Organizational impacts of hypothyroidism on behavior

Thyroid hormones regulate embryonic and fetal neurodevelopment, with the maternal thyroid gland exclusively producing these hormones for the first half of gestation and then a combination of maternal and fetal production occurring during the second half of gestation. Hypothyroidism during pregnancy is common in humans, particularly due to the additional demand put on the thyroid gland as pregnancy proceeds. Epidemiological studies have linked maternal hypothyroidism to an increased risk of attention-deficit/hyperactivity disorder and autism spectrum disorder diagnosis in these children, as well as cognitive deficits and delays. Rodent models have been extensively used to model developmental hypothyroidism and study the long-term effects on offspring. Increases in activity, reductions in anxiety, cognitive impairments, and social alterations have been observed. In this review, I discuss the current understanding of the organizational impacts of hypothyroidism on activity, affective behaviors, cognition, and social behaviors in humans and animal models, paying special attention to critical periods that may underlie these effects. I also review potential interactions between thyroid hormones and steroid hormones known to be important for organization of the brain and behavior during perinatal and adolescent development. Understanding the effects of developmental hypothyroidism is critical, as early developmental exposure to many endocrine-disrupting chemicals may alter behavior through reducing thyroid hormone signaling, and the final section of the paper reviews these interactions. Understanding the organizational effects of thyroid hormones is important for decisions related to screening and interventions during pregnancy.