Background: Both genetic and environmental factors are involved in the etiology of bipolar disorder; however, biological markers for the transmission of the bipolar genotype ("endophenotypes") have not been found. Autoimmune thyroiditis with raised levels of thyroperoxidase antibodies (TPO-Abs) is related to bipolar disorder and may be such an endophenotype. This study was intended to examine whether autoimmune thyroiditis is related to the disease itself, to the (genetic) vulnerability to develop bipolar disorder, or both. Method: Blood was collected from 22 monozygotic (MZ) and 29 dizygotic (DZ) bipolar twins and 35 healthy matched control twins to determine TPO-Abs. Results: The TPO-Abs were positive in 27% of the bipolar index twins, 29% of the monozygotic bipolar cotwins, 27% of the monozygotic nonbipolar cotwins, 25% of the dizygotic bipolar cotwins, 17% of the dizygotic nonbipolar cotwins, and in 16% of the control twins. Repeated measures analysis of covariance on log-transformed absolute TPO-Abs values revealed significantly increased mean TPO-Abs levels in discordant twin pairs as compared with healthy twin pairs, whereas no difference was found between bipolar patients and their (discordant) nonbipolar cotwins. Conclusions: This study shows that autoimmune thyroiditis is related not only to bipolar disorder itself but also to the genetic vulnerability to develop the disorder. Autoimmune thyroiditis, with TPO-Abs as marker, is a possible endophenotype for bipolar disorder.

Bipolar disorder, endophenotype, genetic risk, immunology, thyroid autoimmunity, twins,
Biological Psychiatry
Erasmus MC: University Medical Center Rotterdam

Vonk, R, van der Schot, A.C, Kahn, R.S, Nolen, W.A, & Drexhage, H.A. (2007). Is Autoimmune Thyroiditis Part of the Genetic Vulnerability (or an Endophenotype) for Bipolar Disorder?. Biological Psychiatry, 62(2), 135–140. doi:10.1016/j.biopsych.2006.08.041