Reported Childhood Abuse is Associated With Low Serotonin Transporter Binding In Vivo in Major Depressive Disorder

Background: Physical or psychological adversity in childhood is associated with a higher risk for depression in adulthood, and with persistent serotonergic abnormalities in humans and in animal models. We hypothesized that reported childhood abuse would be associated with lower brain serotonin transporter (5-HTT) binding potential (BPP, proportional to the number of available transporters) in adults. We examined healthy volunteers and subjects with major depressive disorder, a sample enriched for childhood abuse. Methods: Regional brain 5-HTT BPP was measured using positron emission tomography (PET) with [C-11]McN 5652 and a metabolite-corrected arterial input function in 43 healthy volunteers and 23 subjects in a major depressive episode, ten of whom reported a history of sexual and/or physical abuse before age 15, and 13 of whom did not. As only two healthy volunteers reported childhood abuse, primary analyses were restricted to the depressed sample, with healthy controls presented as comparators. Results: Depressed subjects reporting childhood abuse had lower 5-HTT BPP than nonabused depressed subjects across all brain regions examined (P = 0.017). The groups did not differ in relevant demographic or clinical variables. Genotype frequencies of a functional polymorphism in the 5-HTT gene promoter (5-HTTLPR) did not differ between the groups. Conclusions: Reported childhood abuse is associated with lower 5-HTT BPP in this sample of subjects with major depression, consistent with other reports that childhood adversity can lower serotonergic function permanently. Lower 5-HTT BPP may represent a biological pathway through which early life stress predisposes to the development of subsequent psychiatric illness, including major depressive disorder. Synapse 63:565573, 2009. (C) 2009 Wiley-Liss, Inc.