Our long range goals have been to clarify the nature of the right hemisphere abnormalities in different diagnostic subtypes of affective illness, to evaluate the effects of antidepressant medications of these abnormalities and to assess the potential value of hemispheric asymmetry measures for predicting therapeutic response to treatment with antidepressants. We have made progress in identifying specific abnormalities of behavioral laterality associated with diagnostic subtypes and treatment responsive subgroups of depression. Our aims in the proposed project are not only to replicate these findings, but to expand out measurements of cortical event-related potentials (ERPs) and regional cerebral blood flow (rCBF) so as to study, more directly, the CNS mechanisms that might underlie alterations in cerebral laterality in affective disorders. The clinical significance of this research lies in the need for more precise diagnostic tests that could serve as predictors of treatment outcome with specific antidepressants. We propose to test a sample of 150 depressed outpatients on a brief test battery consisting of the dichotic listening tasks that show promise of being predictors of clinical response to a tricyclic antidepressant (TCA). Half of these patients will be tested on a long test battery. This includes temporal and spatial discrimination tasks during which ERPs are measured and visual tachistoscopic tasks. ERPs will also be measured during the Complex Tone Test that appears to be our most sensitive measure of laterality differences between diagnostic and treatment responsive subgroups. In addition, 50 of these depressed patients will receive rCBF tests. The patients are tested after a minimum drug-free period of 10 days and retested following 6 weeks of treatment with either a TCA, MAOI or placebo. Clinical responders are tested again on the dichotic tasks after 12 weeks of treatment. Normal controls (N=30) will be tested at the same test-retest intervals as patients. We also propose to test 60 inpatients having bipolar disorders with mania. Our aims here are to confirm preliminary evidence of an association between dichotic asymmetry and response to treatment with lithium, and to further investigate changes in hemispheric asymmetry in manic as compared to euthymic states.