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Zizkind-somerfeld research award 1992| Volume 32, ISSUE 6, P469-484, September 15, 1992

Endogenous biochemical abnormalities in affective illness: Therapeutic versus pathogenic

  • Robert M. Post
    Correspondence
    Address reprint requests to Robert M. Post, M.D., Chief, Biological Psychiatry Branch, NIMH, Bldg. 10, Room 3N212, 9000 Rockville Pike, Bethesda, MD 20892.
    Affiliations
    Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland, USA
    Search for articles by this author
  • Susan R.B. Weiss
    Affiliations
    Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland, USA
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DOI:https://doi.org/10.1016/0006-3223(92)90216-M
Endogenous biochemical abnormalities in affective illness: Therapeutic versus pathogenic
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      Abstract

      Examination of the neurobiology of psychiatric illness in general, and of affective disorders in particular, reveals a variety of associated biochemical abnormalities. These have generally been assumed to be part of the pathological process or secondary to it, and thus deserving of therapeutic efforts aimed at reversal. However, recent clinical and preclinical data suggest that some alterations occurring in the affective disorders may be compensatory and adaptive; that is, part of an endogenous therapeutic mechanism rather than part of the evolving disease process. For example, the symptom of sleep loss in depression seems to fall under this rubric inasmuch as sleep deprivation induced mood improvement in depressed patients. Preclinical data are presented that another primary pathological process—the occurrence of kindled seizures—can evoke endogenous compensatory processes that are either anticonvulsant in their own right, or enable the anticonvulsant effects of a drug such as carbamazepine. It may be that some biochemical abnormalities occurring in affective illness are similarly adaptive. As one example, increased thyrotropin-releasing hormone (TRH) has been reported in the cerebrospinal fluid (CSF) of depressed patients. This elevation of TRH and the resulting neuroendocrine profile may be part of an endogenous counter-regulatory process aimed at mood improvement. Again, preclinical seizure models are supportive in that TRH not only is induced following repeated seizures, but also exerts anticonvulsant effects on these same seizures. In an analogous fashion, TRH elevations in depressed patients may also exert ameliorating effects on depressive symptomatology. This formulation presents directly testable hypotheses that could importantly impact on our understanding of the pathophysiology of affective disorders, and suggests novel therapeutic strategies through the enhancement of endogenous compensatory mechanisms.
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      Article info

      Publication history

      Accepted: May 19, 1992

      Identification

      DOI: https://doi.org/10.1016/0006-3223(92)90216-M

      Copyright

      © 1992 Published by Elsevier Inc.

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