¹University of California Los Angeles (UCLA), Neuropsychiatric Institute & Hospital, Department of Psychiatry and Biobehavioral Sciences, 760 Westwood Plaza, Los Angeles, CA 90024, USA

²Central Institute of Mental Health, Department of Addictive Behavior and Addiction Research, 68159 Mannheim, Germany

Correspondence to: M Bauer, MD, PhD, Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (UCLA), 300 Medical Plaza, Suite 2330, Los Angeles, CA 90095, USA. E-mail: mjbauer@mednet.ucla.edu

The use of thyroid hormones as an effective adjunct treatment for affective disorders has been studied over the past three decades and has been confirmed repeatedly. Interaction of the thyroid and monoamine neurotransmitter systems has been suggested as a potential underlying mechanism of action. While catecholamine and thyroid interrelationships have been reviewed in detail, the serotonin system has been relatively neglected. Thus, the goal of this article is to review the literature on the relationships between thyroid hormones and the brain serotonin (5-HT) system, limited to studies in adult humans and adult animals. In humans, neuroendocrine challenge studies in hypothyroid patients have shown a reduced 5-HT responsiveness that is reversible with thyroid replacement therapy. In adult animals with experimentally-induced hypothyroid states, increased 5-HT turnover in the brainstem is consistently reported while decreased cortical 5-HT concentrations and 5-HT_2A receptor density are less frequently observed. In the majority of studies, the effects of thyroid hormone administration in animals with experimentally-induced hypothyroid states include an increase in cortical 5-HT concentrations and a desensitization of autoinhibitory 5-HT_1A receptors in the raphe area, resulting in disinhibition of cortical and hippocampal 5-HT release. Furthermore, there is some indication that thyroid hormones may increase cortical 5-HT₂ receptor sensitivity. In conclusion, there is robust evidence, particularly from animal studies, that the thyroid economy has a modulating impact on the brain serotonin system. Thus it is postulated that one mechanism, among others, through which exogenous thyroid hormones may exert their modulatory effects in affective illness is via an increase in serotonergic neurotransmission, specifically by reducing the sensitivity of 5-HT_1A autoreceptors in the raphe area, and by increasing 5-HT₂ receptor sensitivity.

Molecular Psychiatry (2002) 7, 140-156. DOI: 10.1038/sj/mp/4000963

thyroid system; T₄; T₃; serotonin system; adult brain; 5-HT receptor; mood modulation; affective disorders; depression