Developmental psychobiology of cyclic affective illness: Implications for early therapeutic intervention

The recurrent affective disorders are discussed from the perspective of accumulating inherited and experiential effects on gene expression. Stress and episodes of affective illness are viewed as leaving biochemical and microstructural residues in the central nervous system (CNS) in relation to their patterning, severity, and recurrence. Comorbid factors such as substance abuse and developmental disturbances may also interact with these illness-related variables. In addition to the primary pathological processes, secondary adaptive changes can also be induced, which, in concert with pharmacological interventions, may be sufficient to counter episode occurrences and illness progression. We postulate that the balance of primary pathological and secondary adaptive changes at multiple levels of CNS regulation accounts for recurrence and cyclicity in the affective disorders. The importance of early, effective, long-term interventions in the recurrent affective disorders and the therapeutic potential of several new treatment modalities including repeated transcranial magnetic stimulation (rTMS) are discussed.