Attachment style moderates polygenic risk for incident posttraumatic stress in U.S. military veterans: A 7-year, nationally representative, prospective cohort study

Published on Oct 6, 2021in Biological Psychiatry13.382
路 DOI :10.1016/J.BIOPSYCH.2021.09.025
Amanda J.F. Tamman3
Estimated H-index: 3
(BCM: Baylor College of Medicine),
Frank R. Wendt14
Estimated H-index: 14
(Yale University)
+ 6 AuthorsRobert H. Pietrzak77
Estimated H-index: 77
(Yale University)
Sources
Abstract
ABSTRACT null null Background null Posttraumatic stress disorder (PTSD) develops consequent to complex gene-environment interactions beyond the precipitating trauma. To date, however, no known study has used a prospective design to examine how polygenic risk scores (PRS) interact with social-environmental factors such as attachment style to predict PTSD development. null null null Methods null PRS were derived from a GWAS of PTSD symptoms (N=186,689, Million Veteran Program cohort). We evaluated combined effects of PRS and attachment style in predicting incident PTSD in a 7-year, nationally representative cohort of trauma-exposed, European-American (EA) U.S. military veterans without PTSD (N=1,083). We also conducted multivariate gene-by-environment interaction and drug repositioning analyses to identify loci that interact with multiple environmental factors and potential pharmacotherapies that may be repurposed for this disorder. null null null Results null Veterans with higher PTSD PRS were more likely to have an incident positive screen for PTSD over 7 years. A gene-environment interaction was also observed, such that higher PRS only predicted incident PTSD in veterans with an insecure attachment style, and not those with a secure attachment style. At an individual locus level, the strongest gene-environment interaction was observed for the rs4702 variant of the FURIN gene with cumulative lifetime trauma burden. Drug repositioning revealed that genes implicated in the PRS are perturbated by the drug doxylamine. null null null Conclusions null Attachment style moderates polygenic risk for the development of PTSD in EA veterans. These findings may inform PTSD prevention and treatment for veterans with high polygenic risk for PTSD, and suggest a potential pharmacotherapeutic target for risk genes moderated by social-environmental factors.
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#2Kenneth N. Levy (PSU: Pennsylvania State University)H-Index: 57
Abstract null null Background null Most people will experience a traumatic event in their lifetime, but only a subset ( null null null Objective null To facilitate prevention and intervention of PTSD, it is important to understand how risk and resilience factors interact with one another to explain individual differences in risk for PTSD, especially in underprivileged groups, who often experience greater burden of trauma and PTSD. null null null Method null The current study utilized multiple an...
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#1Molly J. Sullan (UCSD: University of California, San Diego)H-Index: 2
Abstract null null Poor sleep quality is common among Veterans with posttraumatic stress disorder (PTSD) and history of traumatic brain injury (TBI). However, the relationship between sleep quality and treatment outcomes following trauma-focused interventions is less well-understood in this population. We sought to better understand whether 1) sleep quality changed as a result of trauma-focused treatment and 2) if baseline sleep quality moderated psychological and neurobehavioral treatment outco...
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#1Ruth Asch (Yale University)H-Index: 3
#2Irina Esterlis (Yale University)H-Index: 25
Last. Robert H. Pietrzak (Yale University)H-Index: 77
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OBJECTIVES To examine whether attachment style moderates the relationship between polygenic risk scores (PRS) for posttraumatic stress disorder (PTSD) re-experiencing (PTSDREX) symptoms and the severity of and positive screen for traumatic loss-related PTSD. METHODS Data were analyzed from 631鈥塙.S. veterans who endorsed "unexpected death of a loved one" as their 'worst' traumatic event. Multivariable models evaluated the association between PRS for PTSDREX, attachment style, and their interactio...
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#317Roel A. OphoffH-Index: 95
#318Ole A. Andreassen (University of Oslo)H-Index: 127
Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in ge...
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#1Amanda J.F. Tamman (Yale University)H-Index: 3
#2Frank R. Wendt (Yale University)H-Index: 14
Last. Robert H. Pietrzak (Yale University)H-Index: 77
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Abstract Background A polygenic risk score (PRS) derived from genome-wide association studies of posttraumatic stress disorder (PTSD) may inform risk for this disorder. To date, however, no known study has examined whether social environmental factors such as attachment style may moderate the relation between PRS and PTSD. Methods We evaluated main and interactive effects of PRS and attachment style on PTSD symptoms in a nationally representative sample of trauma-exposed European-American U.S. m...
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#1Jason C. DeViva (Yale University)H-Index: 13
#2Elissa McCarthyH-Index: 4
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Abstract Sleep and posttraumatic stress disorder (PTSD) have a complex relationship, with some studies showing that disrupted sleep is associated with subsequent development of PTSD. The purpose of the current study was to examine the relationship between sleep quality and the development of probable PTSD in U.S. veterans surveyed as part of the National Health and Resilience in Veterans Study, a 7-year, nationally representative, prospective cohort study with four waves of data collection. Soci...
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#1Richard A. Bryant (UNSW: University of New South Wales)H-Index: 128
Abstract Although many attempts have been made to limit development of posttraumatic stress disorder (PTSD) by early intervention after trauma exposure, these attempts have achieved only modest success. This review critiques the biological and cognitive strategies used for early intervention and outlines the extent to which they have prevented PTSD. The major predictors of PTSD are reviewed, with an emphasis on potential mechanisms that may underpin the transition from acute stress reaction to d...
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Despite experiencing a significant trauma, only a subset of World Trade Center (WTC) rescue and recovery workers developed posttraumatic stress disorder (PTSD). Identification of biomarkers is critical to the development of targeted interventions for treating disaster responders and potentially preventing the development of PTSD in this population. Analysis of gene expression from these individuals can help in identifying biomarkers of PTSD. We established a well-phenotyped sample of 371 WTC res...
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#1Yabing Wang (Guangdong University of Foreign Studies)H-Index: 2
#2Man Cheung Chung (CUHK: The Chinese University of Hong Kong)H-Index: 32
Last. Justin Kenardy (UQ: University of Queensland)H-Index: 70
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Abstract Social support has long been associated with posttraumatic stress disorder (PTSD), but there is no consistent evidence on the strength and direction of this relationship. Whereas the social causation model claims that social support buffers against PTSD, the social selection model states that PTSD reduces social support resources. As the first meta-analysis of the prospective relationships between social support and PTSD, this study synthesized the available longitudinal data (75 sample...
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#1Renato Polimanti (Yale University)H-Index: 30
#2Frank R. Wendt (VA: United States Department of Veterans Affairs)H-Index: 14
Posttraumatic stress disorder (PTSD) is a complex mental disorder afflicting approximately 7% of the population. The diverse number of traumatic events and the wide array of symptom combinations leading to PTSD diagnosis contribute substantial heterogeneity to studies of the disorder. Genomic and complimentary-omic investigations have rapidly increased our understanding of the heritable risk for PTSD. In this review, we emphasize the contributions of genome-wide association, epigenome-wide assoc...
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