The HPA System and Neuroendocrine Models of Depression

  • Ned H. Kalin


For years, clinicians have known that depression is associated with specific endocrine abnormalities. Perhaps the most frequent examples are found in patients who suffer from primary disorders of the pituitary-adrenal system. In 1913, Harvey Cushing published a landmark paper in the American Journal of Insanity titled “Psychiatric Disturbances Associated with Disorders of the Ductless Glands” (Cushing, 1913). In addition to reporting case histories where cognitive, affective, and vegetative symptoms occurred in individuals with hypercortisolism (Cushing’s syndrome), he astutely commented on the complex relationship between the central nervous system and altered endocrine function:

Psychic conditions profoundly influence the discharges from the glands of internal secretion, but we are on a much less secure footing when we come to the reverse, namely the effect on psyche and nervous system of chronic states of glandular overactivity or underactivity. However, ... it is fair to assume that each of the resultant clinical types will exhibit more or less characteristic mental deviations; for the influence of the somatic condition on the mind is certainly as great as that of mind on body. (Cushing, 1913)


Glucocorticoid Receptor Locus Coeruleus Acoustic Startle Depressive Syndrome Comp Physiol Psychol 
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© Birkhäuser Boston 1989

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  • Ned H. Kalin

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