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.
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.
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DOI：
10.1017/s0954579412000673
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发表时间：
2012-11
影响因子：
3.3
通讯作者：
Cicchetti D
中科院分区：
文献类型：
--
作者：
Dackis MN;Rogosch FA;Oshri A;Cicchetti D
儿童期虐待与神经内分泌调节的持久变化、大脑结构和功能的改变以及“边缘系统易激惹”症状有关。边缘系统易激惹症状包括躯体、感觉和行为现象，可能源于虐待后兴奋性神经传递增加。在这项调查中，我们测试的假设，儿童虐待是间接相关的抑郁症和解离性痴呆症通过指标的边缘系统易激惹，和FKBP 5，一个基因参与糖皮质激素受体功能的变化，缓和这些影响。样本包括高风险，低收入的妇女（N = 236）生活在市中心的环境。儿童虐待，边缘易怒，抑郁症和解离症状进行了测量横截面使用自我报告评估。在四个FKBP 5 SNP（rs3800373、rs 9296158、rs 1360870、rs 9470080）上进行单倍型分析。使用自举程序进行路径分析，以检验有关间接和条件间接效应的假设。我们发现虐待对抑郁（β = 0.088，p<0.01）和分离（β = 0.105，p<0.01）的间接影响是通过边缘系统的应激性实现的。此外，FKBP 5内的变异缓和了这些显著的间接效应。对于有1-2个CATT单倍型拷贝的个体，虐待对抑郁症的间接影响（β = 0.137，p<0.01）和解离（β = 0.132，p<0.01），而间接途径在无该单倍型拷贝的个体中不显著（抑郁：β = 0.037，p>0.05;分离：β = 0.002，p>0.05）。这些结果增加了越来越多的证据表明，儿童虐待可能会导致内化的精神病理学症状，通过其对边缘系统的影响。此外，这项研究揭示了FKBP 5基因变异在导致边缘系统功能障碍风险中的潜在作用。
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.