Neurosteroid influence on affective tone.

ABSTRACT

Affective disorders such as depression and anxiety are among the most prevalent psychiatric illnesses and causes of disability worldwide. The recent FDA-approval of a novel antidepressant treatment, ZULRESSO® (Brexanolone), a synthetic neurosteroid has fueled interest into the role of neurosteroids in the pathophysiology of depression as well as the mechanisms mediating the antidepressant effects of these compounds. The majority of studies examining the impact of neurosteroids on affective states have relied on the administration of exogenous neurosteroids; however, neurosteroids can also be synthesized endogenously from cholesterol or steroid hormone precursors. Despite the well-established influence of exogenous neurosteroids on affective states, we still lack an understanding of the role of endogenous neurosteroids in modulating affective tone. This review aims to summarize the current literature supporting the influence of neurosteroids on affective states in clinical and preclinical studies, as well as recent evidence suggesting that endogenous neurosteroids may set a baseline affective tone.