Problem-solving skills appraisal mediates hardiness and suicidal ideation among malaysian undergraduate students.

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Abdollahi, Abbas; Talib, Mansor Abu; Yaacob, Siti Nor; Ismail, Zanariah

2015-01-01

Recent evidence suggests that suicidal ideation is increased among university students, it is essential to increase our knowledge concerning the etiology of suicidal ideation among university students. This study was conducted to examine the relationships between problem-solving skills appraisal, hardiness, and suicidal ideation among university students. In addition, this study was conducted to examine problem-solving skills appraisal (including the three components of problem-solving confidence, approach-avoidance style, and personal control of emotion) as a potential mediator between hardiness and suicidal ideation. The participants consisted of 500 undergraduate students from Malaysian public universities. Structural Equation Modelling (SEM) estimated that undergraduate students with lower hardiness, poor problem-solving confidence, external personal control of emotion, and avoiding style was associated with higher suicidal ideation. Problem-solving skills appraisal (including the three components of problem-solving confidence, approach-avoidance style, and personal control of emotion) partially mediated the relationship between hardiness and suicidal ideation. These findings underline the importance of studying mediating processes that explain how hardiness affects suicidal ideation.

The Relationship between Childhood Trauma and Suicidal Ideation: Role of Maltreatment and Potential Mediators

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Bahk, Yong-Chun; Jang, Seon-Kyeong; Choi, Kee-Hong; Lee, Seung-Hwan

2016-01-01

Objective Childhood trauma is recognized as an important risk factor in suicidal ideation, however it is not fully understood how the different types of childhood maltreatment influence suicidal ideation nor what variables mediate the relationship between childhood trauma and suicidal ideation. This study examined the path from childhood trauma to suicidal ideation, including potential mediators. Methods A sample of 211 healthy adults completed the Childhood Trauma Questionnaire (CTQ), Beck s...

The development of herpes simplex virus thymidine kinase suicide gene imaging

International Nuclear Information System (INIS)

Xing Yan; Zhao Jinhua

2006-01-01

Suicide gene treatment of tumor catches more and more attention in recent years. Cells transferred with suicide gene from virus or bacteria will express specific enzymes and transform innocuous prodrugs into highly toxic chemotherapeutic drugs. As a result, the cells will be killed. Radionuclide labeled probe can display the biologic characteristics of suicide gene in vivo. This article reviews the development of HSV-tk gene imaging. (authors)

Perceived Interpersonal Burdensomeness as a Mediator between Nightmare Distress and Suicidal ideation in Nightmare Sufferers

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Sooyeon Suh

2016-11-01

Full Text Available Previous studies have supported the significant association between nightmares and suicidal ideation, but the underlying mechanisms are largely unknown. The purpose of the present study was to investigate perceived burdensomeness and thwarted belongingness as mediators in the relationship between nightmare distress and suicidal ideation. This sample consisted of 301 undergraduate students who endorsed experiencing nightmares (mean age 21.87 ± 2.17, 78.1% female. All participants completed questionnaires on nightmare distress (Nightmare Distress Questionnaire, unmet interpersonal needs (Interpersonal Needs Questionnaire, and suicidal ideation (Depressive Symptom Inventory - Suicidality Subscale. Analyses were performed using multiple mediation regression. Results indicated that nightmare distress was associated with perceived burdensomeness (r = .17, p < .001 and suicidal ideation (r = .24, p < .001, but was not related to thwarted belongingness (r = .10, p = .06. Multiple mediation analyses revealed that perceived burdensomeness partially mediated the relationship between nightmares and suicidal ideation, but thwarted belongingness did not. Additionally, this mediating relationship for perceived burdensomeness was moderated by gender, being significant only for females. These findings highlight the important role of interpersonal factors in the relationship between nightmares and suicidal ideation.

Glucocorticoid Receptor Related Genes: Genotype And Brain Gene Expression Relationships To Suicide And Major Depressive Disorder

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Pantazatos, Spiro P.; Huang, Yung-yu; Rosoklija, Gorazd B.; Dwork, Andrew J.; Burke, Ainsley; Arango, Victoria; Oquendo, Maria A.; Mann, J. John

2016-01-01

Introduction We tested the relationship between genotype, gene expression and suicidal behavior and MDD in live subjects and postmortem samples for three genes, associated with the hypothalamic-pituitary-adrenal axis, suicidal behavior and major depressive disorder (MDD); FK506 binding protein 5 (FKBP5), Spindle and kinetochore-associated protein 2 (SKA2) and Glucocorticoid Receptor (NR3C1). Materials and Methods Single-nucleotide polymorphisms (SNPs) and haplotypes were tested for association with suicidal behavior and MDD in a live (N=277) and a postmortem sample (N=209). RNA-seq was used to examine gene and isoform-level brain expression postmortem (Brodmann Area 9) (N=59). Expression quantitative trait loci (eQTL) relationships were examined using a public database (UK Brain Expression Consortium). Results We identified a haplotype within the FKBP5 gene, present in 47% of the live subjects, that was associated with increased risk of suicide attempt (OR=1.58, t=6.03, p=0.014). Six SNPs on this gene, three SNPs on SKA2 and one near NR3C1 showed before-adjustment association with attempted suicide, and two SNPs of SKA2 with suicide death, but none stayed significant after adjustment for multiple testing. Only the SKA2 SNPs were related to expression in the prefrontal cortex. One NR3C1 transcript had lower expression in suicide relative to non-suicide sudden death cases (b=-0.48, SE=0.12, t=-4.02, adjusted p=0.004). Conclusion We have identified an association of FKBP5 haplotype with risk of suicide attempt and found an association between suicide and altered NR3C1 gene expression in the prefrontal cortex. Our findings further implicate hypothalamic pituitary axis dysfunction in suicidal behavior. PMID:27030168

Suicide and the selfish gene.

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Satora, Leszek

2005-01-01

The application of an evolutionary perspective to human behaviour generates philosophical, political and scientific controversy. Modern human symbolic consciousness is not the cumulation of the long trend that natural selection would predict. The new archaeological data suggested the anatomical and behavioural innovation has been episodic and rare separated by long periods of stagnate. New behavioural mode and the new skeletal structure of modem human arose as an incidental exaptation. Additionally the genetic basis dysfunction connected with suicide behaviour and growing statistic suicide among teenager is contradictory to the theory that our behaviour are programmed in any detail by selfish genes. In this cases genetically determined suicidal behaviour should be rapidly eliminated by natural selection.

Suicidal ideation and suicidal behavior according to the C-SSRS in a European cohort of Huntington's disease gene expansion carriers.

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van Duijn, Erik; Vrijmoeth, Eslie M; Giltay, Erik J; Bernhard Landwehrmeyer, G

2018-03-01

Huntington's disease (HD) gene expansion carriers are at an increased risk of suicide, but so far, no studies have investigated the full spectrum of suicidality, including suicidal ideation, suicidal behavior and self-injurious behavior. We included 1451 HD gene expansion carriers (age 48.4 years (SD 14.0), 54.8% female) of the REGISTRY study of the European Huntington's Disease Network. Lifetime suicidal ideation and suicidal behavior were assessed with the Columbia-Suicidal Severity Rating Scale. Motor symptoms and disease stage were assessed using subscales of the Unified Huntington's Disease Rating Scale, and depressed mood and irritability were assessed by the Problem Behaviors Assessment. Lifetime passive suicidal ideation was reported by 21.2%. Participants in stage II showed the highest prevalence rate of suicidal ideation, while participants in stage IV/V showed the highest prevalence of suicidal behavior. A lifetime suicide attempt was reported by 6.5% of the HD gene expansion carriers. In multivariate regression analyses, both suicidal ideation and suicidal behavior were associated with a depressed mood, and to a lesser extend to irritability. Results may have been affected by denial or recall bias and no conclusions can be made about the temporal and causal relationships with depressed mood and irritability because of the cross-sectional analyses. Given the high prevalence of suicidal ideation and suicidal behavior in all stages of HD, it is important to screen HD gene expansion carriers for suicidal ideation and suicidal behavior on a regular basis in clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.

Suicidality in male prisoners: influence of childhood adversity mediated by dimensions of personality.

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Godet-Mardirossian, Hélène; Jehel, Louis; Falissard, Bruno

2011-07-01

This study aims to study the influence of childhood adversity on suicidal behavior in male prisoners. Including a random sample of 899 male prisoners (French National Mental Health Prison Survey, 2003), this paper studied suicidal ideations and suicide attempts using MINI criteria, and personality using Temperament and Character Inventory. Risk factors of suicidality were examined, and structural equations studied the influence of childhood trauma on suicidality, mediated by personality dimensions. The prisoners reported high levels of childhood adversity. More than a third reported recent suicidal ideations. Childhood adversity and dimensions of personality were associated with suicidality. Structural equations showed that childhood adversity was positively associated with suicidality, mediated by poor dimensions of character (affective stability, self-cooperativeness, and self-transcendence). In conclusion, these results confirm the importance of screening and treatment of childhood trauma among male prisoners. They suggest the importance to study dimensions of personality and tailor treatment to specific needs. © 2011 American Academy of Forensic Sciences.

GLUCOCORTICOID RECEPTOR-RELATED GENES: GENOTYPE AND BRAIN GENE EXPRESSION RELATIONSHIPS TO SUICIDE AND MAJOR DEPRESSIVE DISORDER.

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Yin, Honglei; Galfalvy, Hanga; Pantazatos, Spiro P; Huang, Yung-Yu; Rosoklija, Gorazd B; Dwork, Andrew J; Burke, Ainsley; Arango, Victoria; Oquendo, Maria A; Mann, J John

2016-06-01

We tested the relationship between genotype, gene expression and suicidal behavior and major depressive disorder (MDD) in live subjects and postmortem samples for three genes, associated with the hypothalamic-pituitary-adrenal axis, suicidal behavior, and MDD; FK506-binding protein 5 (FKBP5), Spindle and kinetochore-associated protein 2 (SKA2), and Glucocorticoid Receptor (NR3C1). Single-nucleotide polymorphisms (SNPs) and haplotypes were tested for association with suicidal behavior and MDD in a live (N = 277) and a postmortem sample (N = 209). RNA-seq was used to examine gene and isoform-level brain expression postmortem (Brodmann Area 9; N = 59). Expression quantitative trait loci (eQTL) relationships were examined using a public database (UK Brain Expression Consortium). We identified a haplotype within the FKBP5 gene, present in 47% of the live subjects, which was associated with increased risk of suicide attempt (OR = 1.58, t = 6.03, P = .014). Six SNPs on this gene, three SNPs on SKA2, and one near NR3C1 showed before-adjustment association with attempted suicide, and two SNPs of SKA2 with suicide death, but none stayed significant after adjustment for multiple testing. Only the SKA2 SNPs were related to expression in the prefrontal cortex (pFCTX). One NR3C1 transcript had lower expression in suicide relative to nonsuicide sudden death cases (b = -0.48, SE = 0.12, t = -4.02, adjusted P = .004). We have identified an association of FKBP5 haplotype with risk of suicide attempt and found an association between suicide and altered NR3C1 gene expression in the pFCTX. Our findings further implicate hypothalamic pituitary axis dysfunction in suicidal behavior. © 2016 Wiley Periodicals, Inc.

Procrastination and suicide proneness: A moderated-mediation model for cognitive schemas and gender.

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Klibert, Jeffrey; LeLeux-LaBarge, Kayla; Tarantino, Nicholas; Yancey, Thresa; Lamis, Dorian A

2016-07-01

This study examined the direct and indirect paths between procrastination and suicide proneness while considering gender differences. Participants included 547 undergraduates from a southeastern university. Procrastination was positively related to suicide proneness for both genders, although this relation was stronger for women. Moderated-mediation analyses with bootstrapping highlighted insufficient self-control schemas as a mediator in the relation between procrastination and suicide proneness. However, indirect pathways did not vary by gender. Results represent an extension of the Procrastination-Health Model by highlighting the contribution of cognitive factors in explaining the relation between procrastination and suicide proneness.

Tumor Restrictive Suicide Gene Therapy for Glioma Controlled by the FOS Promoter.

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Jianqing Pan

Full Text Available Effective suicide gene delivery and expression are crucial to achieving successful effects in gene therapy. An ideal tumor-specific promoter expresses therapeutic genes in tumor cells with minimal normal tissue expression. We compared the activity of the FOS (FBJ murine osteosarcoma viral oncogene homolog promoter with five alternative tumor-specific promoters in glioma cells and non-malignant astrocytes. The FOS promoter caused significantly higher transcriptional activity in glioma cell lines than all alternative promoters with the exception of CMV. The FOS promoter showed 13.9%, 32.4%, and 70.8% of the transcriptional activity of CMV in three glioma cell lines (U87, U251, and U373. Importantly, however, the FOS promoter showed only 1.6% of the transcriptional activity of CMV in normal astrocytes. We also tested the biologic activity of recombinant adenovirus containing the suicide gene herpes simplex virus thymidine kinase (HSV-tk driven by the FOS promoter, including selective killing efficacy in vitro and tumor inhibition rate in vivo. Adenoviral-mediated delivery of the HSV-tk gene controlled by the FOS promoter conferred a cytotoxic effect on human glioma cells in vitro and in vivo. This study suggests that use of the FOS-tk adenovirus system is a promising strategy for glioma-specific gene therapy but still much left for improvement.

Mediating role of borderline personality disorder traits in the effects of childhood maltreatment on suicidal behaviour among mood disorder patients.

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Aaltonen, K I; Rosenström, T; Baryshnikov, I; Karpov, B; Melartin, T; Suominen, K; Heikkinen, M; Näätänen, P; Koivisto, M; Joffe, G; Isometsä, E

2017-07-01

Substantial evidence supports an association between childhood maltreatment and suicidal behaviour. However, few studies have examined factors mediating this relationship among patients with unipolar or bipolar mood disorders. Depressive disorder and bipolar disorder (ICD-10-DCR) patients (n=287) from the Helsinki University Psychiatric Consortium (HUPC) Study were surveyed on self-reported childhood experiences, current depressive symptoms, borderline personality disorder traits, and lifetime suicidal behaviour. Psychiatric records served to complement the information on suicide attempts. We examined by formal mediation analyses whether (1) the effect of childhood maltreatment on suicidal behaviour is mediated through borderline personality disorder traits and (2) the mediation effect differs between lifetime suicidal ideation and lifetime suicide attempts. The impact of childhood maltreatment in multivariate models on either lifetime suicidal ideation or lifetime suicide attempts showed comparable total effects. In formal mediation analyses, borderline personality disorder traits mediated all of the total effect of childhood maltreatment on lifetime suicide attempts, but only one fifth of the total effect on lifetime suicidal ideation. The mediation effect was stronger for lifetime suicide attempts than for lifetime suicidal ideation (P=0.002) and independent of current depressive symptoms. The mechanisms of the effect of childhood maltreatment on suicidal ideation versus suicide attempts may diverge among psychiatric patients with mood disorders. Borderline personality disorder traits may contribute to these mechanisms, although the influence appears considerably stronger for suicide attempts than for suicidal ideation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Improving the Safety of Cell Therapy Products by Suicide Gene Transfer

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Antonio eDi Stasi

2014-11-01

Full Text Available Adoptive T-cell therapy can involve donor lymphocyte infusion (DLI after allogeneic hematopoietic stem cell transplantation, the administration of tumor infiltrating lymphocyte (TILs expanded ex-vivo, or more recently the use of T cell receptor (TCR or chimeric antigen receptor (CAR redirected T cells. However cellular therapies can pose significant risks, including graft-versus-host-disease and other on and off-target effects, and therefore strategies need to be implemented to permanently reverse any sign of toxicity. A suicide gene is a genetically encoded molecule that allows selective destruction of adoptively transferred cells. Suicide gene addition to cellular therapeutic products can lead to selective ablation of gene-modified cells, preventing collateral damage to contiguous cells and/or tissues. The ‘ideal’ suicide gene would ensure the safety of gene modified cellular applications by granting irreversible elimination of ‘all’ and ‘only’ the cells responsible for the unwanted toxicity. This review presents the suicide gene safety systems reported to date, with a focus on the state-of-the-art and potential applications regarding two of the most extensively validated suicide genes, including the clinical setting: herpes-simplex-thymidine-kinase (HSV-TK and inducible-caspase-9 (iCasp9.

Youth Engagement and Suicide Risk: Testing a Mediated Model in a Canadian Community Sample

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Ramey, Heather L.; Busseri, Michael A.; Khanna, Nishad; Rose-Krasnor, Linda

2010-01-01

Suicide is a leading cause of death among adolescents in many industrialized countries. We report evidence from a mediation model linking greater youth activity engagement, spanning behavioral and psychological components, with lower suicide risk through five hypothesized intrapersonal and interpersonal mediating factors. Self-report survey data…

Utilized social support and self-esteem mediate the relationship between perceived social support and suicide ideation. A test of a multiple mediator model.

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Kleiman, Evan M; Riskind, John H

2013-01-01

While perceived social support has received considerable research as a protective factor for suicide ideation, little attention has been given to the mechanisms that mediate its effects. We integrated two theoretical models, Joiner's (2005) interpersonal theory of suicide and Leary's (Leary, Tambor, Terdal, & Downs, 1995) sociometer theory of self-esteem to investigate two hypothesized mechanisms, utilization of social support and self-esteem. Specifically, we hypothesized that individuals must utilize the social support they perceive that would result in increased self-esteem, which in turn buffers them from suicide ideation. Participants were 172 college students who completed measures of social support, self-esteem, and suicide ideation. Tests of simple mediation indicate that utilization of social support and self-esteem may each individually help to mediate the perceived social support/suicide ideation relationship. Additionally, a test of multiple mediators using bootstrapping supported the hypothesized multiple-mediator model. The use of a cross-sectional design limited our ability to find true cause-and-effect relationships. Results suggested that utilized social support and self-esteem both operate as individual moderators in the social support/self-esteem relationship. Results further suggested, in a comprehensive model, that perceived social support buffers suicide ideation through utilization of social support and increases in self-esteem.

[Mediating effects on depression regarding the relationship between negative life events and suicide ideation among college students].

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Wu, Jiao; Wu, Yun-tao; Feng, Shu-xiu; Meng, Heng; Chen, Hui

2012-11-01

To understand the relationship between negative life events and suicide ideation, and how it was influenced by the mediating effect of depression. 1145 college students from one university were selected using cluster sampling. Both Symptom Check List (SCL-90) and Questionnaire were administered to measure depression and suicide ideation in the past week and on the prevalence of negative life events and related information. Recent negative life events would include physical illness, academic problem, financial problem and interpersonal conflict etc. Multiple logistic regressions were used to identify the mediating effect of depression. Physical illness (OR = 2.5, P = 0.028), interpersonal conflict (OR = 7.2, P = 0.002) and financial problem (OR = 1.6, P = 0.026) were significantly associated with suicide ideation, but academically-related problems did not seem to be significantly associated with suicide ideation (OR = 1.8, P = 0.090). After adjusted for depression, both physical illness and interpersonal conflicts were not but financial problem remained significantly associated with suicide ideation (OR = 1.7, P = 0.014). Our data showed that depression fully mediated the relationship between physical illness, interpersonal conflict and suicide ideation, but did not mediate the relationship between financial problem and suicide ideation. Depression played different mediating roles between different negative life events and suicide ideation. The findings from this study might be able to provide some clues for the prevention interventions on college students.

Gene expression associated with suicide attempts in US veterans (Open Access)

Science.gov (United States)

2017-09-05

depression , bipolar disorder, alcohol use disorder9 and intermittent explosive disorder.8 However, because suicide attempts occur in the context of many... suicidal ideation in a genome wide associa- tion study of depressed inpatients.25 These results provide partial replication of gene expression...OPEN ORIGINAL ARTICLE Gene expression associated with suicide attempts in US veterans JD Flory1,2,7, D Donohue3,7, S Muhie3, R Yang4, SA Miller3, R

Impulsivity and suicidality: the mediating role of painful and provocative experiences.

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Bender, Theodore W; Gordon, Kathryn H; Bresin, Konrad; Joiner, Thomas E

2011-03-01

Multiple studies have reported a link between high levels of impulsivity and suicidal behavior. Joiner's (2005) explanation for this link is that impulsive individuals have a greater tendency to experience painful and provocative events that habituate them to fear and pain, which leads to an acquired capability for engaging in suicidal behavior. Study 1 tested Joiner's (2005) hypothesis in a sample of 182 undergraduate students who completed self-report questionnaires on impulsivity, frequency of painful and provocative events, and acquired capability for suicide. In addition to self-report, pain tolerance (an aspect of acquired capability for suicide) was measured with a pressure algometer. Study 2 sought to replicate our findings from Study 1 in a sample of 516 clinical outpatients using a multi-faceted measure of impulsivity. Consistent with prediction, product of coefficients tests for mediation (MacKinnon et al., 2002) revealed that impulsivity has an indirect relationship with acquired capability for suicidal behavior, and that this relationship is mediated by painful and provocative events. Data from our studies are cross-sectional in nature, which does not allow for conclusions about the temporal ordering of our variables. In addition, self-report was used to measure most variables. Future research may benefit from a longitudinal design and the inclusion of other modes of assessment (e.g., behavioral measures of impulsivity). Our findings suggest that the link between impulsivity and suicidal behavior occurs because impulsive people tend to have a greater capability for suicidal behavior, which they have acquired through experiencing painful and provocative events. Copyright © 2010 Elsevier B.V. All rights reserved.

Parenting behavior and the Interpersonal-Psychological Theory of Suicide: a mediated moderation analysis with adolescents.

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Cero, Ian; Sifers, Sarah K

2013-09-25

Multiple features of parenting have been associated with development of suicide-related behaviors in adolescents. However, findings are inconsistent on which aspects of parenting are protective or harmful and why. This investigation sought to reconcile these discrepancies through the Interpersonal-Psychological Theory of Suicide (IPTS), which argues that suicide ideation and the capability to attempt suicide are etiologically distinct. Responses of 200 Midwestern public school students to the Profiles of Student Life: Attitudes and Behavior survey were analyzed using mediated moderation analysis. Participant sex significantly moderated the relationships between parenting variables and suicide attempts and these relationships were accounted for by IPTS variables. Specifically, the effect of parental support on suicide attempts was twice as strong for girls. Self-esteem mediated this interaction (b=-.011, SE(boot)=.008, p<.05, κ(2)=.07). Conversely, the effect of parental boundaries on suicide attempts was significant for boys, but not for girls, and was mediated by exposure to violence (b=.029, SE(boot)=.021, p<.05, κ(2)=.07). This study involved retrospective report with proxy-measures of IPTS constructs. Future research should consider multiple informants and additional measures. Findings highlight potential mechanisms by which parenting behaviors could influence sex differences in adolescent suicide-relate behaviors, and that some parenting behavior is associated with reduced adolescent suicide attempts. Findings also suggest the IPTS is able to account for previously identified inconsistencies in the effects of parenting behaviors on adolescent suicide-related behaviors. Implications for theory and intervention are discussed. © 2013 Elsevier B.V. All rights reserved.

Different stress-related gene expression in depression and suicide

NARCIS (Netherlands)

Zhao, J; Qi, X-R; Gao, S-F; Lu, J; van Wamelen, D J; Kamphuis, W; Bao, A-M; Swaab, D F

OBJECTIVE: Suicide occurs in some, but not all depressed patients. So far, it remains unknown whether the studied stress-related candidate genes change in depression, suicide or both. The prefrontal cortex (PFC) is involved in, among other things, impulse control and inhibitory behavior and plays an

Mediating Effects of Positive Thinking and Social Support on Suicide Resilience.

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Matel-Anderson, Denise M; Bekhet, Abir K; Garnier-Villarreal, Mauricio

2018-02-01

Suicide has been the second leading cause of death for 18- to 24-year-olds in the United States since 2011. The stress experienced by undergraduate college students has the potential to increase one's risk for suicide. Resilience theory was used as a theoretical framework to examine the interplay between risk and protective factors. A cross-sectional and correlational design was used to assess the mediating effects of positive thinking and/or social support on suicide resilience in 131 college students 18 to 24 years old who completed an online survey. The study found an indirect effect of self-esteem on suicide resilience through positive thinking and social support indicating that as self-esteem increases, positive thinking and social support also increase, which leads to an increase in resilience. The study also found a direct effect of self-esteem, positive thinking, and social support on suicide resilience. The findings inform the development of tailored interventions to build suicide resilience in college students.

A suicide gene therapy approach to treat epidermolysis bullosa-associated skin cancer

International Nuclear Information System (INIS)

Gruber, C.

2009-01-01

Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited disease causing extensive blister formation within the basal membrane zone (BMZ) of the skin and mucous membranes. It is caused by premature STOP mutations in the COL7A1 gene, which is indispensable for proper skin assembling. RDEB is associated with the development of a highly malignant skin cancer (squamous cell carcinoma, SCC) in early adulthood that displays a life threatening complication within this patient group. To date, neither chemo- nor radiotherapies showed successful results and due to the high metastatic potential of RDEB SCC wide surgical excision is still favoured. In this study we could reveal a new promising cancer treatment using spliceosome mediated RNA trans-splicing (SMaRT) using a suicide gene therapy approach. First we identified the tumour marker gene MMP-9 expressed by RDEB SCC cells in cell culture which was used to generate various pre-mRNA trans-splicing molecules (PTM). PTMs are able to facilitate trans-splicing between a tumour target gene and a cell death inducing peptide/toxin, encoded by the PTM. As a consequence the toxin is expressed in cancer cells leading to the induction of cell death. This technique offers high specificity in cancer cell targeting compared to other conventional cDNA expression studies. Various trans-splicing molecules were pre-evaluated in a fluorescence screening model for their best trans-splicing efficiency with the target molecule. Herein we identified two potent PTMs (PTM BD0 and PTM BD6), that were further adapted for endogenous suicide studies by inserting the toxin streptolysin O. In two independent in vitro cell culture assays we were able to confirm that the trans-splicing molecules are able to induce expression of the toxin resulting in cell membrane permeabilization and increased cell death induction. The results indicate that SMaRT technology offers a new platform for a suicide gene therapy approach to treat malignant squamous cell

Different stress-related gene expression in depression and suicide.

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Zhao, J; Qi, X-R; Gao, S-F; Lu, J; van Wamelen, D J; Kamphuis, W; Bao, A-M; Swaab, D F

2015-09-01

Suicide occurs in some, but not all depressed patients. So far, it remains unknown whether the studied stress-related candidate genes change in depression, suicide or both. The prefrontal cortex (PFC) is involved in, among other things, impulse control and inhibitory behavior and plays an important role in both suicide and depression. We have employed qPCR to study 124 anterior cingulate cortex (ACC) and dorsolateral PFC (DLPFC) brain samples, obtained from two brain banks, from: i) young depressed patients (average age 43 years) who committed suicide (MDD-S) and depressed patients who died from causes other than suicide (MDD-NS) and from ii) elderly depressed patients (average age 75 years) who did not commit suicide (DEP). Both cohorts were individually matched with non-psychiatric non-suicide control subjects. We determined the transcript levels of hypothalamic-pituitary-adrenal axis-regulating molecules (corticotropin-releasing hormone (CRH), CRH receptors, CRH binding protein, mineralocorticoid receptor/glucocorticoid receptor), transcription factors that regulate CRH expression, CRH-stimulating cytokines, chaperone proteins, retinoid signaling, brain-derived neurotrophic factor and tropomyosin-related kinase B, cytochrome proteins, nitric oxide synthase (NOS) and monoamines. In the MDD-S group, expression levels of CRH and neuronal NOS-interacting DHHC domain-containing protein with dendritic mRNA (NIDD) were increased. Other changes were only present in the DEP group, i.e. decreased NIDD, and increased and 5-hydroxytryptamine receptor 1A (5-HT1A) expression levels. Changes were found to be more pronounced in the anterior cingulate cortex than in the dorsolateral PFC. Depressed patients who committed suicide have different gene expression patterns than depressed patients who died of causes other than suicide. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Mediating Roles of Anxiety Depression, and Hopelessness on Adolescent Suicidal Behaviors

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Thompson, Elaine Adams; Mazza, James J.; Herting, Jerald R.; Randell, Brooke P.; Eggert, Leona L.

2005-01-01

The purpose of this study was to explore the roles of anxiety, depression, and hopelessness as mediators between known risk factors and suicidal behaviors among 1,287 potential high school dropouts. As a step toward theory development, a model was tested that posited the relationships among these variables and their effects on suicidal behaviors.…

Self-reported peer victimization and suicidal ideation in adolescent psychiatric inpatients: the mediating role of negative self-esteem.

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Jones, Heather A; Bilge-Johnson, Sumru; Rabinovitch, Annie E; Fishel, Hazel

2014-10-01

The current study investigated relationships among self-reported peer victimization, suicidality, and depression in adolescent psychiatric inpatients. Sixty-seven adolescent psychiatric inpatients at a Midwestern children's hospital completed measures of bullying and peer victimization, suicidal ideation, and depression during their inpatient stay. Analyses indicated significant moderate correlations among victimization, suicidal ideation, and depression in adolescents. Results from mediational analyses found that negative self-esteem mediated the relationship between peer victimization and suicidal ideation. To date, this study is the first to directly examine the mechanisms underlying the relationship between peer victimization and suicidal ideation in adolescent psychiatric inpatients. © The Author(s) 2013.

Future orientation and suicide risk in Hungarian college students: Burdensomeness and belongingness as mediators.

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Chang, Edward C; Chang, Olivia D; Martos, Tamás; Sallay, Viola

2017-01-01

We tested a model consistent with the notion that perceived burdensomeness and thwarted belongingness mediate the association between future orientation and suicide risk (viz., depressive symptoms and suicide ideation) in college students. The sample was comprised of 195 Hungarian college students. Results indicated that the negative associations found between future orientation and suicide risk outcomes were accounted for by both perceived burdensomeness and thwarted belongingness. The present findings highlight the importance of studying positive future cognitions in suicide risk and provide support for perceived burdensomeness and thwarted belongingness as potential proximal mechanisms associated with heighted suicide risk in adults.

Examining anxiety sensitivity as a mediator of the association between PTSD symptoms and suicide risk among women firefighters.

Science.gov (United States)

Stanley, Ian H; Hom, Melanie A; Spencer-Thomas, Sally; Joiner, Thomas E

2017-08-01

Posttraumatic stress disorder (PTSD) symptoms are associated with increased suicide risk. Anxiety sensitivity (AS)-the fear of anxiety-related sensations-is both a vulnerability factor for and consequence of PTSD symptoms. AS also predicts suicide risk. To our knowledge, no study has examined whether AS concerns account for the association between PTSD symptoms and suicide risk. A total of 254 women firefighters completed a web-based mental health survey. The Life Events Checklist for DSM-5 (LEC-5) was administered as a prelude to the PTSD Checklist for DSM-5 (PCL-5) to assess for exposure to a Criterion A event. The PCL-5, Anxiety Sensitivity Index-3 (ASI-3), and Suicidal Behaviors Questionnaire-Revised (SBQ-R) were utilized to assess PTSD symptoms, AS concerns, and suicide risk, respectively. Bootstrap mediation analyses were conducted, controlling for depression symptoms as measured by the Center for Epidemiologic Studies Depression Scale-Revised (CESD-R). Global and cognitive AS concerns, but neither physical nor social AS concerns, were statistically significant mediators of the relationship between PTSD symptoms (total score, re-experiencing and numbing clusters) and suicide risk. Alternate mediation models testing PTSD symptoms as a mediator of the relationship between AS concerns and suicide risk were not statistically significant, supporting the specificity of our proposed model. Anxiety sensitivity concerns-specifically, cognitive AS concerns-account for the link between PTSD symptoms and suicide risk among women firefighters. Among firefighters with elevated PTSD symptoms, interventions that address cognitive AS concerns may thwart the trajectory to suicidal thoughts and behaviors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain.

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Patrick O McGowan

Full Text Available BACKGROUND: Alterations in gene expression in the suicide brain have been reported and for several genes DNA methylation as an epigenetic regulator is thought to play a role. rRNA genes, that encode ribosomal RNA, are the backbone of the protein synthesis machinery and levels of rRNA gene promoter methylation determine rRNA transcription. METHODOLOGY/PRINCIPAL FINDINGS: We test here by sodium bisulfite mapping of the rRNA promoter and quantitative real-time PCR of rRNA expression the hypothesis that epigenetic differences in critical loci in the brain are involved in the pathophysiology of suicide. Suicide subjects in this study were selected for a history of early childhood neglect/abuse, which is associated with decreased hippocampal volume and cognitive impairments. rRNA was significantly hypermethylated throughout the promoter and 5' regulatory region in the brain of suicide subjects, consistent with reduced rRNA expression in the hippocampus. This difference in rRNA methylation was not evident in the cerebellum and occurred in the absence of genome-wide changes in methylation, as assessed by nearest neighbor. CONCLUSIONS/SIGNIFICANCE: This is the first study to show aberrant regulation of the protein synthesis machinery in the suicide brain. The data implicate the epigenetic modulation of rRNA in the pathophysiology of suicide.

Perceived racism and suicide ideation: mediating role of depression but moderating role of religiosity among African American adults.

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Walker, Rheeda L; Salami, Temilola K; Carter, Sierra E; Flowers, Kelci

2014-10-01

Suicide is a public health problem for African Americans who are young and of working age. The purpose of this study was to examine mediated and moderated effects of perceived racism on suicide ideation in a community sample of 236 African American men and women. Measures of suicide ideation, depression symptoms, intrinsic/extrinsic religiosity, and perceived racism were administered. Perceived racial discrimination was directly and indirectly associated with suicide ideation. For participants who reported low levels of extrinsic religiosity, the mediated effect of perceived racism (via depression symptoms) was significant. These findings provide some insight into suicide vulnerability for specific subgroups of African Americans. © 2014 The American Association of Suicidology.

Impulsivity as a mediator in the relationship between problem solving and suicidal ideation.

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Gonzalez, Vivian M; Neander, Lucía L

2018-03-15

This study examined whether three facets of impulsivity previously shown to be associated with suicidal ideation and attempts (negative urgency, lack of premeditation, and lack of perseverance) help to account for the established association between problem solving deficits and suicidal ideation. Emerging adult college student drinkers with a history of at least passive suicidal ideation (N = 387) completed measures of problem solving, impulsivity, and suicidal ideation. A path analysis was conducted to examine the mediating role of impulsivity variables in the association between problem solving (rational problem solving, positive and negative problem orientation, and avoidance style) and suicidal ideation. Direct and indirect associations through impulsivity, particularly negative urgency, were found between problem solving and severity of suicidal ideation. Interventions aimed at teaching problem solving skills, as well as self-efficacy and optimism for solving life problems, may help to reduce impulsivity and suicidal ideation. © 2018 Wiley Periodicals, Inc.

Thwarted Belongingness Mediates the Relationship between Fear of Negative Evaluation and Suicidal Ideation.

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Chu, Carol; Buchman-Schmitt, Jennifer M; Moberg, Fallon; Joiner, Thomas E

2016-02-01

Fear of negative evaluation has been documented as a mechanism that explains variations in feelings of belongingness. According to the interpersonal theory of suicide (Joiner, 2005), feelings of thwarted belongingness, that one does not belong, can significantly increase desire and risk for suicide. We proposed that differences in thwarted belongingness may explain variations in suicidal ideation and behavior as a function of levels of fear of negative evaluation. This hypothesis was tested by examining self-reported fears of negative evaluation, thwarted belongingness, and suicidal ideation in 107 young adults, many who were explicitly targeted for recruitment due to a history of suicidal ideation and behavior (13.1% had thoughts about suicide without a previous attempt; 15.9% reported at least one previous attempt [max = 5 attempts]). Mediation analyses were conducted with suicidal ideation entered as the outcome variable. Results indicated that greater fears of negative evaluation were significantly and positively associated with levels of suicidal ideation. Differences in thwarted belongingness fully accounted for the relationship between fears of negative evaluation and suicidal ideation. We conclude with clinical implications and future directions.

Rumination, Suicidal Ideation, and the Mediating Effect of Self-Defeating Humor

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Raymond P. Tucker

2014-08-01

Full Text Available Research has demonstrated that a self-defeating humor style is related to indicators of psychopathology and interpersonal dysfunction, including depression, anxiety, loneliness, thwarted belongingness, and perceived burdensomeness. The current study continued this investigation by examining how self-defeating humor is related to suicidal ideation and a ruminative response style. Analyses indicated that a self-defeating humor style was positively associated to rumination, brooding, reflection, and suicidal ideation. Results of bootstrapping analyses indicated that self-defeating humor mediated the relationship between rumination and suicidal ideation. This same effect was seen for both brooding and reflection individually. Results indicate that self-defeating humor may serve as an interpersonal means of ruminating as this humor style involves consistent focus on perceived flaws and weaknesses. The assessment of this humor style may provide additional information about the maintenance of suicidal thinking.

Suicide attempts in children and adolescents: The place of clock genes and early rhythm dysfunction.

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Olliac, Bertrand; Ouss, Lisa; Charrier, Annaëlle

2016-11-01

Suicide remains one of the leading causes of death among young people, and suicidal ideation and behavior are relatively common in healthy and clinical populations. Suicide risk in childhood and adolescence is often approached from the perspective of nosographic categories to which predictive variables for suicidal acts are often linked. The cascading effects resulting from altered clock genes in a pediatric population could participate in biological rhythm abnormalities and the emergence of suicide attempts through impaired regulation of circadian rhythms and emotional states with neurodevelopmental effects. Also, early trauma and stressful life events can alter the expression of clock genes and contribute to the emergence of suicide attempts. Alteration of clock genes might lead to desynchronized and abnormal circadian rhythms impairing in turn the synchronization between external and internal rhythms and therefore the adaptation of the individual to his/her internal and external environment with the development of psychiatric disorders associated with increased risk for suicide attempts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Does Perceived Social Support Mediate or Moderate the Relationship between Victimisation and Suicidal Ideation among Chinese Adolescents?

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Liu, Xiaoqun; Chen, Gui; Hu, Peng; Guo, Guipin; Xiao, Shuiyuan

2017-01-01

Bullying is a common problem in school. Engagement in bullying has been known to have many adverse effects, even including suicide. Examining which factor will moderate or mediate the pathway from victimisation to suicidal ideation is needed to develop effective intervention initiatives. This study aimed to examine the mediator and moderator roles…

Double suicide genes selectively kill human umbilical vein endothelial cells

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Liu Lunxu

2011-02-01

Full Text Available Abstract Background To construct a recombinant adenovirus containing CDglyTK double suicide genes and evaluate the killing effect of the double suicide genes driven by kinase domain insert containing receptor (KDR promoter on human umbilical vein endothelial cells. Methods Human KDR promoter, Escherichia coli (E. coli cytosine deaminase (CD gene and the herpes simplex virus-thymidine kinase (TK gene were cloned using polymerase chain reaction (PCR. Plasmid pKDR-CDglyTK was constructed with the KDR promoter and CDglyTK genes. A recombinant adenoviral plasmid AdKDR-CDglyTK was then constructed and transfected into 293 packaging cells to grow and harvest adenoviruses. KDR-expressing human umbilical vein endothelial cells (ECV304 and KDR-negative liver cancer cell line (HepG2 were infected with the recombinant adenoviruses at different multiplicity of infection (MOI. The infection rate was measured by green fluorescent protein (GFP expression. The infected cells were cultured in culture media containing different concentrations of prodrugs ganciclovir (GCV and/or 5-fluorocytosine (5-FC. The killing effects were measured using two different methods, i.e. annexin V-FITC staining and terminal transferase-mediated dUTP nick end-labeling (TUNEL staining. Results Recombinant adenoviruses AdKDR-CDglyTK were successfully constructed and they infected ECV304 and HepG2 cells efficiently. The infection rate was dependent on MOI of recombinant adenoviruses. ECV304 cells infected with AdKDR-CDglyTK were highly sensitive to GCV and 5-FC. The cell survival rate was dependent on both the concentration of the prodrugs and the MOI of recombinant adenoviruses. In contrast, there were no killing effects in the HepG2 cells. The combination of two prodrugs was much more effective in killing ECV304 cells than GCV or 5-FC alone. The growth of transgenic ECV304 cells was suppressed in the presence of prodrugs. Conclusion AdKDR-CDglyTK/double prodrog system may be a useful

Relationships between anhedonia, suicidal ideation and suicide attempts in a large sample of physicians.

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Gwenolé Loas

Full Text Available The relationships between anhedonia and suicidal ideation or suicide attempts were explored in a large sample of physicians using the interpersonal psychological theory of suicide. We tested two hypotheses: firstly, that there is a significant relationship between anhedonia and suicidality and, secondly, that anhedonia could mediate the relationships between suicidal ideation or suicide attempts and thwarted belongingness or perceived burdensomeness.In a cross-sectional study, 557 physicians filled out several questionnaires measuring suicide risk, depression, using the abridged version of the Beck Depression Inventory (BDI-13, and demographic and job-related information. Ratings of anhedonia, perceived burdensomeness and thwarted belongingness were then extracted from the BDI-13 and the other questionnaires.Significant relationships were found between anhedonia and suicidal ideation or suicide attempts, even when significant variables or covariates were taken into account and, in particular, depressive symptoms. Mediation analyses showed significant partial or complete mediations, where anhedonia mediated the relationships between suicidal ideation (lifetime or recent and perceived burdensomeness or thwarted belongingness. For suicide attempts, complete mediation was found only between anhedonia and thwarted belongingness. When the different components of anhedonia were taken into account, dissatisfaction-not the loss of interest or work inhibition-had significant relationships with suicidal ideation, whereas work inhibition had significant relationships with suicide attempts.Anhedonia and its component of dissatisfaction could be a risk factor for suicidal ideation and could mediate the relationship between suicidal ideation and perceived burdensomeness or thwarted belongingness in physicians. Dissatisfaction, in particular in the workplace, may be explored as a strong predictor of suicidal ideation in physicians.

[Effect of Adolescents' Abuse Experience on Suicidal Ideation: Focused on Moderated Mediation Effect of Self-esteem on Depression and Anxiety].

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Kim, Ji Young; Lee, Kyunghee

2015-10-01

The purpose of this study was to examine the moderating mediation effect of self-esteem on the relations among adolescents' abuse experiences, depression and anxiety, and suicidal ideation. The participants were selected using secondary data from a population in the 2012 Korea Welfare Panel Survey (KOWEPS). Data were analyzed using SPSS 15.0 and SPSS Macro, and bootstrapping and hierarchical regression analysis were performed to analyze multilevel models. First, analysis of the mediating effect of the adolescents' abuse showed that there was significant mediating influence between suicidal ideation and depression and anxiety. Second, hierarchical regression analysis showed that self-esteem had significant mediation effect on depression and anxiety in adolescents' suicidal ideation. Third, SPSS Macro showed that self-esteem also significantly moderated the mediating effect of adolescents' abuse experiences on suicidal ideation through depression and anxiety. The study results suggest that in future research on adolescent's abuse experience, the risk of suicide in depression and anxiety scores should be selected through evaluation of each individual's self-esteem scale. Coping strategies with immediate early intervention should be suggested.

Gene environment interaction studies in depression and suicidal behavior: An update.

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Mandelli, Laura; Serretti, Alessandro

2013-12-01

Increasing evidence supports the involvement of both heritable and environmental risk factors in major depression (MD) and suicidal behavior (SB). Studies investigating gene-environment interaction (G × E) may be useful for elucidating the role of biological mechanisms in the risk for mental disorders. In the present paper, we review the literature regarding the interaction between genes modulating brain functions and stressful life events in the etiology of MD and SB and discuss their potential added benefit compared to genetic studies only. Within the context of G × E investigation, thus far, only a few reliable results have been obtained, although some genes have consistently shown interactive effects with environmental risk in MD and, to a lesser extent, in SB. Further investigation is required to disentangle the direct and mediated effects that are common or specific to MD and SB. Since traditional G × E studies overall suffer from important methodological limitations, further effort is required to develop novel methodological strategies with an interdisciplinary approach. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Relationship Between Regulatory Emotional Self-Efficacy and Core Self-Evaluation of College Students: The Mediation Effects of Suicidal Attitude

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Zhao, Xiaojun; Shi, Changxiu

2018-01-01

This study analyzed the mediation effect of a suicidal attitude from regulatory emotional self-efficacy to core self-evaluation. A measurement study was conducted among 438 college students using the Regulatory Emotional Self-Efficacy Scale, the Core Self-Evaluation Scale, and the Suicide Attitude Questionnaire. Results from the plug-in process in SPSS and the bootstrap method showed that the attitude toward suicidal behavior and the attitude toward family members of an individual who has committed suicide played a double-mediation role, from perceived self-efficacy in managing happiness to core self-evaluation. The results also showed that the attitude toward a person who committed suicide or attempted suicide played a mediation effect from perceived self-efficacy in managing curiousness to core self-evaluation. This research has great significance for improving the understanding of college students’ sense of happiness and prevention for self-evaluation. PMID:29740378

The Relationship Between Regulatory Emotional Self-Efficacy and Core Self-Evaluation of College Students: The Mediation Effects of Suicidal Attitude.

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Zhao, Xiaojun; Shi, Changxiu

2018-01-01

This study analyzed the mediation effect of a suicidal attitude from regulatory emotional self-efficacy to core self-evaluation. A measurement study was conducted among 438 college students using the Regulatory Emotional Self-Efficacy Scale, the Core Self-Evaluation Scale, and the Suicide Attitude Questionnaire. Results from the plug-in process in SPSS and the bootstrap method showed that the attitude toward suicidal behavior and the attitude toward family members of an individual who has committed suicide played a double-mediation role, from perceived self-efficacy in managing happiness to core self-evaluation. The results also showed that the attitude toward a person who committed suicide or attempted suicide played a mediation effect from perceived self-efficacy in managing curiousness to core self-evaluation. This research has great significance for improving the understanding of college students' sense of happiness and prevention for self-evaluation.

Relationships between anhedonia, suicidal ideation and suicide attempts in a large sample of physicians

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Lefebvre, Guillaume; Rotsaert, Marianne; Englert, Yvon

2018-01-01

Background The relationships between anhedonia and suicidal ideation or suicide attempts were explored in a large sample of physicians using the interpersonal psychological theory of suicide. We tested two hypotheses: firstly, that there is a significant relationship between anhedonia and suicidality and, secondly, that anhedonia could mediate the relationships between suicidal ideation or suicide attempts and thwarted belongingness or perceived burdensomeness. Methods In a cross-sectional study, 557 physicians filled out several questionnaires measuring suicide risk, depression, using the abridged version of the Beck Depression Inventory (BDI-13), and demographic and job-related information. Ratings of anhedonia, perceived burdensomeness and thwarted belongingness were then extracted from the BDI-13 and the other questionnaires. Results Significant relationships were found between anhedonia and suicidal ideation or suicide attempts, even when significant variables or covariates were taken into account and, in particular, depressive symptoms. Mediation analyses showed significant partial or complete mediations, where anhedonia mediated the relationships between suicidal ideation (lifetime or recent) and perceived burdensomeness or thwarted belongingness. For suicide attempts, complete mediation was found only between anhedonia and thwarted belongingness. When the different components of anhedonia were taken into account, dissatisfaction—not the loss of interest or work inhibition—had significant relationships with suicidal ideation, whereas work inhibition had significant relationships with suicide attempts. Conclusions Anhedonia and its component of dissatisfaction could be a risk factor for suicidal ideation and could mediate the relationship between suicidal ideation and perceived burdensomeness or thwarted belongingness in physicians. Dissatisfaction, in particular in the workplace, may be explored as a strong predictor of suicidal ideation in physicians

Anti-tumor effect of adenovirus-mediated suicide gene therapy under control of tumor-specific and radio-inducible chimeric promoter in combination with γ-ray irradiation in vivo

International Nuclear Information System (INIS)

Sun Wenjie; Yu Haijun; Xiongjie; Xu Yu; Liao Zhengkai; Zhou Fuxiang; Xie Conghua; Zhou Yunfeng

2011-01-01

Objective: To detect the selective inhibitory effects of irradiation plus adenovirus-mediated horseradish peroxidase (HRP)/indole-3-acetic acid (IAA) suicide gene system using tumor-specific and radio-inducible chimeric promoter on human hepatocellular carcinoma subcutaneously xenografted in nude mouse. Methods: Recombinant replicated-deficient adenovirus vector containing HRP gene and chimeric human telomerase reverse transcriptase (hTERT) promoter carrying 6 radio-inducible CArG elements was constructed. A human subcutaneous transplanting hepatocellular carcinoma (MHCC97 cell line) model was treated with γ-ray irradiation plus intra-tumor injections of adenoviral vector and intra-peritoneal injections of prodrug IAA. The change of tumor volume and tumor growth inhibiting rate, the survival time of nude mice, as well as histopathology of xenograft tumor and normal tissues were evaluated. Results: Thirty one days after the treatment, the relative tumor volumes in the negative, adenovirus therapy, irradiation, and combination groups were 49.23±4.55, 27.71±7.74, 28.53±10.48 and 11.58±3.23, respectively.There was a significantly statistical difference among them (F=16.288, P<0.01).The inhibition effect in the combination group was strongest as compared with that in other groups, and its inhibition ratio was 76.5%. The survival period extended to 43 d in the combination group, which showed a significantly difference with that in the control group (χ 2 =18.307, P<0.01). The area of tumors necrosis in the combination group was larger than that in the other groups, and the normal tissues showed no treatment-related toxic effect in all groups. However, multiple hepatocellular carcinoma metastases were observed in the liver in the control group, there were a few metastases in the monotherapy groups and no metastasis in the combination group. Conclusions: Adenovirus-mediated suicide gene therapy plus radiotherapy dramatically could inhibit tumor growth and prolong

Analysis of Kinase Gene Expression in the Frontal Cortex of Suicide Victims: Implications of Fear and Stress

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Kwang eChoi

2011-07-01

Full Text Available Suicide is a serious public health issue that results from an interaction between multiple risk factors including individual vulnerabilities to complex feelings of hopelessness, fear and stress. Although kinase genes have been implicated in fear and stress, including the consolidation and extinction of fearful memories, expression profiles of those genes in the brain of suicide victims are less clear. Using gene expression microarray data from the Online Stanley Genomics Database (www.stanleygenomics.org and a quantitative PCR, we investigated the expression profiles of multiple kinase genes including the calcium calmodulin-dependent kinase (CAMK, the cyclin-dependent kinase (CDK, the mitogen-activated protein kinase (MAPK, and the protein kinase C (PKC in the prefrontal cortex (PFC of mood disorder patients died with suicide (n=45 and without suicide (N=38. We also investigated the expression pattern of the same genes in the PFC of developing humans ranging in age from birth to 49 year (n=46. The expression levels of CAMK2B, CDK5, MAPK9, and PRKCI were increased in the PFC of suicide victims as compared to non-suicide controls (FDR-adjusted p < 0.05, fold change > 1.1. Those genes also showed changes in expression pattern during the postnatal development (FDR-adjusted p < 0.05. These results suggest that multiple kinase genes undergo age-dependent changes in normal brains as well as pathological changes in suicide brains. These findings may provide an important link to protein kinases known to be important for the development of fear memory, stress-associated neural plasticity and up-regulation in the PFC of suicide victims. More research is needed to better understand the functional role of these kinase genes that may be associated with the pathophysiology of suicide.

Prefrontal alterations in GABAergic and glutamatergic gene expression in relation to depression and suicide.

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Zhao, Juan; Verwer, R.W.H.; Gao, S.; Qi, Xin-Rui; Lucassen, P.J.; Kessels, H.W.; Swaab, D.F.

2018-01-01

People that committed suicide were reported to have enhanced levels of gene transcripts for synaptic proteins in their prefrontal cortex (PFC). Given the close association of suicide with major depressive disorder (MDD), we here assessed whether these changes are related to suicide or rather to

Prefrontal alterations in GABAergic and glutamatergic gene expression in relation to depression and suicide

NARCIS (Netherlands)

Zhao, J.; Verwer, R.W.H.; Gao, S.-F.; Qi, X.-R.; Lucassen, P.J.; Kessels, H.W.; Swaab, D.F.

People that committed suicide were reported to have enhanced levels of gene transcripts for synaptic proteins in their prefrontal cortex (PFC). Given the close association of suicide with major depressive disorder (MDD), we here assessed whether these changes are related to suicide or rather to

An association study of suicide and candidate genes in the serotonergic system

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Buttenschøn, Henriette N; Flint, Tracey J; Foldager, Leslie

2013-01-01

Introduction: Strong evidence demonstrates a genetic susceptibility to suicidal behaviour and a relationship between suicide and mental disorders. The aim of this study was to test for association between suicide and five selected genetic variants, which had shown association with suicide in other...... populations. Method: We performed a nationwide case-control study on all suicide cases sent for autopsy in Denmark between the years 2000 and 2007. The study comprised 572 cases and 1049 controls and is one of the largest genetic studies in completed suicide to date. The analysed markers were located within...... the Serotonin Transporter (SLC6A4), Monoamine Oxidase-A (MAOA) and the Ttyptophan Hydroxylase I and II (TPH1 and TPH2) genes. Results: None of the genetic markers within SLC6A4, MAOA, TPH1 and TPH2 were significantly associated with completed suicide or suicide method in the basic association tests. Exploratory...

A Multiple Mediational Test of the Relationship between Childhood Maltreatment and Non-Suicidal Self-Injury

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Shenk, Chad E.; Noll, Jennie G.; Cassarly, Jennifer A.

2010-01-01

Post-traumatic stress symptoms, depressive symptoms, and psychological dysregulation have been shown to mediate the relationship between child maltreatment and non-suicidal self-injury. However, these proposed mediators often co-occur and previous research has not tested mediation when all variables are assessed simultaneously. The current study…

Problem-Solving Skills and Suicidal Ideation Among Malaysian College Students: the Mediating Role of Hopelessness.

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Abdollahi, Abbas; Talib, Mansor Abu; Yaacob, Siti Nor; Ismail, Zanariah

2016-04-01

Recent evidence suggests that suicidal ideation has increased among Malaysian college students over the past two decades; therefore, it is essential to increase our knowledge concerning the etiology of suicidal ideation among Malaysian college students. This study was conducted to examine the relationships between problem-solving skills, hopelessness, and suicidal ideation among Malaysian college students. The participants included 500 undergraduate students from two Malaysian public universities who completed the self-report questionnaires. Structural equation modeling estimated that college students with poor problem-solving confidence, external personal control of emotion, and avoiding style were more likely to report suicidal ideation. Hopelessness partially mediated the relationship between problem-solving skills and suicidal ideation. These findings reinforce the importance of poor problem-solving skills and hopelessness as risk factors for suicidal ideation among college students.

Understanding the Links Between Self-Report Emotional Intelligence and Suicide Risk: Does Psychological Distress Mediate This Relationship Across Time and Samples?

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Sergio Mérida-López

2018-05-01

Full Text Available Objective: In the last decades, increasing attention has been paid to examining psychological resources that might contribute to our understanding of suicide risk. Although Emotional Intelligence (EI is one dimension that has been linked with decreased suicidal ideation and behaviors, we detected several gaps in the literature in this area regarding the research designs and samples involved. In this research, we aimed to test a mediator model considering self-report EI, psychological distress and suicide risk across samples adopting both cross-sectional and prospective designs in two independent studies.Method: In Study 1, our purpose was to examine the potential role of psychological distress as a mediator in the relationship between self-report EI and suicide risk in a community sample comprised of 438 adults (270 women; mean age: 33.21 years. In Study 2, we sought to examine the proposed mediator model considering a 2-month prospective design in a sample of college students (n = 330 in T1; n = 311 in T2; 264 women; mean age: 22.22 years.Results: In Study 1, we found that psychological distress partially mediated the effect of self-report EI on suicide risk. More interestingly, findings from Study 2 showed that psychological distress fully mediated the relationship between self-report EI and suicide risk at Time 2.Conclusion: These results point out the role of psychological distress as a mediator in the association between self-report EI and suicide risk. These findings suggest an underlying process by which self-report EI may act as a protective factor against suicidal ideation and behaviors. In line with the limitations of our work, plausible avenues for future research and interventions are discussed.

The combination of suicide gene therapy and radiation enhances the killing of nasopharyngeal carcinoma xenographs

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Xia Jiahui; Xia Kun; Feng Yong

2004-01-01

Nasopharyngeal carcinoma (NPC) is very common in Southern China and Southeast Asian countries. To explore a novel and more effective approach to NPC therapy, a combined strategy of suicide genes and radiation was designed in this study. Five suicide gene expression cassettes, yeast cytosine deaminase (CD), yeast CD/uracil phosphoribosyl-transferase (UPRT), and yeast CDglyTK gene controlled by CMV, and Egr-1 and a synthetic CMV-enhanced Egr-1 promoter (CE) were constructed in an expression vector p11MS. The expression of suicide genes in NPC CNE-2 cells were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. The cytotoxicity of suicide gene therapy and radiation were analyzed by MTT assay. An animal study in which yeast CD/UPRT-expressing CNE-2 tumors in nude mice were treated with 5-fluorocytosine (5-FC) and radiation was also developed. Our results revealed that p11MSCEyCD/UPRT and p11MSCEyCDglyTK are superior over three other constructs in the killing of NPC cells in vitro. We combined suicide gene-expressing tumors, 5-FC treatment, and radiation in vivo and found that the tumors greatly regressed, some disappeared completely in 3 nude mice in the yCD/UPRT group, and a significant difference of tumor volumes was observed between this group and the other four groups (p<0.05). Our results indicated that suicide gene therapy and radiation have a synergic effect on NPC therapy, and the combined strategy of radiogene therapy is of great potential as a substitute for the traditional method, radiation alone, in NPC therapies. (author)

Suicidal gene therapy with rabbit cytochrome P450 4B1/4-ipomeanol, 2-aminoanthracene system in glioma cell

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Jang, Su Jin; Kang, Joo Hyun; Kim, Kwang Il; Lee, Tae Sup; Lee, Yong Jin; Woo, Kwang Sun; Chung, Wee Sup; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo

2010-01-01

Suicidal gene therapy is based on the transduction of tumor cells with 'suicide' genes encoding for prodrugactivating enzymes that render target cells susceptible to prodrug treatment. Suicidal gene therapy results in the death of tumor with the expression of gene encoding enzyme that converts non-toxic prodrug into cytotoxic product. Cytochrome P450 4B1 (CYP4B1) activates 4- ipomeanol (4-ipo) and 2-aminoanthracene (2-AA) to cytotoxic furane epoxide and unsaturated dialdehyde intermediate. In this study, therapeutic effects of suicidal gene therapy with rabbit CYP4B1/4-ipo or CYP4B1/2-AA system

Sports participation as a protective factor against depression and suicidal ideation in adolescents as mediated by self-esteem and social support.

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Babiss, Lindsay A; Gangwisch, James E

2009-10-01

Participation in sports has been shown to be protective against depression and suicidal ideation, but little is known about what factors mediate these relationships. No previous studies examined potential mediators between sports participation and suicidal ideation and only one study explored possible mediators between sports participation and depression. Increased sports participation could protect against depression and suicidal ideation by increasing endogenous endorphin levels, boosting self-esteem, improving body image, increasing social support, and affecting substance abuse. Multivariate hierarchical logistic regression analyses of Add Health data to explore whether increased participation in sports (none, 1-2, 3-4, or 5 or more times per week) is associated with depression and suicidal ideation and whether exercise, self-esteem, body weight, social support, and substance abuse mediate these relationships. As sports participation increases, the odds of suffering from depression decreases by 25% (OR: 0.75; 95% CI: 0.70-0.82) and the odds of having suicidal ideation decreases by 12% (OR: 0.88; 95% CI: 0.83-0.93) after controlling for sex, age, race/ethnicity, public assistance, and physical limitations. Substance abuse, body weight, and exercise did not mediate these associations. Consistent with self-esteem and social support acting as mediators of these relationships, the inclusion of these variables in the multivariate models attenuated the associations for depression (OR: 0.83; 95% CI: 0.75-0.91) and suicidal ideation (OR: 0.93; 95% CI: 0.88-0.99). Adolescents should be offered ample opportunity and encouragement to participate in sports, which can protect against depression and suicidal ideation by boosting self-esteem and increasing social support.

A national cohort study of parental socioeconomic status and non-fatal suicidal behaviour-the mediating role of school performance

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Jablonska Beata

2012-01-01

Full Text Available Abstract Background A link between low parental socioeconomic status and mental health problems in offspring is well established in previous research. The mechanisms that explain this link are largely unknown. The present study investigated whether school performance was a mediating and/or moderating factor in the path between parental socioeconomic status and the risk of hospital admission for non-fatal suicidal behaviour. Methods A national cohort of 447 929 children born during 1973-1977 was followed prospectively in the National Patient Discharge Register from the end of their ninth and final year of compulsory school until 2001. Multivariate Cox proportional hazards and linear regression analyses were performed to test whether the association between parental socioeconomic status and non-fatal suicidal behaviour was mediated or moderated by school performance. Results The results of a series of multiple regression analyses, adjusted for demographic variables, revealed that school performance was as an important mediator in the relationship between parental socioeconomic status and risk of non-fatal suicidal behaviour, accounting for 60% of the variance. The hypothesized moderation of parental socioeconomic status-non-fatal suicidal behaviour relationship by school performance was not supported. Conclusions School performance is an important mediator through which parental socioeconomic status translates into a risk for non-fatal suicidal behaviour. Prevention efforts aimed to reduce socioeconomic inequalities in non-fatal suicidal behaviour among young people will need to consider socioeconomic inequalities in school performance.

Evidence of Multiple Mediating Pathways in Associations Between Constructs of Stigma and Self-Reported Suicide Attempts in a Cross-Sectional Study of Gay and Bisexual Men.

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Salway, Travis; Gesink, Dionne; Ibrahim, Selahadin; Ferlatte, Olivier; Rhodes, Anne E; Brennan, David J; Marchand, Rick; Trussler, Terry

2018-05-01

Gay and bisexual men (GBM) are more likely to attempt suicide than heterosexual men. This disparity is commonly interpreted using minority stress theory; however, specific pathways from antigay stigma to suicidal behavior are poorly understood. We aimed to estimate associations between multiple constructs of stigma and suicide attempts among adult GBM, and to measure the proportion of these associations mediated by distinct suicide risk factors, thus identifying proximal points of intervention. Data were drawn from a Canadian community-based survey of adult GBM. Structural equation modeling was used to compare associations between three latent constructs-enacted stigma (e.g., discrimination, harassment), anticipated prejudice (worry about encountering antigay/bisexual prejudice), and sexuality concealment-and self-reported suicide attempts (last 12 months). Coefficients were estimated for direct, indirect, and total pathways and evaluated based on magnitude and statistical significance. The proportion of associations mediated by depression, drug/alcohol use, and social isolation was calculated using indirect paths. Among 7872 respondents, 3.4% reported a suicide attempt in the past 12 months. The largest total association was observed for enacted stigma, and this association was partially mediated by depression and drug/alcohol use. The total association of anticipated prejudice was relatively smaller and mediated by depression and social isolation. Concealment had an inverse association with suicide attempts as mediated by depression but was also positively associated with suicide attempts when mediated through social isolation. Multiple constructs of antigay stigma were associated with suicide attempts; however, mediating pathways differed by construct, suggesting that a combination of strategies is required to prevent suicide in adult GBM.

Effect of perceived organizational support on suicidal ideation of young employees: The mediator role of self-esteem.

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Sang, Jinyan; Ji, Yongbao; Li, Ping; Zhao, Hao

2017-09-01

This study aimed to explore the relationships among perceived organizational support, self-esteem, and suicidal ideation of young employees. A total of 447 unmarried employees completed the survey of perceived organizational support, Rosenberg self-esteem scale, and suicide ideation scale. The results revealed that perceived organizational support, self-esteem, and suicidal ideation were significantly correlated with each other. Stepwise regression analysis and path analysis both indicated that self-esteem partially mediated the effect of perceived organizational support on suicidal ideation.

Multimarker analysis suggests the involvement of BDNF signaling and microRNA biosynthesis in suicidal behavior.

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Pulay, Attila J; Réthelyi, János M

2016-09-01

Despite moderate heritability estimates the genetics of suicidal behavior remains unclear, genome-wide association and candidate gene studies focusing on single nucleotide associations reported inconsistent findings. Our study explored biologically informed, multimarker candidate gene associations with suicidal behavior in mood disorders. We analyzed the GAIN Whole Genome Association Study of Bipolar Disorder version 3 (n = 999, suicidal n = 358) and the GAIN Major Depression: Stage 1 Genomewide Association in Population-Based Samples (n = 1,753, suicidal n = 245) datasets. Suicidal behavior was defined as severe suicidal ideation or attempt. Candidate genes were selected based on literature search (Geneset1, n = 35), gene expression data of microRNA genes, (Geneset2, n = 68) and their target genes (Geneset3, n = 11,259). Quality control, dosage analyses were carried out with PLINK. Gene-based associations of Geneset1 were analyzed with KGG. Polygenic profile scores of suicidal behavior were computed in the major depression dataset both with PRSice and LDpred and validated in the bipolar disorder data. Several nominally significant gene-based associations were detected, but only DICER1 associated with suicidal behavior in both samples, while only the associations of NTRK2 in the depression sample reached family wise and experiment wise significance. Polygenic profile scores negatively predicted suicidal behavior in the bipolar sample for only Geneset2, with the strongest prediction by PRSice at Pt  suicide and the cross-disorder association of DICER1. Polygenic risk prediction of the selected miRNA genes indicates that the miRNA system may play a mediating role, but with considerable pleiotropy. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Suicidal gene therapy with rabbit cytochrome P450 4B1/4-ipomeanol, 2-aminoanthracene system in glioma cell

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Jang, Su Jin; Kang, Joo Hyun; Kim, Kwang Il; Lee, Tae Sup; Lee, Yong Jin; Woo, Kwang Sun; Chung, Wee Sup; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2010-10-15

Suicidal gene therapy is based on the transduction of tumor cells with 'suicide' genes encoding for prodrugactivating enzymes that render target cells susceptible to prodrug treatment. Suicidal gene therapy results in the death of tumor with the expression of gene encoding enzyme that converts non-toxic prodrug into cytotoxic product. Cytochrome P450 4B1 (CYP4B1) activates 4- ipomeanol (4-ipo) and 2-aminoanthracene (2-AA) to cytotoxic furane epoxide and unsaturated dialdehyde intermediate. In this study, therapeutic effects of suicidal gene therapy with rabbit CYP4B1/4-ipo or CYP4B1/2-AA system

What Accounts for the Relationship Between Internet Use and Suicidal Ideation of Korean Older Adults? A Mediation Analysis.

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Jun, Hey Jung; Kim, Myoung-Yong

2017-09-01

This study sought to examine the relationship between Internet use and suicidal ideation in Korean older adults and the mediating roles of social relationships and depressive symptoms. A nationally representative sample of older adults aged 50 or older (N = 6,306), from four waves of the Korean Welfare Panel Study, was used in the analyses. All analyses were conducted using generalized estimation equations, and the mediation effects of social relationship satisfaction and depression in the relationship between Internet use and suicidal ideation were calculated using the product-of-coefficients approach. Internet use was linked with lower levels of suicidal ideation directly and indirectly via the protective effects of Internet use on lowering depression, which was partially mediated by the positive influence Internet use has on older adults' social relationship satisfaction. The results support previous theories about the relationship between social relationships, depression, and suicidal behavior and prior results about how the Internet might confer mental and social health benefits to older adults. This suggests that the Internet is an important social and health activity that contributes to lowering suicidal ideation in older adults. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Application of HSVtk suicide gene to X-SCID gene therapy: Ganciclovir treatment offsets gene corrected X-SCID B cells

International Nuclear Information System (INIS)

Uchiyama, Toru; Kumaki, Satoru; Ishikawa, Yoshinori; Onodera, Masafumi; Sato, Miki; Du, Wei; Sasahara, Yoji; Tanaka, Nobuyuki; Sugamura, Kazuo; Tsuchiya, Shigeru

2006-01-01

Recently, a serious adverse effect of uncontrolled clonal T cell proliferation due to insertional mutagenesis of retroviral vector was reported in X-SCID gene therapy clinical trial. To offset the side effect, we have incorporated a suicide gene into therapeutic retroviral vector for selective elimination of transduced cells. In this study, B-cell lines from two X-SCID patients were transduced with bicistronic retroviral vector carrying human γc chain cDNA and Herpes simplex virus thymidine kinase gene. After confirmation of functional reconstitution of the γc chain, the cells were treated with ganciclovir (GCV). The γc chain positive cells were eliminated under low concentration without cytotoxicity on untransduced cells and have not reappeared at least for 5 months. Furthermore, the γc chain transduced cells were still sensitive to GCV after five months. These results demonstrated the efficacy of the suicide gene therapy although further in vivo studies are required to assess feasibility of this approach in clinical trial

Efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in combination with radiation therapy in an orthotopic mouse prostate cancer model

International Nuclear Information System (INIS)

Freytag, Svend O.; Paielli, Dell; Wing, Mark; Rogulski, Ken; Brown, Steve; Kolozsvary, Andy; Seely, John; Barton, Ken; Dragovic, Alek; Kim, Jae Ho

2002-01-01

Purpose: The purpose of this study was to evaluate the efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in an adjuvant setting with external beam radiation therapy (EBRT) in an experimental prostate cancer model in preparation for a Phase I clinical study in humans. Methods: For efficacy studies, i.m. DU145 and intraprostatic LNCaP C4-2 tumors were established in immune-deficient mice. Tumors were injected with the lytic, replication-competent Ad5-CD/TKrep adenovirus containing a cytosine deaminase (CD)/herpes simplex virus thymidine kinase (HSV-1 TK) fusion gene. Two days later, mice were administered 1 week of 5-fluorocytosine + ganciclovir (GCV) prodrug therapy and fractionated doses of EBRT (trimodal therapy). Tumor control rate of trimodal therapy was compared to that of EBRT alone. For toxicology studies, immune-competent male mice received a single intraprostatic injection (10 10 vp) of the replication-competent Ad5-CD/TKrep adenovirus. Two days later, mice were administered 4 weeks of 5-fluorocytosine + GCV prodrug therapy and 56 Gy EBRT to the pelvic region. The toxicity of trimodal therapy was assessed by histopathologic analysis of major organs and clinical chemistries. Results: In both the i.m. DU145 and intraprostatic LNCaP C4-2 tumor models, trimodal therapy significantly improved primary tumor control beyond that of EBRT alone. In the DU145 model, trimodal therapy resulted in a tumor growth delay (70 days) that was more than twice that (32 days) of EBRT alone. Whereas EBRT failed to eradicate DU145 tumors, trimodal therapy resulted in 25% tumor cure. In the LNCaP C4-2 tumor model, EBRT slowed the growth of intraprostatic tumors, but resulted in no tumor cures, and 57% of the mice developed retroperitoneal lymph node metastases at 3 months. By contrast, trimodal therapy resulted in 44% tumor cure and reduced significantly the percentage (13%) of lymph node metastases relative to EBRT alone. Overall

Mediating suicide: print journalism and the categorization of queer youth suicide discourses.

Science.gov (United States)

Cover, Rob

2012-10-01

This article undertakes textual analysis to examine some of the ways in which knowledge around sexuality-related youth suicide and its causes are produced and made available through news media discourses and news-making processes. Four categories of sexuality-related suicide discourses were identified in news stories and features over the past 20 years: statistical research that makes non-heterosexuality implicit as a cause of suicide; stories about deviancy,guilt, and shame; suicide survivor stories; and bullying/harassment of non-heterosexual persons by individuals in schools and other institutions as suicide cause. Through processes of news production and meaning-making, use of expert opinions of primary definers, experiential accounts, reliance on citations of quantitative data, private accounts given as entertainment, and the newsworthiness of suicide as drama, public knowledge on queer youth suicide is guided by contemporary journalism. In all cases, the underlying relationship between heteronormativity, mental health, depression, and despair were frequently excluded in news journalism on queer youth suicide.

Social relationships, depressive symptoms and suicidality in Korea: Examining mediating and moderating effects in men and women.

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Lee, Min-Ah

2016-02-01

It has been widely recognized that social relationships and depressive symptoms predict suicidality. However, there are few empirical studies examining relationships among these three factors using an integrative approach. This study aimed to examine the effects of perceived quality of social relationships and depressive symptoms on suicidality and to analyze whether the effect of perceived quality of social relationships on suicidality is mediated by depressive symptoms or whether the perceived quality of social relationships has a moderating effect on the relationship between depressive symptoms and suicidality in men and women. The data were drawn from the 2012 Korean General Social Survey, a nationally representative survey. Multiple regression models and subsample analyses were conducted according to gender. A higher perceived quality of social relationships decreased suicidality while depressive symptoms increased suicidality. The effect of perceived quality of social relationships was partially mediated by depressive symptoms. Perceived quality of social relationships also significantly interacted with depressive symptoms, suggesting that the harmful effect of depressive symptoms was ameliorated as perceived quality of social relationships increased. A subsample analysis according to gender, however, indicated a significant gender difference in that the perceived quality of social relationships moderated the effect of depressive symptoms only in women. The findings suggest that enhanced quality of social relationships can protect people from suicidal risk and are more effective for women with depressive symptoms than for men with the same symptoms. © The Author(s) 2015.

Relative social standing and suicide ideation among Kenyan males: the interpersonal theory of suicide in context.

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Goodman, M L; Serag, H; Keiser, P K; Gitari, S; Raimer, B G

2017-10-01

The purpose of this study is to investigate the association between subjective social status and suicide ideation in a sample of young Kenyan men (age 18-34 years). Situating insights from the interpersonal theory of suicide within social determinants of health framework, we consider whether lower subjective social status predicts lower collective self-esteem (CSE), hopelessness, less meaning in life and more loneliness, and whether these characteristics mediate associations between subjective social status and suicide ideation. A community-based, semi-rural sample (n = 532) of young men, aged 18-34 years, was collected using a standardized questionnaire. The survey questionnaire included the following validated scale items: the short form of the Social and Emotional Loneliness Scale for Adults, CSE, Herth Hope Index, the Meaning in Life Questionnaire, and the Modified Scale for Suicide Ideation. Regression and mediation analyses were used to test hypotheses. Nearly 12% of respondents reported suicide ideation. Suicide ideation was significantly more common among survey respondents who reported lower subjective social standing. In the first of two mediation models, we found that lower CSE and more loneliness mediate the association between lower subjective social status and suicide ideation. In the second model, we found that respondents with lower CSE and more loneliness expressed lower hope and meaning in life, which also mediated pathways to suicide ideation. Findings show a novel synthesis of social determinants literature with the interpersonal theory of suicide. Suicide ideation, along with other mental and social outcomes, may figure more prominently than previously appreciated in the benefits of socio-economic equality. Those who do not participate equally in socio-economic development may be at greater risk of engaging in suicide ideation and behaviors. Suicide prevention research and programmatic responses should adopt a health equity perspective to

Gene expression changes in the prefrontal cortex, anterior cingulate cortex and nucleus accumbens of mood disorders subjects that committed suicide.

Directory of Open Access Journals (Sweden)

Adolfo Sequeira

Full Text Available Suicidal behaviors are frequent in mood disorders patients but only a subset of them ever complete suicide. Understanding predisposing factors for suicidal behaviors in high risk populations is of major importance for the prevention and treatment of suicidal behaviors. The objective of this project was to investigate gene expression changes associated with suicide in brains of mood disorder patients by microarrays (Affymetrix HG-U133 Plus2.0 in the dorsolateral prefrontal cortex (DLPFC: 6 Non-suicides, 15 suicides, the anterior cingulate cortex (ACC: 6NS, 9S and the nucleus accumbens (NAcc: 8NS, 13S. ANCOVA was used to control for age, gender, pH and RNA degradation, with P ≤ 0.01 and fold change ± 1.25 as criteria for significance. Pathway analysis revealed serotonergic signaling alterations in the DLPFC and glucocorticoid signaling alterations in the ACC and NAcc. The gene with the lowest p-value in the DLPFC was the 5-HT2A gene, previously associated both with suicide and mood disorders. In the ACC 6 metallothionein genes were down-regulated in suicide (MT1E, MT1F, MT1G, MT1H, MT1X, MT2A and three were down-regulated in the NAcc (MT1F, MT1G, MT1H. Differential expression of selected genes was confirmed by qPCR, we confirmed the 5-HT2A alterations and the global down-regulation of members of the metallothionein subfamilies MT 1 and 2 in suicide completers. MTs 1 and 2 are neuro-protective following stress and glucocorticoid stimulations, suggesting that in suicide victims neuroprotective response to stress and cortisol may be diminished. Our results thus suggest that suicide-specific expression changes in mood disorders involve both glucocorticoids regulated metallothioneins and serotonergic signaling in different regions of the brain.

Gene expression changes in the prefrontal cortex, anterior cingulate cortex and nucleus accumbens of mood disorders subjects that committed suicide.

Science.gov (United States)

Sequeira, Adolfo; Morgan, Ling; Walsh, David M; Cartagena, Preston M; Choudary, Prabhakara; Li, Jun; Schatzberg, Alan F; Watson, Stanley J; Akil, Huda; Myers, Richard M; Jones, Edward G; Bunney, William E; Vawter, Marquis P

2012-01-01

Suicidal behaviors are frequent in mood disorders patients but only a subset of them ever complete suicide. Understanding predisposing factors for suicidal behaviors in high risk populations is of major importance for the prevention and treatment of suicidal behaviors. The objective of this project was to investigate gene expression changes associated with suicide in brains of mood disorder patients by microarrays (Affymetrix HG-U133 Plus2.0) in the dorsolateral prefrontal cortex (DLPFC: 6 Non-suicides, 15 suicides), the anterior cingulate cortex (ACC: 6NS, 9S) and the nucleus accumbens (NAcc: 8NS, 13S). ANCOVA was used to control for age, gender, pH and RNA degradation, with P ≤ 0.01 and fold change ± 1.25 as criteria for significance. Pathway analysis revealed serotonergic signaling alterations in the DLPFC and glucocorticoid signaling alterations in the ACC and NAcc. The gene with the lowest p-value in the DLPFC was the 5-HT2A gene, previously associated both with suicide and mood disorders. In the ACC 6 metallothionein genes were down-regulated in suicide (MT1E, MT1F, MT1G, MT1H, MT1X, MT2A) and three were down-regulated in the NAcc (MT1F, MT1G, MT1H). Differential expression of selected genes was confirmed by qPCR, we confirmed the 5-HT2A alterations and the global down-regulation of members of the metallothionein subfamilies MT 1 and 2 in suicide completers. MTs 1 and 2 are neuro-protective following stress and glucocorticoid stimulations, suggesting that in suicide victims neuroprotective response to stress and cortisol may be diminished. Our results thus suggest that suicide-specific expression changes in mood disorders involve both glucocorticoids regulated metallothioneins and serotonergic signaling in different regions of the brain.

Bisexual-Specific Minority Stressors, Psychological Distress, and Suicidality in Bisexual Individuals: the Mediating Role of Loneliness.

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Mereish, Ethan H; Katz-Wise, Sabra L; Woulfe, Julie

2017-08-01

Bisexual individuals are at higher risk for poor mental health outcomes compared to heterosexual as well as lesbian and gay individuals and experience minority stressors, such as discrimination, from both heterosexual and sexual minority communities. However, there is little research examining the negative effects of bisexual-specific minority stressors on bisexual individuals' mental health as well as psychological factors that might help explain minority stressors' deleterious effects. This research examined the effects of distal minority stressors (i.e., anti-bisexual experiences from both heterosexual as well as lesbian and gay people) and proximal stressors (i.e., internalized heterosexism and sexual orientation concealment) on psychological distress and suicidality among bisexual adults (N = 503). Building on the relational framing of the minority stress model, we also tested one relational factor (i.e., loneliness) as a mediator of the associations between distal and proximal minority stressors and poor mental health (i.e., psychological distress and suicidality). Structural equation modeling analyses were used to test the mediating effects of loneliness on the associations between minority stressors and psychological distress and suicidality. Although distal and proximal minority stressors were not associated with each other, loneliness mediated the effects of distal and proximal minority stressors on psychological distress and suicidality. The results of this study underscore the importance of targeting bisexual-specific minority stressors as well as loneliness in preventive interventions to improve the mental health of bisexual individuals.

Effect of suicidal gene combined with irradiation on esophageal carcinoma cell line

International Nuclear Information System (INIS)

Pan Jianji; Wang Jiezhong; Zheng Tianrong; Zheng Qiuhong

2005-01-01

Objective: As generally known that non-cytotoxic pro-drag can be transformed into cytotoxic drug by suicide gene, this work is to investigate the effect of Coli cytosine deaminase/5-fluorocytosine suicide gene (CD/5-FC) used alone or combined with irradiation in esophageal carcinoma cell line(EC). Methods: CD gene was amplified from Coli DNA genome library with PCR technique, with the eukaryotic vector pcDNA3.1-CD then constructed. ECl09 cells were transfected with pcDNA3.1-CD by liposome method. The cytotoxic effect, bystander effect and radiosensitization effect of CD/5-FC in ECl09 was analyzed. Results: The transfection of CD gene into ECl09 and its transcription was confirmed by RT-PCR method. In vitro, 5-FC showed significantly cytotoxic effect on the EPC cell transfected with CD gene. After adding 5-FC , the survival rate of cultured cell containing 5 % transfect CD gene cell was 41.8 % ± 14.2% while that in the control group was 94.6 ± 4.3 %, (t=3.14, P < 0.05). The survival rate of cultured cell containing 10% transfected CD gene cell was 37.8 ± 4.4% compared to 95.6% ± 5.4% in the control group, (t=9.75, P<0.01). CD/5-FC showed significant radiosen-sitization effect, the survival fraction of CD transfected cell was much lower in 5-FC combined with irradiation, when compared with 5-FC alone and radiotherapy alone group together, (F=11.50, P < 0.01 ). When it was compared with 5-FC alone group and irradiation alone group separately, the difference was also significant( F=4.11, P < 0.05 and F10.53, P < 0.01, respectively). Conclusions: Suicide gene CD/5-FC shows conspicuous by-stander effect and radiosensitization effect. (authors)

Association of Hormonal Contraception With Suicide Attempts and Suicides

DEFF Research Database (Denmark)

Skovlund, Charlotte Wessel; Mørch, Lina Steinrud; Kessing, Lars Vedel

2017-01-01

OBJECTIVE: The purpose of this study was to assess the relative risk of suicide attempt and suicide in users of hormonal contraception. METHOD: The authors assessed associations between hormonal contraceptive use and suicide attempt and suicide in a nationwide prospective cohort study of all women...... in Denmark who had no psychiatric diagnoses, antidepressant use, or hormonal contraceptive use before age 15 and who turned 15 during the study period, which extended from 1996 through 2013. Nationwide registers provided individually updated information about use of hormonal contraception, suicide attempt......, suicide, and potential confounding variables. Psychiatric diagnoses or antidepressant use during the study period were considered potential mediators between hormonal contraceptive use and risk of suicide attempt. Adjusted hazard ratios for suicide attempt and suicide were estimated for users of hormonal...

Rumination, Social Problem Solving and Suicide Intent Among Egyptians With a Recent Suicide Attempt.

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Sharaf, Amira Y; Lachine, Ola A; Thompson, Elaine A

2018-02-01

The more complex influences of social problem-solving abilities and rumination-specifically brooding and reflection-on suicide intent is not well understood. We hypothesized that social problem solving would moderate the association between reflection and suicide intent, and mediate the influence of brooding on suicide intent. A convenience sample (N=186) of individuals hospitalized for recent suicide attempt was interviewed, assessing suicide intent, social problem solving, brooding, reflection and depression. Brooding and reflection were positively associated with suicide intent. The mediating, but not the moderating, hypothesis was supported. Brooding was not significant (β=0.15, t=1.92, p=0.06) with social problem solving controlled. Interventions to disengage rumination and improve social problem-solving skills are underscored. Copyright © 2017 Elsevier Inc. All rights reserved.

Assisted suicide of a selfish gene.

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Thomson, M S; Beeman, R W

1999-01-01

Medea (M) factors and the hybrid incompatibility factor (H) are involved in two incompatibility systems in flour beetles that were previously thought to be independent. M factors are a novel class of selfish genes that act by maternal lethality to nonself. The H factor causes the death of hybrids with a paternally derived H gene and previously uncharacterized maternal cofactors. We now find that M factors exhibit their selfish behavior only in the absence of the H factor. Furthermore, we show that the previously uncharacterized maternal cofactors required for H-associated hybrid inviability are identical to M factors. We propose that incompatibility between H strains and M strains is due to suppression by the H factor of the self-rescuing activity of the lethal M genes. This interaction has the effect of converting M elements from selfish into self-destructive or "suicidal" genes. M factors are globally widespread, but are conspicuously absent from India, the only country where the H factor is known to occur. Such a mechanism could prevent the spread of selfish M elements by establishing an absolute barrier to hybridization in the boundary between M and non-M zones.

Mediating Tragedy: Facebook, Aboriginal Peoples and Suicide

Directory of Open Access Journals (Sweden)

Bronwyn Lee Carlson

2015-11-01

Full Text Available Some Australian Aboriginal communities experience suicide rates that are among the highest in the world. They are also, however, avid social media users—approximately 20% higher than the national average. This article presents some preliminary findings from a current national study, funded by the Australian Research Council, titled Aboriginal identity and community online: a sociological exploration of Aboriginal peoples’ use of online social media. The purpose of the study is to gain insights into how Aboriginal peoples utilise and interact on social media, and how these technologies can assist with suicide prevention strategies. It found that Aboriginal people are engaging with Facebook to both seek and offer help for issues relating to suicide and self-harm. An existing continuum of suicide prevention strategies was evident—from light emotional support to direct suicide intervention involving health services. These strategies can be leveraged to implement effective and appropriate suicide prevention programs.

Tolerance of suicide, religion and suicide rates : an ecological and individual study in 19 Western countries

NARCIS (Netherlands)

Neeleman, J; Halpern, D; Leon, D; Lewis, G

Background. Negative associations between religion and suicide, in individuals and countries, may be mediated by the degree to which suicide is tolerated. Methods. Linear regression was used to examine ecological associations between suicide tolerance, religion and suicide rates in 19 Western

Social anxiety symptoms and suicidal ideation in a clinical sample of early adolescents: examining loneliness and social support as longitudinal mediators.

Science.gov (United States)

Gallagher, Michelle; Prinstein, Mitchell J; Simon, Valerie; Spirito, Anthony

2014-08-01

Recent research has shown that social anxiety may be related to increased risk for suicidal ideation in teens, although this research largely has been cross-sectional and has not examined potential mediators of this relationship. A clinical sample of 144 early adolescents (72 % female; 12-15 years old) was assessed during psychiatric inpatient hospitalization and followed up at 9 and 18 months post-baseline. Symptoms of social anxiety, depression, suicidal ideation, loneliness, and perceived social support were assessed via structured interviews and self-report instruments. Structural equation modeling revealed a significant direct relationship between social anxiety symptoms at baseline and suicidal ideation at 18 months post-baseline, even after controlling for baseline depressive symptoms and ideation. A second multiple mediation model revealed that baseline social anxiety had a significant indirect effect on suicidal ideation at 18 months post-baseline through loneliness at 9 months post-baseline. Social anxiety did not have a significant indirect effect on suicidal ideation through perceived social support from either parents or close friends. Findings suggest that loneliness may be particularly implicated in the relationship between social anxiety and suicidality in teens. Clinicians should assess and address feelings of loneliness when treating socially anxious adolescents.

The mediating effects of depressive symptoms and sleep quality on the relationship between the non-medical use of prescription drugs and suicidal behaviors among Chinese adolescents.

Science.gov (United States)

Wang, Juan; Xu, Yan; Guo, Lan; Deng, Jian-Xiong; Huang, Jing-Hui; Huang, Guo-Liang; Gao, Xue; Wu, Hong; Pan, Si-Yuan; Lu, Ci-Yong

2017-09-01

The nature of the relationship between the non-medical use of prescription drugs (NMUPD) and suicide has not been clearly elucidated. Some studies have suggested that the relationship between substance use and suicidal ideation may be spurious and could be explained by other variables. A school-based cross-sectional study was performed in Guangzhou. A total of 5853 students completed questionnaires and were included in the study. NMUPD, alcohol use, illicit drug use, depressive symptoms, sleep quality, and suicidal behaviors were assessed. The mediating effects of depressive symptoms and sleep quality on the relationship between NMUPD and suicidal behaviors were examined using a structural equation model. In the simple model without mediation, a positive relationship between NMUPD and suicidal behaviors in adolescents was found, which was independent of effects from the use of other substances. Both depressive symptoms and sleep quality were significant mediators of this relationship. Public health and educational professionals should survey depressive symptoms and sleep quality and provide interventions when managing suicidal behaviors among adolescents engaging in NMUPD. Copyright © 2017 Elsevier B.V. All rights reserved.

Talking about suicide may not be enough: family reaction as a mediator between disclosure and interpersonal needs.

Science.gov (United States)

Frey, Laura M; Fulginiti, Anthony

2017-08-01

Although most people who make an attempt do not die, attempt survivors remain at particularly elevated risk for suicide in the short- and long-term. Moreover, the research on suicide-related disclosure and subsequent family reactions on risk factors for the development of suicidal desire is limited. This study examined the relationships between disclosure, family reaction and two interpersonal needs connected to the development of suicidal desire. Data from 74 attempt survivors who participated in a larger study were analyzed to assess the relationships between degree of suicide-related disclosure, quality of family reaction and thwarted belongingness and perceived burdensomeness. Results indicated that higher rates of disclosure predicted more positive family reactions, which in turn predicted lower levels of thwarted belongingness and perceived burdensomeness. Although there was no direct relationship between disclosure and the outcome variables, bootstrapping analyses indicated that family reaction mediated the relationship between disclosure and both belongingness and burdensomeness. These findings suggest the need for more family interventions that promote healthy reactions following suicide-related disclosure in order to facilitate the recovery and treatment process.

Adverse Childhood Experiences and Suicide Attempts: The Mediating Influence of Personality Development and Problem Behaviors.

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Perez, Nicholas M; Jennings, Wesley G; Piquero, Alex R; Baglivio, Michael T

2016-08-01

Adverse childhood experiences, comprised of forms of maltreatment and certain dysfunctional household environments, can affect the development of a child in a variety of different ways. This multitude of developmental changes may subsequently produce compounding harmful effects on the child's life and increase acutely maladaptive outcomes, including adolescent suicidal behavior. This study uses data collected from 2007 to 2012 for 64,329 Florida Department of Juvenile Justice youth (21.67 % female, 42.88 % African American, and 15.37 % Hispanic) to examine the direct and indirect effects of adverse childhood experiences on suicide attempts. Using a generalized structural equation model, the effects of adverse childhood experience scores are estimated on suicidal behavior through pathways of certain aspects of a child's personality development (aggression and impulsivity), as well as adolescent problem behaviors (school difficulties and substance abuse). The results show that a large proportion of the relationship between childhood adversity and suicide is mediated by the aforementioned individual characteristics, specifically through the youth's maladaptive personality development. These results suggest that, if identified early enough, the developmental issues for these youth could potentially be addressed in order to thwart potential suicidal behavior.

Childhood adversity and midlife suicidal ideation.

Science.gov (United States)

Stansfeld, S A; Clark, C; Smuk, M; Power, C; Davidson, T; Rodgers, B

2017-01-01

Childhood adversity predicts adolescent suicidal ideation but there are few studies examining whether the risk of childhood adversity extends to suicidal ideation in midlife. We hypothesized that childhood adversity predicts midlife suicidal ideation and this is partially mediated by adolescent internalizing disorders, externalizing disorders and adult exposure to life events and interpersonal difficulties. At 45 years, 9377 women and men from the UK 1958 British Birth Cohort Study participated in a clinical survey. Childhood adversity was prospectively assessed at the ages of 7, 11 and 16 years. Suicidal ideation at midlife was assessed by the depressive ideas subscale of the Revised Clinical Interview Schedule. Internalizing and externalizing disorders were measured by the Rutter scales at 16 years. Life events, periods of unemployment, partnership separations and alcohol dependence were measured through adulthood. Illness in the household, paternal absence, institutional care, parental divorce and retrospective reports of parental physical and sexual abuse predicted suicidal ideation at 45 years. Three or more childhood adversities were associated with suicidal ideation at 45 years [odds ratio (OR) 4.31, 95% confidence interval (CI) 2.67-6.94]. Psychological distress at 16 years partially mediated the associations of physical abuse (OR 3.41, 95% CI 2.29-5.75), sexual abuse (OR 4.99, 95% CI 2.90-11.16) with suicidal ideation. Adult life events partially mediated the association of parental divorce (OR 6.34, 95% CI -7.16 to 36.75) and physical (OR 9.59, 95% CI 4.97-27.88) and sexual abuse (OR 6.59, 95% CI 2.40-38.36) with suicidal ideation at 45 years. Adversity in childhood predicts suicidal ideation in midlife, partially mediated by adolescent internalizing and externalizing disorders, adult life events and interpersonal difficulties. Understanding the pathways from adversity to suicidal ideation can inform suicide prevention and the targeting of preventive

Prodrug encapsulated albumin nanoparticles as an alternative approach to manifest anti-proliferative effects of suicide gene therapy

International Nuclear Information System (INIS)

Tirkey, Bulbul; Bhushan, Bharat; Uday Kumar, S.; Gopinath, P.

2017-01-01

Conventional anticancer agents are associated with limited therapeutic efficacy and substantial nonspecific cytotoxicity. Thus, there is an imminent need for an alternative approach that can specifically annihilate the cancer cells with minimal side effects. Among such alternative approaches, CD::UPRT (cytosine deaminase uracil phosphoribosyl transferase) suicide gene therapy has tremendous potential due to its high efficacy. Prodrug 5-Fluorocytosine (5-FC) used in combination with CD::UPRT suicide gene suffers from limited solubility which subsequently leads to decline in therapeutic efficacy. In order to overcome this, 5-FC encapsulated bovine serum albumin nanoparticles (BSA-5-FC NPs) were prepared in this work by desolvation method. Physico-chemical characterizations studies revealed amorphous nature of BSA-5-FC NPs with uniform spherical morphology. Apart from increase in solubility, encapsulated 5-FC followed slow and sustained release profile. Suicide gene expressing stable clone of L-132 cells were adapted for investigating therapeutic potential of BSA-5-FC NPs. These nanoparticles were readily taken up by the cells in a concentration dependent manner and subsequently manifested apoptosis, which was further confirmed by morphological examination and gene expression analysis. These findings clearly illustrate that CD::UPRT suicide gene therapy can be efficiently utilized in combination with this nanosystem for improved suicide gene therapy and tumor eradication. - Highlights: • In this work, BSA-5-FC NPs has been prepared to achieve its sustained release and also facilitate its uptake by cells. • A protein based system has been realized for the first time to deliver prodrug for cancer therapy. • Physico-chemical characterizations further validate the formation of spherical, monodispersed and stable nanoparticles. • The therapeutic efficacy of BSA-5-FC NPs has been validated against CD::UPRT expressing stable cells.

Prodrug encapsulated albumin nanoparticles as an alternative approach to manifest anti-proliferative effects of suicide gene therapy

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Tirkey, Bulbul [Nanobiotechnology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667 (India); Bhushan, Bharat; Uday Kumar, S. [Nanobiotechnology Laboratory, Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667 (India); Gopinath, P., E-mail: pgopifnt@iitr.ernet.in [Nanobiotechnology Laboratory, Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667 (India); Nanobiotechnology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667 (India)

2017-04-01

Conventional anticancer agents are associated with limited therapeutic efficacy and substantial nonspecific cytotoxicity. Thus, there is an imminent need for an alternative approach that can specifically annihilate the cancer cells with minimal side effects. Among such alternative approaches, CD::UPRT (cytosine deaminase uracil phosphoribosyl transferase) suicide gene therapy has tremendous potential due to its high efficacy. Prodrug 5-Fluorocytosine (5-FC) used in combination with CD::UPRT suicide gene suffers from limited solubility which subsequently leads to decline in therapeutic efficacy. In order to overcome this, 5-FC encapsulated bovine serum albumin nanoparticles (BSA-5-FC NPs) were prepared in this work by desolvation method. Physico-chemical characterizations studies revealed amorphous nature of BSA-5-FC NPs with uniform spherical morphology. Apart from increase in solubility, encapsulated 5-FC followed slow and sustained release profile. Suicide gene expressing stable clone of L-132 cells were adapted for investigating therapeutic potential of BSA-5-FC NPs. These nanoparticles were readily taken up by the cells in a concentration dependent manner and subsequently manifested apoptosis, which was further confirmed by morphological examination and gene expression analysis. These findings clearly illustrate that CD::UPRT suicide gene therapy can be efficiently utilized in combination with this nanosystem for improved suicide gene therapy and tumor eradication. - Highlights: • In this work, BSA-5-FC NPs has been prepared to achieve its sustained release and also facilitate its uptake by cells. • A protein based system has been realized for the first time to deliver prodrug for cancer therapy. • Physico-chemical characterizations further validate the formation of spherical, monodispersed and stable nanoparticles. • The therapeutic efficacy of BSA-5-FC NPs has been validated against CD::UPRT expressing stable cells.

Tumor-specific expression of shVEGF and suicide gene as a novel strategy for esophageal cancer therapy.

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Liu, Ting; Wu, Hai-Jun; Liang, Yu; Liang, Xu-Jun; Huang, Hui-Chao; Zhao, Yan-Zhong; Liao, Qing-Chuan; Chen, Ya-Qi; Leng, Ai-Min; Yuan, Wei-Jian; Zhang, Gui-Ying; Peng, Jie; Chen, Yong-Heng

2016-06-21

To develop a potent and safe gene therapy for esophageal cancer. An expression vector carrying fusion suicide gene (yCDglyTK) and shRNA against vascular endothelial growth factor (VEGF) was constructed and delivered into EC9706 esophageal cancer cells by calcium phosphate nanoparticles (CPNP). To achieve tumor selectivity, expression of the fusion suicide gene was driven by a tumor-specific human telomerase reverse transcriptase (hTERT) promoter. The biologic properties and therapeutic efficiency of the vector, in the presence of prodrug 5-fluorocytosine (5-FC), were evaluated in vitro and in vivo. Both in vitro and in vivo testing showed that the expression vector was efficiently introduced by CPNP into tumor cells, leading to cellular expression of yCDglyTK and decreased VEGF level. With exposure to 5-FC, it exhibited strong anti-tumor effects against esophageal cancer. Combination of VEGF shRNA with the fusion suicide gene demonstrated strong anti-tumor activity. The shVEGF-hTERT-yCDglyTK/5-FC system provided a novel approach for esophageal cancer-targeted gene therapy.

An empirical test of a mediation model of the impact of the traditional male gender role on suicidal behavior in men.

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Houle, Janie; Mishara, Brian L; Chagnon, François

2008-04-01

Men die by suicide three to four times more often than women in Western countries. The adverse impact of the traditional male gender role as well as men's reluctance to seek help are possible explanations of this gender gap, but these hypotheses have not been well documented empirically. This study compares two groups of men who experienced comparable severely stressful life events during the preceding 12 months: 40 men admitted to hospital emergency following suicide attempts, and 40 men with no history of suicide attempts. Structured interviews were conducted to measure adherence to the traditional male gender role, help seeking behaviour, social support, suicide acceptability and mental health. ANOVAS indicated that attempters are more likely to adhere to the traditional masculine gender role and regression analysis revealed that this relationship persists even when the presence of mental disorders is statistically controlled. Sequential regression analysis support the mediation model and show that the effects of the traditional male gender role on suicidal behavior are mediated through protective and risk factors for suicide, namely mental state, help seeking and social support. The traditional male gender role appears to increase the risk of suicidal behavior in men by undermining their mental state and by inhibiting the protective factors of help seeking and social support. This study underscores the importance of encouraging men to seek help.

DNA methylation perturbations in genes involved in polyunsaturated Fatty Acid biosynthesis associated with depression and suicide risk.

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Haghighi, Fatemeh; Galfalvy, Hanga; Chen, Sean; Huang, Yung-Yu; Cooper, Thomas B; Burke, Ainsley K; Oquendo, Maria A; Mann, J John; Sublette, M Elizabeth

2015-01-01

Polyunsaturated fatty acid (PUFA) status has been associated with neuropsychiatric disorders, including depression and risk of suicide. Long-chain PUFAs (LC-PUFAs) are obtained in the diet or produced by sequential desaturation and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3). We compared DNA methylation patterns in genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD) with (n = 22) and without (n = 39) history of suicide attempt, and age- and sex-matched healthy volunteers (n = 59). Plasma levels of selected PUFAs along the LC-PUFA biosynthesis pathway were determined by transesterification and gas chromatography. CpG methylation levels for the main human LC-PUFA biosynthetic genes, fatty acid desaturases 1 (Fads1) and 2 (Fads2), and elongation of very long-chain fatty acids protein 5 (Elovl5), were assayed by bisulfite pyrosequencing. Associations between PUFA levels and diagnosis or suicide attempt status did not survive correction for multiple testing. However, MDD diagnosis and suicide attempts were significantly associated with DNA methylation in Elovl5 gene regulatory regions. Also the relative roles of PUFA levels and DNA methylation with respect to diagnostic and suicide attempt status were determined by least absolute shrinkage and selection operator logistic regression analyses. We found that PUFA associations with suicide attempt status were explained by effects of Elovl5 DNA methylation within the regulatory regions. The observed link between plasma PUFA levels, DNA methylation, and suicide risk may have implications for modulation of disease-associated epigenetic marks by nutritional intervention.

DNA methylation perturbations in genes involved in polyunsaturated fatty acid biosynthesis associated with depression and suicide risk

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Fatemeh eHaghighi

2015-04-01

Full Text Available Polyunsaturated fatty acid (PUFA status has been associated with neuropsychiatric disorders, including depression and risk of suicide. Long-chain PUFAs (LC-PUFAs are obtained in the diet or produced by sequential desaturation and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6 and α-linolenic acid (ALA, 18:3n-3. We compared DNA methylation patterns in genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD with (n=22 and without (n=39 history of suicide attempt, and age- and sex-matched healthy volunteers (n=59. Plasma levels of selected PUFAs along the LC-PUFA biosynthesis pathway were determined by transesterification and gas chromatography. CpG methylation levels for the main human LC-PUFA biosynthetic genes, fatty acid desaturases 1 (Fads1 and 2 (Fads2, and elongation of very long chain fatty acids protein 5 (Elovl5, were assayed by bisulfite pyrosequencing. Associations between PUFA levels and diagnosis or suicide attempt status did not survive correction for multiple testing. However, MDD diagnosis and suicide attempts were significantly associated with DNA methylation in Elovl5 gene regulatory regions. Also the relative roles of PUFA levels and DNA methylation with respect to diagnostic and suicide attempt status were determined by least absolute shrinkage and selection operator (LASSO logistic regression analyses. We found that PUFA associations with suicide attempt status were explained by effects of Elovl5 DNA methylation within the regulatory regions. The observed link between plasma PUFA levels, DNA methylation, and suicide risk may have implications for modulation of disease-associated epigenetic marks by nutritional intervention.

Explanatory risk factors in the relations between schizotypy and indicators of suicide risk.

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Jahn, Danielle R; DeVylder, Jordan E; Hilimire, Matthew R

2016-04-30

Schizotypy has been linked to suicide risk, but it is not known whether established suicide-related risk factors mediate this relation. The aim of this study was to assess the mediating effects of depressive symptoms, social anxiety, self-esteem, and intimate disclosure in peer relationships in the relation between interpersonal schizotypy and suicide ideation or lifetime suicide attempts. This aim was tested in 590 young adults using a nonparametric bootstrapping procedure. After inclusion of the mediators, interpersonal schizotypy was no longer directly associated with either suicide ideation or lifetime suicide attempts. Depression and self-esteem mediated the relation between interpersonal schizotypy and suicide ideation. No variables mediated the relation between interpersonal schizotypy and lifetime suicide attempts, and there were no significant direct relations when mediators were included. Schizotypy appears to be a distal risk factor for suicidal behavior; assessing depressive symptoms and self-esteem may provide more proximal information about suicide risk, and may be targets for mitigating suicide risk in individuals with schizotypy. Published by Elsevier Ireland Ltd.

Social Anxiety Symptoms and Suicidal Ideation in a Clinical Sample of Early Adolescents: Examining Loneliness and Social Support as Longitudinal Mediators

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Prinstein, Mitchell J.; Simon, Valerie; Spirito, Anthony

2014-01-01

Recent research has shown that social anxiety may be related to increased risk for suicidal ideation in teens, although this research largely has been cross-sectional and has not examined potential mediators of this relationship. A clinical sample of 144 early adolescents (72 % female; 12–15 years old) was assessed during psychiatric inpatient hospitalization and followed up at 9 and 18 months post-baseline. Symptoms of social anxiety, depression, suicidal ideation, loneliness, and perceived social support were assessed via structured interviews and self-report instruments. Structural equation modeling revealed a significant direct relationship between social anxiety symptoms at baseline and suicidal ideation at 18 months post-baseline, even after controlling for baseline depressive symptoms and ideation. A second multiple mediation model revealed that baseline social anxiety had a significant indirect effect on suicidal ideation at 18 months post-baseline through loneliness at 9 months post-baseline. Social anxiety did not have a significant indirect effect on suicidal ideation through perceived social support from either parents or close friends. Findings suggest that loneliness may be particularly implicated in the relationship between social anxiety and suicidality in teens. Clinicians should assess and address feelings of loneliness when treating socially anxious adolescents. PMID:24390470

Suicide Gene Therapy to Increase the Safety of Chimeric Antigen Receptor-Redirected T Lymphocytes

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Monica Casucci, Attilio Bondanza

2011-01-01

Full Text Available Chimeric antigen receptors (CARs are generated by fusing the antigen-binding motif of a monoclonal antibody (mAb with the signal transduction machinery of the T-cell receptor (TCR. The genetic modification of T lymphocytes with chimeric receptors specific for tumor-associated antigens (TAAs allows for the redirection towards tumor cells. Clinical experience with CAR-redirected T cells suggests that antitumor efficacy associates with some degree of toxicity, especially when TAA expression is shared with healthy tissues. This situation closely resembles the case of allogeneic hematopoietic stem cell transplantation (HSCT, wherein allorecognition causes both the graft-versus-leukemia (GVL effect and graft-versus-host disease (GVHD. Suicide gene therapy, i.e. the genetic induction of a conditional suicide phenotype into donor T cells, enables dissociating the GVL effect from GVHD. Applying suicide gene modification to CAR-redirected T cells may therefore greatly increase their safety profile and facilitate their clinical development.

The Association of Alcohol Use Disorders with Suicidal Ideation and Suicide Attempts in a Population-Based Sample with Mood Symptoms.

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Sung, Yoon-kyu; La Flair, Lareina N; Mojtabai, Ramin; Lee, Li-Ching; Spivak, Stanislav; Crum, Rosa M

2016-01-01

Using population-based data, we examined associations between alcohol use disorders (AUD) and suicidality, assessing effect modification by mood disorders, and mediation by drinking level. Suicidality was assessed among current drinkers with 2-weeks of low mood (n = 9,173) in the National Epidemiologic Survey on Alcohol and Related Conditions. Independent of mood disorder, alcohol dependence, was associated with suicidal ideation (adjusted odds ratio [AOR] = 1.64; 95% confidence interval [CI] = 1.25-2.14), and suicide attempts (AOR = 2.02; CI = 1.43-2.85) relative to those without AUD. Findings indicate partial mediation by consumption. Associations between AUD and suicidality among those with low mood are not explained by comorbid mood disorder, but are partially mediated by drinking level. Future studies should evaluate transitions in suicidality with change in consumption.

Oxytocin and Social Sensitivity: Gene Polymorphisms in Relation to Depressive Symptoms and Suicidal Ideation

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Robyn Jane McQuaid

2016-07-01

Full Text Available Although the neuropeptide oxytocin has been associated with enhanced prosocial behaviors, it has also been linked to aggression and mental health disorders. Thus, it was suggested that oxytocin might act by increasing the salience of social stimuli, irrespective of whether these are positive or negative, thus increasing vulnerability to negative mental health outcomes. The current study (N = 243, conducted among White university students, examined the relation of trauma, depressive symptoms including suicidal ideation in relation to a single nucleotide polymorphism (SNP within the oxytocin receptor gene (OXTR, rs53576, and a SNP on the CD38 gene that controls oxytocin release, rs3796863. Individuals with the polymorphism on both alleles (AA genotype of the CD38 SNP had previously been linked to elevated plasma oxytocin levels. Consistent with the social sensitivity perspective, however, in the current study, individuals carrying the AA genotype displayed elevated feelings of alienation from parents and peers as well as increased levels of suicidal ideation. Moreover, they tended to report elevated depressive symptoms compared to CC homozygotes. It was also observed that the CD38 genotype moderated the relation between trauma and suicidal ideation scores, such that high levels of trauma were associated with elevated suicidal ideation among all CD38 genotypes, but this relationship was stronger among individuals with the AA genotype. In contrast, there was no relationship between the OXTR SNP, rs53576, depression or suicidal ideation. These findings support a social sensitivity hypothesis of oxytocin, wherein the AA genotype of the CD38 SNP, which has been considered the ‘protective allele’ was associated with increased sensitivity and susceptibility to disturbed social relations and suicidal ideation.

Childhood trajectories of anxiousness and disruptiveness as predictors of suicide attempts.

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Brezo, Jelena; Barker, Edward D; Paris, Joel; Hébert, Martine; Vitaro, Frank; Tremblay, Richard E; Turecki, Gustavo

2008-11-01

To investigate the association of childhood trajectories of anxiousness and disruptiveness with suicide attempts in early adulthood. Prospective cohort study. Public francophone schools in Quebec, Canada, from the 1986 to 1988 school years. Of 4,488 French Canadian children attending kindergarten, a representative group of 1,001 boys and 999 girls was chosen for follow-up. Of these, 1,144 individuals participated in the study during early adulthood. Suicide attempt histories by early adulthood, adjusted odds ratios (ORs) associated with membership in high- vs low-risk trajectories of anxiousness and disruptiveness, moderation (by sex), and mediation (by adolescent Axis I disorders). We observed 4 distinct developmental profiles of anxiousness and disruptiveness and a frequent co-occurrence of similar levels of these traits. In contrast to anxiousness trajectories (OR = 1.60; 95% confidence interval, 1.00-2.65), disruptiveness (OR = 1.80; 95% confidence interval, 1.03-3.13) and joint (OR = 1.88; 95% confidence interval, 1.05-3.37) trajectories made statistically significant contributions to suicide attempts. We found no support for mediation by adolescent anxiety/mood or disruptive disorders. Sex, however, moderated the effect of joint trajectories, increasing the risk of suicide attempts in women (OR = 3.60; Wald chi(2) = 10.93; P anxious and disruptive traits as children. Anxious-disruptive girls and disruptive boys appear to be more likely than their peers to attempt suicide by early adulthood. Preventive efforts will require more research into the possible mechanisms behind this early sex difference, ie, gene-environment interplays and nonpsychiatric mediators.

Gratitude and Suicidal Ideation and Suicide Attempts among Chinese Adolescents: Direct, Mediated, and Moderated Effects

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Li, Dongping; Zhang, Wei; Li, Xian; Li, Nini; Ye, Baojuan

2012-01-01

In a sample of 1252 Chinese adolescents (mean age = 15.00 years), this study examined the direct relations between gratitude and adolescents' suicidal ideation and suicide attempts. This study also examined indirect relations between gratitude and suicidal ideation and suicide attempts via two self-system beliefs--coping efficacy and self-esteem.…

The impact of Cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes on suicide attempt and suicide risk-a European multicentre study on treatment-resistant major depressive disorder.

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Höfer, Peter; Schosser, Alexandra; Calati, Raffaella; Serretti, Alessandro; Massat, Isabelle; Kocabas, Neslihan Aygun; Konstantinidis, Anastasios; Linotte, Sylvie; Mendlewicz, Julien; Souery, Daniel; Zohar, Joseph; Juven-Wetzler, Alzbeta; Montgomery, Stuart; Kasper, Siegfried

2013-08-01

Recently published data have reported associations between cytochrome P450 metabolizer status and suicidality. The aim of our study was to investigate the role of genetic polymorphisms of the cytochrome P450 genes on suicide risk and/or a personal history of suicide attempts. Two hundred forty-three major depressive disorder patients were collected in the context of a European multicentre resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using the Mini International Neuropsychiatric Interview and the Hamilton Rating Scale for Depression (HAM-D). Treatment response was defined as HAM-D ≤ 17 and remission as HAM-D ≤ 7 after 4 weeks of treatment with antidepressants at adequate dose. Genotyping was performed for all relevant variations of the CYP1A2 gene (*1A, *1F, *1C, *1 J, *1 K), the CYP2C9 gene (*2, *3), the CYP2C19 gene (*2, *17) and the CYP2D6 gene (*3, *4, *5, *6, *9, *19, *XN). No association between both suicide risk and personal history of suicide attempts, and the above mentioned metabolic profiles were found after multiple testing corrections. In conclusion, the investigated cytochrome gene polymorphisms do not seem to be associated with suicide risk and/or a personal history of suicide attempts, though methodological and sample size limitations do not allow definitive conclusions.

Associations among bullying, cyberbullying, and suicide in high school students.

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Bauman, Sheri; Toomey, Russell B; Walker, Jenny L

2013-04-01

This study examined associations among depression, suicidal behaviors, and bullying and victimization experiences in 1491 high school students using data from the 2009 Youth Risk Behavior Survey. Results demonstrated that depression mediated the association between bullying/victimization and suicide attempts, but differently for males and females. Specifically, depression mediated the link between traditional victimization and suicide attempts similarly across gender, whereas depression mediated the link between cyber victimization and suicide attempts only for females. Similarly, depression mediated the link between traditional bullying and suicide attempts for females only. Depression did not mediate the link between cyberbullying and suicide attempts for either gender. Implications of the findings are discussed, including the importance of greater detection of depression among students involved in bullying, and the need for a suicide prevention and intervention component in anti-bullying programs. Findings suggest that bullying prevention efforts be extended from middle school students to include high school students. Copyright © 2012 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

A mediation model of professional psychological help seeking for suicide ideation among Asian American and white American college students.

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Wong, Joel; Brownson, Chris; Rutkowski, Leslie; Nguyen, Chi P; Becker, Marty Swanbrow

2014-01-01

This study examined professional psychological help seeking among 1,045 white American and Asian American students from 70 U.S. colleges and universities who had seriously considered attempting suicide. The authors found that Asian American college students had lower rates of professional psychological help seeking for their suicide ideation than White American college students. Guided by social network perspectives on professional psychological help seeking, the authors also tested mediators of this racial disparity. Relative to white Americans, Asian Americans were advised by fewer people (especially fewer family members) to seek professional help, which was, in turn, associated with lower rates of professional psychological help seeking for suicide ideation. These findings underscore the importance of gatekeeping as a suicide prevention strategy for Asian American college students.

X chromosome and suicide.

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Fiori, L M; Zouk, H; Himmelman, C; Turecki, G

2011-02-01

Suicide completion rates are significantly higher in males than females in most societies. Although gender differences in suicide rates have been partially explained by environmental and behavioral factors, it is possible that genetic factors, through differential expression between genders, may also help explain gender moderation of suicide risk. This study investigated X-linked genes in suicide completers using a two-step strategy. We first took advantage of the genetic structure of the French-Canadian population and genotyped 722 unrelated French-Canadian male subjects, of whom 333 were suicide completers and 389 were non-suicide controls, using a panel of 37 microsatellite markers spanning the entire X chromosome. Nine haplotype windows and several individual markers were associated with suicide. Significant results aggregated primarily in two regions, one in the long arm and another in the short arm of chromosome X, limited by markers DXS8051 and DXS8102, and DXS1001 and DXS8106, respectively. The second stage of the study investigated differential brain expression of genes mapping to associated regions in Brodmann areas 8/9, 11, 44 and 46, in an independent sample of suicide completers and controls. Six genes within these regions, Rho GTPase-activating protein 6, adaptor-related protein complex 1 sigma 2 subunit, glycoprotein M6B, ribosomal protein S6 kinase 90  kDa polypeptide 3, spermidine/spermine N(1)-acetyltransferase 1 and THO complex 2, were found to be differentially expressed in suicide completers.

Child and Adolescent Suicide Attempts, Suicidal Behavior, and Adverse Childhood Experiences in South Africa: A Prospective Study.

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Cluver, Lucie; Orkin, Mark; Boyes, Mark E; Sherr, Lorraine

2015-07-01

This is the first known prospective study of child suicidal behavior in sub-Saharan Africa. Aims were to determine whether (1) cumulative exposure to adverse childhood experiences (ACEs) predicts later suicidality and (2) heightened risks are mediated by mental health disorder and drug/alcohol misuse. Longitudinal repeated interviews were conducted 1 year apart (97% retention) with 3,515 adolescents aged 10-18 years in South Africa (56% female; areas from urban/rural sites within two provinces and door-to-door sampling included all homes with a resident adolescent. Measures included past-month suicide attempts, planning, and ideation, mental health disorders, drug/alcohol use, and ACE, for example, parental death by AIDS or homicide, abuse, and exposure to community violence. Analyses included multivariate logistic regression and multiple mediation tests. Past-month suicidality rates were 3.2% of adolescents attempting, 5.8% planning, and 7.2% reporting ideation. After controlling for baseline suicidality and sociodemographics, a strong, graded relationship was shown between cumulative ACE and all suicide behaviors 1 year later. Baseline mental health, but not drug/alcohol misuse, mediated relationships between ACE and subsequent suicidality. Suicide attempts rose from 1.9% among adolescents with no ACE to 6.3% among adolescents with >5 ACEs (cumulative odds ratio [OR], 2.46; confidence interval [CI], 1.00-6.05); for suicide planning, from 2.4% to 12.5% (cumulative OR, 4.40; CI, 2.08-9.29); and for suicide ideation, from 4.2% to 15.6% (cumulative OR, 2.99; CI, 1.68-5.53). Preventing and mitigating childhood adversities have the potential to reduce suicidality. Among adolescents already exposed to adversities, effective mental health services may buffer against future suicidality. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Suicidal behavior and haplotypes of the dopamine receptor gene (DRD2 and ANKK1 gene polymorphisms in patients with alcohol dependence--preliminary report.

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Andrzej Jasiewicz

Full Text Available Suicide is a significant public health issue and a major cause of death throughout the world. According to WHO it accounts for almost 2% of deaths worldwide. The etiology of suicidal behavior is complex but the results of many studies suggest that genetic determinants are of significant importance. In our study,--we have analyzed selected SNPs polymorphisms in the DRD2 and ANKK1 genes in patients with alcohol dependence syndrome (169 Caucasian subjects including a subgroup of individuals (n = 61 who have experienced at least one suicide attempt. The aim of the study was to verify if various haplotypes of selected genes, comprising Taq1A, Taq1B, and Taq1D single nucleotide polymorphisms (SNP, play any role in the development of alcohol dependence and suicidal behavior. The control group comprised 157 unrelated individuals matched for ethnicity, gender,- and age and included no individuals with mental disorders. All subjects were recruited in the North West region of Poland. The study showed that alcohol dependent subjects with a history of at least one suicidal attempt were characterized by a significantly higher frequency of the T-G-A2 haplotype when compared to individuals in whom alcohol dependence was not associated with suicidal behavior (p = 0.006. It appears that studies based on identifying correlation between SNPs is the future for research on genetic risk factors that contribute to the development of alcohol addiction and other associated disorders. To sum up, there is a necessity to perform further research to explain dependencies between the dopaminergic system, alcohol use disorders and suicidal behavior.

Social anxiety and suicidal ideation: Test of the utility of the interpersonal-psychological theory of suicide.

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Buckner, Julia D; Lemke, Austin W; Jeffries, Emily R; Shah, Sonia M

2017-01-01

Social anxiety is related to greater suicidality, even after controlling for depression and other psychopathology. The Interpersonal-Psychological Theory of Suicide (IPTS; Joiner, 2005) proposes that people are vulnerable to wanting to die by suicide if they experience both perceived burdensomeness (sense that one is a burden to others) and thwarted belongingness (a greater sense of alienation from others). Socially anxious persons may be especially vulnerable to these interpersonal factors. The current study tested whether interpersonal IPTS components independently and additively mediate the social anxiety-suicidal ideation (SI) relation among 780 (80.5% female) undergraduates. Social anxiety was significantly, robustly related to SI and to thwarted belongingness and perceived burdensomeness. Social anxiety was indirectly related to SI via thwarted belongingness and perceived burdensomeness. The sum of these indirect effects was significant. Moderated mediation analyses indicated that perceived burdensomeness only mediated the relation between social anxiety and SI at higher levels of thwarted belongingness. Findings highlight that difficulties in interpersonal functioning may serve as potential pathways through which social anxiety may lead to greater suicidality. Findings highlight that difficulties in interpersonal functioning may serve as potential pathways through which social anxiety may lead to greater suicidality. Copyright © 2016 Elsevier Ltd. All rights reserved.

DEPRESSION MEDIATES THE RELATION OF INSOMNIA SEVERITY WITH SUICIDE RISK IN THREE CLINICAL SAMPLES OF U.S. MILITARY PERSONNEL.

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Bryan, Craig J; Gonzales, Jacqueline; Rudd, M David; Bryan, AnnaBelle O; Clemans, Tracy A; Ray-Sannerud, Bobbie; Wertenberger, Evelyn; Leeson, Bruce; Heron, Elizabeth A; Morrow, Chad E; Etienne, Neysa

2015-09-01

A growing body of empirical research suggests insomnia severity is directly related to suicide ideation, attempts, and death in nonmilitary samples, even when controlling for depression and other suicide risk factors. Few studies have explored this relationship in U.S. military personnel. The present study entailed secondary data analyses examining the associations of insomnia severity with suicide ideation and attempts in three clinical samples: Air Force psychiatric outpatients (n = 158), recently discharged Army psychiatric inpatients (n = 168), and Army psychiatric outpatients (n = 54). Participants completed the Beck Scale for Suicide Ideation, the Beck Depression Inventory-II or Patient Health Questionnaire-9, the Insomnia Severity Index, and the Posttraumatic Stress Disorder Checklist at baseline; two samples also completed these measures during follow-up. Sleep disturbance was associated with concurrent (β's > 0.21; P's 0.39; P's suicide ideation in all three samples. When adjusting for age, gender, depression, and posttraumatic stress, insomnia severity was no longer directly associated with suicide ideation either concurrently (β's 0.200) or prospectively (β's 0.063), but depression was (β's > 0.22; P's depression mediated the relation of insomnia severity with suicide ideation. Across three clinical samples of military personnel, depression explained the relationship between insomnia severity and suicide risk. © 2015 Wiley Periodicals, Inc.

Examining the Relationship Between Pain Catastrophizing and Suicide Risk in Patients with Rheumatic Disease: the Mediating Role of Depression, Perceived Social Support, and Perceived Burdensomeness.

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Shim, Eun -Jung; Song, Yeong Wook; Park, Seung-Hee; Lee, Kwang-Min; Go, Dong Jin; Hahm, Bong-Jin

2017-08-01

Little research has examined the role of pain catastrophizing (PC) in predicting suicide among patients with rheumatic disease or the mechanisms through which it works. This study examines whether depression, perceived social support (PSS), and perceived burdensomeness (PB) mediate the relationship between PC and suicide risk. It also examines the relative importance of sociodemographic, clinical, and psychological factors in predicting suicide risk. Three hundred sixty patients from a rheumatology clinic in Korea completed measures of pain catastrophizing, social support, depression, and perceived burdensomeness. In hierarchical multiple regression analysis, the PC magnification, PB, physical disability, and PSS were significantly related to suicide risk. Results of the serial multiple mediation analysis indicated that the total indirect effect of PC magnification on suicide risk was significant while the direct effect was not. Four specific indirect effects of PC magnification were found to be statistically significant. First of all, PC magnification was associated with suicide risk through PB and through depression and PB. PC magnification was also associated with suicide risk through depression and PSS. Lastly, PC magnification was associated with suicide risk through depression, PSS, and PB. The identified pathways through which PC affects suicide risk suggest the importance of depression, PSS, and PB. Evaluation and intervention targeted at physical disability and the psychological factors of PC magnification, depression, PSS, and PB may be integrated into the management of suicide risk in patients with rheumatic disease.

The potential role of attitudes towards suicide between mental health status and suicidal ideation among Chinese children and adolescents.

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Tan, L; Yang, Q H; Chen, J L; Zou, H X; Xia, T S; Liu, Y

2017-09-01

The objective of this study was to investigate the contributions of mental health status and attitudes towards suicide on suicidal ideation in a sample of 6568 Chinese children and adolescents in China. Attitudes towards suicide were investigated as a possible moderator and mediator of the influence of mental health status on suicidal ideation. Descriptive statistical analyses, Pearson correlation analyses and hierarchical regression analyses were adopted as methods of data analyses. Approximately 35.38% of children and adolescents in our study reported having suicidal ideation. Mental health status and attitudes towards suicide both had an independent effect on the severity of suicidal ideation. Results indicated that mental health status was positively associated with suicidal ideation, while attitudes towards suicide were negatively associated with suicidal ideation. Moderation analysis showed that the impact of mental health status on suicidal ideation was significantly greater among children and adolescents who reported favourable attitudes towards suicide. Attitudes towards suicide partially mediated the link between mental health status and the severity of suicidal ideation. Specifically, students who experienced poorer mental health status might be more likely to report significantly more favourable attitudes towards suicide, which in turn promote greater suicidal ideation. These results have implications for the prevention of youth suicide, suggesting that mental health status and attitudes towards suicide could be important targets for prevention and intervention for children and adolescents at risk of suicidal ideation. © 2017 John Wiley & Sons Ltd.

Loneliness and suicidal ideation in drug-using college students.

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Lamis, Dorian A; Ballard, Elizabeth D; Patel, Amee B

2014-12-01

The college years are marked by social changes and behavioral experimentation which may increase risk of suicidal ideation. We propose a novel pathway for the development of suicidal thoughts between two established suicide risk factors, loneliness and drug use, which have not been examined in a nonclinical sample. Data were collected from 207 undergraduate drug-using students at a large southeastern university. As hypothesized, suicidal ideation was positively correlated with both loneliness (r = .40) and drug use (r = .29). After controlling for several demographic variables, social desirability, and anxiety sensitivity, drug use was tested as a potential mediator in the loneliness-suicidal ideation link using a single-mediator model. Results indicated a significant indirect (mediated) effect of loneliness on suicidal ideation via drug use (ab = 0.09, 95% CI: 0.02-0.18), suggesting that loneliness may contribute to suicidal ideation through increased drug use among college students. Identification of and intervention with students reporting loneliness and drug use may be a promising suicide prevention strategy on college campuses. © 2014 The American Association of Suicidology.

Depression, delinquency, and suicidal behaviors among college students.

Science.gov (United States)

Bauer, Rebecca L; Chesin, Megan S; Jeglic, Elizabeth L

2014-01-01

Liu (2004) investigated the interaction between delinquency and depression among adolescents and found that delinquency moderated the relationship between depression and suicidal behaviors. This study also explored the relationship between depression, delinquency, and suicidal behaviors, although delinquency was expected to mediate, as opposed to moderate, the relationship between depression and suicidal behaviors. The participants comprised 354 college students. The students completed a series of questionnaires measuring delinquent behavior, depressive symptoms, and suicidal thoughts and behaviors. Contrary to Liu's (2004) findings, delinquency was found not to moderate but rather to partially mediate the relationship between depression and suicidal behaviors. The findings suggest that for some college students, depression is associated with delinquent behaviors, which, in turn, are associated with suicidal behaviors.

Suicide clusters among young Kenyan men.

Science.gov (United States)

Goodman, Michael L; Puffer, Eve S; Keiser, Philip H; Gitari, Stanley

2017-11-01

Suicide is a leading cause of global mortality. Suicide clusters have recently been identified among peer networks in high-income countries. This study investigates dynamics of suicide clustering within social networks of young Kenya men ( n = 532; 18-34 years). We found a strong, statistically significant association between reported number of friends who previously attempted suicide and present suicide ideation (odds ratio = 1.9; 95% confidence interval (1.42, 2.54); p self-esteem (23% of total effect). Meaning in life further mediated the association between collective self-esteem and suicide ideation. Survivors of peer suicide should be evaluated for suicide risk.

Pathways From Bullying Perpetration, Victimization, and Bully Victimization to Suicidality Among School-Aged Youth: A Review of the Potential Mediators and a Call for Further Investigation.

Science.gov (United States)

Hong, Jun Sung; Kral, Michael J; Sterzing, Paul R

2015-10-01

In the wake of several highly publicized adolescent suicides attributed to bullying victimization, national attention has been brought to bear on the profound public health problem of bullying. This article reviews the extant literature on the associations between bullying perpetration, victimization, and thoughts of or attempts at suicide and proposes five potential mediators, namely depression, anxiety, low self-esteem, loneliness, and hopelessness, that may explain this relationship. Numerous studies have found empirical support for the interrelations between internalizing behaviors and both bullying perpetration and victimization and suicide. We find that further longitudinal research needs to be conducted to more conclusively determine the role and causal ordering these various psychosocial factors may play in bullying perpetration, victimization, and suicide. Although the research literature implies causal directions among all these potential mediators, untangling the unique influence of bullying perpetration, victimization, and bully victimization on suicide and its mechanisms of action has major research and practice implications. © The Author(s) 2014.

Perceived School Climate and Chinese Adolescents' Suicidal Ideation and Suicide Attempts: The Mediating Role of Sleep Quality

Science.gov (United States)

Li, Dongping; Bao, Zhenzhou; Li, Xian; Wang, Yanhui

2016-01-01

Background: School factors play important roles in adolescent suicide. However, little is known about how school climate is associated with adolescent suicide. This study examined the relationship between perceived school climate and adolescent suicidal ideation and suicide attempts, and whether these relations were explained by adolescent sleep…

The mediating effect of depressive symptoms on the relationship between bullying victimization and non-suicidal self-injury among adolescents: Findings from community and inpatient mental health settings in Ontario, Canada.

Science.gov (United States)

Baiden, Philip; Stewart, Shannon L; Fallon, Barbara

2017-09-01

Although bullying victimization has been linked to a number of behavioral and emotional problems among adolescents, few studies have investigate the mechanism through which bullying victimization affect non-suicidal self-injury. The objectives of this study were to examine the effect of bullying victimization on non-suicidal self-injury and the mediating effect of depressive symptoms on the relationship between bullying victimization and non-suicidal self-injury among adolescents. Data for this study came from the interRAI Child and Youth Mental Health dataset. A total of 1650 adolescents aged 12-18 years (M =14.56; SD =1.79; 54.2% males) were analyzed. Binary logistic and Poisson regression models were conducted to identify the mediating effect of depressive symptoms on the relationship between bullying victimization and non-suicidal self-injury. Of the 1650 adolescents studied, 611 representing 37% engaged in non-suicidal self-injury and 26.7% were victims of bullying. The effect of bullying victimization on non-suicidal self-injury was partially mediated by depressive symptoms after adjusting for the effect of demographic characteristics, history of childhood abuse, social support, and mental health diagnoses. The contribution of bullying victimization and depression to non-suicidal self-injury adds to the case for the development of trauma-focused interventions in reducing the risk of non-suicidal self-injury among adolescents. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Monitoring HSVtk suicide gene therapy : the role of [F-18]FHPG membrane transport

NARCIS (Netherlands)

Buursma, AR; van Dillen, IJ; van Waarde, A; Vaalburg, W; Hospers, GAP; Mulder, NH; de Vries, EFJ

2004-01-01

Favourable pharmacokinetics of the prodrug are essential for successful HSVtk/ganciclovir (GCV) suicide gene therapy. [F-18] FHPG PET might be a suitable technique to assess the pharmacokinetics of the prodrug GCV noninvasively, provided that [F-18] FHPG mimics the behaviour of GCV. Since membrane

Relationship between Academic Stress and Suicidal Ideation: Testing for Depression as a Mediator Using Multiple Regression

Science.gov (United States)

Ang, Rebecca P.; Huan, Vivien S.

2006-01-01

Relations among academic stress, depression, and suicidal ideation were examined in 1,108 Asian adolescents 12-18 years old from a secondary school in Singapore. Using Baron and Kenny's [J Pers Soc Psychol 51:1173-1192, 1986] framework, this study tested the prediction that adolescent depression mediated the relationship between academic stress…

Allergy is associated with suicide completion with a possible mediating role of mood disorder - a population-based study.

Science.gov (United States)

Qin, P; Mortensen, P B; Waltoft, B L; Postolache, T T

2011-05-01

With increasing research suggesting a role of allergy on suicidality, this study, on a population level, delved into how allergy affects risk for suicide completion in the context of mood disorder and other factors. Based on the entire population of Denmark, we included 27,096 completed suicides and 467,571 live controls matched on sex and age with a nested case-control design. We retrieved personal information on hospital contacts for allergy and other variables from various Danish longitudinal registries and analyzed the data with conditional logistic regression. We noted that 1.17% suicide victims, compared with 0.79% matched controls, had a history of hospital contact for allergy and that a history of allergy predicted an increased risk for suicide completion; however, the effect was confined to allergy that led to inpatient treatment (IRR: 1.59, 95% CI: 1.41-1.80). The increased risk was attenuated somewhat but remained significant when adjusted for personal psychiatric history and socioeconomic status. Meanwhile, we observed a nonsignificantly stronger effect in women than in men, and a significant age difference with a stronger effect for individuals at high ages. Moreover, we detected a significant interaction between allergy and mood disorder - even an antagonism effect of the two exposures. Allergy increased suicide risk only in persons with no history of mood disorder, whereas it eliminated suicide risk in those with a history of mood disorder. The findings support a link between allergy and suicidality, with a possible mediating role of mood disorder. © 2010 John Wiley & Sons A/S.

Child Maltreatment, Subsequent Non-Suicidal Self-Injury and the Mediating Roles of Dissociation, Alexithymia and Self-Blame

Science.gov (United States)

Swannell, Sarah; Martin, Graham; Page, Andrew; Hasking, Penelope; Hazell, Philip; Taylor, Anne; Protani, Melinda

2012-01-01

Objective: Although child maltreatment is associated with later non-suicidal self-injury (NSSI), the mechanism through which it might lead to NSSI is not well understood. The current retrospective case-control study examined associations between child maltreatment and later NSSI, and investigated the mediating roles of dissociation, alexithymia,…

Suicide in Latin America: a growing public health issue.

Science.gov (United States)

Mascayano, Franco; Irrazabal, Matias; D Emilia, Wyatt; Vaner, Sidney Jane; Sapag, Jaime C; Alvarado, Ruben; Yang, Lawrence Hsin; Sinah, Binoy

2015-01-01

Suicide has become an international public mental health challenge, resulting in a need for interventions to address it as an individual, family, and community levels. The current scope review assesses trends regarding suicide within Latin America and the Caribbean: risk factors, protective factors, and mediators of suicidal ideation and behavior. Body: Our review is split into three sections, as a way of addressing the complex topic of suicide in an organized, comprehensive manner: (i) epidemiology of suicide in Latin America and Caribbean; (ii) factors associated to suicide ideation and attempts; and (iii) cultural factors as a predictors and mediators of suicide. Further, proper evidence about the association between suicide and cultural dimensions such as Familismo, Machismo/Marianismo, Religion and Acculturation is provided. Upon analyzing trends of and factors associated with suicide, we offer recommendations regarding future studies and intervention programs. We conclude that interventions and research should be based on and in response to cultural values and norms related to suicide within each community, in order to make more culturally-specific programs.

Risk of Suicide Attempt in Adopted and Nonadopted Offspring

DEFF Research Database (Denmark)

Keyes, M. A.; Malone, S. M.; Sharma, A.

2013-01-01

OBJECTIVE: We asked whether adoption status represented a risk of suicide attempt for adopted and nonadopted offspring living in the United States. We also examined whether factors known to be associated with suicidal behavior would mediate the relationship between adoption status and suicide att...... of the risk of suicide attempt in adopted offspring may inform the larger investigation of suicidality in all adolescents and young adults.......OBJECTIVE: We asked whether adoption status represented a risk of suicide attempt for adopted and nonadopted offspring living in the United States. We also examined whether factors known to be associated with suicidal behavior would mediate the relationship between adoption status and suicide...... attempt. METHODS: Participants were drawn from the Sibling Interaction and Behavior Study, which included 692 adopted and 540 nonadopted offspring and was conducted at the University of Minnesota from 1998 to 2008. Adoptees were systematically ascertained from records of 3 large Minnesota adoption...

Social Anxiety Symptoms and Suicidal Ideation in a Clinical Sample of Early Adolescents: Examining Loneliness and Social Support as Longitudinal Mediators

OpenAIRE

Gallagher, Michelle; Prinstein, Mitchell J.; Simon, Valerie; Spirito, Anthony

2014-01-01

Recent research has shown that social anxiety may be related to increased risk for suicidal ideation in teens, although this research largely has been cross-sectional and has not examined potential mediators of this relationship. A clinical sample of 144 early adolescents (72 % female; 12?15 years old) was assessed during psychiatric inpatient hospitalization and followed up at 9 and 18 months post-baseline. Symptoms of social anxiety, depression, suicidal ideation, loneliness, and perceived ...

Military Suicide Research Consortium (MSRC)

Science.gov (United States)

2013-10-01

suicide research. Suicide and Life-Threatening Behavior, 40(5), 500- 505 . doi:10.1521/suli.2010.40.5.500 Breshears, R. E., Brenner, L. A., Harwood, J...mood symptoms (Baglioni et al., 2010)—all of which may serve to mediate the relationship between insom- nia symptoms and suicidal ideation and behavior...included baseline insom- nia symptom index, MSSI, BHS, PTSD, and MCMI scores. Addi- tional analyses involved a logistic regression examining the relation of

Suicide and Lyme and associated diseases.

Science.gov (United States)

Bransfield, Robert C

2017-01-01

The aim of this paper is to investigate the association between suicide and Lyme and associated diseases (LAD). No journal article has previously performed a comprehensive assessment of this subject. Multiple case reports and other references demonstrate a causal association between suicidal risk and LAD. Suicide risk is greater in outdoor workers and veterans, both with greater LAD exposure. Multiple studies demonstrate many infections and the associated proinflammatory cytokines, inflammatory-mediated metabolic changes, and quinolinic acid and glutamate changes alter neural circuits which increase suicidality. A similar pathophysiology occurs in LAD. A retrospective chart review and epidemiological calculations were performed. LAD contributed to suicidality, and sometimes homicidality, in individuals who were not suicidal before infection. A higher level of risk to self and others is associated with multiple symptoms developing after acquiring LAD, in particular, explosive anger, intrusive images, sudden mood swings, paranoia, dissociative episodes, hallucinations, disinhibition, panic disorder, rapid cycling bipolar, depersonalization, social anxiety disorder, substance abuse, hypervigilance, generalized anxiety disorder, genital-urinary symptoms, chronic pain, anhedonia, depression, low frustration tolerance, and posttraumatic stress disorder. Negative attitudes about LAD from family, friends, doctors, and the health care system may also contribute to suicide risk. By indirect calculations, it is estimated there are possibly over 1,200 LAD suicides in the US per year. Suicidality seen in LAD contributes to causing a significant number of previously unexplained suicides and is associated with immune-mediated and metabolic changes resulting in psychiatric and other symptoms which are possibly intensified by negative attitudes about LAD from others. Some LAD suicides are associated with being overwhelmed by multiple debilitating symptoms, and others are impulsive

The interpersonal theory of suicide and adolescent suicidal behavior.

Science.gov (United States)

Barzilay, S; Feldman, D; Snir, A; Apter, A; Carli, V; Hoven, C W; Wasserman, C; Sarchiapone, M; Wasserman, D

2015-09-01

Joiner's interpersonal theory of suicide (IPTS) proposes that suicide results from the combination of a perception of burdening others, social alienation, and the capability for self-harm. The theory gained some empirical support, however the overall model has yet to be tested. This study aimed to test the main predictions of IPTS in a large community sample of Israeli adolescents. 1196 Israeli Jewish and Arab high-school pupils participating in the SEYLE project completed a self-report questionnaire measuring perceived burdensomeness, thwarted belongingness, health risk behaviors, and non-suicidal self-injury (risk variables), and suicidal ideation and suicide attempts (outcome measures). The data were tested in cross-sectional regression models. Consistent with IPTS, perceived burdensomeness was found to interact with thwarted belongingness, predicting suicidal ideation. Depression mediated most of the effect of thwarted belongingness and perceived burdensomeness on suicidal ideation. Acquired capability for self-harm, as measured by health risk behaviors and direct non-suicidal self-injurious behaviors, predicted suicide attempt. However, this mechanism operated independently from ideation rather than in interaction with it, at variance with IPTS-based predictions. The cross-sectional design precludes conclusions about causality and directionality. Proxy measures were used to test the interpersonal theory constructs. The findings support some of the IPTS predictions but not all, and imply two separate pathways for suicidal behavior in adolescents: one related to internalizing psychopathology and the other to self-harm behaviors. This conceptualization has clinical implications for the differential identification of adolescents at risk for suicidal behavior and for the development of prevention strategies. Copyright © 2015 Elsevier B.V. All rights reserved.

Higher Childhood Peer Reports of Social Preference Mediates the Impact of the Good Behavior Game on Suicide Attempt.

Science.gov (United States)

Newcomer, Alison R; Roth, Kimberly B; Kellam, Sheppard G; Wang, Wei; Ialongo, Nicholas S; Hart, Shelley R; Wagner, Barry M; Wilcox, Holly C

2016-02-01

The Good Behavior Game (GBG) is a universal classroom-based preventive intervention directed at reducing early aggressive, disruptive behavior and improving children's social adaptation into the classroom. The GBG is one of the few universal preventive interventions delivered in early elementary school that has been shown to reduce the risk for future suicide attempts. This paper addresses one potential mechanism by which the GBG lowers the risk of later suicide attempt. In this study, we tested whether the GBG, by facilitating social adaptation into the classroom early on, including the level of social preference by classmates, thereby lowers future risk of suicide attempts. The measure of social adaptation is based on first and second grade peer reports of social preference ("which children do you like best?"; "which children don't you like?"). As part of the hypothesized meditational model, we examined the longitudinal association between childhood peer social preference and the risk of future suicide attempt, which has not previously been examined. Data were from an epidemiologically based randomized prevention trial, which tested the GBG among two consecutive cohorts of first grade children in 19 public schools and 41 classrooms. Results indicated that peer social preference partially mediated the relationship between the GBG and the associated reduction of risk for later suicide attempts by adulthood, specifically among children characterized by their first grade teacher as highly aggressive, disruptive. These results suggest that positive childhood peer relations may partially explain the GBG-associated reduction of risk for suicide attempts and may be an important and malleable protective factor for future suicide attempt.

Suicide gene reveals the myocardial neovascularization role of mesenchymal stem cells overexpressing CXCR4 (MSC(CXCR4.

Directory of Open Access Journals (Sweden)

Jialiang Liang

Full Text Available BACKGROUND: Our previous studies indicated that MSC(CXCR4 improved cardiac function after myocardial infarction (MI. This study was aimed to investigate the specific role of MSC(CXCR4 in neovascularization of infarcted myocardium using a suicide gene approach. METHODS: MSCs were transduced with either lentivirus-null vector/GFP (MSC(Null as control or vector encoding for overexpressing CXCR4/GFP. The MSC derived-endothelial cell (EC differentiation was assessed by a tube formation assay, Dil-ac-LDL uptake, EC marker expression, and VE-cadherin promoter activity assay. Gene expression was analyzed by quantitative RT-PCR or Western blot. The suicide gene approach was under the control of VE-cadherin promoter. In vivo studies: Cell patches containing MSC(Null or MSC(CXCR4 were transduced with suicide gene and implanted into the myocardium of MI rat. Rats received either ganciclovir (GCV or vehicle after cell implantation. After one month, the cardiac functional changes and neovascularization were assessed by echocardiography, histological analysis, and micro-CT imaging. RESULTS: The expression of VEGF-A and HIF-1α was significantly higher in MSC(CXCR4 as compared to MSC(Null under hypoxia. Additionally, MSC(CXCR4 enhanced new vessel formation and EC differentiation, as well as STAT3 phosphorylation under hypoxia. STAT3 participated in the transcription of VE-cadherin in MSC(CXCR4 under hypoxia, which was inhibited by WP1066 (a STAT3 inhibitor. In addition, GCV specifically induced death of ECs with suicide gene activation. In vivo studies: MSC(CXCR4 implantation promoted cardiac functional restoration, reduced infarct size, improved cardiac remodeling, and enhanced neovascularization in ischemic heart tissue. New vessels derived from MSC(CXCR4 were observed at the injured heart margins and communicated with native coronary arteries. However, the derived vessel networks were reduced by GCV, reversing improvement of cardiac function. CONCLUSION: The

A Model of Sexual Abuse's Effects on Suicidal Behavior and Delinquency: The Role of Emotions as Mediating Factors

Science.gov (United States)

Sigfusdottir, Inga Dora; Asgeirsdottir, Bryndis Bjork; Gudjonsson, Gisli H.; Sigurdsson, Jon Fridrik

2008-01-01

Drawing on Agnew's general strain theory, we examined whether depressed mood and anger mediated the effects of sexual abuse on suicidal behavior and delinquency. Participants included 9,113 students attending high schools in Iceland. Structural equation modeling showed that, while controlling for family structure and parental education, being…

Community Structural Instability, Anomie, Imitation and Adolescent Suicidal Behavior

Science.gov (United States)

Thorlindsson, Thorolfur; Bernburg, Jon Gunnar

2009-01-01

The current study examines the contextual effects of community structural characteristics, as well as the mediating role of key social mechanisms, on youth suicidal behavior in Iceland. We argue that the contextual influence of community structural instability on youth suicidal behavior should be mediated by weak attachment to social norms and…

Body dysmorphic disorder symptoms and risk for suicide: The role of depression.

Science.gov (United States)

Shaw, A M; Arditte Hall, K A; Rosenfield, E; Timpano, K R

2016-12-01

Body dysmorphic disorder (BDD) is associated with elevated suicidality. Little is known about why BDD patients are at increased risk. The interpersonal-psychological theory of suicide (IPTS) could clarify suicidality in BDD, and theorizes that perceived burdensomeness and thwarted belongingness lead to suicidal desire, while an acquired capability for suicide is necessary to attempt suicide. No study has investigated how BDD symptoms relate to IPTS constructs or mediators of the relationship between BDD and suicidality. Individuals (N=235) enrolled in Amazon.com's Mechanical Turk (MTurk), who had appearance concerns, completed questionnaires about BDD, depression, eating pathology, and suicide risk. MTurk is an online data collection platform in which participants complete surveys for payment. BDD symptoms predicted suicidal desire, but not acquired capability for suicide. Depression mediated the relationship between BDD and suicidal desire. Research should examine how fluctuations in BDD affect suicide risk. Replication in a clinical sample may inform treatments for BDD. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Impact of Negative Life Events on Attempted Suicide in Rural China.

Science.gov (United States)

Liu, Yanzheng; Zhang, Jie

2018-03-01

This study aims to explore the impact of negative life events (NLEs) on attempted suicide in a Chinese cultural setting. The sample comprised 791 suicide attempters and an equal number of controls matched on age, sex, and location from selected rural counties in China. Conditional logistic regression model was used to examine the association between NLEs and suicide risk. The impact of NLEs on attempted suicide was further examined using regression-based method to explore its mediation effect. The types of NLEs that were most likely to precede a suicide attempt in rural sample included the events in marriage/love, family/home, and friend/relationship. Rural women were more likely to experience more interpersonal conflicts than rural men. Approximately 75.6% of suicide attempters had experienced at least one NLE, and NLEs were strongly associated with attempted suicide. Total effect (0.676), direct effect (0.501), and the total indirect effect (0.301) of NLEs on suicide attempts were significantly mediated by hopelessness and depression. NLEs play a crucial role in predicting suicidal attempt in rural China, and they are mediated by depression and hopelessness.

Bifidobacterial recombinant thymidine kinase-ganciclovir gene therapy system induces FasL and TNFR2 mediated antitumor apoptosis in solid tumors

International Nuclear Information System (INIS)

Wang, Changdong; Ma, Yongping; Hu, Qiongwen; Xie, Tingting; Wu, Jiayan; Zeng, Fan; Song, Fangzhou

2016-01-01

Directly targeting therapeutic suicide gene to a solid tumor is a hopeful approach for cancer gene therapy. Treatment of a solid tumor by an effective vector for a suicide gene remains a challenge. Given the lack of effective treatments, we constructed a bifidobacterial recombinant thymidine kinase (BF-rTK) -ganciclovir (GCV) targeting system (BKV) to meet this requirement and to explore antitumor mechanisms. Bifidobacterium (BF) or BF-rTK was injected intratumorally with or without ganciclovir in a human colo320 intestinal xenograft tumor model. The tumor tissues were analyzed using apoptosis antibody arrays, real time PCR and western blot. The colo320 cell was analyzed by the gene silencing method. Autophagy and necroptosis were also detected in colo320 cell. Meanwhile, three human digestive system xenograft tumor models (colorectal cancer colo320, gastric cancer MKN-45 and liver cancer SSMC-7721) and a breast cancer (MDA-MB-231) model were employed to validate the universality of BF-rTK + GCV in solid tumor gene therapy. The survival rate was evaluated in three human cancer models after the BF-rTK + GCV intratumor treatment. The analysis of inflammatory markers (TNF-α) in tumor indicated that BF-rTK + GCV significantly inhibited TNF-α expression. The results suggested that BF-rTK + GCV induced tumor apoptosis without autophagy and necroptosis occurrence. The apoptosis was transduced by multiple signaling pathways mediated by FasL and TNFR2 and mainly activated the mitochondrial control of apoptosis via Bid and Bim, which was rescued by silencing Bid or/and Bim. However, BF + GCV only induced apoptosis via Fas/FasL signal pathway accompanied with increased P53 expression. We further found that BF-rTK + GCV inhibited the expression of the inflammatory maker of TNF-α. However, BF-rTK + GCV did not result in necroptosis and autophagy. BF-rTK + GCV induced tumor apoptosis mediated by FasL and TNFR2 through the mitochondrial control of apoptosis via Bid and Bim

Personality disorder traits, risk factors, and suicide ideation among older adults.

Science.gov (United States)

Jahn, Danielle R; Poindexter, Erin K; Cukrowicz, Kelly C

2015-11-01

Personality disorder traits are relatively prevalent among older adults, and can be associated with complex and chronic difficulties, including suicide risk. However, there is a lack of research regarding personality disorders and suicide ideation in older adults. Depressive symptoms and hopelessness may be important to the relation between personality disorders and suicide risk. Additionally, variables from the interpersonal theory of suicide, perceived burdensomeness and thwarted belongingness, may be critical risk factors for suicide in this population. We hypothesized that perceived burdensomeness and thwarted belongingness, theory-based variables, would act as parallel mediators of the relation between personality disorder traits and suicide ideation, whereas depressive symptoms and hopelessness would not. The hypothesis was tested in a sample of 143 older adults recruited from a primary care setting. Participants completed self-report questionnaires of personality traits, suicide ideation, depressive symptoms, hopelessness, perceived burdensomeness, and thwarted belongingness. Findings from a non-parametric bootstrapping procedure indicated that perceived burdensomeness, thwarted belongingness, and depressive symptoms mediated the relation between total personality disorder traits and suicide ideation. Hopelessness did not act as a mediator. These findings indicate that perceived burdensomeness, thwarted belongingness, and depressive symptoms are likely important risk factors for suicide ideation among older adults. Clinicians should be aware of these issues when assessing and treating suicide risk among older adults.

Suicidal ideation in adolescence: examining the role of recent adverse experiences.

Science.gov (United States)

Thompson, Richard; Proctor, Laura J; English, Diana J; Dubowitz, Howard; Narasimhan, Subasri; Everson, Mark D

2012-02-01

Although there is a well-known link between adverse experiences and suicidal ideation, there has been little study of the effects of recent adverse experiences on suicidal ideation in teenagers. This study examined the association between recent adverse experiences and suicidal ideation in a sample of 740 at-risk 16-year-old youth in the LONGSCAN studies, as well as potential mediators. 8.9% of the youth reported suicidal ideation. Recent adverse experiences, as a class, were associated with suicidal ideation; both recent physical abuse and recent psychological maltreatment were uniquely associated with suicidal ideation. The links between recent adverse experiences and suicidal ideation were significantly mediated by psychological distress. There were also significant main effect associations between both internalizing behavioral problems and low positive achievement expectations and suicidal ideation. Recent adverse experiences are important in understanding suicidal ideation in high risk youth. Copyright © 2011 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Posttraumatic stress disorder and suicidal ideation, plans, and impulses: The mediating role of anxiety sensitivity cognitive concerns among veterans.

Science.gov (United States)

Raines, Amanda M; Capron, Daniel W; Stentz, Lauren A; Walton, Jessica L; Allan, Nicholas P; McManus, Eliza S; Uddo, Madeline; True, Gala; Franklin, C Laurel

2017-11-01

Although the relationship between posttraumatic stress disorder (PTSD) and suicide has been firmly established, research on underlying mechanisms has been disproportionately low. The cognitive concerns subscale of anxiety sensitivity (AS), which reflects fears of cognitive dyscontrol, has been linked to both PTSD and suicide and thus may serve as an explanatory mechanism between these constructs. The sample consisted of 60 male veterans presenting to an outpatient Veteran Affairs (VA) clinic for psychological services. Upon intake, veterans completed a diagnostic interview and brief battery of self-report questionnaires to assist with differential diagnosis and treatment planning. Results revealed a significant association between PTSD symptom severity and higher suicidality (i.e., ideation, plans, and impulses), even after accounting for relevant demographic and psychological constructs. Moreover, AS cognitive concerns mediated this association. Limitations include the small sample size and cross-sectional nature of the current study. These findings add considerably to a growing body of literature examining underlying mechanisms that may help to explain the robust associations between PTSD and suicide. Considering the malleable nature of AS cognitive concerns, research is needed to determine the extent to which reductions in this cognitive risk factor are associated with reductions in suicide among at risk samples, such as those included in the present investigation. Published by Elsevier B.V.

Suicide and Lyme and associated diseases

Directory of Open Access Journals (Sweden)

Bransfield RC

2017-06-01

Full Text Available Robert C Bransfield Department of Psychiatry, Rutgers-RWJ Medical School, Piscataway, NJ, USA Purpose: The aim of this paper is to investigate the association between suicide and Lyme and associated diseases (LAD. No journal article has previously performed a comprehensive assessment of this subject.Introduction: Multiple case reports and other references demonstrate a causal association between suicidal risk and LAD. Suicide risk is greater in outdoor workers and veterans, both with greater LAD exposure. Multiple studies demonstrate many infections and the associated proinflammatory cytokines, inflammatory-mediated metabolic changes, and quinolinic acid and glutamate changes alter neural circuits which increase suicidality. A similar pathophysiology occurs in LAD.Method: A retrospective chart review and epidemiological calculations were performed.Results: LAD contributed to suicidality, and sometimes homicidality, in individuals who were not suicidal before infection. A higher level of risk to self and others is associated with multiple symptoms developing after acquiring LAD, in particular, explosive anger, intrusive images, sudden mood swings, paranoia, dissociative episodes, hallucinations, disinhibition, panic disorder, rapid cycling bipolar, depersonalization, social anxiety disorder, substance abuse, hypervigilance, generalized anxiety disorder, genital–urinary symptoms, chronic pain, anhedonia, depression, low frustration tolerance, and posttraumatic stress disorder. Negative attitudes about LAD from family, friends, doctors, and the health care system may also contribute to suicide risk. By indirect calculations, it is estimated there are possibly over 1,200 LAD suicides in the US per year.Conclusion: Suicidality seen in LAD contributes to causing a significant number of previously unexplained suicides and is associated with immune-mediated and metabolic changes resulting in psychiatric and other symptoms which are possibly

Hypoxia-targeted suicidal gene therapy system enhances antitumor effects of radiotherapy

International Nuclear Information System (INIS)

Liu Junye; Guo Yao; Guo Guozhen

2006-01-01

Objective: To explore the effects of hypoxia-targeted suicidal gene therapy system combined with radiotherapy on pancreatic cancer. Methods: The recombinant adenovirus Ad-5HRE/hCMVmp-BCD was constructed by DNA recombinant technique. Western blot was used to detect hypoxia-induced expression of bacterial cytosine deaminase (BCD). Cell growth inhibition assay was used to determine the sensitivity of human pancreatic cancer cells MIA-PACA2 to 5-fluorocytosine (5-FC). Tumor xenograft growth delay assays was used to evaluate the effects of Ad-5HRE/hCMVmp-BCD/5-FC combined with radiotherapy on pancreatic cancer. Results: Western blot analysis demonstrated that hypoxia-induced BCD protein expression was achieved in MIA-PACA2 cells infected with Ad-5HRE/hCMVmp-BCD. With hypoxia treatment, the sensitivity of MIA-PACA2 cells infected with Ad-5HRE/hCMVmp-BCD to 5-FC significantly increased. Administration of either Ad-5HRE/hCMVmp-BCD/5-FC or radiotherapy could inhibit the growth of MIA-PACA2 xenografts in nude mice. Moreover, combination of Ad-5HRE/hCMVmp-BCD/5-FC could significantly enhance suppressing effects of radiotherapy on MIA-PACA2 xenografts. Conclusion: Hypoxia-targeted suicidal gene therapy system Ad-5HRE/hCMVmp-BCD/5-FC could enhance antitumor effects of radiotherapy on pancreatic cancer and can be used as a powerful adjunct to conventional radiotherapy. (authors)

Methylomic profiling of cortex samples from completed suicide cases implicates a role for PSORS1C3 in major depression and suicide.

Science.gov (United States)

Murphy, T M; Crawford, B; Dempster, E L; Hannon, E; Burrage, J; Turecki, G; Kaminsky, Z; Mill, J

2017-01-03

Major depressive disorder (MDD) represents a major social and economic health issue and constitutes a major risk factor for suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesised that regulatory genomic processes are involved in the pathology of both MDD and suicidality. In this study, genome-wide patterns of DNA methylation were assessed in depressed suicide completers (n=20) and compared with non-psychiatric, sudden-death controls (n=20) using tissue from two cortical brain regions (Brodmann Area 11 (BA11) and Brodmann Area 25 (BA25)). Analyses focused on identifying differentially methylated regions (DMRs) associated with suicidal depression and epigenetic variation were explored in the context of polygenic risk scores for major depression and suicide. Weighted gene co-methylation network analysis was used to identify modules of co-methylated loci associated with depressed suicide completers and polygenic burden for MDD and suicide attempt. We identified a DMR upstream of the PSORS1C3 gene, subsequently validated using bisulfite pyrosequencing and replicated in a second set of suicide samples, which is characterised by significant hypomethylation in both cortical brain regions in MDD suicide cases. We also identified discrete modules of co-methylated loci associated with polygenic risk burden for suicide attempt, but not major depression. Suicide-associated co-methylation modules were enriched among gene networks implicating biological processes relevant to depression and suicidality, including nervous system development and mitochondria function. Our data suggest that there are coordinated changes in DNA methylation associated with suicide that may offer novel insights into the molecular pathology associated with depressed suicide completers.

Methylomic profiling of cortex samples from completed suicide cases implicates a role for PSORS1C3 in major depression and suicide

Science.gov (United States)

Murphy, T M; Crawford, B; Dempster, E L; Hannon, E; Burrage, J; Turecki, G; Kaminsky, Z; Mill, J

2017-01-01

Major depressive disorder (MDD) represents a major social and economic health issue and constitutes a major risk factor for suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesised that regulatory genomic processes are involved in the pathology of both MDD and suicidality. In this study, genome-wide patterns of DNA methylation were assessed in depressed suicide completers (n=20) and compared with non-psychiatric, sudden-death controls (n=20) using tissue from two cortical brain regions (Brodmann Area 11 (BA11) and Brodmann Area 25 (BA25)). Analyses focused on identifying differentially methylated regions (DMRs) associated with suicidal depression and epigenetic variation were explored in the context of polygenic risk scores for major depression and suicide. Weighted gene co-methylation network analysis was used to identify modules of co-methylated loci associated with depressed suicide completers and polygenic burden for MDD and suicide attempt. We identified a DMR upstream of the PSORS1C3 gene, subsequently validated using bisulfite pyrosequencing and replicated in a second set of suicide samples, which is characterised by significant hypomethylation in both cortical brain regions in MDD suicide cases. We also identified discrete modules of co-methylated loci associated with polygenic risk burden for suicide attempt, but not major depression. Suicide-associated co-methylation modules were enriched among gene networks implicating biological processes relevant to depression and suicidality, including nervous system development and mitochondria function. Our data suggest that there are coordinated changes in DNA methylation associated with suicide that may offer novel insights into the molecular pathology associated with depressed suicide completers. PMID:28045465

Association between norepinephrine transporter gene (SLC6A2) polymorphisms and suicide in patients with major depressive disorder.

Science.gov (United States)

Kim, Yong-Ku; Hwang, Jung-A; Lee, Heon-Jeong; Yoon, Ho-Kyoung; Ko, Young-Hoon; Lee, Bun-Hee; Jung, Han-Yong; Hahn, Sang-Woo; Na, Kyoung-Sae

2014-04-01

Although several studies have investigated possible associations between norepinephrine neurotransmitter transporter gene (SLC6A2) polymorphisms and depression, few studies have examined associations between SLC6A2 polymorphisms and suicide. Three single-nucleotide polymorphisms (rs2242446, rs28386840, and rs5569) were measured in 550 patients: 201 with major depressive disorder (MDD) and suicide attempt/s, 160 with MDD without suicide attempts, and 189 healthy controls. Analysis of single-nucleotide polymorphisms (SNPs) and haplotype was conducted for the three groups. Subsequently, multivariate logistic regression analysis adjusting for age and gender was conducted to identify independent influences of each SNP. A possible association between suicide lethality and SLC6A2 polymorphisms was also investigated. In the genotype and allele frequency analysis, there were significant differences in rs28386840 between suicidal MDD patients and healthy controls. In the haplotype analysis, TAA (rs2242446-rs28386840-rs5569, from left to right) was associated with suicide attempts in MDD, although the significance (p=0.043) disappeared after Bonferroni correction. There were no relationships between lethality scores and SLC6A2 polymorphisms in suicidal MDD. Modest sample size and a single type of neurotransmitter analyzed (norepinephrine) are the primary limitations. Our results suggest that SLC6A2 polymorphisms were associated with suicide risk in patients with MDD. Future studies are warranted to elucidate possible mechanisms by which SLC6A2 polymorphisms influence suicide risk. Copyright © 2014 Elsevier B.V. All rights reserved.

The Mediating Roles of Stress and Maladaptive Behaviors on Self-Harm and Suicide Attempts among Runaway and Homeless Youth

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Moskowitz, Amanda; Stein, Judith A.; Lightfoot, Marguerita

2013-01-01

Runaway and homeless youth often have a constellation of background behavioral, emotional, and familial problems that contribute to stress and maladaptive behaviors, which, in turn, can lead to self-harming and suicidal behaviors. The current study examined the roles of stress and maladaptive behaviors as mediators between demographic and…

Positive-negative-selection-mediated gene targeting in rice

Directory of Open Access Journals (Sweden)

Zenpei eShimatani

2015-01-01

Full Text Available Gene targeting (GT refers to the designed modification of genomic sequence(s through homologous recombination (HR. GT is a powerful tool both for the study of gene function and for molecular breeding. However, in transformation of higher plants, non-homologous end joining (NHEJ occurs overwhelmingly in somatic cells, masking HR-mediated GT. Positive-negative selection (PNS is an approach for finding HR-mediated GT events because it can eliminate NHEJ effectively by expression of a negative-selection marker gene. In rice—a major crop worldwide—reproducible PNS-mediated GT of endogenous genes has now been successfully achieved. The procedure is based on strong PNS using diphtheria toxin A-fragment as a negative marker, and has succeeded in the directed modification of several endogenous rice genes in various ways. In addition to gene knock-outs and knock-ins, a nucleotide substitution in a target gene was also achieved recently. This review presents a summary of the development of the rice PNS system, highlighting its advantages. Different types of gene modification and gene editing aimed at developing new plant breeding technology (NPBT based on PNS are discussed.

Brain-derived neurotrophic factor: role in depression and suicide

Directory of Open Access Journals (Sweden)

Yogesh Dwivedi

2009-08-01

Full Text Available Yogesh DwivediPsychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USAAbstract: Depression and suicidal behavior have recently been shown to be associated with disturbances in structural and synaptic plasticity. Brain-derived neurotrophic factor (BDNF, one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons and in synaptic plasticity. Several lines of evidence suggest that BDNF is involved in depression, such that the expression of BDNF is decreased in depressed patients. In addition, antidepressants up-regulate the expression of BDNF. This has led to the proposal of the “neurotrophin hypothesis of depression”. Increasing evidence demonstrates that suicidal behavior is also associated with lower expression of BDNF, which may be independent from depression. Recent genetic studies also support a link of BDNF to depression/suicidal behavior. Not only BDNF, but abnormalities in its cognate receptor tropomycin receptor kinase B (TrkB and its splice variant (TrkB.T1 have also been reported in depressed/suicidal patients. It has been suggested that epigenetic modulation of the Bdnf and Trkb genes may contribute to their altered expression and functioning. More recently, impairment in the functioning of pan75 neurotrophin receptor has been reported in suicide brain specimens. pan75 neurotrophin receptor is a low-affinity neurotrophin receptor that, when expressed in conjunction with low availability of neurotropins/Trks, induces apoptosis. Overall, these studies suggest the possibility that BDNF and its mediated signaling may participate in the pathophysiology of depression and suicidal behavior. This review focuses on the critical evidence demonstrating the involvement of BDNF in depression and suicide.Keywords: BDNF, neurotrophins, p75NTR, Trk receptor, depression, antidepressants, suicide, genetics, epigenetics

Mediator and Cohesin Connect Gene Expression and Chromatin Architecture

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Kagey, Michael H.; Newman, Jamie J.; Bilodeau, Steve; Zhan, Ye; Orlando, David A.; van Berkum, Nynke L.; Ebmeier, Christopher C.; Goossens, Jesse; Rahl, Peter B.; Levine, Stuart S.; Taatjes, Dylan J.; Dekker, Job; Young, Richard A.

2010-01-01

Summary Transcription factors control cell specific gene expression programs through interactions with diverse coactivators and the transcription apparatus. Gene activation may involve DNA loop formation between enhancer-bound transcription factors and the transcription apparatus at the core promoter, but this process is not well understood. We report here that Mediator and Cohesin physically and functionally connect the enhancers and core promoters of active genes in embryonic stem cells. Mediator, a transcriptional coactivator, forms a complex with Cohesin, which can form rings that connect two DNA segments. The Cohesin loading factor Nipbl is associated with Mediator/Cohesin complexes, providing a means to load Cohesin at promoters. DNA looping is observed between the enhancers and promoters occupied by Mediator and Cohesin. Mediator and Cohesin occupy different promoters in different cells, thus generating cell-type specific DNA loops linked to the gene expression program of each cell. PMID:20720539

Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro

Science.gov (United States)

Teng, Geling; Ju, Yuanrong; Yang, Yepeng; Hua, Hu; Chi, Jingyu; Mu, Xiuan

2016-01-01

Escherichia coli nitroreductase (NTR) may convert the prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) into a bifunctional alkylating agent, which may lead to DNA crosslinks and the apoptosis of cancer cells. NTR/CB1954 has been demonstrated to be an effective gene therapy in cancer cells. The present study examined whether the NTR/CB1954 suicide gene system had cytotoxic effects on HeLa cells and may improve the radiosensitivity of HeLa cells to γ-rays. It was observed that the NTR/CB1954 suicide gene system exerted marked cytotoxic effects on HeLa cells. The combined therapeutic effects of NTR/CB1954 and γ-rays on HeLa cells demonstrated a synergistic effect. CB1954 at concentrations of 12.5 and 25 µmol/l increased the sensitization enhancement ratio of HeLa cells to 1.54 and 1.66, respectively. Therefore, when compared with monotherapy, the combined therapy of NTR/CB1954 and γ-rays may increase the apoptotic rate and enhance the radiosensitivity of HeLa cells. The combined therapy of γ-ray radiation and the NTR/CB1954 suicide gene system may be a novel and potent therapeutic method for the treatment of cervical carcinoma. PMID:27840931

Study to Examine Psychological Processes in Suicidal Ideation and Behavior (STEPPS)

Science.gov (United States)

2015-05-01

2007). Impulsivity and suicidality : A test of the mediating role of painful experiences. Unpublished manuscript. Univeristy of FloridaBrenner, L.A...diagnoses to better understand suicide ; suicide is the result of a complex interplay of psychological, social and biological factors. A more...sophisticated attempt to model the antecedents of suicidal behavior is needed to understand the basic mechanisms underpinning suicide . Military personnel

Functional disability and suicidal behavior in middle-aged and older adults: A systematic critical review.

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Lutz, Julie; Fiske, Amy

2018-02-01

Middle-aged and older adults have elevated rates of suicide around the globe, but there is a paucity of knowledge about risk factors for suicide in these age groups. One possible risk factor may be functional disability, which is more common at later ages. The current systematic critical review examined findings regarding the associations between functional disability and suicidal behavior (suicidal ideation, suicide attempts, and death by suicide) in middle-aged and older adults (i.e. age 50 and older). Forty-five studies were found that examined these associations. The majority of studies supported a significant association between functional disability and suicidal ideation. In addition, findings to date strongly suggest that depression serves as a mediator of the association between functional disability and suicidal ideation, though most studies did not directly test for mediation. Firm conclusions regarding suicide attempts and death by suicide, as well as mediation, cannot be drawn due to a relative lack of research in these areas. The association between functional disability and suicidal behavior suggests an important area for prevention and intervention among middle-aged and older adults, but additional research is necessary to clarify the specifics of these associations and examine appropriate intervention strategies. Important future directions for research in this area include the direct comparison of associations of risk factors with different types of suicidal behavior, greater use of longitudinal data with multiple time points, and further examination of potential mediators and moderators of the association between functional disability and suicidal behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

Association between a genetic variant in the serotonin transporter gene (SLC6A4 and suicidal behavior in patients with schizophrenia

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Lindholm Carlström Eva

2012-05-01

Full Text Available Abstract Background The serotonin (5-hydroxytryptamin; 5-HT system has a central role in the circuitry of cognition and emotions. Multiple lines of evidence suggest that genetic variation in the serotonin transporter gene (SLC6A4; 5-HTT is associated with schizophrenia and suicidal behavior. In this study, we wanted to elucidate whether SLC6A4 variations is involved in attempted suicide among patients with schizophrenia in a Scandinavian case–control sample. Methods Patients diagnosed with schizophrenia from three Scandinavian samples were assessed for presence or absence of suicide attempts, based on record reviews and interview data. Seven SLC6A4 single nucleotide polymorphisms (SNPs were genotyped in 837 schizophrenia patients and 1,473 control individuals. Association analyses and statistical evaluations were performed with the program UNPHASED (version 3.0.9. Results We observed an allele association between the SNP rs16965628, located in intron one of SLC6A4, and attempted suicide (adjusted p-value 0.01, among patients with schizophrenia. No association was found to a diagnosis of schizophrenia, when patients were compared to healthy control individuals. Conclusion The gene SLC6A4 appears to be involved in suicidal ideation among patients with schizophrenia. Independent replication is needed before more firm conclusions can be drawn.

Mental illness stigma, secrecy and suicidal ideation.

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Oexle, N; Ajdacic-Gross, V; Kilian, R; Müller, M; Rodgers, S; Xu, Z; Rössler, W; Rüsch, N

2017-02-01

Whether the public stigma associated with mental illness negatively affects an individual, largely depends on whether the person has been labelled 'mentally ill'. For labelled individuals concealing mental illness is a common strategy to cope with mental illness stigma, despite secrecy's potential negative consequences. In addition, initial evidence points to a link between stigma and suicidality, but quantitative data from community samples are lacking. Based on previous literature about mental illness stigma and suicidality, as well as about the potential influence of labelling processes and secrecy, a theory-driven model linking perceived mental illness stigma and suicidal ideation by a mediation of secrecy and hopelessness was established. This model was tested separately among labelled and unlabelled persons using data derived from a Swiss cross-sectional population-based study. A large community sample of people with elevated psychiatric symptoms was examined by interviews and self-report, collecting information on perceived stigma, secrecy, hopelessness and suicidal ideation. Participants who had ever used mental health services were considered as labelled 'mentally ill'. A descriptive analysis, stratified logistic regression models and a path analysis testing a three-path mediation effect were conducted. While no significant differences between labelled and unlabelled participants were observed regarding perceived stigma and secrecy, labelled individuals reported significantly higher frequencies of suicidal ideation and feelings of hopelessness. More perceived stigma was associated with suicidal ideation among labelled, but not among unlabelled individuals. In the path analysis, this link was mediated by increased secrecy and hopelessness. Results from this study indicate that among persons labelled 'mentally ill', mental illness stigma is a contributor to suicidal ideation. One explanation for this association is the relation perceived stigma has with

Emotion Reactivity, Comfort Expressing Emotions, and Future Suicidal Ideation in Emerging Adults.

Science.gov (United States)

Polanco-Roman, Lillian; Moore, Alyssa; Tsypes, Aliona; Jacobson, Colleen; Miranda, Regina

2018-01-01

Emotion reactivity and difficulties in expressing emotions have been implicated in risk for suicidal behavior. This study examined comfort in expressing emotions (positive vs. negative) and depressive symptoms as mediators of the prospective relation between emotion reactivity and suicidal ideation. Emerging adults (N = 143; 72% female; 28% White) completed measures of emotion reactivity, comfort expressing emotions, and suicidal ideation at baseline and of depressive symptoms and suicidal ideation 12 months later. Emotion reactivity predicted suicidal ideation at follow-up through depressive symptoms. Difficulty expressing love-but not happiness, sadness, and anger-partially mediated the relationship between emotion reactivity and suicidal ideation at follow-up before but not after adjusting for baseline ideation. The relation between high emotion reactivity and suicidal ideation may be explained by discomfort in the expression of positive emotions and by depressive symptoms. Promotion of comfort in positive emotion expression may reduce vulnerability to suicidal ideation. © 2017 Wiley Periodicals, Inc.

Mental illness stigma and suicidality: the role of public and individual stigma.

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Oexle, N; Waldmann, T; Staiger, T; Xu, Z; Rüsch, N

2018-04-01

Suicide rates are increased among unemployed individuals and mental illness stigma can contribute to both unemployment and suicidality. Persons with mental illness perceive negative attitudes among the general public and experience discrimination in their everyday life (=public stigma components) potentially leading to self-stigma and anticipated discrimination (=individual stigma components). Previous research found evidence for an association between aspects of mental illness stigma and suicidality, but has not yet clarified the underlying pathways explaining how different stigma components interact and contribute to suicidal ideation. Public and individual stigma components and their association with suicidal ideation were examined among 227 unemployed persons with mental illness. A path model linking public stigma components (experienced discrimination, perceived stigma) with suicidal ideation, mediated by individual stigma components (anticipated discrimination, self-stigma), was examined using structural equation modelling within Mplus. Our sample was equally split in terms of gender, on average 43 years old and about half reported no suicidal ideation during the past 30 days. In bivariate analyses all stigma components were significantly associated with suicidal ideation. In the path model and controlling for symptoms, the association between experienced discrimination and suicidal ideation was fully mediated by anticipated discrimination and self-stigma. Perceived stigma's contribution to suicidal ideation was fully mediated by anticipated discrimination, but not by self-stigma. In general, programmes addressing multiple stigma components seem to be most effective in improving suicide prevention. Besides interventions targeting negative attitudes and discriminating behaviours of the general public, programmes to support persons with mental illness in coping with perceived and experienced stigma could improve suicide prevention. Future studies should test

Body mass index, depression, and suicidality: The role of self-esteem in bariatric surgery candidates.

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Yusufov, Miryam; Dalrymple, Kristy; Bernstein, Michael H; Walsh, Emily; Rosenstein, Lia; Chelminski, Iwona; Zimmerman, Mark

2017-01-15

Previous research suggests a relationship between weight and depression/suicidality, although few studies have examined the mechanisms underlying this association. This study examined the mediating role of self-esteem in the relationship between BMI and depression/suicidality, as well as the moderating role of gender in the mediated pathways. As part of a screening process in consideration for bariatric surgery, 3,101 adults (81.4% female, 18.6% male) were assessed one time. Five univariate mediation and five univariate moderated-mediation models were hypothesized and analyzed. For the mediation models, we entered five outcome variables separately: 1) severity of depressed mood, 2) diagnosis of Major Depressive Disorder, 3) lifetime history of suicide attempts, 4) suicidal ideation at the time of evaluation, and 5) severity of suicidality, BMI as the independent variable, and self-esteem as the mediator. For the moderated-mediated models, gender was examined as a moderator to examine whether self-esteem was a stronger mediator for one gender, compared to the other. Findings supported the mediating role of self-esteem across all five outcomes. Further, the mediated effect was moderated by gender, such that the mediation effect was stronger for males, compared to females. The majority of the sample consisted of White females, limiting broad applicability of findings. All variables were assessed simultaneously, at baseline, limiting the ability to make causal attributions. Study findings suggest that self-esteem may help explain the relationship between BMI and depression/suicidality, particularly for men. Thus, interventions targeting self-esteem may be useful for improving psychological outcomes among those presenting for bariatric surgery. Copyright © 2016 Elsevier B.V. All rights reserved.

Single agent- and combination treatment with two targeted suicide gene therapy systems is effective in chemoresistant small cell lung cancer cells

DEFF Research Database (Denmark)

Michaelsen, Signe R; Christensen, Camilla L; Sehested, Maxwell

2012-01-01

Transcriptional targeted suicide gene (SG) therapy driven by the insulinoma-associated 1 (INSM1) promoter makes it possible to target suicide toxin production and cytotoxicity exclusively to small cell lung cancer (SCLC) cells and tumors. It remains to be determined whether acquired chemoresistance......, as observed in the majority of SCLC patients, desensitizes SCLC cells to INSM1 promoter-driven SG therapy....

Traumatic Brain Injury, Sleep Quality, and Suicidal Ideation in Iraq/Afghanistan Era Veterans.

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DeBeer, Bryann B; Kimbrel, Nathan A; Mendoza, Corina; Davidson, Dena; Meyer, Eric C; La Bash, Heidi; Gulliver, Suzy Bird; Morissette, Sandra B

2017-07-01

The objective of this study was to test the hypothesis that sleep quality mediates the association between traumatic brain injury (TBI) history and current suicidal ideation. Measures of TBI history, sleep quality, and suicidal ideation were administered to 130 Iraq/Afghanistan veterans. As expected, sleep quality mediated the effect of TBI history on current suicidal ideation (indirect effect, 0.0082; 95% confidence interval, 0.0019-0.0196), such that history of TBI was associated with worse sleep quality, which was, in turn, associated with increased suicidal ideation. These findings highlight the importance of assessing TBI history and sleep quality during suicide risk assessments for veterans.

Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro.

Science.gov (United States)

Teng, Geling; Ju, Yuanrong; Yang, Yepeng; Hua, Hu; Chi, Jingyu; Mu, Xiuan

2016-12-01

Escherichia coli nitroreductase (NTR) may convert the prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) into a bifunctional alkylating agent, which may lead to DNA crosslinks and the apoptosis of cancer cells. NTR/CB1954 has been demonstrated to be an effective gene therapy in cancer cells. The present study examined whether the NTR/CB1954 suicide gene system had cytotoxic effects on HeLa cells and may improve the radiosensitivity of HeLa cells to γ‑rays. It was observed that the NTR/CB1954 suicide gene system exerted marked cytotoxic effects on HeLa cells. The combined therapeutic effects of NTR/CB1954 and γ‑rays on HeLa cells demonstrated a synergistic effect. CB1954 at concentrations of 12.5 and 25 µmol/l increased the sensitization enhancement ratio of HeLa cells to 1.54 and 1.66, respectively. Therefore, when compared with monotherapy, the combined therapy of NTR/CB1954 and γ‑rays may increase the apoptotic rate and enhance the radiosensitivity of HeLa cells. The combined therapy of γ‑ray radiation and the NTR/CB1954 suicide gene system may be a novel and potent therapeutic method for the treatment of cervical carcinoma.

Cognitive vulnerability to depression, rumination, hopelessness, and suicidal ideation: multiple pathways to self-injurious thinking.

Science.gov (United States)

Smith, Jeannette M; Alloy, Lauren B; Abramson, Lyn Y

2006-08-01

In order to advance the detection and prevention of suicide, recent research has focused on predictors of suicidal ideation and behavior such as negative cognitive styles, dysfunctional attitudes, hopelessness, and rumination. In this study the relationships among these risk factors in the context of the Attention Mediated Hopelessness (AMH) theory of depression are examined. One hundred and twenty-seven undergraduates in the Cognitive Vulnerability to Depression (CVD) project were followed for 2.5 years. The CVD project followed initially nondepressed freshmen, at either high or low cognitive risk for depression, in order to predict onsets and recurrences of depressive disorders. The presence and duration of suicidal ideation were predicted prospectively by rumination and hopelessness, and hopelessness partially mediated the relationship between rumination and ideation and fully mediated the association between rumination and duration of suicidality. Further, rumination mediated the relationship between cognitive vulnerability and suicidal ideation.

Optimizing Screening and Risk Assessment for Suicide Risk in the U.S. Military

Science.gov (United States)

2015-03-01

thoughts of death/ suicide , perceived controllability of suicidal thoughts, and suicidal impulses , all loaded onto a separate factor. These finding... suicidal thoughts as well as plans and impulses for suicidal behavior. For each question, participants are asked to respond using a four-point likert...1222. Bender, T., Gordon, K., Bresin, K., & Joiner, T. (2011). Impulsivity and suicidality : The mediating role of painful and provocative experiences

An experimental study on cervix cancer with combination of HSV-TK/GCV suicide gene therapy system and 60Co radiotherapy

International Nuclear Information System (INIS)

Chen, Daozhen; Tang, Qiusha

2010-01-01

To evaluate the killing effect of HSV-TK/GCV suicide gene therapy system combined with 60 Co radiotherapy on human cervical cancer Hela cell line in vitro and in vivo, and to explore the radiosensitization by HSV-TK/GCV system. HSV-TK/GCV suicide gene therapy system and 60 Co radiotherapy were used separately or in combination on human cervical cancer Hela cell line in vitro and in vivo to compare their effects. Colony formation test and the rate of radiosensitization effect (E/O) were employed to observed the radiosensitization by HSV-TK/GCV system. HSV-TK/GCV suicide gene therapy system had strong therapeutic effects on Hela cells in vitro and in vivo (the inhibition rates were 45.8% and 39.5%, respectively), moreover, the combined administration of gene therapy and radiotherapy had stronger therapeutic effects in vitro and in vivo (the inhibition rate was 87.5% in vitro, and the inhibition rate was 87.9% in vivo) (P < 0.01). The inhibition rate by radiotherapy alone was 42.4% in vitro and 35.8% in vivo. The sensitivity of combined therapy to radiotherapy increased more than that of therapy alone, the ability of colony formation decreased (P < 0.01). The rate of radiosensitivity effect (E/O) was 3.17(> 1.4), indicating HSV-TK/GCV system could exert a sensitizing effect on 60 Co radiotherapy of the transplanted human cervical cancer cell in nude mice. HSV-TK/GCV system had radiosensitization. Gene therapy combined with radiotherapy may be a good supplementary method for cervix cancer synthetic treatment

Common variations in 4p locus are related to male completed suicide.

Science.gov (United States)

Must, Anne; Kõks, Sulev; Vasar, Eero; Tasa, Gunnar; Lang, Aavo; Maron, Eduard; Väli, Marika

2009-01-01

Suicidal behavior is a multifactorial phenomenon, with a significant genetic predisposition. To assess the contribution of genes in the 4p region to suicide risk, we genotyped 36 single nucleotide polymorphisms from a 49Mb region on the chromosome arm 4p11-16 in a total of 288 male suicide victims and 327 healthy male volunteers. The nonsynonymous variants rs1383180 in EVC gene, rs6811863 in TBC1D1 gene, rs362272 in HTT gene, and rs734312 in WFS1 gene were associated to the male completed suicide. However, only EVC polymorphism remained significant after correcting for multiple comparisons (P < .05 after 10 K permutations). The function of these genes is not clear yet. WFS1 and HTT are related to the unfolded protein response and endoplasmic reticulum stress, and TBC1D1 is a GTPase activator. EVC is a protein with transmembrane and leucine zipper domains, its function has not been elucidated yet. Further studies are required in order to reveal the role of these four polymorphisms in the pathoetiology of suicide.

Pathways between stigma and suicidal ideation among people at risk of psychosis.

Science.gov (United States)

Xu, Ziyan; Müller, Mario; Heekeren, Karsten; Theodoridou, Anastasia; Metzler, Sibylle; Dvorsky, Diane; Oexle, Nathalie; Walitza, Susanne; Rössler, Wulf; Rüsch, Nicolas

2016-04-01

Mental illness stigma may contribute to suicidality and is associated with social isolation and low self-esteem among young people at risk of psychosis. However, it is unclear whether mental illness stigma contributes to suicidality in this population. We therefore examined the associations of self-labeling and stigma stress with suicidality among young people at risk. Self-labeling as "mentally ill", stigma stress, social isolation, self-esteem, symptoms and suicidal ideation were assessed in 172 individuals at risk of psychosis. Self-labeling and stigma stress were examined as predictors of suicidality by path analysis. Increased self-labeling as "mentally ill" was associated with suicidality, directly as well as indirectly mediated by social isolation. More stigma stress was related to social isolation which in turn was associated with low self-esteem, depression and suicidal ideation. Social isolation fully mediated the link between stigma stress and suicidal ideation. Interventions to reduce the public stigma associated with risk of psychosis as well as programs to facilitate non-stigmatizing awareness of at-risk mental state and to reduce stigma stress among young people at risk of psychosis might strengthen suicide prevention in this population. Copyright © 2016 Elsevier B.V. All rights reserved.

Trauma-Related Guilt Mediates the Relationship between Posttraumatic Stress Disorder and Suicidal Ideation in OEF/OIF/OND Veterans.

Science.gov (United States)

Tripp, Jessica C; McDevitt-Murphy, Meghan E

2017-02-01

Posttraumatic stress disorder (PTSD) and trauma-related guilt are risk factors for suicidal ideation (SI) in veterans. Components of trauma-related guilt were examined as serial mediators of the relationship between PTSD and SI. In a sample of 53 OEF/OIF/OND combat veterans, PTSD had an indirect effect on SI through a serial mediation chain of guilt cognitions, distress, and global guilt, suggesting that trauma-related guilt via cognitions, distress, and global guilt is a pathway from PTSD to SI. Attention should be given to assessing and addressing trauma-related guilt in veterans experiencing PTSD to prevent SI. © 2016 The American Association of Suicidology.

Parents and Friendships: A Longitudinal Examination of Interpersonal Mediators of the Relationship between Child Maltreatment and Suicidal Ideation

OpenAIRE

Miller, Adam B.; Adams, Leah M.; Esposito-Smythers, Christianne; Thompson, Richard; Proctor, Laura J.

2014-01-01

This study examined parental relationship quality, friendship quality, and depression as mediators of the association between child maltreatment (CM) and adolescent suicidal ideation (SI). Participants were 674 adolescents (46% female; 55% African American) involved in the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). Data were collected via youth self-report at ages 12, 16, and 18. CM before age 12 predicted poor parental relationships and depression, but not poor friendships, ...

Suicide and War: The Mediating Effects of Negative Mood, Posttraumatic Stress Disorder Symptoms, and Social Support among Army National Guard Soldiers

Science.gov (United States)

Griffith, James

2012-01-01

The mediating effects of posttraumatic stress disorder (PTSD) symptoms, negative mood, and social support on the relationship of war experiences to suicidality were examined. The research literature suggested a sequence among study scales representing these constructs, which was then tested on survey data obtained from a sample of National Guard…

Disability, depression and suicide ideation in people with multiple sclerosis.

Science.gov (United States)

Lewis, V M; Williams, K; KoKo, C; Woolmore, J; Jones, C; Powell, T

2017-01-15

Depressive symptoms occur frequently in people with Multiple Sclerosis (MS) and rates of suicide ideation are higher than the general population. There is evidence for a direct association between disability and depression, disability and suicide ideation, and depression and suicide ideation in MS. However, the relationship between all three, i.e. the mediating role of depression between disability and suicidal ideation, has not been investigated. Exploring this relationship could highlight risk factors, alerting clinicians to the need for timely intervention. Seventy five people with progressive MS attending two out-patient clinics took part in this cross-sectional study. Participants completed the Beck Suicide Scale, Beck Depression Inventory, Multiple Sclerosis Impact Scale and Guy's Neurological Disability Scale. Depressive symptoms mediated the relationship between perceived and actual disability and suicide ideation. Different types of disability were associated with suicidality, including: 'tremors' and 'taking longer to do things'. A small sub-group of participants were identified who reported suicide ideation in the presence of only mild levels of depression. There may be a sample bias in this study as all participants were attending out-patient clinics and receiving support which may not be available to everyone with MS. It is important for clinicians to screen regularly for both depression and suicide ideation, to be alert to specific types of disability for which a higher level of suicide ideation might be present and to consider the possibility of suicidal thoughts being present in people who show minimal or no depressive symptoms. Copyright © 2016 Elsevier B.V. All rights reserved.

Mediating effects of bullying involvement on the relationship of body mass index with social phobia, depression, suicidality, and self-esteem and sex differences in adolescents in Taiwan.

Science.gov (United States)

Yen, Cheng-Fang; Liu, Tai-Ling; Ko, Chih-Hung; Wu, Yu-Yu; Cheng, Chung-Ping

2014-03-01

The aims of this study were to examine the mediating effect of bullying involvement on the relationships between body mass index (BMI) and mental health problems, including social phobia, depression, suicidality, and low self-esteem among adolescents in Taiwan. The moderation effect of sex on the mediating role of bullying involvement was also examined. Five thousand two hundred and fifty-two students of high schools completed the questionnaires. Victimization and perpetration of passive and active bullying were assessed using the Chinese version of the School Bullying Experience Questionnaire. BMI was calculated from self-reported weight and height measurements. The Social Phobia Inventory, the Mandarin Chinese version of the Center for Epidemiological Studies-Depression Scale, the suicidality-related questionnaire from the epidemiological version of the Kiddie-Schedule for Affective Disorders and Schizophrenia, and the Rosenberg Self-Esteem Scale were applied to assess social phobia, depression, suicidality, and low self-esteem, respectively. The mediating effect of bullying involvement on the associations between increased BMI and mental health problems was examined by the Sobel test. The moderation effect of sex on the mediating role of bullying involvement was tested by the multiple-group structural equation model. Victimization of passive and active bullying and perpetration of passive bullying, but not perpetration of active bullying, had a mediating effect on the relationships between increased BMI and all four mental health problems. Sex did not have a significant moderation effect on the mediating role of bullying involvement. Bullying involvement should be a target of prevention and intervention in developing a strategy to improve mental health among adolescents with increased BMI. Copyright © 2013 Elsevier Ltd. All rights reserved.

Escape from Discrepancy: Self-Esteem and Quality of Life as Predictors of Current Suicidal Ideation Among Individuals with Schizophrenia.

Science.gov (United States)

Fulginiti, Anthony; Brekke, John S

2015-08-01

While suicidal ideation represents an "early warning" sign for suicidal behavior, studies examining suicidal ideation have been limited and largely atheorethical among those with schizophrenia. Informed by the Escape Theory of Suicide, we investigated the relationship between discrepancy factors, in the form of self-esteem and quality of life (QoL), and suicidal ideation. In a sample of 162 individuals with Schizophrenia, hierarchical logistic regression was employed to examine the contribution of (1) demographic (2) clinical and (3) discrepancy factors to suicidal ideation. A mediation analysis was performed to determine if self-esteem mediated the relationship between QoL and suicidal ideation. While QoL (in social relationships) and self-esteem collectively added value to predicting suicidal ideation beyond other factors, only self-esteem remained significant in the final hierarchical model. Self-esteem was found to mediate the relationship between QoL and suicidal ideation. Findings support Escape Theory in schizophrenia, marking self-esteem and QoL as targets for intervention.

Mechanisms of Action Contributing to Reductions in Suicide Attempts Following Brief Cognitive Behavioral Therapy for Military Personnel: A Test of the Interpersonal-Psychological Theory of Suicide.

Science.gov (United States)

Bryan, Craig J; Wood, David S; May, Alexis; Peterson, Alan L; Wertenberger, Evelyn; Rudd, M David

2018-01-01

Brief cognitive behavioral therapy (BCBT) is associated with significant reductions in suicide attempts among military personnel. However, the underlying mechanisms of action contributing to reductions in suicide attempts in effective psychological treatments remain largely unknown. The present study conducted a secondary analysis of a randomized controlled trial of BCBT versus treatment as usual (TAU) to examine the mechanisms of action hypothesized by the interpersonal-psychological theory of suicide (IPT): perceived burdensomeness, thwarted belongingness, and fearlessness about death. In a sample of 152 active duty U.S. Army personnel with recent suicide ideation or attempts, there were significantly fewer suicide attempts in BCBT, but there were no differences between treatment groups from baseline to 6 months postbaseline on any of the 3 IPT constructs or their interactions. Tests of the moderated mediation failed to support an indirect effect for the IPT model, regardless of which IPT variables were specified as mediators or moderators. Results suggest that the IPT's hypothesized mechanisms of action do not account for reductions in suicide attempts in BCBT. Implications for clinical practice and research are discussed.

Suicidal communication signifies suicidal intent in Chinese completed suicides.

Science.gov (United States)

Zhou, Xue Mei; Jia, Shu Hua

2012-11-01

Recognizing suicidal communication from the distressful catharsis in a high-risk group with suicidal tendencies is essential for suicide prevention. This study analyzes whether suicidal communication can indicate the severity of suicidal intent. Various types of suicidal communication are defined, and their clinical significance is further explored. A comprehensive analysis of the psychological autopsy data of 200 victims of completed suicide, including their general socio-demographic status, suicidal communication methods, previous suicide attempts, mental disorders, and psychosocial situation. Our results showed that 39.5% of all the subjects were suicidal communicators, 23.0% had previously attempted suicide, and 14.0% left suicide notes; 32.4% of 142 subjects free of physical disease suffered from mental disorders. Suicidal communication included verbal communication, behavioral communication, and suicidal notes. Younger people with a higher level of education were more inclined to communicate their suicidal intent by leaving a suicide note. Suicide notes, but not previous suicide attempts or psychosocial situation, were significantly correlated with suicidal intent. Suicidal communicators showed higher depression scores than non-communicators. Those who suffered from mood disorders with higher levels of both depression and suicidal intent were more likely to expose their intent through behavioral communication. The present study provides strong evidence that suicidal communication can indicate the severity of suicidal intent. Current findings help interpret high-risk, self-destructive behavior and consequently provide the theoretical basis for a feasible suicide prevention program.

Host genes involved in Agrobacterium-mediated transformation

NARCIS (Netherlands)

Soltani, Jalal

2009-01-01

Agrobacterium is the nature’s genetic engineer that can transfer genes across the kingdom barriers to both prokaryotic and eukaryotic host cells. The host genes which are involved in Agrobacterium-mediated transformatiom (AMT) are not well known. Here, I studied in a systematic way to identify the

Probing the implicit suicidal mind: does the Death/Suicide Implicit Association Test reveal a desire to die, or a diminished desire to live?

Science.gov (United States)

Harrison, Dominique P; Stritzke, Werner G K; Fay, Nicolas; Ellison, T Mark; Hudaib, Abdul-Rahman

2014-09-01

Assessment of implicit self-associations with death relative to life, measured by a death/suicide implicit association test (d/s-IAT), has shown promise in the prediction of suicide risk. The current study examined whether the d/s-IAT reflects an individual's desire to die or a diminished desire to live and whether the predictive utility of implicit cognition is mediated by life-oriented beliefs. Four hundred eight undergraduate students (285 female; Mage = 20.36 years, SD = 4.72) participated. Participants completed the d/s-IAT and self-report measures assessing 6 indicators of suicide risk (suicide ideation frequency and intensity, depression, nonsuicidal self-harm thoughts frequency and intensity, and nonsuicidal self-harm attempts), as well as survival and coping beliefs and history of prior suicide attempts. The d/s-IAT significantly predicted 5 out of the 6 indicators of suicide risk above and beyond the strongest traditional indicator of risk, history of prior suicide attempts. However, the effect of the d/s-IAT on each of the risk indicators was mediated by individuals' survival and coping beliefs. Moreover, the distribution of d/s-IAT scores primarily reflected variability in self-associations with life. Implicit suicide-related cognition appears to reflect a gradual diminishing of the desire to live, rather than a desire to die. Contemporary theories of suicide and risk assessment protocols need to account for the dynamic relationship between both risk and life-oriented resilience factors, and intervention strategies aimed at enhancing engagement with life should be a routine part of suicide risk management. PsycINFO Database Record (c) 2014 APA, all rights reserved.

The role of the Cys23Ser (rs6318) polymorphism of the HTR2C gene in suicidal behavior: systematic review and meta-analysis.

Science.gov (United States)

González-Castro, Thelma B; Hernandez-Diaz, Yazmín; Juárez-Rojop, Isela E; López-Narváez, Lilia; Tovilla-Zárate, Carlos A; Rodriguez-Perez, José M; Sánchez-de la Cruz, Juan P

2017-12-01

The polymorphisms of the serotonin receptor 2C (HTR2C) gene have been proposed to influence suicidal behavior. The aim of our study was to explore the role of the HTR2C gene variant Cys23Ser (rs6318) in the pathogenesis of suicidal behavior through a systematic review and meta-analysis. The search was performed using EBSCO and PubMed databases. To be included in the analysis, the studies had to evaluate suicidal behavior (attempted, ideation, or completed suicide). The results of the meta-analysis were expressed as odds ratios (ORs). Because HTR2C lies on chromosome X, pooled ORs were calculated, respectively, for each of the models used, namely: allelic, homozygous, dominant, and recessive for the female group and allelic for the male group. The meta-analysis comprised 3867 individuals, including 1668 cases and 2199 controls. The HTR2C Cys23Ser (rs6318) polymorphism did not show a significant association with suicidal behavior either in women (OR: 0.75; 95% confidence interval: 0.55-1.00) or in men (OR: 0.89; 95% confidence interval: 0.64-1.23). Similarly, nonsignificant associations were observed for all of the genetic models used in any of the populations/subgroups studied. Our findings suggest that the rs6318 (Cys23Ser) polymorphism is not associated with suicidal behavior. However, because of the study limitations, we suggest more researches should be performed, increasing the sample sizes and statistical power, to determine the association between the rs6318 variant and suicidal behavior.

Clinical and genetic factors associated with suicide in mood disorder patients.

Science.gov (United States)

Antypa, Niki; Souery, Daniel; Tomasini, Mario; Albani, Diego; Fusco, Federica; Mendlewicz, Julien; Serretti, Alessandro

2016-03-01

Suicidality is a continuum ranging from ideation to attempted and completed suicide, with a complex etiology involving both genetic heritability and environmental factors. The majority of suicide events occur in the context of psychiatric conditions, preeminently major depression and bipolar disorder. The present study investigates clinical factors associated with suicide in a sample of 553 mood disorder patients, recruited within the 'Psy Pluriel' center, Centre Européen de Psychologie Médicale, and the Department of Psychiatry of Erasme Hospital (Brussels). Furthermore, genetic association analyses examining polymorphisms within COMT, BDNF, MAPK1 and CREB1 genes were performed in a subsample of 259 bipolar patients. The presence or absence of a previous suicide attempt and of current suicide risk were assessed. A positive association with suicide attempt was reported for younger patients, females, lower educated, smokers, those with higher scores on depressive symptoms and higher functional disability and those with anxiety comorbidity and familial history of suicidality in first- and second-degree relatives. Anxiety disorder comorbidity was the stronger predictor of current suicide risk. No associations were found with polymorphisms within COMT and BDNF genes, whereas significant associations were found with variations in rs13515 (MAPK1) and rs6740584 (CREB1) polymorphisms. From a clinical perspective, our study proposes several clinical characteristics, such as increased depressive symptomatology, anxiety comorbidity, functional disability and family history of suicidality, as correlates associated with suicide. Genetic risk variants in MAPK1 and CREB1 genes might be involved in a dysregulation of inflammatory and neuroplasticity pathways and are worthy of future investigation.

Temperament, character, and suicide attempts in unipolar and bipolar mood disorders.

Science.gov (United States)

Jylhä, Pekka J; Rosenström, Tom; Mantere, Outi; Suominen, Kirsi; Melartin, Tarja K; Vuorilehto, Maria S; Holma, Mikael K; Riihimäki, Kirsi A; Oquendo, Maria A; Keltikangas-Järvinen, Liisa; Isometsä, Erkki T

2016-02-01

Personality features may indicate risk for both mood disorders and suicidal acts. How dimensions of temperament and character predispose to suicide attempts remains unclear. Patients (n = 597) from 3 prospective cohort studies (Vantaa Depression Study [VDS], Jorvi Bipolar Study [JoBS], and Vantaa Primary Care Depression Study [PC-VDS]) were interviewed at baseline, at 18 months, and, in VDS and PC-VDS, at 5 years (1997-2003). Personality was measured with the Temperament and Character Inventory-Revised (TCI-R), and follow-up time spent in major depressive episodes (MDEs) as well as lifetime (total) and prospectively ascertained suicide attempts during the follow-up were documented. Overall, 219 patients had 718 lifetime suicide attempts; 88 patients had 242 suicide attempts during the prospective follow-up. The numbers of both the total and prospective suicide attempts were associated with low self-directedness (β = -0.266, P = .004, and β = -0.294, P suicide attempts were linked to high novelty seeking (β = 0.195, P = .05). Prospective, but not total, suicide attempts were associated with high harm avoidance (β = 0.322, P suicide attempts during MDEs were included. After adjustment was made for total time spent in MDEs, only high persistence predicted suicide attempts (β = 0.190, P suicide attempts indicated significant mediated effect through time at risk in MDEs, but no significant direct effect. Among mood disorder patients, suicide attempt risk is associated with temperament and character dimensions. However, their influence on predisposition to suicide attempts is likely to be mainly indirect, mediated by more time spent in depressive episodes. © Copyright 2016 Physicians Postgraduate Press, Inc.

Differentiation of direct and indirect socioeconomic effects on suicide attempts in South Korea.

Science.gov (United States)

Ki, Myung; Seong Sohn, Eui; An, Byungduck; Lim, Jiseun

2017-12-01

Despite the wide recognition of the inverse association between socioeconomic position (SEP) and suicidal behaviors, its underlying process and potential mediators are little known. This study investigated the pathway from SEP to suicide attempts with attention to potential mediators.From the Korean Health and Nutrition Examination Survey 2007-2013, which is a nationwide cross-sectional survey of the health and nutritional status, a total of 34,565 participants (≥30 years) were included in the analysis. To unfold the pathways linking SEP to suicide attempts, the direct and indirect effects of 3 SEP measures (educational attainment, household income, and occupational group) and 3 mediators (physical illness, mental health problems, and problematic drinking) were differentiated using structured equation model (SEM).Most of direct and indirect effects of educational attainment, household income, and occupational group on suicide attempts were significant; Nonemployment status had the largest total (β = 0.291, P suicide attempts, compared to mental health problem and problem drinking.Overall, experience of socioeconomic disadvantage increased suicide attempts independently of mental and physical problems. An extension of suicide prevention program is required for comprehensively targeting people with general problems such as physical illness and low SEP, complemented to narrowly targeting high risk group with, such as mental health problem. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Reconsidering the link between impulsivity and suicidal behavior.

Science.gov (United States)

Anestis, Michael D; Soberay, Kelly A; Gutierrez, Peter M; Hernández, Theresa D; Joiner, Thomas E

2014-11-01

It is widely accepted that suicidal behavior often occurs with little planning. We propose, however, that suicidal behavior is rarely if ever impulsive-that it is too frightening and physically distressing to engage in without forethought-and that suicidal behavior in impulsive individuals is accounted for by painful and fearsome behaviors capable of enhancing their capacity for suicide. We conducted a meta-analysis of the association between trait impulsivity and suicidal behavior and a critical review of research considering the impulsiveness of specific suicide attempts. Meta-analytic results suggest the relationship between trait impulsivity and suicidal behavior is small. Furthermore, studies examining a mediating role of painful and provocative behaviors have uniformly supported our model. Results from our review suggest that researchers have been unable to adequately measure impulsivity of attempts and that measures sensitive to episodic planning must be developed to further our understanding of this phenomenon. © 2014 by the Society for Personality and Social Psychology, Inc.

Pain and suicidality: insights from reward and addiction neuroscience.

Science.gov (United States)

Elman, Igor; Borsook, David; Volkow, Nora D

2013-10-01

Suicidality is exceedingly prevalent in pain patients. Although the pathophysiology of this link remains unclear, it may be potentially related to the partial congruence of physical and emotional pain systems. The latter system's role in suicide is also conspicuous during setbacks and losses sustained in the context of social attachments. Here we propose a model based on the neural pathways mediating reward and anti-reward (i.e., allostatic adjustment to recurrent activation of the reward circuitry); both are relevant etiologic factors in pain, suicide and social attachments. A comprehensive literature search on neurobiology of pain and suicidality was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) physical and emotional pain, (2) emotional pain and social attachments, (3) pain- and suicide-related alterations of the reward and anti-reward circuits as compared to addiction, which is the premier probe for dysfunction of these circuits and (4) mechanistically informed treatments of co-occurring pain and suicidality. Pain-, stress- and analgesic drugs-induced opponent and proponent states of the mesolimbic dopaminergic pathways may render reward and anti-reward systems vulnerable to sensitization, cross-sensitization and aberrant learning of contents and contexts associated with suicidal acts and behaviors. These findings suggest that pain patients exhibit alterations in the brain circuits mediating reward (depressed function) and anti-reward (sensitized function) that may affect their proclivity for suicide and support pain and suicidality classification among other "reward deficiency syndromes" and a new proposal for "enhanced anti-reward syndromes". We suggest that interventions aimed at restoring the balance between the reward and anti-reward networks in patients with chronic pain may help decreasing their suicide risk. Published by Elsevier Ltd.

Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer-specific cytotoxicity and tumor growth delay

DEFF Research Database (Denmark)

Christensen, Camilla L; Gjetting, Torben; Poulsen, Thomas Tuxen

2010-01-01

Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment. Novel therapies are therefore in great demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine...... deaminase (YCD) gene alone or fused with the yeast uracil phosphoribosyl transferase (YUPRT) gene followed by administration of 5-fluorocytosine (5-FC) prodrug. Experimental design: The YCD gene or the YCD-YUPRT gene was placed under regulation of the SCLC-specific promoter insulinoma-associated 1 (INSM1...

'Molecular switch' vectors for hypoxia- and radiation-mediated gene therapy of cancer

International Nuclear Information System (INIS)

Greco, O.; Marples, B.; Joiner, M.C.; Scott, S.D.

2003-01-01

Intratumoral areas of low oxygen concentration are known to be refractive to radiotherapy treatment. However, this physiological condition can be exploited for selective cancer gene therapy. We have developed a series of synthetic promoters selectively responsive to both hypoxia and ionizing radiation (IR). These promoters contain hypoxia regulatory elements (HREs) from the erythropoietin (Epo), the phosphoglycerate kinase1(PGK1) and vascular endothelial growth factor (VEGF) genes, and/or IR-responsive CArG elements from the Early Growth Response 1 (Egr1) gene. The HRE and CArG promoters were able to regulate expression of reporter and suicide genes in human tumor cells, following corresponding stimulation with hypoxia (0.1% O2) or X-irradiation (5Gy) [Greco et al, 2002, Gene Therapy 9:1403]. Furthermore, the chimeric HRE + CArG promoters could be activated by these stimuli independently or even more significantly when given in combination, with the Epo HRE/CArG promoter proving to be the most responsive and robust. In order to amplify and maintain transgene expression even following withdrawal of the triggering stimuli, we have developed a 'molecular switch' system [Scott et al, 2000, Gene Therapy 7:1121]. This 'switch' system has now been engineered as a single vector molecule, containing HRE and CArG promoters. This new series of HRE/CArG switch vectors have been tested in a herpes simplex thymidine kinase (HSVtk)/ganciclovir (GCV) suicide gene assay. Results indicate that a) higher and more selective tumor cell kill is achieved with the switch when compared with the HRE and CArG promoters directly driving HSVtk expression and b) the Epo HRE/CArG switch vectors appear to function as efficiently as the strong constitutive cytomegalovirus (CMV) promoter construct

Dual monitoring using 124I-FIAU and bioluminescence for HSV1-tk suicide gene therapy

International Nuclear Information System (INIS)

Lee, T. S.; Kim, J. H.; Kwon, H. C.

2007-01-01

Herpes simplex virus type I thymidine kinase (HSV-tk) is the most common reporter gene and is used in cancer gene therapy with a prodrug nucleoside analog, ganciclovir (GCV). The aim of this study is to evaluate therapeutic efficacy of suicide gene therapy with 2'-fluoro-2'-deoxy-1-D-arabinofuranosyl-5-[ 124 I] iodouracil ( 124 I - FIAU) and bioluminescence in retrovirally HSV -tk and firefly luciferase transduced hepatoma model. The HSV -tk and firefly luciferase (Luc) was retrovirally transduced and expressed in MCA rat Morris hepatoma cells. Nude mice with subcutaneous tumors, MCA and MCA-TK-Luc, were subjected to GCV treatment (50mg/Kg/d intraperitoneally) for 5 day. PET imaging and biodistribution with ( 124 I-FIAU) were performed at before and after initiation of therapy with GCV. Bioluminescent signal was also measured during GCV treatment. Before GCV treatment, no significant difference in tumor volume was found in tumors between MCA and MCA-TK-Luc. After GCV treatment, tumor volume of MCA-TK-Luc markedly reduced compared to that of MCA. In biodistribution study, 124 I-FIAU uptake after GCV therapy significantly decreased compared with pretreatment levels (34.8 13.67 %ID/g vs 7.6 2.59 %ID/g) and bioluminescent signal was also significantly decreased compared with pretreatment levels. In small animal PET imaging, 124 I-FIAU selectively localized in HSV -tk expressing tumor and the therapeutic efficacy of GCV treatment was evaluated by 124 I-FIAU PET imaging. 124 I-FIAU PET and bioluminescence imaging in HSV-tk suicide gene therapy were effective to evaluate the therapeutic response. 124 I-FIAU may serve as an efficient and selective agent for monitoring of transduced HSV1-tk gene expression in vivo in clinical trials

The tryptophan hydroxylase 1 (TPH1) gene, schizophrenia susceptibility, and suicidal behavior: a multi-centre case-control study and meta-analysis

DEFF Research Database (Denmark)

Saetre, Peter; Lundmark, Per; Wang, August

2010-01-01

Serotonin (5-hydroxytryptamin; 5-HT) alternations has since long been suspected in the pathophysiology of schizophrenia. Tryptophan hydroxylase (tryptophan 5-monooxygenase; TPH) is the rate-limiting enzyme in the biosynthesis of 5-HT, and sequence variation in intron 6 of the TPH1 gene has been...... affected individuals having attempted suicide at least once and patients with no history of suicide attempts (P = 0.84). A systematic literature review and meta-analysis support the A218C polymorphism as a susceptibility locus for schizophrenia (odds ratio 1.17, 95% confidence interval 1.......07-1.29). Association studies on suicide attempts are however conflicting (heterogeneity index I(2) = 0.54) and do not support the A218C/A779C polymorphisms being a susceptibility locus for suicidal behavior among individuals diagnosed with a psychiatric disorder (OR = 0.96 [0.80-1.16]). We conclude that the TPH1 A218...

Ultrasound-mediated interferon β gene transfection inhibits growth of malignant melanoma

International Nuclear Information System (INIS)

Yamaguchi, Kazuki; Feril, Loreto B.; Tachibana, Katsuro; Takahashi, Akira; Matsuo, Miki; Endo, Hitomi; Harada, Yoshimi; Nakayama, Juichiro

2011-01-01

Highlights: → Successful ultrasound-mediated transfection of melanoma (C32) cells with IFN-β genes both in vitro and in vivo. → Ultrasound-mediated IFN-β transfection inhibited proliferation of melanoma cells in vitro. → Ultrasound-mediated IFN-β transfection inhibited melanoma tumor growth in vivo. -- Abstract: We investigated the effects of ultrasound-mediated transfection (sonotransfection) of interferon β (IFN-β) gene on melanoma (C32) both in vitro and in vivo. C32 cells were sonotransfected with IFN-β in vitro. Subcutaneous C32 tumors in mice were sonicated weekly immediately after intra-tumor injection with IFN-β genes mixed with microbubbles. Successful sonotransfection with IFN-β gene in vitro was confirmed by ELISA, which resulted in C32 growth inhibition. In vivo, the growth ratio of tumors transfected with IFN-β gene was significantly lower than the other experimental groups. These results may lead to a new method of treatment against melanoma and other hard-to-treat cancers.

In vivo and in vitro experimental study on cervix cancer with combination of HSV-TK/GCV suicide gene therapy system and 60Co radiotherapy

International Nuclear Information System (INIS)

Chen Daozhen; Xue Wenqun; Zhan Huiying; Zhu Yunxia; Yang Youyi; Liu Lu; Tang Qiusha

2006-01-01

Objective: To evaluate the killing effect of HSV-TK/GCV suicide gene therapy system combined with 60 Co radiotherapy on human cervical cancer HeLa cell line in vivo and in vitro, and to explore radiosensitization by the HSV-TK/GCV system. Methods: The HSV-TK/GCV suicide gene therapy system and 60 Co radiotherapy were used separately or in combination for human cervical cancer HeLa cell line in vivo and in vitro to compare their effects. Colony formation test and the rate of radiosensitization effect(E/O) were employed to observed the radiosensitization by the HSV-TK/GCV system. Results: The HSV-TK/GCV suicide gene therapy system showed strong therapeutic effects on HeLa cells both in vitro and in vivo (the inhibition rates were 45.8% and 39.5%, respectively). Moreover, the combined application of gene therapy and radiotherapy exhibited stronger therapeutic effects in vitro and in vivo (the inhibition rate was 87.5% in vitro, and was 87.9% in vivo) (P 1.4), indicating the HSV-TK/GCV system could exert a sensitizing effect on 60 Co radiotherapy of the transplanted human cervical cancer cells in nude mice. Conclusion: The HSV-TK/GCV system has radiosensitizationaction. Gene therapy combined with radiotherapy may be a good supplementary method for synthetic treatment of cervical cancer. (authors)

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

Science.gov (United States)

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

2015-09-01

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

Suicidal Ideation in College Students Varies across Semesters: The Mediating Role of Belongingness

Science.gov (United States)

Van Orden, Kimberly A.; Witte, Tracy K.; James, Lisa M.; Castro, Yessenia; Gordon, Kathryn H.; Braithwaite, Scott R.; Hollar, Daniel L.; Joiner, Thomas E., Jr.

2008-01-01

The interpersonal-psychological theory of suicidal behavior (Joiner, 2005) proposes that the need to belong is fundamental; when met it can prevent suicide and when thwarted it can substantially increase the risk for suicide. We investigate one source of group-wide variation in belongingness among college students--changes in the social…

A pilot integrative genomics study of GABA and glutamate neurotransmitter systems in suicide, suicidal behavior, and major depressive disorder.

Science.gov (United States)

Yin, Honglei; Pantazatos, Spiro P; Galfalvy, Hanga; Huang, Yung-Yu; Rosoklija, Gorazd B; Dwork, Andrew J; Burke, Ainsley; Arango, Victoria; Oquendo, Maria A; Mann, John J

2016-04-01

Gamma-amino butyric acid (GABA) and glutamate are the major inhibitory and excitatory neurotransmitters in the mammalian central nervous system, respectively, and have been associated with suicidal behavior and major depressive disorder (MDD). We examined the relationship between genotype, brain transcriptome, and MDD/suicide for 24 genes involved in GABAergic and glutamatergic signaling. In part 1 of the study, 119 candidate SNPs in 24 genes (4 transporters, 4 enzymes, and 16 receptors) were tested for associations with MDD and suicidal behavior in 276 live participants (86 nonfatal suicide attempters with MDD and 190 non-attempters of whom 70% had MDD) and 209 postmortem cases (121 suicide deaths of whom 62% had MDD and 88 sudden death from other causes of whom 11% had MDD) using logistic regression adjusting for sex and age. In part 2, RNA-seq was used to assay isoform-level expression in dorsolateral prefrontal cortex of 59 postmortem samples (21 with MDD and suicide, 9 MDD without suicide, and 29 sudden death non-suicides and no psychiatric illness) using robust regression adjusting for sex, age, and RIN score. In part 3, SNPs with subthreshold (uncorrected) significance levels below 0.05 for an association with suicidal behavior and/or MDD in part 1 were tested for eQTL effects in prefrontal cortex using the Brain eQTL Almanac (www.braineac.org). No SNPs or transcripts were significant after adjustment for multiple comparisons. However, a protein coding transcript (ENST00000414552) of the GABA A receptor, gamma 2 (GABRG2) had lower brain expression postmortem in suicide (P = 0.01) and evidence for association with suicide death (P = 0.03) in a SNP that may be an eQTL in prefrontal cortex (rs424740, P = 0.02). These preliminary results implicate GABRG2 in suicide and warrant further investigation and replication in larger samples. © 2016 Wiley Periodicals, Inc.

Tumor targeted gene therapy

International Nuclear Information System (INIS)

Kang, Joo Hyun

2006-01-01

Knowledge of molecular mechanisms governing malignant transformation brings new opportunities for therapeutic intervention against cancer using novel approaches. One of them is gene therapy based on the transfer of genetic material to an organism with the aim of correcting a disease. The application of gene therapy to the cancer treatment had led to the development of new experimental approaches such as suicidal gene therapy, inhibition of oncogenes and restoration of tumor-suppressor genes. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a prodrug into a toxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1-tk) and cytosine deaminase (CD). Especially, physicians and scientists of nuclear medicine field take an interest in suicidal gene therapy because they can monitor the location and magnitude, and duration of expression of HSV1-tk and CD by PET scanner

Stress, Coping and Suicide Ideation in Chinese College Students

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Zhang, Xiaoyun; Wang, Haiping; Xia, Yan; Liu, Xiaohong; Jung, Eunju

2012-01-01

The study was to examine 1) whether stress and coping styles could significantly predict the probability of suicide ideation; 2) and whether coping styles were mediators or moderators on the association between life stress and suicide ideation. The survey was conducted in a sample of 671 Chinese college students. Approximately twenty percent…

Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder

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Tzeng Dong-Sheng

2011-05-01

Full Text Available Abstract Background The MAOA uVNTR polymorphism has been documented to affect the MAOA gene at the transcriptional level and is associated with aggressive impulsive behaviors, depression associated with suicide (depressed suicide, and major depressive disorder (MDD. We hypothesized that the uVNTR polymorphism confers vulnerability to MDD, suicide or both. The aim of this study was to explore the association between the MAOA uVNTR and depressed suicide, using multiple controls. Methods Four different groups were included: 432 community controls, 385 patients with MDD who had not attempted suicide, 96 community subjects without mental disorders who had attempted suicide, and 109 patients with MDD who had attempted suicide. The MAOA uVNTR polymorphism was genotyped by a PCR technique. The symptom profiles and personal characteristics in each group were also compared. Results The MAOA 4R allele was more frequent in males with MDD than in male community controls (χ2 = 4.182, p = 0.041. Logistic regression analysis showed that, among the depressed subjects, those younger in age, more neurotic or who smoked had an increased risk of suicide (β = -0.04, p = 0.002; β = 0.15, p = 0.017; β = 0.79, p = 0.031, respectively. Moreover, among those who had attempted suicide, those younger in age, with more paternal overprotection, and more somatic symptoms were more likely to be in the MDD group than in the community group (β = -0.11, p Conclusion The MAOA 4R allele is associated with enhanced vulnerability to suicide in depressed males, but not in community subjects. The MAOA 4R allele affects vulnerability to suicide through the mediating factor of depressive symptoms. Further large-scale studies are needed to verify the psychopathology of the relationships among MAOA uVNTR polymorphism, symptom profiles, and suicidal behavior.

Associations between cyberbullying and school bullying victimization and suicidal ideation, plans and attempts among Canadian schoolchildren.

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Sampasa-Kanyinga, Hugues; Roumeliotis, Paul; Xu, Hao

2014-01-01

The negative effects of peer aggression on mental health are key issues for public health. The purpose of this study was to examine the associations between cyberbullying and school bullying victimization with suicidal ideation, plans and attempts among middle and high school students, and to test whether these relationships were mediated by reports of depression. Data for this study are from the 2011 Eastern Ontario Youth Risk Behaviour Survey, which is a cross-sectional regional school-based survey that was conducted among students in selected Grade 7 to 12 classes (1658 girls, 1341 boys; mean ± SD age: 14.3 ± 1.8 years). Victims of cyberbullying and school bullying incurred a significantly higher risk of suicidal ideation (cyberbullying: crude odds ratio, 95% confidence interval  = 3.31, 2.16-5.07; school bullying: 3.48, 2.48-4.89), plans (cyberbullying: 2.79, 1.63-4.77; school bullying: 2.76, 2.20-3.45) and attempts (cyberbullying: 1.73, 1.26-2.38; school bullying: 1.64, 1.18-2.27) compared to those who had not encountered such threats. Results were similar when adjusting for sociodemographic characteristics, substance use, and sedentary activities. Mediation analyses indicated that depression fully mediated the relationship between cyberbullying victimization and each of the outcomes of suicidal ideation, plans and attempts. Depression also fully mediated the relationship between school bullying victimization and suicide attempts, but partially mediated the relationship between school bullying victimization and both suicidal ideation and plans. These findings support an association between both cyberbullying and school bullying victimization and risk of suicidal ideation, plans and attempts. The mediating role of depression on these links justifies the need for addressing depression among victims of both forms of bullying to prevent the risk of subsequent suicidal behaviours.

Associations between cyberbullying and school bullying victimization and suicidal ideation, plans and attempts among Canadian schoolchildren.

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Hugues Sampasa-Kanyinga

Full Text Available The negative effects of peer aggression on mental health are key issues for public health. The purpose of this study was to examine the associations between cyberbullying and school bullying victimization with suicidal ideation, plans and attempts among middle and high school students, and to test whether these relationships were mediated by reports of depression.Data for this study are from the 2011 Eastern Ontario Youth Risk Behaviour Survey, which is a cross-sectional regional school-based survey that was conducted among students in selected Grade 7 to 12 classes (1658 girls, 1341 boys; mean ± SD age: 14.3 ± 1.8 years.Victims of cyberbullying and school bullying incurred a significantly higher risk of suicidal ideation (cyberbullying: crude odds ratio, 95% confidence interval  = 3.31, 2.16-5.07; school bullying: 3.48, 2.48-4.89, plans (cyberbullying: 2.79, 1.63-4.77; school bullying: 2.76, 2.20-3.45 and attempts (cyberbullying: 1.73, 1.26-2.38; school bullying: 1.64, 1.18-2.27 compared to those who had not encountered such threats. Results were similar when adjusting for sociodemographic characteristics, substance use, and sedentary activities. Mediation analyses indicated that depression fully mediated the relationship between cyberbullying victimization and each of the outcomes of suicidal ideation, plans and attempts. Depression also fully mediated the relationship between school bullying victimization and suicide attempts, but partially mediated the relationship between school bullying victimization and both suicidal ideation and plans.These findings support an association between both cyberbullying and school bullying victimization and risk of suicidal ideation, plans and attempts. The mediating role of depression on these links justifies the need for addressing depression among victims of both forms of bullying to prevent the risk of subsequent suicidal behaviours.

Association between serotonin 2A receptor genetic variations, stressful life events and suicide.

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Ghasemi, Asghar; Seifi, Morteza; Baybordi, Fatemeh; Danaei, Nasim; Samadi Rad, Bahram

2018-06-05

Life events are series of events that disrupt a person's psychological equilibrium and may enhance the development of a disorder such as suicide. Several studies have assessed a relationship between 5-hydroxytryptamine (serotonin) 2A receptor (5-HTR2A) gene polymorphisms with an increased risk of suicide. However, there has been no study about the association between three 5-HTR2A gene polymorphisms, A1438G (rs6311), T102C (rs6313) and C1354T (rs6314), suicide, stressful life, and loss events in a same time. Relatives of 191 suicide victims were interviewed using a semi-structured questionnaire designed according to Iranian culture. Venous blood was taken from all subjects for DNA isolation. 5-HTR2A polymorphisms in a total of 191 suicide victims and 218 healthy controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chi-squared and Fisher's exact tests were used to compare genotype and allele frequencies between suicide and control groups. Correction for multiple comparisons was calculated using Bonferroni correction. There was a significant association between the 102 C/C genotype of 5-HTR2A gene and suicide (к 2  = 8.700, P = 0.012). Furthermore, we found that suicide victims with a 102 C/C genotype had a significantly higher number of stressful life and loss events (P suicide victims and control participants and there was no association between genotype distribution and higher number of stressful life and loss events (P > 0.05). Our results suggest that C102T (rs6313) polymorphism of 5-HTR2A gene may be involved in the susceptibility to suicide, higher number of stressful life and loss events, but A1438G (rs6311) and C1354T (rs6314) polymorphisms of 5-HTR2A gene were not associated with suicide, higher number of stressful life and loss events. Copyright © 2018 Elsevier B.V. All rights reserved.

Enhanced combined tumor-specific oncolysis and suicide gene therapy for prostate cancer using M6 promoter.

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Ahn, M; Lee, S-J; Li, X; Jiménez, J A; Zhang, Y-P; Bae, K-H; Mohammadi, Y; Kao, C; Gardner, T A

2009-01-01

Enzyme pro-drug suicide gene therapy has been hindered by inefficient viral delivery and gene transduction. To further explore the potential of this approach, we have developed AdIU1, a prostate-restricted replicative adenovirus (PRRA) armed with the herpes simplex virus thymidine kinase (HSV-TK). In our previous Ad-OC-TK/ACV phase I clinical trial, we demonstrated safety and proof of principle with a tissue-specific promoter-based TK/pro-drug therapy using a replication-defective adenovirus for the treatment of prostate cancer metastases. In this study, we aimed to inhibit the growth of androgen-independent (AI), PSA/PSMA-positive prostate cancer cells by AdIU1. In vitro the viability of an AI- PSA/PSMA-expressing prostate cancer cell line, CWR22rv, was significantly inhibited by treatment with AdIU1 plus GCV (10 microg ml(-1)), compared with AdIU1 treatment alone and also cytotoxicity was observed following treatment with AdIU1 plus GCV only in PSA/PSMA-positive CWR22rv and C4-2 cells, but not in the PSA/PSMA-negative cell line, DU-145. In vivo assessment of AdIU1 plus GCV treatment revealed a stronger therapeutic effect against CWR22rv tumors in nude mice than treatment with AdIU1 alone, AdE4PSESE1a alone or in combination with GCV. Our results demonstrate the therapeutic potential of specific-oncolysis and suicide gene therapy for AI-PSA/PSMA-positive prostate cancer gene therapy.

Suicidal ideation is associated with individual differences in prescription opioid craving and cue-reactivity among chronic pain patients.

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Garland, Eric L; Riquino, Michael R; Priddy, Sarah E; Bryan, Craig J

2017-01-01

Given that chronic pain patients experience significant rates of suicidal ideation and suicide attempts, access to prescription opioids compounds the risk of death by suicide. These patients may experience heightened opioid craving and exhibit increased cue-reactivity to stimuli associated with past opioid use when suicidal ideation produces negative affective states. Because both opioids and suicidal behavior are used to alleviate emotional and physical pain through a process of negative reinforcement, elucidating factors that mediate this association may yield insight into suicide risk among chronic pain patients. This study examined the relationship between suicidal ideation and opioid craving and cue-reactivity, and tested opioid self-medication as a mediator of associations between those factors after controlling for the impact of pain severity. A sample of 115 chronic pain patients provided demographic and clinical information on the Obsessive Compulsive Drug Use Scale, the Current Opioid Misuse Measure, and the Brief Pain Inventory before completing an opioid dot probe task in which heart rate variability was recorded. As hypothesized, suicidal ideation was positively correlated with subjective opioid craving and physiological cue-reactivity. Self-medication significantly mediated the association between suicidal ideation, craving, and cue-reactivity. As opioids relieve the emotional pain linked with suicidal thoughts, chronic pain patients with higher levels of suicidal ideation may experience more intense opioid craving and exhibit heightened physiological cue-reactivity when compared to patients with low levels of suicidal ideation.

Suicide: Neurochemical Approaches

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Ritabrata Banerjee

2013-10-01

Full Text Available Despite the devastating effect of suicide on numerous lives, there is still a dearthof knowledge concerning its neurochemical aspects. There is increasing evidence that brain-derived neurotrophic factor (BDNF and Nerve growth factor (NGF are involved in the pathophysiology and treatment of depression through binding and activating their cognate receptors trk B and trk A respectively. The present study was performed to examine whether the expression profiles of BDNF and/or trk B as well as NGF and/or trk A were altered in postmortem brain in subjects who commitsuicide and whether these alterations were associated with specific psychopathologic conditions. These studies were performed in hippocampus obtained 21 suicide subjects and 19 non-psychiatric control subjects. The protein and mRNA levels of BDNF, trk B and NGF, trk A were determined with Sandwich ELISA, Western Blot and RT PCR respectively. Given the importance of BDNFand NGF along with their cognate receptors in mediating physiological functions, including cell survival and synaptic plasticity, our findings of reduced expression of BDNF, Trk B and NGF, Trk A in both protein and mRNA levels of postmortem brain in suicide subjects suggest that these molecules may play an important role in the pathophysiological aspects of suicidal behavior.

Insight and suicidality in psychosis: A cross-sectional study.

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Massons, Carmen; Lopez-Morinigo, Javier-David; Pousa, Esther; Ruiz, Ada; Ochoa, Susana; Usall, Judith; Nieto, Lourdes; Cobo, Jesus; David, Anthony S; Dutta, Rina

2017-06-01

We aimed to test whether specific insight dimensions are associated with suicidality in patients with psychotic disorders. 143 patients with schizophrenia spectrum disorders were recruited. Suicidality was assessed by item 8 of the Calgary Depression Scale for Schizophrenia (CDSS). Insight was measured by the Scale of Unawareness of Mental Disorder (SUMD) and the Markova and Berrios Insight Scale. Bivariate analyses and multivariable logistic regression models were conducted. Those subjects aware of having a mental illness and its social consequences had higher scores on suicidality than those with poor insight. Awareness of the need for treatment was not linked with suicidality. The Markova and Berrios Insight scale total score and two specific domains (awareness of "disturbed thinking and loss of control over the situation" and "having a vague feeling that something is wrong") were related to suicidality. However, no insight dimensions survived the multivariable regression model, which found depression and previous suicidal behaviour to predict suicidality. Suicidality in psychosis was linked with some insight dimensions: awareness of mental illness and awareness of social consequences, but not compliance. Depression and previous suicidal behaviour mediated the associations with insight; thus, predicting suicidality. Copyright © 2017. Published by Elsevier B.V.

Suicidal ideation, suicide attempts, and psychological distress among intoxicated adolescents in the pediatric emergency department.

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Puuskari, Varpu; Aalto-Setälä, Terhi; Komulainen, Erkki; Marttunen, Mauri

2018-02-01

Studies have emphasized screening for psychiatric disorders, especially suicide risk in emergency departments. Psychiatric disorders and experimentation with alcohol increase in adolescence and intoxications among patients challenge the staff in emergency departments. This study examined the degree of suicidal ideation (SI) and suicidal behavior in adolescents, and the extent to which they differed from non-suicidal patients in terms of alcohol use, psychological distress, self-esteem, and perceived social support. The study comprised 120 adolescents, a mean age of 14.2 years. Of them 60% were females. We collected data on the clinical characteristics and assessed the patient's psychiatric status using self-report scales and analyzed blood samples for alcohol. A consulting psychiatrist interviewed each patient before discharge to evaluate potential SI or suicide attempt (SA) using structured and semi-structured scales. Of the 120 patients 20% had SI or had made a SA. High psychological distress in girls, low blood alcohol levels (BALs), as well as low scores on self-esteem, on social support and on familial support were associated with patients with SI/SA. Logistic regression showed that the most significant variables with suicidal patients included low BAL and low self-esteem and high alcohol consumption. Psychological distress had a direct and mediational role in the suicidal patients. Adolescents referred to the pediatric emergency department with intoxication displaying high psychological distress and low self-esteem represent a high-risk group of teens. In this group, careful assessment of mental health status, screening for suicidal ideation, and SAs seems warranted.

Development of suicidality within socioeconomic context: mediation effect of parental control and anomie.

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Heydari, Arash; Teymoori, Ali; Nasiri, Hedayat

Despite some scientific research on suicide as one of the most serious social and mental health problems in Iran, there is still lack of research on the effective structural and socio-familial factors contributing to the issue in Iran. The purpose of this study is to investigate some of the effective variables conditioning suicidality while also establishing a synthetic model. Three hundred-fifty university students (165 males, 185 females) were randomly chosen from Shahid Chamran University, Ahvaz, Iran. The participants were asked to complete a package of self-report questionnaires including subjective socioeconomic status (SES), feeling of anomie, perceived parental control, and suicidality. The results show that all correlations among variables are significant. For testing the theoretical model, results of standardized regression coefficients suggest that SES has direct effect on suicidality and indirect effect via anomie and parental control. In addition, parental control has direct effects on suicidality and indirect effect via anomie as well. The findings confirm the expected paths hypothesized among variables which are consistent with the theories of Durkheim, Merton, Kohn, and Agnew. It implies that the development of suicidality takes place within socioeconomic context through the influence of parental control and feeling of anomie.

Cross-sectional and temporal association between non-suicidal self-injury and suicidal ideation in young adults: The explanatory roles of thwarted belongingness and perceived burdensomeness

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Chu, Carol; Rogers, Megan L.; Joiner, Thomas E.

2016-01-01

Non-suicidal self-injury (NSSI) is a strong predictor of suicidal ideation and attempts. Consistent with the interpersonal theory of suicide, preliminary evidence suggests that NSSI is associated with higher levels of perceived burdensomeness (PB) and thwarted belongingness (TB). However, no study to date has examined the cross-sectional and prospective relationships between NSSI, TB, PB, and suicidal ideation (SI). To fill this gap, this study examined the mediating role of TB and PB in the relationship between NSSI and SI at baseline and follow-up. Young adults (N=49) with and without histories of NSSI completed self-report measures of TB, PB, and SI at three time points over two months. NSSI history was associated with higher levels of PB, TB, and SI at all time points. TB and PB significantly accounted for the relationship between NSSI history and SI at baseline. However, the relationship between NSSI history and SI at follow-up was mediated by PB, not TB. Findings provide evidence for the roles of TB and PB in the relationship between NSSI and SI, and partial support for the interpersonal theory of suicide. Future research and clinical implications are discussed. PMID:27835855

Crisis of Meaning Predicts Suicidality in Youth Independently of Depression.

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Schnell, Tatjana; Gerstner, Rebekka; Krampe, Henning

2018-02-23

At times, the question for meaning comes to nothing and a crisis of meaning ensues. This state is very painful, but difficult to account. Both those who suffer from it and care professionals find themselves at a loss for words. This study introduces an operationalization of a crisis of meaning. It aims to distinguish the concept from depression, and to investigate whether a crisis of meaning can explain suicidality beyond the known protective and risk factors self-esteem, family functioning, life-event load, and depression. Final-year school pupils in Ecuador (N = 300) completed questionnaires assessing the above variables. Data were analyzed using chi-square, hierarchic multiple regression, serial mediation, and moderator analyses. Crisis of meaning was distinguished from depression. It explained a significant amount of variance in suicidality beyond the mentioned protective and risk factors. For males, crisis of meaning was the only significant risk factor, and the strongest predictor overall. The acute risk factors depression and crisis of meaning mediated the effects of the baseline factors self-esteem, family functioning, and life-event load on suicidality. The study was cross-sectional; assessed factors predicted variance in suicidal thoughts, plans, and past suicide attempts, while their relevance cannot be generalized to actual future suicide attempts. A crisis of meaning is an important factor to take into account in further research on the prevention and treatment of people at risk of suicide.

The potential role of meaning in life in the relationship between bullying victimization and suicidal ideation.

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Henry, Kimberly L; Lovegrove, Peter J; Steger, Michael F; Chen, Peter Y; Cigularov, Konstantin P; Tomazic, Rocco G

2014-02-01

Adolescent bullying is a common problem in schools across America. The consequences of bullying are significant, and can include severe psychological trauma and suicide. A better understanding of the mechanisms that link bullying and suicidal ideation is needed in order to develop effective prevention and intervention initiatives. Meaning in life is a potential mechanism that has not been studied in this context. It was hypothesized that meaning in life could serve as both a mediator and a moderator of the relationship between bullying victimization and suicidal ideation. As a mediator, meaning in life is considered to explain why bullying victimization leads to suicidal ideation. As a moderator, meaning in life is considered to buffer the ill effect of bullying victimization on suicidal ideation. Data collected from an ethnically diverse sample of 2,936 (50% female), 6th-12th grade students from one urban school district in the Northeastern US were used to examine the hypotheses. The model for girls was consistent with mediation (i.e., meaning in life may explain how victimization leads to suicidal ideation). The model for boys was consistent with moderation (i.e., the ill effect of victimization on suicidal ideation was attenuated as meaning in life increased). Implications for prevention are discussed.

Dual monitoring using {sup 124}I-FIAU and bioluminescence for HSV1-tk suicide gene therapy

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Lee, T. S.; Kim, J. H.; Kwon, H. C. [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)] (and others)

2007-07-01

Herpes simplex virus type I thymidine kinase (HSV-tk) is the most common reporter gene and is used in cancer gene therapy with a prodrug nucleoside analog, ganciclovir (GCV). The aim of this study is to evaluate therapeutic efficacy of suicide gene therapy with 2'-fluoro-2'-deoxy-1-D-arabinofuranosyl-5-[{sup 124}I] iodouracil ({sup 124}I - FIAU) and bioluminescence in retrovirally HSV -tk and firefly luciferase transduced hepatoma model. The HSV -tk and firefly luciferase (Luc) was retrovirally transduced and expressed in MCA rat Morris hepatoma cells. Nude mice with subcutaneous tumors, MCA and MCA-TK-Luc, were subjected to GCV treatment (50mg/Kg/d intraperitoneally) for 5 day. PET imaging and biodistribution with ({sup 124}I-FIAU) were performed at before and after initiation of therapy with GCV. Bioluminescent signal was also measured during GCV treatment. Before GCV treatment, no significant difference in tumor volume was found in tumors between MCA and MCA-TK-Luc. After GCV treatment, tumor volume of MCA-TK-Luc markedly reduced compared to that of MCA. In biodistribution study, {sup 124}I-FIAU uptake after GCV therapy significantly decreased compared with pretreatment levels (34.8 13.67 %ID/g vs 7.6 2.59 %ID/g) and bioluminescent signal was also significantly decreased compared with pretreatment levels. In small animal PET imaging, {sup 124}I-FIAU selectively localized in HSV -tk expressing tumor and the therapeutic efficacy of GCV treatment was evaluated by {sup 124}I-FIAU PET imaging. {sup 124}I-FIAU PET and bioluminescence imaging in HSV-tk suicide gene therapy were effective to evaluate the therapeutic response. {sup 124}I-FIAU may serve as an efficient and selective agent for monitoring of transduced HSV1-tk gene expression in vivo in clinical trials.

Interrelationships between LGBT-Based Victimization, Suicide, and Substance Use Problems in a Diverse Sample of Sexual and Gender Minority Men and Women

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Mereish, Ethan H.; O'Cleirigh, C; Bradford, Judith B.

2013-01-01

Research has documented significant relationships between sexual and gender minority stress and higher rates of suicidality (i.e., suicidal ideation and attempts) and substance use problems. We examined the potential mediating role of substance use problems on the relationship between sexual and gender minority stress (i.e., victimization based on lesbian, gay, bisexual, or transgender identity; LGBT) and suicidality. A non-probability sample of LGBT patients from a community health center (N = 1457) ranged in age 19 to 70 years. Participants reported history of lifetime suicidal ideation and attempts, and substance use problems, as well as experiences of LGBT-based verbal and physical attacks. Substance use problems were a significant partial mediator between LGBT-based victimization and suicidal ideation and between LGBT-based victimization and suicide attempts for sexual and gender minorities. Nuanced gender differences revealed that substance use problems did not significantly mediate the relationship between victimization and suicide attempts for sexual minority men. Substance use problems may be one insidious pathway that partially mediates the risk effects of sexual and gender minority stress on suicidality. Substances might be a temporary and deleterious coping resource in response to LGBT-based victimization, which have serious effects on suicidal ideation and behaviors. PMID:23535038

Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder

Science.gov (United States)

2011-01-01

Background The MAOA uVNTR polymorphism has been documented to affect the MAOA gene at the transcriptional level and is associated with aggressive impulsive behaviors, depression associated with suicide (depressed suicide), and major depressive disorder (MDD). We hypothesized that the uVNTR polymorphism confers vulnerability to MDD, suicide or both. The aim of this study was to explore the association between the MAOA uVNTR and depressed suicide, using multiple controls. Methods Four different groups were included: 432 community controls, 385 patients with MDD who had not attempted suicide, 96 community subjects without mental disorders who had attempted suicide, and 109 patients with MDD who had attempted suicide. The MAOA uVNTR polymorphism was genotyped by a PCR technique. The symptom profiles and personal characteristics in each group were also compared. Results The MAOA 4R allele was more frequent in males with MDD than in male community controls (χ2 = 4.182, p = 0.041). Logistic regression analysis showed that, among the depressed subjects, those younger in age, more neurotic or who smoked had an increased risk of suicide (β = -0.04, p = 0.002; β = 0.15, p = 0.017; β = 0.79, p = 0.031, respectively). Moreover, among those who had attempted suicide, those younger in age, with more paternal overprotection, and more somatic symptoms were more likely to be in the MDD group than in the community group (β = -0.11, p depressed suicide were associated with severity of depression, personality traits, age, marital status, and inversely associated with anxiety symptoms. However, depression did not affect suicidal behavior in the community group. Conclusion The MAOA 4R allele is associated with enhanced vulnerability to suicide in depressed males, but not in community subjects. The MAOA 4R allele affects vulnerability to suicide through the mediating factor of depressive symptoms. Further large-scale studies are needed to verify the psychopathology of the

Psychosocial correlates of suicidal ideation in rural South African adolescents.

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Shilubane, Hilda N; Ruiter, Robert A C; Bos, Arjan E R; van den Borne, Bart; James, Shamagonam; Reddy, Priscilla S

2014-01-01

Suicide is a prevalent problem among young people in Southern Africa, but prevention programs are largely absent. This survey aimed to identify the behavioral and psychosocial correlates of suicidal ideation among adolescents in Limpopo. A two-stage cluster sample design was used to establish a representative sample of 591 adolescents. Bivariate correlations and multiple linear regression analyses were conducted. Findings show that suicidal ideation is prevalent among adolescents. The psychosocial factors perceived social support and negative feelings about the family and the behavioral factors forced sexual intercourse and physical violence by the partner were found to increase the risk of suicidal ideation. Depression mediated the relationship between these psychosocial and behavioral risk factors and suicidal ideation. This study increased our understanding of the psychosocial and behavioral predictors of adolescent suicidal ideation. The findings provide target points for future intervention programs and call for supportive structures to assist adolescents with suicidal ideation.

Belief system, meaningfulness, and psychopathology associated with suicidality among Chinese college students: a cross-sectional survey.

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Zhao, Jiubo; Yang, Xueling; Xiao, Rong; Zhang, Xiaoyuan; Aguilera, Diane; Zhao, Jingbo

2012-08-17

Research suggests that Chinese religious believers are more likely to commit suicide than those identifying as non-religious among rural young adults, contrary to findings in Western countries. However, one cannot conclude that religiosity is associated with elevated suicide risk without examining the effect of political and religious beliefs in a generally atheist country like China where political belief plays a dominant role in the belief system of young adults. The present study investigated the effects of political and religious belief on suicidality with meaningfulness and psychopathology as potential mediators in a large representative sample of Chinese college students. A cross-sectional survey was conducted among 1390 first-year college students randomly sampled from 10 colleges and universities in mainland China. A total of 1168 respondents (84.0%) provided complete data on all variables. Lifetime prevalence of suicidal ideation, plan, and attempt were 45.1%, 6.8%, and 1.9% respectively, with one-year suicidal ideation showing at 19.3%. Female gender was associated with elevated risk of suicidality. Political belief but not religious belief was associated with decreased suicide risk. A significant interactive effect of political belief and religious belief was found, indicating that for political believers, being religious was associated with decreased suicide risk; for non-political believers, being religious was associated with increased suicide risk. Multi-group structural equation modeling showed that meaningfulness completely mediated and psychopathology partially mediated the effect of belief system on suicidality. Gender differences were found in pathways of political belief by religious beliefs to suicidality and political belief to psychopathology. The coefficients were significant for males but not for females. In less religious societies, political belief may serve as a means of integration as does religious affiliation in religious societies

Suicide Gene-Engineered Stromal Cells Reveal a Dynamic Regulation of Cancer Metastasis

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Shen, Keyue; Luk, Samantha; Elman, Jessica; Murray, Ryan; Mukundan, Shilpaa; Parekkadan, Biju

2016-02-01

Cancer-associated fibroblasts (CAFs) are a major cancer-promoting component in the tumor microenvironment (TME). The dynamic role of human CAFs in cancer progression has been ill-defined because human CAFs lack a unique marker needed for a cell-specific, promoter-driven knockout model. Here, we developed an engineered human CAF cell line with an inducible suicide gene to enable selective in vivo elimination of human CAFs at different stages of xenograft tumor development, effectively circumventing the challenge of targeting a cell-specific marker. Suicide-engineered CAFs were highly sensitive to apoptosis induction in vitro and in vivo by the addition of a simple small molecule inducer. Selection of timepoints for targeted CAF apoptosis in vivo during the progression of a human breast cancer xenograft model was guided by a bi-phasic host cytokine response that peaked at early timepoints after tumor implantation. Remarkably, we observed that the selective apoptosis of CAFs at these early timepoints did not affect primary tumor growth, but instead increased the presence of tumor-associated macrophages and the metastatic spread of breast cancer cells to the lung and bone. The study revealed a dynamic relationship between CAFs and cancer metastasis that has counter-intuitive ramifications for CAF-targeted therapy.

Familial aggregation of suicide explained by cluster B traits: a three-group family study of suicide controlling for major depressive disorder.

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McGirr, Alexander; Alda, Martin; Séguin, Monique; Cabot, Sophie; Lesage, Alain; Turecki, Gustavo

2009-10-01

There is substantial evidence suggesting that suicide aggregates in families. However, the extent of overlap between the liability to suicide and psychiatric disorders, particularly major depressive disorder, remains an important issue. Similarly, factors that account for the familial transmission of suicidal behavior remain unclear. Thus, through direct and blind assessment of first-degree relatives, the authors conducted a family study of suicide by examining three proband groups: probands who committed suicide in the context of major depressive disorder, living depressed probands with no history of suicidal behavior, and psychiatrically normal community comparison probands. Participants were 718 first-degree relatives from 120 families: 296 relatives of 51 depressed probands who committed suicide, 185 relatives of 34 nonsuicidal depressed probands, and 237 relatives of 35 community comparison subjects. Psychopathology, suicidal behavior, and behavioral measures were assessed via interviews. The relatives of probands who committed suicide had higher levels of suicidal behavior (10.8%) than the relatives of nonsuicidal depressed probands (6.5%) and community comparison probands (3.4%). Testing cluster B traits as intermediate phenotypes of suicide showed that the relatives of depressed probands who committed suicide had elevated levels of cluster B traits; familial predisposition to suicide was associated with increased levels of cluster B traits; cluster B traits demonstrated familial aggregation and were associated with suicide attempts among relatives; and cluster B traits mediated, at least in part, the relationship between familial predisposition and suicide attempts among relatives. Analyses were repeated for severity of attempts, where cluster B traits also met criteria for endophenotypes of suicide. Familial transmission of suicide and major depression, while partially overlapping, are distinct. Cluster B traits and impulsive-aggressive behavior represent

Potential Mediating Pathways through Which Sports Participation Relates to Reduced Risk of Suicidal Ideation

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Taliaferro, Lindsay A.; Rienzo, Barbara A.; Miller, M. David; Pigg, R. Morgan; Dodd, Virginia J.

2010-01-01

Suicide ranks as the third leading cause of death for American youth. Researchers examining sport participation and suicidal behavior have regularly found inverse relationships. This study represents the first effort to test a model depicting potential mechanisms through which sport participation relates to reduced risk of suicidal ideation. The…

Suicide and suicidal behavior

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... than prescribed medicines) can reduce the risk of suicide. In homes with children or teenagers: Keep all prescription medicines high up ... or attempted suicide. Alternative Names Depression - suicide; Bipolar - suicide ... in children Depression among the elderly References American Psychiatric Association. ...

Determinants of suicidal ideation in gynecological cancer patients.

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Tang, G X; Yan, P P; Yan, C L; Fu, B; Zhu, S J; Zhou, L Q; Huang, X; Wang, Y; Lei, J

2016-01-01

Gynecological cancer survivors are at increased risk of psychological problems including suicide risk. Suicidal ideation, which was thought to be precursor to suicide attempts, has not been well studied. This study aimed to investigate the prevalence, and determinants of suicidal ideation for women with gynecological cancer, and then to assess the effect of coping style and social support on suicidal ideation. Patients with cervical, ovarian and endometrial cancers seen at Hunan Provincial Tumor Hospital from September 2012 to June 2013 were consecutively recruited and were asked to complete the Zung Self-Rating Depression Scale, Suicidal Ideation of Self-rating Scale, Medical Coping Modes Questionnaire and Social Support Rating Scale. Path analysis was used to examine the relationship among coping style, social support, depression symptoms and suicidal ideation. A total of 579 (579/623, 93.0%) gynecological cancer patients were enrolled in this study and completed all investigations between September 2012 and June 2013. Among them, 105 (18.1%) patients reported suicidal ideation, with the highest rate in patients with ovarian cancer (30.16%). Suicidal ideation was associated with depression symptoms, care providers, chemotherapy history and acceptance-resignation. Path analysis showed that the acceptance-resignation affected suicidal ideation directly as well as mediated by social support and depression symptoms, while confrontation and avoidance affected suicidal ideation entirely through social support and depression symptoms. Suicidal ideation is high among patients with gynecological cancer, especially among ovarian cancer patients. Coping strategies such as confrontation and avoidance, and social support may be helpful for preventing suicidal ideation among them. Copyright © 2015 John Wiley & Sons, Ltd.

Mind full of life: Does mindfulness confer resilience to suicide by increasing zest for life?

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Collins, Khan R L; Stritzke, Werner G K; Page, Andrew C; Brown, Julia D; Wylde, Tricia J

2018-01-15

Mindfulness is a trainable skill that may enhance resilience to suicidality among vulnerable groups such as young people. The current study examined whether mindfulness protects against suicidal desire in the face of heightened risk and adversity by increasing zest for life in a sample of university students. In a prospective design, participants (N = 233) were assessed at two time points over eight weeks. Online surveys included the Mindful Attention and Awareness Scale, Zest for Life Scale, Interpersonal Needs Questionnaire, Kessler Psychological Distress Scale, and items assessing suicidal ideation and suicidal intent. Baseline mindfulness was associated with lower suicidal ideation and intent at follow-up. Moderated mediation analyses confirmed the effects of mindfulness on ideation and intent were mediated by zest for life and these indirect effects were stronger at higher versus lower levels of general (psychological distress) and suicide-specific (perceived burdensomeness and thwarted belongingness) risk. Single item assessments of suicidal desire. Findings suggest that mindfulness protects against suicidal desire in conditions of heightened risk and adversity by enhancing one's orientation towards a life worth living. Theories of suicide should consider the dynamic interplay between risk and life-sustaining resilience, while clinicians treating suicidality could use mindfulness strategies to strengthen the desire to (re)engage with life, thereby complementing direct amelioration of suicide risk factors. Copyright © 2017 Elsevier B.V. All rights reserved.

The mediating role of non-suicidal self-injury in the relationship between impulsivity and suicidal behavior among inpatients receiving treatment for substance use disorders.

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Anestis, Michael D; Tull, Matthew T; Lavender, Jason M; Gratz, Kim L

2014-08-15

Several theories posit a direct role of impulsivity in suicidal behavior. The interpersonal-psychological theory of suicidal behavior (IPTS) argues that the relationship between impulsivity and suicidal behavior is explained by the painful and/or provocative experiences (PPEs) often encountered by impulsive individuals. It thus seems plausible that nonsuicidal self-injury (NSSI), itself associated with impulsivity, might account for the relationship between impulsivity and suicidal behavior. We examined data from 93 adult inpatients (54.8% male) seeking treatment for substance use disorders. Patients completed a structured interview assessing prior suicidal behavior and a series of self-report questionnaires examining impulsivity, NSSI, and psychopathology. Four impulsivity dimensions (negative urgency, positive urgency, lack of premeditation, lack of perseverance) were associated with lifetime number of suicide attempts and/or suicide potential. Furthermore, results supported our hypotheses, as all but one relation was better accounted for by NSSI and, in the one exception, the direct effect was non-significant. Findings are consistent with the IPTS and suggest that suicidal behavior may not be a direct manifestation of impulsivity, but facilitated through exposure to PPEs capable of altering an individual׳s relationship to pain and fear of death. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Genetic association studies of suicidal behaviour: A review of the past 10 years, progress, limitations and future directions.

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BOJAN MIRKOVIC

2016-09-01

Full Text Available Suicidal behaviours, which range from suicidal ideation to suicide attempts and completed suicide, represent a fatal dimension of mental ill-health. The involvement of genetic risk factors in suicidal behaviour is supported by family, twin, and adoption studies. The aim of this paper is to review recent genetic association studies in suicidal behaviours including (i case-control studies, (ii family-based association studies and (iii genome-wide association studies (GWAS. Various studies on genetic associations have tended to suggest that a number of genes (e.g., tryptophan hydroxylase, serotonin receptors and transporters or brain-derived neurotrophic factors are linked to suicidal behaviours, but these findings are not consistently supported by the results obtained. Although the candidate-gene approach is useful, it is hampered by the present state of knowledge concerning the pathophysiology of diseases. Interpretations of GWAS results are mostly hindered by a lack of annotation describing the functions of most variation throughout the genome.Association studies have addressed a wide range of SNPs in numerous genes. We have included 104 such studies, of which 10 are family-based association studies and 11 are GWAS studies. Numerous meta-analyses of case-control studies have shown significant associations of suicidal behaviour with variants in the serotonin transporter gene (5-HTT or SLC6A4 and the tryptophane hydroxylase1 gene (TPH1, but others report contradictory results. The gene encoding brain-derived neurotrophic factor (BDNF and its receptor (NTRK2 are also promising candidates. Only two of the GWAS studies showed any significant associations. Several pathways are mentioned in an attempt to understand the lack of reproducibility and the disappointing results. Consequently, we review and discuss here the following aspects: (i sample characteristics and confounding factors; (ii statistical limits; (iii gene-gene interactions; (iv gene

Predictors of suicidal ideation in older individuals receiving home-care services.

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Park, Jong-Il; Han, Myeong-Il; Kim, Myung Sig; Yoon, Myeong-Sook; Ko, Sung-Hee; Cho, Hye-Chung; Chung, Young-Chul

2014-04-01

Despite the importance of tending to older individuals who are vulnerable to suicide, little is known about suicidal ideation in the portion of this population receiving home-care services in Asian countries. The objective of this cross-sectional study was to examine predictors of suicidal ideation in older individuals using home-care service. Participants were randomly selected from the individuals 50 years old and over using home-care services across Jeollabuk-do Province, Korea. A total of 697 subjects participated in this study. Each participant completed the short version of the Geriatric Depression Scale, the Scale for Suicidal Ideation, the Multidimensional Scale of Perceived Social Support, and the World Health Organization Disability Assessment Schedule II. Hierarchical regression analyses revealed that depression, perceived social support, and disability were significant predictors of suicidal ideation, whereas the roles of subjective health status and fish consumption remained ambiguous in this regard. In terms of social support, we also found that less perceived social support from family members was related to higher levels of suicidal ideation. The associations between various categories of disability and suicidal ideation disappeared after controlling for depression. Our investigation of the mediating effect of depression on the relationship between disability and suicidal ideation revealed that depression was either a complete (disability related to cognition, self-care, getting along with others, and life activities) or partial (disability related to participation) mediator. Preventive strategies focusing on depression, social support, and disability should be emphasized during encounters with older people receiving home-care services. Copyright © 2013 John Wiley & Sons, Ltd.

Psychological Distress Following Suicidality Among Gay, Lesbian, and Bisexual Youths: Role of Social Relationships

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Rosario, Margaret; Schrimshaw, Eric W.; Hunter, Joyce

2011-01-01

Longitudinal relations between past suicidality and subsequent changes in psychological distress at follow-up were examined among gay, lesbian, and bisexual (GLB) youths, as were psychosocial factors (e.g., self-esteem, social support, negative social relationships) that might mediate or moderate this relation. Past suicide attempters were found to have higher levels of depressive symptoms, anxious symptoms, and conduct problems at a later time than youths who neither attempted nor ideated. Psychosocial factors failed to mediate this relation. The interaction among past suicidality, social support, and negative relationships was associated with subsequent changes in all three psychological distress indicators six months later. Specifically, high levels of support (either from family or friends) or negative relationships were found to predict increased psychological distress among those with a history of suicide attempts, but not among youths without a history of suicidality. The findings suggest that GLB youths who attempt suicide continue to have elevated levels of psychological distress long after their attempt and they highlight the importance of social relationships in the youths’ psychological distress at follow-up. PMID:22162620

Membrane fusion inducers, chloroquine and spermidine increase lipoplex-mediated gene transfection

International Nuclear Information System (INIS)

Wong-Baeza, Carlos; Bustos, Israel; Serna, Manuel; Tescucano, Alonso; Alcantara-Farfan, Veronica; Ibanez, Miguel; Montanez, Cecilia; Wong, Carlos; Baeza, Isabel

2010-01-01

Gene transfection into mammalian cells can be achieved with viral and non-viral vectors. Non-viral vectors, such as cationic lipids that form lipoplexes with DNA, are safer and more stable than viral vectors, but their transfection efficiencies are lower. Here we describe that the simultaneous treatment with a membrane fusion inducer (chlorpromazine or procainamide) plus the lysosomotropic agent chloroquine increases lipoplex-mediated gene transfection in human (HEK293 and C-33 A) and rat (PC12) cell lines (up to 9.2-fold), as well as in situ in BALB/c mice spleens and livers (up to 6-fold); and that the polyamine spermidine increases lipoplex-mediated gene transfection and expression in cell cultures. The use of these four drugs provides a novel, safe and relatively inexpensive way to considerably increase lipoplex-mediated gene transfection efficiency.

Explaining risk for suicidal ideation in adolescent offspring of mothers with depression.

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Hammerton, G; Zammit, S; Thapar, A; Collishaw, S

2016-01-01

It is well-established that offspring of depressed mothers are at increased risk for suicidal ideation. However, pathways involved in the transmission of risk for suicidal ideation from depressed mothers to offspring are poorly understood. The aim of this study was to examine the contribution of potential mediators of this association, including maternal suicide attempt, offspring psychiatric disorder and the parent-child relationship. Data were utilized from a population-based birth cohort (ALSPAC). Three distinct classes of maternal depression symptoms across the first 11 years of the child's life had already been identified (minimal, moderate, chronic-severe). Offspring suicidal ideation was assessed at age 16 years. Data were analysed using structural equation modelling. There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms compared to offspring of mothers with minimal symptoms (odds ratio 3.04, 95% confidence interval 2.19-4.21). The majority of this association was explained through maternal suicide attempt and offspring psychiatric disorder. There was also evidence for an independent indirect effect via the parent-child relationship in middle childhood. There was no longer evidence of a direct effect of maternal depression on offspring suicidal ideation after accounting for all three mediators. The pattern of results was similar when examining mechanisms for maternal moderate depression symptoms. Findings highlight that suicide prevention efforts in offspring of depressed mothers should be particularly targeted at both offspring with a psychiatric disorder and offspring whose mothers have made a suicide attempt. Interventions aimed at improving the parent-child relationship may also be beneficial.

The Mediator Complex MED15 Subunit Mediates Activation of Downstream Lipid-Related Genes by the WRINKLED1 Transcription Factor.

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Kim, Mi Jung; Jang, In-Cheol; Chua, Nam-Hai

2016-07-01

The Mediator complex is known to be a master coordinator of transcription by RNA polymerase II, and this complex is recruited by transcription factors (TFs) to target promoters for gene activation or repression. The plant-specific TF WRINKLED1 (WRI1) activates glycolysis-related and fatty acid biosynthetic genes during embryogenesis. However, no Mediator subunit has yet been identified that mediates WRI1 transcriptional activity. Promoter-β-glucuronidase fusion experiments showed that MEDIATOR15 (MED15) is expressed in the same cells in the embryo as WRI1. We found that the Arabidopsis (Arabidopsis thaliana) MED15 subunit of the Mediator complex interacts directly with WRI1 in the nucleus. Overexpression of MED15 or WRI1 increased transcript levels of WRI1 target genes involved in glycolysis and fatty acid biosynthesis; these genes were down-regulated in wild-type or WRI1-overexpressing plants by silencing of MED15 However, overexpression of MED15 in the wri1 mutant also increased transcript levels of WRI1 target genes, suggesting that MED15 also may act with other TFs to activate downstream lipid-related genes. Chromatin immunoprecipitation assays confirmed the association of MED15 with six WRI1 target gene promoters. Additionally, silencing of MED15 resulted in reduced fatty acid content in seedlings and mature seeds, whereas MED15 overexpression increased fatty acid content in both developmental stages. Similar results were found in wri1 mutant and WRI1 overexpression lines. Together, our results indicate that the WRI1/MED15 complex transcriptionally regulates glycolysis-related and fatty acid biosynthetic genes during embryogenesis. © 2016 American Society of Plant Biologists. All Rights Reserved.

Effect of Tryptophan Hydroxylase-2 rs7305115 SNP on suicide attempts risk in major depression

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Zhang Yuqi

2010-08-01

Full Text Available Abstract Background Suicide and major depressive disorders (MDD are strongly associated, and genetic factors are responsible for at least part of the variability in suicide risk. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2 gene rs7305115 SNP may predispose to suicide attempts in MDD. Methods We genotyped TPH2 gene rs7305115 SNP in 215 MDD patients with suicide and matched MDD patients without suicide. Differences in behavioral and personality traits according to genotypic variation were investigated by logistic regression analysis. Results There were no significant differences between MDD patients with suicide and controls in genotypic (AG and GG frequencies for rs7305115 SNP, but the distribution of AA genotype differed significantly (14.4% vs. 29.3%, p p p Conclusions The study suggested that hopelessness, negative life events and family history of suicide were risk factors of attempted suicide in MDD while the TPH2 rs7305115A remained a significant protective predictor of suicide attempts.

Perceived stress, depressive symptoms, and suicidal ideation in undergraduate women with varying levels of mindfulness.

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Anastasiades, Maria H; Kapoor, Shweta; Wootten, Jennifer; Lamis, Dorian A

2017-02-01

Research has demonstrated that perceived stress and depression are risk factors for suicidal ideation in young adults, particularly women attending college. Female undergraduate students (N = 928) were administered measures assessing their levels of stress, depressive symptoms, suicidal thoughts, and mindfulness. A moderated-mediation analysis was conducted to examine the complex associations among these variables. Results indicated that mindfulness moderated the mediated effect of depressive symptoms on perceived stress and suicidal ideation. Specifically, the indirect effect was stronger in college women with lower levels of mindfulness as compared to those students who reported higher mindfulness. Thus, teaching mindfulness techniques on college campuses may be an important strategy for preventing suicide, especially among young adult women experiencing stress and depressive symptoms.

Associations among daytime sleepiness, depression and suicidal ideation in Korean adolescents.

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Yang, Boksun; Choe, Kwisoon; Park, Youngrye; Kang, Youngmi

2017-06-09

The aim of this study was to examine the effects of daytime sleepiness on depression and suicidal ideation in adolescent high-school students. A survey of 538 high school students aged 16-17 years attending two academic schools was conducted. The Epworth Sleepiness Scale (ESS), the Beck Depression Inventory and the Scale for Suicide Ideation were used to assess subjects' daytime sleepiness, depression and suicidal ideation. The mean score for daytime sleepiness was 8.52, which indicates a sleep deficit. Significant positive correlations were found between daytime sleepiness and depression, between daytime sleepiness and suicidal ideation and between depression and suicidal ideation. Gender and depression were significant predictors of suicidal ideation, accounting for 48% of the variance in this measure. Depression acts as a mediator of the relationship between daytime sleepiness and suicidal ideation. High school students in Korea generally have insufficient sleep time and feel sleepy during the day; insufficient sleep during adolescence may be associated with depression and suicidal ideation.

miRNA-mediated functional changes through co-regulating function related genes.

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Jie He

Full Text Available BACKGROUND: MicroRNAs play important roles in various biological processes involving fairly complex mechanism. Analysis of genome-wide miRNA microarray demonstrate that a single miRNA can regulate hundreds of genes, but the regulative extent on most individual genes is surprisingly mild so that it is difficult to understand how a miRNA provokes detectable functional changes with such mild regulation. RESULTS: To explore the internal mechanism of miRNA-mediated regulation, we re-analyzed the data collected from genome-wide miRNA microarray with bioinformatics assay, and found that the transfection of miR-181b and miR-34a in Hela and HCT-116 tumor cells regulated large numbers of genes, among which, the genes related to cell growth and cell death demonstrated high Enrichment scores, suggesting that these miRNAs may be important in cell growth and cell death. MiR-181b induced changes in protein expression of most genes that were seemingly related to enhancing cell growth and decreasing cell death, while miR-34a mediated contrary changes of gene expression. Cell growth assays further confirmed this finding. In further study on miR-20b-mediated osteogenesis in hMSCs, miR-20b was found to enhance osteogenesis by activating BMPs/Runx2 signaling pathway in several stages by co-repressing of PPARγ, Bambi and Crim1. CONCLUSIONS: With its multi-target characteristics, miR-181b, miR-34a and miR-20b provoked detectable functional changes by co-regulating functionally-related gene groups or several genes in the same signaling pathway, and thus mild regulation from individual miRNA targeting genes could have contributed to an additive effect. This might also be one of the modes of miRNA-mediated gene regulation.

Suicide and Murder-Suicide Involving Aircraft.

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Kenedi, Christopher; Friedman, Susan Hatters; Watson, Dougal; Preitner, Claude

2016-04-01

This is a systematic review of suicide and homicide-suicide events involving aircraft. In aeromedical literature and in the media, these very different events are both described as pilot suicide, but in psychiatry they are considered separate events with distinct risk factors. Medical databases, internet search engines, and aviation safety databases were searched in a systematic way to obtain relevant cases. Relevant articles were searched for additional references. There were 65 cases of pilot suicide and 6 cases of passengers who jumped from aircraft found. There were also 18 cases of homicide-suicide found involving 732 deaths. Pilots perpetrated 13 homicide-suicide events. Compared to non-aviation samples, a large percentage of pilot suicides in this study were homicide-suicides (17%). Homicide-suicide events occur extremely rarely. However, their impact in terms of the proportion of deaths is significant when compared to deaths from accidents. There is evidence of clustering where pilot suicides occur after by media reports of suicide or homicide-suicide. Five of six homicide-suicide events by pilots of commercial airliners occurred after they were left alone in the cockpit. This, along with a sixth incident in which active intervention by a Japan Air crew saved 147 lives, suggests that having two flight members in the cockpit is potentially protective. No single factor was associated with the risk for suicide or homicide-suicide. Factors associated with both events included legal and financial crises, occupational conflict, mental illness, and relationship stressors. Drugs and/or alcohol played a role in almost half of suicides, but not in homicide-suicides.

Follistatin allows efficient retroviral-mediated gene transfer into rat liver

International Nuclear Information System (INIS)

Borgnon, Josephine; Djamouri, Fatima; Lorand, Isabelle; Rico, Virginie Di; Loux, Nathalie; Pages, Jean-Christophe; Franco, Dominique; Capron, Frederique; Weber, Anne

2005-01-01

Retroviral vectors are widely used tools for gene therapy. However, in vivo gene transfer is only effective in dividing cells, which, in liver, requires a regenerative stimulus. Follistatin is effective in promoting liver regeneration after 90% and 70% hepatectomy in rats. We studied its efficacy on liver regeneration and retroviral-mediated gene delivery in 50% hepatectomized rats. When human recombinant follistatin was infused into the portal vein immediately after 50% hepatectomy, hepatocyte proliferation was significantly higher than in control 50% hepatectomized rats. A single injection of virus particles administered 23 h after follistatin infusion resulted in more than 20% gene transduction efficiency in hepatocytes compared to 3% in control rats. It is concluded that a single injection of follistatin induces onset of proliferation in 50% hepatectomized rats and allows efficient retroviral-mediated gene transfer to the liver

Imaging gene expression in gene therapy

International Nuclear Information System (INIS)

Wiebe, Leonard I.

1997-01-01

Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on 'suicide gene therapy' of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k + ) has been use for 'suicide' in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k + gene expression where the H S V-1 t k + gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([ 18 F]F H P G; [ 18 F]-A C V), and pyrimidine- ([ 123 / 131 I]I V R F U; [ 124 / 131I ]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [ 123 / 131I ]I V R F U imaging with the H S V-1 t k + reporter gene will be presented

Noninvasive theranostic imaging of HSV-TK/GCV suicide gene therapy in liver cancer by folate-targeted quantum dot-based liposomes

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Shao, D.; Li, J.; Pan, Y.; Zhang, X.; Zheng, X.; Wang, Z.; Zhang, M.; Zhang, H.; Chen, L.

2015-01-01

Theranostics is emerging as a popular strategy for cancer therapy; thanks to the development of nano-technology. In this work, we have combined an HSV-TK/GCV suicide gene system and near-infrared quantum dots, as the former is quite effective in liver cancer treatment and the latter facilitates

The Effectiveness of Family-Based Cognitive-Behavior Grief Therapy to Prevent Complicated Grief in Relatives of Suicide Victims: The Mediating Role of Suicide Ideation

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de Groot, Marieke; Neeleman, Jan; van der Meer, Klaas; Burger, Huibert

2010-01-01

Grief interventions are more effective for high risk individuals. The presence of suicide ideation following suicide bereavement was examined to determine whether it indicates a high risk status. Using data from a randomized controlled trial (n = 122) on the effectiveness of cognitive-behavior therapy, the effect of suicide ideation on the…

Recent Trends of Polymer Mediated Liposomal Gene Delivery System

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Shyamal Kumar Kundu

2014-01-01

Full Text Available Advancement in the gene delivery system have resulted in clinical successes in gene therapy for patients with several genetic diseases, such as immunodeficiency diseases, X-linked adrenoleukodystrophy (X-ALD blindness, thalassemia, and many more. Among various delivery systems, liposomal mediated gene delivery route is offering great promises for gene therapy. This review is an attempt to depict a portrait about the polymer based liposomal gene delivery systems and their future applications. Herein, we have discussed in detail the characteristics of liposome, importance of polymer for liposome formulation, gene delivery, and future direction of liposome based gene delivery as a whole.

The effect of macroeconomic variables on suicide.

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Berk, Michael; Dodd, Seetal; Henry, Margaret

2006-02-01

There are a large number of factors mediating suicide. Many studies have searched for a direct causal relationship between economic hardship and suicide, however, findings have been varied. Suicide data was obtained from the Australian Bureau of Statistics for the period between January 1968 and August 2002. These were correlated with a suite of macroeconomic data including housing loan interest rates, unemployment rates, days lost to industrial disputes, Consumer Price Index, gross domestic product, and the Consumer Sentiment Index. A total of 51845 males and 16327 females committed suicide between these dates. There were significant associations between suicide rates and eleven macroeconomic indicators for both genders in at least one age range. Data was divided into male and female and five age ranges and pooled ages. Analyses were conducted on these 132 datasets resulting in 80 significant findings. The data was generally stronger for indices measuring economic performance than indices measuring consumers' perceptions of the state of the economy. A striking difference between male and female trends was seen. Generally, male suicide rates increased with markers of economic adversity, while the opposite pattern was seen in females. There were significantly different patterns in age-stratified data, with for example higher housing loan interest rates having a positive association with suicide in younger people and a negative association in older age groups. Macroeconomic trends are significantly associated with suicide. The patterns in males and females are very different, and there are further substantial age-related differences.

Wolfram syndrome and suicide: Evidence for a role of WFS1 in suicidal and impulsive behavior.

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Sequeira, Adolfo; Kim, Caroline; Seguin, Monique; Lesage, Alain; Chawky, Nadia; Desautels, Alex; Tousignant, Michel; Vanier, Claude; Lipp, Olivier; Benkelfat, Chawki; Rouleau, Guy; Turecki, Gustavo

2003-05-15

There is evidence suggesting that subjects affected with the Wolfram syndrome (WFS) and normal carriers present an increased risk of psychiatric disorders, particularly depression and suicidal behavior. We investigated a possible role of the gene involved in WFS (WFS1) in the neurobiology of suicide and the potential modulatory effect on traits associated to suicidal behavior. Genetic variation at WFS1 (H611R, R456H, and I333V) was investigated in 111 suicide victims and 129 normal controls. Possible effects on psychopathology and behavioral traits were investigated in a subsample of suicide cases (N = 31) for whom phenotyping was carried out by means of structured psychiatric interviews and questionnaires adapted for psychological autopsies. We found a significantly higher frequency of the 611R/611R genotype in suicide completers as compared to controls (chi(2) = 19.21, df=2, P = 0.001). Suicide completers with this genotype had higher scores on measures of impulsivity (t = -3.15, df = 15.3, P = 0.006); novelty seeking (NS) (t = -3.35, df = 13.8, P = 0.005); and conversely, lower scores of persistence (t = 2.4, df = 16.6, P = 0.028). Scores of impulsivity and NS remained higher in subjects with the associated genotype after adjusting for age, gender, and psychopathology. These results suggest a role for WFS1 in the pathophysiology of impulsive suicide, and are consistent with previous clinical reports suggesting an increased risk of suicidal behavior in WFS homozygotes and heterozygotes. However, these findings are preliminary and should be confirmed in independent samples. Copyright 2003 Wiley-Liss, Inc.

Belief system, meaningfulness, and psychopathology associated with suicidality among Chinese college students: a cross-sectional survey

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Zhao Jiubo

2012-08-01

Full Text Available Abstract Background Research suggests that Chinese religious believers are more likely to commit suicide than those identifying as non-religious among rural young adults, contrary to findings in Western countries. However, one cannot conclude that religiosity is associated with elevated suicide risk without examining the effect of political and religious beliefs in a generally atheist country like China where political belief plays a dominant role in the belief system of young adults. The present study investigated the effects of political and religious belief on suicidality with meaningfulness and psychopathology as potential mediators in a large representative sample of Chinese college students. Methods A cross-sectional survey was conducted among 1390 first-year college students randomly sampled from 10 colleges and universities in mainland China. Results A total of 1168 respondents (84.0% provided complete data on all variables. Lifetime prevalence of suicidal ideation, plan, and attempt were 45.1%, 6.8%, and 1.9% respectively, with one-year suicidal ideation showing at 19.3%. Female gender was associated with elevated risk of suicidality. Political belief but not religious belief was associated with decreased suicide risk. A significant interactive effect of political belief and religious belief was found, indicating that for political believers, being religious was associated with decreased suicide risk; for non-political believers, being religious was associated with increased suicide risk. Multi-group structural equation modeling showed that meaningfulness completely mediated and psychopathology partially mediated the effect of belief system on suicidality. Gender differences were found in pathways of political belief by religious beliefs to suicidality and political belief to psychopathology. The coefficients were significant for males but not for females. Conclusions In less religious societies, political belief may serve as a means of

Childhood Maltreatment, Pathological Personality Dimensions, and Suicide Risk in Young Adults.

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Falgares, Giorgio; Marchetti, Daniela; Manna, Giovanna; Musso, Pasquale; Oasi, Osmano; Kopala-Sibley, Daniel C; De Santis, Sandro; Verrocchio, Maria C

2018-01-01

Several studies have demonstrated that child maltreatment (psychological, physical, and sexual abuse, and neglect) may be a significant factor in the development of pathological personality traits that increase the risk for suicidal ideation and behavior from adolescence to adulthood. Currently, the challenge is to understand how different forms of early negative experiences render an individual prone to develop specific personality traits and, in turn, be more vulnerable to suicide risk. To understand the relationship between childhood maltreatment and personality dimensions in suicide risk, our study aims to explore the role of self-criticism and dependency, two different pathological personality traits, as potential mediators of the link between different types of childhood maltreatment and suicide risk in young adults. For this purpose, 306 students from three Italian public universities were recruited. We used the Italian version of the Childhood Experience of Care and Abuse Questionnaire (CECA.Q) to assess experiences of lack of care by parents (i.e., antipathy and neglect) as well as psychological and physical abuse before the age of 17 years. The Depressive Experiences Questionnaire (DEQ) was used to assess the personality dimensions of self-criticism and dependency, and the Suicide History Self-Rating Screening Scale was administered to assess suicide risk. Results revealed that lack of care and psychological abuse were significantly associated with suicide risk and this association was partially mediated by the maladaptive personality dimension of self-criticism. These findings suggest that the combined effect of specific forms of dysfunctional parental behavior during childhood and the development of rigid and dysfunctional negative personality traits may increase the risk for suicidal ideation and behavior during adulthood.

The Interrelations Between Internalized Homophobia, Depressive Symptoms, and Suicidal Ideation Among Australian Gay Men, Lesbians, and Bisexual Women.

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McLaren, Suzanne

2016-01-01

Internalized homophobia has been linked to depression among gay men, lesbians, and bisexuals. Relatively little research has investigated the link between internalized homophobia and suicidal thoughts and behaviors. The current research investigated the interrelations among internalized homophobia, depressive symptoms, and suicidal ideation by testing additive, mediation, and moderation models. Self-identified Australian gay men (n = 360), lesbians (n = 444), and bisexual women (n = 114) completed the Internalized Homophobia Scale, the Center for Epidemiological Studies Depression Scale, and the suicide subscale of the General Health Questionnaire. Results supported the additive and partial mediation models for gay men and the mediation and moderation models for lesbians. None of the models were supported for bisexual women. The findings imply that clinicians should focus on reducing internalized homophobia and depressive symptoms among gay men and lesbians, and depressive symptoms among bisexual women, to reduce suicidal ideation.

Gene structure and expression characteristic of a novel odorant receptor gene cluster in the parasitoid wasp Microplitis mediator (Hymenoptera: Braconidae).

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Wang, S-N; Shan, S; Zheng, Y; Peng, Y; Lu, Z-Y; Yang, Y-Q; Li, R-J; Zhang, Y-J; Guo, Y-Y

2017-08-01

Odorant receptors (ORs) expressed in the antennae of parasitoid wasps are responsible for detection of various lipophilic airborne molecules. In the present study, 107 novel OR genes were identified from Microplitis mediator antennal transcriptome data. Phylogenetic analysis of the set of OR genes from M. mediator and Microplitis demolitor revealed that M. mediator OR (MmedOR) genes can be classified into different subfamilies, and the majority of MmedORs in each subfamily shared high sequence identities and clear orthologous relationships to M. demolitor ORs. Within a subfamily, six MmedOR genes, MmedOR98, 124, 125, 126, 131 and 155, shared a similar gene structure and were tightly linked in the genome. To evaluate whether the clustered MmedOR genes share common regulatory features, the transcription profile and expression characteristics of the six closely related OR genes were investigated in M. mediator. Rapid amplification of cDNA ends-PCR experiments revealed that the OR genes within the cluster were transcribed as single mRNAs, and a bicistronic mRNA for two adjacent genes (MmedOR124 and MmedOR98) was also detected in female antennae by reverse transcription PCR. In situ hybridization experiments indicated that each OR gene within the cluster was expressed in a different number of cells. Moreover, there was no co-expression of the two highly related OR genes, MmedOR124 and MmedOR98, which appeared to be individually expressed in a distinct population of neurons. Overall, there were distinct expression profiles of closely related MmedOR genes from the same cluster in M. mediator. These data provide a basic understanding of the olfactory coding in parasitoid wasps. © 2017 The Royal Entomological Society.

Family support, family stress, and suicidal ideation in a combat-exposed sample of Operation Enduring Freedom/Operation Iraqi Freedom veterans.

Science.gov (United States)

Gradus, Jaimie L; Smith, Brian N; Vogt, Dawne

2015-01-01

Deployment-related risk factors for suicidal ideation among Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) veterans have received a great deal of attention. Studies show that mental health symptoms mediate the association between most deployment stressors and suicidal ideation; however, family-related factors during deployment are largely unexplored. We examined posttraumatic stress disorder (PTSD) and depression symptoms as mediators of the associations between deployment family support and stress and post-deployment suicidal ideation in combat-exposed OEF/OIF veterans. National cross-sectional mail survey. 1046 veterans responded to the survey. The sample for this study was 978 veterans who experienced combat. Regression-based path analyses were conducted. Family support and stress had direct associations with suicidal ideation. When PTSD and depression symptoms were examined as mediators of these associations, results revealed significant indirect paths through these symptoms. This study contributes to the literature on suicidal ideation risk factors among OEF/OIF veterans. Deployment family support and family stress are associated with suicidal ideation; however these associations occur primarily through mental health symptomatology, consistent with findings observed for other deployment factors. This research supports ongoing efforts to treat mental health symptomatology as a means of suicide prevention.

Suicidal behavior and assisted suicide in dementia.

Science.gov (United States)

Draper, Brian M

2015-10-01

Concerns about suicide risk in people with dementia have been increasing in recent years along with a discourse about rational suicide and assisted suicide. A systematic narrative literature review of suicidal behavior and assisted suicide in persons with dementia. Most studies that have examined the spectrum of suicidal ideation, attempted suicide and suicide in dementia have methodological limitations but the overall suicide risk does not appear to be increased. When suicidal behavior does occur, common themes include the presence of psychiatric comorbidity, mainly depression; occurrence early in the dementia course with preserved insight and capacity; and an increased risk in younger people. The emerging discourse on rational and assisted suicide has been spurred by early and pre-symptomatic diagnosis and poses a number of ethical challenges for clinicians including the role of proxy decision-makers. Although dementia might not confer a significant overall risk for suicidal behavior, clinicians still need to consider the potential for suicide in vulnerable individuals particularly early in the dementia course.

Dysregulation of RNA Mediated Gene Expression in Motor Neuron Diseases.

Science.gov (United States)

Gonçalves, Inês do Carmo G; Rehorst, Wiebke A; Kye, Min Jeong

2016-01-01

Recent findings indicate an important role for RNA-mediated gene expression in motor neuron diseases, including ALS (amyotrophic lateral sclerosis) and SMA (spinal muscular atrophy). ALS, also known as Lou Gehrig's disease, is an adult-onset progressive neurodegenerative disorder, whereby SMA or "children's Lou Gehrig's disease" is considered a pediatric neurodevelopmental disorder. Despite the difference in genetic causes, both ALS and SMA share common phenotypes; dysfunction/loss of motor neurons that eventually leads to muscle weakness and atrophy. With advanced techniques in molecular genetics and cell biology, current data suggest that these two distinct motor neuron diseases share more than phenotypes; ALS and SMA have similar cellular pathological mechanisms including mitochondrial dysfunction, oxidative stress and dysregulation in RNA-mediated gene expression. Here, we will discuss the current findings on these two diseases with specific focus on RNA-mediated gene regulation including miRNA expression, pre-mRNA processing and RNA binding proteins.

Suicide and Suicidal Thoughts

Science.gov (United States)

... the best way to identify risk. Murder and suicide In rare cases, people who are suicidal are ... access to a firearm Starting antidepressants and increased suicide risk Most antidepressants are generally safe, but the ...

The Arabidopsis mediator complex subunits MED16, MED14, and MED2 regulate mediator and RNA polymerase II recruitment to CBF-responsive cold-regulated genes.

Science.gov (United States)

Hemsley, Piers A; Hurst, Charlotte H; Kaliyadasa, Ewon; Lamb, Rebecca; Knight, Marc R; De Cothi, Elizabeth A; Steele, John F; Knight, Heather

2014-01-01

The Mediator16 (MED16; formerly termed SENSITIVE TO FREEZING6 [SFR6]) subunit of the plant Mediator transcriptional coactivator complex regulates cold-responsive gene expression in Arabidopsis thaliana, acting downstream of the C-repeat binding factor (CBF) transcription factors to recruit the core Mediator complex to cold-regulated genes. Here, we use loss-of-function mutants to show that RNA polymerase II recruitment to CBF-responsive cold-regulated genes requires MED16, MED2, and MED14 subunits. Transcription of genes known to be regulated via CBFs binding to the C-repeat motif/drought-responsive element promoter motif requires all three Mediator subunits, as does cold acclimation-induced freezing tolerance. In addition, these three subunits are required for low temperature-induced expression of some other, but not all, cold-responsive genes, including genes that are not known targets of CBFs. Genes inducible by darkness also required MED16 but required a different combination of Mediator subunits for their expression than the genes induced by cold. Together, our data illustrate that plants control transcription of specific genes through the action of subsets of Mediator subunits; the specific combination defined by the nature of the stimulus but also by the identity of the gene induced.

Association between a genetic variant in the serotonin transporter gene (SLC6A4) and suicidal behavior in patients with schizophrenia

DEFF Research Database (Denmark)

Lindholm Carlstrom, Eva; Saetre, Peter; Rosengren, Anders

2012-01-01

ABSTRACT: BACKGROUND: The serotonin (5-hydroxytryptamin; 5-HT) system has a central role in the circuitry of cognition and emotions. Multiple lines of evidence suggest that genetic variation in the serotonin transporter gene (SLC6A4; 5-HTT) is associated with schizophrenia and suicidal behavior. ...

Association of Cumulative Childhood Adversity and Adolescent Violent Offending With Suicide in Early Adulthood.

Science.gov (United States)

Björkenstam, Emma; Hjern, Anders; Björkenstam, Charlotte; Kosidou, Kyriaki

2018-02-01

Childhood adversity (CA) is associated with an increased risk of suicide in young adulthood that might be explained by maladaptive trajectories during adolescence. Although adolescent violent offending is linked with suicide, little is known about its role in the association between CA and suicide. To examine whether adolescent violent offending mediates the association between CA and suicide in early adulthood. This population-based, longitudinal cohort study with a follow-up time spanning 5 to 9 years included 476 103 individuals born in Sweden between 1984 and 1988. The study population was prospectively followed up from 20 years of age until December 31, 2013, with respect to suicide. Data analysis was performed from January 1, 1984, to December 31, 2013. Register-based CAs included parental death, parental substance abuse and psychiatric disorder, parental criminal offending, parental separation, public assistance recipiency, child welfare intervention, and residential instability. Adolescent violent offending was defined as being convicted of a violent crime between the ages of 15 and 19 years. Estimates of risk of suicide after 20 years of age (from 2004 if born in 1984 and from 2008 if born in 1988) until the end of 2013 were calculated as incidence rate ratios (IRRs) with 95% CIs using Poisson regression analysis. Adjustments were made for demographics and psychiatric disorder. In addition, binary mediation analysis with logistic regression was used. A total of 476 103 individuals (231 699 [48.7%] female) were included in the study. Those with a conviction for violent offending had been exposed to all CAs to a greater extent than those with no violent offending. Cumulative CA was associated with risk of suicide in nonconvicted (adjusted IRR, 2.4; 95% CI, 1.5-3.9) and convicted youths, who had a higher risk of suicide (adjusted IRR, 8.5; 95% CI, 4.6-15.7). Adolescent violent offending partly mediated the association between CA and suicide. Individuals

Imaging gene expression in gene therapy

Energy Technology Data Exchange (ETDEWEB)

Wiebe, Leonard I. [Alberta Univ., Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research

1997-12-31

Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on `suicide gene therapy` of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k{sup +}) has been use for `suicide` in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k{sup +} gene expression where the H S V-1 t k{sup +} gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([{sup 18} F]F H P G; [{sup 18} F]-A C V), and pyrimidine- ([{sup 123}/{sup 131} I]I V R F U; [{sup 124}/{sup 131I}]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [{sup 123}/{sup 131I}]I V R F U imaging with the H S V-1 t k{sup +} reporter gene will be presented

Adolescent Suicide and Suicidal Behavior

Science.gov (United States)

Bridge, Jeffrey A.; Goldstein, Tina R.; Brent, David A.

2006-01-01

This review examines the descriptive epidemiology, and risk and protective factors for youth suicide and suicidal behavior. A model of youth suicidal behavior is articulated, whereby suicidal behavior ensues as a result of an interaction of socio-cultural, developmental, psychiatric, psychological, and family-environmental factors. On the basis of…

The Role of Cytokines in the Pathophysiology of Suicidal Behavior

Science.gov (United States)

Ganança, Licínia; Oquendo, Maria A.; Tyrka, Audrey R.; Cisneros-Trujillo, Sebastian; Mann, J. John; Sublette, M. Elizabeth

2016-01-01

Objective Immune dysregulation has been implicated in depression and other psychiatric disorders. What is less clear is how immune dysregulation can affect risk of suicidal behavior. We reviewed the scientific literature concerning cytokines related to suicidal ideation, suicidal behavior and suicide, and surveyed clinical and neurobiological factors associated with cytokine levels that may modulate effects of inflammation on suicide risk. Methods We searched PubMed, Embase, Scopus and PsycINFO for relevant studies published from 1980 through February, 2015. Papers were included if they were written in English and focused on cytokine measurements in patients with suicidal behaviors. Results The literature search yielded 22 studies concerning cytokines and suicidal ideation, suicide attempts or suicide completion. The most consistent finding was elevated interleukin (IL)-6, found in 8 out of 14 studies, in CSF, blood, and postmortem brain. In one study, IL-6 in CSF was also found to be higher in violent than nonviolent attempters and to correlate with future suicide completion. Low plasma IL-2 was observed in 2 studies of suicide attempters, while divergent results were seen for tumor necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, IL-4, and soluble Il-2 receptors. Conclusions Given the complexity suggested by the heterogenous cytokine findings, putative mediators and moderators of inflammation on suicidal behavior merit further study. Elevated IL-6 was the most robust cytokine finding, associated with suicidal ideation and both nonfatal suicide attempts and suicides. Future studies should evaluate the predictive value of high IL-6, consider how this may alter brain function to impact suicidal behavior, and explore the potential beneficial effects of reducing IL-6 on suicide risk. PMID:26546783

A genome-wide association study of attempted suicide

Science.gov (United States)

Willour, Virginia L.; Seifuddin, Fayaz; Mahon, Pamela B.; Jancic, Dubravka; Pirooznia, Mehdi; Steele, Jo; Schweizer, Barbara; Goes, Fernando S.; Mondimore, Francis M.; MacKinnon, Dean F.; Perlis, Roy H.; Lee, Phil Hyoun; Huang, Jie; Kelsoe, John R.; Shilling, Paul D.; Rietschel, Marcella; Nöthen, Markus; Cichon, Sven; Gurling, Hugh; Purcell, Shaun; Smoller, Jordan W.; Craddock, Nicholas; DePaulo, J. Raymond; Schulze, Thomas G.; McMahon, Francis J.; Zandi, Peter P.; Potash, James B.

2011-01-01

The heritable component to attempted and completed suicide is partly related to psychiatric disorders and also partly independent of them. While attempted suicide linkage regions have been identified on 2p11–12 and 6q25–26, there are likely many more such loci, the discovery of which will require a much higher resolution approach, such as the genome-wide association study (GWAS). With this in mind, we conducted an attempted suicide GWAS that compared the single nucleotide polymorphism (SNP) genotypes of 1,201 bipolar (BP) subjects with a history of suicide attempts to the genotypes of 1,497 BP subjects without a history of suicide attempts. 2,507 SNPs with evidence for association at p<0.001 were identified. These associated SNPs were subsequently tested for association in a large and independent BP sample set. None of these SNPs were significantly associated in the replication sample after correcting for multiple testing, but the combined analysis of the two sample sets produced an association signal on 2p25 (rs300774) at the threshold of genome-wide significance (p= 5.07 × 10−8). The associated SNPs on 2p25 fall in a large linkage disequilibrium block containing the ACP1 gene, a gene whose expression is significantly elevated in BP subjects who have completed suicide. Furthermore, the ACP1 protein is a tyrosine phosphatase that influences Wnt signaling, a pathway regulated by lithium, making ACP1 a functional candidate for involvement in the phenotype. Larger GWAS sample sets will be required to confirm the signal on 2p25 and to identify additional genetic risk factors increasing susceptibility for attempted suicide. PMID:21423239

Mediator Recruitment to Heat Shock Genes Requires Dual Hsf1 Activation Domains and Mediator Tail Subunits Med15 and Med16*

Science.gov (United States)

Kim, Sunyoung; Gross, David S.

2013-01-01

The evolutionarily conserved Mediator complex is central to the regulation of gene transcription in eukaryotes because it serves as a physical and functional interface between upstream regulators and the Pol II transcriptional machinery. Nonetheless, its role appears to be context-dependent, and the detailed mechanism by which it governs the expression of most genes remains unknown. Here we investigate Mediator involvement in HSP (heat shock protein) gene regulation in the yeast Saccharomyces cerevisiae. We find that in response to thermal upshift, subunits representative of each of the four Mediator modules (Head, Middle, Tail, and Kinase) are rapidly, robustly, and selectively recruited to the promoter regions of HSP genes. Their residence is transient, returning to near-background levels within 90 min. Hsf1 (heat shock factor 1) plays a central role in recruiting Mediator, as indicated by the fact that truncation of either its N- or C-terminal activation domain significantly reduces Mediator occupancy, whereas removal of both activation domains abolishes it. Likewise, ablation of either of two Mediator Tail subunits, Med15 or Med16, reduces Mediator recruitment to HSP promoters, whereas deletion of both abolishes it. Accompanying the loss of Mediator, recruitment of RNA polymerase II is substantially diminished. Interestingly, Mediator antagonizes Hsf1 occupancy of non-induced promoters yet facilitates enhanced Hsf1 association with activated ones. Collectively, our observations indicate that Hsf1, via its dual activation domains, recruits holo-Mediator to HSP promoters in response to acute heat stress through cooperative physical and/or functional interactions with the Tail module. PMID:23447536

Globalisation and suicide: an empirical investigation in 35 countries over the period 1980-2006.

Science.gov (United States)

Milner, Allison; McClure, Rod; Sun, Jing; De Leo, Diego

2011-07-01

Globalisation is mediated through a variety of flows including persons, information and ideas, capital, and goods. The process is increasingly recognised as a potential mediator of changes in attitudes and habits around the globe. This research investigated the relationship between globalisation and suicide rates in 35 countries over the period 1980-2006. The association between a globalisation "index" and suicide rates was tested using a fixed-effects regression model. The model also tested the influence of eleven other socio-economic variables on male and female suicide rates. Overall, high levels of the globalisation index were associated with higher male and female suicide rates; however, the significance of this association dropped when assessed alongside other social and economic variables. While the nature of these findings should be regarded as exploratory, this paper highlights the need for researchers to consider the influence of world-changing phenomena like globalisation on suicide, which might deeply upset the traditional structure of societies with mixed types of impact. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Personality traits as an endophenotype in genetic studies on suicidality in bipolar disorder.

Science.gov (United States)

Pawlak, J; Dmitrzak-Węglarz, M; Maciukiewicz, M; Kapelski, P; Czerski, P; Leszczyńska-Rodziewicz, A; Zaremba, D; Hauser, J

2017-04-01

Introduction The influence of personality traits on suicidal behaviour risk has been well documented. Personality traits and suicidal behaviour are partially genetically determined and personality has been described as an endophenotype of suicidal behaviour. The aim of this study was to investigate a possible association between personality traits with suicidal behaviour and selected serotonergic gene polymorphisms. In the study we included 156 patients meeting DSM-IV criteria for bipolar disorder (BP) and 93 healthy controls. The personality dimensions were assessed using the Temperament and Character Inventory (TCI). We genotyped two selected polymorphisms of the tryptophan hydroxylase 1 (TPH1) gene (rs1800532 218A>C and rs1799913 779A>C) and polymorphism in the promoter region of serotonin transporter gene (5-HTTLPR, rs25531) related to serotoninergic neurotransmission. Multiple poisson regression, logistic regression and Kruskal-Wallis tests were applied. We found numerous differences between the BP patients and the control group in terms of their TCI dimensions/subdimensions. Significant differences were found between patients with, and without, suicidal attempts in fatigability and asthenia (Ha4), as well as in harm avoidance (Ha). We also found that the interactions between TCI subdimensions (the interaction of disordiness (Ns4) and spiritual acceptance (St3), disordiness (Ns4) and integrated conscience (C5), extravagance (Ns3) and resourcefulness (Sd3)) were significantly contributing for suicidal behaviour risk. We found association between all studied genetic polymorphisms and several TCI dimensions and subdimensions. Our results confirm that personality traits are partially determined by genes. Both personality traits and the interactions between temperament and character traits, may be helpful in predicting suicidal behaviour.

Efficient Oligo nucleotide mediated CRISPR-Cas9 Gene Editing in Aspergilli

DEFF Research Database (Denmark)

Nødvig, Christina Spuur; Hoof, Jakob Blæsbjerg; Kogle, Martin Engelhard

2018-01-01

CRISPR-Cas9 technologies are revolutionizing fungal gene editing. Here we show that survival of specific Cas9/sgRNA mediated DNA double strand breaks (DSBs) depends on the non-homologous end-joining, NHEJ, DNA repair pathway and we use this observation to develop a tool to assess protospacer....... niger, and in A. oryzae indicating that this type of repair may be wide spread in filamentous fungi. Importantly, we demonstrate that by using single-stranded oligo nucleotides for CRISPR-Cas9 mediated gene editing it is possible to introduce specific point mutations as well gene deletions...

Minority stress and mechanisms of risk for depression and suicidal ideation among lesbian, gay, and bisexual youth.

Science.gov (United States)

Baams, Laura; Grossman, Arnold H; Russell, Stephen T

2015-05-01

The experience of minority stress is often named as a cause for mental health disparities among lesbian, gay, and bisexual (LGB) youth, including higher levels of depression and suicidal ideation. The processes or mechanisms through which these disparities occur are understudied. The interpersonal-psychological theory of suicide posits 2 key mechanisms for suicidal ideation: perceived burdensomeness and thwarted belongingness (Joiner et al., 2009). The aim of the current study is to assess the mental health and adjustment among LGB youth emphasizing the minority stress model (Meyer, 2003) and the interpersonal-psychological theory of suicide (Joiner et al., 2009). With a survey of 876 LGB self-identified youth, levels of coming-out stress, sexual orientation victimization, perceived burdensomeness, thwarted belongingness, depression, and suicidal ideation were examined. The results of a multigroup mediation model show that for all gender and sexual identity groups, the association of sexual orientation victimization with depression and suicidal ideation was mediated by perceived burdensomeness. For gay, lesbian, and bisexual girls coming-out stress was also found to be related to depression and suicidal ideation, mediated by perceived burdensomeness. The results suggest that feeling like a burden to "people in their lives" is a critical mechanism in explaining higher levels of depression and suicidal ideation among LGB youth. These results have implications for community and social support groups, many of which base their interventions on decreasing social isolation rather than addressing youths' beliefs of burdensomeness. Implications for future research, clinical and community settings are discussed. (c) 2015 APA, all rights reserved).

TPH2 -703G/T SNP may have important effect on susceptibility to suicidal behavior in major depression.

Science.gov (United States)

Yoon, Ho-Kyoung; Kim, Yong-Ku

2009-04-30

Serotonergic system-related genes can be good candidate genes for both major depressive disorder (MDD) and suicidal behavior. In this study, we aimed to investigate the association of serotonin 2A receptor gene -1438A/G SNP (HTR2A -1438A/G), tryptophan hydroxylase 2 gene -703G/T SNP (TPH2 -703G/T) and serotonin 1A receptor C-1019G (HTR1A C-1019G) with suicidal behavior. One hundred and eighty one suicidal depressed patients and 143 non-suicidal depressed patients who met DSM-IV criteria for major depressive disorder were recruited from patients who were admitted to Korea University Ansan Hospital. One hundred seventy six normal controls were healthy volunteers who were recruited by local advertisement. Patients and normal controls were genotyped for HTR2A -1438A/G, TPH2 -703G/T and 5-HT1A C-1019G. The suicidal depressed patients were evaluated by the lethality of individual suicide attempts using Weisman and Worden's risk-rescue rating (RRR) and the Lethality Suicide Attempt Rating Scale-updated (LSARS-II). In order to assess the severity of depressive symptoms of patients, Hamilton's Depression Rating Scale (HDRS) was administered. Genotype and allele frequencies were compared between groups by chi(2) statistics. Association of genotype of the candidate genes with the lethality of suicidal behavior was examined with ANOVA by comparing the mean scores of LSARS and RRR according to the genotype. There were statistically significant differences in the genotype distributions and allele frequencies of TPH2 -703G/T between the suicidal depressive group and the normal control group. The homozygous allele G (G/G genotype) frequency was significantly higher in suicidal depressed patients than in controls. However, no differences in either genotype distribution or in allele frequencies of HTR2A -1438A/G and HTR1A C-1019G were observed between the suicidal depressed patients, the non-suicidal depressed patients, and the normal controls. There were no differences in the

Agrobacterium-mediated gene transfer in plants and biosafety considerations.

Science.gov (United States)

Mehrotra, Shweta; Goyal, Vinod

2012-12-01

Agrobacterium, the natures' genetic engineer, has been used as a vector to create transgenic plants. Agrobacterium-mediated gene transfer in plants is a highly efficient transformation process which is governed by various factors including genotype of the host plant, explant, vector, plasmid, bacterial strain, composition of culture medium, tissue damage, and temperature of co-cultivation. Agrobacterium has been successfully used to transform various economically and horticulturally important monocot and dicot species by standard tissue culture and in planta transformation techniques like floral or seedling infilteration, apical meristem transformation, and the pistil drip methods. Monocots have been comparatively difficult to transform by Agrobacterium. However, successful transformations have been reported in the last few years based on the adjustment of the parameters that govern the responses of monocots to Agrobacterium. A novel Agrobacterium transferred DNA-derived nanocomplex method has been developed which will be highly valuable for plant biology and biotechnology. Agrobacterium-mediated genetic transformation is known to be the preferred method of creating transgenic plants from a commercial and biosafety perspective. Agrobacterium-mediated gene transfer predominantly results in the integration of foreign genes at a single locus in the host plant, without associated vector backbone and is also known to produce marker free plants, which are the prerequisites for commercialization of transgenic crops. Research in Agrobacterium-mediated transformation can provide new and novel insights into the understanding of the regulatory process controlling molecular, cellular, biochemical, physiological, and developmental processes occurring during Agrobacterium-mediated transformation and also into a wide range of aspects on biological safety of transgenic crops to improve crop production to meet the demands of ever-growing world's population.

DNA-mediated gene transfer into ataxia-telangiectasia cells

International Nuclear Information System (INIS)

Crescenzi, M.; Pulciani, S.; Carbonari, M.; Tedesco, L.; Russo, G.; Gaetano, C.; Fiorilli, M.

1986-01-01

The complete description of the genetic lesion(s) underlying the AT mutation might, therefore, highlight not only a DNA-repair pathwa, but also an important aspect of the physiology of lymphocytes. DNA-mediated gene transfer into eukaryotic cells has proved a powerful tool for the molecular cloning of certain mammalian genes. The possibility to clone a given gene using this technology depends, basically, on the availability of a selectable marker associated with the expression of the transfected gene in the recipient cell. Recently, a human DNA repair gene has been cloned in CHO mutant cells by taking advantage of the increased resistance to ultraviolet radiation of the transformants. As a preliminary step toward the molecular cloning of the AT gene(s), the authors have attempted to confer radioresistance to AT cells by transfection with normal human DNA

Host-Induced Gene Silencing of Rice Blast Fungus Magnaporthe oryzae Pathogenicity Genes Mediated by the Brome Mosaic Virus.

Science.gov (United States)

Zhu, Lin; Zhu, Jian; Liu, Zhixue; Wang, Zhengyi; Zhou, Cheng; Wang, Hong

2017-09-26

Magnaporthe oryzae is a devastating plant pathogen, which has a detrimental impact on rice production worldwide. Despite its agronomical importance, some newly-emerging pathotypes often overcome race-specific disease resistance rapidly. It is thus desirable to develop a novel strategy for the long-lasting resistance of rice plants to ever-changing fungal pathogens. Brome mosaic virus (BMV)-induced RNA interference (RNAi) has emerged as a useful tool to study host-resistance genes for rice blast protection. Planta-generated silencing of targeted genes inside biotrophic pathogens can be achieved by expression of M. oryzae -derived gene fragments in the BMV-mediated gene silencing system, a technique termed host-induced gene silencing (HIGS). In this study, the effectiveness of BMV-mediated HIGS in M. oryzae was examined by targeting three predicted pathogenicity genes, MoABC1, MoMAC1 and MoPMK1 . Systemic generation of fungal gene-specific small interfering RNA (siRNA) molecules induced by inoculation of BMV viral vectors inhibited disease development and reduced the transcription of targeted fungal genes after subsequent M. oryzae inoculation. Combined introduction of fungal gene sequences in sense and antisense orientation mediated by the BMV silencing vectors significantly enhanced the efficiency of this host-generated trans-specific RNAi, implying that these fungal genes played crucial roles in pathogenicity. Collectively, our results indicated that BMV-HIGS system was a great strategy for protecting host plants against the invasion of pathogenic fungi.

Enhancement of plasmid-mediated stable gene expression by ...

African Journals Online (AJOL)

ARL

2012-06-12

Jun 12, 2012 ... production and faithful translation and processing of proteins (Baldi et al., ..... deeper understanding of the interaction of cellular factors and regulatory DNA .... mediated transgene expression in the rat brain. Gene Ther., 7: ...

Suicide note themes and suicide prevention.

Science.gov (United States)

Foster, Tom

2003-01-01

The aim was to determine if suicide note themes might inform suicide prevention strategies. The themes of 42 suicide notes from the Northern Ireland Suicide Study (major psychological autopsy study) were examined. The commonest themes were "apology/shame" (74%), "love for those left behind" (60%), "life too much to bear" (48%), "instructions regarding practical affairs post-mortem" (36%), "hopelessness/nothing to live for" (21%) and "advice for those left behind" (21%). Notes of suicides with major unipolar depression were more likely than notes of suicides without major unipolar depression to contain the themes "instructions regarding practical affairs post-mortem" (67% versus 19%, p = 0.005) and "hopelessness/nothing to live for" (40% versus 11%, p = 0.049). Notes of suicides with a previous history of deliberate self-harm were less likely than notes of suicides without a history of deliberate self-harm to contain the theme "apology/shame" (58% versus 87%, p = 0.04). Notes of elderly suicides were more likely than non-elderly notes to contain the theme "burden to others" (40% versus 3%, p = 0.03). The fact that three quarters of suicide notes contained the theme "apology/shame" suggests that the deceased may have welcomed alternative solutions for their predicaments. Scrutiny of suicide note themes in the light of previous research findings suggests that cognitive therapy techniques, especially problem solving, may have an important role to play in suicide prevention and that potential major unipolar depressive (possibly less impulsive) suicides, in particular, may provide fertile ground for therapeutic intervention (physical and psychological). Ideally all primary care doctors and mental health professionals working with (potentially) suicidal people should be familiar with basic cognitive therapy techniques, especially problem solving skills training.

An Integrated Model of Suicidal Ideation in Transcultural Populations of Chinese Adolescents.

Science.gov (United States)

Leung, Cyrus L K; Kwok, Sylvia Y C L; Ling, Chloe C Y

2016-07-01

This study tested the model of suicidal ideation, incorporating family and personal factors to predict suicidal ideation with hopelessness as a mediating factor in the Hong Kong sample, to a sample in Shanghai. Using MGSEM, the study aims to investigate the personal correlates and the family correlates of suicidal ideation in Hong Kong and Shanghai adolescents. We integrated the family ecological and diathesis-stress-hopelessness models of suicidal ideation in connecting the correlates. A cross-sectional design was used. The full model achieved metric invariance and partial path-loading invariance. Family functioning and social problem solving negatively predicted hopelessness or suicidal ideation in both the Hong Kong and Shanghai adolescents. The results supported an integrative approach in facilitating parent-adolescent communication and strengthening family functioning, and reducing the use of negative social problem-solving styles in adolescent suicide prevention.

Exploring lag and duration effect of sunshine in triggering suicide.

Science.gov (United States)

Papadopoulos, Fotios C; Frangakis, Constantine E; Skalkidou, Alkistis; Petridou, Eleni; Stevens, Richard G; Trichopoulos, Dimitrios

2005-11-01

Sunshine is considered to have a beneficial impact on mood. Interestingly, it has been consistently found that the incidence of suicide reaches a peak during early summer. In order to explore the pattern of sunshine and suicide risk in a time frame of up to nine days and investigate possible lag and duration parameters of sunshine in the triggering of suicide, Greek daily suicide and solar radiance data were analyzed for a 10-year period using logistic regression models. The solar radiance during the day before the suicide event was significantly associated with an increased suicide risk (OR=1.020 per MW/m2). The average solar radiance during the four previous days was also significantly associated with an increased suicide risk (OR=1.031 per MW/m2). Differences among genders include the longer sunshine exposure needed in males to trigger suicide, compared to females and a lag period of three to four days that was found to lapse in females till the suicide. The increase in suicide risk in June compared to December, attributable to the daily sunshine effect, varies from 52% to 88%, thus explaining the already known suicide monthly seasonality. No individual data on solar radiance exposure, mental disorders, alcohol consumption or suicide method were available. The effect of sunshine in the triggering of suicide may be mediated through a mechanism with a specific lag and duration effect, during the nine days preceding suicide. We hypothesize that sunshine acts as a natural antidepressant which first improves motivation, then only later improves mood, thereby creating a potential short-term increased risk of suicide initially upon its application.

Can sports events affect suicidal behavior? A review of the literature and implications for prevention.

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Andriessen, Karl; Krysinska, Karolina

2009-01-01

Engagement in sports and physical activity, either actively as an athlete or in a passive way as a spectator, impacts interpersonal behavior and physical and mental health. The study reviews literature on the relationship between sports spectatorship and suicidal behavior to ascertain whether sports spectatorship has an impact on suicidal behavior, either increasing the risk or being a protective factor. The literature was searched via PubMed/MEDLINE and PsycINFO. Nine studies published between 1986 and 2006 were identified. The reviewed studies focused on the impact of sports events on the societal level, and analyzed data regarding national or local suicide rates. Their results indicate that sports events can have an impact on suicide mortality and morbidity, but this relationship seems to be mediated by age, gender, marital status, and alcohol consumption, as well as the process and outcome of the game (e.g., victory vs. defeat of the favored team). There is some evidence that sports events can reduce the rates of suicide on the societal level; however, there is a lack of studies exploring how sports spectatorship might influence levels of suicide risk in individuals and how mediating variables might operate on the individual level.

Air pollution, aeroallergens and suicidality: a review of the effects of air pollution and aeroallergens on suicidal behavior and an exploration of possible mechanisms.

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Ragguett, Renee-Marie; Cha, Danielle S; Subramaniapillai, Mehala; Carmona, Nicole E; Lee, Yena; Yuan, Duanduan; Rong, Carola; McIntyre, Roger S

2017-12-20

Risk factors for suicide can be broadly categorized as sociodemographic, clinical and treatment. There is interest in environmental risk and protection factors for suicide. Emerging evidence suggests a link between environmental factors in the form of air pollution and aeroallergens in relation to suicidality. Herein, we conducted a systematic review of 15 articles which have met inclusion criteria on the aforementioned effects. The majority of the reviewed articles reported an increased suicide risk alongside increased air pollutants or aeroallergens (i.e. pollen) increase; however, not all environmental factors were explored equally. In specific, studies that were delimited to evaluating particulate matter (PM) reported a consistent association with suicidality. We also provide a brief description of putative mechanisms (e.g. inflammation and neurotransmitter dysregulation) that may mediate the association between air pollution, aeroallergens and suicidality. Available evidence suggests that exposure to harmful air quality may be associated with suicidality. There are significant public health implications which are amplified in regions and countries with greater levels of air pollution and aeroallergens. In addition, those with atopic sensitivity may represent a specific subgroup that is at risk.

Strategies used for genetically modifying bacterial genome: ite-directed mutagenesis, gene inactivation, and gene over-expression*

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Xu, Jian-zhong; Zhang, Wei-guo

2016-01-01

With the availability of the whole genome sequence of Escherichia coli or Corynebacterium glutamicum, strategies for directed DNA manipulation have developed rapidly. DNA manipulation plays an important role in understanding the function of genes and in constructing novel engineering bacteria according to requirement. DNA manipulation involves modifying the autologous genes and expressing the heterogenous genes. Two alternative approaches, using electroporation linear DNA or recombinant suicide plasmid, allow a wide variety of DNA manipulation. However, the over-expression of the desired gene is generally executed via plasmid-mediation. The current review summarizes the common strategies used for genetically modifying E. coli and C. glutamicum genomes, and discusses the technical problem of multi-layered DNA manipulation. Strategies for gene over-expression via integrating into genome are proposed. This review is intended to be an accessible introduction to DNA manipulation within the bacterial genome for novices and a source of the latest experimental information for experienced investigators. PMID:26834010

The chronic impact of work on suicides and under-utilization of psychiatric and psychosocial services.

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Law, Yik Wa; Yip, Paul S F; Zhang, Yi; Caine, Eric D

2014-10-01

Work-related stress appears to be a contributing factor in the lives of employed people who kill themselves, particularly during economic downturns. However, few studies have compared them with working community controls who may be experiencing similar strains, in order to explore the role of mental disorders in these deaths and the implication of such strains on their service use pattern. We hypothesized that both work stress and mental illness were associated with suicides, and that mental illness served as the mediator between work stress and suicide. Based on the Behavioral Model, we also assumed work stress associated with their use of services. A sample of 175 employed individuals (suicides=63; controls=112) drawn from a psychological autopsy (PA) dataset was examined based on demographics and socioeconomic factors, psychiatric diagnoses and use of services, psychosocial factors, and life events. A mediator analysis was conducted to examine the impact of work on suicides. Suicides generally had depression and anxiety, debts, higher impulsivity and poorer social support in comparison to controls. Chronic impact from work, which was fully mediated by psychiatric illness, was found higher among those suicides that did not seek contact with clinical service providers. PA is a post-hoc cross-sectional comparison method which does not allow causal analyses. It is important to develop new approaches for engaging vulnerable individuals in the workplace before they become suicidal, as their depression and social isolation can serve to cut them off from help when they are most in need. Occupational mental health programs should be made available for employees and their families. Copyright © 2014 Elsevier B.V. All rights reserved.

Pain and suicidality: Insights from reward and addiction neuroscience

OpenAIRE

Elman, Igor; Borsook, David; Volkow, Nora D.

2013-01-01

Suicidality is exceedingly prevalent in pain patients. Although the pathophysiology of this link remains unclear, it may be potentially related to the partial congruence of physical and emotional pain systems. The latter system’s role in suicide is also conspicuous during setbacks and losses sustained in the context of social attachments. Here we propose a model based on the neural pathways mediating reward and anti-reward (i.e., allostatic adjustment to recurrent activation of the reward cir...

Suicide Methods in Asia: Implications in Suicide Prevention

Directory of Open Access Journals (Sweden)

Paul S. F. Yip

2012-03-01

Full Text Available As the largest continent in the World, Asia accounts for about 60% of World suicides. Preventing suicide by restricting access to suicide methods is one of the few evidence-based suicide prevention strategies. However, there has been a lack of systematic exploration of suicide methods in Asian countries. To amend this shortage, the current review examines the leading suicide methods in different Asian countries, their trend, their age- and sex- specific characteristics, and their implications for suicide prevention. In total, 42 articles with leading suicide methods data in 17 Asian countries/regions were retrieved. The epidemiologic characteristics and recent trends of common suicide methods reflect specific socio-cultural, economic, and religious situations in the region. Common suicide methods shift with the introduction of technologies and constructions, and have specific age- or sex-characteristics that may render the restriction of suicide methods not equally effective for all sex and age sub-groups. Charcoal burning, pesticide poisoning, native plant poisoning, self-immolation, and jumping are all prominent examples. In the information society, suicide prevention that focuses on suicide methods must monitor and control the innovation and spread of knowledge and practices of suicide “technologies”. It may be more cost-effective to design safety into technologies as a way of suicide prevention while there is no rash of suicides yet by the new technologies. Further research on suicide methods is important for public health approaches to suicide prevention with sensitivity to socio-cultural, economic, and religious factors in different countries.

Suicide Methods in Asia: Implications in Suicide Prevention

Science.gov (United States)

Wu, Kevin Chien-Chang; Chen, Ying-Yeh; Yip, Paul S. F.

2012-01-01

As the largest continent in the World, Asia accounts for about 60% of World suicides. Preventing suicide by restricting access to suicide methods is one of the few evidence-based suicide prevention strategies. However, there has been a lack of systematic exploration of suicide methods in Asian countries. To amend this shortage, the current review examines the leading suicide methods in different Asian countries, their trend, their age- and sex- specific characteristics, and their implications for suicide prevention. In total, 42 articles with leading suicide methods data in 17 Asian countries/regions were retrieved. The epidemiologic characteristics and recent trends of common suicide methods reflect specific socio-cultural, economic, and religious situations in the region. Common suicide methods shift with the introduction of technologies and constructions, and have specific age- or sex-characteristics that may render the restriction of suicide methods not equally effective for all sex and age sub-groups. Charcoal burning, pesticide poisoning, native plant poisoning, self-immolation, and jumping are all prominent examples. In the information society, suicide prevention that focuses on suicide methods must monitor and control the innovation and spread of knowledge and practices of suicide “technologies”. It may be more cost-effective to design safety into technologies as a way of suicide prevention while there is no rash of suicides yet by the new technologies. Further research on suicide methods is important for public health approaches to suicide prevention with sensitivity to socio-cultural, economic, and religious factors in different countries. PMID:22690187

Are autistic traits associated with suicidality? A test of the interpersonal‐psychological theory of suicide in a non‐clinical young adult sample

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Pelton, M. K.

2017-01-01

Autism spectrum conditions (ASC) has recently been associated with increased risk of suicidality. However, no studies have explored how autistic traits may interact with current models of suicidal behavior in a non‐clinical population. The current study therefore explored how self‐reported autistic traits interact with perceived burdensomeness and thwarted belongingness in predicting suicidal behavior, in the context of the Interpersonal‐Psychological Theory of Suicide (IPTS). 163 young adults (aged 18–30 years) completed an online survey including measures of thwarted belonging and perceived burdensomeness (Interpersonal Needs Questionnaire), self‐reported autistic traits (Autism Spectrum Quotient), current depression (Centre for Epidemiological Studies Depression Scale), and lifetime suicidality (Suicide Behavior Questionnaire‐Revised). Results showed that burdensomeness and thwarted belonging significantly mediated the relationship between autistic traits and suicidal behavior. Both depression and autistic traits significantly predicted thwarted belonging and perceived burdensomeness. Autistic traits did not significantly moderate the relationship between suicidal behavior and thwarted belonging or perceived burdensomeness. Results suggest that the IPTS provides a useful framework for understanding the influence of autistic traits on suicidal behavior. However, the psychometric properties of these measures need be explored in those with clinically confirmed diagnosis of ASC. Autism Res 2017, 10: 1891–1904. © 2017 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. Lay Summary Recent research has shown that people with high autistic traits are more likely to attempt suicide. However, no studies have explored why. We found that people with high autistic traits were more likely to experience feelings that they do not belong in the world, are a burden on others, and depression, which may

A Content Analysis of Online Suicide Notes: Attempted Suicide Versus Attempt Resulting in Suicide.

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Synnott, John; Ioannou, Maria; Coyne, Angela; Hemingway, Siobhan

2017-09-28

Fifty suicide notes of those who died by suicide and 50 suicide notes of those who survived their suicide attempt were analyzed using Smallest Space Analysis. The core of all suicide notes was discovered to be constructed with the use of four variables: saying goodbye to their audience, feelings of loneliness, method used to attempt suicide, and negative self-image. Furthermore, three different suicide note themes of those who died and three suicide note themes from those who survived were also identified. The analysis revealed that suicide note writers who died by their attempt were more likely to combine a dislike of themselves and a concern for loved ones. The implications of the work in terms of suicide prevention are discussed. © 2017 The American Association of Suicidology.

Identification of certain cancer-mediating genes using Gaussian ...

Indian Academy of Sciences (India)

2015-09-29

Sep 29, 2015 ... mance of GFI is compared with 19 exiting cluster validity indices. The results .... Using k-means algorithm on human lung expression data, we have found ... of possible genes that mediate the development of a cancer. In other ...

Perceived Problem-Solving Deficits and Suicidal Ideation: Evidence for the Explanatory Roles of Thwarted Belongingness and Perceived Burdensomeness in Five Samples.

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Chu, Carol; Walker, Kristin L; Stanley, Ian H; Hirsch, Jameson K; Greenberg, Jeffrey H; Rudd, M David; Joiner, Thomas E

2017-06-26

Perceived social problem-solving deficits are associated with suicide risk; however, little research has examined the mechanisms underlying this relationship. The interpersonal theory of suicide proposes 2 mechanisms in the pathogenesis of suicidal desire: intractable feelings of thwarted belongingness (TB) and perceived burdensomeness (PB). This study tested whether TB and PB serve as explanatory links in the relationship between perceived social problem-solving (SPS) deficits and suicidal thoughts and behaviors cross-sectionally and longitudinally. The specificity of TB and PB was evaluated by testing depression as a rival mediator. Self-report measures of perceived SPS deficits, TB, PB, suicidal ideation, and depression were administered in 5 adult samples: 336 and 105 undergraduates from 2 universities, 53 homeless individuals, 222 primary care patients, and 329 military members. Bias-corrected bootstrap mediation and meta-analyses were conducted to examine the magnitude of the direct and indirect effects, and the proposed mediation paths were tested using zero-inflated negative binomial regressions. Cross-sectionally, TB and PB were significant parallel mediators of the relationship between perceived SPS deficits and ideation, beyond depression. Longitudinally and beyond depression, in 1 study, both TB and PB emerged as significant explanatory factors, and in the other, only PB was a significant mediator. Findings supported the specificity of TB and PB: Depression and SPS deficits were not significant mediators. The relationship between perceived SPS deficits and ideation was explained by interpersonal theory variables, particularly PB. Findings support a novel application of the interpersonal theory, and bolster a growing compendium of literature implicating perceived SPS deficits in suicide risk. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Biological basis of suicide and suicidal behavior

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Pandey, Ghanshyam N

2013-01-01

Objective Suicide is a major public health concern as each year 30,000 people die by suicide in the US alone. In the teenage population, it is the second leading cause of death. There have been extensive studies of psychosocial factors associated with suicide and suicidal behavior. However, very little is known about the neurobiology of suicide. Recent research has provided some understanding of the neurobiology of suicide, which is the topic of this review. Methods Neurobiology of suicide has been studied using peripheral tissues, such as platelets, lymphocytes, and cerebral spinal fluid obtained from suicidal patients or from the postmortem brains of suicide victims. Results These studies have provided encouraging information with regard to the neurobiology of suicide. They show an abnormality of serotonergic mechanism, such as increased serotonin receptor subtypes and decreased serotonin metabolites, such as 5-hydroxyindoleacetic acid. These studies also suggest abnormalities of receptor-linked signaling mechanisms, such as phosphoinositide and adenylyl cyclase signaling mechanisms. Other biological systems that appear to be dysregulated in suicide are the hypothalamic-pituitary-adrenal (HPA) axis, and abnormalities of neurotrophins and neurotrophin receptors. More recently, several studies also indicate abnormalities of neuroimmune functions in suicide. Conclusions These studies have been discussed in detail in the following review. Some encouraging information has emerged, primarily related to some of these neurobiological mechanisms. It is hoped that neurobiological studies may eventually result in identifying appropriate biomarkers for suicidal behavior as well as appropriate therapeutic targets for its treatment. PMID:23773657

Mesenchymal stromal cells retrovirally transduced with prodrug-converting genes are suitable vehicles for cancer gene therapy.

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Ďuriniková, E; Kučerová, L; Matúšková, M

2014-01-01

Mesenchymal stem/stromal cells (MSC) possess a set of several fairly unique properties which make them ideally suitable both for cellular therapies and regenerative medicine. These include: relative ease of isolation, the ability to differentiate along mesenchymal and non-mesenchymal lineages in vitro and the ability to be extensively expanded in culture without a loss of differentiative capacity. MSC are not only hypoimmunogenic, but they mediate immunosuppression upon transplantation, and possess pronounced anti-inflammatory properties. They are able to home to damaged tissues, tumors, and metastases following systemic administration. The ability of homing holds big promise for tumor-targeted delivery of therapeutic agents. Viruses are naturally evolved vehicles efficiently transferring their genes into host cells. This ability made them suitable for engineering vector systems for the delivery of genes of interest. MSC can be retrovirally transduced with genes encoding prodrug-converting genes (suicide genes), which are not toxic per se, but catalyze the formation of highly toxic metabolites following the application of a nontoxic prodrug. The homing ability of MSC holds advantages compared to virus vehicles which display many shortcomings in effective delivery of the therapeutic agents. Gene therapies mediated by viruses are limited by their restricted ability to track cancer cells infiltrating into the surrounding tissue, and by their low migratory capacity towards tumor. Thus combination of cellular therapy and gene delivery is an attractive option - it protects the vector from immune surveillance, and supports targeted delivery of a therapeutic gene/protein to the tumor site.

Environmental factors influencing gene transfer agent (GTA mediated transduction in the subtropical ocean.

Directory of Open Access Journals (Sweden)

Lauren D McDaniel

Full Text Available Microbial genomic sequence analyses have indicated widespread horizontal gene transfer (HGT. However, an adequate mechanism accounting for the ubiquity of HGT has been lacking. Recently, high frequencies of interspecific gene transfer have been documented, catalyzed by Gene Transfer Agents (GTAs of marine α-Proteobacteria. It has been proposed that the presence of bacterial genes in highly purified viral metagenomes may be due to GTAs. However, factors influencing GTA-mediated gene transfer in the environment have not yet been determined. Several genomically sequenced strains containing complete GTA sequences similar to Rhodobacter capsulatus (RcGTA, type strain were screened to ascertain if they produced putative GTAs, and at what abundance. Five of nine marine strains screened to date spontaneously produced virus-like particles (VLP's in stationary phase. Three of these strains have demonstrated gene transfer activity, two of which were documented by this lab. These two strains Roseovarius nubinhibens ISM and Nitratireductor 44B9s, were utilized to produce GTAs designated RnGTA and NrGTA and gene transfer activity was verified in culture. Cell-free preparations of purified RnGTA and NrGTA particles from marked donor strains were incubated with natural microbial assemblages to determine the level of GTA-mediated gene transfer. In conjunction, several ambient environmental parameters were measured including lysogeny indicated by prophage induction. GTA production in culture systems indicated that approximately half of the strains produced GTA-like particles and maximal GTA counts ranged from 10-30% of host abundance. Modeling of GTA-mediated gene transfer frequencies in natural samples, along with other measured environmental variables, indicated a strong relationship between GTA mediated gene transfer and the combined factors of salinity, multiplicity of infection (MOI and ambient bacterial abundance. These results indicate that GTA-mediated

Factors accounting for youth suicide attempt in Hong Kong: a model building.

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Wan, Gloria W Y; Leung, Patrick W L

2010-10-01

This study aimed at proposing and testing a conceptual model of youth suicide attempt. We proposed a model that began with family factors such as a history of physical abuse and parental divorce/separation. Family relationship, presence of psychopathology, life stressors, and suicide ideation were postulated as mediators, leading to youth suicide attempt. The stepwise entry of the risk factors to a logistic regression model defined their proximity as related to suicide attempt. Path analysis further refined our proposed model of youth suicide attempt. Our originally proposed model was largely confirmed. The main revision was dropping parental divorce/separation as a risk factor in the model due to lack of significant contribution when examined alongside with other risk factors. This model was cross-validated by gender. This study moved research on youth suicide from identification of individual risk factors to model building, integrating separate findings of the past studies.

The Mediator subunit SFR6/MED16 controls defence gene expression mediated by salicylic acid and jasmonate responsive pathways.

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Wathugala, Deepthi L; Hemsley, Piers A; Moffat, Caroline S; Cremelie, Pieter; Knight, Marc R; Knight, Heather

2012-07-01

• Arabidopsis SENSITIVE TO FREEZING6 (SFR6) controls cold- and drought-inducible gene expression and freezing- and osmotic-stress tolerance. Its identification as a component of the MEDIATOR transcriptional co-activator complex led us to address its involvement in other transcriptional responses. • Gene expression responses to Pseudomonas syringae, ultraviolet-C (UV-C) irradiation, salicylic acid (SA) and jasmonic acid (JA) were investigated in three sfr6 mutant alleles by quantitative real-time PCR and susceptibility to UV-C irradiation and Pseudomonas infection were assessed. • sfr6 mutants were more susceptible to both Pseudomonas syringae infection and UV-C irradiation. They exhibited correspondingly weaker PR (pathogenesis-related) gene expression than wild-type Arabidopsis following these treatments or after direct application of SA, involved in response to both UV-C and Pseudomonas infection. Other genes, however, were induced normally in the mutants by these treatments. sfr6 mutants were severely defective in expression of plant defensin genes in response to JA; ectopic expression of defensin genes was provoked in wild-type but not sfr6 by overexpression of ERF5. • SFR6/MED16 controls both SA- and JA-mediated defence gene expression and is necessary for tolerance of Pseudomonas syringae infection and UV-C irradiation. It is not, however, a universal regulator of stress gene transcription and is likely to mediate transcriptional activation of specific regulons only. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

Field distribution and DNA transport in solid tumors during electric field-mediated gene delivery.

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Henshaw, Joshua W; Yuan, Fan

2008-02-01

Gene therapy has a great potential in cancer treatment. However, the efficacy of cancer gene therapy is currently limited by the lack of a safe and efficient means to deliver therapeutic genes into the nucleus of tumor cells. One method under investigation for improving local gene delivery is based on the use of pulsed electric field. Despite repeated demonstration of its effectiveness in vivo, the underlying mechanisms behind electric field-mediated gene delivery remain largely unknown. Without a thorough understanding of these mechanisms, it will be difficult to further advance the gene delivery. In this review, the electric field-mediated gene delivery in solid tumors will be examined by following individual transport processes that must occur in vivo for a successful gene transfer. The topics of examination include: (i) major barriers for gene delivery in the body, (ii) distribution of electric fields at both cell and tissue levels during the application of external fields, and (iii) electric field-induced transport of genes across each of the barriers. Through this approach, the review summarizes what is known about the mechanisms behind electric field-mediated gene delivery and what require further investigations in future studies.

C/EBPβ Mediates Growth Hormone-Regulated Expression of Multiple Target Genes

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Cui, Tracy X.; Lin, Grace; LaPensee, Christopher R.; Calinescu, Anda-Alexandra; Rathore, Maanjot; Streeter, Cale; Piwien-Pilipuk, Graciela; Lanning, Nathan; Jin, Hui; Carter-Su, Christin; Qin, Zhaohui S.

2011-01-01

Regulation of c-Fos transcription by GH is mediated by CCAAT/enhancer binding protein β (C/EBPβ). This study examines the role of C/EBPβ in mediating GH activation of other early response genes, including Cyr61, Btg2, Socs3, Zfp36, and Socs1. C/EBPβ depletion using short hairpin RNA impaired responsiveness of these genes to GH, as seen for c-Fos. Rescue with wild-type C/EBPβ led to GH-dependent recruitment of the coactivator p300 to the c-Fos promoter. In contrast, rescue with C/EBPβ mutated at the ERK phosphorylation site at T188 failed to induce GH-dependent recruitment of p300, indicating that ERK-mediated phosphorylation of C/EBPβ at T188 is required for GH-induced recruitment of p300 to c-Fos. GH also induced the occupancy of phosphorylated C/EBPβ and p300 on Cyr61, Btg2, and Socs3 at predicted C/EBP-cAMP response element-binding protein motifs in their promoters. Consistent with a role for ERKs in GH-induced expression of these genes, treatment with U0126 to block ERK phosphorylation inhibited their GH-induced expression. In contrast, GH-dependent expression of Zfp36 and Socs1 was not inhibited by U0126. Thus, induction of multiple early response genes by GH in 3T3-F442A cells is mediated by C/EBPβ. A subset of these genes is regulated similarly to c-Fos, through a mechanism involving GH-stimulated ERK 1/2 activation, phosphorylation of C/EBPβ, and recruitment of p300. Overall, these studies suggest that C/EBPβ, like the signal transducer and activator of transcription proteins, regulates multiple genes in response to GH. PMID:21292824

Trait liabilities and specific promotive processes in psychopathology: The example of suicidal behavior.

Science.gov (United States)

Buchman-Schmitt, Jennifer M; Brislin, Sarah J; Venables, Noah C; Joiner, Thomas E; Patrick, Christopher J

2017-07-01

The RDoC matrix framework calls for investigation of mental health problems through analysis of core biobehavioral processes quantified and studied across multiple domains of measurement. Critics have raised concerns about RDoC, including overemphasis on biological concepts/measures and disregard for the principle of multifinality, which holds that identical biological predispositions can give rise to differing behavioral outcomes. The current work illustrates an ontogenetic process approach to addressing these concerns, focusing on biobehavioral traits corresponding to RDoC constructs as predictors, and suicidal behavior as the outcome variable. Data were collected from a young adult sample (N=105), preselected to enhance rates of suicidality. Participants completed self-report measures of traits (threat sensitivity, response inhibition) and suicide-specific processes. We show that previously reported associations for traits of threat sensitivity and weak inhibitory control with suicidal behavior are mediated by more specific suicide-promoting processes-namely, thwarted belongingness, perceived burdensomeness, and capability for suicide. The sample was relatively small and the data were cross-sectional, limiting conclusions that can be drawn from the mediation analyses. Given prior research documenting neurophysiological as well as psychological bases to these trait dispositions, the current work sets the stage for an intensive RDoC-oriented investigation of suicidal tendencies in which both traits and suicide-promoting processes are quantified using indicators from different domains of measurement. More broadly, this work illustrates how an RDoC research approach can contribute to a nuanced understanding of specific clinical problems, through consideration of how general biobehavioral liabilities interface with distinct problem-promoting processes. Copyright © 2016 Elsevier B.V. All rights reserved.

Understanding Suicidal Ideation in Latino/a Adolescents Living in Puerto Rico.

Science.gov (United States)

Duarté-Vélez, Yovanska; Jones, Richard N; Spirito, Anthony

2017-12-05

Puerto Rican adolescents, as well as other Latinos/as, have been identified at higher risk for suicidal ideation and attempts compared to other ethnic groups. However, research designed to better understand suicidality among Puerto Rican adolescents is rare. A socio-cognitive vulnerability model of suicidal ideation was tested in adolescents living in Puerto Rico. Multiple group path analyses were performed to assess the effect of self-reported socio-environmental and vulnerability factors on suicidal ideation, by sex, in 233 students from the metropolitan area of San Juan, Puerto Rico. Overall, the model explained a large amount of the variance in suicidal ideation (r 2  = .59 for females and r2 = .48 for males). Depressive symptoms had the strongest total effect on suicidal ideation for both sexes (r = .69 for females and r = .53 for males) and negative life events were the most salient socio-environmental factor. Hopelessness had a direct effect on suicidal ideation for males only. Externalizing behaviors had a direct effect on suicidal ideation for both males and females, but it was particularly strong for females. Results support the mediating role of vulnerability factors and the differential importance of socio-environmental and vulnerability factors in understanding suicidal ideation among Puerto Rican adolescents. The relevance of exploring different developmental paths to suicidal ideation, separately by sex, is discussed.

Depletion of Mediator Kinase Module Subunits Represses Superenhancer-Associated Genes in Colon Cancer Cells.

Science.gov (United States)

Kuuluvainen, Emilia; Domènech-Moreno, Eva; Niemelä, Elina H; Mäkelä, Tomi P

2018-06-01

In cancer, oncogene activation is partly mediated by acquired superenhancers, which therefore represent potential targets for inhibition. Superenhancers are enriched for BRD4 and Mediator, and both BRD4 and the Mediator MED12 subunit are disproportionally required for expression of superenhancer-associated genes in stem cells. Here we show that depletion of Mediator kinase module subunit MED12 or MED13 together with MED13L can be used to reduce expression of cancer-acquired superenhancer genes, such as the MYC gene, in colon cancer cells, with a concomitant decrease in proliferation. Whereas depletion of MED12 or MED13/MED13L caused a disproportional decrease of superenhancer gene expression, this was not seen with depletion of the kinases cyclin-dependent kinase 9 (CDK8) and CDK19. MED12-MED13/MED13L-dependent superenhancer genes were coregulated by β-catenin, which has previously been shown to associate with MED12. Importantly, β-catenin depletion caused reduced binding of MED12 at the MYC superenhancer. The effect of MED12 or MED13/MED13L depletion on cancer-acquired superenhancer gene expression was more specific than and partially distinct from that of BRD4 depletion, with the most efficient inhibition seen with combined targeting. These results identify a requirement of MED12 and MED13/MED13L for expression of acquired superenhancer genes in colon cancer, implicating these Mediator subunits as potential therapeutic targets for colon cancer, alone or together with BRD4. Copyright © 2018 American Society for Microbiology.

The Arabidopsis Mediator Complex Subunits MED16, MED14, and MED2 Regulate Mediator and RNA Polymerase II Recruitment to CBF-Responsive Cold-Regulated Genes[C][W][OPEN

Science.gov (United States)

Hemsley, Piers A.; Hurst, Charlotte H.; Kaliyadasa, Ewon; Lamb, Rebecca; Knight, Marc R.; De Cothi, Elizabeth A.; Steele, John F.; Knight, Heather

2014-01-01

The Mediator16 (MED16; formerly termed SENSITIVE TO FREEZING6 [SFR6]) subunit of the plant Mediator transcriptional coactivator complex regulates cold-responsive gene expression in Arabidopsis thaliana, acting downstream of the C-repeat binding factor (CBF) transcription factors to recruit the core Mediator complex to cold-regulated genes. Here, we use loss-of-function mutants to show that RNA polymerase II recruitment to CBF-responsive cold-regulated genes requires MED16, MED2, and MED14 subunits. Transcription of genes known to be regulated via CBFs binding to the C-repeat motif/drought-responsive element promoter motif requires all three Mediator subunits, as does cold acclimation–induced freezing tolerance. In addition, these three subunits are required for low temperature–induced expression of some other, but not all, cold-responsive genes, including genes that are not known targets of CBFs. Genes inducible by darkness also required MED16 but required a different combination of Mediator subunits for their expression than the genes induced by cold. Together, our data illustrate that plants control transcription of specific genes through the action of subsets of Mediator subunits; the specific combination defined by the nature of the stimulus but also by the identity of the gene induced. PMID:24415770

Computational modeling identifies key gene regulatory interactions underlying phenobarbital-mediated tumor promotion

Science.gov (United States)

Luisier, Raphaëlle; Unterberger, Elif B.; Goodman, Jay I.; Schwarz, Michael; Moggs, Jonathan; Terranova, Rémi; van Nimwegen, Erik

2014-01-01

Gene regulatory interactions underlying the early stages of non-genotoxic carcinogenesis are poorly understood. Here, we have identified key candidate regulators of phenobarbital (PB)-mediated mouse liver tumorigenesis, a well-characterized model of non-genotoxic carcinogenesis, by applying a new computational modeling approach to a comprehensive collection of in vivo gene expression studies. We have combined our previously developed motif activity response analysis (MARA), which models gene expression patterns in terms of computationally predicted transcription factor binding sites with singular value decomposition (SVD) of the inferred motif activities, to disentangle the roles that different transcriptional regulators play in specific biological pathways of tumor promotion. Furthermore, transgenic mouse models enabled us to identify which of these regulatory activities was downstream of constitutive androstane receptor and β-catenin signaling, both crucial components of PB-mediated liver tumorigenesis. We propose novel roles for E2F and ZFP161 in PB-mediated hepatocyte proliferation and suggest that PB-mediated suppression of ESR1 activity contributes to the development of a tumor-prone environment. Our study shows that combining MARA with SVD allows for automated identification of independent transcription regulatory programs within a complex in vivo tissue environment and provides novel mechanistic insights into PB-mediated hepatocarcinogenesis. PMID:24464994

The insomnia and suicide link: toward an enhanced understanding of this relationship.

Science.gov (United States)

Woznica, Andrea A; Carney, Colleen E; Kuo, Janice R; Moss, Taryn G

2015-08-01

Despite current knowledge of risk factors for suicidal behaviors, suicide remains a leading cause of death worldwide. This suggests a strong need to identify and understand additional risk factors. A number of recent studies have identified insomnia as a modifiable, independent suicide risk factor. Although a link between insomnia and suicide is emerging, further research is required in order to understand the nature of the relationship. Accordingly, this paper presents an overview of the insomnia and suicide literature to-date, and a discussion of two major limitations within this literature that hinder its progress. First, the classification and assessment of insomnia and suicide-related thoughts and behaviors are inconsistent across studies; and second, there is a lack of empirical studies focused on investigating mediators of the insomnia and suicide relationship. Suggestions are offered within this paper for future studies to address these issues and facilitate new developments in this important research area. Following these suggested lines of research will ultimately inform whether insomnia treatments, particularly cognitive-behavioral therapy for insomnia, can be used to target suicide risk prevention and intervention. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Effectiveness of Family-Based Cognitive-Behavior Grief Therapy to Prevent Complicated Grief in Relatives of Suicide Victims : The Mediating Role of Suicide Ideation

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de Groot, M.; Neeleman, J.; van der Meer, K.; Burger, H.

2010-01-01

Grief interventions are more effective for high risk individuals. The presence of suicide ideation following suicide bereavement was examined to determine whether it indicates a high risk status. Using data from a randomized controlled trial (n =122) on the effectiveness of cognitive-behavior

Factors predicting recovery from suicide in attempted suicide patients.

Science.gov (United States)

Sun, Fan-Ko; Lu, Chu-Yun; Tseng, Yun Shan; Chiang, Chun-Ying

2017-12-01

The aim of this study was to explore the factors predicting suicide recovery and to provide guidance for healthcare professionals when caring for individuals who have attempted suicide. The high rate of suicide is a global health problem. Suicide prevention has become an important issue in contemporary mental health. Most suicide research has focused on suicidal prevention and care. There is a lack of research on the factors predicting suicidal recovery. A cross-sectional design was adopted. A correlational study with a purposive sample of 160 individuals from a suicide prevention centre in southern Taiwan was conducted. The questionnaires included the Brief Symptom Rating Scale-5, Suicidal Recovery Assessment Scale and Beck Hopelessness Scale. Descriptive statistics and linear regressions were used for the analysis. The mean age of the participants was 40.2 years. Many participants were striving to make changes to create a more stable and fulfilling life, had an improved recovery from suicide and had a good ability to adapt or solve problems. The linear regression showed that the Beck Hopelessness Scale scores (ß = -.551, p suicidal behaviour (ß = -.145, p = .008) were significant predictors of individuals' recovery from suicide. They accounted for 57.1% of the variance. Suicidal individuals who have a lower level of hopelessness, a better ability to cope with their mental condition and fewer past suicidal behaviours may better recover from suicide attempts. The nurses could use the results of this study to predict recovery from suicide in patients with attempted suicide. © 2017 John Wiley & Sons Ltd.

Suicide Neurosis--A Study of Sixty Young Suicide Attempters.

Science.gov (United States)

Chinnian, R. Rawlin; Johnson, Shelonitda

Suicide and deviance are related because loss in social interaction is a consequence of deviance and an antecedent to suicide. This study examined the cognitive and affective experiences of suicidal individuals for evidence of neurosis. Sixty young attempted suicides with a history of a serious suicidal attempts attending the suicide prevention…

Family history of suicide and exposure to interpersonal violence in childhood predict suicide in male suicide attempters.

Science.gov (United States)

Rajalin, Mia; Hirvikoski, Tatja; Jokinen, Jussi

2013-05-15

Family studies, including twin and adoption designs, have shown familial transmission of suicidal behaviors. Early environmental risk factors have an important role in the etiology of suicidal behavior. The aim of the present study was to assess the impact of family history of suicide and childhood trauma on suicide risk and on severity of suicide attempt in suicide attempters. A total of 181 suicide attempters were included. Family history of suicide was assessed with the Karolinska Suicide History Interview or through patient records. Childhood trauma was assessed with the Karolinska Interpersonal Violence Scale (KIVS) measuring exposure to violence and expressed violent behavior in childhood (between 6 and 14 years of age) and during adult life (15 years or older). Suicide intent was measured with the Freeman scale. Male suicide attempters with a positive family history of suicide made more serious and well planned suicide attempts and had a significantly higher suicide risk. In logistic regression, family history of suicide and exposure to interpersonal violence as a child were independent predictors of suicide in male suicide attempters. The information about family history of suicide and exposure to interpersonal violence as a child derives from the patients only. In the first part of the inclusion period the information was collected from patient records. The results of this study imply that suicides among those at biological risk might be prevented with the early recognition of environmental risks. Copyright © 2012 Elsevier B.V. All rights reserved.

Strategies in Gene Therapy for Glioblastoma

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Kwiatkowska, Aneta; Nandhu, Mohan S.; Behera, Prajna; Chiocca, E. Antonio; Viapiano, Mariano S.

2013-01-01

Glioblastoma (GBM) is the most aggressive form of brain cancer, with a dismal prognosis and extremely low percentage of survivors. Novel therapies are in dire need to improve the clinical management of these tumors and extend patient survival. Genetic therapies for GBM have been postulated and attempted for the past twenty years, with variable degrees of success in pre-clinical models and clinical trials. Here we review the most common approaches to treat GBM by gene therapy, including strategies to deliver tumor-suppressor genes, suicide genes, immunomodulatory cytokines to improve immune response, and conditionally-replicating oncolytic viruses. The review focuses on the strategies used for gene delivery, including the most common and widely used vehicles (i.e., replicating and non-replicating viruses) as well as novel therapeutic approaches such as stem cell-mediated therapy and nanotechnologies used for gene delivery. We present an overview of these strategies, their targets, different advantages, and challenges for success. Finally, we discuss the potential of gene therapy-based strategies to effectively attack such a complex genetic target as GBM, alone or in combination with conventional therapy

Strategies in Gene Therapy for Glioblastoma

Energy Technology Data Exchange (ETDEWEB)

Kwiatkowska, Aneta; Nandhu, Mohan S.; Behera, Prajna; Chiocca, E. Antonio; Viapiano, Mariano S., E-mail: mviapiano@partners.org [Department of Neurosurgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115 (United States)

2013-10-22

Glioblastoma (GBM) is the most aggressive form of brain cancer, with a dismal prognosis and extremely low percentage of survivors. Novel therapies are in dire need to improve the clinical management of these tumors and extend patient survival. Genetic therapies for GBM have been postulated and attempted for the past twenty years, with variable degrees of success in pre-clinical models and clinical trials. Here we review the most common approaches to treat GBM by gene therapy, including strategies to deliver tumor-suppressor genes, suicide genes, immunomodulatory cytokines to improve immune response, and conditionally-replicating oncolytic viruses. The review focuses on the strategies used for gene delivery, including the most common and widely used vehicles (i.e., replicating and non-replicating viruses) as well as novel therapeutic approaches such as stem cell-mediated therapy and nanotechnologies used for gene delivery. We present an overview of these strategies, their targets, different advantages, and challenges for success. Finally, we discuss the potential of gene therapy-based strategies to effectively attack such a complex genetic target as GBM, alone or in combination with conventional therapy.

DMPD: Signalling pathways mediating type I interferon gene expression. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17904888 Signalling pathways mediating type I interferon gene expression. Edwards M...hways mediating type I interferon gene expression. PubmedID 17904888 Title Signalling pathways...R, Slater L, Johnston SL. Microbes Infect. 2007 Sep;9(11):1245-51. Epub 2007 Jul 1. (.png) (.svg) (.html) (.csml) Show Signalling pat

Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein

International Nuclear Information System (INIS)

Lee, Na-Rae; Shin, Han-Bo; Kim, Hye-In; Choi, Myung-Soo; Inn, Kyung-Soo

2013-01-01

Highlights: •TRK-fused gene product (TFG) interacts with TRIM25 upon viral infection. •TFG negatively regulates RIG-I mediated antiviral signaling. •TFG depletion leads to enhanced viral replication. •TFG act downstream of MAVS. -- Abstract: RIG-I (retinoic acid inducible gene I)-mediated antiviral signaling serves as the first line of defense against viral infection. Upon detection of viral RNA, RIG-I undergoes TRIM25 (tripartite motif protein 25)-mediated K63-linked ubiquitination, leading to type I interferon (IFN) production. In this study, we demonstrate that TRK-fused gene (TFG) protein, previously identified as a TRIM25-interacting protein, binds TRIM25 upon virus infection and negatively regulates RIG-I-mediated type-I IFN signaling. RIG-I-mediated IFN production and nuclear factor (NF)-κB signaling pathways were upregulated by the suppression of TFG expression. Furthermore, vesicular stomatitis virus (VSV) replication was significantly inhibited by small inhibitory hairpin RNA (shRNA)-mediated knockdown of TFG, supporting the suppressive role of TFG in RIG-I-mediated antiviral signaling. Interestingly, suppression of TFG expression increased not only RIG-I-mediated signaling but also MAVS (mitochondrial antiviral signaling protein)-induced signaling, suggesting that TFG plays a pivotal role in negative regulation of RNA-sensing, RIG-I-like receptor (RLR) family signaling pathways

Are autistic traits associated with suicidality? A test of the interpersonal-psychological theory of suicide in a non-clinical young adult sample.

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Pelton, M K; Cassidy, S A

2017-11-01

Autism spectrum conditions (ASC) has recently been associated with increased risk of suicidality. However, no studies have explored how autistic traits may interact with current models of suicidal behavior in a non-clinical population. The current study therefore explored how self-reported autistic traits interact with perceived burdensomeness and thwarted belongingness in predicting suicidal behavior, in the context of the Interpersonal-Psychological Theory of Suicide (IPTS). 163 young adults (aged 18-30 years) completed an online survey including measures of thwarted belonging and perceived burdensomeness (Interpersonal Needs Questionnaire), self-reported autistic traits (Autism Spectrum Quotient), current depression (Centre for Epidemiological Studies Depression Scale), and lifetime suicidality (Suicide Behavior Questionnaire-Revised). Results showed that burdensomeness and thwarted belonging significantly mediated the relationship between autistic traits and suicidal behavior. Both depression and autistic traits significantly predicted thwarted belonging and perceived burdensomeness. Autistic traits did not significantly moderate the relationship between suicidal behavior and thwarted belonging or perceived burdensomeness. Results suggest that the IPTS provides a useful framework for understanding the influence of autistic traits on suicidal behavior. However, the psychometric properties of these measures need be explored in those with clinically confirmed diagnosis of ASC. Autism Res 2017, 10: 1891-1904. © 2017 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. Recent research has shown that people with high autistic traits are more likely to attempt suicide. However, no studies have explored why. We found that people with high autistic traits were more likely to experience feelings that they do not belong in the world, are a burden on others, and depression, which may increase their likelihood of

Stigma, Attitudes, and Help-Seeking Intentions for Psychological Problems in Relation to Regional Suicide Rates.

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Reynders, Alexandre; Kerkhof, Ad J F M; Molenberghs, Geert; Van Audenhove, Chantal

2016-02-01

In this ecological study, we investigated whether help-seeking related to stigma, intentions, and attitudes toward suicide are associated with the suicide rates of 20 regions within the Netherlands and Belgium. Significant associations were found between regional suicide rates and the intention to seek informal help (β = -1.47, p = .001), self-stigma (β = 1.33, p = .038), and shame (β = .71, p = .030). The association between self-stigma and suicide rate was mediated by intentions to seek informal help. These results suggest that to promote suicide prevention at the level of the regional population, stigma, shame, and intentions to seek help should be targeted in the public domain. © 2015 The American Association of Suicidology.

Psychiatric diagnoses in 3275 suicides: a meta-analysis

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Turecki Gustavo

2004-11-01

Full Text Available Abstract Background It is well known that most suicide cases meet criteria for a psychiatric disorder. However, rates of specific disorders vary considerably between studies and little information is known about gender and geographic differences. This study provides overall rates of total and specific psychiatric disorders in suicide completers and presents evidence supporting gender and geographic differences in their relative proportion. Methods We carried out a review of studies in which psychological autopsy studies of suicide completers were performed. Studies were identified by means of MEDLINE database searches and by scanning the reference list of relevant publications. Twenty-three variables were defined, 16 of which evaluating psychiatric disorders. Mantel-Haenszel Weighted Odds Ratios were estimated for these 16 outcome variables. Results Twenty-seven studies comprising 3275 suicides were included, of which, 87.3% (SD 10.0% had been diagnosed with a mental disorder prior to their death. There were major gender differences. Diagnoses of substance-related problems (OR = 3.58; 95% CI: 2.78–4.61, personality disorders (OR = 2.01; 95% CI: 1.38–2.95 and childhood disorders (OR = 4.95; 95% CI: 2.69–9.31 were more common among male suicides, whereas affective disorders (OR = 0.66; 95% CI: 0.53–0.83, including depressive disorders (OR = 0.53; 95% CI: 0.42–0.68 were less common among males. Geographical differences are also likely to be present in the relative proportion of psychiatric diagnoses among suicides. Conclusions Although psychopathology clearly mediates suicide risk, gender and geographical differences seem to exist in the relative proportion of the specific psychiatric disorders found among suicide completers.

Personal suicidality in reception and identification with suicidal film characters.

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Till, Benedikt; Vitouch, Peter; Herberth, Arno; Sonneck, Gernot; Niederkrotenthaler, Thomas

2013-04-01

The authors investigated the impact of suicidality on identity work during film exposure. Adults with low suicidality (n = 150) watched either It's My Party or The Fire Within, censored versions of these films not depicting the suicide, or the control film that concluded with a non-suicidal death. Baseline suicidality was measured with questionnaires before the movie. Identity work and identification with the protagonist were measured after the movie. Suicidality was directly associated with identity work during film dramas depicting suicide methods. The reception of suicide-related media content seems to partially depend on personal suicidality. Potential implications for suicide prevention are discussed.

The Mediating Role of Parental Support in the Relationship between Life Stress and Suicidal Ideation among Middle School Students.

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Kang, Bong-Hee; Kang, Jae-Heon; Park, Hyun-Ah; Cho, Young-Gyu; Hur, Yang-Im; Sim, Won Yong; Byeon, Gyeong-Ran; Kim, Kyoungwoo

2017-07-01

Youth suicide is increasingly being recognized as a major social problem in South Korea. In this study, we aimed to explore the effects of parental support on the relationship between life stress and suicidal ideation among middle-school students. This study analyzed data from a cross-sectional study on mental health conducted by the South Korea National Youth Policy Institute between May and July of 2013. Questionnaire responses from 3,007 middle-school students regarding stress factors, thoughts of suicide during the past year, and parental support were analyzed in terms of 3 subscale elements: emotional, academic, and financial support. Among the participants, 234 male students (7.8%) and 476 female students (15.8%) reported experiencing suicidal ideation in the past year. Life stress significantly influenced suicidal ideation (Pstress increased suicidal ideation (adjusted odds ratio [aOR], 1.318; Pstress on suicidal ideation decreased with parental support (aOR, 1.238; Pstress was independently related to an increase in suicidal ideation. Parental support buffered the relationship between life stress and suicidal ideation.

Suicide and Suicidal Behavior among Transgender Persons.

Science.gov (United States)

Virupaksha, H G; Muralidhar, Daliboyina; Ramakrishna, Jayashree

2016-01-01

Suicide rate and suicidal tendencies among transgender persons are considerably high compared to general population. Hence, this review is an attempt to understand the issues around the suicide and suicidal behavior among transgender persons. The literature search conducted using three sources, i.e., electronic databases (PubMed, ProQuest, Google Scholar, PsycInfo), manual search (library catalog), and gray literature (consultation with experts). The suicide attempt rate among transgender persons ranges from 32% to 50% across the countries. Gender-based victimization, discrimination, bullying, violence, being rejected by the family, friends, and community; harassment by intimate partner, family members, police and public; discrimination and ill treatment at health-care system are the major risk factors that influence the suicidal behavior among transgender persons. In spite of facing a number of hardships in their day-to-day life, the transgender community holds a number of resiliency factors. Further, this community needs to be supported to strengthen their resiliency factors and draw culturally sensitive and transgender-inclusive suicide prevention strategies and increase protective factors to tackle this high rate of suicidality.

Caring stress, suicidal attitude and suicide care ability among family caregivers of suicidal individuals: a path analysis.

Science.gov (United States)

Chiang, C-Y; Lu, C-Y; Lin, Y-H; Lin, H-Y; Sun, F-K

2015-12-01

What is known on the subject? Suicide is a global mental health issue. Taking care of suicidal individuals is a substantial challenge. Most studies emphasize the suicidal individual. Few studies have emphasized the family caregivers of suicidal individuals. No study has explored the relationship between family caregivers' caring stress with suicidal attitudes and suicide care ability. What this paper adds to existing knowledge? The main results indicated that the older family caregivers tended to have a more negative attitude towards suicidal individuals. Female family caregivers' stress was higher than that of male family caregivers. A mild level of caring stress would help family caregivers have a more positive attitude towards suicidal individuals. Furthermore, a positive attitude would help family caregivers improve their caring ability. What are the implications for practice? Mental health nurses could help family caregivers, especially female family caregivers, reduce their holistic caring burden by looking for support resources and enhancing their coping strategies. Mental health nurses could help family caregivers promote positive attitudes towards suicidal relatives by understanding suicidal individuals' suffering. Suicide is a global mental health issue. Family caregivers play a key role in preventing suicide attempts. The aim of this study was to examine the relationship among stress due to the family caregiver's role, suicidal attitude of the family caregiver and suicide care ability among family caregivers. Additionally, instruments of caring stress, attitudes towards suicidal relatives and caring abilities used in the study were tested to measure construct validity. A cross-sectional correlational study was conducted with 164 family caregivers of people who are suicidal. The following three questionnaires were used: the Caring Stress Scale, the Suicidal Attitudes Scale and the Suicidal Caring Ability Scale. Structural equation modelling was performed

Alexithymia and Suicide Risk in Psychiatric Disorders: A Mini-Review

Directory of Open Access Journals (Sweden)

Domenico De Berardis

2017-08-01

Full Text Available It is well known that alexithymic individuals may show significantly higher levels of anxiety, depression, and psychological suffering than non-alexithymics. There is an increasing evidence that alexithymia may be considered a risk factor for suicide, even simply increasing the risk of development of depressive symptoms or per se. Therefore, the purpose of this narrative mini-review was to elucidate a possible relationship between alexithymia and suicide risk. The majority of reviewed studies pointed out a relationship between alexithymia and an increased suicide risk. In several studies, this relationship was mediated by depressive symptoms. In conclusion, the importance of alexithymia screening in everyday clinical practice and the evaluation of clinical correlates of alexithymic traits should be integral parts of all disease management programs and, especially, of suicide prevention plans and interventions. However, limitations of studies are discussed and must be considered.

Prioritizing research to reduce youth suicide and suicidal behavior.

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Bridge, Jeffrey A; Horowitz, Lisa M; Fontanella, Cynthia A; Grupp-Phelan, Jackie; Campo, John V

2014-09-01

The goal of the National Action Alliance for Suicide Prevention is to reduce suicide and suicide attempts in the U.S. by 40% in the next decade. In this paper, a public health approach is applied to suicide prevention to illustrate how reductions in youth suicide and suicidal behavior might be achieved by prioritizing research in two areas: (1) increasing access to primary care-based behavioral health interventions for depressed youth and (2) improving continuity of care for youth who present to emergency departments after a suicide attempt. Finally, some scientific, clinical, and methodologic breakthroughs needed to achieve rapid, substantial, and sustained reductions in youth suicide and suicidal behavior are discussed. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Middle-aged and older adults who had serious suicidal thoughts: who made suicide plans and nonfatal suicide attempts?

Science.gov (United States)

Choi, Namkee G; DiNitto, Diana M; Marti, C Nathan

2015-03-01

High suicide rates in late middle-aged and older adults are significant public health problems. Although suicide risk and protective factors are well established, more research is needed about suicide planners and attempters. Using multi-year, national epidemiologic survey data, this study identified correlates of making suicide plans and nonfatal suicide attempts among U.S. adults aged 50+ years. Data are from the 2008 to 2012 U.S. National Survey on Drug Use and Health (NSDUH). Descriptive statistics were used to examine sample characteristics by past-year serious suicidal thoughts, suicide plans, and suicide attempts. Binary logistic regression analyses were used to examine potential correlates (sociodemographic factors, health status, religiosity, psychiatric and substance use disorders (SUDs), and mental health and substance abuse treatment use) of suicide plans and suicide attempts among those who reported serious suicidal thoughts. Of the 2.5% of the study population that had serious suicidal thoughts (n = 804), 28% made suicide plans and 11.5% attempted suicide. Although 42% of those with serious suicidal thoughts had major depressive episode (MDE), MDE was not significantly associated with suicide plans or attempts in multivariate models. Being employed decreased the odds of making suicide plans, while mental health service use was associated with increased odds of suicide plans. SUDs increased the odds of suicide attempts. It is important to screen middle-aged and older adults for severe mental and SUDs and suicidal thoughts and to target interventions for likely planners and attempters.

In vivo preclinical low field MRI monitoring of tumor growth following a suicide gene therapy in an ortho-topic mice model of human glioblastoma;Controle par IRM bas champ in vivo de l'efficacite d'une therapie genique par gene suicide dans un modele murin de glioblastome orthotopique

Energy Technology Data Exchange (ETDEWEB)

Breton, E.; Goetz, Ch.; Aubertin, G.; Constantinesco, A.; Choquet, Ph. [Service de biophysique et medecine nucleaire, hopital de Hautepierre, CHRU de Strasbourg, 67 - Strasbourg (France); Institut de mecanique des fluides et des solides, CNRS, universite de Strasbourg, 67 - Strasbourg (France); Kintz, J.; Accart, N.; Grellier, B.; Erbs, Ph.; Rooke, R. [Transgene SA, parc d' innovation, 67 - Illkirch Graffenstaden (France)

2010-03-15

Purpose The aim of this study was to monitor in vivo with low field MRI growth of a murine ortho-topic glioma model following a suicide gene therapy. Methods The gene therapy consisted in the stereotactic injection in the mice brain of a modified vaccinia virus Ankara (M.V.A.) vector encoding for a suicide gene (FCU1) that transforms a non toxic pro-drug 5-fluoro-cytosine (5-F.C.) to its highly cytotoxic derivatives 5-fluorouracil (5-F.U.) and 5-fluoro-uridine-5 monophosphate (5-F.U.M.P.). Using a warmed-up imaging cell, sequential 3D T1 and T2 0.1T MRI brain examinations were performed on 16 Swiss female nu/nu mice bearing ortho-topic human glioblastoma (U 87-MG cells). The 6-week in vivo MRI follow-up consisted in a weekly measurement of the intracerebral tumor volume leading to a total of 65 examinations. Mice were divided in four groups: sham group (n = 4), sham group treated with 5-F.C. only (n = 4), sham group with injection of M.V.A.-FCU1 vector only (n = 4), therapy group administered with M.V.A.-FCU1 vector and 5-F.C. (n = 4). Measurements of tumor volumes were obtained after manual segmentation of T1- and T2-weighted images. Results Intra-observer and inter-observer tumor volume measurements show no significant differences. No differences were found between T1 and T2 volume tumor doubling times between the three sham groups. A significant statistical difference (p < 0.05) in T1 and T2 volume tumor doubling times between the three sham groups and the animals treated with the intratumoral injection of M.V.A.-FCU1 vector in combination with 2 weeks per os 5-F.C. administration was demonstrated. Conclusion Preclinical low field MRI was able to monitor efficacy of suicide gene therapy in delaying the tumor growth in an in vivo mouse model of ortho-topic glioblastoma. (authors)

Googling suicide: surfing for suicide information on the Internet.

Science.gov (United States)

Recupero, Patricia R; Harms, Samara E; Noble, Jeffrey M

2008-06-01

This study examined the types of resources a suicidal person might find through search engines on the Internet. We were especially interested in determining the accessibility of potentially harmful resources, such as prosuicide forums, as such resources have been implicated in completed suicides and are known to exist on the Web. Using 5 popular search engines (Google, Yahoo!, Ask.com, Lycos, and Dogpile) and 4 suicide-related search terms (suicide, how to commit suicide, suicide methods, and how to kill yourself), we collected quantitative and qualitative data about the search results. The searches were conducted in August and September 2006. Several coraters assigned codes and characterizations to the first 30 Web sites per search term combination (and "sponsored links" on those pages), which were then confirmed by consensus ratings. Search results were classified as being prosuicide, antisuicide, suicide-neutral, not a suicide site, or error (i.e., page would not load). Additional information was collected to further characterize the nature of the information on these Web sites. Suicide-neutral and anti-suicide pages occurred most frequently (of 373 unique Web pages, 115 were coded as suicide-neutral, and 109 were anti-suicide). While pro-suicide resources were less frequent (41 Web pages), they were nonetheless easily accessible. Detailed how-to instructions for unusual and lethal suicide methods were likewise easily located through the searches. Mental health professionals should ask patients about their Internet use. Depressed, suicidal, or potentially suicidal patients who use the Internet may be especially at risk. Clinicians may wish to assist patients in locating helpful, supportive resources online so that patients' Internet use may be more therapeutic than harmful.

Extracellular NGFR Spacers Allow Efficient Tracking and Enrichment of Fully Functional CAR-T Cells Co-Expressing a Suicide Gene.

Science.gov (United States)

Casucci, Monica; Falcone, Laura; Camisa, Barbara; Norelli, Margherita; Porcellini, Simona; Stornaiuolo, Anna; Ciceri, Fabio; Traversari, Catia; Bordignon, Claudio; Bonini, Chiara; Bondanza, Attilio

2018-01-01

Chimeric antigen receptor (CAR)-T cell immunotherapy is at the forefront of innovative cancer therapeutics. However, lack of standardization of cellular products within the same clinical trial and lack of harmonization between different trials have hindered the clear identification of efficacy and safety determinants that should be unveiled in order to advance the field. With the aim of facilitating the isolation and in vivo tracking of CAR-T cells, we here propose the inclusion within the CAR molecule of a novel extracellular spacer based on the low-affinity nerve-growth-factor receptor (NGFR). We screened four different spacer designs using as target antigen the CD44 isoform variant 6 (CD44v6). We successfully generated NGFR-spaced CD44v6 CAR-T cells that could be efficiently enriched with clinical-grade immuno-magnetic beads without negative consequences on subsequent expansion, immuno-phenotype, in vitro antitumor reactivity, and conditional ablation when co-expressing a suicide gene. Most importantly, these cells could be tracked with anti-NGFR monoclonal antibodies in NSG mice, where they expanded, persisted, and exerted potent antitumor effects against both high leukemia and myeloma burdens. Similar results were obtained with NGFR-enriched CAR-T cells specific for CD19 or CEA, suggesting the universality of this strategy. In conclusion, we have demonstrated that the incorporation of the NGFR marker gene within the CAR sequence allows for a single molecule to simultaneously work as a therapeutic and selection/tracking gene. Looking ahead, NGFR spacer enrichment might allow good manufacturing procedures-manufacturing of standardized CAR-T cell products with high therapeutic potential, which could be harmonized in different clinical trials and used in combination with a suicide gene for future application in the allogeneic setting.

Extracellular NGFR Spacers Allow Efficient Tracking and Enrichment of Fully Functional CAR-T Cells Co-Expressing a Suicide Gene

Science.gov (United States)

Casucci, Monica; Falcone, Laura; Camisa, Barbara; Norelli, Margherita; Porcellini, Simona; Stornaiuolo, Anna; Ciceri, Fabio; Traversari, Catia; Bordignon, Claudio; Bonini, Chiara; Bondanza, Attilio

2018-01-01

Chimeric antigen receptor (CAR)-T cell immunotherapy is at the forefront of innovative cancer therapeutics. However, lack of standardization of cellular products within the same clinical trial and lack of harmonization between different trials have hindered the clear identification of efficacy and safety determinants that should be unveiled in order to advance the field. With the aim of facilitating the isolation and in vivo tracking of CAR-T cells, we here propose the inclusion within the CAR molecule of a novel extracellular spacer based on the low-affinity nerve-growth-factor receptor (NGFR). We screened four different spacer designs using as target antigen the CD44 isoform variant 6 (CD44v6). We successfully generated NGFR-spaced CD44v6 CAR-T cells that could be efficiently enriched with clinical-grade immuno-magnetic beads without negative consequences on subsequent expansion, immuno-phenotype, in vitro antitumor reactivity, and conditional ablation when co-expressing a suicide gene. Most importantly, these cells could be tracked with anti-NGFR monoclonal antibodies in NSG mice, where they expanded, persisted, and exerted potent antitumor effects against both high leukemia and myeloma burdens. Similar results were obtained with NGFR-enriched CAR-T cells specific for CD19 or CEA, suggesting the universality of this strategy. In conclusion, we have demonstrated that the incorporation of the NGFR marker gene within the CAR sequence allows for a single molecule to simultaneously work as a therapeutic and selection/tracking gene. Looking ahead, NGFR spacer enrichment might allow good manufacturing procedures-manufacturing of standardized CAR-T cell products with high therapeutic potential, which could be harmonized in different clinical trials and used in combination with a suicide gene for future application in the allogeneic setting. PMID:29619024

Extracellular NGFR Spacers Allow Efficient Tracking and Enrichment of Fully Functional CAR-T Cells Co-Expressing a Suicide Gene

Directory of Open Access Journals (Sweden)

Monica Casucci

2018-03-01

Full Text Available Chimeric antigen receptor (CAR-T cell immunotherapy is at the forefront of innovative cancer therapeutics. However, lack of standardization of cellular products within the same clinical trial and lack of harmonization between different trials have hindered the clear identification of efficacy and safety determinants that should be unveiled in order to advance the field. With the aim of facilitating the isolation and in vivo tracking of CAR-T cells, we here propose the inclusion within the CAR molecule of a novel extracellular spacer based on the low-affinity nerve-growth-factor receptor (NGFR. We screened four different spacer designs using as target antigen the CD44 isoform variant 6 (CD44v6. We successfully generated NGFR-spaced CD44v6 CAR-T cells that could be efficiently enriched with clinical-grade immuno-magnetic beads without negative consequences on subsequent expansion, immuno-phenotype, in vitro antitumor reactivity, and conditional ablation when co-expressing a suicide gene. Most importantly, these cells could be tracked with anti-NGFR monoclonal antibodies in NSG mice, where they expanded, persisted, and exerted potent antitumor effects against both high leukemia and myeloma burdens. Similar results were obtained with NGFR-enriched CAR-T cells specific for CD19 or CEA, suggesting the universality of this strategy. In conclusion, we have demonstrated that the incorporation of the NGFR marker gene within the CAR sequence allows for a single molecule to simultaneously work as a therapeutic and selection/tracking gene. Looking ahead, NGFR spacer enrichment might allow good manufacturing procedures-manufacturing of standardized CAR-T cell products with high therapeutic potential, which could be harmonized in different clinical trials and used in combination with a suicide gene for future application in the allogeneic setting.

Up-regulation of integrin β3 in radioresistant pancreatic cancer impairs adenovirus-mediated gene therapy

International Nuclear Information System (INIS)

Egami, Takuya; Ohuchida, Kenoki; Yasui, Takaharu; Onimaru, Manabu; Toma, Hiroki; Sato, Norihiro; Tanaka, Masao; Mizumoto, Kazuhiro; Matsumoto, Kunio

2009-01-01

Adenovirus-mediated gene therapy is a promising approach for the treatment of pancreatic cancer. We previously reported that radiation enhanced adenovirus-mediated gene expression in pancreatic cancer, suggesting that adenoviral gene therapy might be more effective in radioresistant pancreatic cancer cells. In the present study, we compared the transduction efficiency of adenovirus-delivered genes in radiosensitive and radioresistant cells, and investigated the underlying mechanisms. We used an adenovirus expressing the hepatocyte growth factor antagonist, NK4 (Ad-NK4), as a representative gene therapy. We established two radioresistant human pancreatic cancer cell lines using fractionated irradiation. Radiosensitive and radioresistant pancreatic cancer cells were infected with Ad-NK4, and NK4 levels in the cells were measured. In order to investigate the mechanisms responsible for the differences in the transduction efficiency between these cells, we measured expression of the genes mediating adenovirus infection and endocytosis. The results revealed that NK4 levels in radioresistant cells were significantly lower (P<0.01) than those in radiosensitive cells, although there were no significant differences in adenovirus uptake between radiosensitive cells and radioresistant cells. Integrin β3 was up-regulated and the Coxsackie virus and adenovirus receptor was down-regulated in radioresistant cells, and inhibition of integrin β3 promoted adenovirus gene transfer. These results suggest that inhibition of integrin β3 in radioresistant pancreatic cancer cells could enhance adenovirus-mediated gene therapy. (author)

Nipbl and mediator cooperatively regulate gene expression to control limb development.

Directory of Open Access Journals (Sweden)

Akihiko Muto

2014-09-01

Full Text Available Haploinsufficiency for Nipbl, a cohesin loading protein, causes Cornelia de Lange Syndrome (CdLS, the most common "cohesinopathy". It has been proposed that the effects of Nipbl-haploinsufficiency result from disruption of long-range communication between DNA elements. Here we use zebrafish and mouse models of CdLS to examine how transcriptional changes caused by Nipbl deficiency give rise to limb defects, a common condition in individuals with CdLS. In the zebrafish pectoral fin (forelimb, knockdown of Nipbl expression led to size reductions and patterning defects that were preceded by dysregulated expression of key early limb development genes, including fgfs, shha, hand2 and multiple hox genes. In limb buds of Nipbl-haploinsufficient mice, transcriptome analysis revealed many similar gene expression changes, as well as altered expression of additional classes of genes that play roles in limb development. In both species, the pattern of dysregulation of hox-gene expression depended on genomic location within the Hox clusters. In view of studies suggesting that Nipbl colocalizes with the mediator complex, which facilitates enhancer-promoter communication, we also examined zebrafish deficient for the Med12 Mediator subunit, and found they resembled Nipbl-deficient fish in both morphology and gene expression. Moreover, combined partial reduction of both Nipbl and Med12 had a strongly synergistic effect, consistent with both molecules acting in a common pathway. In addition, three-dimensional fluorescent in situ hybridization revealed that Nipbl and Med12 are required to bring regions containing long-range enhancers into close proximity with the zebrafish hoxda cluster. These data demonstrate a crucial role for Nipbl in limb development, and support the view that its actions on multiple gene pathways result from its influence, together with Mediator, on regulation of long-range chromosomal interactions.

The Suicidal Narrative and Its Relationship to the Suicide Crisis Syndrome and Recent Suicidal Behavior.

Science.gov (United States)

Cohen, Lisa Janet; Gorman, Bernard; Briggs, Jessica; Jeon, Min Eun; Ginsburg, Tal; Galynker, Igor

2018-02-04

In this study, we introduce the construct of the suicidal narrative, a hypothetical personal narrative linked to imminent suicide, and explore its relationship to near-term suicidal risk and the suicide crisis syndrome (SCS). Psychiatric outpatients (N = 289) were administered the Columbia Suicide-Severity Rating Scale (C-SSRS), Suicide Crisis Inventory (SCI), and Suicide Narrative Inventory (SNI), a novel instrument combining the documented risk factors of Thwarted Belongingness, Perceived Burdensomeness, Humiliation, Social Defeat, Goal Disengagement, and Goal Reengagement. Dimensional measures of past month, lifetime, and past suicidal phenomena, incorporating ideation and behavior, were calculated from the C-SSRS. Structural equation modeling was used to explore the interaction among variables. Factor analysis of the SNI yielded two orthogonal factors, termed Interpersonal and Goal Orientation. The former factor was comprised of Perceived Burdensomeness, Social Defeat, Humiliation, and Thwarted Belongingness, the latter of Goal Disengagement and Goal Reengagement. The Interpersonal factor correlated with both SCS severity and suicidal phenomena in each time frame and the Goal Orientation factor with no other variable. As hypothesized, the proposed model was significant for the past month only. Our findings support the construct of the suicidal narrative and its function as a near-term suicidal risk factor. © 2018 The American Association of Suicidology.

BDNF, impulsiveness and avoidant focused coping in suicide attempters

OpenAIRE

AMBRUS, LIVIA

2016-01-01

Brain-derived neurotrophic factor (BDNF) is an important protein for neuroplasticity and neurogenesis. In this thesis the role of BDNF, in suicidal behaviour was investigated with focus on possible risk factors for suicidal behaviour such as avoidant focused coping, dysfuntional personality traits like impulsiveness and hyperactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis.Paper I: The association between avoidant focused coping and the BDNF Val66Met gene polymorphism in two differen...

Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis.

Science.gov (United States)

Huang, Cuiyuan; Zhang, Hong; Bai, Ruidan

2017-07-01

Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM) and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble-mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.

Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis

Directory of Open Access Journals (Sweden)

Cuiyuan Huang

2017-07-01

Full Text Available Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble–mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.

Area-Specific Cell Stimulation via Surface-Mediated Gene Transfer Using Apatite-Based Composite Layers

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Yushin Yazaki

2015-04-01

Full Text Available Surface-mediated gene transfer systems using biocompatible calcium phosphate (CaP-based composite layers have attracted attention as a tool for controlling cell behaviors. In the present study we aimed to demonstrate the potential of CaP-based composite layers to mediate area-specific dual gene transfer and to stimulate cells on an area-by-area basis in the same well. For this purpose we prepared two pairs of DNA–fibronectin–apatite composite (DF-Ap layers using a pair of reporter genes and pair of differentiation factor genes. The results of the area-specific dual gene transfer successfully demonstrated that the cells cultured on a pair of DF-Ap layers that were adjacently placed in the same well showed specific gene expression patterns depending on the gene that was immobilized in theunderlying layer. Moreover, preliminary real-time PCR results indicated that multipotential C3H10T1/2 cells may have a potential to change into different types of cells depending on the differentiation factor gene that was immobilized in the underlying layer, even in the same well. Because DF-Ap layers have a potential to mediate area-specific cell stimulation on their surfaces, they could be useful in tissue engineering applications.

Intravascular local gene transfer mediated by protein-coated metallic stent.

Science.gov (United States)

Yuan, J; Gao, R; Shi, R; Song, L; Tang, J; Li, Y; Tang, C; Meng, L; Yuan, W; Chen, Z

2001-10-01

To assess the feasibility, efficiency and selectivity of adenovirus-mediated gene transfer to local arterial wall by protein-coated metallic stent. A replication-defective recombinant adenovirus carrying the Lac Z reporter gene for nuclear-specific beta-galactosidase (Ad-beta gal) was used in this study. The coating for metallic stent was made by immersing it in a gelatin solution containing crosslinker. The coated stents were mounted on a 4.0 or 3.0 mm percutaneous transluminal coronary angioplasty (PTCA) balloon and submersed into a high-titer Ad-beta gal viral stock (2 x 10(10) pfu/ml) for 3 min, and then implanted into the carotid arteries in 4 mini-swines and into the left anterior descending branch of the coronary artery in 2 mini-swines via 8F large lumen guiding catheters. The animals were sacrificed 7 (n = 4), 14 (n = 1) and 21 (n = 1) days after implantation, respectively. The beta-galactosidase expression was assessed by X-gal staining. The results showed that the expression of transgene was detected in all animal. In 1 of carotid artery with an intact intima, the beta-gal expression was limited to endothelial cells. In vessels with denuded endothelium, gene expression was found in the sub-intima, media and adventitia. The transfection efficiency of medial smooth muscle cells was 38.6%. In 2 animals sacrificed 7 days after transfection, a microscopic examination of X-gal-stained samples did not show evidence of transfection in remote organs and arterial segments adjacent to the treated arterial site. Adenovirus-mediated arterial gene transfer to endothelial, smooth muscle cells and adventitia by protein-coated metallic stent is feasible. The transfection efficiency is higher. The coated stent may act as a good carrier of adenovirus-mediated gene transfer and have a potential to prevent restenosis following PTCA.

Gold nanoparticle mediated laser transfection for efficient siRNA mediated gene knock down.

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Dag Heinemann

Full Text Available Laser based transfection methods have proven to be an efficient and gentle alternative to established molecule delivery methods like lipofection or electroporation. Among the laser based methods, gold nanoparticle mediated laser transfection bears the major advantage of high throughput and easy usability. This approach uses plasmon resonances on gold nanoparticles unspecifically attached to the cell membrane to evoke transient and spatially defined cell membrane permeabilization. In this study, we explore the parameter regime for gold nanoparticle mediated laser transfection for the delivery of molecules into cell lines and prove its suitability for siRNA mediated gene knock down. The developed setup allows easy usage and safe laser operation in a normal lab environment. We applied a 532 nm Nd:YAG microchip laser emitting 850 ps pulses at a repetition rate of 20.25 kHz. Scanning velocities of the laser spot over the sample of up to 200 mm/s were tested without a decline in perforation efficiency. This velocity leads to a process speed of ∼8 s per well of a 96 well plate. The optimal particle density was determined to be ∼6 particles per cell using environmental scanning electron microscopy. Applying the optimized parameters transfection efficiencies of 88% were achieved in canine pleomorphic adenoma ZMTH3 cells using a fluorescent labeled siRNA while maintaining a high cell viability of >90%. Gene knock down of d2-EGFP was demonstrated and validated by fluorescence repression and western blot analysis. On basis of our findings and established mathematical models we suppose a mixed transfection mechanism consisting of thermal and multiphoton near field effects. Our findings emphasize that gold nanoparticle mediated laser transfection provides an excellent tool for molecular delivery for both, high throughput purposes and the transfection of sensitive cells types.

Gold nanoparticle mediated laser transfection for efficient siRNA mediated gene knock down.

Science.gov (United States)

Heinemann, Dag; Schomaker, Markus; Kalies, Stefan; Schieck, Maximilian; Carlson, Regina; Murua Escobar, Hugo; Ripken, Tammo; Meyer, Heiko; Heisterkamp, Alexander

2013-01-01

Laser based transfection methods have proven to be an efficient and gentle alternative to established molecule delivery methods like lipofection or electroporation. Among the laser based methods, gold nanoparticle mediated laser transfection bears the major advantage of high throughput and easy usability. This approach uses plasmon resonances on gold nanoparticles unspecifically attached to the cell membrane to evoke transient and spatially defined cell membrane permeabilization. In this study, we explore the parameter regime for gold nanoparticle mediated laser transfection for the delivery of molecules into cell lines and prove its suitability for siRNA mediated gene knock down. The developed setup allows easy usage and safe laser operation in a normal lab environment. We applied a 532 nm Nd:YAG microchip laser emitting 850 ps pulses at a repetition rate of 20.25 kHz. Scanning velocities of the laser spot over the sample of up to 200 mm/s were tested without a decline in perforation efficiency. This velocity leads to a process speed of ∼8 s per well of a 96 well plate. The optimal particle density was determined to be ∼6 particles per cell using environmental scanning electron microscopy. Applying the optimized parameters transfection efficiencies of 88% were achieved in canine pleomorphic adenoma ZMTH3 cells using a fluorescent labeled siRNA while maintaining a high cell viability of >90%. Gene knock down of d2-EGFP was demonstrated and validated by fluorescence repression and western blot analysis. On basis of our findings and established mathematical models we suppose a mixed transfection mechanism consisting of thermal and multiphoton near field effects. Our findings emphasize that gold nanoparticle mediated laser transfection provides an excellent tool for molecular delivery for both, high throughput purposes and the transfection of sensitive cells types.

Gold Nanoparticle Mediated Laser Transfection for Efficient siRNA Mediated Gene Knock Down

Science.gov (United States)

Heinemann, Dag; Schomaker, Markus; Kalies, Stefan; Schieck, Maximilian; Carlson, Regina; Escobar, Hugo Murua; Ripken, Tammo; Meyer, Heiko; Heisterkamp, Alexander

2013-01-01

Laser based transfection methods have proven to be an efficient and gentle alternative to established molecule delivery methods like lipofection or electroporation. Among the laser based methods, gold nanoparticle mediated laser transfection bears the major advantage of high throughput and easy usability. This approach uses plasmon resonances on gold nanoparticles unspecifically attached to the cell membrane to evoke transient and spatially defined cell membrane permeabilization. In this study, we explore the parameter regime for gold nanoparticle mediated laser transfection for the delivery of molecules into cell lines and prove its suitability for siRNA mediated gene knock down. The developed setup allows easy usage and safe laser operation in a normal lab environment. We applied a 532 nm Nd:YAG microchip laser emitting 850 ps pulses at a repetition rate of 20.25 kHz. Scanning velocities of the laser spot over the sample of up to 200 mm/s were tested without a decline in perforation efficiency. This velocity leads to a process speed of ∼8 s per well of a 96 well plate. The optimal particle density was determined to be ∼6 particles per cell using environmental scanning electron microscopy. Applying the optimized parameters transfection efficiencies of 88% were achieved in canine pleomorphic adenoma ZMTH3 cells using a fluorescent labeled siRNA while maintaining a high cell viability of >90%. Gene knock down of d2-EGFP was demonstrated and validated by fluorescence repression and western blot analysis. On basis of our findings and established mathematical models we suppose a mixed transfection mechanism consisting of thermal and multiphoton near field effects. Our findings emphasize that gold nanoparticle mediated laser transfection provides an excellent tool for molecular delivery for both, high throughput purposes and the transfection of sensitive cells types. PMID:23536802

Clinically relevant risk factors for suicide: Comparison between clinical group with passive suicidal ideation, active suicidal ideation and without suicidal ideation

OpenAIRE

Miloseva, Lence; Cuijpers, Pim; Stojcev, Saso; Niklewski, Gunter; Richter, Kneginja; Jovevska, Svetlana; Arsova, Roza; Serafimov, Aleksandar

2015-01-01

Introduction: In recent years, researchers and clinicians do not treat passive suicidal ideation as a clinically relevant risk factor for suicide, while underestimating the strength of this desire to die, compared with making a plan for suicide in individuals having active suicidal ideation. This research study is clinically prospective, cross-sequential, but also partly retrospective because it involves also variables from the past, such as patients’ history data (number of suicidal attempts...

VE-Cadherin-Mediated Epigenetic Regulation of Endothelial Gene Expression.

Science.gov (United States)

Morini, Marco F; Giampietro, Costanza; Corada, Monica; Pisati, Federica; Lavarone, Elisa; Cunha, Sara I; Conze, Lei L; O'Reilly, Nicola; Joshi, Dhira; Kjaer, Svend; George, Roger; Nye, Emma; Ma, Anqi; Jin, Jian; Mitter, Richard; Lupia, Michela; Cavallaro, Ugo; Pasini, Diego; Calado, Dinis P; Dejana, Elisabetta; Taddei, Andrea

2018-01-19

data extend the knowledge of polycomb-mediated regulation of gene expression to endothelial cell differentiation and vessel maturation. The identified mechanism opens novel therapeutic opportunities to modulate endothelial gene expression and induce vascular normalization through pharmacological inhibition of the polycomb-mediated repression system. © 2017 The Authors.

Predictors of suicide ideation and depression in Hong Kong adolescents: perceptions of academic and family climates.

Science.gov (United States)

Lee, Margaret T Y; Wong, Betty P; Chow, Bonnie W Y; McBride-Chang, Catherine

2006-02-01

The unique dimensions of perceptions of school and family contributing to depression and suicide ideation in Hong Kong adolescents were examined in two studies. In Study 1, among 327 Hong Kong Chinese female students ages 13-18, 47% reported some suicide ideation. Suicide ideation was significantly associated with depression, test anxiety, academic self-concept, and adolescents' perceived parental dissatisfaction with academic performance. The correlation between test anxiety and depression was especially high (r = .51). Study 2 examined how three different aspects of perceived family relationship were associated with depression and suicide ideation. Among 371 Hong Kong Chinese adolescents ages 14-20, 52.6% reported suicide ideation. Low levels of family cohesion and support and high levels of parent-adolescent conflict were positively related to depression and suicide ideation in both genders. Across both studies, depression mediated associations between academic- and family-related variables and suicide ideation. Findings underscore the importance of both academic and family climate in understanding depression and suicide ideation among Chinese adolescents.

Interaction of child maltreatment and 5-HTT polymorphisms: suicidal ideation among children from low-SES backgrounds.

Science.gov (United States)

Cicchetti, Dante; Rogosch, Fred A; Sturge-Apple, Melissa; Toth, Sheree L

2010-06-01

To investigate whether genotypic variation of the serotonin transporter gene-linked promoter region (5-HTTLPR) moderates the effect of maltreatment on suicidal ideation in school-aged children. Eight hundred and fifty low-income children (478 maltreated; 372 non-maltreated) provided DNA samples and self-reported depressive and suicidal symptoms. Genotypes of 5-HTTLPR (s/s or s/l vs. l/l) were determined by fragment analyses. Higher suicidal ideation was found among maltreated than non-maltreated children; the groups did not differ in 5-HTTLPR genotype frequencies. Children with one to two maltreatment subtypes and s/s or s/l genotypes had higher suicidal ideation than those with the l/l genotype; suicidal ideation did not differ in non-maltreated children or children with three to four maltreatment subtypes based on 5-HTTLPR variation. The results were applicable to emotionally maltreated/neglected and to physically/sexually abused children. Gene-environment interaction was not found for depressive symptoms. The protective effect of the 5-HTTLPR l/l genotype on suicidal ideation was limited to maltreated children experiencing fewer subtypes.

Suicidal behaviour and suicide prevention in later life.

Science.gov (United States)

Draper, Brian M

2014-10-01

Despite a general decline in late life suicide rates over the last 30 years, older people have the highest rates of suicide in most countries. In contrast, non-fatal suicidal behaviour declines with age and more closely resembles suicide than in younger age groups. There are difficulties in the detection and determination of pathological suicidal ideation in older people. Multiple factors increase suicide risk ranging from distal early and mid-life issues such as child abuse, parental death, substance misuse and traumatic life experiences to proximal precipitants in late life such as social isolation and health-related concerns. Clinical depression is the most frequently identified proximal mental health concern and in many cases is a first episode of major depression. Recent studies have identified changes on neuroimaging and neurocognitive factors that might distinguish suicidal from non-suicidal depression in older people. Strategies for suicide prevention need to be 'whole of life' and, as no single prevention strategy is likely to be successful alone, a multi-faceted, multi-layered approach is required. This should include optimal detection and management of depression and of high risk individuals as available evidence indicates that this can reduce suicidal behaviour. How best to improve the quality of depression management in primary and secondary care requires further research. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Association between level of suicide risk, characteristics of suicide attempts, and mental disorders among suicide attempters.

Science.gov (United States)

Park, Subin; Lee, Yeeun; Youn, Tak; Kim, Byung Soo; Park, Jong Ik; Kim, Haesoo; Lee, Hyo Chu; Hong, Jin Pyo

2018-04-11

Past attempted suicide is a strong predictor of future suicide risk, but the risk varies among suicide attempters. Hence, it is important to clarify distinguishing features of lifetime attempters with a high level of current suicide risk for efficient preventive management. We compared characteristics of suicide attempts and clinical characteristics among high-, moderate-, and low-risk attempters. Among the total of 6022 participants in the Korean Epidemiologic Catchment Area study, 193 reported a suicide attempt in their lifetime, 36 of which had high, 126 moderate, and 30 low levels of current suicide risk (1 incomplete response). High-risk suicide attempters had more past attempts compared with moderate- and low-risk suicide attempters. Suicide attempts were closely linked to a wide range of psychiatric comorbidities regardless of degree of current level of suicide risk, but the relative risk for having at least one mental disorder was the highest in high-risk attempters. Specifically, the relative risks for depressive disorder, anxiety disorders including obsessive-compulsive disorder and post-traumatic stress disorder, and substance use disorders were higher in high-risk attempters, and relative risk for somatoform disorder was higher in low-risk attempters than others. Our findings indicated that special attention is required for suicide attempters with a history of repeated attempts and current mental disorders, particularly anxiety disorders.

Suicide

Science.gov (United States)

Suicide is the tenth most common cause of death in the United States. People may consider suicide when they are hopeless and can't see ... event. People who have the highest risk of suicide are white men. But women and teens report ...

AAV2-mediated in vivo immune gene therapy of solid tumours

LENUS (Irish Health Repository)

Collins, Sara A

2010-12-20

Abstract Background Many strategies have been adopted to unleash the potential of gene therapy for cancer, involving a wide range of therapeutic genes delivered by various methods. Immune therapy has become one of the major strategies adopted for cancer gene therapy and seeks to stimulate the immune system to target tumour antigens. In this study, the feasibility of AAV2 mediated immunotherapy of growing tumours was examined, in isolation and combined with anti-angiogenic therapy. Methods Immune-competent Balb\\/C or C57 mice bearing subcutaneous JBS fibrosarcoma or Lewis Lung Carcinoma (LLC) tumour xenografts respectively were treated by intra-tumoural administration of AAV2 vector encoding the immune up-regulating cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) and the co-stimulatory molecule B7-1 to subcutaneous tumours, either alone or in combination with intra-muscular (IM) delivery of AAV2 vector encoding Nk4 14 days prior to tumour induction. Tumour growth and survival was monitored for all animals. Cured animals were re-challenged with tumourigenic doses of the original tumour type. In vivo cytotoxicity assays were used to investigate establishment of cell-mediated responses in treated animals. Results AAV2-mediated GM-CSF, B7-1 treatment resulted in a significant reduction in tumour growth and an increase in survival in both tumour models. Cured animals were resistant to re-challenge, and induction of T cell mediated anti-tumour responses were demonstrated. Adoptive transfer of splenocytes to naïve animals prevented tumour establishment. Systemic production of Nk4 induced by intra-muscular (IM) delivery of Nk4 significantly reduced subcutaneous tumour growth. However, combination of Nk4 treatment with GM-CSF, B7-1 therapy reduced the efficacy of the immune therapy. Conclusions Overall, this study demonstrates the potential for in vivo AAV2 mediated immune gene therapy, and provides data on the inter-relationship between tumour

Family history of suicide and high motor impulsivity distinguish suicide attempters from suicide ideators among college students.

Science.gov (United States)

Wang, Yong-Guang; Chen, Shen; Xu, Zhi-Ming; Shen, Zhi-Hua; Wang, Yi-Quan; He, Xiao-Yan; Cao, Ri-Fang; Roberts, David L; Shi, Jian-Fei; Wang, Yi-Qiang

2017-07-01

Suicide in college students has become an important public health issue in China. The aim of this study was to identify the differences between suicide attempters and suicide ideators based on a cross-sectional survey. Our results indicate that although female gender, positive screening for psychiatric illness, positive family history of suicide, elevated overall impulsivity, and elevated motor impulsivity were correlated with suicidal ideation, only positive family history of suicide and high motor impulsivity could differentiate suicide attempters from suicidal ideators. Future research with a longitudinal and prospective study design should be conducted to confirm these findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

The tryptophan hydroxylase 1 (TPH1) gene, schizophrenia susceptibility, and suicidal behavior: a multi-centre case-control study and meta-analysis

DEFF Research Database (Denmark)

Saetre, Peter; Lundmark, Per; Wang, August

2010-01-01

Serotonin (5-hydroxytryptamin; 5-HT) alternations has since long been suspected in the pathophysiology of schizophrenia. Tryptophan hydroxylase (tryptophan 5-monooxygenase; TPH) is the rate-limiting enzyme in the biosynthesis of 5-HT, and sequence variation in intron 6 of the TPH1 gene has been...... associated with schizophrenia. The minor allele (A) of this polymorphism (A218C) is also more frequent in patients who have attempted suicide and individuals who died by suicide, than in healthy control individuals. In an attempt to replicate previous findings, five single nucleotide polymorphisms (SNPs......) were genotyped in 837 Scandinavian schizophrenia patients and 1,473 controls. Three SNPs spanning intron 6 and 7, including the A218C and A779C polymorphisms, were associated with schizophrenia susceptibility (P = 0.019). However there were no differences in allele frequencies of these loci between...

Diversification of the Primary Antibody Repertoire by AID-Mediated Gene Conversion.

Science.gov (United States)

Lanning, Dennis K; Knight, Katherine L

2015-01-01

Gene conversion, mediated by activation-induced cytidine deaminase (AID), has been found to contribute to generation of the primary antibody repertoire in several vertebrate species. Generation of the primary antibody repertoire by gene conversion of immunoglobulin (Ig) genes occurs primarily in gut-associated lymphoid tissues (GALT) and is best described in chicken and rabbit. Here, we discuss current knowledge of the mechanism of gene conversion as well as the contribution of the microbiota in promoting gene conversion of Ig genes. Finally, we propose that the antibody diversification strategy used in GALT species, such as chicken and rabbit, is conserved in a subset of human and mouse B cells.

Can Better Mother-Daughter Relations Reduce the Chance of a Suicide Attempt among Latinas?

Directory of Open Access Journals (Sweden)

Luis H. Zayas

2011-01-01

Full Text Available National surveys and other research on adolescent Latinas show that adolescent females have higher rates of suicidal ideation, planning, and attempts than other ethnic and racial minority youth. Internalizing behaviors and family conflicts are commonly associated with suicidality in research on adolescents. In the case of Latinas, we explore the connection between adolescent Hispanic cultural involvement, mother-adolescent mutuality, internalizing behaviors, and suicidality. This paper presents data from a study of 232 Latinas, some with a recent history of suicide attempts (n=122. The results show that higher adolescent Hispanic cultural involvement was associated with greater mother-daughter mutuality and thus led to reduction in the likelihood of suicide attempts. The relationship between mother-daughter mutuality and suicide attempts among Latinas is mediated by specific internalizing behaviors (withdrawn depressive. Our findings highlight the positive effect that Latino cultural values have in the relationship between Latina adolescent and their mothers and confirm the importance that internalizing behaviors and the mother-daughter relationship have for suicide attempters.

Hypoxia targeted bifunctional suicide gene expression enhances radiotherapy in vitro and in vivo

International Nuclear Information System (INIS)

Sun, Xiaorong; Xing, Ligang; Deng, Xuelong; Hsiao, Hung Tsung; Manami, Akiko; Koutcher, Jason A.; Clifton Ling, C.; Li, Gloria C.

2012-01-01

Purpose: To investigate whether hypoxia targeted bifunctional suicide gene expression-cytosine deaminase (CD) and uracil phosphoribosyltransferase (UPRT) with 5-FC treatments can enhance radiotherapy. Materials and methods: Stable transfectants of R3327-AT cells were established which express a triple-fusion-gene: CD, UPRT and monomoric DsRed (mDsRed) controlled by a hypoxia inducible promoter. Hypoxia-induced expression/function of CDUPRTmDsRed was verified by western blot, flow cytometry, fluorescent microscopy, and cytotoxicity assay of 5-FU and 5-FC. Tumor-bearing mice were treated with 5-FC and local radiation. Tumor volume was monitored and compared with those treated with 5-FC or radiation alone. In addition, the CDUPRTmDsRed distribution in hypoxic regions of tumor sections was visualized with fluorescent microscopy. Results: Hypoxic induction of CDUPRTmDsRed protein correlated with increased sensitivity to 5-FC and 5-FU. Significant radiosensitization effects were detected after 5-FC treatments under hypoxic conditions. In the tumor xenografts, the distribution of CDUPRTmDsRed expression visualized with fluorescence microscopy was co-localized with the hypoxia marker pimonidazole positive staining cells. Furthermore, administration of 5-FC to mice in combination with local irradiation resulted in significant tumor regression, as in comparison with 5-FC or radiation treatments alone. Conclusions: Our data suggest that the hypoxia-inducible CDUPRT/5-FC gene therapy strategy has the ability to specifically target hypoxic cancer cells and significantly improve the tumor control in combination with radiotherapy.

A structural equation model of perceived and internalized stigma, depression, and suicidal status among people living with HIV/AIDS.

Science.gov (United States)

Zeng, Chengbo; Li, Linghua; Hong, Yan Alicia; Zhang, Hanxi; Babbitt, Andrew Walker; Liu, Cong; Li, Lixia; Qiao, Jiaying; Guo, Yan; Cai, Weiping

2018-01-15

Previous studies have shown positive association between HIV-related stigma and depression, suicidal ideation, and suicidal attempt among people living with HIV/AIDS (PLWH). But few studies have examined the mechanisms among HIV-related stigma, depression, and suicidal status (suicidal ideation and/or suicidal attempt) in PLWH. The current study examined the relationships among perceived and internalized stigma (PIS), depression, and suicidal status among PLWH in Guangzhou, China using structural equation modeling. Cross-sectional study by convenience sampling was conducted and 411 PLWH were recruited from the Number Eight People's Hospital from March to June, 2013 in Guangzhou, China. Participants were interviewed on their PIS, depressive symptoms, suicidal status, and socio-demographic characteristics. PLWH who had had suicidal ideation and suicidal attempts since HIV diagnosis were considered to be suicidal. Structural equation model was performed to examine the direct and indirect associations of PIS and suicidal status. Indicators to evaluate goodness of fit of the structural equation model included Chi-square Statistic, Comparative Fit Index (CFI), Root Mean Square Error of Approximation (RMSEA), Standardized Root Mean Square Residual (SRMR), and Weighted Root Mean Square Residual (WRMR). More than one-third (38.4%) of the PLWH had depressive symptoms and 32.4% reported suicidal ideation and/or attempt since HIV diagnosis. The global model showed good model fit (Chi-square value = 34.42, CFI = 0.98, RMSEA = 0.03, WRMR = 0.73). Structural equation model revealed that direct pathway of PIS on suicidal status was significant (standardized pathway coefficient = 0.21), and indirect pathway of PIS on suicidal status via depression was also significant (standardized pathway coefficient = 0.24). There was a partial mediating effect of depression in the association between PIS and suicidal status. Our findings suggest that PIS is associated

Emotional Impact of a Video-Based Suicide Prevention Program on Suicidal Viewers and Suicide Survivors

Science.gov (United States)

Bryan, Craig J.; Dhillon-Davis, Luther E.; Dhillon-Davis, Kieran K.

2009-01-01

In light of continuing concerns about iatrogenic effects associated with suicide prevention efforts utilizing video-based media, the impact of emotionally-charged videos on two vulnerable subgroups--suicidal viewers and suicide survivors--was explored. Following participation in routine suicide education as a part of the U.S. Air Force Suicide…

The role of DSM-5 borderline personality symptomatology and traits in the link between childhood trauma and suicidal risk in psychiatric patients.

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Bach, Bo; Fjeldsted, Rita

2017-01-01

Childhood traumas appear to be linked to suicidal behavior. However, the factors that mediate between these two phenomena are not sufficiently understood. Recent findings suggest that borderline personality disorder (BPD) may explain some of the association. The present study investigated the potential mediating role of BPD symptomatology and traits between reported childhood trauma and suicidal risk in adult psychiatric outpatients ( N  = 124). BPD symptomatology was measured with DSM-5 Section II criterion-counts (SCID-II; Structured Clinical Interview for DSM-IV Axis II), whereas BPD traits were measured with specified DSM-5 Section III traits (PID-5; Personality Inventory for DSM-5). Childhood traumas were self-reported (CTQ; Childhood Trauma Questionnaire), whereas level of suicidal risk was measured with a structured interview (MINI Suicidality Module; Mini International Neuropsychiatric Interview). Mediation effects were tested by bias-corrected (10.000 boot-strapped samples) confidence intervals. BPD features account for a considerable part of the cross-sectional association between childhood trauma and level of suicidal risk, even when controlling for the influence of gender, age, and educational level. This finding remained stable when testing the model without the suicidality-related BPD criterion and PID-5 items. DSM-5 Section II BPD criterion-counts explained 67% of the total effect, whereas DSM-5 Section III BPD traits accounted for 82% of the total effect. The specific DSM-5 Section III trait facets of "Depressivity" (52%) and "Perceptual Dysregulation" (37%) accounted for most of this effect. The findings provide preliminary support for the proposed mediation model indicating that BPD features may help explain relations between childhood trauma and elevated suicidal risk in adult life, in particular for DSM-5 Section III personality traits of depressivity (e.g., pessimism, guilt, and shame) and perceptual dysregulation (e.g., dissociation). To

Gender differences in suicide and suicide attempts among US Army soldiers.

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Maguen, Shira; Skopp, Nancy A; Zhang, Ying; Smolenski, Derek J

2015-02-28

In order to best tailor suicide prevention initiatives and programs, it is critical to gain an understanding of how service members׳ suicide risk factors may differ by gender. We aimed to better understand gender differences in suicide and suicide attempts among soldiers, including demographic, military, mental health, and other risk factors. We also examined risk factors uniquely associated with suicide and suicide attempts. We conducted a retrospective study of 1857 US Army soldiers who died by suicide or attempted suicide between 2008 and 2010 and had a Department of Defense Suicide Event Report. Female and male soldiers had more similarities than differences when examining risk factors associated with suicide. The only gender difference approaching significance was workplace difficulties, which was more strongly associated with suicide for female soldiers, compared to their male counterparts. Among suicide decedents, the most common risk factor was having a failed intimate relationship in the 90 days prior to suicide. Among those who attempted suicide, the most common risk factor was a major psychiatric diagnosis. Better understanding both gender differences and risk factors uniquely associated with suicide has critical prevention and public health implications as we work to better understand preventable mortality in our youngest generation of service members. Published by Elsevier Ireland Ltd.

Globalization and suicide: an ecological study across five regions of the world.

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Milner, Allison; McClure, Rod; De Leo, Diego

2012-01-01

The impact of globalization on health is recognized to be influenced by country and regional-level factors. This study aimed to investigate the possible relationship between globalization and suicide in five world regions. An index measure of globalization was developed at the country level over 1980 to 2006. The association between the index and sex specific suicide rates was tested using a fixed-effect regression model. Over time, the globalization index seemed to be associated with increased suicide rates in Asia and the Eastern European/Baltic region. In contrast, it was associated with decreased rates in Scandinavia. There was no significant relationship between globalization and suicide in Southern and Western Europe. The effects of globalization could be determined by specific regional (i.e., cultural and societal) factors. Identification of these mediators might provide opportunities to protect countries from the adverse impacts of globalization.

Impacts of stress, self-efficacy, and optimism on suicide ideation among rehabilitation patients with acute pesticide poisoning.

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Feng, Jun; Li, Shusheng; Chen, Huawen

2015-01-01

The high incidence of pesticide ingestion as a means to commit suicide is a critical public health problem. An important predictor of suicidal behavior is suicide ideation, which is related to stress. However, studies on how to defend against stress-induced suicidal thoughts are limited. This study explores the impact of stress on suicidal ideation by investigating the mediating effect of self-efficacy and dispositional optimism. Direct and indirect (via self-efficacy and dispositional optimism) effects of stress on suicidal ideation were investigated among 296 patients with acute pesticide poisoning from four general hospitals. For this purpose, structural equation modeling (SEM) and bootstrap method were used. Results obtained using SEM and bootstrap method show that stress has a direct effect on suicide ideation. Furthermore, self-efficacy and dispositional optimism partially weakened the relationship between stress and suicidal ideation. The final model shows a significant relationship between stress and suicidal ideation through self-efficacy or dispositional optimism. The findings extended prior studies and provide enlightenment on how self-efficacy and optimism prevents stress-induced suicidal thoughts.

Ruminative subtypes and impulsivity in risk for suicidal behavior.

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Valderrama, Jorge; Miranda, Regina; Jeglic, Elizabeth

2016-02-28

Rumination has been previously linked to negative psychological outcomes, including depression and suicidal behavior. However, there has been conflicting research on whether or not two different subtypes of rumination - brooding and reflection - are more or less maladaptive. The present research sought to (1) examine whether individuals high in brooding but lower in reflection would show higher trait and behavioral impulsivity, relative to individuals low in brooding and low in reflection; and (2) examine impulsivity as a mediator of the relation between ruminative subtypes and suicidal ideation. In Study 1, participants (N=78) were recruited based on high, average, and low scores on a measure of brooding and reflective rumination. Individuals who scored high in brooding and average in reflection scored significantly higher in negative urgency, that is, in the tendency to act rashly in an attempt to reduce negative affect, than did those who scored low in brooding and low in reflection. Study 2 (N=1638) examined the relationship between ruminative subtypes, impulsivity, and suicide risk. We found an indirect relationship between brooding and suicide risk through lack of premeditation and lack of perseverance, independently of reflection. These findings are discussed in relation to cognitive risk for suicide. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

In vivo preclinical low field MRI monitoring of tumor growth following a suicide gene therapy in an ortho-topic mice model of human glioblastoma

International Nuclear Information System (INIS)

Breton, E.; Goetz, Ch.; Aubertin, G.; Constantinesco, A.; Choquet, Ph.; Kintz, J.; Accart, N.; Grellier, B.; Erbs, Ph.; Rooke, R.

2010-01-01

Purpose The aim of this study was to monitor in vivo with low field MRI growth of a murine ortho-topic glioma model following a suicide gene therapy. Methods The gene therapy consisted in the stereotactic injection in the mice brain of a modified vaccinia virus Ankara (M.V.A.) vector encoding for a suicide gene (FCU1) that transforms a non toxic pro-drug 5-fluoro-cytosine (5-F.C.) to its highly cytotoxic derivatives 5-fluorouracil (5-F.U.) and 5-fluoro-uridine-5 monophosphate (5-F.U.M.P.). Using a warmed-up imaging cell, sequential 3D T1 and T2 0.1T MRI brain examinations were performed on 16 Swiss female nu/nu mice bearing ortho-topic human glioblastoma (U 87-MG cells). The 6-week in vivo MRI follow-up consisted in a weekly measurement of the intracerebral tumor volume leading to a total of 65 examinations. Mice were divided in four groups: sham group (n = 4), sham group treated with 5-F.C. only (n = 4), sham group with injection of M.V.A.-FCU1 vector only (n = 4), therapy group administered with M.V.A.-FCU1 vector and 5-F.C. (n = 4). Measurements of tumor volumes were obtained after manual segmentation of T1- and T2-weighted images. Results Intra-observer and inter-observer tumor volume measurements show no significant differences. No differences were found between T1 and T2 volume tumor doubling times between the three sham groups. A significant statistical difference (p < 0.05) in T1 and T2 volume tumor doubling times between the three sham groups and the animals treated with the intratumoral injection of M.V.A.-FCU1 vector in combination with 2 weeks per os 5-F.C. administration was demonstrated. Conclusion Preclinical low field MRI was able to monitor efficacy of suicide gene therapy in delaying the tumor growth in an in vivo mouse model of ortho-topic glioblastoma. (authors)

Perfectionistic Self-Presentation, Socially Prescribed Perfectionism, and Suicide in Youth: A Test of the Perfectionism Social Disconnection Model

Science.gov (United States)

Roxborough, Heather M.; Hewitt, Paul L.; Kaldas, Janet; Flett, Gordon L.; Caelian, Carmen M.; Sherry, Simon; Sherry, Dayna L.

2012-01-01

The role of interpersonal components of perfectionism in suicide outcomes among youth was assessed and the Perfectionism Social Disconnection Model (PSDM) was tested by determining whether the links between socially prescribed perfectionism (SPP) and perfectionistic self-presentation (PSP) and suicide outcomes are mediated by experiences of social…

Co-factors necessary for PPAR mediated transactivation of endogenous target genes

DEFF Research Database (Denmark)

Grøntved, Lars; Nielsen, Ronni; Stunnenberg, Henk

of endogenous target gene in different cell types are elusive. To mutually compare the ability of the PPAR subtypes to activate endogenous target genes in a given cell, PPARa, PPARb/d and PPARg2 were HA tagged and rapidly, equally and synchronously expressed using adenoviral delivery. Within a few hours after...... subtype specific activation of target genes. Accumulating evidence suggests that transcriptional co-factors can function as master regulators for nuclear receptors and impose promoter selectivity. To study co-factor necessity for PPAR mediated transactivation of endogenous target genes, specific co...

Gene transfection mediated by polyethyleneimine-polyethylene glycol nanocarrier prevents cisplatin-induced spiral ganglion cell damage

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Guan-gui Chen

2015-01-01

Full Text Available Polyethyleneimine-polyethylene glycol (PEI-PEG, a novel nanocarrier, has been used for transfection and gene therapy in a variety of cells. In our previous study, we successfully carried out PEI-PEG-mediated gene transfer in spiral ganglion cells. It remains unclear whether PEI-PEG could be used for gene therapy with X-linked inhibitor of apoptosis protein (XIAP in the inner ear. In the present study, we performed PEI-PEG-mediated XIAP gene transfection in the cochlea of Sprague-Dawley rats, via scala tympani fenestration, before daily cisplatin injections. Auditory brainstem reflex tests demonstrated the protective effects of XIAP gene therapy on auditory function. Immunohistochemical staining revealed XIAP protein expression in the cytoplasm of cells in the spiral ganglion, the organ of Corti and the stria vascularis. Reverse transcription-PCR detected high levels of XIAP mRNA expression in the cochlea. The present findings suggest that PEI-PEG nanocarrier-mediated XIAP gene transfection results in XIAP expression in the cochlea, prevents damage to cochlear spiral ganglion cells, and protects hearing.

Investigating Gene Function in Cereal Rust Fungi by Plant-Mediated Virus-Induced Gene Silencing.

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Panwar, Vinay; Bakkeren, Guus

2017-01-01

Cereal rust fungi are destructive pathogens, threatening grain production worldwide. Targeted breeding for resistance utilizing host resistance genes has been effective. However, breakdown of resistance occurs frequently and continued efforts are needed to understand how these fungi overcome resistance and to expand the range of available resistance genes. Whole genome sequencing, transcriptomic and proteomic studies followed by genome-wide computational and comparative analyses have identified large repertoire of genes in rust fungi among which are candidates predicted to code for pathogenicity and virulence factors. Some of these genes represent defence triggering avirulence effectors. However, functions of most genes still needs to be assessed to understand the biology of these obligate biotrophic pathogens. Since genetic manipulations such as gene deletion and genetic transformation are not yet feasible in rust fungi, performing functional gene studies is challenging. Recently, Host-induced gene silencing (HIGS) has emerged as a useful tool to characterize gene function in rust fungi while infecting and growing in host plants. We utilized Barley stripe mosaic virus-mediated virus induced gene silencing (BSMV-VIGS) to induce HIGS of candidate rust fungal genes in the wheat host to determine their role in plant-fungal interactions. Here, we describe the methods for using BSMV-VIGS in wheat for functional genomics study in cereal rust fungi.

Co-Targeting Prostate Cancer Epithelium and Bone Stroma by Human Osteonectin-Promoter-Mediated Suicide Gene Therapy Effectively Inhibits Androgen-Independent Prostate Cancer Growth.

Directory of Open Access Journals (Sweden)

Shian-Ying Sung

Full Text Available Stromal-epithelial interaction has been shown to promote local tumor growth and distant metastasis. We sought to create a promising gene therapy approach that co-targets cancer and its supporting stromal cells for combating castration-resistant prostate tumors. Herein, we demonstrated that human osteonectin is overexpressed in the prostate cancer epithelium and tumor stroma in comparison with their normal counterpart. We designed a novel human osteonectin promoter (hON-522E containing positive transcriptional regulatory elements identified in both the promoter and exon 1 region of the human osteonectin gene. In vitro reporter assays revealed that the hON-522E promoter is highly active in androgen receptor negative and metastatic prostate cancer and bone stromal cells compared to androgen receptor-positive prostate cancer cells. Moreover, in vivo prostate-tumor-promoting activity of the hON-522E promoter was confirmed by intravenous administration of an adenoviral vector containing the hON-522E promoter-driven luciferase gene (Ad-522E-Luc into mice bearing orthotopic human prostate tumor xenografts. In addition, an adenoviral vector with the hON-522E-promoter-driven herpes simplex virus thymidine kinase gene (Ad-522E-TK was highly effective against the growth of androgen-independent human prostate cancer PC3M and bone stromal cell line in vitro and in pre-established PC3M tumors in vivo upon addition of the prodrug ganciclovir. Because of the heterogeneity of human prostate tumors, hON-522E promoter-mediated gene therapy has the potential for the treatment of hormone refractory and bone metastatic prostate cancers.

Social networking sites and mental health problems in adolescents: The mediating role of cyberbullying victimization.

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Sampasa-Kanyinga, H; Hamilton, H A

2015-11-01

Previous research has suggested an association between the use of social networking sites (SNSs) and mental health problems such as psychological distress, suicidal ideation and attempts in adolescents. However, little is known about the factors that might mediate these relationships. The present study examined the link between the use of social networking sites and psychological distress, suicidal ideation and suicide attempts, and tested the mediating role of cyberbullying victimization on these associations in adolescents. The sample consisted of a group of 11-to-20-year-old individuals (n=5126, 48% females; mean±SD age: 15.2±1.9 years) who completed the mental health portion of the Ontario Student Drug Use and Health Survey (OSDUHS) in 2013. Multiple logistic regression analyses were used to test the mediation models. After adjustment for age, sex, ethnicity, subjective socioeconomic status (SES), and parental education, use of SNSs was associated with psychological distress (adjusted odds ratio, 95% confidence interval=2.03, 1.22-3.37), suicidal ideation (3.44, 1.54-7.66) and attempts (5.10, 1.45-17.88). Cyberbullying victimization was found to fully mediate the relationships between the use of SNSs with psychological distress and attempts; whereas, it partially mediated the link between the use of SNSs and suicidal ideation. Findings provide supporting evidence that addressing cyberbullying victimization and the use of SNSs among adolescents may help reduce the risk of mental health problems. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Experimental research on treating hepatic carcinoma by arterial injection of liposome mediated p53 genes

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Guangyu, Zhu; Qin, Lu; Gaojun, Teng; Jinhe, Guo; Hui, Yu; Gang, Deng; Shicheng, He; Wen, Fang; Guozhao, Li; Xiaoying, Wei [Zhongda Hospital, Southeast Univ., Nanjing (China)

2007-02-15

Objective: To investigate the transfection and expression of p53 genes mediated by liposome and its feasibility in treatment of liver cancer by transcatheter arterial injection on rabbit VX2 hepatocarcinoma model. Methods: pCMV-myc-p53 plasmids, LipofectAMINE and p53-LipofectAMINE complex were infused into tumor's feeding artery of rabbit VX2 hepatocarcinoma model, respectively, and then protein of cancer tissue was extracted, followed by measuring gene transfection and expression by western blot and immunohistochemistry, p53-LipofectAMlNE complex in different doses were infused into tumor's feeding artery of rabbit VX2 hepatocarcinoma model with the gene transfection and expression detected by the same way. Results: Liposome-mediated p53 gene injected through catheter could be successfully transfected and expressed in the cancer tissue of rabbit VX2 hepatocarcinoma model, with transfection efficiency higher than the gene delivery alone. The efficiency and the gene dose has dose-effect relationship. Conclusions: Treatment of liver cancer by transcatheter arterial injection of p53 genes mediated by liposome is a feasible and effective method, with wide prospect of application. (authors)

Experimental research on treating hepatic carcinoma by arterial injection of liposome mediated p53 genes

International Nuclear Information System (INIS)

Zhu Guangyu; Lu Qin; Teng Gaojun; Guo Jinhe; Yu Hui; Deng Gang; He Shicheng; Fang Wen; Li Guozhao; Wei Xiaoying

2007-01-01

Objective: To investigate the transfection and expression of p53 genes mediated by liposome and its feasibility in treatment of liver cancer by transcatheter arterial injection on rabbit VX2 hepatocarcinoma model. Methods: pCMV-myc-p53 plasmids, LipofectAMINE and p53-LipofectAMINE complex were infused into tumor's feeding artery of rabbit VX2 hepatocarcinoma model, respectively, and then protein of cancer tissue was extracted, followed by measuring gene transfection and expression by western blot and immunohistochemistry, p53-LipofectAMlNE complex in different doses were infused into tumor's feeding artery of rabbit VX2 hepatocarcinoma model with the gene transfection and expression detected by the same way. Results: Liposome-mediated p53 gene injected through catheter could be successfully transfected and expressed in the cancer tissue of rabbit VX2 hepatocarcinoma model, with transfection efficiency higher than the gene delivery alone. The efficiency and the gene dose has dose-effect relationship. Conclusions: Treatment of liver cancer by transcatheter arterial injection of p53 genes mediated by liposome is a feasible and effective method, with wide prospect of application. (authors)