Brain Chemistry Researcher Dies at 72. (New York Times ) Schildkraut, if anyone, deserves to be known as the father of biological psychiatry, with seminal contributions to both the catecholamine (norepinephrine and serotonin) theory of depression and the dopamine theory of schizophrenia. His methodology, for better or worse, has been the dominant one in the field for four decades — you look at the changes in brain chemistry that result from treatment with a drug known to have clinical benefit to a psychiatric condition. If a particular change is consistently associated with clinical improvement (e.g. an increase in low catecholamine levels after antidepressant treatment), you infer that that change is responsible for the improvement. You go further and conclude that the original abnormality, in this case the low catecholamine levels, was the cause of the condition.

This way of doing things, indeed biological psychiatry as a whole, has several problems. First, it it has enshrined reductionism at the heart of psychiatric theory and solidified the error of mistaking correlation for causation. The observed chemical abnormality in a mental illness may be an epiphenomenon of other, more causal, neurochemical changes in the condition, not the cause itself. As a corollary, it constrains new drug development. If you believe catecholamine deficit is the root cause of depression, the only new substances you are going to screen for clinical effectiveness as antidepressants are those shown in the laboratory to increase brain catecholamines. If you believe that dopamine excess is the root cause of schizophrenia, the only medications you are going to screen for utility as antipsychotics are dopamine blockers. We have many counterexamples, discovered by accident, of antidepressants and antipsychotics that, while clinically effective, do not appear to work by the required biochemical mechanisms. Perhaps, if a different paradigm had dominated drug development over the last forty years, we would have many more.

Most profoundly, it has solidified a divide between those, patients and practitioners, who struggle with the meaning of mental suffering in a patient’s life and those who merely throw pills at that suffering. The notion that their illness has been caused by a ‘chemical imbalance’, as numerous patients and families have come to believe, has become a barrier to experiencing themselves as having any control over their recovery. This is a profound problem because the alteration of experience and sense of self in various mental illnesses is all about loss of agency, responsibility and locus of control in the first place.

Schildkraut himself was no such reductionist, however. Another of his areas of interest in mental illness was the relationship between depression and creativity, and he observed in 1994 that depression in artists “may have put them in touch with the inexplicable mystery at the very heart of the tragic and timeless art they aspired to produce.”