The association of serologically documented maternal thyroid conditions during pregnancy with bipolar disorder in offspring.

Abstract

Higher rates of thyroid conditions are reported in individuals with bipolar disorder. However, no study to date has considered whether maternal thyroid conditions during pregnancy are associated with offspring risk of bipolar disorder, even though the fetus exclusively relies on maternal thyroid hormones through the early second trimester. We therefore examined the association between offspring bipolar disorder and serologically documented maternal thyroid conditions. The study was based on a nested case-control design that utilized data from the Child Health and Development Study, a birth cohort that enrolled pregnant women from 1959 to 1966. Eighty-five cases with DSM-IV-TR were ascertained and matched to controls (1:2) by date of birth, sex, gestational timing of the serum draws, and residence in Alameda County the first year receiving treatment. Archived prenatal maternal serum drawn during early to mid-gestation was used to measure two thyroid hormones, free thyroxine (fT4) and thyroid stimulating hormone (TSH). Subclinical and clinical hypothyroxinemia, hypothyroidism, and hyperthyroidism were determined based on standard methods. Exposure to maternal hypothyroxinemia was associated with a five-fold increased risk of offspring bipolar disorder with psychotic features, but not without psychotic features. In stratified analysis, female offspring demonstrated increased risk for bipolar disorder with exposure to maternal hypothyroxinemia. No significant association was found between maternal hypothyroidism and offspring bipolar disorder. These findings suggest that prenatal thyroid hormone deficiency, particularly a thyroid condition marked by low levels of thyroxine, may be an important developmental mechanism related to the risk of bipolar disorder with psychotic features.