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The role of limbic system irritability in linking history of childhood maltreatment and psychiatric outcomes in low-income, high-risk women: moderation by FK506 binding protein 5 haplotype.

ABSTRACT: Childhood maltreatment is associated with lasting changes in neuroendocrine regulation, alterations in brain structure and function, and symptoms of "limbic irritability." Limbic irritability symptoms include somatic, sensory, and behavioral phenomena and may stem from increased excitatory neurotransmission following maltreatment. We tested the hypotheses that child maltreatment is indirectly associated with depressive and dissociative symptomatology via indicators of limbic irritability and that variation within the FK506 binding protein 5 gene (FKBP5), a gene involved in glucorticoid receptor functioning, moderates these effects. The sample consisted of high-risk, low-income women (N = 236) living in an inner-city environment. Child maltreatment, limbic irritability, and symptoms of depression and dissociation were measured cross-sectionally using self-report assessments. Haplotype analyses were conducted across four FKBP5 single nucleotide polymorphisms: rs3800373, rs9296158, rs1360870, and rs9470080. Path analysis using bootstrapping procedures was performed to test hypotheses regarding indirect and conditional indirect effects. We found significant indirect effects of maltreatment on depression (? = 0.088, p < .01) and dissociation (? = 0.105, p < .01) via limbic irritability. In addition, variation within FKBP5 moderated these significant indirect effects. For individuals with one to two copies of the CATT haplotype, the indirect effects of maltreatment on depression (? = 0.137, p < .01) and dissociation (? = 0.132, p < .01) via limbic irritability were significant, whereas the indirect paths were not significant for individuals with no copies of this haplotype (depression: ? = 0.037, p > .05; dissociation: ? = 0.002, p > .05). These results add to the growing evidence that child maltreatment may lead to symptoms of internalizing psychopathology through its impact on the limbic system. In addition, this study revealed a potential role of FKBP5 gene variants in contributing to risk for limbic system dysfunction.

SUBMITTER: Dackis MN

PROVIDER: S-EPMC3697116 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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The role of limbic system irritability in linking history of childhood maltreatment and psychiatric outcomes in low-income, high-risk women: moderation by FK506 binding protein 5 haplotype.

Dackis Melissa N MN Rogosch Fred A FA Oshri Assaf A Cicchetti Dante D

Development and psychopathology 20121101 4

Childhood maltreatment is associated with lasting changes in neuroendocrine regulation, alterations in brain structure and function, and symptoms of "limbic irritability." Limbic irritability symptoms include somatic, sensory, and behavioral phenomena and may stem from increased excitatory neurotransmission following maltreatment. We tested the hypotheses that child maltreatment is indirectly associated with depressive and dissociative symptomatology via indicators of limbic irritability and tha ...[more]

PMID: 23062294

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Project description:ImportanceSubstance use disorders (SUDs) are among the most common sequelae of childhood maltreatment, yet the independent contributions of SUDs and childhood maltreatment to neurobiological changes and the effect of the latter on relapse risk (a critical variable in addiction treatment) are relatively unknown.ObjectivesTo identify structural neural characteristics independently associated with childhood maltreatment (CM; a common type of childhood adversity), comparing a sample with SUD with a demographically comparable control sample, and to examine the relationship between CM-related structural brain changes and subsequent relapse.Design, setting, and participantsStructural magnetic resonance imaging study comparing 79 treatment-engaged participants with SUD in acute remission in inpatient treatment at a community mental health center vs 98 healthy control participants at an outpatient research center at an academic medical center. Both groups included individuals with a range of CM experiences. Participants with SUD were followed up prospectively for 90 days to assess relapse and relapse severity.InterventionStandard 12-step, recovery-based, inpatient addiction treatment for all participants with SUD.Main outcomes and measuresGray matter volume (GMV), subsequent substance use relapse, days to relapse, and severity of relapse.ResultsControlling for SUD and psychiatric comorbidity, CM (dichotomously classified) was uniquely associated with lower GMV across all participants in the left hippocampus (cornu ammonis 1-3, dentate gyrus), parahippocampus (presubiculum, parasubiculum, prosubiculum, subiculum, and entorhinal cortex), and anterior fusiform gyrus (corrected P < .05; uncorrected P = .001). Among the sample with SUD, CM prospectively predicted a shorter relapse to use of any drug (P = .048), while CM-related GMV reductions predicted severity of substance use relapse (P = .04).Conclusions and relevanceFindings indicate that CM was related to decreased GMV in limbic regions, which in turn predicted increased risk of relapse in SUD. These results suggest that CM may significantly affect the course of SUD treatment outcomes and that SUD treatment planning may benefit from identifying and addressing CM.

Dataset Information

The role of limbic system irritability in linking history of childhood maltreatment and psychiatric outcomes in low-income, high-risk women: moderation by FK506 binding protein 5 haplotype.

Publications

The role of limbic system irritability in linking history of childhood maltreatment and psychiatric outcomes in low-income, high-risk women: moderation by FK506 binding protein 5 haplotype.

Similar Datasets

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