A Few Bars

Dr. Philip Grossi
Monday, 05 January 2015

I have recently been thinking of the evolution of psychiatry from the later part of the nineteenth century and my own exposure, as a psychiatrist, to this evolution over the last half century.  During the later part of the nineteenth century psychiatric illnesses were conceptualized as either organic or functional based on the findings at postmortem examination. At that time the tools for examination of the brain were too crude to reveal subtle organic changes to nerve cells and brain tissue.  Thus alcoholism, Huntington's disease and Alzheimer's were classified as organic diseases but schizophrenia, bipolar disorder, mood disorders, and anxiety disorders were classified as functional mental illnesses because no brain pathology could be identified. These illnesses were often thought of as being in a person's head and were often considered a result of pathological rearing, e.g., the schizophrenogenic mother.

This distinction is no longer consistent with our modern concept of mental states. Psychiatrists no longer believe that only certain mental states are mediated by biological processes; but, now we believe that all mental processes are biological and are the result of cellular processes which are in turn dependent on biochemical processes and their genetic underpinnings. The process of coming to these conclusions has been convoluted and tortuous. Starting in the 1880s Freud began his investigation of hysteria. He developed a new method of investigating manifest and latent verbal content produced by patients. Freud's prolific and elegant writing (he was nominated for a Nobel prize in literature) propelled psychoanalysis into the dominant theoretical formulation of mental states for the first half of the twentieth century.  During the 1950s the investigative power of psychoanalysis was exhausted and its reliance on the subjective interpretation of the psychoanalyst came under heightened scrutiny because it did not allow for empirical testing of its conclusions. It lost any claim to scientific inquiry and became more a therapeutic art which was exactly the opposite direction of the rest of medicine.

There were other developments which moved psychiatry away from psychoanalysis and toward biology and empirical testing. In 1952 chlorpromazine was discovered in France.  It was the first of a class of tranquilizers which were used to suppress hallucinations and other psychotic phenomena.  Derivatives of that class are still used today. Also in 1952 several new drugs were tested in the treatment of tuberculosis. The researchers found that patients treated with those agents became "energized, were inappropriately happy, and even discipline problems." Upon further investigation these drugs were discovered to function a monoamine oxidase inhibitors (MAOI). In the late fifties several drugs with this mode of action were introduced into the marketplace and promoted as antidepressants. Keep in mind that prior to 1952 there were no antidepressants and the word "antodepressant" was not even in the English language. People who were depressed prior to 1952 were given either opiates or stimulants.

In 1965 Joseph Schildkraut published an article in the American Journal of Psychiatry entitled "The Catecholamine Hypothesis of Affective Disorders". This article documented the neuropharmacological studies which suggested that the newly introduced antidepressants produced their clinical effects by altering catecholamine metabolism. This stimulated research which eventuated in the introduction of the SSRIs in the late 1980s and early 1990s. In the last fifteen years other attempts to elucidate higher order mental processes, emotions and thinking, using genetic tools have been gaining research prominence.  Determining the genetics of mental illnesses has been much more challenging than neurological illnesses because there is no single gene causing the illness such as in Huntington's disease. The mental illnesses appear to be caused by many genes of small effect which interact with one another and with the environment to cause a genetic predisposition. Once certain environmental factors are added to this predisposition, the illness is expressed.  A good example of this is the work done on identical twins where one twin meets criteria for the illness. Since the genes are identical in the twins, one would expect a concordance rate of 100%, that is, all of the twins would have the illness.  Turns out that only 69 twin pairs have the illness. 

I have tried to whistle a few bars of a very long and involved song and dance.  I hope I have conveyed an overall sense of the trends in psychiatry over the last fifty years.





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