DRUG-INDUCED ACTIONS ON BRAIN NEUROTRANSMITTER SYSTEMS AND CHANGES INTHE BEHAVIORS AND EMOTIONS OF DEPRESSED-PATIENTS

Despite cumulative evidence that the tricyclic drugs result in signifi cant changes in the functioning of brain serotonergic (5-HT) and nordr energic (NE) systems, such changes have not been found to be associate d with recovery from depression. Based upon evidence that the 5-HT ant i NE systems were associated with different emotions, it was hypothesi zed that changes in these systems were associated with different compo nents of behavior in drug-responsive patients and not with changes in the ''whole'' disorder. Findings from this multihospital study of 104 unipolar and bipolar depressed patients showed early drug-associated r eductions in anxiety and hostility in treatment responders to precede changes in motor retardation and depressed mood. Adopting this approac h of looking for relationships between changes in components of major depression and changes in neurotransmitter system function, decreases in 5-HT and NE metabolite concentrations in cerebrospinal fluid (CSF) in patients treated with tricyclics, were found to be correlated with changes in specific behaviors. Results indicated the following: (1) dr ug-induced changes in the 5-HT system to be associated with mood aspec ts, notably anxiety, and depressed mood; changes in NE primarily with the psychomotor, secondarily with the mood components of the depressed state; (2) the pattern of relationships between changes in 5-HT and i n mood in the unipolar was different than that in the bipolar subtype. The results indicate that in determining the relationships of biochem ical changes to behavioral ones, that it is important to take into acc ount the type of depression (bipolar or unipolar), as well as examinin g individually and over time those components that make up the disorde r of depression. These results support evidence that tricyclics have m ultiple behavioral actions, that response is mediated through changes in specific behaviors and that this approach warrants further applicat ion in prospective studies of antidepressant drug mechanisms and their therapeutic actions.