Interaction of theADRB2Gene Polymorphism With Childhood Trauma in Predicting Adult Symptoms of Posttraumatic Stress Disorder

Israel Liberzon · Anthony P. J. King · Kerry James Ressler · Lynn M. Almli · Peng Zhang · Sean T. Ma +4 more

85 citations0/0 files storedJAMA Psychiatry

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Posttraumatic Stress Disorder Research Genetic Associations and Epidemiology Child Abuse and Trauma

Abstract

IMPORTANCE: Posttraumatic stress disorder (PTSD), while highly prevalent (7.6% over a lifetime), develops only in a subset of trauma-exposed individuals. Genetic risk factors in interaction with trauma exposure have been implicated in PTSD vulnerability. OBJECTIVE: To examine the association of 3755 candidate gene single-nucleotide polymorphisms with PTSD development in interaction with a history of childhood trauma. DESIGN, SETTING, AND PARTICIPANTS: Genetic association study in an Ohio National Guard longitudinal cohort (n = 810) of predominantly male soldiers of European ancestry, with replication in an independent Grady Trauma Project (Atlanta, Georgia) cohort (n = 2083) of predominantly female African American civilians. MAIN OUTCOMES AND MEASURES: Continuous measures of PTSD severity, with a modified (interview) PTSD checklist in the discovery cohort and the PTSD Symptom Scale in the replication cohort. RESULTS: Controlling for the level of lifetime adult trauma exposure, we identified the novel association of a single-nucleotide polymorphism within the promoter region of the ADRB2 (Online Mendelian Inheritance in Man 109690) gene with PTSD symptoms in interaction with childhood trauma (rs2400707, P = 1.02 × 10-5, significant after correction for multiple comparisons). The rs2400707 A allele was associated with relative resilience to childhood adversity. An rs2400707 × childhood trauma interaction predicting adult PTSD symptoms was replicated in the independent predominantly female African American cohort. CONCLUSIONS AND RELEVANCE: Altered adrenergic and noradrenergic function has been long believed to have a key etiologic role in PTSD development; however, direct evidence of this link has been missing. The rs2400707 polymorphism has been linked to function of the adrenergic system, but, to our knowledge, this is the first study to date linking the ADRB2 gene to PTSD or any psychiatric disorders. These findings have important implications for PTSD etiology, chronic pain, and stress-related comorbidity, as well as for both primary prevention and treatment strategies.

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References

1995Posttraumatic Stress Disorder in the National Comorbidity Survey 1995The development of a Clinician-Administered PTSD Scale 1996Psychometric properties of the PTSD checklist (PCL)2001Childhood Abuse, Household Dysfunction, and the Risk of Attempted Suicide Throughout the Life Span 2008Invisible Wounds of War: Psychological and Cognitive Injuries, Their Consequences, and Services to Assist Recovery 2012Biological studies of post-traumatic stress disorder 2013Diagnostic and Statistical Manual of Mental Disorders 2008Association of FKBP5 Polymorphisms and Childhood Abuse With Risk of Posttraumatic Stress Disorder Symptoms in Adults

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