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A preliminary investigation of rare variants associated with genetic risk for PTSD in a natural disaster-exposed adolescent sample.

ABSTRACT: Background: Posttraumatic stress disorder (PTSD) involves a complex interaction of biological, psychological, and social factors. Numerous studies have demonstrated genetic variation associated with the development of PTSD, primarily in adults. However, the contribution of low frequency and rare genetic variants to PTSD is unknown to date. Moreover, there is limited work on genetic risk for PTSD in child and adolescent populations. Objective: This preliminary study aimed to identify the low frequency and rare genetic variation that contributes to PTSD using an exome array. Method: This post-disaster, adolescent sample (n = 707, 51% females, M _age = 14.54) was assessed for PTSD diagnosis and symptom count following tornado exposure. Results: Gene-based models, covarying for ancestry principal components, age, sex, tornado severity, and previous trauma identified variants in four genes associated with diagnosis and 276 genes associated with symptom count (at p _adj < .001). Functional class analyses suggested an association with variants in the nonsense class (nonsynonymous variant that results in truncation of, and usually non-functional, protein) with both outcomes. An exploratory gene network pathway analysis showed a great number of significant genes involved in brain and immune function, illustrating the usefulness of downstream examination of gene-based findings that may point to relevant biological processes. Conclusions: While further investigation in larger samples is warranted, findings align with extant PTSD literature that has identified variants associated with biological conditions such as immune function.

SUBMITTER: Sheerin CM

PROVIDER: S-EPMC6896412 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A preliminary investigation of rare variants associated with genetic risk for PTSD in a natural disaster-exposed adolescent sample.

Sheerin Christina M CM Vladimirov Vladimir V Williamson Vernell V Bountress Kaitlin K K Danielson Carla C Ruggiero Kenneth K Amstadter Ananda B AB

European journal of psychotraumatology 20191202 1

<b>Background</b>: Posttraumatic stress disorder (PTSD) involves a complex interaction of biological, psychological, and social factors. Numerous studies have demonstrated genetic variation associated with the development of PTSD, primarily in adults. However, the contribution of low frequency and rare genetic variants to PTSD is unknown to date. Moreover, there is limited work on genetic risk for PTSD in child and adolescent populations. <b>Objective</b>: This preliminary study aimed to identif ...[more]

PMID: 31839899

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Project description:BackgroundRecent neuroimaging work suggests that increased amygdala responses to emotional stimuli and dysfunction within regions mediating top down attentional control (dorsomedial frontal, lateral frontal and parietal cortices) may be associated with the emergence of anxiety disorders, including posttraumatic stress disorder (PTSD). This report examines amygdala responsiveness to emotional stimuli and the recruitment of top down attention systems as a function of task demands in a population of U.S. military service members who had recently returned from combat deployment in Afghanistan/Iraq. Given current interest in dimensional aspects of pathophysiology, it is worthwhile examining patients who, while not meeting full PTSD criteria, show clinically significant functional impairment.MethodsFifty-seven participants with sub-threshold levels of PTSD symptoms completed the affective Stroop task while undergoing fMRI. Participants with PTSD or depression at baseline were excluded.ResultsGreater PTSD symptom severity scores were associated with increased amygdala activation to emotional, particularly positive, stimuli relative to neutral stimuli. Furthermore, greater PTSD symptom severity was associated with increased superior/middle frontal cortex response during task conditions relative to passive viewing conditions. In addition, greater PTSD symptom severity scores were associated with: (i) increased activation in the dorsolateral prefrontal, lateral frontal, inferior parietal cortices and dorsomedial frontal cortex/dorsal anterior cingulate cortex (dmFC/dACC) in response to emotional relative to neutral stimuli; and (ii) increased functional connectivity during emotional trials, particularly positive trials, relative to neutral trials between the right amygdala and dmFC/dACC, left caudate/anterior insula cortex, right lentiform nucleus/caudate, bilateral inferior parietal cortex and left middle temporal cortex.ConclusionsWe suggest that these data may reflect two phenomena associated with increased PTSD symptomatology in combat-exposed, but PTSD negative, armed services members. First, these data indicate increased emotional responsiveness by: (i) the positive relationship between PTSD symptom severity and amygdala responsiveness to emotional relative to neutral stimuli; (ii) greater BOLD response as a function of PTSD symptom severity in regions implicated in emotion (striatum) and representation (occipital and temporal cortices) during emotional relative to neutral conditions; and (iii) increased connectivity between the amygdala and regions implicated in emotion (insula/caudate) and representation (middle temporal cortex) as a function of PTSD symptom severity during emotional relative to neutral trials. Second, these data indicate a greater need for the recruitment of regions implicated in top down attention as indicated by (i) greater BOLD response in superior/middle frontal gyrus as a function of PTSD symptom severity in task relative to view conditions; (ii) greater BOLD response in dmFC/dACC, lateral frontal and inferior parietal cortices as a function of PTSD symptom severity in emotional relative to neutral conditions and (iii) greater functional connectivity between the amygdala and inferior parietal cortex as a function of PTSD symptom severity during emotional relative to neutral conditions.

Dataset Information

A preliminary investigation of rare variants associated with genetic risk for PTSD in a natural disaster-exposed adolescent sample.

Publications

A preliminary investigation of rare variants associated with genetic risk for PTSD in a natural disaster-exposed adolescent sample.

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