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ADCYAP1R1 genotype associates with post-traumatic stress symptoms in highly traumatized African-American females.

ABSTRACT: Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor (PAC1) play a critical role in biological processes that mediate stress response and have been implicated in psychological outcome following trauma. Our previous work [Ressler et al. (2011); Nature 470:492-497] demonstrated that a variant, rs2267735, in the gene encoding PAC1 (ADCYAP1R1) is associated with post-traumatic stress disorder (PTSD) in a primarily African-American cohort of highly traumatized females. We sought to extend and replicate our previous finding in a similarly trauma-exposed, replicate sample of 1,160 African-American adult male and female patients. Self-reported psychiatric measures were collected, and DNA was obtained for genetic analysis. Using linear regression models to test for association with PTSD symptom severity under an additive (allelic) model, we found a genotype × trauma interaction in females (P < 0.001), but not males (P > 0.1); however, there was no main effect of genotype as in our previous study. The observed interaction suggests a genetic association that increases with the degree of trauma exposure in females only. This interaction remained significant in females, but not males, after controlling for age (P < 0.001), income (P < 0.01), past substance abuse (P < 0.001), depression severity (P = 0.02), or child abuse (P < 0.0005), and all five combined (P = 0.01). No significant effects of genotype (or interactions) were found when modeling depression severity when controlling for comorbid PTSD symptom severity (P > 0.1), demonstrating the relative specificity of this variant for PTSD symptoms. A meta-analysis with the previously reported African-American samples revealed a strong association between PTSD symptom severity and the interaction between trauma and genotype in females (N = 1424, P < 0.0001).

SUBMITTER: Almli LM

PROVIDER: S-EPMC3738001 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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ADCYAP1R1 genotype associates with post-traumatic stress symptoms in highly traumatized African-American females.

Almli Lynn M LM Mercer Kristina B KB Kerley Kimberly K Feng Hao H Bradley Bekh B Conneely Karen N KN Ressler Kerry J KJ

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20130315 3

Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor (PAC1) play a critical role in biological processes that mediate stress response and have been implicated in psychological outcome following trauma. Our previous work [Ressler et al. (2011); Nature 470:492-497] demonstrated that a variant, rs2267735, in the gene encoding PAC1 (ADCYAP1R1) is associated with post-traumatic stress disorder (PTSD) in a primarily African-American cohort of highly traumatized females. We sough ...[more]

PMID: 23505260

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Project description:Background: Previous studies showed that self-stigma is associated with poor clinical outcomes in people with serious mental illness, and is associated with post-traumatic stress disorder (PTSD). However, less is known about self-stigma in people with dissociative symptoms, which are often related to psychological trauma. This study examined whether baseline self-stigma would be associated with dissociative, PTSD and depressive symptoms at post-intervention, after controlling for treatment usage and baseline symptom severity, in a sample of traumatized Chinese adults undertaking a psychoeducation intervention for dissociative symptoms.Methods: We conducted a secondary analysis of data from a 60-day web-based psychoeducation programme. A total of 58 participants who provided data before and after the intervention were included for analysis. Hierarchical regression analyses were conducted.Results: In this highly traumatized, dissociative, and symptomatic help-seeking sample, baseline self-stigma was associated with PTSD (β = .203, p = .032) and depressive (β = .264, p = .025) symptoms at post-intervention, even after controlling for baseline symptom severity, age, location, number of sessions attended in the web-based psychoeducation programme, and use of psychological treatments for PTSD/dissociative symptoms. However, self-stigma was not associated with dissociative symptoms (p = .108).Conclusions: This is the first study showing that self-stigma is a significant predictor of comorbid symptoms (i.e. PTSD and depressive symptoms) in people seeking interventions for dissociative symptoms. The findings that post-traumatic and dissociative symptoms have different relationships to self-stigma also highlight the possibility dissociation might be an independent psychological construct closely associated with trauma, but not merely a PTSD symptom, although further studies are necessary. The preliminary findings call for more efforts to understand, prevent, and address self-stigma in people with trauma-related mental health issues such as dissociative symptoms.

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ADCYAP1R1 genotype associates with post-traumatic stress symptoms in highly traumatized African-American females.

Publications

ADCYAP1R1 genotype associates with post-traumatic stress symptoms in highly traumatized African-American females.

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