Schildkraut, Joseph

Schildkraut, Joseph J., The Catecholamine Hypothesis of Affective Disorders A Review of Supporting Evidence , American Journal of Psychiatry 122 (1965) 509-22... 

Iproniazid and imipramine seemed to work as antidepressants, but how did they achieve their effects It would be another decade before the chemical-imbalance theory was launched. In 1965, Joseph Schildkraut at the National Institute of Mental Health in Washington, DC, published a groundbreaking paper in which he argued that depression was caused by a deficiency of the neurotransmitter norepinephrine in the gaps between neurons in the brain.8 Two years later Alec Coppen, a physician at West Park Hospital in Surrey, published another version of the chemical-imbalance theory. His version differed from Schildkraut s in that it put most of the blame on a different neurotransmitter, emphasizing serotonin rather than norepinephrine as the neurotransmitter that was lacking.9... 

Cassens, Geraldine, Carol Actor, Mitchel Kling, and Joseph J. Schildkraut. 1981. "Amphetamine Withdrawal Effects on Threshold of Intracranial Reinforcement." Psychopharmacology 73 318-22. 

So in the hands of Joseph Schildkraut and Seymour Kety, the hypothesis became decreased biogenic amine efficacy = depression. Its corollary was increased biogenic amine efficacy = antidepression. So simple. So clear. So basically correct. But so incomplete. And so unsatisfying because (a) we don t really know how or why biogenic amine deficiencies develop in depression, and (b) we don t really know why the antidepressant effects take so long to kick in. The synaptic deficiencies, if any, must be corrected immediately, but the desired clinical consequences are not. What s going on ... 

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