G Proteins in the Pathophysiology and Treatment of Mood and Anxiety Disorders

Mood and anxiety disorders are common, severe, chronic, and often life-threatening illnesses. Despite wellestablished genetic diatheses and extensive research, the biochemical abnormalities underlying the predisposition to, and the pathophysiology of, these disorders remain to be clearly established. Early biologic theories regarding the etiology of anxiety disorders and, in particular, mood disorders, have focused on various neurotransmitters, in particular the biogenie amines. In recent years, however, advances in our understanding of the molecular mechanisms underlying neuronal communication have focused research into the role of receptor and postreceptor sites, and indeed, numerous findings from both clinical and preclinical studies suggest that abnormalities in receptor-effector responsiveness may be involved in the pathophysiology of mood and anxiety disorders. Data from a complementary line of research on the cellular mechanism(s) of action of antidepressants, mood-stabilizing agents, and antianxiety agents have also been used to provide clues about the biochemical processes involved in the pathogenesis of these disorders. There has been a growing appreciation that neurotransmitter function might be altered indirectly through alterations in intracellular signaling, and antidepressants, mood-stabilizing agents, and antianxiety agents might be effective not because they are “catecholaminergic” or “serotonergic” agents per se, but because they alter the postsynaptic signal generated in response to multiple, endogenous neurotransmitters.