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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 (<jats:italic>FKBP5<\/jats:italic>), a gene involved in glucorticoid receptor functioning, moderates these effects. The sample consisted of high-risk, low-income women (<jats:italic>N<\/jats:italic>= 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<jats:italic>FKBP5<\/jats:italic>single nucleotide polymorphisms:<jats:italic>rs3800373<\/jats:italic>,<jats:italic>rs9296158<\/jats:italic>,<jats:italic>rs1360870<\/jats:italic>, and<jats:italic>rs9470080<\/jats:italic>. 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 (\u03b2 = 0.088,<jats:italic>p<\/jats:italic>&lt; .01) and dissociation (\u03b2 = 0.105,<jats:italic>p<\/jats:italic>&lt; .01) via limbic irritability. In addition, variation within<jats:italic>FKBP5<\/jats:italic>moderated these significant indirect effects. For individuals with one to two copies of the CATT haplotype, the indirect effects of maltreatment on depression (\u03b2 = 0.137,<jats:italic>p &lt;<\/jats:italic>.01) and dissociation (\u03b2 = 0.132,<jats:italic>p<\/jats:italic>&lt; .01) via limbic irritability were significant, whereas the indirect paths were not significant for individuals with no copies of this haplotype (depression: \u03b2 = 0.037,<jats:italic>p &gt;<\/jats:italic>.05; dissociation: \u03b2 = 0.002,<jats:italic>p<\/jats:italic>&gt; .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<jats:italic>FKBP5<\/jats:italic>gene variants in contributing to risk for limbic system dysfunction.<\/jats:p>","DOI":"10.1017\/s0954579412000673","type":"journal-article","created":{"date-parts":[[2012,10,15]],"date-time":"2012-10-15T10:57:16Z","timestamp":1350298636000},"page":"1237-1252","source":"Crossref","is-referenced-by-count":64,"title":["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"],"prefix":"10.1017","volume":"24","author":[{"given":"Melissa N.","family":"Dackis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred A.","family":"Rogosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assaf","family":"Oshri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dante","family":"Cicchetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2012,10,15]]},"reference":[{"key":"S0954579412000673_ref89","first-page":"578","volume-title":"Developmental psychopathology: Vol. 2. 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