Bipolar Disorder is associated with the rs6971 polymorphism in the gene encoding 18kDa Translocator Protein (TSPO)

TY - JOUR

T1 - Bipolar Disorder is associated with the rs6971 polymorphism in the gene encoding 18kDa Translocator Protein (TSPO)

AU - Colasanti, Alessandro

AU - Owen, David R

AU - Grozeva, Detelina

AU - Rabiner, Eugenii A

AU - Matthews, Paul

AU - Craddock, Nick

AU - Young, Allan H

PY - 2013/11

Y1 - 2013/11

N2 - 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.

AB - 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.

KW - Translocator Protein

KW - Cortisol

KW - HPA

KW - Neurosteroids

KW - rs6971

KW - Genome-wide

KW - WTCCC

KW - Polymorphism

KW - Mitochondria

KW - Bipolar Disorder

KW - BENZODIAZEPINE-RECEPTOR

KW - DEPRESSION

KW - BINDING

KW - ANXIETY

U2 - 10.1016/j.psyneuen.2013.07.007

DO - 10.1016/j.psyneuen.2013.07.007

M3 - Article

C2 - 23942012

SN - 0306-4530

VL - 38

SP - 2826

EP - 2829

JO - Psychoneuroendocrinology

JF - Psychoneuroendocrinology

IS - 11

ER -