Neuroplasticity and cellular resilience in mood disorders

Although mood disorders have traditionally been regarded as good prognosis diseases, a growing body of data suggests that the long-term outcome for ma ny patients is often much less favorable than previously thought, Recent mo rphometric studies have been investigating potential structural brain chang es in mood disorders, and there is now evidence from a variety of sources d emonstrating significant reductions in regional CNS volume, as well as regi onal reductions in the numbers and/or sizes of glia and neurons. Furthermor e, results from recent clinical and preclinical studies investigating the m olecular and cellular targets of mood stabilizers and antidepressants sugge st that a reconceptualization about the pathophysiology and optimal long-te rm treatment of recurrent mood disorders may be warranted. It is proposed t hat impairments of neuroplasticity and cellular resilience may underlie the pathophysiology of mood disorders, and further that optimal long-term trea tment for these severe illnesses may only be achieved by the early and aggr essive use of agents with neurotrophic/neuroprotective effects, It is notew orthy that lithium, valproate and antidepressants indirectly regulate a num ber of factors involved in cell survival pathways including CREB, BDNF, bcl -2 and MAP kinases, and may thus bring about some of their delayed long-ter m beneficial effects via underappreciated neurotrophic effects. The develop ment of novel treatments which more directly target molecules involved in c ritical CNS cell survival and cell death pathways have the potential to enh ance neuroplasticity and cellular resilience, and thereby modulate the long -term course and trajectory of these devastating illnesses.