Endocrine Psychiatry: Solving the Riddle of Melancholia (review)

In the late 1960s Australian psychiatrist Bernard Carroll administered an oral dose of the synthetic glucocorticoid dexamethosone to twenty-seven "typical" melancholic patients and twenty patients with no depressive illness. Both groups exhibited the same cortisol levels prior to the administration of dexamethosone; but afterward the cortisol in controls remained stable, while in the melancholic patients levels rose dramatically. Seventeen of the twenty-seven severely depressed patients subsequently were treated with electro-convulsive therapy (ECT), after which their cortisol levels dropped to the normal range.¹ Based on this and subsequent studies, Carroll concluded that suppression of cortisol was an effective intervention for severe melancholia.

Carroll, who would soon move to the University of Michigan, believed that his dexamethosone suppression test (DST) could aid clinicians in determining which interventions were most appropriate for depressive patients. For those with high cortisol levels, treatment with ECT or tricyclic antidepressants was necessary, but if cortisol levels following the DST were normal, a patient would be referred to more traditional psychotherapies. In studies published over the following decade Carroll and his collaborators claimed that monitoring via the DST provided an accurate way to determine a patient's risk for relapse.

Carroll's findings and claims provide the frame of Endocrine Psychiatry: Solving the Riddle of Melancholia, a collaboration of medical historian Edward Shorter with psychiatrist Max Fink. Their book aims not only to rescue a now forgotten chapter of the history of psychiatry but also to advocate its validity and resurrection. Endocrine psychiatry was based on the belief that there were two types of depressive illness: the first, melancholia, was biological, while the second was mood based and situational. However, the 1980 third revision of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-III) merged both forms into a category labeled "major depression." Based on the criteria of major depression, the DST test proved unreliable because it identified only a minority of the now redefined depressed population. "With the DSM-III's major depression, both the sensitivity and the specificity of the DST sank," write Shorter and Fink (p. 79). The DST, recalled psychiatrist Paul McHugh, "does not fit DSM major depression . . . not because DST is not specific, it's because DSM is not specific enough" (p. 79). Carroll himself concluded that "the DSM-III killed the DST," a view endorsed by Shorter and Fink: "Confronted with measuring an entity that was very poorly defined, the test performed even more poorly, causing a loss in confidence in a profession prone to herd behavior" (p. 80).

Although others, most notably Edward Sachar at Columbia University, would both widen and refine endocrine psychiatry to include mania and anxiety disorders, the combination of the DSM phenotype and the identification of affective neurotransmitters changed the focus of psychiatry from hormones to affective neurotransmitters. This developing emphasis on brain transmission and receptor uptake ensured the demise of endocrine psychiatry in the early 1980s. The new phenotype of "major depression" became the target of pharmaceuticals, ultimately the lucrative SSRIs and their atypical offspring. As a result, few of those trained in psychiatry in the past two decades are aware of endocrine psychiatry, let alone its putative efficacy.

Shorter and Fink retell this rise and fall of endocrine psychiatry in great detail. Along the way they provide an accessible discussion of the wider scientific context in which endocrine psychiatry emerged. In particular, their discussion of the emergence of neuroendocrinology elucidates the mechanisms of the thyrotropin-releasing hormone (TRH) for which Roger Guillemin and Andrew Schally would be awarded the Nobel Prize in 1977. Understanding the action of TRH, according to Shorter and Fink, gives additional scientific validity to the DST as it provided evidence that melancholia and other severe mental disorders resulted from a disordered neuroendocrine system.

Although he concedes that "the DST methodology has limitations," Fink insists that it is "a positive test [which] verifies the diagnosis of melancholia much...