Recent concepts of neuromodulators in affective disorders

Though certain controversies exist current hypotheses on the etiopathogenesis of affective disorders postulate a dysfunction in central neurotransmitter systems, mainly of the biogenic amines serotonin (5-HT) and/or noradrenaline (NA). As antidepressants have differential influence on neurotransmitter function and prediction of clinical response is unreliable, recent investigations attempt to define more "serotoninergic" or "noradrenergic" types of endogenous depression. Results of our as well as of other groups indicate that NA turnover (as measured by the excretion of 3-methoxy-4-hydroxymethylglycol-MHPG-) is low in patients who respond to imipramine and amphetamine and high in subjects who respond to amitriptyline and sleep deprivation. Conversely, 5-HT turnover (as measured by 5-hydroxyindole acetic acid concentration in cerebrospinal fluid) has been found to be low in patients who respond to clomipramine and amitriptyline and to be normal or high in those who respond tp nortriptyline. These findings suggest biochemical heterogeneity of depressions which are largely uniform in their clinical appearance. Further investigations are presented which indicate that, in addition to NA and 5-HT, acetylcholine functions contribute significantly to the regulation of mood and drive.