Serotonin and Major Depression

  • Kevin Malone
  • J. John Mann
Part of the The Depressive Illness Series book series (DISS, volume 3)


In 1948, a serum tonic factor released from platelets during blood clotting was first isolated, identified as a monoamine, 5-hydroxytryptamine, synthesized by Rappaport, Green, and Page (1968), and named serotonin (Page, 1968). By 1953, serotonin had been isolated from gut smooth muscle and from extracts of brain. In the 1960s a role for serotonin in the etiology of major depression was proposed. Reserpine, a drug that triggered depression in some patients, was found to deplete serotonin in brain (Pletscher, Shore & Brodie, 1955). Monoamine oxidase inhibitors (MAOI) increased serotonin content and were found to be antidepressants (Pletscher, 1991). The serotonin hypothesis of depression was developed, (Coppen, 1969; Lapin & Oxenkrug, 1969; Coppen, Prange, & Whybrow, 1972), and proposed that an increased vulnerability to either depression or mania was related to decreased serotonergic activity. Over the last 25 years, studies on blood platelets, plasma, and cerebrospinal fluid (CSF) of depressed patients reported serotonergic abnormalities. The last decade of clinical research on serotonin dysfunction in mental illness has utilized advances in neuroimaging, neuroendocrinology, neuropsychopharmacology, and molecular biology, as well as refinements in the classification of mental disorders. There has been a rapid increase in knowledge about the serotonergic system, which requires a reconsideration of the serotonin hypothesis of depression.


Major Depression Depressed Patient Suicidal Behavior Serotonergic System Suicide Victim 
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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Kevin Malone
    • 1
  • J. John Mann
    • 1
  1. 1.Laboratories of Neuropharmacology, Western Psychiatric Institute and Clinic, Department of PsychiatryUniversity of PittsburghPittsburghUSA

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