Role of serotonin in the pathophysiology of depression

Focus on the serotonin transporter

Michael J. Owens, Charles Nemeroff

Research output: Contribution to journalArticle

744 Citations (Scopus)

Abstract

Considerable evidence has accrued in the last two decades to support the hypothesis that alterations in serotonergic neuronal function in the central nervous system occur in patients with major depression. These findings include the following: (a) reduced cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of serotonin (5- HT) in drug-free depressed patients; (b) reduced concentrations of 5-HT and 5-HIAA in postmortem brain tissue of depressed and (or) suicidal patients; (c) decreased plasma tryptophan concentrations in depressed patients and a profound relapse in remitted depressed patients who have responded to a serotonergic antidepressant when brain tryptophan availability s reduced; (d) in general, all clinically efficacious antidepressants augment 5-HT neurotransmission following chronic treatment; (e) clinically efficacious antidepressant action by all inhibitors of 5-HT uptake; (f) increases in the density of 5-HT2 binding sites in postmortem brain tissue of depressed patients and suicide victims, as well as in platelets of drug-free depressed patients; (g) decreased number of 5-HT transporter (determined with [3H]imipramine or [3H]paroxetine) binding sites in postmortem brain tissue of suicide victims and depressed patients and in platelets of drug-free depressed patients. In our studies, this reduction in platelet 5-HT transporter binding is not due to prior antidepressant treatment or hypercortisolemia and is not observed in mania, Alzheimer disease, schizophrenia, panic disorder, fibromyalgia, or atypical depression. In a pilot study, this deficit predicted treatment response to an experimental antidepressant. These findings support the hypothesis that alterations in 5- HT neurons play a role in the pathophysiology of depression.

Original languageEnglish
Pages (from-to)288-295
Number of pages8
JournalClinical Chemistry
Volume40
Issue number2
StatePublished - Mar 15 1994
Externally publishedYes

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Serotonin
Depression
Antidepressive Agents
Brain
Platelets
Hydroxyindoleacetic Acid
Tissue
Tryptophan
Blood Platelets
Binding Sites
Suicide
Pharmaceutical Preparations
Cerebrospinal fluid
Paroxetine
Imipramine
Serotonin Uptake Inhibitors
Neurology
Metabolites
Fibromyalgia

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Role of serotonin in the pathophysiology of depression : Focus on the serotonin transporter. / Owens, Michael J.; Nemeroff, Charles.

In: Clinical Chemistry, Vol. 40, No. 2, 15.03.1994, p. 288-295.

Research output: Contribution to journalArticle

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