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Science 5 October 1973:
Vol. 182. no. 4107, pp. 20 - 29
DOI: 10.1126/science.182.4107.20
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Articles

Depressive Disorders: Toward a Unified Hypothesis

Clinical, experimental, genetic, biochemical, and neurophysiological data are integrated

Hagop S. Akiskal 1 and William T. McKinney Jr. 2

1 University of Tennessee College of Medicine, 42 North Dunlap St., Memphis 38103
2 University of Wisconsin School of Medicine, 1300 University Avenue, Madison 53706

Our scientific understanding of psychiatric syndromes, including the phenomena of depression, has been hampered because of: (i) the use of metapsychological concepts that are difficult to test; (ii) methodological and linguistic barriers that prevent communication among psychoanalysts, behaviorists, experimental psychologists, and psychiatrists; and (iii) the reluctance of psychiatrists to accept animal models as possible approximations of certain aspects of human psychopathology.

We have attempted to demonstrate that the animal models simulate some of the central features of clinical depression (for example, helplessness and object loss), thereby allowing one to rigorously investigate them from developmental, behavioral, and biochemical perspectives.

The object loss model, as a concrete version of a metapsychological-psychoanalytic concept, has enabled primatologists to study the disruption of an attachment bond. The behavioral model accommodates this concept to a broader generalization: loss of reinforcement or loss of control over reinforcement. We have reviewed the evidence that these processes involve the diencephalic centers of reward or reinforcement, thereby permitting integration of the psychoanalytical and behavioral formulations with the biochemical hypotheses. Also, we have presented data strongly suggesting that the breaking of an attachment bond in the primate represents significant loss of reinforcement that induces helplessness and disrupts motivated behavior.

Finally, we have argued that the depressive syndrome could be caused by interactions of genetic, chemical, developmental, and interpersonal factors, all of which impinge on the diencephalic centers of reinforcement.


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