The Role of Limbic System Irritability in Linking History of Childhood Maltreatment and Psychiatric Outcomes in Low-Income, High-Risk Women: Moderation by FKBP5
Date
2012
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Development and Psychopathology
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. In this investigation, we tested the hypotheses that child maltreatment is indirectly associated with depressive and dissociative symptomatology via indicators of limbic irritability, and that variation within 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 SNPs (rs3800373, rs9296158, rs1360870, 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 (β = 0.088, p<0.01) and dissociation (β = 0.105, p<0.01) via limbic irritability. In addition, variation within FKBP5 moderated these significant indirect effects. For individuals with 1–2 copies of the CATT haplotype, the indirect effects of maltreatment on depression (β = 0.137, p<0.01) and dissociation (β = 0.132, p<0.01) via limbic irritability were significant, whereas the indirect paths were not significant for individuals with no copies of this haplotype (depression: β = 0.037, p>0.05; dissociation: β = 0.002, p>0.05). 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. (Author Abstract)
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Keywords
child abuse, long term effects, mothers, risk factors, research
Citation
Dackis, M. N., Rogosch, F. A., Oshri, A., & Cicchetti, D. (2012). 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. Development and psychopathology, 24(04), 1237-1252.