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The PPM1F gene moderates the association between PTSD and cortical thickness.

ABSTRACT: BACKGROUND:Evidence suggests that single nucleotide polymorphisms (SNPs) in genes involved in serotonergic signaling and stress response pathways moderate associations between PTSD and cortical thickness. This study examined a genetic regulator of these pathways, the PPM1F gene, which has also been implicated in mechanisms of stress responding and is differentially expressed in individuals with comorbid PTSD and depression compared to controls. METHODS:Drawing from a sample of 240 white non-Hispanic trauma-exposed veterans, we tested 18 SNPs spanning the PPM1F gene for association with PTSD and cortical thickness. RESULTS:Analyses revealed six PPM1F SNPs that moderated associations between PTSD symptom severity and cortical thickness of bilateral superior frontal and orbitofrontal regions as well as the right pars triangularis (all corrected p's < 0.05) such that greater PTSD severity was related to reduced cortical thickness as a function of genotype. A whole-cortex vertex-wise analysis using the most associated SNP (rs9610608) revealed this effect to be localized to a cluster in the right superior frontal gyrus (cluster-corrected p < 0.02). LIMITATIONS:Limitations of this study include the small sample size and that the sample was all-white, non-Hispanic predominately male veterans. CONCLUSIONS:These results extend prior work linking PPM1F to PTSD and suggest that variants in this gene may have bearing on the neural integrity of the prefrontal cortex (PFC).

SUBMITTER: Sullivan DR

PROVIDER: S-EPMC6791735 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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The PPM1F gene moderates the association between PTSD and cortical thickness.

Sullivan Danielle R DR Morrison Filomene G FG Wolf Erika J EJ Logue Mark W MW Fortier Catherine B CB Salat David H DH Fonda Jennifer R JR Stone Annjanette A Schichman Steven S Milberg William W McGlinchey Regina R Miller Mark W MW

Journal of affective disorders 20190819

<h4>Background</h4>Evidence suggests that single nucleotide polymorphisms (SNPs) in genes involved in serotonergic signaling and stress response pathways moderate associations between PTSD and cortical thickness. This study examined a genetic regulator of these pathways, the PPM1F gene, which has also been implicated in mechanisms of stress responding and is differentially expressed in individuals with comorbid PTSD and depression compared to controls.<h4>Methods</h4>Drawing from a sample of 240 ...[more]

PMID: 31446381

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Project description:Structural neuroimaging studies of posttraumatic stress disorder (PTSD) have typically reported reduced cortical thickness (CT) and gray matter volume (GMV) in subcortical structures and networks involved in memory retrieval, emotional processing and regulation, and fear acquisition and extinction. Although PTSD is more common in women, and interpersonal violence (IPV) exposure is a more potent risk factor for developing PTSD relative to other forms of trauma, most of the existing literature examined combat-exposed men with PTSD. Vertex-wise CT and subcortical GMV analyses were conducted to examine potential differences in a large, well-characterized sample of women with PTSD stemming from IPV-exposure (n = 99) compared to healthy trauma-free women without a diagnosis of PTSD (n = 22). Subgroup analyses were also conducted to determine whether symptom severity within specific PTSD symptom clusters (e.g., re-experiencing, active avoidance, hyperarousal) predict CT and GMV after controlling for comorbid depression and anxiety. Results indicated that a diagnosis of PTSD in women with IPV-exposure did not significantly predict differences in CT across the cortex or GMV in the amygdala or hippocampus compared to healthy controls. However, within the PTSD group, greater re-experiencing symptom severity was associated with decreased CT in the left inferior and middle temporal gyrus, and decreased CT in the right parahippocampal and medial temporal gyrus. In contrast, greater active avoidance symptom severity was associated with greater CT in the left lateral fissure, postcentral gyrus, and middle/lateral occipital cortex, and greater CT in the right paracentral, posterior cingulate, and superior occipital gyrus. In terms of GMV, greater hyperarousal symptom severity was associated with reduced left amygdala GMV, while greater active avoidance symptom severity was associated with greater right amygdala GMV. These findings suggest that structural brain alterations among women with IPV-related PTSD may be driven by symptom severity within specific symptom clusters and that PTSD symptom clusters may have a differential (increased or decreased) association with brain structures.

Dataset Information

The PPM1F gene moderates the association between PTSD and cortical thickness.

Publications

The PPM1F gene moderates the association between PTSD and cortical thickness.

Similar Datasets

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