SynopsisThis research was aimed at studying the rate of action of tricyclic drugs in depressive disorders, specifying the behavioural effects associated with recovery, and predicting clinical response. The research design involved comparison of a recovered group with a group treated for the equivalent four weeks, who showed minimal to no response. The findings indicated significant differences in baseline characteristics between responders and non-responders. Further, the drugs were found to act early in the responders, within the first week of treatment. Specific changes at one week which distinguished responder and non-responder groups occurred in the disturbed affects, and in cognitive functioning. Improvements also occurred in somatic symptoms, but these latter changes were general and not associated with later recovery. At 2½ weeks, all facets of the depressed condition showed positive change in the responders. Implications of the results for assessing rate of tricyclic drug actions, their effects on the interaction of affect and neurochemistry, and the practical application of the results for the clinical situation, are discussed.

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SynopsisThis research is part of the NIMH-CRB Collaborative Study on the psychobiology of depression. The main objective of the research programme is to test hypotheses concerning the interaction of neurobiological mechanisms and behaviour in the depressive disorders. Part I of the report describes the rationale and the overall approach to measuring behavioural state and outcome in the research programme. Part II reports on the results of applying the behavioural methods to a comparison of the clinical phenomenology of unipolar and bipolar depression. The behavioural patterns expressed during the episode by the two groups are different. Further, the two types are shown to react differently to treatment with tricyclic drugs, reinforcing the thesis that they are qualitatively distinct forms of the depressive disorders.

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SYNOPSISA preceding paper has reviewed the history, background, and rationale for this collaborative effort exploring the biologic basis of the affective disorders. This paper details the ‘flow’ of a subject through the experimental protocol, the instrumentation used to obtain the clinical and behavioural data, and the biologic methodologies employed in the analysis of the body fluids. Data management and analysis techniques developed for this study are also examined.

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We investigated the perceived role of stressful events in episodes of major affective disorder in patients studied in the NIMH Clinical Research Branch Collaborative Program on the Psychobiology of Depression (Biological Studies). Using items from the Schedule for Affective Disorders and Schizophrenia (SADS), episodes were divided into environment-sensitive (high perceived role of stressful events) and autonomous (minimal or no perceived role of stressful events). Patients with environment-sensitive episodes had fewer previous episodes and a longer index episode. The groups did not differ with respect to age, gender, education, socioeconomic group, diagnosis, severity of illness, or eventual response to treatment. Unipolar depressed patients with environment-sensitive episodes had lower CSF 5-HIAA than those with autonomous episodes. Among bipolar depressed patients, those with autonomous episodes had elevated excretion of O-methylated catecholamine metabolites and of epinephrine, while those with environment-sensitive episodes had normal excretion of catecholamines and metabolites. Manic subjects with environment-sensitive episodes had elevated norepinephrine excretion, while this was normal in manics with autonomous episodes. Relationships between environmental sensitivity of affective episodes and neurotransmitter function therefore appear to be related to the type of episode.