The long-range objectives are to clarify the nature of abnormalities of cerebral laterality in diagnostic subtypes of affective illness, and to assess the potential value of behavioral and electrophysiologic measures of hemispheric asymmetry for predicting therapeutic response to treatment with antidepressants. Specific aims are: (1) to bring together, in a collaborative study at Columbia (NYSPI) and Yale (CMHC), a battery of laterality tests that show potential for identifying pathologically distinct subtypes of depression; (2) to obtain converging evidence from EEG and event-related potential (ERP) measures so as to evaluate three models hypothesized to account for abnormal cerebral laterality in depression -- the right frontal inhibition, asymmetric hemispheric arousal, and left anterior/right posterior inactivation models; (3) to expand our electrode array in order to begin to localize ERP sources that relate to hemispheric function in depression; (4) to extend our measurements of brain ERPs in patients having a bipolar disorder with mania. Three studies are proposed to accomplish these aims. The first will test depressed patients and normal controls from NYSPI and CMHC on a battery of laterality tests including: dichotic complex tones, dichotic fused words and syllables, visual dot enumeration, and a free-field faces task. A separate sample of 100 depressed patients and 30 normal controls will be tested at each center. A second study will record electrophysiologic measures in 60 of the patients and all 30 controls at NYSPI. The measures include: resting EEG alpha and ERPs recorded during the dichotic complex tone and visuospatial tests. ERPs of an additional 30 depressed patients and all 30 controls will also be recorded in a RT attention paradigm so as to provide measures of attention-related cortical activation. A third study will test 40 patients having a bipolar disorder with mania. These patients will be tested in a manic and a euthymic state so as to further investigate changes in hemispheric asymmetry accompanying these emotional states.