Serotonergic dysfunction in depression

H. Meltzer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

205 Scopus citations


Various irregularities in serotonin (5-HT) function have been postulated as causes of affective disorders. Serotonin has been related to many of the major symptoms of depression, e.g. mood, appetite, sleep, activity, and cognitive dysfunction. Interference with 5-HT synthesis or storage has been shown to induce depression in vulnerable individuals. Decreased levels of 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid, decreased plasma tryptophan, low tryptophan neutral amino acid ratio, abnormalities in serotonergic function indicated by neuroendocrine challenge tests and various platelet measures, have been reported in depressed patients. Concentrations of 5-HIAA, the major metabolite of 5-HT in plasma, were found to be significantly negatively correlated with severity of depression as measured by the Hamilton Rating Scale for Depression score and specific depressive symptoms, despite the fact that plasma 5-HIAA is largely peripheral in origin. Blood platelets, which have been suggested as models for serotonergic nerve terminals, have a significantly decreased number of 5-HT uptake sites and 3 H-imipramine binding sites in depressed patients. Antidepressant drugs may act, in part, by enhancing serotonergic activity. The serotonergic deficit may occur at any of several levels: diminished availability of precursor, impaired activity of tryptophan hydroxylase, abnormalities in 5-HT release or uptake, 5-HT receptor abnormalities or interactions with other neurotransmitters.

Original languageEnglish (US)
Pages (from-to)25-31
Number of pages7
JournalBritish Journal of Psychiatry
Issue numberDEC. SUPPL. 8
StatePublished - Dec 1 1989

ASJC Scopus subject areas

  • Psychiatry and Mental health


Dive into the research topics of 'Serotonergic dysfunction in depression'. Together they form a unique fingerprint.

Cite this