198 research outputs found
Analysis of Kinase Gene Expression in the Frontal Cortex of Suicide Victims: Implications of Fear and Stress†
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 Database1 and a quantitative PCR, we investigated the expression profiles of multiple kinase genes including the calcium calmodulin-dependent kinase (CAMK), the cyclin-dependent kinase, 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 (false discovery rate, 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
Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation
Post-traumatic stress disorder (PTSD), characterized by abnormally persistent and distressing memories, is a chronic debilitating condition in need of new treatment options. Current treatment guidelines recommend psychotherapy as first line management with only two drugs, sertraline and paroxetine, approved by U.S. Food and Drug Administration (FDA) for treatment of PTSD. These drugs have limited efficacy as they only reduce symptoms related to depression and anxietywithout producing permanent remission. PTSD remains a significant public health problem with high morbidity and mortality requiring major advances in therapeutics. Early evidence
has emerged for the beneficial effects of psychedelics particularly in combination with psychotherapy for management of PTSD, including psilocybin,MDMA, LSD, cannabinoids, ayahuasca and ketamine. MDMA and psilocybin reduce barrier to therapy by increasing trust between therapist and patient, thus allowing for modification of
trauma related memories. Furthermore, research into the memory reconsolidation mechanisms has allowed for identification of various pharmacological targets to disrupt abnormally persistent memories. A number of preclinical and clinical studies have investigated novel and re-purposed pharmacological agents to disrupt fear
memory in PTSD. Novel therapeutic approaches like neuropeptide Y, oxytocin, cannabinoids and neuroactive steroids have also shown potential for PTSD treatment. Here,we focus on the role of fear memory in the pathophysiology of PTSD and propose that many of these newtherapeutic strategies produce benefits through the effect on
fear memory. Evaluation of recent research findings suggests that while a number of drugs have shown promising results in preclinical studies and pilot clinical trials, the evidence from large scale clinical trials would be needed for these drugs to be incorporated in clinical practice
Attention Deficit Hyperactivity Disorder and Risk of Posttraumatic Stress and Related Disorders: A Prospective Longitudinal Evaluation in U.S. Army Soldiers
Crossâ sectional associations between attention deficit hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) have been observed, but longitudinal studies assessing this association are lacking. This prospective study evaluated the association between predeployment ADHD and postdeployment PTSD among U.S. Army soldiers. Soldiers who deployed to Afghanistan were surveyed before deployment (T0) and approximately 1 month (T1), 3 months (T2), and 9 months (T3) after their return. Logistic regression was performed to estimate the association between predeployment ADHD and postdeployment (T2 or T3) PTSD among 4,612 soldiers with data at all waves and no record of stimulant medication treatment during the study. To evaluate specificity of the ADHDâ PTSD association, we examined associations among predeployment ADHD, postdeployment major depressive episode (MDE), generalized anxiety disorder (GAD), and suicidal ideation. Weighted prevalence of ADHD predeployment was 6.1% (SE = 0.4%). Adjusting for other risk factors, predeployment ADHD was associated with risk of postdeployment PTSD, adjusted odds ratio (AOR) = 2.13, 95% CI [1.51, 3.00], p < .001, including incidence among soldiers with no predeployment history of PTSD, AOR = 2.50, 95% CI [1.69, 3.69], p < .001. ADHD was associated with postdeployment MDE, AOR = 2.80, 95% CI [2.01, 3.91], p < .001, and GAD, AOR = 3.04, 95% CI [2.10, 4.42], p < .001, but not suicidal ideation. Recognition of associations between predeployment ADHD and postdeployment PTSD, MDE, and GAD may inform targeted prevention efforts. Future research should examine whether treatment of ADHD is protective against PTSD and related disorders in traumaâ exposed individuals.ResumenSpanish Abstracts by Asociación Chilena de Estrés Traumático (ACET)El trastorno de déficit atencional con hiperactividad y el riesgo del trastorno de estrés postraumático y trastornos relacionados: Una evaluación longitudinal prospectiva en soldados del ejército estadounidenseTDAH Y RIESGO DE TEPT EN SOLDADOS DEL EJà RCITO DE EE.UU.Se han observado asociaciones transversales entre el trastorno por déficit de atención con hiperactividad (TDAH) y el trastorno por estrés postraumático (TEPT), pero faltan estudios longitudinales que evalúen esta asociación. Este estudio prospectivo evaluó la asociación entre el TDAH previo al despliegue y el TEPT posterior al despliegue entre los soldados del Ejército de Estados Unidos. Los soldados desplegados en Afganistán fueron encuestados antes del despliegue (T0) y aproximadamente 1 mes (T1), 3 meses (T2), y 9 meses (T3) después de su regreso del despliegue. Se realizó una regresión logÃstica para estimar la asociación entre el TDAH previo al despliegue y el TEPT posterior al despliegue (T2 o T3) en 4.612 soldados con datos en todas las etapas y sin registro de tratamiento con medicamentos estimulantes durante el estudio. Para evaluar la especificidad de la asociación TDAHâ TEPT, examinamos las asociaciones entre el TDAH previo al despliegue, el episodio depresivo mayor posterior al despliegue (EDM), el trastorno de ansiedad generalizada (TAG), y la ideación suicida. La prevalencia ponderada del TDAH previo al despliegue fue de 6.1% (SE = 0.4%). Al controlar los otros factores de riesgo, el TDAH previo al despliegue se asoció con el riesgo de TEPT posterior al despliegue, odds ratio ajustado (AOR en su sigla en inglés) = 2.13, IC del 95% [1.51, 3.00], p <.001, incluida la incidencia entre soldados sin historial previo al despliegue de TEPT, AOR = 2.50, IC del 95% [1.69, 3.69], p <.001. El TDAH se asoció con el EDM posterior al despliegue, AOR = 2.80, IC del 95% [2.01, 3.91], p <.001, y TAG, AOR = 3.04, IC del 95% [2.10, 4.42], p <.001, pero no con ideación suicida. El reconocimiento de las asociaciones entre el TDAH previo al despliegue y el TEPT, el EDM, y el TAG posterior al despliegue puede informar los esfuerzos de prevención especÃficos. Las investigaciones futuras deberÃan examinar si el tratamiento del TDAH protege contra el TEPT y los trastornos relacionados en personas expuestas a trauma.æ ½è±¡Traditional and Simplified Chinese Abstracts by the Asian Society for Traumatic Stress Studies (AsianSTSS)ç°¡é« å ç¹ é« ä¸æ æ ®è¦ ç ±äº æ´²å µå ·å¿ ç ç 究å¸æ ç¿»è¯Attention Deficit Hyperactivity Disorder and Risk of Posttraumatic Stress and Related Disorders: A Prospective Longitudinal Evaluation in US Army SoldiersTraditional Chineseæ¨ é¡ : å° æ³¨å ä¸ è¶³æ é åº¦æ´»èº ç è æ £å µå ·å¾ å£ å ç å ç ¸é ç ¾ç ç é¢¨é ª:å° ç¾ å è» äººé ²è¡ ç å ç »ç¸±è²«ç ç©¶æ ®è¦ : é å¾ ä¸ ç ´æ ç ç©¶æª¢è¦ å° æ³¨å ä¸ è¶³æ é åº¦æ´»èº ç (ADHD)è å µå ·å¾ å£ å ç (PTSD)ä¹ é ç æ©«æ ·æ §é é £, å ¯æ ¯, æ å ä» æ¬ ç¼ºæª¢è¦ å ©è é é £ç 縱貫ç 究ã æ ¬å ç »ç ç©¶æ ¨å ¨é é ç¾ è» æ¨£æ ¬, è© ä¼°æ å½¹å ADHDè· æ å½¹å¾ PTSDç é é £ã æ¨£æ ¬ç ºå å¾ é ¿å¯ æ± æ å½¹ç è» äºº, å ¨æ å½¹å (T0)å å® æ æ å½¹å¾ ç´ 1å æ (T1)ã 3å æ (T2)å 9å æ (T3)æ ¥å èª¿æ ¥ã æ å 以é 輯迴æ¸å æ å æ æ 波段ç æ ¸æ , ä¼°è¨ 4,612å è» äººæ å½¹å ADHDè· æ å½¹å¾ (T2 æ T3)PTSDç é é £ã ç 究ä¸, æ¨£æ ¬ä¸¦ç ¡æ ç ¨è å¥®è ¥ç ©ã ç ºäº è§£ADHDâ PTSDç ç ¹æ® é é £, æ å æª¢è¦ ä»¥ä¸ é ç ®ä¹ é ç é é £:æ å½¹å ADHDã å® æ æ å½¹å¾ ç å ´é æ é¬±ç¯ æ®µ(MDE)ã å»£æ³ æ §ç ¦æ ®ç (GAD)ã è ªæ®ºæ 念ã æ å½¹å ADHDæ ®é åº¦ç º6.1% (SE = 0.4%)ã å° å ¶ä» é¢¨é ªå ç´ ä½ èª¿ç¯ å¾ , æ å½¹å ADHDè· æ å½¹å¾ æ £PTSDç é¢¨é ªæ æ é é £(å·²èª¿ç¯ å ç® æ¯ (AOR) = 2.13, 95% CI [1.51, 3.00], p < .001), ç ¶ä¸å æ ¬æ å½¹å ä¸¦ç ¡PTSDç è» äºº(AOR = 2.50, 95% CI [1.69, 3.69], p < .001)ã ADHDè· å® æ æ å½¹å¾ æ £MDEç (AOR = 2.80, 95% CI [2.01, 3.91], p < .001)å GAD(AOR = 3.04, 95% CI [2.10, 4.42] p < .001)é ½æ é , ä½ è· è ªæ®ºæ å¿µç ¡é ã äº è§£æ å½¹å ADHDè· æ å½¹å¾ PTSDã MDEå GADç é é £, å ¯è ½æ å ©ç ¼å± é å° æ §ç é é ²å·¥ä½ ã æ ªä¾ ç 究æ æª¢è¦ å° å å µäººå£«æ ä¾ ADHDæ²»ç , æ ¯å ¦å° å ¶PTSDå ç ¸é ç ¾ç æ ä¿ è·æ æ ã Simplified Chineseæ é¢ : ä¸ æ³¨å ä¸ è¶³æ è¿ åº¦æ´»è· ç ä¸ æ £å 伤å å å ç å ç ¸å ³ç ¾ç ç é£ é ©:å¯¹ç¾ å ½å äººè¿ è¡ ç å ç »çºµè´¯ç ç©¶æ ®è¦ : è¿ å¾ ä¸ ç ´æ ç ç©¶æ£ è§ ä¸ æ³¨å ä¸ è¶³æ è¿ åº¦æ´»è· ç (ADHD)ä¸ å 伤å å å ç (PTSD)ä¹ é ´ç 横æ æ §å ³è¿ , å ¯æ ¯, æ ä»¬ä» æ¬ ç¼ºæ£ è§ ä¸¤è å ³è¿ ç 纵贯ç 究ã æ ¬å ç »ç ç©¶æ ¨å ¨é è¿ ç¾ å æ ·æ ¬, è¯ ä¼°æ å½¹å ADHDè· æ å½¹å PTSDç å ³è¿ ã æ ·æ ¬ä¸ºå å¾ é ¿å¯ æ± æ å½¹ç å 人, å ¨æ å½¹å (T0)å å® æ æ å½¹å 约1个æ (T1)ã 3个æ (T2)å 9个æ (T3)æ ¥å è° æ ¥ã æ ä»¬ä»¥é »è¾ å å½ å æ å æ æ 波段ç æ °æ ®, 估计4,612å å 人æ å½¹å ADHDè· æ å½¹å (T2 æ T3)PTSDç å ³è¿ ã ç 究ä¸, æ ·æ ¬å¹¶æ æ ç ¨å ´å¥ è ¯ç ©ã ä¸ºäº è§£ADHDâ PTSDç ç ¹æ® å ³è¿ , æ ä»¬æ£ è§ ä»¥ä¸ é¡¹ç ®ä¹ é ´ç å ³è¿ :æ å½¹å ADHDã å® æ æ å½¹å ç 严é æ é è 段(MDE)ã å¹¿æ³ æ §ç ¦è ç (GAD)ã è ªæ æ 念ã æ å½¹å ADHDæ ®é 度为6.1% (SE = 0.4%)ã å¯¹å ¶ä» é£ é ©å ç´ ä½ è° è å , æ å½¹å ADHDè· æ å½¹å æ £PTSDç é£ é ©æ æ å ³è¿ (å·²è° è è ç® æ¯ (AOR) = 2.13, 95% CI [1.51, 3.00], p < .001), å½ ä¸å æ ¬æ å½¹å 并æ PTSDç å 人(AOR = 2.50, 95% CI [1.69, 3.69], p < .001)ã ADHDè· å® æ æ å½¹å æ £MDEç (AOR = 2.80, 95% CI [2.01, 3.91], p < .001)å GAD(AOR = 3.04, 95% CI [2.10, 4.42] p < .001)é ½æ å ³, ä½ è· è ªæ æ 念æ å ³ã äº è§£æ å½¹å ADHDè· æ å½¹å PTSDã MDEå GADç å ³è¿ , å ¯è ½æ å ©å å± é å¯¹æ §ç é¢ é ²å·¥ä½ ã æ ªæ ¥ç ç©¶åº æ£ è§ å¯¹å å 人士æ ä¾ ADHDæ²»ç , æ ¯å ¦å¯¹å ¶PTSDå ç ¸å ³ç ¾ç æ ä¿ æ ¤æ åº ãPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146971/1/jts22347_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146971/2/jts22347.pd
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A genome-wide gene-by-trauma interaction study of alcohol misuse in two independent cohorts identifies PRKG1 as a risk locus
Traumatic life experiences are associated with alcohol use problems, an association that is likely to be moderated by genetic predisposition. To understand these interactions, we conducted a gene-by-environment genome-wide interaction study (GEWIS) of alcohol use problems in two independent samples, the Army STARRS (ASTARRS, N=16,361) and the Yale-Penn (N=8,084) cohorts. Because the two cohorts were assessed using different instruments, we derived separate dimensional alcohol misuse scales and applied a proxy-phenotype study design. In African-American subjects, we identified an interaction of PRKG1 rs1729578 with trauma exposure in the ASTARRS cohort and replicated its interaction with trauma exposure in the Yale-Penn cohort (discovery-replication meta-analysis: z=5.64, p=1.69*10−8). PRKG1 encodes cGMP-dependent protein kinase 1, which is involved in learning, memory, and circadian rhythm regulation. Considering the loci identified in stage-1 that showed same effect directions in stage-2, the gene ontology (GO) enrichment analysis showed several significant results, including calcium-activated potassium channels (GO:0016286; p=2.30*10−5), cognition (GO:0050890; p=1.90*10−6), locomotion (GO:0040011; p=6.70*10−5), and Stat3 protein regulation (GO:0042517; p=6.4*10−5). To our knowledge, this is the largest GEWIS performed in psychiatric genetics, and the first GEWIS examining risk for alcohol misuse. Our results add to a growing body of literature highlighting the dynamic impact of experience on individual genetic risk
Salud mental en la comunidad en situaciones de desastre. Una revisión de los modelos de abordaje en la comunidad
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Understanding the elevated suicide risk of female soldiers during deployments
Background
The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) has found that the proportional elevation in the US Army enlisted soldier suicide rate during deployment (compared with the never-deployed or previously deployed) is significantly higher among women than men, raising the possibility of gender differences in the adverse psychological effects of deployment.
Method
Person-month survival models based on a consolidated administrative database for active duty enlisted Regular Army soldiers in 2004–2009 (n = 975 057) were used to characterize the gender × deployment interaction predicting suicide. Four explanatory hypotheses were explored involving the proportion of females in each soldier’s occupation, the proportion of same-gender soldiers in each soldier’s unit, whether the soldier reported sexual assault victimization in the previous 12 months, and the soldier’s pre-deployment history of treated mental/behavioral disorders.
Results
The suicide rate of currently deployed women (14.0/100 000 person-years) was 3.1–3.5 times the rates of other (i.e. never-deployed/previously deployed) women. The suicide rate of currently deployed men (22.6/100 000 person-years) was 0.9–1.2 times the rates of other men. The adjusted (for time trends, sociodemographics, and Army career variables) female:male odds ratio comparing the suicide rates of currently deployed v. other women v. men was 2.8 (95% confidence interval 1.1–6.8), became 2.4 after excluding soldiers with Direct Combat Arms occupations, and remained elevated (in the range 1.9–2.8) after adjusting for the hypothesized explanatory variables.
Conclusions
These results are valuable in excluding otherwise plausible hypotheses for the elevated suicide rate of deployed women and point to the importance of expanding future research on the psychological challenges of deployment for women.Psycholog
A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder
Background: The nature and underlying mechanisms of the observed increased vulnerability to posttraumatic stress disorder (PTSD) in women are unclear. Methods: We investigated the genetic overlap of PTSD with anthropometric traits and reproductive behaviors and functions in women. The analysis was conducted using female-specific summary statistics from large genome-wide association studies (GWAS) and a cohort of 3577 European American women (966 PTSD cases and 2611 trauma-exposed controls). We applied a high-resolution polygenic score approach and Mendelian randomization analysis to investigate genetic correlations and causal relationships. Results: We observed an inverse association of PTSD with genetically determined anthropometric traits related to body shape, independent of body mass index (BMI). The top association was related to BMI-adjusted waist circumference (WCadj; R = -0.079, P < 0.001, Q = 0.011). We estimated a relative decrease of 64.6% (95% confidence interval = 27.5-82.7) in the risk of PTSD per 1-SD increase in WCadj. MR-Egger regression intercept analysis showed no evidence of pleiotropic effects in this association (Ppleiotropy = 0.979). We also observed associations of genetically determined WCadj with age at first sexual intercourse and number of sexual partners (P = 0.013 and P < 0.001, respectively). Conclusions: There is a putative causal relationship between genetically determined female body shape and PTSD, which could be mediated by evolutionary mechanisms involved in human sexual behaviors
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Sociodemographic and career history predictors of suicide mortality in the United States Army 2004–2009
The US Army suicide rate has increased sharply in recent years. Identifying significant predictors of Army suicides in Army and Department of Defense (DoD) administrative records might help focus prevention efforts and guide intervention content. Previous studies of administrative data, although documenting significant predictors, were based on limited samples and models. A career history perspective is used here to develop more textured models.
The analysis was carried out as part of the Historical Administrative Data Study (HADS) of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). De-identified data were combined across numerous Army and DoD administrative data systems for all Regular Army soldiers on active duty in 2004–2009. Multivariate associations of sociodemographics and Army career variables with suicide were examined in subgroups defined by time in service, rank and deployment history.
Several novel results were found that could have intervention implications. The most notable of these were significantly elevated suicide rates (69.6–80.0 suicides per 100 000 person-years compared with 18.5 suicides per 100 000 person-years in the total Army) among enlisted soldiers deployed either during their first year of service or with less than expected (based on time in service) junior enlisted rank; a substantially greater rise in suicide among women than men during deployment; and a protective effect of marriage against suicide only during deployment.
A career history approach produces several actionable insights missed in less textured analyses of administrative data predictors. Expansion of analyses to a richer set of predictors might help refine understanding of intervention implications.Psycholog
Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability.
The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (
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