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CHILDHOOD MALTREATMENT PREDICTS REDUCED INHIBITION-RELATED ACTIVITY IN THE ROSTRAL ANTERIOR CINGULATE IN PTSD, BUT NOT TRAUMA-EXPOSED CONTROLS.

ABSTRACT: BACKGROUND:A deficit in the ability to inhibit fear has been proposed as a biomarker of posttraumatic stress disorder (PTSD). Previous research indicates that individuals with PTSD show reduced inhibition-related activation in rostral anterior cingulate cortex (rACC). The goal of the current study was to investigate differential influences of an early environmental risk factor for PTSD-childhood maltreatment-on inhibition-related brain function in individuals with PTSD versus trauma-exposed controls. METHODS:Individuals with PTSD (n = 37) and trauma-exposed controls (n = 53) were recruited from the primary care waiting rooms of an urban public hospital in Atlanta, GA. Participants completed an inhibition task during fMRI, and reported childhood and adult traumatic experiences. The groups were matched for adult and child trauma load. RESULTS:We observed an interaction between childhood maltreatment severity and PTSD status in the rACC (P < .05, corrected), such that maltreatment was negatively associated with inhibition-related rACC activation in the PTSD group, but did not influence rACC activation in the TC group. Rostral ACC activation was associated with inhibition-related task performance in the TC group but not the PTSD group, suggesting a possible contribution to stress resilience. CONCLUSIONS:Findings highlight individual differences in neural function following childhood trauma, and point to inhibition-related activation in rostral ACC as a risk factor for PTSD.

SUBMITTER: Stevens JS

PROVIDER: S-EPMC4930398 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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CHILDHOOD MALTREATMENT PREDICTS REDUCED INHIBITION-RELATED ACTIVITY IN THE ROSTRAL ANTERIOR CINGULATE IN PTSD, BUT NOT TRAUMA-EXPOSED CONTROLS.

Stevens Jennifer S JS Ely Timothy D TD Sawamura Takehito T Guzman Dora D Bradley Bekh B Ressler Kerry J KJ Jovanovic Tanja T

Depression and anxiety 20160408 7

<h4>Background</h4>A deficit in the ability to inhibit fear has been proposed as a biomarker of posttraumatic stress disorder (PTSD). Previous research indicates that individuals with PTSD show reduced inhibition-related activation in rostral anterior cingulate cortex (rACC). The goal of the current study was to investigate differential influences of an early environmental risk factor for PTSD-childhood maltreatment-on inhibition-related brain function in individuals with PTSD versus trauma-expo ...[more]

PMID: 27062552

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Project description:OBJECTIVE:The anterior cingulate cortex (ACC) is critical for both stress and inhibitory control processes and has been implicated in childhood trauma. This prospective study tested the hypothesis that early trauma moderates the association between inhibitory control during late childhood and ACC stress reactivity during adolescence. METHOD:Sixty-four adolescents were stratified into higher- or lower-childhood-trauma groups. Inhibitory control was indicated by fewer errors on a Stroop Color-Word task. Personalized stress cues during functional magnetic resonance imaging assessed neural correlates of stress in adolescents. RESULTS:Using a priori-defined anterior (rCZa) and posterior rostral cingulate zones of the ACC, associated with Stroop Color-Word task performance in prior meta-analyses, Stroop errors correlated inversely with activation in the rCZa during stress-cue exposure (r?=?-.23, p?=?.04). Childhood trauma moderated the association between Stroop errors and rCZa stress reactivity (interaction?=?-1.26, p?=?.02, 95%CI?=?-2.33,-0.20), where Stroop errors were inversely associated with brain activation among those with higher childhood trauma (simple slopes?=?-.83, p?=?.007, 95%CI?=?-1.40,-0.25). Low stress-related rCZa activation inversely (R2?=?0.19, b?=?-0.43, p?=?.001, 95%CI?=?-4.11,-1.06) and Stroop errors directly (R2?=?0.09, b?=?0.27, p?=?.048, 95%CI?=?0.02, 5.8) associated with baseline subjective anxiety while controlling for childhood trauma. CONCLUSIONS:This is the first study to demonstrate a moderating role of childhood trauma on the relationship between inhibitory control and stress-related ACC activation. Childhood trauma may portend neurodevelopmental changes that impede recruitment of control-associated ACC-functioning during distress, which may relate to dysregulation of stress-induced affective responses. Further work is needed to elucidate relationships between childhood trauma and addictive behaviors precipitated by stress.

Project description:Behavioural, structural, and functional neuroimaging have implicated the hippocampus as a critical brain region in posttraumatic stress disorder (PTSD) pathogenesis. Recent work in a normative, primarily European, sample identified 15 unique genetic loci contributing to structural variability in six hippocampal subfield volumes. We explored the relevance of these loci in two samples (Mental Illness Research Education and Clinical Centre [MIRECC] and Grady; n = 290) of trauma-exposed individuals enriched for PTSD and of diverse ancestry. Four of the previous loci demonstrated nominal evidence of replication in the MIRECC dataset, primarily within non-Hispanic whites (NHW). One locus replicated in the Grady cohort, which was composed exclusively of non-Hispanic blacks (NHB). Our data supported genetic interactions with diagnosis of lifetime PTSD and genetic interactions with childhood trauma in the MIRECC sample, but not the Grady sample. Given the racial, diagnostic, and trauma-exposure differences with the original genome-wide association study (GWAS) report, we conducted a full GWAS in the MIRECC and Grady datasets. Interactions between genetic variants and lifetime PTSD or childhood trauma were interrogated for single nucleotide polymorphisms (SNPs) with evidence of main effects. Genetic associations surpassed false discovery rate (FDR)-correction within hippocampal subfields in fimbria, subiculum, cornu ammonis-1 (CA1), and hippocampal amygdala transition area (HATA). One association was replicated in the Grady cohort (rs12880795 in TUNAR with left (L)-HATA volume). The most significant association in the MIRECC dataset was between rs6906714 in LINC02571 and right (R)-fimbria volume (p = 5.99×10-8, q = 0.0056). Interestingly, the effect of rs6906714 on R-fimbria volume increased with exposure to childhood trauma (gene*environment [G*E] interaction p = 0.022). These preliminary results argue for G*E interactions between genetic loci with PTSD and childhood trauma on hippocampal phenotypes. Our results underscore the need for larger neuroimaging-genetic studies in PTSD, trauma, and ancestrally diverse populations.

Dataset Information

CHILDHOOD MALTREATMENT PREDICTS REDUCED INHIBITION-RELATED ACTIVITY IN THE ROSTRAL ANTERIOR CINGULATE IN PTSD, BUT NOT TRAUMA-EXPOSED CONTROLS.

Publications

CHILDHOOD MALTREATMENT PREDICTS REDUCED INHIBITION-RELATED ACTIVITY IN THE ROSTRAL ANTERIOR CINGULATE IN PTSD, BUT NOT TRAUMA-EXPOSED CONTROLS.

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