Abstract
TSPO mediated transport of cholesterol into the mitochondrion is a necessary step in steroid synthesis. The rs6971 polymorphism in the TSPO gene causes an amino acid substitution (Ala147Thr) within the transmembrane domain where the cholesterol-binding pocket is located, and has been shown to affect the steroidogenic pathway. We report a nominal association between this TSPO polymorphism and the diagnosis of Bipolar Disorder in both the genome-wide dataset of the Wellcome Trust Case-Control Consortium and the Psychiatric Genome-Wide Association Study Consortium Bipolar Disorder group (OR=1.11, p=0.007; OR=1.10, p=0.011, respectively). We propose that the amino acid substitution affects hypothalamic-pituitary-adrenal (HPA) regulation, and hence may predispose to Bipolar Disorder. This supports the hypothesis that HPA dysregulation has a causal role in Bipolar Disorder, and is not just a consequence of the disease.