The Harold E. Himwich Memorial Lecture. Significance of biochemical parameters in the diagnosis, treatment, and prevention of depressive disorders.

There is a suggestive evidence for a relationship between central 5-HT and the occurrence of certain types of depressions. This evidence is derived from three sources: postmortem studies; measurement of CSF 5-HIAA; accumulation of CSF 5-HIAA after transport blockade by probenecid. Disturbances of central 5-HT metabolism are not typical for any depression but for certain types of vital (endogenous) depression. This implies that the group of vital depression, though tending towards homogeneity in terms of symptomatology, is heterogenous in biochemical terms and comprises patients with and without disorders in central 5-HT metabolism. It is plausible that disorders of the 5-HT metabolism play a role in the pathogenesis of depression, instead of resulting from them. This statement is based on the following findings: (i) 5-HTP can abolish or alleviate the depressive syndrome or some of its elements. (ii) This 5-HTP effect can be potentiated by clomipramine (Anafranil), a relative selective inhibitor of 5-HT reuptake. (iii) There exists a negative correlation between 5-HT turnover in the CNS and the therapeutic effect of clomipramine. The alleged distrurbances in central 5-HT are more likely to be predisposing than of direct causative significance. This assumption is based on two observations: (i) In more that 50% of cases, the 5-HT turnover remains low after clinical recovery, the patient being drug-free. (ii) There is suggestive evidence that abolition of the 5-HT deficit (by means of 5-HTP) exerts a prophylactic effect in uni-and bipolar depression.