, and their ethnic/religious community rather than seeking professional treatment from public health services (e.g., medical doctors, psychologists. Depressive symptoms were conceptualized as a problem related to cognition (thinking too much and emotion (sadness, but not with biological mechanisms, and were thought to result from spiritual possessions, stress from social isolation, and/or past trauma. Independent of time in exile, the participants showed a strong identification with their ethnic origin and associated values. As participants emphasized the need to obey and follow the viewpoint of elders, fathers, and spiritual leaders, these authorities seemed to be gatekeepers for access to mental health services. Conclusion. The results highlight that mental health programs for Somali refugees
Markova, Valeria; Sandal, Gro M
Objective: Refugees are at high risk of experiencing mental health problems due to trauma in their pasts and to acculturation stress as they settle in a new country. To develop efficient health services that meet the needs of refugees from different regions, an understanding is required of how they make sense of and prefer to cope with mental health problems. This study aims to investigate lay explanatory models of depression and preferred coping strategies among Somali refugees in Norway. Methods: The study used a mixed-method design with a vignette describing a moderately depressed person based on ICD-10 criteria. Firstly, a survey study was performed among Somali refugees (n = 101). Respondents were asked to give advice to the vignette character and complete the Cross-Cultural Depression Coping Inventory and the General Help-Seeking Questionnaire. Secondly, focus group interviews (n = 10) were conducted separately with males and females to examine the relationship between the explanatory models of depression and the preferred coping strategies. Results: The participants showed a strong preference for coping with depression by religious practices and reliance on family, friends, and their ethnic/religious community, rather than by seeking professional treatment from public health services (e.g., medical doctors, psychologists). Depressive symptoms were conceptualized as a problem related to cognition (thinking too much) and emotion (sadness), but not to biological mechanisms, and they were thought to result from spiritual possession, stress as a result of social isolation, and/or past trauma. Independently of time in exile, the participants showed a strong identification with their ethnic origin and associated values. Because participants emphasized the need to obey and follow the views of elders, fathers, and spiritual leaders, these authorities seemed to be "gatekeepers" for access to mental health services. Conclusion: The results highlight that mental health
Markova, Valeria; Sandal, Gro M.
Objective: Refugees are at high risk of experiencing mental health problems due to trauma in their pasts and to acculturation stress as they settle in a new country. To develop efficient health services that meet the needs of refugees from different regions, an understanding is required of how they make sense of and prefer to cope with mental health problems. This study aims to investigate lay explanatory models of depression and preferred coping strategies among Somali refugees in Norway. Methods: The study used a mixed-method design with a vignette describing a moderately depressed person based on ICD-10 criteria. Firstly, a survey study was performed among Somali refugees (n = 101). Respondents were asked to give advice to the vignette character and complete the Cross-Cultural Depression Coping Inventory and the General Help-Seeking Questionnaire. Secondly, focus group interviews (n = 10) were conducted separately with males and females to examine the relationship between the explanatory models of depression and the preferred coping strategies. Results: The participants showed a strong preference for coping with depression by religious practices and reliance on family, friends, and their ethnic/religious community, rather than by seeking professional treatment from public health services (e.g., medical doctors, psychologists). Depressive symptoms were conceptualized as a problem related to cognition (thinking too much) and emotion (sadness), but not to biological mechanisms, and they were thought to result from spiritual possession, stress as a result of social isolation, and/or past trauma. Independently of time in exile, the participants showed a strong identification with their ethnic origin and associated values. Because participants emphasized the need to obey and follow the views of elders, fathers, and spiritual leaders, these authorities seemed to be “gatekeepers” for access to mental health services. Conclusion: The results highlight that mental
Lu, Ming; Yang, Jing-Zhe; Geng, Fan; Ding, Jian-Hua; Hu, Gang
Depression is a serious mental disorder in the world, but the underlying mechanisms remain unclear and the effective cures are scarce. Iptakalim (Ipt), an ATP-sensitive potassium (K-ATP) channel opener that can cross the blood-brain barrier freely, has been demonstrated to inhibit neuro-inflammation and enhance adult hippocampal neurogenesis. But it is unknown whether Ipt is beneficial to therapy of depression by modulating neurogenesis and neuro-inflammation. This study aimed to determine the potential antidepressant efficacy of Ipt in a chronic mild stress (CMS) mouse model of depression. We showed that treatment with Ipt (10 mg/kg/day, i.p) for 4 wk restored the decrease of sucrose preference and shortened the immobile time in forced swimming tests (FST) and tail suspension tests (TST) in CMS model mice. We further found that Ipt reversed the CMS-induced reduction of the adult hippocampal neurogenesis and improved cerebral insulin signalling in the CMS mice. Furthermore, Ipt negatively regulated nod-like receptor protein 3 (NLRP3) expression and, in turn, inhibited microglia-mediated neuro-inflammation by suppressing the activation of NLRP3-inflammasome/caspase-1/interleukin 1β axis in the hippocampus of CMS mice. Taken together, our findings demonstrate that Ipt plays a potential antidepressant role in CMS model mice through regulating neuro-inflammation and neurogenesis, which will provide potential for Ipt in terms of opening up novel therapeutic avenues for depression.
Friedman, Elliot; Berman, Marissa; Overstreet, David
The Flinders sensitive line (FSL) genetic animal model of depression exhibits marked immobility during forced swimming, an accepted index of depressive like behavior in rodent depression models. The present experiment tested the hypothesis that swim test behavior in the FSL rats is influenced in part by early experience, specifically maternal environment. Male FSL and control Flinders resistant line (FRL) pups were cross fostered onto dams of the same or complementary strain. Nest quality and dam behavior during pup retrieval were measured on PN5 and PN8, and swim test behavior assessed in the adult males on PN60. FSL rats reared by foster FRL dams were significantly less immobile than FSL rats raised by FSL dams, but still significantly more immobile that the two FRL groups, which did not differ from each other. FSL dams took significantly longer to retrieve their pups and dropped them more often than the FRL control dams. Moreover, strain differences in maternal retrieval behavior significantly predicted later swim test immobility in the FSL animals. These findings suggest that swim test immobility in the FSL rats is modified by maternal environment. In contrast, the FRL control rats were relatively insensitive to the influence of maternal environment. The FSL model offers promise for understanding the interactions of genetic vulnerabilities and environmental influences in the etiology of clinical depression.
Schellinger, Kriston B.; Holmbeck, Grayson N.; Essner, Bonnie S.; Alvarez, Renae
The purpose of the study was to examine the extent to which parenting behaviors influence the relation between maternal and child depressive symptoms in youth with spina bifida and a comparison sample. Previous research has found that maternal depression not only negatively impacts the mother-child relationship, but also places the child at risk…
Bilican, F. Isil; Yapici, Asim; Kutlu, M. Oguz
This study aimed to examine which values predicted depressive symptoms and hopelessness in Turkey. While it was hypothesized that values emphasizing universalism, benevolence, conformity, security, tradition, spirituality, self-direction, and achievement would predict lower levels of depressive symptoms and hopelessness, those values emphasizing…
Schellinger, Kriston B.; Holmbeck, Grayson N.; Essner, Bonnie S.; Alvarez, Renae
The purpose of the study was to examine the extent to which parenting behaviors influence the relation between maternal and child depressive symptoms in youth with spina bifida and a comparison sample. Previous research has found that maternal depression not only negatively impacts the mother-child relationship, but also places the child at risk…
Noh, Jin-Won; Kwon, Young Dae; Park, Jumin; Oh, In-Hwan; Kim, Jinseok
Background Depression in persons with physical disabilities may be more common than in the general population. The purpose of this study was to examine the relationship between physical disability and depression by gender among adults, using a large, nationally representative sample. Methods This
Nieboer, AP; Schulz, R; Matthews, KA; Scheier, MF; Ormel, J; Lindenberg, SM
In this paper we examine the effects of increasing as well as decreasing caregiving demands on depressive symptomatology. In addition, we focus on spousal caregivers' activity restriction as an explanatory mechanism for changes in depressive symptomatology in the caregiving context. Two databases ar
Yang, Jae-Won; Hong, Sungdo D; Joung, Yoo Sook; Kim, Ji-Hae
Although the currently available literature has provided some empirical support for a tripartite model of child and adolescent anxiety and depression, one of the limitations of these studies was that they have been conducted in America, primarily with Caucasians. In order to make this model more applicable to diverse ethnic and cultural groups, this study used a tripartite model for child and adolescent anxiety and depression in Korea, using confirmatory factor analysis with logically selected items from the Revised Children's Manifest Anxiety Scale (RCMAS), as well as the Children's Depression Inventory (CDI). The results indicated that the model fit of a three-factor model was superior to one- and two-factor models. In addition, the findings of discriminant analysis demonstrated that the correct classification rate with three factors of the tripartite model was superior to the classification rate achievable using CDI and RCMAS. In a departure from Clark and Watson's hypothesis, however, the correlations of three factors were significantly higher than had been expected. The results are discussed on the basis of cultural background.
Tortella-Feliu, Miquel; Balle, Maria; Sesé, Albert
The relationship between negative affectivity (NA) and emotion regulation (ER) in determining anxiety and depressive symptomatology was examined in a large (n=1441) sample of adolescents (12-17 years old). Two models, diverging only as to inclusion or exclusion of a path from NA to negative ER, were analyzed through structural equation modeling; the goal was to explore the mediational or non-mediational role of ER in determining anxiety symptoms. The models yielded similar adequate fit to data, indicating that both NA and negative ER contribute to anxiety symptoms which, in turn, significantly determine depressive symptomatology. The mediational model better captures the relationships revealed in the data, with NA determining negative ER to a great extent. Additionally, most individuals scoring highly in NA also tend to score highly in negative ER, indicating that adolescents with heightened NA are prone to a dysfunctional style of ER.
Norr, Aaron M; Allan, Nicholas P; Macatee, Richard J; Capron, Daniel W; Schmidt, Norman B
Suicide constitutes a significant public health burden as global suicide rates continue to increase. Thus, it is crucial to identify malleable suicide risk factors to develop prevention protocols. Anxiety sensitivity, or a fear of anxiety-related sensations, is a potential malleable risk factor for the development of suicidal ideation. The Depression-Distress Amplification Model (DDAM) posits that the anxiety sensitivity cognitive concerns (ASCC) subfactor interacts with depressive symptoms to amplify the effects of depression and lead to suicidal ideation. The current study tested the DDAM across the two most widely-replicated factors of depressive symptoms (cognitive and affective/somatic) in comparison to a risk factor mediation model where ASCC are related to suicidal ideation via depressive symptoms. Participants included 295 clinical outpatients from a community clinic. The interaction between ASCC and depressive symptoms in the prediction of suicidal ideation was not significant for either cognitive or affective/somatic symptoms of depression. However, results revealed a significant indirect effect of ASCC through cognitive symptoms of depression in the prediction of suicidal ideation. These cross sectional findings are not consistent with the DDAM. Rather, the relationship may be better conceptualized with a model in which ASCC is related to suicidal ideation via cognitive symptoms of depression.
Gross, Heather E; Shaw, Daniel S; Moilanen, Kristin L; Dishion, Thomas J; Wilson, Melvin N
Although much has been written about transactional models in the study of parenting practices, relatively few researchers have used this approach to examine how child behavior might be related to parental well-being. This study used latent growth curve modeling to test transactional models of age 2 child noncompliance, parental depressive symptoms, and age 4 internalizing and externalizing behaviors using a subsample of families in the Early Steps Multisite Study. In unconditional models, maternal depressive symptoms showed a linear decrease from child ages 2 to 4, whereas paternal depression did not show significant change. Observed child noncompliance at age 2 showed significant associations with concurrent reports of maternal depressive symptoms and trend-level associations with paternal depressive symptoms. For both parents, higher levels of initial depressive symptoms were related to increased age 4 child internalizing behaviors. The findings provide support for reciprocal process models of parental depression and child behavior, and this study is one of the first to present empirical evidence that fathers' depressive symptoms have bidirectional associations with their children's behavior in early childhood. Copyright 2008 APA, all rights reserved.
QIN Xiao-song; JIN Kui-he; DING Bao-kun; XIE Shou-fu; MA Hui
Background Recent studies have indicated that chronic stress may give rise to brain damage, which is related to the genesis of depression. The purpose of this study is to investigate the effects of extract of Ginkgo biloba (EGb) and venlafaxine on depression.Methods Rats were treated with chronic and comprehensive stress to create a depression model. Immunohistochemistry was used to detect the expression of brain-derived neurotrophic factor (BDNF) in the hippocampal CA3 neurons of rats treated with different drugs. Behavioral changes of these rats were also examined. Results The expression of BDNF in the hippocampal CA3 neurons of the depression model decreased with a reduction in exploring behavior and a significant increase in fecal production. The expression of neuron nitric-oxide synthase (nNOS) protein also increased in the rats compared to normal controls. The rats treated with EGb and venlafaxine showed an increase in expression of BDNF and exploring behavior compared to untreated rats, but a decrease in nNOS and fecal production.Conclusions Rats sustain damage to the brain after being subjected to chronic and comprehensive stress. Our research has indicated that combined EGb with venlafaxine enhances the protection of neurons and decreases damage to the brain, while relieving the side effects of synthetic antidepressants.
Kroes, R A; Panksepp, J; Burgdorf, J; Otto, N J; Moskal, J R
Gene expression profiles in the cortex of adult Long-Evans rats as a function of a stressful social loss and victory in inter-male fighting encounters were examined. This social dominance and subordination model has been postulated to simulate early changes in the onset of depression in the losers. Microarrays were fabricated containing 45mer oligonucleotides spotted in quadruplicate and representing 1178 brain-associated genes. Dynamic range, discrimination power, accuracy and reproducibility were determined with standard mRNA "spiking" studies. Gene expression profiles in dominant and subordinate animals were compared using a "universal" reference design [Churchill GA (2002) Fundamentals of experimental design for cDNA microarrays. Nat Genet 32 (Suppl):490-495]. Data were analyzed by significance analysis of microarrays using rank scores [Tusher VG, Tibshirani R, Chu G (2001) Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 98:5116-5121; van de Wiel MA (2004) Significance analysis of microarrays using rank scores. Kwantitatieve Methoden 71:25-37]. Ontological analyses were then performed using the GOMiner algorithm [Zeeberg BR, Feng W, Wang G, Wang MD, Fojo AT, Sunshine M, Narasimhan S, Kane DW, Reinhold WC, Lababidi S, Bussey KJ, Riss J, Barrett JC, Weinstein JN (2003) GoMiner: a resource for biological interpretation of genomic and proteomic data. Genome Biol 4(4):R28]. And finally, genes of special interest were further studied using quantitative reverse transcriptase polymerase chain reaction. Twenty-two transcripts were statistically significantly differentially expressed in the neocortex between dominant and subordinate animals. Ontological analyses revealed that significant gene changes were clustered primarily into functional neurochemical pathways associated with protein biosynthesis and cytoskeletal dynamics. The most robust of these were the increased expression of interleukin-18, heat shock
Zhou, Jian-Fang; Yuan, Wu-Jie; Zhou, Zhao; Zhou, Changsong
Recently, the significant microsaccade-induced neural responses have been extensively observed in experiments. To explore the underlying mechanisms of the observed neural responses, a feedforward network model with short-term synaptic depression has been proposed [Yuan, W.-J., Dimigen, O., Sommer, W. and Zhou, C. Front. Comput. Neurosci. 7, 47 (2013)]. The depression model not only gave an explanation for microsaccades in counteracting visual fading, but also successfully reproduced several microsaccade-related features in experimental findings. These results strongly suggest that, the depression model is very useful to investigate microsaccade-related neural responses. In this paper, by using the model, we extensively study and predict the dependance of microsaccade-related neural responses on several key parameters, which could be tuned in experiments. Particularly, we provide a significant prediction that microsaccade-related neural response also complies with the property "sharper is better" observed in many contexts in neuroscience. Importantly, the property exhibits a power-law relationship between the width of input signal and the responsive effectiveness, which is robust against many parameters in the model. By using mean field theory, we analytically investigate the robust power-law property. Our predictions would give theoretical guidance for further experimental investigations of the functional role of microsaccades in visual information processing.
Oltean, Horea-Radu; Hyland, Philip; Vallières, Frédérique; David, Daniel Ovidiu
This study aimed to assess the validity of two models which integrate the cognitive (satisfaction with life) and affective (symptoms of anxiety and depression) aspects of subjective well-being within the framework of rational emotive behaviour therapy (REBT) theory; specifically REBT's theory of psychopathology and theory of psychological health. 397 Irish and Northern Irish undergraduate students completed measures of rational/irrational beliefs, satisfaction with life, and anxiety/depression symptoms. Structural equation modelling techniques were used in order to test our hypothesis within a cross-sectional design. REBT's theory of psychopathology (χ2 = 373.78, d.f. = 163, p < .001; comparative fit index (CFI) = .92; Tucker Lewis index (TLI) = .91; root mean square error of approximation (RMSEA) = .06 (95% CI = .05 to .07); standardized root mean square residual (SRMR) = .07) and psychological health (χ2 = 371.89, d.f. = 181, p < .001; CFI = .93; TLI = .92; RMSEA = .05 (95% CI = .04 to .06); SRMR = .06) provided acceptable fit of the data. Moreover, the psychopathology model explained 34% of variance in levels of anxiety/depression, while the psychological health model explained 33% of variance. This study provides important findings linking the fields of clinical and positive psychology within a comprehensible framework for both researchers and clinicians. Findings are discussed in relation to the possibility of more effective interventions, incorporating and targeting not only negative outcomes, but also positive concepts within the same model.
Edwards, Michael C.; Cheavens, Jennifer S.; Heiy, Jane E.; Cukrowicz, Kelly C.
The Center for Epidemiologic Studies Depression Scale (CES-D) is one of the most widely used measures of depressive symptoms in research today. The original psychometric work in support of the CES-D (Radloff, 1977) described a 4-factor model underlying the 20 items on the scale. Despite a long history of evidence supporting this structure,…
Izaque S Maciel
Full Text Available This study was aimed to characterize the depression-like behaviour in the classical model of chronic inflammation induced by Complete Freund's Adjuvant (CFA. Male Swiss mice received an intraplantar (i.pl. injection of CFA (50 µl/paw or vehicle. Behavioural and inflammatory responses were measured at different time-points (1 to 4 weeks, and different pharmacological tools were tested. The brain levels of IL-1β and BDNF, or COX-2 expression were also determined. CFA elicited a time-dependent edema formation and mechanical allodynia, which was accompanied by a significant increase in the immobility time in the tail suspension (TST or forced-swimming (FST depression tests. Repeated administration of the antidepressants imipramine (10 mg/kg, fluoxetine (20 mg/kg and bupropion (30 mg/kg significantly reversed depression-like behaviour induced by CFA. Predictably, the anti-inflammatory drugs dexamethasone (0.5 mg/kg, indomethacin (10 mg/kg and celecoxib (30 mg/kg markedly reduced CFA-induced edema. The oral treatment with the analgesic drugs dipyrone (30 and 300 mg/kg or pregabalin (30 mg/kg significantly reversed the mechanical allodyinia induced by CFA. Otherwise, either dipyrone or pregabalin (both 30 mg/kg did not significantly affect the paw edema or the depressive-like behaviour induced by CFA, whereas the oral treatment with dipyrone (300 mg/kg was able to reduce the immobility time in TST. Noteworthy, CFA-induced edema was reduced by bupropion (30 mg/kg, and depression behaviour was prevented by celecoxib (30 mg/kg. The co-treatment with bupropion and celecoxib (3 mg/kg each significantly inhibited both inflammation and depression elicited by CFA. The same combined treatment reduced the brain levels of IL-1β, as well as COX-2 immunopositivity, whilst it failed to affect the reduction of BDNF levels. We provide novel evidence on the relationship between chronic inflammation and depression, suggesting that combination of antidepressant and
Full Text Available Abstract Background In order to elucidate the complex relationship between co-occurring depression and anxiety with cardiac autonomic function in the elderly, this study examined the correlation between cardiac vagal control (CVC and pre-defined, theoretical factors from the Hospital Anxiety and Depression Scale (HADS. Methods Three hundred fifty-four randomly selected Chinese male subjects aged ≥65 years and living in the community were enrolled. CVC was measured using a frequency-domain index of heart rate variability. Results Confirmatory factor analysis showed that the flat tripartite model of HADS provided a modest advantage in model fit when compared with other theoretical factor solutions. In the flat tripartite model, there was a significant negative association between anhedonic depression and CVC. In contrast, autonomic anxiety showed a significant positive correlation with CVC. In the hierarchical tripartite model, negative affectivity was not directly associated with CVC; instead, it had positive and negative indirect effects on CVC via autonomic anxiety and anhedonic depression, respectively. As scores for negative affectivity increased, these specific indirect effects diminished. Conclusions Among competing models of co-occurring depression and anxiety, constructs from tripartite models demonstrate fair conformity with the data but unique and distinct correlations with CVC. Negative affectivity may determine the relationship of anhedonic depression and autonomic anxiety with CVC. Separating affective symptoms under the constructs of the tripartite models helps disentangle complex associations between co-occurring depression and anxiety with CVC.
Full Text Available Abstract Background There is a growing awareness of the need for easily administered, psychometrically sound screening tools to identify individuals with elevated levels of psychological distress. Although support has been found for the psychometric properties of the Depression, Anxiety and Stress Scales (DASS using classical test theory approaches it has not been subjected to Rasch analysis. The aim of this study was to use Rasch analysis to assess the psychometric properties of the DASS-21 scales, using two different administration modes. Methods The DASS-21 was administered to 420 participants with half the sample responding to a web-based version and the other half completing a traditional pencil-and-paper version. Conformity of DASS-21 scales to a Rasch partial credit model was assessed using the RUMM2020 software. Results To achieve adequate model fit it was necessary to remove one item from each of the DASS-21 subscales. The reduced scales showed adequate internal consistency reliability, unidimensionality and freedom from differential item functioning for sex, age and mode of administration. Analysis of all DASS-21 items combined did not support its use as a measure of general psychological distress. A scale combining the anxiety and stress items showed satisfactory fit to the Rasch model after removal of three items. Conclusion The results provide support for the measurement properties, internal consistency reliability, and unidimensionality of three slightly modified DASS-21 scales, across two different administration methods. The further use of Rasch analysis on the DASS-21 in larger and broader samples is recommended to confirm the findings of the current study.
Redfield, T. F.; Wheeler, W. H.; Often, M.
The Afar Depression is a highly extended region of continental to transitional oceanic crust lying at the junction of the Red Sea, the Gulf of Aden and the Ethiopian rifts. We analyze the evolution of the Afar crust using plate kinematics and published crustal models to constrain the temporal and volumetric evolution of the rift basin. Our reconstruction constrains the regional-scale initial 3D geometry and subsequent extension and is well calibrated at the onset of rifting (˜20 Ma) and from the time of earliest documented sea-floor spreading anomalies (˜6 Ma Red Sea; ˜10 Ma Gulf of Aden). It also suggests the Danakil block is a highly extended body, having undergone between ˜200% and ˜400% stretch. Syn-rift sedimentary and magmatic additions to the crust are taken from the literature. Our analysis reveals a discrepancy: either the base of the crust has not been properly imaged, or a (plume-related?) process has somehow caused bulk removal of crustal material since extension began. Inferring subsidence history from thermal modeling and flexural considerations, we conclude subsidence in Afar was virtually complete by Mid Pliocene time. Our analysis contradicts interpretations of late (post 3 Ma) large (˜2 km) subsidence of the Hadar area near the Ethiopian Plateau, suggesting paleoclimatic data record regional, not local, climate change. Tectonic reconstruction (supported by paleontologic and isotopic data) suggests that a land bridge connected Africa and Arabia, via Danakil, up to the Early to Middle Pliocene. The temporal constraints on land bridge and escarpment morphology constrain Afar paleogeography, climate, and faunal migration routes. These constraints (particularly the development of geographic isolation) are fundamentally important for models evaluating and interpreting biologic evolution in the Afar, including speciation and human origins.
Full Text Available Familial hemiplegic migraine type 2 (FHM2 is an autosomal dominant form of migraine with aura that is caused by mutations of the α2-subunit of the Na,K-ATPase, an isoform almost exclusively expressed in astrocytes in the adult brain. We generated the first FHM2 knock-in mouse model carrying the human W887R mutation in the Atp1a2 orthologous gene. Homozygous Atp1a2(R887/R887 mutants died just after birth, while heterozygous Atp1a2(+/R887 mice showed no apparent clinical phenotype. The mutant α2 Na,K-ATPase protein was barely detectable in the brain of homozygous mutants and strongly reduced in the brain of heterozygous mutants, likely as a consequence of endoplasmic reticulum retention and subsequent proteasomal degradation, as we demonstrate in transfected cells. In vivo analysis of cortical spreading depression (CSD, the phenomenon underlying migraine aura, revealed a decreased induction threshold and an increased velocity of propagation in the heterozygous FHM2 mouse. Since several lines of evidence involve a specific role of the glial α2 Na,K pump in active reuptake of glutamate from the synaptic cleft, we hypothesize that CSD facilitation in the FHM2 mouse model is sustained by inefficient glutamate clearance by astrocytes and consequent increased cortical excitatory neurotransmission. The demonstration that FHM2 and FHM1 mutations share the ability to facilitate induction and propagation of CSD in mouse models further support the role of CSD as a key migraine trigger.
Steven John Shabel
Full Text Available The lateral habenula (LHb is activated by aversive stimuli and the omission of reward, inhibited by rewarding stimuli and is hyperactive in helpless rats – an animal model of depression. Here we test the hypothesis that congenital learned helpless (cLH rats are more sensitive to decreases in reward size and/or less sensitive to increases in reward than wild-type (WT control rats. Consistent with the hypothesis, we found that cLH rats were slower to switch preference between two responses after a small upshift in reward size on one of the responses but faster to switch their preference after a small downshift in reward size. cLH rats were also more risk-averse than WT rats – they chose a response delivering a constant amount of reward (safe response more often than a response delivering a variable amount of reward (risky response compared to WT rats. Interestingly, the level of bias towards negative events was associated with the rat’s level of risk aversion when compared across individual rats. cLH rats also showed impaired appetitive Pavlovian conditioning but more accurate responding in a two-choice sensory discrimination task. These results are consistent with a negative learning bias and risk aversion in cLH rats, suggesting abnormal processing of rewarding and aversive events in the LHb of cLH rats.
Full Text Available Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP – a marker of neuronal activation – in c-fosGFP transgenic mice subjected to the learned helplessness (LH procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing helpless behavior had an overall brain-wide reduction in the level of neuronal activation compared with mice showing resilient behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. Our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses to stress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses.
Eising, Else; Shyti, Reinald; 't Hoen, Peter A C; Vijfhuizen, Lisanne S; Huisman, Sjoerd M H; Broos, Ludo A M; Mahfouz, Ahmed; Reinders, Marcel J T; Ferrari, Michel D; Tolner, Else A; de Vries, Boukje; van den Maagdenberg, Arn M J M
Familial hemiplegic migraine type 1 (FHM1) is a rare monogenic subtype of migraine with aura caused by mutations in CACNA1A that encodes the α1A subunit of voltage-gated CaV2.1 calcium channels. Transgenic knock-in mice that carry the human FHM1 R192Q missense mutation ('FHM1 R192Q mice') exhibit an increased susceptibility to cortical spreading depression (CSD), the mechanism underlying migraine aura. Here, we analysed gene expression profiles from isolated cortical tissue of FHM1 R192Q mice 24 h after experimentally induced CSD in order to identify molecular pathways affected by CSD. Gene expression profiles were generated using deep serial analysis of gene expression sequencing. Our data reveal a signature of inflammatory signalling upon CSD in the cortex of both mutant and wild-type mice. However, only in the brains of FHM1 R192Q mice specific genes are up-regulated in response to CSD that are implicated in interferon-related inflammatory signalling. Our findings show that CSD modulates inflammatory processes in both wild-type and mutant brains, but that an additional unique inflammatory signature becomes expressed after CSD in a relevant mouse model of migraine.
Wei, Xiao-Hui; Chang, Hong-Sheng; Zhai, Wei-Feng; Wang, Zheng-Tao
To evaluate the pre-clinical effect of YJ-XCC1Z3 on the treatment of depression with the mice mouse. YJ-XCC1Z3 was administered at the dose of 405 mg x kg(-1) and 135 mg x kg(-1) to observe the locomotor activity with the mouse locomotor activity recorder apparatus, to observe the effect of YJ-XCC1Z3 on the duration of immohility in the mouse forced swimming test and tail suspension test, to observe the effect of YJ-XCC1Z3 on the body temperature and the metabolism of monoamine neurotransmitters in mouse brain in the mouse model of reserpine induced hypothermia, and to observe the effect of YJ-XCC1 Z3 on the times of 5-HTP induced head-twitches in mice. There were no significant changes in the locomotor activity, but a significant reduction in the immobility time was observed in the mice treated with YJ-XCC1Z3 405 mg x kg(-1) and imipramine in the forced swimming test and the tail suspension test. YJ-XCC1Z3 135 mg x kg(-1) and 405 mg x kg(-1) could improve the range of reserpine induced hypothermia in mice, and the latter could also enhance the times of 5-HTP induced head-twitches in mice. YJ-XCC1Z3 405 mg x kg(-1) and 135 mg x kg(-1) could increase the content of 5-HT and NE and decrease the ratio of 5-HIAA/5-HT in mouse brain, but the dose of 405 mg x kg(-1) could decrease the content of DA. The dose of 405 mg x kg(-1) could increase the content of 5-HIAA and had no obvious effect on the content of HVA and DOPAC. YJ-XCC1Z3 shows potent antidepressant effect by improving the behaviour of the mouse in depression and not inducing hyperlocomotion in the mice. This effect results in the increase of the content of 5-HT and NE in the mouse brain. YJ-XCC1Z3 can decrease the metabolism of 5-HT to effect the content of 5-HT.
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Animal models are invaluable in preclinical research on human psychopathology. Valid animal models to study the pathophysiology of depression and specific biological and behavioral responses to antidepressant drug treatments are of prime interest. In order to improve our knowledge of the causal mechanisms of stress-related disorders such as depression, we need animal models that mirror the situation seen in patients. One promising model is the chronic psychosocial stress paradigm in male tree shrews. Coexistence of two males in visual and olfactory contact leads to a stable dominant/subordinate relationship, with the subordinates showing obvious changes in behavioral, neuroendocrine, and central nervous activity that are similar to the signs and symptoms observed during episodes of depression in patients. To discover whether this model, besides its "face validity" for depression, also has "predictive validity," we treated subordinate animals with the tricyclic antidepressant clomipramine and found a time-dependent recovery of both endocrine function and normal behavior. In contrast, the anxiolytic diazepam was ineffective. Chronic psychosocial stress in male tree shrews significantly decreased hippocampal volume and the proliferation rate of the granule precursor cells in the dentate gyrus. These stress-induced changes can be prevented by treating the animals with clomipramine, tianeptine, or the selective neurokinin receptor antagonist L-760,735. In addition to its apparent face and predictive validity, the tree shrew model also has a "molecular validity" due to the degradation routes of psychotropic compounds and gene sequences of receptors are very similar to those in humans. Although further research is required to validate this model fully, it provides an adequate and interesting non-rodent experimental paradigm for preclinical research on depression.
Holahan, Charles J.; Moos, Rudolf H.; Holahan, Carole K.; Brennan, Penny L.; Schutte, Kathleen K.
This study examined (a) the role of avoidance coping in prospectively generating both chronic and acute life stressors and (b) the stress-generating role of avoidance coping as a prospective link to future depressive symptoms. Participants were 1,211 late-middle-aged individuals (500 women and 711 men) assessed 3 times over a 10-year period. As predicted, baseline avoidance coping was prospectively associated with both more chronic and more acute life stressors 4 years later. Furthermore, as predicted, these intervening life stressors linked baseline avoidance coping and depressive symptoms 10 years later, controlling for the influence of initial depressive symptoms. These findings broaden knowledge about the stress-generation process and elucidate a key mechanism through which avoidance coping is linked to depressive symptoms. PMID:16173853
Park, A J; COLLINS, J.; Blennerhassett, P. A.; Ghia, J E; Verdu, E F; Bercik, P; Collins, S.M.
Background Depression often coexists with the irritable bowel syndrome (IBS) which is characterized by alterations in gut function. There is emerging evidence that the microbial composition (microbiota) of the gut is altered in IBS, but the basis for this is poorly understood. The aim of this study was to determine whether the induction of chronic depression results in changes in the colonic function and in its microbial community, and to explore underlying mechanisms. Methods Bilateral olfac...
Abstract Collaborative care models for depression in primary care are effective and cost-effective, but difficult to spread to new sites. Translating Initiatives for Depression into Effective Solutions (TIDES) is an initiative to promote evidence-based collaborative care in the U.S. Veterans Health Administration (VHA). Social marketing applies marketing techniques to promote positive behavior change. Described in this paper, TIDES used a social marketing approach to foster national spread of collaborative care models. TIDES social marketing approach The approach relied on a sequential model of behavior change and explicit attention to audience segmentation. Segments included VHA national leadership, Veterans Integrated Service Network (VISN) regional leadership, facility managers, frontline providers, and veterans. TIDES communications, materials and messages targeted each segment, guided by an overall marketing plan. Results Depression collaborative care based on the TIDES model was adopted by VHA as part of the new Primary Care Mental Health Initiative and associated policies. It is currently in use in more than 50 primary care practices across the United States, and continues to spread, suggesting success for its social marketing-based dissemination strategy. Discussion and conclusion Development, execution and evaluation of the TIDES marketing effort shows that social marketing is a promising approach for promoting implementation of evidence-based interventions in integrated healthcare systems. PMID:19785754
Parker Louise E
Full Text Available Abstract Collaborative care models for depression in primary care are effective and cost-effective, but difficult to spread to new sites. Translating Initiatives for Depression into Effective Solutions (TIDES is an initiative to promote evidence-based collaborative care in the U.S. Veterans Health Administration (VHA. Social marketing applies marketing techniques to promote positive behavior change. Described in this paper, TIDES used a social marketing approach to foster national spread of collaborative care models. TIDES social marketing approach The approach relied on a sequential model of behavior change and explicit attention to audience segmentation. Segments included VHA national leadership, Veterans Integrated Service Network (VISN regional leadership, facility managers, frontline providers, and veterans. TIDES communications, materials and messages targeted each segment, guided by an overall marketing plan. Results Depression collaborative care based on the TIDES model was adopted by VHA as part of the new Primary Care Mental Health Initiative and associated policies. It is currently in use in more than 50 primary care practices across the United States, and continues to spread, suggesting success for its social marketing-based dissemination strategy. Discussion and conclusion Development, execution and evaluation of the TIDES marketing effort shows that social marketing is a promising approach for promoting implementation of evidence-based interventions in integrated healthcare systems.
Luck, Jeff; Hagigi, Fred; Parker, Louise E; Yano, Elizabeth M; Rubenstein, Lisa V; Kirchner, JoAnn E
Collaborative care models for depression in primary care are effective and cost-effective, but difficult to spread to new sites. Translating Initiatives for Depression into Effective Solutions (TIDES) is an initiative to promote evidence-based collaborative care in the U.S. Veterans Health Administration (VHA). Social marketing applies marketing techniques to promote positive behavior change. Described in this paper, TIDES used a social marketing approach to foster national spread of collaborative care models. The approach relied on a sequential model of behavior change and explicit attention to audience segmentation. Segments included VHA national leadership, Veterans Integrated Service Network (VISN) regional leadership, facility managers, frontline providers, and veterans. TIDES communications, materials and messages targeted each segment, guided by an overall marketing plan. Depression collaborative care based on the TIDES model was adopted by VHA as part of the new Primary Care Mental Health Initiative and associated policies. It is currently in use in more than 50 primary care practices across the United States, and continues to spread, suggesting success for its social marketing-based dissemination strategy. Development, execution and evaluation of the TIDES marketing effort shows that social marketing is a promising approach for promoting implementation of evidence-based interventions in integrated healthcare systems.
Shetty, Reshma A; Sadananda, Monika
The Wistar-Kyoto rat (WKY) model has been suggested as a model of adult and adolescent depression though face, predictive and construct validities of the model to depression remain equivocal. The suitability of the WKY as a diathesis model that tests the double-hit hypothesis, particularly during critical periods of brain and behavioural development remains to be established. Here, effects of post-weaning social isolation were assessed during early adolescence (~30pnd) on behavioural despair and learned helplessness in the forced swim test (FST), plasma corticosterone levels and tissue monoamine concentrations in brain areas critically involved in depression, such as prefrontal cortex, nucleus accumbens, striatum and hippocampus. Significantly increased immobility in the FST was observed in socially-isolated, adolescent WKY with a concomitant increase in corticosterone levels over and above the FST-induced stress. WKY also demonstrated a significantly increased release and utilization of dopamine, as manifested by levels of metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid in nucleus accumbens, indicating that the large dopamine storage pool evident during adolescence induces greater dopamine release when stimulated. The serotonin metabolite 5-hydroxy-indoleacetic acid was also significantly increased in nucleus accumbens, indicating increased utilization of serotonin, along with norepinephrine levels which were also signficantly elevated in socially-isolated adolescent WKY. Differences in neurochemistry suggest that social or environmental stimuli during critical periods of brain and behavioural development can determine the developmental trajectories of implicated pathways.
Full Text Available To explore new noninvasive treatment options for depression, this study investigated the effects of electroacupuncture (EA at the auricular concha region (ACR of depression rat models. Depression in rats was induced by unpredictable chronic mild stress (UCMS combined with isolation for 21 days. Eighty male Wistar rats were randomly assigned into four groups: normal, UCMS alone, UCMS with EA-ACR treatment, and UCMS with EA-ear-tip treatment. Rats under inhaled anesthesia were treated once daily for 14 days. The results showed that blood pressure and heart rate were significantly reduced in the EA-ACR group than in the UCMS alone group or the EA-ear-tip group. The open-field test scores significantly decreased in the UCMS alone and EA-ear-tip groups but not in the EA-ACR group. Both EA treatments downregulated levels of plasma cortisol and ACTH in UCMS rats back to normal levels. The present study suggested that EA-ACR can elicit similar cardioinhibitory effects as vagus nerve stimulation (VNS, and EA-ACR significantly antagonized UCMS-induced depressive status in UCMS rats. The antidepressant effect of EA-ACR is possibly mediated via the normalization of the hypothalamic-pituitary-adrenal (HPA axis hyperactivity.
Drago, F; Arezzi, A; Virzì, A
The effects of substituted benzamides, sulpiride and raclopride on experimental models of depression were studied in male rats after acute or chronic administration in comparison to those of the classical antidepressant, clomipramine. In contrast to clomipramine (50 mg/kg), acute doses of sulpiride or raclopride (1 or 5 mg/kg) failed to change the behavioral response of animals tested in the despair (constrained swim) test or in the model of reserpine-induced changes in the open field behavior. These doses also did not modify the grooming response of rats exposed to a novel environment. Sulpiride or raclopride 10 mg/kg increased the immobility time in the despair test and reduced novelty-induced grooming. The repeated injection for 21 days of sulpiride or raclopride (1 or 5 mg/kg, but not 10 mg/kg) induced a reduction of the immobility period during the constrained swim test similar to that following the chronic treatment with clomipramine 50 mg/kg. This appeared to be a clear-cut reversed dose-response relationship for both substituted benzamides, being the dose potency 1 mg/kg>5 mg/kg>10 mg/kg. Raclopride was more potent than sulpiride in this respect. Furthermore, like clomipramine, sulpiride (1 or 5 mg/kg) and raclopride (1 mg/kg) antagonized reserpine-induced changes in the open field behavior and enhanced novelty-induced grooming. These results indicate that, in contrast to acute injection, repeated administration of small doses of the substituted benzamides, sulpiride or raclopride induce an effect similar to that of the classical antidepressant, clomipramine. The reverse dose-response relationship suggests that these drugs in small doses act on presynaptic dopamine D(2) receptors. This may be consistent with a postsynaptic action of greater doses that exert sedative effects and increase immobility time in the despair test.
Chang, Ling-Yin; Wu, Shan-Ying; Chiang, Chern-En; Tsai, Pei-Shan
Despite the recognition of the negative effects of depressive symptoms on self-care confidence and self-care maintenance in patients with heart failure, little is known about the moderating role of resilience underlying these relations. To explore whether depressive symptoms affect self-care maintenance through self-care confidence and whether this mediating process was moderated by resilience. The sample comprised 201 community-dwelling and medically stable patients with echocardiographically documented heart failure. A moderated mediation model was conducted to test whether self-care confidence mediated the association between depressive symptoms and self-care maintenance, and whether resilience moderated the direct and indirect effects of depressive symptoms after adjustment for covariates. Depressive symptoms reduced self-care maintenance indirectly by decreasing self-care confidence (indirect effect: -0.22, 95% confidence interval: -0.36, -0.11), and this pathway was only significant for patients with moderate and high levels and not with low levels of resilience. Resilience also moderated the direct effects of depressive symptoms on self-care maintenance such that the negative association between depressive symptoms and self-care maintenance was reversed by the existence of high resilience. Resilience moderated the direct and indirect effects of depressive symptoms through self-care confidence on self-care maintenance in heart failure patients. Efforts to improve self-care maintenance by targeting depressive symptoms may be more effective when considering self-care confidence in patients with moderate to high levels of resilience.
Valeria Markova; Gro Mjeldheim Sandal
Objective: Refugees are at high risk of experiencing mental health problems due to trauma in their pasts and to acculturation stress as they settle in a new country. To develop efficient health services that meet the needs of refugees from different regions, an understanding is required of how they make sense of and prefer to cope with mental health problems. This study aims to investigate lay explanatory models of depression and preferred coping strategies among Somali refugees in Norway. ...
Solskov, Lasse; Løfgren, Bo; Pold, Rasmus; Kristiansen, Steen B; Nielsen, Torsten T; Overstreet, David H; Schmitz, Ole; Bøtker, Hans Erik; Lund, Sten; Wegener, Gregers
Major depression is associated with medical co-morbidity, such as ischaemic heart disease and diabetes, but the underlying pathophysiological mechanisms remain unclear. The FSL (Flinders Sensitive Line) rat is a genetic animal model of depression exhibiting features similar to those of depressed individuals. The aim of the present study was to compare the myocardial responsiveness to I/R (ischaemia/reperfusion) injury and the effects of IPC (ischaemic preconditioning) in hearts from FSL rats using SD (Sprague-Dawley) rats as controls and to characterize differences in glucose metabolism and insulin sensitivity between FSL and SD rats. Hearts were perfused in a Langendorff model and were subjected or not to IPC before 40 min of global ischaemia, followed by 120 min of reperfusion. Myocardial infarct size was found to be significantly larger in the FSL rats than in the SD rats following I/R injury (62.4+/-4.2 compared with 46.9+/-2.9%; P<0.05). IPC reduced the infarct size (P<0.01) and improved haemodynamic function (P<0.01) in both FSL and SD rats. No significant difference was found in blood glucose levels between the two groups measured after 12 h of fasting, but fasting plasma insulin (70.1+/-8.9 compared with 40.9+/-4.7 pmol/l; P<0.05) and the HOMA (homoeostatic model assessment) index (P<0.01) were significantly higher in FSL rats compared with SD rats. In conclusion, FSL rats had larger infarct sizes following I/R injury and were found to be hyperinsulinaemic compared with SD rats, but appeared to have a maintained cardioprotective mechanism against I/R injury, as IPC reduced infarct size in these rats. This animal model may be useful in future studies when examining the mechanisms that contribute to the cardiovascular complications associated with depression.
Bendayan, Rebecca; Ramírez-Maestre, Carmen; Ferrer, Emilio; López, Alicia; Esteve, Rosa
This longitudinal study investigated the pattern of change in pain intensity, disability, and depression in 232 chronic pain patients who were followed up for 2 years since pain onset. Most studies that have investigated changes in these variables over time have used participants who had already been in pain for more than 3 months. Few studies have followed up individuals from the acute phase onward and such studies used traditional statistical methods that cannot identify transition points over time or measure inter-individual variability. We followed up individuals with chronic pain from pain onset up to 18 months and we examined their pain intensity, disability and depression trajectories using a modelling approach that allows to account for between and within-individual variability. We compared three patterns of change based on theoretical criterions: a simple linear growth model; a spline model with a 3-month transition point; and a spline model with a 6-month transition point. Time with pain was selected as time metric to characterise the change in these variables in the transition from acute to chronic pain. Sex and age differences were also examined. The results showed that the pain intensity trajectory was best represented by the spline model with a 3-month transition point, whereas disability and depression were best explained by linear growth models. There were sex differences at intercept level in all the models. There were age differences at baseline for pain intensity. No sex or age differences were found for the slope. Pain intensity decreased in the first 3 months but underwent no further change. Disability and depression slightly but constantly decreased over time. Although women and older individuals are more likely to report higher pain intensity or pain-related disability in the first three months with pain, no differences by sex or age appear to be associated with the changes in pain intensity, depression and disability through the process of
Tosh, Jonathan; Kearns, Ben; Brennan, Alan; Parry, Glenys; Ricketts, Thomas; Saxon, David; Kilgarriff-Foster, Alexis; Thake, Anna; Chambers, Eleni; Hutten, Rebecca
The purpose of the analysis was to develop a health economic model to estimate the costs and health benefits of alternative National Health Service (NHS) service configurations for people with longer-term depression. Modelling methods were used to develop a conceptual and health economic model of the current configuration of services in Sheffield, England for people with longer-term depression. Data and assumptions were synthesised to estimate cost per Quality Adjusted Life Years (QALYs). Three service changes were developed and resulted in increased QALYs at increased cost. Versus current care, the incremental cost-effectiveness ratio (ICER) for a self-referral service was £11,378 per QALY. The ICER was £2,227 per QALY for the dropout reduction service and £223 per QALY for an increase in non-therapy services. These results were robust when compared to current cost-effectiveness thresholds and accounting for uncertainty. Cost-effective service improvements for longer-term depression have been identified. Also identified were limitations of the current evidence for the long term impact of services.
Lin, Chung-Ying; Pakpour, Amir H
The problems of mood disorders are critical in people with epilepsy. Therefore, there is a need to validate a useful tool for the population. The Hospital Anxiety and Depression Scale (HADS) has been used on the population, and showed that it is a satisfactory screening tool. However, more evidence on its construct validity is needed. A total of 1041 people with epilepsy were recruited in this study, and each completed the HADS. Confirmatory factor analysis (CFA) and Rasch analysis were used to understand the construct validity of the HADS. In addition, internal consistency was tested using Cronbachs' α, person separation reliability, and item separation reliability. Ordering of the response descriptors and the differential item functioning (DIF) were examined using the Rasch models. The HADS showed that 55.3% of our participants had anxiety; 56.0% had depression based on its cutoffs. CFA and Rasch analyses both showed the satisfactory construct validity of the HADS; the internal consistency was also acceptable (α=0.82 in anxiety and 0.79 in depression; person separation reliability=0.82 in anxiety and 0.73 in depression; item separation reliability=0.98 in anxiety and 0.91 in depression). The difficulties of the four-point Likert scale used in the HADS were monotonically increased, which indicates no disordering response categories. No DIF items across male and female patients and across types of epilepsy were displayed in the HADS. The HADS has promising psychometric properties on construct validity in people with epilepsy. Moreover, the additive item score is supported for calculating the cutoff. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Zhang, Guang-Fen; Wang, Jing; Han, Jin-Feng; Guo, Jie; Xie, Ze-Min; Pan, Wei; Yang, Jian-Jun; Sun, Kang-Jian
Both chronic pain and depression are debilitating diseases, which often coexist in clinic. However, current analgesics and antidepressants exhibit limited efficacy for this comorbidity. The present study aimed to investigate the effect of ketamine on the comorbidity of inflammatory pain and consequent depression-like behaviors in a rat model established by intraplantar administration of complete Freunds adjuvant (CFA). The mechanical withdrawal threshold, thermal withdrawal latency, open field test, forced swimming test, and sucrose preference test were evaluated after the CFA injection and ketamine treatment. The hippocampus was harvested to determine the levels of interleukin (IL)-6, IL-1β, indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), 5-hydroxytryptamine (5-HT), and tryptophan (TRP). The inflammatory pain-induced depression-like behaviors presented on 7days and lasted to at least 14days after the CFA injection. Single dose of ketamine at 20mg/kg relieved both the mechanical allodynia and the associated depression-like behaviors as demonstrated by the attenuated mechanical withdrawal threshold, reduced immobility time in the forced swim test, and increased sucrose preference after ketamine treatment. The total distance had no significant change after the CFA injection or ketamine treatment in the open field test. Simultaneously, ketamine reduced the levels of IL-6, IL-1β, IDO, and KYN/TRP ratio and increased the 5-HT/TRP ratio in the hippocampus. In conclusion, acute single dose of ketamine can rapidly attenuate mechanical allodynia and consequent depression-like behaviors and down-regulate hippocampal proinflammatory responses and IDO/KYN signal pathway in rats. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Braet, Caroline; Van Vlierberghe, Leen; Vandevivere, Eva; Theuwis, Lotte; Bosmans, Guy
Cognitive theory is a prominent framework to study depression in both adults and adolescents. This theory stated that dysfunctional schemas are moderators (known as diathesis) in the association of current stress and psychopathology. However, in adolescents, less evidence has been found so far to corroborate the importance of these schemas. This study aimed to investigate in a cross-sectional design the moderating role of adolescents' early maladaptive schemas (EMS) on depressive symptoms. This will be studied in relation to both important daily stressors (i.e., maternal, paternal and peer rejection) and stressful life events. Adolescents (N = 228, age 12-18 years), selected from inpatient and outpatient clinical settings and a non-referred sample, completed questionnaires and interviews measuring psychopathology, cognitive schemas, peer rejection, maternal and paternal rejection, and stressful life events. Parents completed questionnaires about their adolescent measuring psychopathology, stressful life events and peer rejection, as well as their own parental behaviour. Correlational analyses revealed significant associations between the study variables. Evidence was found for an interaction effect between the adolescents' EMS and peer rejection in explaining depressive symptoms, but only in late adolescents. Stress induced by maternal and, in lesser extent, paternal rejection is contributing to depressive symptoms primarily in younger and to lesser extent in older age groups. The quality of peer relationships becomes an increasingly salient source of distress as adolescence unfolds and is certainly an important mechanism affecting depression in adolescence. Maladaptive schemas only start functioning as a cognitive diathesis in late adolescence, increasing depression in response to peer-related distress. Since maladaptive schemas are not yet operating as cognitive vulnerability factors in early and middle adolescence, early interventions for depressive disorders
Perona, Maria T G; Waters, Shonna; Hall, Frank Scott; Sora, Ichiro; Lesch, Klaus-Peter; Murphy, Dennis L; Caron, Marc; Uhl, George R
Antidepressant drugs produce therapeutic actions and many of their side effects via blockade of the plasma membrane transporters for serotonin (SERT/SLC6A2), norepinephrine (NET/SLC6A1), and dopamine (DAT/SLC6A3). Many antidepressants block several of these transporters; some are more selective. Mouse gene knockouts of these transporters provide interesting models for possible effects of chronic antidepressant treatments. To examine the role of monoamine transporters in models of depression DAT, NET, and SERT knockout (KO) mice and wild-type littermates were studied in the forced swim test (FST), the tail suspension test, and for sucrose consumption. To dissociate general activity from potential antidepressant effects three types of behavior were assessed in the FST: immobility, climbing, and swimming. In confirmation of earlier reports, both DAT KO and NET KO mice exhibited less immobility than wild-type littermates whereas SERT KO mice did not. Effects of DAT deletion were not simply because of hyperactivity, as decreased immobility was observed in DAT+/- mice that were not hyperactive as well as in DAT-/- mice that displayed profound hyperactivity. Climbing was increased, whereas swimming was almost eliminated in DAT-/- mice, and a modest but similar effect was seen in NET KO mice, which showed a modest decrease in locomotor activity. Combined increases in climbing and decreases in immobility are characteristic of FST results in antidepressant animal models, whereas selective effects on swimming are associated with the effects of stimulant drugs. Therefore, an effect on climbing is thought to more specifically reflect antidepressant effects, as has been observed in several other proposed animal models of reduced depressive phenotypes. A similar profile was observed in the tail suspension test, where DAT, NET, and SERT knockouts were all found to reduce immobility, but much greater effects were observed in DAT KO mice. However, to further determine whether these
Reddy, Aditya J.; Handu, Shailendra S.; Dubey, Ashok Kumar; Mediratta, Pramod Kumari; Shukla, Rimi; Ahmed, Qazi Mushtaq
Background: Musa sapientum, the banana plant, has shown to possess antioxidant activity in previous studies. Oxidative stress has been linked to the pathogenesis of major depressive disorder (MDD) with evidence of increased serum levels of oxidative stress biomarkers in MDD patients. Objective: The present study aimed to evaluate the antidepressant activity of M. sapientum stem extract (MSSE) in experimental models in mice. Materials and Methods: Forced swim test (FST) and tail suspension test (TST) were carried out in five different groups (n = 6/group) of mice. The vehicle, standard drug, and the three test groups were orally administered distilled water (10 mL/kg), fluoxetine (25 mg/kg), and incremental doses of 25, 50, and 100 mg of MSSE, respectively, 45 min prior to the experiment. Results: On FST, the duration of immobility in control group, which was 161.5 ± 6.78 (in seconds, mean ± standard error of mean [SEM]), decreased to 149.33 ± 2.70 (25 mg/kg MSSE), 120.17 ± 8.35 (50 mg/kg MSSE), and 45.17 ± 4.11 (100 mg/kg MSSE) in the treated groups. On TST, the duration of immobility in control group, which was 173.83 ± 12.65 (mean ± SEM), decreased to 163.17 ± 6.91 (25 mg/kg MSSE), 139.0 ± 5.9 (50 mg/kg MSSE), and 124.0 ± 4.42 (100 mg/kg MSSE) in the treated groups. The difference in the duration of immobility was statistically significant at middle and higher doses, i.e. 50 and 100 mg/kg MSSE (P Forced swim test; TST: Tail suspension test; GSH: Glutathione, MDA: Malondialdehyde; SOD: Superoxide dismutase PMID:27695263
Burke, N. N; Geoghegan, E; Kerr, D. M; Moriarty, O; Finn, D. P; Roche, M
... ) rat model of depression. Associated changes in the expression of genes encoding for markers of glial activation and cytokines were subsequently examined in the amygdala, a key brain region for the modulation of emotion and pain...
Chow, Philip I; Fua, Karl; Huang, Yu; Bonelli, Wesley; Xiong, Haoyi; Teachman, Bethany A
Background Research in psychology demonstrates a strong link between state affect (moment-to-moment experiences of positive or negative emotionality) and trait affect (eg, relatively enduring depression and social anxiety symptoms), and a tendency to withdraw (eg, spending time at home). However, existing work is based almost exclusively on static, self-reported descriptions of emotions and behavior that limit generalizability. Despite adoption of increasingly sophisticated research designs and technology (eg, mobile sensing using a global positioning system [GPS]), little research has integrated these seemingly disparate forms of data to improve understanding of how emotional experiences in everyday life are associated with time spent at home, and whether this is influenced by depression or social anxiety symptoms. Objective We hypothesized that more time spent at home would be associated with more negative and less positive affect. Methods We recruited 72 undergraduate participants from a southeast university in the United States. We assessed depression and social anxiety symptoms using self-report instruments at baseline. An app (Sensus) installed on participants’ personal mobile phones repeatedly collected in situ self-reported state affect and GPS location data for up to 2 weeks. Time spent at home was a proxy for social isolation. Results We tested separate models examining the relations between state affect and time spent at home, with levels of depression and social anxiety as moderators. Models differed only in the temporal links examined. One model focused on associations between changes in affect and time spent at home within short, 4-hour time windows. The other 3 models focused on associations between mean-level affect within a day and time spent at home (1) the same day, (2) the following day, and (3) the previous day. Overall, we obtained many of the expected main effects (although there were some null effects), in which higher social anxiety was
Liping Zhang; Li Wu; Meng Xia; Xueli Shi; Man Zhang; Chi Tan; Rui Yang
Rats were subjected to unpredictable chronic stress and isolation-induced depression, and were then intragastrically perfused with Jieyu No.1 decoction or amitriptyline water solution for 21 consecutive days. Open-field test showed that Jieyu No.1 decoction and amitriptyline water solution significantly improved the abnormal behaviors of the depressed rats; it reduced plasma surfactant protein, corticosterone, and corticotropin releasing hormone levels, increased neuropeptide Y and somatostatin levels, and upregulated interleukin-1β, -2, -6 protein expression in the hippocampal CA3 region. Somatostatin and interleukin-1β protein expression were negatively correlated with corticosterone level, and interleukin-1β protein expression was negatively correlated with corticotropin releasing hormone level. Results demonstrated that Jieyu No.1 decoction improved abnormal behaviors of depressed animals by regulating the function of the neuroimmunoendocrine system.
Full Text Available Depression is the most common psychiatric disorder in Huntington's disease (HD patients. In the general population, women are more prone to develop depression and such susceptibility might be related to serotonergic dysregulation. There is yet to be a study of sexual dimorphism in the development and presentation of depression in HD patients. We investigated whether 8-week-old male and female R6/1 transgenic HD mice display depressive-like endophenotypes associated with serotonergic impairments. We also studied the behavioral effects of acute treatment with sertraline. We found that only female HD mice exhibited a decreased preference for saccharin as well as impaired emotionality-related behaviors when assessed on the novelty-suppressed feeding test (NSFT and the forced-swimming test (FST. The exaggerated immobility time displayed by female HD in the FST was reduced by acute administration of sertraline. We also report an increased response to the 5-HT(1A receptor agonist 8-OH-DPAT in inducing hypothermia and a decreased 5-HT(2A receptor function in HD animals. While tissue levels of serotonin were reduced in both male and female HD mice, we found that serotonin concentration and hydroxylase-2 (TPH2 mRNA levels were higher in the hippocampus of males compared to female animals. Finally, the antidepressant-like effects of sertraline in the FST were blunted in male HD animals. This study reveals sex-specific depressive-related behaviors during an early stage of HD prior to any cognitive and motor deficits. Our data suggest a crucial role for disrupted serotonin signaling in mediating the sexually dimorphic depression-like phenotype in HD mice.
Yun Li; Chun Peng; Xu Guo; Jun-Jie You; Harishankar Prasad Yadav
Background:The pathophysiology of poststroke depression (PSD) remains elusive because of its proposed multifactorial nature.Accumulating evidence suggests that brain-derived neurotrophic factor (BDNF) plays a key role in the pathophysiology of depression and PSD.And the cerebellar dysfunction may be important in the etiology of depression;it is not clear whether it also has a major effect on the risk of PSD.This study aimed to explore the expression of BDNF and high-affinity receptors tyrosine kinase B (TrkB) in the cerebellum of rats with PSD.Methods:The rat models with focal cerebral ischemic were made using a thread embolization method.PSD rat models were established with comprehensive separate breeding and unpredicted chronic mild stress (UCMS) on this basis.A normal control group,depression group,and a stroke group were used to compare with the PSD group.Thirteen rats were used in each group.Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) for detecting the expression of BDNF and TrkB protein and mRNA in the cerebellum were used at the 29th day following the UCMS.Results:Compared with the normal control group and the stroke group,the number ofBDNF immunoreactive (IR) positive neurons was less in the PSD group (P ＜ 0.05).Furthermore,the number ofTrkB IR positive cells was significantly less in the PSD group than that in the normal control group (P ＜ 0.05).The gene expression of BDNF and TrkB in the cerebellum of PSD rats also decreased compared to the normal control group (P ＜ 0.05).Conclusions:These findings suggested a possible association between expression of BDNF and TrkB in the cerebellum and the pathogenesis of PSD.
Full Text Available Background: The pathophysiology of poststroke depression (PSD remains elusive because of its proposed multifactorial nature. Accumulating evidence suggests that brain-derived neurotrophic factor (BDNF plays a key role in the pathophysiology of depression and PSD. And the cerebellar dysfunction may be important in the etiology of depression; it is not clear whether it also has a major effect on the risk of PSD. This study aimed to explore the expression of BDNF and high-affinity receptors tyrosine kinase B (TrkB in the cerebellum of rats with PSD. Methods: The rat models with focal cerebral ischemic were made using a thread embolization method. PSD rat models were established with comprehensive separate breeding and unpredicted chronic mild stress (UCMS on this basis. A normal control group, depression group, and a stroke group were used to compare with the PSD group. Thirteen rats were used in each group. Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR for detecting the expression of BDNF and TrkB protein and mRNA in the cerebellum were used at the 29 th day following the UCMS. Results: Compared with the normal control group and the stroke group, the number of BDNF immunoreactive (IR positive neurons was less in the PSD group (P < 0.05. Furthermore, the number of TrkB IR positive cells was significantly less in the PSD group than that in the normal control group (P < 0.05. The gene expression of BDNF and TrkB in the cerebellum of PSD rats also decreased compared to the normal control group (P < 0.05. Conclusions: These findings suggested a possible association between expression of BDNF and TrkB in the cerebellum and the pathogenesis of PSD.
Over recent decades, encouraging preclinical evidence using rodent models pointed to innovative pharmacological targets to treat major depressive disorder. However, subsequent clinical trials have failed to show convincing results. Two explanations for these rather disappointing results can be put forward, either animal models of psychiatric disorders have failed to predict the clinical effectiveness of treatments or clinical trials have failed to detect the effects of these new drugs. A careful analysis of the literature reveals that both statements are true. Indeed, in some cases, clinical efficacy has been predicted on the basis of inappropriate animal models, although the contrary is also true, as some clinical trials have not targeted the appropriate dose or clinical population. On the one hand, refinement of animal models requires using species that have better homological validity, designing models that rely on experimental manipulations inducing pathological features, and trying to model subtypes of depression. On the other hand, clinical research should consider carefully the results from preclinical studies, in order to study these compounds at the correct dose, in the appropriate psychiatric nosological entity or symptomatology, in relevant subpopulations of patients characterized by specific biomarkers. To achieve these goals, translational research has to strengthen the dialogue between basic and clinical science.
Full Text Available Background: Women are twice as likely as men to develop major depression (MD. The brain mechanisms underlying this sex disparity are not clear. Disruption of the glutamate-glutamine cycle has been implicated in psychiatric disturbances. This study identifies sex-based impairments in the glutamate-glutamine cycle involving astrocytes using an animal model of depression. Methods: Male and female adult Long-Evans rats were exposed to chronic social defeat stress (CSDS for 21 days, using a modified resident-intruder paradigm. Territorial aggression was used for males and maternal aggression was used for females to induce depressive-like deficits for intruders. The depressive-like phenotype was assessed with intake for saccharin solution, weight gain, estrous cycle, and corticosterone (CORT. Behaviors displayed by the intruders during daily encounters with residents were characterized. Rats with daily handling were used as controls for each sex. Ten days after the last encounter, both the intruders and controls were subjected to a no-net-flux in vivo microdialysis to assess glutamate accumulation and extracellular glutamine in the nucleus accumbens (NAc. The contralateral hemispheres were used for determining changes in astrocytic markers, including glial fibrillary acidic protein (GFAP and glutamate transporter-1 (GLT-1. Results: Both male and female intruders reduced saccharin intake over the course of CSDS, compared to their pre-stress period and to their respective controls. Male intruders exhibited submissive/defensive behaviors to territorial aggression by receiving sideways threats and bites. These males showed reductions in striatal GLT-1 and spontaneous glutamine in the NAc, compared to controls. Female intruders exhibited isolated behaviors to maternal aggression, including immobility, rearing, and self-grooming. Their non-reproductive days were extended. Also, they showed reductions in prefrontal and accumbal GFAP+ cells and prefrontal GLT
Pedersen, Kamilla Sofie; Pedersen, Louise Dybdahl; Sorensen, Anders Christian; Nielsen, Anna Busch; Kristensen, Torsten Nygaard
Mating between closely related individuals often causes reduced fitness, which is termed "inbreeding depression". Inbreeding is, therefore, a threat towards the persistence of animal and plant populations. Here we present methods and results from a practical for high-school and first-year university students and discuss learning outcomes…
Beaulac, Julie; Edwards, Jeanette; Steele, Angus
Aim To investigate the implementation and initial impact of the Physician Integrated Network (PIN) mental health indicators, which are specific to screening and managing follow-up for depression, in three primary care practices with Shared Mental Health Care in Manitoba.
Karstoft, Karen-Inge; Nielsen, Anni Brit Sternhagen; Nielsen, Tine
a measure of depression distributed to all personnel deployed with the Danish Defense since 1998. The main focus was establishing a sufficient sum score and measurement invariance relative to deployment cohort. Method: Two cohorts of the International Security Assistance Force (ISAF) deployed to Afghanistan...
Sburlati, Elizabeth S.; Lyneham, Heidi J.; Mufson, Laura H.; Schniering, Carolyn A.
In order to treat adolescent depression, a number of empirically supported treatments (ESTs) have been developed from both the cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT-A) frameworks. Research has shown that in order for these treatments to be implemented in routine clinical practice (RCP), effective therapist…
Pedersen, Kamilla Sofie; Pedersen, Louise Dybdahl; Sorensen, Anders Christian; Nielsen, Anna Busch; Kristensen, Torsten Nygaard
Mating between closely related individuals often causes reduced fitness, which is termed "inbreeding depression". Inbreeding is, therefore, a threat towards the persistence of animal and plant populations. Here we present methods and results from a practical for high-school and first-year university students and discuss learning outcomes…
Schijven, D.; Sousa, V. C.; Roelofs, J.; Olivier, B.; Olivier, J. D. A.
The Flinder Sensitive Line (FSL) is a rat strain that displays distinct behavioral and neurochemical features of major depression. Chronic selective serotonin reuptake inhibitors (SSRls) are able to reverse these symptoms in FSL rats. It is well known that several abnormalities in the serotonergic s
Pedersen, Kamilla Sofie; Pedersen, Louise Dybdahl; Sorensen, Anders Christian; Nielsen, Anna Busch; Kristensen, Torsten Nygaard
Mating between closely related individuals often causes reduced fitness, which is termed "inbreeding depression". Inbreeding is, therefore, a threat towards the persistence of animal and plant populations. Here we present methods and results from a practical for high-school and first-year university students and discuss learning outcomes of the…
Holahan, Charles J.; Moos, Rudolf H.; Holahan, Carole K.; Brennan, Penny L.; Schutte, Kathleen K.
This study examined (a) the role of avoidance coping in prospectively generating both chronic and acute life stressors and (b) the stress-generating role of avoidance coping as a prospective link to future depressive symptoms. Participants were 1,211 late-middle-aged individuals (500 women and 711 men) assessed 3 times over a 10-year period. As…
Grippo, Angela J; Johnson, Alan Kim
Bidirectional associations between mood disorders and cardiovascular diseases are extensively documented. However, the precise physiological and biochemical mechanisms that underlie such relationships are not well understood. This review focuses on the neurobiological processes and mediators that are common to both mood and cardiovascular disorders. The discussion places an emphasis on the role of exogenous stressors in addition to: (a) neuroendocrine and neurohumoral changes involving dysfunction of the hypothalamic-pituitary-adrenal axis and the activation of the renin-angiotensin-aldosterone system, (b) immune alterations including activation of pro-inflammatory cytokines, (c) autonomic and cardiovascular dysregulation including increased sympathetic drive, withdrawal of parasympathetic tone, cardiac rate and rhythm disturbances, and altered baroreceptor reflex function, (d) central neurotransmitter system dysfunction involving the dopamine, norepinephrine and serotonin systems, and (e) behavioral changes including fatigue and physical inactivity. The review also discusses experimental investigations using preclinical disease models to elucidate the neurobiological mechanisms underlying the link between mood disorders and cardiovascular disease. These include: (a) the chronic mild stress model of depression, (b) a model of congestive heart failure, (c) a model of cardiovascular deconditioning, (d) pharmacological manipulations of body fluid and sodium balance, and (e) pharmacological manipulations of the central serotonergic system. In combination with an extensive human research literature, the investigation of mechanisms underlying mood and cardiovascular regulation using animal models will enhance understanding the association between depression and cardiovascular disease. This will ultimately promote the development of better treatments and interventions for individuals with co-morbid psychological and somatic pathologies.
Melas, P A; Lennartsson, A; Vakifahmetoglu-Norberg, H; Wei, Y; Åberg, E; Werme, M; Rogdaki, M; Mannervik, M; Wegener, G; Brené, S; Mathé, A A; Lavebratt, C
Neuropeptide Y (NPY) has been implicated in depression, emotional processing and stress response. Part of this evidence originates from human single-nucleotide polymorphism (SNP) studies. In the present study, we report that a SNP in the rat Npy promoter (C/T; rs105431668) affects in vitro transcription and DNA-protein interactions. Genotyping studies showed that the C-allele of rs105431668 is present in a genetic rat model of depression (Flinders sensitive line; FSL), while the SNP's T-allele is present in its controls (Flinders resistant line; FRL). In vivo experiments revealed binding of a transcription factor (CREB2) and a histone acetyltransferase (Ep300) only at the SNP locus of the FRL. Accordingly, the FRL had increased hippocampal levels of Npy mRNA and H3K18 acetylation; a gene-activating histone modification maintained by Ep300. Next, based on previous studies showing antidepressant-like effects of physical activity in the FSL, we hypothesized that physical activity may affect Npy's epigenetic status. In line with this assumption, physical activity was associated with increased levels of Npy mRNA and H3K18 acetylation. Physical activity was also associated with reduced mRNA levels of a histone deacetylase (Hdac5). Conclusively, the rat rs105431668 appears to be a functional Npy SNP that may underlie depression-like characteristics. In addition, the achieved epigenetic reprogramming of Npy provides molecular support for the putative effectiveness of physical activity as a non-pharmacological antidepressant.
Morris, Mary L.
Depression and learning problems are strongly associated. It is important to integrate learning disabilities and depression in terms of delivery of psychological services. Dependency fostering processes can be identified as correlates of relief from depression. Depression impedes normal teacher/pupil relationships. (JN)
Armey, Michael F.; Fresco, David M.; Moore, Michael T.; Mennin, Douglas S.; Turk, Cynthia L.; Heimberg, Richard G.; Kecmanovic, Jelena; Alloy, Lauren B.
Depressive rumination, as assessed by Nolen-Hoeksema's Response Styles Questionnaire (RSQ), predicts the onset, chronicity, and duration of depressed mood. However, some RSQ items contain depressive content and result in a heterogeneous factor structure. After the a priori elimination of items potentially confounded with depressed item content,…
Tak, Y.R.; Brunwasser, S.M.; Lichtwarck-Aschoff, A.; Engels, R.C.M.E.
Over the course of adolescence, an increasing number of adolescents experience depression. In order to effectively target depression, identifying risk factors for depressive symptoms is pivotal. Since low levels of self-efficacy were associated with higher levels of depressive symptoms in previous s
Hed Myrberg, Ida; Omerov, Pernilla; Steineck, Gunnar; Nyberg, Ullakarin
Background Parents who lose a child by suicide have elevated risks of depression. No clinical prediction tools exist to identify which suicide-bereaved parents will be particularly vulnerable; we aimed to create a prediction model for long-term depression for this purpose. Method During 2009 and 2010 we collected data using a nationwide study-specific questionnaire among parents in Sweden who had lost a child aged 15-30 by suicide in years 2004-2007. Current depression was assessed with the Patient Health Questionnaire (PHQ-9) and a single question on antidepressant use. We considered 26 potential predictors assumed clinically assessable at the time of loss, including socio-economics, relationship status, history of psychological stress and morbidity, and suicide-related circumstances. We developed a novel prediction model using logistic regression with all subsets selection and stratified cross-validation. The model was assessed for classification performance and calibration, overall and stratified by time since loss. Results In total 666/915 (73%) participated. The model showed acceptable classification performance (adjusted area under the curve [AUC] = 0.720, 95% confidence interval [CI] 0.673-0.766), but performed classification best for those at shortest time since loss. Agreement between model-predicted and observed risks was fair, but with a tendency for underestimation and overestimation for individuals with shortest and longest time since loss, respectively. The identified predictors include female sex (odds ratio [OR] = 1.84); sick-leave (OR = 2.81) or unemployment (OR = 1.64); psychological premorbidity debuting during the last 10 years, before loss (OR = 3.64), or more than 10 years ago (OR = 4.96); suicide in biological relatives (OR = 1.54); with non-legal guardianship during the child’s upbringing (OR = 0.48); and non-biological parenthood (OR = 0.22) found as protective. Conclusions Our prediction model shows promising internal validity, but
Marieke Karlijn Van Vugt
Full Text Available Objectives: Converging research suggests that mindfulness training exerts its therapeutic effectson depression by reducing rumination. Theoretically, rumination is a multifaceted construct thataggregates multiple neurocognitive aspects of depression, including poor executive control,negative and overgeneral memory bias, and persistence or stickiness of negative mind states.Current measures of rumination, most often self-reports, do not capture these different aspects ofruminative tendencies, and therefore are limited in providing detailed information about themechanisms of mindfulness.Methods: We developed new insights into the potential mechanisms of rumination, based onthree model-based metrics of free recall dynamics. These three measures reflect the patterns ofmemory retrieval of valenced information: The probability of first recall (Pstart whichrepresents initial affective bias, the probability of staying with the same valence category ratherthan switching, which indicates strength of positive or negative association networks (Pstay;and probability of stopping (Pstop or ending recall within a given valence, which indicatesdrift persistence or stickiness of a mind state. We then investigated the effects of MBCT(N=29 vs wait-list control (N=23 on these recall dynamics in a Randomized Controlled Trial(RCT in individuals with recurrent depression. Participants completed a standard laboratorystressor, the Trier Social Stress Test (TSST, to induce negative mood and activate ruminativetendencies. Then, participants completed a free recall task consisting of three word lists. Thisassessment was conducted both before and after treatment or wait-list.Results: While MBCT participant’s Pstart remained relatively stable, controls showed multipleindications of depression-related deterioration towards more negative and less positive bias.Following the intervention, MBCT participants decreased in their tendency to sustain trains ofnegative words
Zhang, Wenjing; Zhao, Xinmei; Xiao, Ying; Chen, Jianmin; Han, Pengfei; Zhang, Jingyao; Fu, Haiying; James Kang, Y
Depressed capillary density is associated with myocardial ischemic infarction, in which hypoxia-inducible factor 1α (HIF-1α) is increased. The present study was undertaken to examine changes in the angiogenic factors whose expression is regulated by HIF-1 and their relation to the depressed capillary density in the Rhesus monkey model of myocardial ischemic infarction. Male Rhesus monkeys 2-3 years old were subjected to myocardial ischemia by permanent ligation of left anterior descending (LAD) artery leading to the development of myocardial infarction. Eight weeks after LAD ligation, copper concentrations, myocardial histological changes and capillary density were examined, along with Western blot and immunohistochemical analysis of angiogenic factors and detection of HIF-1 activity. Capillary density was significantly decreased but the concentrations of HIF-1α and HIF-1β were significantly increased in the infarct area. However, the levels of mRNA and protein for VEGF and VEGFR1 were significantly decreased. Other HIF-1 regulated angiogenic factors, including Tie-2, Ang-1 and FGF-1, were also significantly depressed, but vascular destabilizing factor Ang-2 was significantly increased. Copper concentrations were depressed in the infarct area. Copper-independent HIF-1 activity was increased shown by the elevated mRNA level of IGF-2, a HIF-1 target gene. Removal of copper by a copper chelator, tetraethylenepentamine, from primary cultures of neonatal rat cardiomyocytes also suppressed the expression of HIF-1 regulated VEGF and BNIP3, but not IGF-2. The data suggest that under ischemic conditions, copper loss suppressed the expression of critical angiogenic genes regulated by HIF-1, but did not affect copper-independent HIF-1 activation of gene expression. This copper-dependent dysregulation of angiogenic gene expression would contribute to the pathogenesis of myocardial ischemic infarction.
Wentao Fan; Qian Wang; Yongmei Yan
The present study established a rat model of post-stroke depression using incomplete ischemia induced by unilateral carotid artery ligation in combination with solitary raising and subcutaneous injection of a small dose of reserpine. After intragastric perfusion with 45 mg/100 g, 15 mg/100 g, and 7.5 mg/100 g of Xingnao Jieyu for 7, 14 and 21 days, neuronal morphology in the frontal lobe and hippocampus was improved, depression state and voluntary behaviors were also effectively improved in rats with post-stroke depression. Moreover, the effects of Xingnao Jieyu at a dose of 45 and 15 mg/100 g were similar to the traditional antidepressant Prozac.
Gene-environment interaction affects substance P and neurokinin A in the entorhinal cortex and periaqueductal grey in a genetic animal model of depression: implications for the pathophysiology of depression
Husum, Henriette; Wörtwein, Gitta; Andersson, Weronika
of the congenitally 'depressed' Flinders Sensitive Line (FSL) compared to the Flinders Resistant Line (FRL) control rats. It is also known that environmental stress may affect brain levels of tachykinins. In view of these results we decided to superimpose maternal deprivation, an early life environmental stressor......, onto the genetically predisposed 'depressed' FSL rats and the FRL control rats and use this paradigm as a model of gene-environment interaction. The adult animals were sacrificed, adrenal glands and brains dissected out and SP-, NKA- and CRH-LI levels were determined in ten discrete brain regions....... Maternal deprivation led to a marked increase in SP-LI and NKA-LI levels in the periaqueductal grey (PAG) and entorhinal cortex of the 'depressed' FSL strain while it had no significant effect in the FRL controls. Furthermore, specific strain differences in peptide-LI content were confirmed. No difference...
Yu, J S; Xue, A Y; Redei, E E; Bagheri, N
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
Barucci, M; Cossio, M
Several subjects who tell their depression and play a part of it in front of the doctor without being really depressed are reported. Some of them try to hide the symptoms (irritability or erethism, ceremonials of obsessive neurosis, shunning of phobia) which, in their opinion, might be detrimental to their reputation. Others neglect to describe some of the symptoms of their polymorphous clinical picture only underlining the depressive signs. Some others play a part of depression because they have believed to recognize themselves in persons presented by mass media, because it seems to them a duty to show an adequate depression in case of mournful event, or because they "convert" their problem into a depression. Some others use depression as a blackmail, or to obtain an advantage from doctor's conviction about their illness. The reason for the high frequency of similar cases in the present time are examined: the scientific divulgation and the acceptance of depression by the modern society are among the most important ones. The peculiar semantic vicissitudes of the word depression are also reviewed. A widening of the boundaries of depression has contributed to an increase in the number of the cases. Finally, in addition to patients who are depressed without being aware of it, the authors focus the inverse possibility: patients who believed or try to make their doctor believe (playing the part of depression in front of them) that they are depressed.
Xiang Yuan; Bin Zhang
Objective:To study the effect of ketamine combined with fluoxetine on behavior indexes and related gene expression in depression rat model.Methods:SD rats were used as experimental animals and randomly divided into control group (C group), model group (M group), ketamine group (K group), fluoxetine group (F group) and ketamine combined with fluoxetine group (KF group); chronic unpredictable stress depression models were built and different medications were given. Then behavior indicators were detected by tail suspension test and open field test; contents of monoamine neurotransmitters were determined by HPLC-electrochemical detection assay; mRNA contents of monoamine neurotransmitter-metabolizing enzymes, BDNF and its receptor were detected by PCR method.Results: (1)behavior indexes: compared with M group, behavior indexes of K group, F group and KF group were all improved; tail suspension immobility time and central grid staying time of KF group were shorter than those of K group and F group; squares crossed number, standing up number and decoration number were more than those of K group and F group; (2) molecular indexes: compared with M group, molecular markers of K group, F group and KF group were all improved; NE, 5-HT, TH, TPH, BDNF and TrkB contents in hippocampal and prefrontal cortex tissue of KF group were higher than those of K group and F group.Conclusion:Ketamine combined with fluoxetine therapy can more effectively reduce depression-related behavior; its mechanism may be related to the regulation of monoamine neurotransmitter metabolism and brain-derived neurotrophic factor expression in hippocampus and prefrontal cortex.
Hattiangady, Bharathi; Mishra, Vikas; Kodali, Maheedhar; Shuai, Bing; Rao, Xiolan; Shetty, Ashok K
Memory and mood deficits are the enduring brain-related symptoms in Gulf War illness (GWI). Both animal model and epidemiological investigations have indicated that these impairments in a majority of GW veterans are linked to exposures to chemicals such as pyridostigmine bromide (PB, an antinerve gas drug), permethrin (PM, an insecticide) and DEET (a mosquito repellant) encountered during the Persian Gulf War-1. Our previous study in a rat model has shown that combined exposures to low doses of GWI-related (GWIR) chemicals PB, PM, and DEET with or without 5-min of restraint stress (a mild stress paradigm) causes hippocampus-dependent spatial memory dysfunction in a water maze test (WMT) and increased depressive-like behavior in a forced swim test (FST). In this study, using a larger cohort of rats exposed to GWIR-chemicals and stress, we investigated whether the memory deficiency identified earlier in a WMT is reproducible with an alternative and stress free hippocampus-dependent memory test such as the object location test (OLT). We also ascertained the possible co-existence of hippocampus-independent memory dysfunction using a novel object recognition test (NORT), and alterations in mood function with additional tests for motivation and depression. Our results provide new evidence that exposure to low doses of GWIR-chemicals and mild stress for 4 weeks causes deficits in hippocampus-dependent object location memory and perirhinal cortex-dependent novel object recognition memory. An open field test performed prior to other behavioral analyses revealed that memory impairments were not associated with increased anxiety or deficits in general motor ability. However, behavioral tests for mood function such as a voluntary physical exercise paradigm and a novelty suppressed feeding test (NSFT) demonstrated decreased motivation levels and depression. Thus, exposure to GWIR-chemicals and stress causes both hippocampus-dependent and hippocampus-independent memory
Leventhal, Allan M.
Research into genetic, psychosocial, and cognitive explanations for depression (biopsychosocial models) provides support for the role of these variables in the etiology of depression. Regularly identified as basic to depression is loss, and the experience of loss has been found to be more influential than genetic factors in the causation of…
Chen, Fenghua; Wegener, Gregers; Madsen, Torsten Meldgaard;
investigated the changes in mitochondrial plasticity and its correlation to morphological alterations of neuroplasticity in the hippocampus, both associated with a depressive phenotype, and after treatment, with antidepressant imipramine. Design-based stereological methods were used to estimate the number...... and volume of mitochondria in CA1 of the hippocampus in two different strains of rats, the Sprague-Dawley (SD) and Flinders rats, which display a genetic susceptibility to depressive behavior, the Flinders-sensitive line (FSL) and their corresponding controls, the Flinders-resistant line (FRL). Results...... of mitochondrial plasticity in the hippocampus and antidepressant treatment may counteract with the structural impairments. Moreover, the changes in mitochondrial morphology and number are a consistent feature of neuroplasticity. Synapse, 2013. © 2012 Wiley Periodicals, Inc....
Huston, J P; van den Brink, J; Komorowski, M; Huq, Y; Topic, B
The withholding of expected rewards results in extinction of behavior and, hypothetically, to depression-like symptoms. In a test of this hypothesis, we examined the effects of extinction of food-reinforced lever-pressing on collateral behaviors that might be indices of depression. Operant extinction is known to be aversive to the organism and results in avoidance behavior. We hypothesized that avoidance of, or withdrawal from, the former source of reward may serve as a marker for "despair." Adult male Wistar rats (n=6-7 animals per group) were exposed to a Skinner box attached to a second compartment of the same size, providing opportunity for the animals to leave the operant chamber and to enter the "withdrawal" compartment. The animals spent a portion of the time during the extinction trials in this second chamber. To assess the predictive validity of this behavior as a potential marker of "despair," we tested the effects of chronic administration of two common antidepressant drugs on this measure. The tricyclic antidepressant imipramine (20 mg/kg) as well as the selective serotonin reuptake inhibitor citalopram (20 mg/kg) reduced the number of entries and time spent in the withdrawal compartment. We propose that entries into and time spent in the withdrawal compartment may operationalize "avoidance," a core symptom of major depression. Rearing as well as biting behaviors during the extinction trials were also attenuated by the antidepressant treatment. These results lend support to the hypothesis that extinction of positively reinforced operants evokes behaviors that reflect elements of "despair/depression" because these behaviors are modulated by antidepressant treatment. The avoidance of the operant chamber as a consequence of extinction, together with rearing and biting behaviors, may serve as useful measures for the testing of antidepressant treatments.
Tennant Alan; Shea Tracey L; Pallant Julie F
Abstract Background There is a growing awareness of the need for easily administered, psychometrically sound screening tools to identify individuals with elevated levels of psychological distress. Although support has been found for the psychometric properties of the Depression, Anxiety and Stress Scales (DASS) using classical test theory approaches it has not been subjected to Rasch analysis. The aim of this study was to use Rasch analysis to assess the psychometric properties of the DASS-21...
Holahan, Charles J.; Moos, Rudolf H.; Holahan, Carole K.; Brennan, Penny L.; Schutte, Kathleen K.
This study examined (a) the role of avoidance coping in prospectively generating both chronic and acute life stressors and (b) the stress-generating role of avoidance coping as a prospective link to future depressive symptoms. Participants were 1,211 late-middle-aged individuals (500 women and 711 men) assessed 3 times over a 10-year period. As predicted, baseline avoidance coping was prospectively associated with both more chronic and more acute life stressors 4 years later. Furthermore, as ...
Gawali, Nitin B; Bulani, Vipin D; Gursahani, Malvika S; Deshpande, Padmini S; Kothavade, Pankaj S; Juvekar, Archana R
Agmatine, a neurotransmitter/neuromodulator, has shown to exert numerous effects on the CNS. Chronic stress is a risk factor for development of depression, anxiety and deterioration of cognitive performance. Compelling evidences indicate an involvement of nitric oxide (NO) pathway in these disorders. Hence, investigation of the beneficial effects of agmatine on chronic unpredictable mild stress (CUMS)-induced depression, anxiety and cognitive performance with the involvement of nitrergic pathway was undertaken. Mice were subjected to a battery of stressors for 28days. Agmatine (20 and 40mg/kg, i.p.) alone and in combination with NO modulators like L-NAME (15mg/kg, i.p.) and l-arginine (400mg/kg i.p.) were administered daily. The results showed that 4-weeks CUMS produces significant depression and anxiety-like behaviour. Stressed mice have also shown a significant high serum corticosterone (CORT) and low BDNF level. Chronic treatment with agmatine produced significant antidepressant-like behaviour in forced swim test (FST) and sucrose preference test, whereas, anxiolytic-like behaviour in elevated plus maze (EPM) and open field test (OFT) with improved cognitive impairment in Morris water maze (MWM). Furthermore, agmatine administration reduced the levels of acetylcholinesterase and oxidative stress markers. In addition, agmatine treatment significantly increased the BDNF level and inhibited serum CORT level in stressed mice. Treatment with L-NAME (15mg/kg) potentiated the effect of agmatine whereas l-arginine abolished the anxiolytic, antidepressant and neuroprotective effects of agmatine. Agmatine showed marked effect on depression and anxiety-like behaviour in mice through nitrergic pathway, which may be related to modulation of oxidative-nitrergic stress, CORT and BDNF levels. Copyright © 2017 Elsevier B.V. All rights reserved.
Full Text Available OBJECTIVE: This study systematically investigated the effect of chronic mild stress and response to antidepressant treatment in the lateral habenula at the whole genome level. METHODS: Rat whole genome expression chips (Affymetrix were used to detect gene expression regulations in the lateral habenula of rats subjected to chronic mild stress (mild stressors exchanged twice a day for 8 weeks. Some rats received antidepressant treatment during fifth to eights week of CMS. The lateral habenula gene expression profile was studied through the gene ontology and signal pathway analyses using bioinformatics. Real-time quantitative polymerase chain reaction (RT-PCR was used to verify the microarray results and determine the expression of the Fcrla, Eif3k, Sec3l1, Ubr5, Abca8a, Ankrd49, Cyp2j10, Frs3, Syn2, and Znf503 genes in the lateral habenula tissue. RESULTS: In particular we found that stress and antidepressant treatment affected intracellular cascades like growth factor receptor signaling, G-protein-coupled receptor signaling, and Wnt signaling - processes involved in the neuroplastic changes observed during the progression of depression and antidepressant treatment. CONCLUSION: The present study suggests an important role of the lateral habenula in the development of depression-like conditions and correlates to previous studies demonstrating a significant role of the lateral habenula in depressive-like conditions and antidepressant treatment.
Steiger, Andrea E.; Fend, Helmut A.; Allemand, Mathias
The vulnerability model states that low self-esteem functions as a predictor for the development of depressive symptoms whereas the scar model assumes that these symptoms leave scars in individuals resulting in lower self-esteem. Both models have received empirical support, however, they have only been tested within individuals and not across…
Steiger, Andrea E.; Fend, Helmut A.; Allemand, Mathias
The vulnerability model states that low self-esteem functions as a predictor for the development of depressive symptoms whereas the scar model assumes that these symptoms leave scars in individuals resulting in lower self-esteem. Both models have received empirical support, however, they have only been tested within individuals and not across…
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Li, Ruipeng; Wang, Xiangxiang; Qin, Tingting; Qu, Rong; Ma, Shiping
Increasing evidence suggests that inflammation and oxidative stress may contribute to the development of major depressive disorder (MDD). Apigenin, a type of bioflavonoid widely found in citrus fruits, has a number of biological actions including anti-inflammatory and antioxidant effects. Although apigenin has potential antidepressant activity, the mechanisms of this effect remain unclear. The present study aims to investigate the effects of apigenin on behavioral changes and inflammatory responses induced by chronic unpredictable mild stress (CUMS) in rats. GW9662, a selective peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor, was administered 30 min before apigenin. We found that treatment with apigenin (20mg/kg, intragastrically) for three weeks remarkably ameliorated CUMS-induced behavioral abnormalities, such as decreased locomotor activity and reduced sucrose consumption. In response to oxidative stress, the NLRP3 inflammasome was activated and IL-1β secretion increased in the prefrontal cortex (PFC) of CUMS rats. However, apigenin treatment upregulated PPARγ expression and downregulated the expression of NLRP3, which subsequently downregulated the production of IL-1β. In addition, GW9662 diminished the inhibitory effects of apigenin on the NLRP3 inflammasome. In conclusion, our results demonstrate that apigenin exhibits antidepressant-like effects in CUMS rats, possibly by inhibiting IL-1β production and NLRP3 inflammasome expression via the up-regulation of PPARγ expression.
Hu, Bing; Doods, Henri; Treede, Rolf-Detlef; Ceci, Angelo
The current study assessed whether antidepressant and/or antinociceptive drugs, duloxetine, fluoxetine as well as (±)-8-hydroxy-2-[di-n-propylamino] tetralin (8-OH-DPAT), are able to reverse depression-like behaviour in animals with chronic neuropathic pain. Chronic constriction injury (CCI) of the sciatic nerve in rats was selected as neuropathic pain model. Mechanical hypersensitivity and depression-like behaviour were evaluated 4 weeks after surgery by "electronic algometer" and forced swimming test (FST), which measured the time of immobility, and active behaviours climbing and swimming. The selective noradrenergic and serotonergic uptake blocker duloxetine (20mg/kg) and the selective 5-HT1A agonist 8-OH-DPAT (0.5mg/kg) significantly reversed both mechanical hypersensitivity and depression-like behaviour in CCI animals. Duloxetine significantly reversed depression-like behaviour in CCI rats by increasing the time of climbing and swimming, while 8-OH-DPAT attenuated depression-like behaviour mainly by increasing the time of swimming. However, the selective serotonergic uptake blocker fluoxetine (20mg/kg) failed to attenuate mechanical hypersensitivity and depression-like behaviour, possibly due to confounding pro-nociceptive actions at 5-HT3 receptors. These data suggest to target noradrenergic and 5-HT1A receptors for treatment of chronic pain and its comorbidity depression.
Steiger, Andrea E; Fend, Helmut A; Allemand, Mathias
The vulnerability model states that low self-esteem functions as a predictor for the development of depressive symptoms whereas the scar model assumes that these symptoms leave scars in individuals resulting in lower self-esteem. Both models have received empirical support, however, they have only been tested within individuals and not across generations (i.e., between family members). Thus, we tested the scope of these competing models by (a) investigating whether the effects hold from adolescence to middle adulthood (long-term vulnerability and scar effects), (b) whether the effects hold across generations (intergenerational vulnerability and scar effects), and (c) whether intergenerational effects are mediated by parental self-esteem and depressive symptoms and parent-child discord. We used longitudinal data from adolescence to middle adulthood (N = 1,359) and from Generation 1 adolescents (G1) to Generation 2 adolescents (G2) (N = 572 parent-child pairs). Results from latent cross-lagged regression analyses demonstrated that both adolescent self-esteem and depressive symptoms were prospectively related to adult self-esteem and depressive symptoms 3 decades later. That is, both the vulnerability and scar models are valid over decades with stronger effects for the vulnerability model. Across generations, we found a substantial direct transmission effect from G1 to G2 adolescent depressive symptoms but no evidence for the proposed intergenerational vulnerability and scar effect or for any of the proposed mediating mechanisms.
Peng, Wei-Feng; Ding, Jing; Li, Xin; Fan, Fan; Zhang, Qian-Qian; Wang, Xin
Depression is a common comorbidity in patients with epilepsy with unclear mechanisms. This study is to explore the role of glutamate N-methyl-D-aspartate (NMDA) receptor NR1, NR2A and NR2B subunits in epilepsy-associated depression. Lithium chloride (Licl)-pilocarpine chronic rat epilepsy model was established and rats were divided into epilepsy with depression (EWD) and epilepsy without depression (EWND) subgroups based on forced swim test. Expression of NMDA receptor NR1, NR2A and NR2B subunits was measured by western blot and immunofluorescence methods. The immobility time (IMT) was significantly greater in Licl-pilocarpine model group than in Control group, which was also greater in EWD group than in EWND group. No differences of spontaneous recurrent seizure (SRS) counts over two weeks and latency were found between EWD and EWND groups. The number of NeuN positive cells was significantly less in Licl-pilocarpine model group than in Control group, but had no difference between EWD and EWND groups. The ratios of phosphorylated NR1 (p-NR1)/NR1 and p-NR2B/NR2B were significantly greater in the hippocampus in EWD group than in EWND group. Moreover, the expression of p-NR1 and p-NR2B in the CA1 subfield of hippocampus were both greater in Licl-pilocarpine model group than Control group. Selective blockage of NR2B subunit with ifenprodil could alleviate depression-like behaviours of Licl-pilocarpine rat epilepsy model. In conclusion, glutamate NMDA receptor NR2B subunit was involved in promoting depression-like behaviours in the Licl-pilocarpine chronic rat epilepsy model and might be a target for treating epilepsy-associated depression.
Wan-Fei, Khaw; Hassan, Syed Tajuddin Syed; Sann, Lye Munn; Ismail, Siti Irma Fadhilah; Raman, Rosna Abdul; Ibrahim, Faisal
Background Depression and anxiety are common in stroke survivors as well as their family caregivers. However, it is not known whether each person’s emotional distress contributes to their partner’s quality of life (QOL). Objective This study aimed to examine the effect of depression and anxiety on QOL in stroke survivor-caregiver dyads using dyadic analysis technique - the Actor-Partner Interdependence Model (APIM). Methods This was a cross-sectional pilot study with a total of 30 participating dyads (30 stroke survivors and 30 family caregivers) from Hospital Rehabilitasi Cheras, Kuala Lumpur, Malaysia. This pilot study was conducted over a period of 3 months, between December 2014 and February 2015. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale (HADS). QOL was assessed using the Short Form-12 Health Survey (SF-12). All analyses were carried out using IBM SPSS version 22. Dyadic data were analysed using multilevel modelling (MLM). Results Depression was uniquely associated with an individual’s own QOL. Survivors and caregivers with higher depression had poorer physical component summary (PCS) scores and mental component summary (MCS) scores. Stroke survivor’s depression exerted a significant actor effect on their PCS (b=−1.42, p=0.001) and MCS (b=−1.52, pCaregiver’s depression exerted a significant actor effect on their PCS (b=−2.53, pCaregivers’ anxiety negatively influenced their own MCS (b=−0.58, p=0.031). Furthermore, depression exerted a significant partner effect on PCS in stroke survivors (b=−1.19, p=0.003). Caregivers’ depression was also related to their stroke survivors’ poorer QOL, particularly PCS. Conclusion The findings suggest that depression affects the QOL of both stroke survivors and caregivers, not only emotionally but also physically. This dyadic study also has evidence pointing to depression in caregivers and its association with stroke survivors’ physical QOL. PMID:28979724
Full Text Available Memory and mood deficits are the enduring brain-related symptoms in Gulf War illness (GWI. Both animal model and epidemiological investigations have indicated that these impairments in a majority of GW veterans are linked to exposures to chemicals such as pyridostigmine bromide (PB, an anti nerve gas drug, permethrin (PM, an insecticide and DEET (a mosquito repellant encountered during the Persian Gulf War-1. Our previous study in a rat model has shown that combined exposures to low doses of GWI-related (GWIR chemicals PB, PM and DEET with or without 5-minutes of restraint stress (a mild stress paradigm causes hippocampus-dependent spatial memory dysfunction in a water maze test and increased depressive-like behavior in a forced swim test. In this study, using a larger cohort of rats exposed to GWIR-chemicals and stress, we investigated whether the memory deficiency identified earlier in a water maze test is reproducible with an alternative and stress free hippocampus-dependent memory test such as the object location test. We also ascertained the possible co-existence of hippocampus-independent memory dysfunction using a novel object recognition test, and alterations in mood function with additional tests for motivation and depression. Our results provide new evidence that exposure to low doses of GWIR-chemicals and stress for four weeks causes deficits in hippocampus-dependent object location memory and perirhinal cortex-dependent novel object recognition memory. An open field test performed prior to other behavioral analyses revealed that memory impairments were not associated with increased anxiety or deficits in general motor ability. However, behavioral tests for mood function such as a voluntary physical exercise paradigm and a novelty suppressed feeding test showed decreased motivation and depression. Thus, exposure to GWIR-chemicals and stress causes both hippocampus-dependent and hippocampus-independent memory impairments as well as
The importance of statistical modelling in clinical research : Comparing multidimensional Rasch-, structural equation and linear regression models for analyzing the depression of relatives of psychiatric patients.
Alexandrowicz, Rainer W; Jahn, Rebecca; Friedrich, Fabian; Unger, Anne
Various studies have shown that caregiving relatives of schizophrenic patients are at risk of suffering from depression. These studies differ with respect to the applied statistical methods, which could influence the findings. Therefore, the present study analyzes to which extent different methods may cause differing results. The present study contrasts by means of one data set the results of three different modelling approaches, Rasch Modelling (RM), Structural Equation Modelling (SEM), and Linear Regression Modelling (LRM). The results of the three models varied considerably, reflecting the different assumptions of the respective models. Latent trait models (i. e., RM and SEM) generally provide more convincing results by correcting for measurement error and the RM specifically proves superior for it treats ordered categorical data most adequately.
Lebedeva, Aleksandra K.; Westman, Eric; Borza, Tom; Beyer, Mona K.; Engedal, Knut; Aarsland, Dag; Selbaek, Geir; Haberg, Asta K.
Objective: Late-life depression (LLD) is associated with development of different types of dementia. Identification of LLD patients, who will develop cognitive decline, i.e., the early stage of dementia would help to implement interventions earlier. The purpose of this study was to assess whether structural brain magnetic resonance imaging (MRI) in LLD patients can predict mild cognitive impairment (MCI) or dementia 1 year prior to the diagnosis. Methods: LLD patients underwent brain MRI at baseline and repeated clinical assessment after 1-year. Structural brain measurements were obtained using Freesurfer software (v. 5.1) from the T1W brain MRI images. MRI-based Random Forest classifier was used to discriminate between LLD who developed MCI or dementia after 1-year follow-up and cognitively stable LLD. Additionally, a previously established Random Forest model trained on 185 patients with Alzheimer’s disease (AD) vs. 225 cognitively normal elderly from the Alzheimer’s disease Neuroimaging Initiative was tested on the LLD data set (ADNI model). Results: MCI and dementia diagnoses were predicted in LLD patients with 76%/68%/84% accuracy/sensitivity/specificity. Adding the baseline Mini-Mental State Examination (MMSE) scores to the models improved accuracy/sensitivity/specificity to 81%/75%/86%. The best model predicted MCI status alone using MRI and baseline MMSE scores with accuracy/sensitivity/specificity of 89%/85%/90%. The most important region for all the models was right ventral diencephalon, including hypothalamus. Its volume correlated negatively with the number of depressive episodes. ADNI model trained on AD vs. Controls using SV could predict MCI-DEM patients with 67% accuracy. Conclusion: LDD patients developing MCI and dementia can be discriminated from LLD patients remaining cognitively stable with good accuracy based on baseline structural MRI alone. Baseline MMSE score improves prediction accuracy. Ventral diencephalon, including the hypothalamus
Wright, Kevin B; Rosenberg, Jenny; Egbert, Nicole; Ploeger, Nicole A; Bernard, Daniel R; King, Shawn
This study examined the influence of the social networking site Facebook and face-to-face support networks on depression among (N = 361) college students. The authors used the Relational Health Communication Competence Model as a framework for examining the influence of communication competence on social support network satisfaction and depression. Moreover, they examined the influence of interpersonal and social integrative motives as exogenous variables. On the basis of previous work, the authors propose and test a theoretical model using structural equation modeling. The results indicated empirical support for the model, with interpersonal motives predicting increased face-to-face and computer-mediated competence, increased social support satisfaction with face-to-face and Facebook support, and lower depression scores. The implications of the findings for theory, key limitations, and directions for future research are discussed.
Dodd, Seetal; Berk, Michael; Kelin, Katarina; Mancini, Michele; Schacht, Alexander
Mental illness has been observed to follow a neuroprogressive course, commencing with prodrome, then onset, recurrence and finally chronic illness. In bipolar disorder and schizophrenia responsiveness to treatment mirrors these stages of illness progression, with greater response to treatment in the earlier stages of illness and greater treatment resistance in chronic late stage illness. Using data from 5627 participants in 15 controlled trials of duloxetine, comparator arm (paroxetine, venlafaxine, escitalopram) or placebo for the treatment of an acute depressive episode, the relationship between treatment response and number of previous depressive episodes was determined. Data was dichotomised for comparisons between participants who had >3 previous episodes (n=1697) or ≤3 previous episodes (n=3930), and additionally for no previous episodes (n=1381) or at least one previous episode (n=4246). Analyses were conducted by study arm for each clinical trial, and results were then pooled. There was no significant difference between treatment response and number of previous depressive episodes. This unexpected finding suggests that treatments to reduce symptoms of depression during acute illness do not lose efficacy for patients with a longer history of illness.
Valvassori, Samira S; Resende, Wilson R; Budni, Josiane; Dal-Pont, Gustavo C; Bavaresco, Daniela V; Réus, Gislaine Z; Carvalho, André F; Gonçalves, Cinara L; Furlanetto, Camila B; Streck, Emilio L; Quevedo, João
The aim of the present study was to evaluate the effects of sodium butyrate on depressive-like behavior and mitochondrial alteration parameters in animal models of depression induced by maternal deprivation or chronic mild stress in Wistar rats. maternal deprivation was established by separating pups from their mothers for 3 h daily from postnatal day 1 to day 10. Chronic mild stress was established by water deprivation, food deprivation, restraint stress, isolation and flashing lights. Sodium butyrate or saline was administered twice a day for 7 days before the behavioral tests. Depressive behavior was evaluated using the forced swim test. The activity of tricarboxylic acid cycle enzymes (succinate dehydrogenase and malate dehydrogenase) and of mitochondrial chain complexes (I, II, II-III and IV) was measured in the striatum of rats. From these analyses it can be observed that sodium butyrate reversed the depressive-like behavior observed in both animal models of depression. Additionally, maternal deprivation and chronic mild stress inhibited mitochondrial respiratory chain complexes and increased the activity of tricarboxylic acid cycle enzymes. Sodium butyrate treatment reversed -maternal deprivation and chronic mild stress- induced dysfunction in the striatum of rats. In conclusion, sodium butyrate showed antidepressant effects in maternal deprivation and chronic mild stress-treated rats, and this effect can be attributed to its action on the neurochemical pathways related to depression.
Cano, Miguel Ángel; de Dios, Marcel A; Castro, Yessenia; Vaughan, Ellen L; Castillo, Linda G; Lorenzo-Blanco, Elma I; Piña-Watson, Brandy; Berger Cardoso, Jodi; Ojeda, Lizette; Cruz, Rick A; Correa-Fernandez, Virmarie; Ibañez, Gladys; Auf, Rehab; Molleda, Lourdes M
Research has indicated that Hispanics have high rates of heavy drinking and depressive symptoms during late adolescence. The purpose of this study was to test a bicultural transaction model composed of two enthnocultural orientations (acculturation and enculturation); and stressful cultural transactions with both the U.S. culture (perceived ethnic discrimination) and Hispanic culture (perceived intragroup marginalization) to predict alcohol use severity and depressive symptoms among a sample of 129 (men=39, women=90) late adolescent Hispanics (ages 18-21) enrolled in college. Results from a path analysis indicated that the model accounted for 18.2% of the variance in alcohol use severity and 24.3% of the variance in depressive symptoms. None of the acculturation or enculturation domains had statistically significant direct effects with alcohol use severity or depressive symptoms. However, higher reports of ethnic discrimination were associated with higher reports of alcohol use severity and depressive symptoms. Similarly, higher reports of intragroup marginalization were associated with higher depressive symptoms. Further, both ethnic discrimination and intragroup marginalization functioned as mediators of multiple domains of acculturation and enculturation. These findings highlight the need to consider the indirect effects of enthnocultural orientations in relation to health-related outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.
Yu, Xiaocan; Wang, Chunlian; Liu, Chenglin; Zhang, Zhaochong; Xu, Haiming; Huang, Hua; Xie, Tengxiao; Li, Haonan; Liu, Jinlei
We studied the sedimentary characteristics of a Paleocene-Eocene salt lake in the Jiangling Depression through field core observation, thin section identification, scanning electron microscopy, and X-ray diffraction analysis. On the basis of sedimentary characteristics we have summarized the petrological and mineralogical characteristics of the salt lake and proposed 9 types of grade IV salt rhythms. The deposition shows a desalting to salting order of halite-argillaceous-mudstone-mud dolostonemud anhydrock-glauberite-halite. The relationship among grade IV rhythms, water salinity and climate fluctuations was analyzed. Based on the analysis of the relationship between boron content and mudstone color and by combining the mineralogy and sedimentary environment characteristics, we propose that the early and late Paleocene Shashi Formation in the Jiangling Depression was a paleolacustrine depositional environment with a high salt content, which is a representation of the shallow water salt lake depositional model. The middle Paleocene Shashi Formation and the early Eocene Xingouzui Formation were salt and brackish sedimentary environments with low salt content in a deep paleolake, which represents a deep salt lake depositional model.
Williams, Amanda L; Merten, Michael J
Family stress models illustrate how communities affect youth outcomes through effects on parents and studies consistently show the enduring effects of early community context. The present study takes a different approach identifying human agency during adolescence as a potentially significant promotive factor mediating the relationship between community, parenting, and mental health. While agency is an important part of resilience, its longitudinal effects are unknown, particularly based on gender and race/ethnicity. The purpose of this research was to model the long-term effects of community structural adversity and social resources as predictors of adolescent depressive symptom trajectories via indirect effects of parental happiness, parent-child relationships, and human agency. Latent growth analyses were conducted with 1,796 participants (53% female; 56% White) across four waves of the National Longitudinal Study of Adolescent Health spanning adolescence (Wave 1) through adulthood (Wave 4). The results identified agency as an important promotive factor during adolescence with long-term mental health benefits, but only for White and male participants. For these individuals, community social resources and the quality of the parent-child relationship were related to higher levels of agency and more positive mental health trajectories. Although community social resources similarly benefitted parenting and agency among females and non-White participants, there were no significant links between agency and depressive symptoms for these youth. The results suggest that agency remains an important, but poorly understood concept and additional work is necessary to continue unpacking its meaning for diverse groups of youth.
Benjamin W. Van Voorhees
Full Text Available Efforts to prevent depression have become a key health system priority. Currently, there is a high prevalence of depression among adolescents, and treatment has become costly due to the recurrence patterns of the illness, impairment among patients, and the complex factors needed for a treatment to be effective. Primary care may be the optimal location to identify those at risk by offering an Internet-based preventive intervention to reduce costs and improve outcomes. Few practical interventions have been developed. The models for Internet intervention development that have been put forward focus primarily on the Internet component rather than how the program fits within a broader context. This paper describes the conceptualization for developing technology based preventive models for primary care by integrating the components within a behavioral vaccine framework. CATCH-IT (Competent Adulthood Transition with Cognitive-behavioral, Humanistic and Interpersonal Training has been developed and successfully implemented within various health systems over a period of 14 years among adolescents and young adults aged 13–24.
van Vugt, Marieke K.; Hitchcock, Peter; Shahar, Ben; Britton, Willoughby
Objectives: Converging research suggests that mindfulness training exerts its therapeutic effects on depression by reducing rumination. Theoretically, rumination is a multifaceted construct that aggregates multiple neurocognitive aspects of depression, including poor executive control, negative and
van Vugt, Marieke K.; Hitchcock, Peter; Shahar, Ben; Britton, Willoughby
Objectives: Converging research suggests that mindfulness training exerts its therapeutic effects on depression by reducing rumination. Theoretically, rumination is a multifaceted construct that aggregates multiple neurocognitive aspects of depression, including poor executive control, negative and
Borre, Yuliya E; Panagaki, Theodora; Koelink, Pim J; Morgan, Mary E; Hendriksen, Hendrikus; Garssen, Johan; Kraneveld, Aletta D; Olivier, Berend; Oosting, Ronald S
Rising neurodegenerative and depressive disease prevalence combined with the lack of effective pharmaceutical treatments and dangerous side effects, has created an urgent need for the development of effective therapies. Considering that these disorders are multifactorial in origin, treatments designed to interfere at different mechanistic levels may be more effective than the traditional single-targeted pharmacological concepts. To that end, an experimental diet composed of zinc, melatonin, curcumin, piperine, eicosapentaenoic acid (EPA, 20:5, n-3), docosahexaenoic acid (DHA, 22:6, n-3), uridine, and choline was formulated. This diet was tested on the olfactory bulbectomized rat (OBX), an established animal model of depression and cognitive decline. The ingredients of the diet have been individually shown to attenuate glutamate excitoxicity, exert potent anti-oxidant/anti-inflammatory properties, and improve synaptogenesis; processes that all have been implicated in neurodegenerative diseases and in the cognitive deficits following OBX in rodents. Dietary treatment started 2 weeks before OBX surgery, continuing for 6 weeks in total. The diet attenuated OBX-induced cognitive and behavioral deficits, except long-term spatial memory. Ameliorating effects of the diet extended to the control animals. Furthermore, the experimental diet reduced hippocampal atrophy and decreased the peripheral immune activation in the OBX rats. The ameliorating effects of the diet on the OBX-induced changes were comparable to those of the NMDA receptor antagonist, memantine, a drug used for the management of Alzheimer's disease. This proof-of-concept study suggests that a diet, which simultaneously targets multiple disease etiologies, can prevent/impede the development of a neurodegenerative and depressive disorders and the concomitant cognitive deficits.
du Jardin, Kristian Gaarn; Liebenberg, Nico; Müller, Heidi Kaastrup; Elfving, Betina; Sanchez, Connie; Wegener, Gregers
The mechanisms mediating ketamine's antidepressant effect have only been partly resolved. Recent preclinical reports implicate serotonin (5-hydroxytryptamine; 5-HT) in the antidepressant-like action of ketamine. Vortioxetine is a multimodal-acting antidepressant that is hypothesized to exert its therapeutic activity through 5-HT reuptake inhibition and modulation of several 5-HT receptors. The objective of this study was to evaluate the therapeutic-like profiles of S-ketamine, vortioxetine, and the serotonin reuptake inhibitor fluoxetine in response to manipulation of 5-HT tone. Flinders Sensitive Line (FSL) rats, a genetic model of depression, were depleted of 5-HT by repeated administration of 4-chloro-DL-phenylalanine methyl ester HCl (pCPA). Using pCPA-pretreated and control FSL rats, we investigated the acute and sustained effects of S-ketamine (15 mg/kg), fluoxetine (10 mg/kg), or vortioxetine (10 mg/kg) on recognition memory and depression-like behavior in the object recognition task (ORT) and forced swim test (FST), respectively. The behavioral phenotype of FSL rats was unaffected by 5-HT depletion. Vortioxetine, but not fluoxetine or S-ketamine, acutely ameliorated the memory deficits of FSL rats in the ORT irrespective of 5-HT tone. No sustained effects were observed in the ORT. In the FST, all three drugs demonstrated acute antidepressant-like activity but only S-ketamine had sustained effects. Unlike vortioxetine, the antidepressant-like responses of fluoxetine and S-ketamine were abolished by 5-HT depletion. These observations suggest that the acute and sustained antidepressant-like effects of S-ketamine depend on endogenous stimulation of 5-HT receptors. In contrast, the acute therapeutic-like effects of vortioxetine on memory and depression-like behavior may be mediated by direct activity at 5-HT receptors.
Silva, Márcia Calheiros Chaves; de Sousa, Caren Nádia Soares; Gomes, Patrícia Xavier Lima; de Oliveira, Gersilene Valente; Araújo, Fernanda Yvelize Ramos; Ximenes, Naiara Coelho; da Silva, Jéssica Calheiros; Vasconcelos, Germana Silva; Leal, Luzia Kalyne Almeida Moreira; Macêdo, Danielle; Vasconcelos, Silvânia Maria Mendes
Oxidative stress is implicated in the neurobiology of depression. Here we investigated oxidative alterations in brain areas of animals submitted to the model of depression induced by corticosterone (CORT) and the effects of the antioxidant compound alpha-lipoic acid (ALA) alone or associated with the antidepressant desvenlafaxine (DVS) in these alterations. Female mice received vehicle or CORT (20 mg/kg) during 14 days. From the 15th to 21st days different animals received further administrations of: vehicle, DVS (10 or 20 mg/kg), ALA (100 or 200 mg/kg), or the combinations of DVS10+ALA100, DVS20+ALA100, DVS10+ALA200, or DVS20+ALA200. Twenty-four hours after the last drug administration prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) were dissected for the determination of the activity of superoxide dismutase (SOD), reduced glutathione (GSH) and lipid peroxidation (LP) levels. CORT significantly increased SOD activity in the PFC and HC, decreased GSH levels in the HC and increased LP in all brain areas studied when compared to saline-treated animals. Decrements of SOD activity were observed in all groups and brain areas studied when compared to controls and CORT. The hippocampal decrease in GSH was reversed by ALA100, DVS10+ALA100, DVS20+ALA100 and DVS20+ALA200. The same DVS+ALA combination groups presented increased levels of GSH in the PFC and ST. The greater GSH levels were observed in the PFC, HC and ST of DVS20+ALA200 mice. LP was reversed in the groups ALA200 (PFC), DVS10+ALA100, DVS20+ALA100 (PFC, HC and ST), and DVS20+ALA200 (PFC, HC). Our findings contribute to the previous preclinical evidences implicating ALA as a promising agent for augmentation therapy in depression. Copyright © 2015 Elsevier Inc. All rights reserved.
Babinska, Zuzana; Ruda-Kucerova, Jana
Ketamine has been extensively studied for its antidepressant potential, with promising results in both preclinical and clinical studies. However, concerns regarding its abuse liabilities greatly limit its potential to become an approved treatment for depression. Therefore, a better understanding the risks and benefits of ketamine use in depression is needed. This study aimed to assess the characteristics of operant intravenous (IV) ketamine self-administration and relapse-like behavior in the olfactory bulbectomy (OBX) model of depression in male rats. Twenty-five male Wistar rats were divided randomly into 2 groups; in 1 group the bilateral olfactory bulbectomy was performed, whereas the other group was sham-operated. Intravenous self-administration of ketamine (.5 mg/kg/infusion) was conducted under a fixed ratio 1 schedule of reinforcement. After reaching stable drug intakes, rats then underwent a 14-day period of forced abstinence followed by a drug-free relapse-like session. The forced swim test was conducted before the commencement of the self-administration protocol and on the 1st day of abstinence. Consistent with findings in previous studies on other substances, OBX animals showed increased operant IV ketamine self-administration. In contrast, ketamine-seeking behavior in the OBX group did not differ from sham-operated animals during the relapse-like session, whereas previous studies on other psychostimulants like methamphetamine and cocaine reported increases. Our findings suggest substantially different underlying neuroadaptations between chronic ketamine and psychostimulant exposure. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Markus A. Dahlem
Full Text Available Familial hemiplegic migraine (FHM is a rare subtype of migraine with aura. A mutation causing FHM type 3 (FHM3 has been identified in SCN1A encoding the Nav1.1 Na+ channel. This genetic defect affects the inactivation gate. While the Na+ tail currents following voltage steps are consistent with both hyperexcitability and hypoexcitability, in this computational study, we investigate functional consequences beyond these isolated events. Our extended Hodgkin–Huxley framework establishes a connection between genotype and cellular phenotype, i.e., the pathophysiological dynamics that spans over multiple time scales and is relevant to migraine with aura. In particular, we investigate the dynamical repertoire from normal spiking (milliseconds to spreading depression and anoxic depolarization (tens of seconds and show that FHM3 mutations render gray matter tissue more vulnerable to spreading depression despite opposing effects associated with action potential generation. We conclude that the classification in terms of hypoexcitability vs. hyperexcitability is too simple a scheme. Our mathematical analysis provides further basic insight into also previously discussed criticisms against this scheme based on psychophysical and clinical data.
Mori-Okamoto, Junko; Otawara-Hamamoto, Yoko; Yamato, Hideyuki; Yoshimura, Hiroyuki
Pomegranate is known to contain estrogens (estradiol, estrone, and estriol) and show estrogenic activities in mice. In this study, we investigated whether pomegranate extract is effective on experimental menopausal syndrome in ovariectomized mice. Prolongation of the immobility time in forced swimming test, an index of depression, was measured 14 days after ovariectomy. The bone mineral density (BMD) of the tibia was measured by X-ray absorptiometry and the structure and metabolism of bone were also analyzed by bone histomorphometry. Administration of pomegranate extract (juice and seed extract) for 2 weeks to ovariectomized mice prevented the loss of uterus weight and shortened the immobility time compared with 5% glucose-dosed mice (control). In addition, ovariectomy-induced decrease of BMD was normalized by administration of the pomegranate extract. The bone volume and the trabecular number were significantly increased and the trabecular separation was decreased in the pomegranate-dosed group compared with the control group. Some histological bone formation/resorption parameters were significantly increased by ovariectomy but were normalized by administration of the pomegranate extract. These changes suggest that the pomegranate extract inhibits ovariectomy-stimulated bone turnover. It is thus conceivable that pomegranate is clinically effective on a depressive state and bone loss in menopausal syndrome in women.
Huipeng Li; Fengli An; Shucheng An
BACKGROUND: The orbitofrontal cortex (OFC) is a brain region closely associated with emotion.5-hydroxytryptamine (5-HT) has been shown to be involved in human depression.OBJECTIVE: To investigate OFC actions and mechanisms of 5-HT and 5-HT1A receptor (5-HT1AR)in stress-induced depression.DESIGN, TIME AND SEI-rlNG: A randomized, controlled, animal experiment was performed at Laboratory of Neurobiology, College of Life Science, Shaanxi Normal University between May 2006 and March 2008.MATERIALS: 5-HT, p-chlorophenylalanine (PCPA, an inhibitor to tryptophan hydroxylase) andspiperone (5-HT1AR antagonist) were provided by Sigma, USA; rabbit anti-rat 5-HT1AR antibody was provided by Tlanjin Haoyang Biological Manufacture.METHODS: A total of 40 male Sprague Dawley rats, aged 3 months, were randomly divided into five groups: control, model, 5-HT, spiperone+5-HT, and PCPA, with 8 rats in each group. Except for control group, rats in the other four groups were used to establish depression models by forced swimming for 15 minutes. At 30 minutes before forced swimming test, 0.5μL of 5-HT (12.5μg/pL),PCPA (20μg/μL), spiperone (1.3 μg/μL)+5-HT (12.5μg/μL, 10 minutes later), and saline were respectively injected into the OFC of 5-HT, PCPA, spiperone+5-HT, and model groups, respectively.The control group received a saline microinjection into the OFC.MAIN OUTCOME MEASURES: Forced swimming and open field tests were employed to measure animal behaviors, and immunohistochemistry was used to analyze 5-HT1AR expression in the OFC,cingulate cortex, and piriform cortex.RESULTS: (1) Compared with the model group, 5-HT microinjection into the OFC prominently reduced immobility time in the forced swimming test and rearing in open field test (P0.05). Furthermore, following PCPA microinjection into the OFC (PCPA + forced swimming stress),immobility time in forced swimming test increased dramatically (P<0.01), locomotion and rearing inopen field test declined (P<0.05 and P<0
Hung Sa Lee, PhD, RN
Conclusions: This study found that social support and discrimination had indirect effects on depression through stress. More specifically, decreased stress led to a reduction of depression. Therefore, social support based on a thorough understanding of stress is very important for caring elderly who are depressive.
Monroe, Scott M.; Harkness, Kate L.
Theory and research on major depression have increasingly assumed a recurrent and chronic disease model. Yet not all people who become depressed suffer recurrences, suggesting that depression is also an acute, time-limited condition. However, few if any risk indicators are available to forecast which of the initially depressed will or will not…
Bühler, Joël; Keller, Ferdinand; Läge, Damian
An adequate assessment of depression has been of concern to many researchers over the last half-century. These efforts have brought forth a manifold of depression rating scales, of which the Beck Depression Inventory (BDI) is 1 of the most commonly used self-assessment scales. Since its revision, the item structure of the BDI-II has been examined in many factor analytic studies, yet it has not been possible to achieve a consensus about the underlying factor structure. Recent findings from a nonmetric multidimensional scaling (NMDS) analysis (Bühler, Keller, & Läge, 2012) of the German norming sample of the BDI-II emphasized a structure with different qualitative aspects of depression, which suggested that the existing factor models do not adequately represent the data. The NMDS results were reviewed, and on the basis of these findings, a different factor model is proposed. In contrast to the common factor models in the literature, the presented model includes an additional factor, which is associated with the activation level of the BDI-II symptoms. The model was evaluated with a 2nd sample of patients diagnosed with a primary affective disorder (N = 569) and obtained good fit indices that even exceeded the fit of the most reliable factor model (Ward, 2006) described in the literature so far. Furthermore, emphasis is placed on the methodological question of how factor models may be derived from the results of NMDS analyses. PsycINFO Database Record (c) 2014 APA, all rights reserved.
Xiong, Zhili; Yang, Jie; Huang, Yue; Zhang, Kuo; Bo, Yunhai; Lu, Xiumei; Su, Guangyue; Ma, Jie; Yang, Jingyu; Zhao, Longshan; Wu, Chunfu
Xiao-Chai-Hu-Tang (XCHT) has been proven to be effective for the clinical treatment of depression. However, the mechanisms of definite antidepressant-like effects and detailed metabolic biomarkers were still unclear in this prior study. Here, we have investigated the metabolic profiles and potential biomarkers in a chronic unpredictable mild stress model after treatment with XCHT. Metabonomics based on ultra-high performance liquid chromatography coupled with mass spectrometry was used to profile the metabolic fingerprints of serum obtained from a rat model with chronic unpredictable mild stress with and without XCHT treatment. The model rats showed a significant decrease in sucrose preference and food consumption, and these depression-like symptoms were significantly improved by XCHT. Through principal component analysis (PCA), nine potential biomarkers of tryptophan, uric acid, phenylalanine, cholic acid and lysophosphatidylcholine (C18:0 LPC, C16:0 LPC, C16:1 LPC, C18:1 LPC, C20:4 LPC) were characterized as potential biomarkers involved the pathogenesis of depression. The therapeutic effect of XCHT on depression may involve in amino acid metabolism, lipid metabolism, oxidative stress and inflammation response. The present investigation highlights that metabonomics is a valuable tool for studying the essence of depression as well as evaluating the efficacy of the corresponding drug treatment.
Zada, Wahid; Zeeshan, Sara; Bhatti, Huma Aslam; Mahmood, Wajahat; Rauf, Khalid; Abbas, Ghulam
The aim of the study was to explore the traditional use of Cinnamomum cassia against depression. The standardised methanolic extract of the bark of C. cassia was evaluated for antidepressant activity using various behavioural tests, i.e. tail suspension test (TST), forced swim test (FST) and locomotor activity test. The serotonergic and noradrenergic modulation was assessed using 5-hydroxytryptophan (5-HTP)-induced head twitches and yohimbine potentiation tests, respectively. The fluoxetine and phenelzine were used as positive controls in the study. The C. cassia extract significantly decreased the immobility time in TST (maximum effective dose tested was 50 mg/kg) while no effect was observed in FST and locomotor activity test. The extract significantly increased the 5-HTP-induced head twitches while yohimbine-induced lethality remained unaltered. The aforementioned results are similar to that caused by fluoxetine. The standardised methanolic extract of C. cassia demonstrated antidepressant activity that can be attributed to rise in serotonin levels.
Pedersen, Mikael Egebjerg; Szewczyk, Bernadeta; Stachowicz, Katarzyna
ETHNOPHARMACOLOGICAL RELEVANCE: The four South African medicinal plants Agapanthus campanulatus (AC), Boophone distica (BD), Mondia whitei (MW) and Xysmalobium undulatum (XU) are used in traditional medicine to treat depression. AIM: To evaluate the effect of ethanolic extracts of the plants...... the antidepressant activity of four South African medicinal plants in vitro and in vivo, supporting their rational use in traditional medicine....... in a functional uptake inhibition assay. Antidepressant-like effects of the extracts were investigated using the tail suspension test (TST) and the forced swim test in both rats (rFST) and mice (mFST). RESULTS: All four plants showed affinity for SERT in the binding assay. AC and BD showed functional inhibition...
Ashwini V Karve
Full Text Available Objective: To evaluate the effects of allopurinol and febuxostat on depression using Forced Swim Test (FST in mice. Materials and Methods: Allopurinol (39 mg/kg p. o and febuxostat (15.6 mg/kg p. o were administered once daily for 21 successive days to Swiss Albino mice. On the 21 st day, the effect of the drug on locomotion was tested using photo-actometer followed by the recording of immobility period in the FST and the results were compared with the standard drug fluoxetine (10 mg/kg p. o. Results: Allopurinol and febuxostat expressed significant antidepressant like effect as indicated by reduction in the immobility period of mice in the FST as compared to control group. The effects of allopurinol and febuxostat were found to be comparable to that of fluoxetine. Conclusion: The results of the present study indicate that allopurinol and febuxostat possess significant antidepressant like activity.
Kostowski, W; Danysz, W; Dyr, W; Jankowska, E; Krzaścik, P; Pałejko, W; Stefański, R; Płaźnik, A
In the present paper, the effect of simultaneous treatment of rats with low doses of MIF-1 and tricyclic antidepressants on rat behavior in the forced swim test was studied. It was found that MIF-1 stimulated in a dose-dependent manner "active" behavior of animals in this paradigm. The effect of MIF-1 appeared to be independent of changes in rats' locomotion in the open field test. The combined treatment of rats with MIF-1 (0.01 mg/kg IP) and amitriptyline (5 mg/kg IP) or desipramine (1.25 mg/kg) IP) significantly stimulated active behavior in the forced swim test above the level obtained with each of the drugs given separately. The present data suggest the potential clinical efficacy of a combined therapy of depressive patients with MIF-1 and small doses of tricyclic antidepressants.
M. J. Rossi
Full Text Available Water infiltration and overland flow are relevant in considering water partition among plant life forms, the sustainability of vegetation and the design of sustainable hydrological models and management. In arid and semi-arid regions, these processes present characteristic trends imposed by the prevailing physical conditions of the upper soil as evolved under water-limited climate. A set of plot-scale field experiments at the semi-arid Patagonian Monte (Argentina were performed in order to estimate the effect of depression storage areas and infiltration rates on depths, velocities and friction of overland flows. The micro-relief of undisturbed field plots was characterized at z-scale 1 mm through close-range stereo-photogrammetry and geo-statistical tools. The overland flow areas produced by controlled water inflows were video-recorded and the flow velocities were measured with image processing software. Antecedent and post-inflow moisture were measured, and texture, bulk density and physical properties of the upper soil were estimated based on soil core analyses. Field data were used to calibrate a physically-based, mass balanced, time explicit model of infiltration and overland flows. Modelling results reproduced the time series of observed flow areas, velocities and infiltration depths. Estimates of hydrodynamic parameters of overland flow (Reynolds-Froude numbers are informed. To our knowledge, the study here presented is novel in combining several aspects that previous studies do not address simultaneously: (1 overland flow and infiltration parameters were obtained in undisturbed field conditions; (2 field measurements of overland flow movement were coupled to a detailed analysis of soil microtopography at 1 mm depth scale; (3 the effect of depression storage areas in infiltration rates and depth-velocity friction of overland flows is addressed. Relevance of the results to other similar desert areas is justified by the accompanying
Lai, C M; Mak, K K; Watanabe, H; Jeong, J; Kim, D; Bahar, N; Ramos, M; Chen, S H; Cheng, C
This study examines the associations of Internet addiction with social anxiety, depression, and psychosocial well-being among Asian adolescents. A self-medication model conceptualizing Internet addiction as a mediating role in relating depression and social anxiety to negative psychosocial well-being was tested. A cross-sectional survey. In the Asian Adolescent Risk Behavior Survey (AARBS), 5366 adolescents aged 12-18 years from six Asian countries (China, Hong Kong, Japan, South Korea, Malaysia, and Philippines) completed a questionnaire with items of the Internet Addiction Test (IAT), Social Anxiety Scale for Adolescents (SAS-A), Center for Epidemiological Studies Depression Scale (CESD), Self-Rated Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA-SR) in the 2012-2013 school year. Structural equation modelling was used to examine the mediating role of Internet addiction in depression, social anxiety, and subjective psychosocial well-being. Significant differences on the scores of IAT, SAS-A, CESD, and HoNOSCA-SR across the six countries were found. The proposed self-medication model of Internet addiction received satisfactory goodness-of-fit with data of all countries. After the path from social anxiety to Internet addiction had been discarded in the revised model, there was a significant improvement of the goodness-of-fit in the models for Japan, South Korea, and the Philippines. Depression and social anxiety reciprocally influenced, whereas depression associated with poorer psychosocial well-being directly and indirectly through Internet addiction in all six countries. Internet addiction mediated the association between social anxiety and poor psychosocial well-being in China, Hong Kong, and Malaysia. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
Stanley, Ian H; Joiner, Thomas E; Bryan, Craig J
Research has demonstrated a robust link between traumatic brain injuries (TBIs) and suicide risk. Yet, few studies have investigated factors that account for this link. Utilizing a clinical sample of deployed military personnel, this study aimed to examine a serial meditation model of anger and depression in the association of mild TBI and suicide risk. A total of 149 military service members referred for evaluation/treatment of a suspected head injury at a military hospital participated in the present study (92.6% male; Mage = 27.9y). Self-report measures included the Suicidal Behaviors Questionnaire-Revised (SBQ-R), Automated Neuropsychological Assessment Metrics (ANAM) anger and depression subscales, and Behavioral Health Measure-20 depression subscale. A current mild TBI diagnosis was confirmed by a licensed clinical psychologist/physician. Overall, 84.6% (126/149) of participants met diagnostic criteria for a current mild TBI. Bootstrapped serial mediation analyses indicated that the association of mild TBI and suicide risk is serially mediated by anger and depression symptoms (bias-corrected 95% confidence interval [CI] for the indirect effect = 0.044, 0.576). An alternate serial mediation model in which depression symptoms precede anger was not statistically significant (bias-corrected 95% CI for the indirect effect = -0.405, 0.050). Among a clinical sample of military personnel, increased anger and depression statistically mediated the association of mild TBI and suicide risk, and anger appears to precede depression in this pathway. Findings suggest that therapeutically targeting anger may serve to thwart the trajectory to suicide risk among military personnel who experience a mild TBI. Future research should investigate this conjecture within a prospective design to establish temporality. Copyright Â© 2016 Elsevier Ltd. All rights reserved.
Hedegaard, A; Lehnhoff, J; Moldovan, M; Grøndahl, L; Petersen, N C; Meehan, C F
Postactivation depression (PActD) of Ia afferent excitatory postsynaptic potentials (EPSPs) in spinal motoneurons results in a long-lasting depression of the stretch reflex. This phenomenon (PActD) is of clinical interest as it has been shown to be reduced in a number of spastic disorders. Using in vivo intracellular recordings of Ia EPSPs in adult mice, we demonstrate that PActD in adult (100-220 days old) C57BL/6J mice is both qualitatively and quantitatively similar to that which has been observed in larger animals with respect to both the magnitude (with ∼20% depression of EPSPs at 0.5 ms after a train of stimuli) and the time course (returning to almost normal amplitudes by 5 ms after the train). This validates the use of mouse models to study PActD. Changes in such excitatory inputs to spinal motoneurons may have important implications for hyperreflexia and/or glutamate-induced excitotoxicity in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). With the use of the G127X SOD1 mutant mouse, an ALS model with a prolonged asymptomatic phase and fulminant symptom onset, we observed that PActD is significantly reduced at both presymptomatic (16% depression) and symptomatic (17.3% depression) time points compared with aged-matched controls (22.4% depression). The PActD reduction was not markedly altered by symptom onset. Comparing these PActD changes at the EPSP with the known effect of the depression on the monosynaptic reflex, we conclude that this is likely to have a much larger effect on the reflex itself (a 20-40% difference). Nevertheless, it should also be accounted that in aged (580 day old) C57BL/6J mice there was also a reduction in PActD although, aging is not usually associated with spasticity.
Lonigan, C J; Hooe, E S; David, C F; Kistner, J A
The positive affect (PA) and negative affect (NA) framework that is embodied in the tripartite model of anxiety and depression has proved useful with adult populations; however, there is as yet little investigation with children concerning either the measurement of PA and NA or the relation between PA and NA and levels of adjustment. A confirmatory factor analysis was used in this study to examine the structure of self-reported affect and its relation to depressive and anxious symptoms in school children (4th to 11th grade). Results supported a 2-factor orthogonal model that was invariant across age and sex. Support for the expected pattern of relations between NA and PA with symptoms of depression and anxiety was strong for the older sample (M = 14.2 years) but weaker for the younger sample (M = 10.3 years). Results also provide preliminary support for the reliability and validity of the Positive and Negative Affect Schedule for children.
M. T. Tadaiesky
Full Text Available A previous study from our laboratory revealed that moderate nigral dopaminergic degeneration caused emotional and cognitive deficits in rats, paralleling early signs of Parkinson's disease. Recent evidence suggests that the blockade of cannabinoid CB1 receptors might be beneficial to alleviate motor inhibition typical of Parkinson's disease. Here, we investigated whether antagonism of CB1 receptors would improve emotional and cognitive deficits in a rat model of premotor Parkinson's disease. Depression-like behavior and cognition were assessed with the forced swim test and the social recognition test, respectively. Confirming our previous study, rats injected with 6-hydroxydopamine in striatum presented emotional and cognitive alterations which were improved by acute injection of SR141716A. HPLC analysis of monoamine levels demonstrated alterations in the striatum and prefrontal cortex after SR141716A injection. These findings suggest a role for CB1 receptors in the early symptoms caused by degeneration of dopaminergic neurons in the striatum, as observed in Parkinson's disease.
Liping Zhang; Meng Xia; Li Wu; Boli Zhang
BACKGROUND: Jiawei Wendan decoction can elevate hippocampal brain-derived neurotrophic factor (BDNF) protein expression in rats with depression. It has been hypothesized that Jiawei Wendan decoction can exhibit antidepressant effects through the hippocampal signal transduction pathway of cyclic adenosine monophosphate response element binding protein (CREB)-BDNF. OBJECTIVE: Using phosphorylated-CREB (p-CREB) as an entry point, the present study was designed to observe intervention eftects ofJiawei Wendan decoction compared with fluoxetine. DESIGN, TIME AND SETTING: A randomized, controlled, cellular biology experiment was performed at the Central Laboratory of Guangxi University of Traditional Chinese Medicine. MATERIALS: A total of 40 healthy, male, Sprague-Dawley rats were included in the present study. Rhizoma Acori Talarinowii (Shichangpu), Flos Albiziae (Hehuanhua), Rhizoma Pinelliae (Banxia), Caulis Bambusae in Taeniam (Zhuru), Fructus Aurantii Immaturus (Zhishi), Poria (Fuling), and Radix Bupleuri (Chaihu), the primary ingredients ofJiawei Wendan decoction, were purchased from First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine. The raw drug was decocted at a concentration of 1.5 g/mL. Fluoxetine capsules were purchased from Shanghai Zhongxi Pharmaceutical Co., Ltd., China. METHODS: Following behavioral testing, 36 rats were selected from the initial 40 rats according to similar behavioral scores, and were randomly divided into 4 groups: model (n = 8), Jiawei Wendan decoction-treated (n = 10), fluoxetine-treated (n = 10), and normal control (n = 8). All rats, except for those in the normal control group, were separately raised in a chronic and unpredictable, mild-stimulation environment for 21 days to establish a depression model. The Jiawei Wendan decoction-treated and fluoxetine-treated groups were intragastrically administered Jiawei Wendan decoction ( 12 g/kg/d) and fluoxetine ( 1.8 mg/kg/d), respectively. The model and normal
Gurguis, G N; Kramer, G; Petty, F
Both stress response and antidepressant drug action may be mediated by beta-adrenergic receptors (beta AR). Since learned helplessness is a stress-induced animal model of depression, beta AR are relevant to investigate in this model. To date, studies have measured changes in total receptor density (RT), but have not examined more detailed aspects of signal transduction mechanisms such as coupling of the receptor to GS protein. We have investigated brain beta AR coupling in the frontal cortex, hippocampus and hypothalamus of rats exposed to inescapable shock and then tested for learned helplessness, and in both tested and naive controls using [125I]-iodocyanopindolol (ICYP) as the ligand. Both antagonist-saturation and agonist-displacement experiments were conducted, and the specificity for the beta AR was optimized by excluding ICYP binding to 5HT1B receptors. The percentage receptor density in the high-conformational state (%RH) and the ratio of agonist (isoproterenol) dissociation constant from the receptor in the low-/high-conformational states (KL/KH) were used as indices of coupling to GS protein. No significant differences were found between rats developing learned helplessness and non-helpless rats after inescapable stress in any parameter measured in any brain region. In the frontal cortex, exposure to inescapable shock induced beta AR uncoupling from GS protein as suggested by a low KL/KH ratio both in helpless and non-helpless rats but not in either control group. In the hypothalamus, there were trends for higher RL, RT and KL/KH ratio in helpless rats and stressed controls compared to naive controls. These findings suggest that beta AR binding parameters in frontal cortex, hippocampus or hypothalamus did not differentiate between helpless and non-helpless rats. Changes in beta AR coupling observed in these brain regions may reflect effects of stress, which appeared to be region-specific, rather than stress-induced behavioral depression.
Weeks, Justin W
Wang, Hsu, Chiu, and Liang (2012, Journal of Anxiety Disorders, 26, 215-224) recently proposed a hierarchical model of social interaction anxiety and depression to account for both the commonalities and distinctions between these conditions. In the present paper, this model was extended to more broadly encompass the symptoms of social anxiety disorder, and replicated in a large unselected, undergraduate sample (n = 585). Structural equation modeling (SEM) and hierarchical regression analyses were employed. Negative affect and positive affect were conceptualized as general factors shared by social anxiety and depression; fear of negative evaluation (FNE) and disqualification of positive social outcomes were operationalized as specific factors, and fear of positive evaluation (FPE) was operationalized as a factor unique to social anxiety. This extended hierarchical model explicates structural relationships among these factors, in which the higher-level, general factors (i.e., high negative affect and low positive affect) represent vulnerability markers of both social anxiety and depression, and the lower-level factors (i.e., FNE, disqualification of positive social outcomes, and FPE) are the dimensions of specific cognitive features. Results from SEM and hierarchical regression analyses converged in support of the extended model. FPE is further supported as a key symptom that differentiates social anxiety from depression.
Solem, Stian; Hagen, Roger; Wang, Catharina E A; Hjemdal, Odin; Waterloo, Knut; Eisemann, Martin; Halvorsen, Marianne
The primary aim of the study was to test (1) how metacognition relates to the concept of mindful attention awareness, and (2) whether metacognitions or mindful attention awareness best predicted symptoms of depression. Data was collected from three samples: currently depressed (n = 37), previously depressed (n = 81) and never depressed controls (n = 50). There was a moderate correlation between mindful attention awareness and three of five metacognitive subscales. Both mindful attention awareness and metacognition were significantly correlated with depression severity scores after controlling for anxiety. The depressed group had significantly more dysfunctional metacognitions and less mindful attention awareness than the never depressed group. Negative beliefs about worry and mindful attention awareness were also significantly different in the previously depressed group compared with the never depressed. This suggests that metacognitions and mindful attention awareness can be vulnerability factors for depression. The results also indicated that anxiety symptoms and negative beliefs about worry were the most important factors in predicting depression. In conclusion, the study shows that metacognitions and mindful attention awareness are two related but separate constructs and that metacognitions emerged as the best predictor of depression. These results provide support for the metacognitive model of emotional disorders. Copyright © 2015 John Wiley & Sons, Ltd. Metacognitions and mindful attention awareness are related but separate constructs Both mindful attention awareness and metacognition are associated with depression Anxiety and negative beliefs about worry (metacognitions) are most important in predicting depression Addressing metacognitions in therapy should be considered in treatment of depression. Copyright © 2015 John Wiley & Sons, Ltd.
Rivera, Gustavo; Diamessis, Peter
The shoaling of an internal solitary wave (ISW) of depression over gentle slopes is explored through fully nonlinear and non-hydrostatic simulations based on a high-accuracy deformed spectral multidomain penalty method. As recently observed in the South China Sea, in high-amplitude shoaling ISWs, the along-wave current can exceed the wave celerity resulting in convective instabilities. If the slope is less than 3%, the wave does not disintegrate as in the case of steeper slope shoaling but, instead, maintains its symmetric shape; the above convective instability may drive the formation of a turbulent recirculating core. The sensitivity of convective instabilities in an ISW is examined as a function of the bathymetric slope and wave steepness. ISWs are simulated propagating over both idealized and realistic bathymetry. Emphasis is placed on the structure of the above instabilities, the persistence of trapped cores and their potential for particle entrainment and transport. Additionally, the role of the baroclinic background current on the development of convective instabilities is explored. A preliminary understanding is obtained of the transition to turbulence within a high-amplitude ISW shoaling over progressively varying bathymetry.
据世界卫生组织预测,抑郁症将成为“2020年全球疾病负担”排名第二的重大疾病,防治抑郁症的创新药物研发已成为医药科学发展的重要内容.本文在总结近年来关于抑郁症临床治疗和抑郁症动物模型进展的基础上,围绕“如何提高抑郁症动物模型临床预测效度”这一亟待解决的问题,采用“转化医学”的研究模式,提出关于抑郁症动物模型转换研究的一些策略,以期能为建立临床预测效度高的抑郁症动物模型和创新抗抑郁药物研发的革命性突破奠定基础和提供思路.%According to the World Health Organization, major depression disorder is projected to reach second place as leading contributor to the global burden of disease by the year 2020. Despite the emergency need for better therapies of depression, and major advances in the understanding of the molecular basis of this disorder in recent years, efforts to discover and develop new drugs for major depression disorder , especially those which might revolutionize disease treatment, have been relatively unsuccessful. An important reason for this is that it is exceedingly difficult to build an animal model that perfectly recapitulates the symptoms of depression in human patients. In order to enhance clinical validity of animal models of depression,we reviewed the recent animal models of depression and discussed its transnational research here.
Orth, Ulrich; Robins, Richard W; Meier, Laurenz L; Conger, Rand D
A growing body of research supports the vulnerability model of low self-esteem and depression, which states that low self-esteem is a risk factor for depression. The goal of the present research was to refine the vulnerability model, by testing whether the self-esteem effect is truly due to a lack of genuine self-esteem or due to a lack of narcissistic self-enhancement. For the analyses, we used data from 6 longitudinal studies consisting of 2,717 individuals. In each study, we tested the prospective effects of self-esteem and narcissism on depression both separately for each construct and mutually controlling the constructs for each other (i.e., a strategy that informs about effects of genuine self-esteem and pure narcissism), and then meta-analytically aggregated the findings. The results indicated that the effect of low self-esteem holds when narcissism is controlled for (uncontrolled effect = -.26, controlled effect = -.27). In contrast, the effect of narcissism was close to zero when self-esteem was controlled for (uncontrolled effect = -.06, controlled effect = .01). Moreover, the analyses suggested that the self-esteem effect is linear across the continuum from low to high self-esteem (i.e., the effect was not weaker at very high levels of self-esteem). Finally, self-esteem and narcissism did not interact in their effect on depression; that is, individuals with high self-esteem have a lower risk for developing depression, regardless of whether or not they are narcissistic. The findings have significant theoretical implications because they strengthen the vulnerability model of low self-esteem and depression.
Wang, Chao; Li, Shuang; Li, Tao; Yu, Shanfa; Dai, Junming; Liu, Xiaoman; Zhu, Xiaojun; Ji, Yuqing; Wang, Jin
Background: This study aimed to identify the association between occupational stress and depression-well-being by proposing a comprehensive and flexible job burden-capital model with its corresponding hypotheses. Methods: For this research, 1618 valid samples were gathered from the electronic manufacturing service industry in Hunan Province, China; self-rated questionnaires were administered to participants for data collection after obtaining their written consent. The proposed model was fitted and tested through structural equation model analysis. Results: Single-factor correlation analysis results indicated that coefficients between all items and dimensions had statistical significance. The final model demonstrated satisfactory global goodness of fit (CMIN/DF = 5.37, AGFI = 0.915, NNFI = 0.945, IFI = 0.952, RMSEA = 0.052). Both the measurement and structural models showed acceptable path loadings. Job burden and capital were directly associated with depression and well-being or indirectly related to them through personality. Multi-group structural equation model analyses indicated general applicability of the proposed model to basic features of such a population. Gender, marriage and education led to differences in the relation between occupational stress and health outcomes. Conclusions: The job burden-capital model of occupational stress-depression and well-being was found to be more systematic and comprehensive than previous models. PMID:27529267
Full Text Available Background: This study aimed to identify the association between occupational stress and depression-well-being by proposing a comprehensive and flexible job burden-capital model with its corresponding hypotheses. Methods: For this research, 1618 valid samples were gathered from the electronic manufacturing service industry in Hunan Province, China; self-rated questionnaires were administered to participants for data collection after obtaining their written consent. The proposed model was fitted and tested through structural equation model analysis. Results: Single-factor correlation analysis results indicated that coefficients between all items and dimensions had statistical significance. The final model demonstrated satisfactory global goodness of fit (CMIN/DF = 5.37, AGFI = 0.915, NNFI = 0.945, IFI = 0.952, RMSEA = 0.052. Both the measurement and structural models showed acceptable path loadings. Job burden and capital were directly associated with depression and well-being or indirectly related to them through personality. Multi-group structural equation model analyses indicated general applicability of the proposed model to basic features of such a population. Gender, marriage and education led to differences in the relation between occupational stress and health outcomes. Conclusions: The job burden-capital model of occupational stress-depression and well-being was found to be more systematic and comprehensive than previous models.
King, Daniel W.; King, Lynda A.; McArdle, John J.; Shalev, Arieh Y.; Doron-LaMarca, Susan
Depression and posttraumatic stress disorder (PTSD) are highly comorbid conditions that may arise following exposure to psychological trauma. This study examined their temporal sequencing and mutual influence using bivariate latent difference score structural equation modeling. Longitudinal data from 182 emergency room patients revealed level of…
目的：研究沙苑子水煎液对小鼠抑郁模型的影响。方法：采用小鼠悬尾法、小鼠强迫游泳、小鼠自主活动的抑郁模型对沙苑子水煎液对小鼠抑郁症的改善作用。结果：实验结果表示沙苑子水煎液对小鼠悬尾、小鼠强迫游泳、小鼠自主活动造成的抑郁症状都有很好的改善作用。结论：沙苑子水煎液能明显的改善小鼠抑郁动物模型的症状。%Objective:To study the effect of Yang nourishing medicine complanatus on depression model mice. Methods: To study the effects by the tail suspension test, mouse forced swim, complanatus decoction of mouse models of depression improved locomotor activity in mice the role of depression. Results: The experimental results indicated complanatus decoction had good effect ondepression model mice by mouse tail suspension, forced swimming mice. Conclusion: Complanatus decoction can significantly improve symptoms of depression animal model in mice.
Sun, Fei; Hodge, David R
This study used stress coping theory to examine the effects of spirituality and religion on depression among a sample of Latino family members caring for a person with Alzheimer's disease (AD) in the United States. Participants consisted of 209 Latino caregivers (CGs) drawn from baseline data from the Resource for Enhancing Alzheimer's Caregivers Health (REACH) II clinical trial. The findings indicate that church attendance moderates the relationship between subjective forms of stress and depression in tandem with exhibiting direct effects on depression. Consistent with the central role religion plays in Latino culture, the results imply that religious involvement may play an important role in mitigating depression through indirect and direct pathways.
Morokoff, Patricia J.; Redding, Colleen A.; Harlow, Lisa L.; Cho, Sookhyun; Rossi, Joseph S.; Meier, Kathryn S.; Mayer, Kenneth H.; Koblin, Beryl; Brown-Peterside, Pamela
This study examined whether the Multifaceted Model of HIV Risk (MMOHR) would predict unprotected sex based on predictors including gender, childhood sexual abuse (CSA), sexual victimization (SV), depression, and sexual assertiveness for condom use. A community-based sample of 473 heterosexually active men and women, aged 18–46 years completed survey measures of model variables. Gender predicted several variables significantly. A separate model for women demonstrated excellent fit, while the model for men demonstrated reasonable fit. Multiple sample model testing supported the use of MMOHR in both men and women, while simultaneously highlighting areas of gender difference. Prevention interventions should focus on sexual assertiveness, especially for CSA and SV survivors, as well as targeting depression, especially among men. PMID:25018617
Jinnin, Ran; Okamoto, Yasumasa; Takagaki, Koki; Nishiyama, Yoshiko; Yamamura, Takanao; Okamoto, Yuri; Miyake, Yoshie; Takebayashi, Yoshitake; Tanaka, Keisuke; Sugiura, Yoshinori; Shimoda, Haruki; Kawakami, Norito; Furukawa, Toshi A; Yamawaki, Shigeto
Purpose Despite its clinical importance, adolescent subthreshold depression remains a largely neglected topic. The aims of this study were to accurately identify the natural course of depressive symptoms and the risk for developing major depressive episode (MDE) in late adolescents with subthreshold depression over 1 year. Patients and methods One hundred and seventy-two participants <20 years of age (mean age: 18.32 years, standard deviation: 0.50), who did not meet the full criteria for an MDE, were selected from 2,494 screened freshmen based on the Beck Depression Inventory, 2nd edition (BDI-II). We conducted a cohort study of three groups (low-, middle-, and high-symptom groups) divided based on BDI-II scores, over a 1 year period with the use of bimonthly assessments. Temporal changes of depressive symptoms were analyzed using linear mixed modeling and growth mixture modeling. Results First, we found that late adolescents with subthreshold depression (high depressive symptoms) were split between the increasing and decreasing depressive symptoms groups, whereas the majority of the less-symptoms group remained stable during 1 year. Second, in comparison with late adolescents with less depressive symptoms, those with subthreshold depression had an elevated risk of later depression. Conclusion Some late adolescents with subthreshold depression had increased depressive symptoms and developed an MDE during 1 year. Therefore, it is necessary for us to rigorously assess the changes in subthreshold depressive symptoms over time in late adolescents. PMID:28053534
Hesselberg, Marie Louise; Wegener, Gregers; Buchholtz, Poul Erik
Repetitive Magnetic Stimulation (rTMS) has appeared to be a potential non-invasive antidepressant method, which implies non-convulsive focal stimulation of the brain through a time varying magnetic field. The antidepressant potential of rTMS has been supported by animal studies showing a number of interesting similarities between magnetic stimulation and electroconvulsive stimulation (ECS). Despite these positive results, this method still contains many unknown issues. Importantly, there are fundamental uncertainties concerning the optimal combination of stimulus parameters (frequency, intensity, duration, and number of pulses) to obtain an antidepressant effect. Therefore, the present study aimed to qualify the choice of rTMS stimulus frequency in a well-validated genetic animal model of depression, the FSL/FRL rats. We compared the antidepressant effect of low frequency, high frequency rTMS and ECS to sham treatment in FRL and FSL rats using 6 parallel groups. We used the Forced Swim Test and the Open Field Test to screen the depression-like state in rats. We found that both the high frequency and the low frequency rTMS resulted in a significant antidepressant effect. However, this effect was inferior to the effect of ECS. The low frequency and high frequency groups, which received the same total impulse load and stimulus intensity, did not differ with respect to antidepressant efficacy in this study. In conclusion, this study provides robust evidence that both rTMS interventions are efficacious, although not as efficient as ECS. Copyright © 2016 Elsevier B.V. All rights reserved.
Montalvo-Ortiz, Janitza L; Bordner, Kelly A.; Carlyle, Becky C.; Gelernter, Joel; Simen, Arthur A.; Kaufman, Joan
Early life neglect increases risk for the development of psychopathologies during childhood and adulthood, including depression and anxiety disorders. We recently reported epigenetic changes in DNA derived from saliva in three genes predicted depression in a cohort of maltreated children: DNA-binding protein inhibitor ID-3 (ID3), Glutamate NMDA Receptor (GRIN1), and Tubulin Polymerization Promoting Protein (TPPP). To validate the role of these genes in depression risk, secondary analyses were conducted of gene expression data obtained from medial prefrontal cortex (mPFC) tissue of mice subjected to a model of maternal neglect which included maternal separation and early weaning (MSEW). Anxiety and depression-like phenotype data derived using the elevated plus maze (EPM) and forced swimming test (FST), respectively, were also available for secondary analyses. Behavioral tests were conducted in MSEW and control adult male mice when they were between 65 and 80 days old. ID3, GRIN1 and TPPP gene expression in the mPFC were found to significantly predict behavioral differences in the EPM and FST. These results further support the role of these genes in the etiology of depressive and anxiety phenotypes following early life stress. PMID:27506655
Santiago, R M; Tonin, F S; Barbiero, J; Zaminelli, T; Boschen, S L; Andreatini, R; Da Cunha, C; Lima, M M S; Vital, M A B F
Depression is one of the most common psychiatric symptoms in patients with Parkinson's disease (PD). Some authors have reported that depression is characterized by activation of the inflammatory response. Animal models of PD also present with depressive-like behavior, such as increased immobility time in the modified forced swim test and anhedonia-like behavior in the sucrose preference test. Considering the potential neuroprotective effect of nonsteroidal antiinflammatory drugs in neurodegenerative diseases, the objective of the present study was to investigate the effects of piroxicam on depressive-like behavior in male Wistar rats lesioned with 6-hydroxydopamine (6-OHDA) in the substantia nigra (SN). Antidepressant-like effects were observed after prolonged administration of piroxicam for 21days. In the forced swim test, the 6-OHDA+saline group exhibited significant reductions in swimming time and increased immobility time compared with the sham+saline. In the sucrose preference test, the 6-OHDA+piroxicam group exhibited no reduction of sucrose preference compared with the sham+saline, with significant effects of treatment and time and a significant treatment×time interaction. 5-Hydroxytryptamine (5-HT) levels significantly decreased in the hippocampus in the 6-OHDA+saline group and not changed in the 6-OHDA+piroxicam group when compared with the sham+saline on day 21. In conclusion, 21-day treatment with piroxicam reversed the onset of depressive-like behavior and prevented the reduction of hippocampal 5-HT levels.
Wang, Junhui; Qiao, Jinping; Zhang, Yanbo; Wang, Hongxing; Zhu, Shenghua; Zhang, Handi; Hartle, Kelly; Guo, Huining; Guo, Wei; He, Jue; Kong, Jiming; Huang, Qingjun; Li, Xin-Min
Serotonin/norepinephrine reuptake inhibitors antidepressants exert their effects by increasing serotonin and norepinephrine in the synaptic cleft. Studies show it takes 2-3 weeks for the mood-enhancing effects, which indicate other mechanisms may underlie their treatment effects. Here, we investigated the role of white matter in treatment and pathogenesis of depression using an unpredictable chronic mild stress (UCMS) mouse model. Desvenlafaxine (DVS) was orally administrated to UCMS mice at the dose of 10 mg/kg/day 1 week before they went through a 7-week stress procedure and lasted for over 8 weeks before the mice were killed. No significant changes were found for protein markers of neurons and astrocytes in UCMS mice. However, myelin and oligodendrocyte-related proteins were significantly reduced in UCMS mice. DVS prevented the stress-induced injury to white matter and the decrease of phosphorylated 5'-AMP-activated protein kinase and 3-hydroxy-3-methyl-glutaryl-CoA reductase protein expression. DVS increased open arm entries in an elevated plus-maze test, sucrose consumption in the sucrose preference test and decreased immobility in tail suspension and forced swimming tests. These findings suggest that stress induces depression-like behaviors and white matter deficits in UCMS mice. DVS may ameliorate the oligodendrocyte dysfunction by affecting cholesterol synthesis, alleviating the depression-like phenotypes in these mice. We examined the possible role of oligodendrocyte and myelin in the pathological changes of depression with an unpredictable chronic mild stress (UCMS) mouse model. Oligodendrocyte-related proteins in the mouse brain were specifically changed during the stress period. The depressive-like behaviors and oligodendrocyte deficits could be prevented by the administration of desvenlafaxine. Oligodendrocyte and myelin may be an essential target of desvenlafaxine for the treatment of depression. © 2014 International Society for Neurochemistry.
Caspani, Ombretta; Reitz, Marie-Céline; Ceci, Angelo; Kremer, Andreas; Treede, Rolf-Detlef
Depression and anxiety are common comorbidities of neuropathic pain (NP). Pharmacological preclinical studies on NP have given abundant information on the effects of drugs on reflex measures of stimulus-evoked pain. However, few preclinical studies focus on relief of comorbidities evoked by NP. In this study, we investigated the effects of tramadol on nociceptive reflex, depression-associated and anxiety-related behaviors in a NP model in rats. We used chronic constriction injury (CCI) of the sciatic nerve as an animal model of neuropathic pain. We performed electronic von Frey tests (evF) to measure mechanical sensitivity, elevated plus maze tests (EPM) to record anxiety-related behaviors and forced swimming tests (FST) to evaluate depression-associated behaviors. In the evF, CCI rats showed a decrease of 82% of the paw withdrawal threshold (PWT) compared to sham (PTramadol increased the PWT by 336% in CCI rats (PTramadol increased the time spent on the open arms of CCI rats by 67% (PTramadol reduced the immobility time in CCI rats by 22% (PTramadol reversed the changes in mechanical sensitivity as well as anxiety-related and depression-associated behaviors that are caused by injury of the sciatic nerve with only minor effects in the absence of injury. These data suggest that tramadol relieves chronic pain and its indirect consequences and comorbidities, and that this study also is a model for pharmacological studies seeking to investigate the effect of drugs on the major disabling symptoms of NP.
Jung, Seung Eun; Bishop, Alex J; Kim, Minjung; Hermann, Janice; Kim, Giyeon; Lawrence, Jeannine
This study examined the relationships of self-care capacity and depressive affect on nutritional status and whether depressive affect mediated the relationship of self-care capacity on nutritional status. A convenience sample of 171 rural community-dwelling older adults, 65 years and above, participated. Structural equation modeling (SEM) was conducted to test a mediation model. The hypothesized SEM model was supported with adequate fit (χ(2) (1) = 1.87, p = 0.17; CFI = 0.94; RMSEA = 0.07; SRMR = 0.03). SEM analysis revealed a significant positive direct effect of self-care capacity on nutritional status (γ = 0.14, p = 0.042). Significant negative direct effects were observed for self-care capacity on depressive affect (γ = -0.15, p = 0.027) and for depressive affect on nutritional status (β = -0.27, p nutrition status (γ = 0.04, p = 0.046). Findings highlight the importance of emotional well-being on rural older adults' nutritional status, particularly those with decreased ability to engage in self-care practices.
Ashby, Jeffrey S.; Noble, Christina L.; Gnilka, Philip B.
This study examined the relationship between adaptive and maladaptive perfectionism, stress, depression, and satisfaction with life in a sample of undergraduate women. The authors found that maladaptive perfectionists had lower satisfaction with life and higher stress and depression scores compared with adaptive perfectionists. Results also…
Olivier, J D A; Van Der Hart, M G C; Van Swelm, R P L; Dederen, P J; Homberg, J R; Cremers, T; Deen, P M T; Cuppen, E; Cools, A R; Ellenbroek, B A
Human studies have shown that a reduction of 5-HT transporter (SERT) increases the vulnerability for anxiety and depression. Moreover, women are more vulnerable to develop depression and anxiety disorders than men. For that reason we hypothesized that homozygous 5-HT transporter knockout rat (SERT-/
Manohar M. Bende
Conclusions: The results of present study suggest that the areca catechu nut ethanolic extract 50mg/kg possess potential anti-depression like effect without generalized CNS depression. Further studies are needed to confirm this. [Int J Basic Clin Pharmacol 2016; 5(5.000: 2098-2102
Olivier, J.; Van Der Hart, M.G.C.; Van Swelm, R.P.L.; Dederen, P.J.; Homberg, J.R.; Cremers, T.; Deen, P.M.T.; Cuppen, E.; Cools, A.R.; Ellenbroek, B.A.
Human studies have shown that a reduction of 5-HT transporter (SERT) increases the vulnerability for anxiety and depression. Moreover, women are more vulnerable to develop depression and anxiety disorders than men. For that reason we hypothesized that homozygous 5-HT transporter knockout rat (SERT(-
抑郁症在全球范围内高发，目前尚无有效的治疗手段，使其成为全球性卫生问题之一。抑郁症动物模型作为疾病机理研究以及药物筛选的主要手段，一直以来备受关注，现有的抑郁模型创新性地融合了比较行为学以及最新的分子生物学等相关技术。本文将结合模型的表面效度、结构效度及预测效度对现有的抑郁症动物模型及发病机制研究的最新进展进行综述，主要包括应激模型、损伤模型、化学诱导模型及转基因模型，这些模型均能不同程度的模拟人抑郁症的特征，在抗抑郁药物开发及发病机理研究中发挥重要作用。%The incidence of depressive illness is high worldwide, and the inadequacy of currently available drug treatments contributes to the significant health burden associated with depression. Animal models of depression used as the main methods to study the pathogenesis mechanism and select effective drugs receive increasing concerns. Current popular models of depression creatively merge ethologically valid behavioral assays with the latest technological advances in molecu-lar biology. In this context, this study aims to review the animal models of depression and pathogenesis related with face va-lidity, construct validity, and predictive validity of these models. These models include stress-induced models, injury-in-duced models, drug-induced models and transgenic models which all mimic the depression symptoms of human to some de-gree and are of great value for developing new antidepressant drugs and studying the pathogenesis of this disease.
Johnson Jeffrey A
Full Text Available Abstract Background When depression accompanies diabetes, it complicates treatment, portends worse outcomes and increases health care costs. A collaborative care case-management model, previously tested in an urban managed care organization in the US, achieved significant reduction of depressive symptoms, improved diabetes disease control and patient-reported outcomes, and saved money. While impressive, these findings need to be replicated and extended to other healthcare settings. Our objective is to comprehensively evaluate a collaborative care model for comorbid depression and type 2 diabetes within a Canadian primary care setting. Methods/design We initiated the TeamCare model in four Primary Care Networks in Northern Alberta. The intervention involves a nurse care manager guiding patient-centered care with family physicians and consultant physician specialists to monitor progress and develop tailored care plans. Patients eligible for the intervention will be identified using the Patient Health Questionnaire-9 as a screen for depressive symptoms. Care managers will then guide patients through three phases: 1 improving depressive symptoms, 2 improving blood glucose, blood pressure and cholesterol, and 3 improving lifestyle behaviors. We will employ the RE-AIM framework for a comprehensive and mixed-methods approach to our evaluation. Effectiveness will be assessed using a controlled “on-off” trial design, whereby eligible patients would be alternately enrolled in the TeamCare intervention or usual care on a monthly basis. All patients will be assessed at baseline, 6 and 12 months. Our primary analyses will be based on changes in two outcomes: depressive symptoms, and a multivariable, scaled marginal model for the combined outcome of global disease control (i.e., A1c, systolic blood pressure, LDL cholesterol. Our planned enrolment of 168 patients will provide greater than 80% power to observe clinically important improvements in all
Moon, Henry; Hollenbeck, John R; Humphrey, Stephen E; Maue, Brian
We found evidence of a mutual suppression effect between anxiety and depression on an individual's level of commitment within escalation dilemmas. On the one hand, our results demonstrate a positive relationship between anxiety and level of commitment; on the other, our results demonstrate a negative relationship between depression and level of commitment. Based on the opposing relationships between anxiety and depression and commitment, the broad factor of neuroticism does not demonstrate any relationship with level of commitment, and the significant effects of anxiety and depression on commitment is contingent upon partialling the effect of the other facet of neuroticism. Thus, we contend that applied psychologists, who have focused on neuroticism as a broad construct, should consider the large body of work among clinical psychologists, who argue that anxiety and depression have unique variance associated with them. We conclude by addressing organizational implications of measuring the broad trait of neuroticism more narrowly.
Milne, Lisa A.; Lancaster, Sandra
Study examined factors associated with symptoms of depression in female adolescents. Specifically, the relationship between theoretically related measures-separation-individuation; interpersonal concerns; attachment style; parental representations-and symptoms of depression was investigated. The model developed explained interrelationships of…
Full Text Available Two antiform structures in the Mura Depression were selected as the most promising in Slovenia for the construction of an underground gas storage facility in an aquifer. Seventeen reflection lines with a total length of 157km were recorded, and three boreholes were drilled. Structural models corresponding to two different horizons (the pre-Tertiary basement and the Badenian-Sarmatianboundary were constructed using the Sierra Mimic program. Evaluation of different velocity data (velocity analysis, sonic log, the down-hole method, and laboratory measurements on cores was carried out in order to perform correct timeto-depth conversion and to estabUsh lateral velocity variations. The porous rock in Pečarovci structure is 70m thick layer of dolomite, occurring at a depth of 1900m, whereas layers of marl, several hundred meter thick, represent the impermeable cap-rock. Due to faults, the Dankovci structure, at a depth of 1200m,where the reservoir rocks consist of thin layers of conglomerate and sandstone,was proved to be less reliable. ID synthetic seismograms were used to correlatethe geological and seismic data at the borehole locations, especially at intervals with thin layers. The raytracing method on 2D models (the Sierra Quik packagewas applied to confirm lateral continuity of some horizons and to improve the interpretation of faults which are the critical factor for gas storage.
Matot, J P
This article considers the depressive problematics emerging during adolescence in the frame of the transformations that characterize this period of life, with a focus on the interference of socio-cultural dimensions...
Background: In three academic articles, this PhD thesis investigates maternal postpartum depression (PPD) as a risk factor for the infant-mother attachment and infant development. Previous studies have been contradictory with respect to the question of whether PPD can have long term effects...... on offspring. This may be due to not differing between when PPD is only occurring in the postpartum period and when effects are also due to ongoing or recurrent depression. However, it may also be due to viewing maternal depression as a unitary construct, and not considering underlying maternal psychological...... difficulties which may moderate potential adverse effects. The present thesis investigates two potential maternal moderators of risk:. Comorbid personality disorder and adult attachment insecurity. Moreover, the question of early environmental effects of PPD versus effects of later or ongoing depression...
Mezerai, Mustapha; Dahane, Abdelkrim; Tachon, Jean-Paul
Depression is the object of a dense literature, and synthesizing it is more of a utopian ideal rather than a concrete possibility. Several specific risk factors for mental health are found in the workplace: work overloads, defective communications, role conflicts, competitive climate, and tolerance of violence. At the same time, few preventive measures have been implemented against mental disorders at work, nor are many protective factors present. One worker in ten suffers from depression, anxiety, stress, or overwork. To be distinguished from "burnout", depressive symptoms must induce clinically significant suffering with substantial deterioration in functioning at work. For depression to be recognized as a workplace accident, the employee must show that it was triggered by an unforeseen and sudden event (or at least one certainly) due to or at work. The causal link between an event at work and the depression must be shown (in particular by expert medical testimony about stress factors and indicators of vulnerability to depression). Its recognition as an occupational disease can be based on the presence of psychosocial factors described by models of workplace stress and on its description by the occupational physician.
Digital elevation model (DEM) data are essential to hydrological applications and have been widely used to calculate a variety of useful topographic characteristics, e.g., slope, flow direction, flow accumulation area, stream channel network, topographic index, and others. Excep...
薛涛; 邬丽莎; 刘新民; 王琼
Depression, a seriously harmful disease to peoples ’ physical and mental health , is prevailing world-wide.But the etiology and pathological mechanism is still not fully uncovered .With the development of social economy and the pace of life speeding up , increasing pressure and vulnerable emotion cause depression incidence increased rapidly .For the further research on depression , study of depression mechanism and antidepressant drugs highly depends on effective ani -mal models .The degree of similarity of animal models to human disease status and the accuracy and reliability of evaluation methods of animal models directly influence the value of the resuts of experiments .In this article we introduce the common-ly used animal models of depression , the evaluation indicators at organism , organ, and molecular levels , and to provide theoretical references for the further studies on depression .%抑郁症（ depression ）是一种严重危害人类身心健康的全球性的主要精神卫生问题。目前病因及病理机制尚不完全清楚，但随着社会经济的发展，生活节奏加快，人们的压力增加，情感冲击加大，造成抑郁症发病率逐年增长。随着对抑郁症研究的深入，抑郁症动物模型及其评价方法被广泛运用于抑郁症发病机制研究和抗抑郁新药的研发。动物模型模拟人类疾病状态的程度以及评价方法的可靠性和准确性直接影响实验研究结果的价值。本综述主要介绍了常用的抑郁症动物模型，及整体、器官、分子水平的评价指标，为后续新型抗抑郁药物的研发提供文献参考。
Sørensen, Jan; Stage, Kurt B; Damsbo, Niels
The objective of this study was to model the cost-effectiveness of escitalopram in comparison with generic citalopram and venlafaxine in primary care treatment of major depressive disorder (baseline scores 22-40 on the Montgomery-Asberg Depression Rating Scale, MADRS) in Denmark. A three-path dec......The objective of this study was to model the cost-effectiveness of escitalopram in comparison with generic citalopram and venlafaxine in primary care treatment of major depressive disorder (baseline scores 22-40 on the Montgomery-Asberg Depression Rating Scale, MADRS) in Denmark. A three...... in 2004 DDK. The expected overall 6-month remission rate was higher for escitalopram (64.1%) than citalopram (58.9%). From both perspectives, the total expected cost per successfully treated patient was lower for escitalopram (DKK 22,323 healthcare, DKK 72,399 societal) than for citalopram (DKK 25......,778 healthcare, DKK 87,786 societal). Remission rates and costs were similar for escitalopram and venlafaxine. Robustness of the findings was verified in multivariate sensitivity analyses. For patients in primary care, escitalopram appears to be a cost-effective alternative to (generic) citalopram, with greater...
Wang, Ying-Chou; Wang, En-Nan; Wang, Chia-Chuan; Huang, Chung-Lei; Huang, Andrew Chih Wei
Lithium (LiCl) and carbamazepine (CBZ), the common mood stabilizers, are thought to be effective treatments for bipolar disorder. The aim of the present study was to investigate whether LiCl as well as CBZ has similar effects on the bipolar disorder-associated cognitive dysfunctions in rats, particularly the spatial learning and depressive responses. Adult male Wistar rats were administered intracerebroventricularly with 5μl of 10(-3)M ouabain on session 1, and then received an intraperitoneal injection of LiCl or CBZ for 4 sessions (1 session/2days). For the behavioral tests, all rats were subjected to the water maze 15min for spatial learning and the forced swimming test 5min for depression on each session. The present results showed that ouabain resulted in increased latency and longer distance traveled to reach the hidden platform in the water maze, indicating that ouabain impaired the spatial learning. However, ouabain did not affect swimming velocity in the water maze and depressive responses in the forced swimming test. LiCl treatment decreased the ouabain-enhanced latency and the total distance, but not the velocity, swam to reach the hidden platform in the water maze task. Additionally, LiCl did not result in changes of any depressive indices, such as struggling behavior, swimming behavior, and floating behavior. Likewise, CBZ did not affect any behavioral indices of spatial learning and depression. A linear regression analysis suggested that LiCl, but not CBZ, could predict the decreased latency and total distance traveled except the velocity of swimming