Neurosteroids in the Pathophysiology and Treatment of Mood and Anxiety Disorders

Purpose of reviewNeurosteroids have been implicated in the pathophysiology of mood, anxiety, and trauma-related disorders, as well as syndromes specific to women such as premenstrual syndrome, premenstrual dysphoric disorder, postpartum depression, peri- and post-menopausal depression. This review summarizes the role of neurosteroids in the neurobiology of stress and that of pharmaceuticals that modulate neurosteroids in the treatment of these disorders. Recent findingsNeurosteroids may provide novel treatments of mood and anxiety disorders. While endogenous neurosteroids have poor bioavailability, there are other means by which neurosteroid activity may be pharmacologically modulated. Various synthetic neurosteroids are under investigation. In addition, naturally produced exogenous molecules that positively modulate neurosteroid action at GABA _A , as well as agents targeting enzymes that degrade or promote synthesis of neurosteroids, are being used to manipulate neurosteroid systems. SummaryNeurosteroids act on a wide variety of neuroreceptors, particularly GABA _A , playing roles in both homeostasis and the pathophysiology of stress. There is evidence that many pharmaceuticals used for mood and anxiety disorders including antidepressants, antipsychotics, and mood stabilizers may be effective secondary to their ability to modulate neurosteroids. Synthetic versions of neurosteroids, as well as pharmaceuticals that act indirectly to increase synthesis of neurosteroids, are being studied as possible treatments for a variety of mood and anxiety disorders.