3 - Psychoneuroendocrine aspects of treatment-resistant mood disorders

Summary

Introduction

Recent advances in our understanding of hormone action in the brain, coupled with growing evidence of hormonal dysregulation in affective disorders, have prompted the use of hormones and hormone antagonists as endocrinologically based treatments of depression. Since hormonally based treatments presumably act at sites distinct from those of traditional antidepressants, they may specifically benefit patients unresponsive to the latter drugs. Clinical applications of psychoneuroendocrinology are largely in their infancy, but certain strategies have already entered clinical practice and others appear promising. The following selective review begins with the more well-established hormonal therapies for treatment-resistant depression and concludes with less well-studied, but nonetheless biologically informed ones.

Thyroid

Although interest in the role of thyroid hormones in the biology of mood disorders is longstanding, the prevalence of abnormalities and their pathophysiologic significance remains controversial (Fava et al., 1995; Howland, 1995). Some, but not all, investigators have found a higher rate of elevations in total T₄ and FT₄ in the depressed population than in controls (JoVe & Sokolov, 1994; Nader et al., 1995; Scherer, 1994). Alterations in T₃ level and an increased prevalence of antithyroid antibodies have also been reported (Reus & Freimer, 1990), as have low levels of CSF transthyretin (Sullivan et al., 1999). Frank hypothyroidism is rarely found upon routine screening of patients with major depression, but subtle alterations in basal TSH and TSH response to TRH infusion are quite common (Bunevicius et al., 1994, 1996).