National Center for at Boston Healthcare System

Boston, MA, United States

National Center for at Boston Healthcare System

Boston, MA, United States
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Nievergelt C.M.,University of California at San Diego | Maihofer A.X.,University of California at San Diego | Mustapic M.,University of California at San Diego | Schork N.J.,J. Craig Venter Institute | And 7 more authors.
Psychoneuroendocrinology | Year: 2015

Background: Research on the etiology of post-traumatic stress disorder (PTSD) has rapidly matured, moving from candidate gene studies to interrogation of the entire human genome in genome-wide association studies (GWAS). Here we present the results of a GWAS performed on samples from combat-exposed U.S. Marines and Sailors from the Marine Resiliency Study (MRS) scheduled for deployment to Iraq and/or Afghanistan. The MRS is a large, prospective study with longitudinal follow-up designed to identify risk and resiliency factors for combat-induced stress-related symptoms. Previously implicated PTSD risk loci from the literature and polygenic risk scores across psychiatric disorders were also evaluated in the MRS cohort. Methods: Participants (. N=. 3494) were assessed using the Clinician-Administered PTSD Scale and diagnosed using the DSM-IV diagnostic criterion. Subjects with partial and/or full PTSD diagnosis were called cases, all other subjects were designated controls, and study-wide maximum CAPS scores were used for longitudinal assessments. Genomic DNA was genotyped on the Illumina HumanOmniExpressExome array. Individual genetic ancestry was determined by supervised cluster analysis for subjects of European, African, Hispanic/Native American, and other descent. To test for association of SNPs with PTSD, logistic regressions were performed within each ancestry group and results were combined in meta-analyses. Measures of childhood and adult trauma were included to test for gene-by-environment (GxE) interactions. Polygenic risk scores from the Psychiatric Genomic Consortium were used for major depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia (SCZ). Results: The array produced >800K directly genotyped and >21M imputed markers in 3494 unrelated, trauma-exposed males, of which 940 were diagnosed with partial or full PTSD. The GWAS meta-analysis identified the phosphoribosyl transferase domain containing 1 gene (PRTFDC1) as a genome-wide significant PTSD locus (rs6482463; OR=1.47, SE=0.06, p=2.04×10-9), with a similar effect across ancestry groups. Association of PRTFDC1 with PTSD in an independent military cohort showed some evidence for replication. Loci with suggestive evidence of association (n=25 genes, p<5×10-6) further implicated genes related to immune response and the ubiquitin system, but these findings remain to be replicated in larger GWASs. A replication analysis of 25 putative PTSD genes from the literature found nominally significant SNPs for the majority of these genes, but associations did not remain significant after correction for multiple comparison. A cross-disorder analysis of polygenic risk scores from GWASs of BPD, MDD, and SCZ found that PTSD diagnosis was associated with risk sores of BPD, but not with MDD or SCZ. Conclusions: This first multi-ethnic/racial GWAS of PTSD highlights the potential to increase power through meta-analyses across ancestry groups. We found evidence for PRTFDC1 as a potential novel PTSD gene, a finding that awaits further replication. Our findings indicate that the genetic architecture of PTSD may be determined by many SNPs with small effects, and overlap with other neuropsychiatric disorders, consistent with current findings from large GWAS of other psychiatric disorders. © 2014 .


Kilpatrick D.G.,Medical University of South Carolina | Resnick H.S.,Medical University of South Carolina | Milanak M.E.,Medical University of South Carolina | Miller M.W.,National Center for at Boston Healthcare System | And 3 more authors.
Journal of Traumatic Stress | Year: 2013

Prevalence of posttraumatic stress disorder (PTSD) defined according to the American Psychiatric Association's Diagnostic and Statistical Manual fifth edition (DSM-5; 2013) and fourth edition (DSM-IV; 1994) was compared in a national sample of U.S. adults (N = 2,953) recruited from an online panel. Exposure to traumatic events, PTSD symptoms, and functional impairment were assessed online using a highly structured, self-administered survey. Traumatic event exposure using DSM-5 criteria was high (89.7%), and exposure to multiple traumatic event types was the norm. PTSD caseness was determined using Same Event (i.e., all symptom criteria met to the same event type) and Composite Event (i.e., symptom criteria met to a combination of event types) definitions. Lifetime, past-12-month, and past 6-month PTSD prevalence using the Same Event definition for DSM-5 was 8.3%, 4.7%, and 3.8% respectively. All 6 DSM-5 prevalence estimates were slightly lower than their DSM-IV counterparts, although only 2 of these differences were statistically significant. DSM-5 PTSD prevalence was higher among women than among men, and prevalence increased with greater traumatic event exposure. Major reasons individuals met DSM-IV criteria, but not DSM-5 criteria were the exclusion of nonaccidental, nonviolent deaths from Criterion A, and the new requirement of at least 1 active avoidance symptom. © 2013 International Society for Traumatic Stress Studies.


Wolf E.J.,National Center for at Boston Healthcare System | Wolf E.J.,Boston University | Harrington K.M.,VA Boston Healthcare System | Reardon A.F.,National Center for at Boston Healthcare System | And 5 more authors.
Journal of Traumatic Stress | Year: 2013

This study used structural equation modeling to evaluate a mediation model of the relationship between trauma exposure, posttraumatic stress disorder (PTSD) symptoms, and perpetration of intimate partner physical and psychological aggression in trauma-exposed veterans and their cohabitating spouses (n = 286 couples; 88% male veteran and female spouse, 80.8% White, non-Hispanic). Dyadic data analyses were used to simultaneously evaluate actor and partner effects using the actor-partner interdependence model (Kashy & Kenny, 2000). The primary hypothesis was that PTSD would mediate the association between trauma exposure and intimate partner physical and psychological aggression with these effects evident both within and across members of a couple (i.e., actor and partner effects). The best-fitting model included (a) equivalent actor and partner direct effects of trauma on veterans' acts of psychological aggression (β = .17 to .20, p = .001), and (b) equivalent actor and partner indirect effects via PTSD on veterans' acts of physical aggression (β = .08 to .10, p < .001). There were no direct or indirect effects predicting the spouses' aggression. Results suggest it is important to consider the trauma histories and possible presence of PTSD in both partners as this may be a point of intervention when treating distressed couples. © 2013 International Society for Traumatic Stress Studies.


PubMed | University of Michigan, Boston College, University of Washington, Fairfield University and 14 more.
Type: Journal Article | Journal: Depression and anxiety | Year: 2016

According to current treatment guidelines for Complex PTSD (cPTSD), psychotherapy for adults with cPTSD should start with a stabilization phase. This phase, focusing on teaching self-regulation strategies, was designed to ensure that an individual would be better able to tolerate trauma-focused treatment. The purpose of this paper is to critically evaluate the research underlying these treatment guidelines for cPTSD, and to specifically address the question as to whether a phase-based approach is needed. As reviewed in this paper, the research supporting the need for phase-based treatment for individuals with cPTSD is methodologically limited. Further, there is no rigorous research to support the views that: (1) a phase-based approach is necessary for positive treatment outcomes for adults with cPTSD, (2) front-line trauma-focused treatments have unacceptable risks or that adults with cPTSD do not respond to them, and (3) adults with cPTSD profit significantly more from trauma-focused treatments when preceded by a stabilization phase. The current treatment guidelines for cPTSD may therefore be too conservative, risking that patients are denied or delayed in receiving conventional evidence-based treatments from which they might profit.


Logue M.W.,Boston University | Baldwin C.,Boston University | Guffanti G.,Columbia University | Melista E.,Boston University | And 9 more authors.
Molecular Psychiatry | Year: 2013

We describe the results of the first genome-wide association study (GWAS) of post-traumatic stress disorder (PTSD) performed using trauma-exposed white non-Hispanic participants from a cohort of veterans and their intimate partners (295 cases and 196 controls). Several single-nucleotide polymorphisms (SNPs) yielded evidence of association. One SNP (rs8042149), located in the retinoid-related orphan receptor alpha gene (RORA), reached genome-wide significance. Nominally significant associations were observed for other RORA SNPs in two African-American replication samples - one from the veteran cohort (43 cases and 41 controls) and another independent cohort (100 cases and 421 controls). However, only the associated SNP from the veteran African-American replication sample survived gene-level multiple-testing correction. RORA has been implicated in prior GWAS studies of psychiatric disorders and is known to have an important role in neuroprotection and other behaviorally relevant processes. This study represents an important step toward identifying the genetic underpinnings of PTSD. © 2013 Macmillan Publishers Limited.


Mitchell K.S.,National Center for at Boston Healthcare System | Mitchell K.S.,Boston University | Aiello A.E.,University of Michigan | Galea S.,Columbia University | And 3 more authors.
General Hospital Psychiatry | Year: 2013

Objective: Posttraumatic stress disorder (PTSD) has been associated with adverse health consequences, including overweight, obesity and cardiovascular disease. African Americans, particularly women, have among the highest rates of overweight and obesity in the U.S. compared to other racial groups. High rates of violence exposure in urban African Americans may lead to the development of PTSD and increase risk for overweight and obesity. The current study investigated the comorbidity of lifetime PTSD and overweight/obesity in a population-based African American, urban sample. Method: Data were from 463 African American male and female participants of the Detroit Neighborhood Health Study. Multivariable logistic regression models estimated the impact of lifetime PTSD on risk for overweight and obesity. Results: The prevalence of obesity was significantly higher among women (60.9%) than men (33.1%; P< .001). In sex-stratified models, after controlling for demographic variables, PTSD was associated obesity (odds ratio=4.4, 95% confidence interval: 1.3, 14.3) only among women. Conclusions: PTSD was associated with obesity, after controlling for confounding variables, among African American women. Results underscore the contribution of PTSD to obesity among African American women and the importance of addressing the physical health correlates of women with PTSD. © 2013.


Miller M.W.,Boston University | Miller M.W.,National Center for at Boston Healthcare System | Wolf E.J.,Boston University | Wolf E.J.,National Center for at Boston Healthcare System | And 4 more authors.
Journal of Anxiety Disorders | Year: 2012

This study examined the structure of PTSD comorbidity and its relationship to personality in a sample of 214 veterans using data from diagnostic interviews and the Multidimensional Personality Questionnaire-Brief Form (MPQ-BF; . Patrick, Curtin, & Tellegen, 2002). Confirmatory factor analyses supported a three factor model composed of Externalizing, Fear and Distress factors. Analyses that examined the location of borderline personality disorder revealed significant cross-loadings for this disorder on both Externalizing and Distress. Structural equation models showed trait negative emotionality to be significantly related to all three comorbidity factors whereas positive emotionality and constraint evidenced specific associations with Distress and Externalizing, respectively. These results shed new light on the location of borderline personality disorder within the internalizing/externalizing model and clarify the relative influence of broad dimensions of personality on patterns of comorbidity. © 2012 .


Miller M.W.,National Center for at Boston Healthcare System | Miller M.W.,Boston University | Wolf E.J.,National Center for at Boston Healthcare System | Wolf E.J.,Boston University | And 2 more authors.
Journal of Affective Disorders | Year: 2013

Background This study followed on findings from a recent genome-wide association study of PTSD that implicated the retinoid-related orphan receptor alpha (RORA) gene (Logue et al.; 2012) by examining its relationship to broader array of disorders. Methods Using data from the same cohort (N=540), we analyzed patterns of association between 606 single nucleotide polymorphisms (SNPs) spanning the RORA gene and comorbidity factors termed fear, distress (i.e.; internalizing factors) and externalizing. Results Results showed that rs17303244 was associated with the fear component of internalizing (i.e.; defined by symptoms of panic, agoraphobia, specific phobia, and obsessive-compulsive disorder) at a level of significance that withstood correction for gene-wide multiple testing. Limitations The primary limitations were the modest size of the cohort and the absence of a replication sample. Conclusions Results add to a growing literature implicating the RORA gene in a wide range of neuropsychiatric disorders and offer new insight into possible molecular mechanisms of the effects of traumatic stress on the brain and the role of genetic factors in those processes.


Mathew A.R.,Medical University of South Carolina | Cook J.W.,University of Wisconsin - Madison | Japuntich S.J.,National Center for at Boston Healthcare System | Leventhal A.M.,University of Southern California
American Journal on Addictions | Year: 2015

Background and Objectives Post-traumatic stress disorder (PTSD) is overrepresented among cigarette smokers. It has been hypothesized that those with PTSD smoke to alleviate negative affect and counteract deficient positive affect commonly associated with the disorder; however, limited research has examined associations between PTSD symptoms, smoking motives, and affective vulnerability factors. In the current study, we examined (1) whether PTSD symptoms were associated with positive reinforcement and negative reinforcement smoking motives; and (2) whether two affective vulnerability factors implicated in PTSD - anxiety sensitivity and anhedonia - mediated relationships between PTSD symptoms and smoking motives. Methods Data were drawn from a community sample of non-treatment-seeking smokers recruited without regard for trauma history (N = 342; 10+ cig/day). We used the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C) to assess overall PTSD symptom severity as well as individual PTSD subfactors. Results Overall, PTSD symptom severity was significantly associated with negative reinforcement, but not positive reinforcement, smoking motives. Variation in anxiety sensitivity significantly mediated the relation between PTSD symptom severity and negative reinforcement smoking motives, whereas anhedonia did not. Regarding PTSD subfactors, emotional numbing was the only PTSD subfactor associated with smoking rate, while re-experiencing symptoms were uniquely associated with both positive reinforcement and negative reinforcement smoking motives. Conclusions and Scientific Significance Findings suggest that anxiety sensitivity may be an important feature associated with PTSD that enhances motivation to smoke for negative reinforcement purposes. Smoking cessation interventions that alleviate anxiety sensitivity and enhance coping with negative affect may be useful for smokers with elevated PTSD symptoms. (Am J Addict 2015;24:39-46) © American Academy of Addiction Psychiatry.


PubMed | Boston University, National Center for at Boston Healthcare System, New England Research Institutes, Inc., Boston VA Research Institute and Research Service
Type: Journal Article | Journal: Psychological medicine | Year: 2016

Post-traumatic stress disorder (PTSD) is associated with elevated risk for metabolic syndrome (MetS). However, the direction of this association is not yet established, as most prior studies employed cross-sectional designs. The primary goal of this study was to evaluate bidirectional associations between PTSD and MetS using a longitudinal design.A total of 1355 male and female veterans of the conflicts in Iraq and Afghanistan underwent PTSD diagnostic assessments and their biometric profiles pertaining to MetS were extracted from the electronic medical record at two time points (spanning ~2.5 years, n = 971 at time 2).The prevalence of MetS among veterans with PTSD was just under 40% at both time points and was significantly greater than that for veterans without PTSD; the prevalence of MetS among those with PTSD was also elevated relative to age-matched population estimates. Cross-lagged panel models revealed that PTSD severity predicted subsequent increases in MetS severity ( = 0.08, p = 0.002), after controlling for initial MetS severity, but MetS did not predict later PTSD symptoms. Logistic regression results suggested that for every 10 PTSD symptoms endorsed at time 1, the odds of a subsequent MetS diagnosis increased by 56%.Results highlight the substantial cardiometabolic concerns of young veterans with PTSD and raise the possibility that PTSD may predispose individuals to accelerated aging, in part, manifested clinically as MetS. This demonstrates the need to identify those with PTSD at greatest risk for MetS and to develop interventions that improve both conditions.

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