Psychiatry is Warming up to Personalized Medicine 2.0

During the era of classical psychiatry, doctors already suspected that heredity might well be the main driving force behind mental disorders. Today, with an estimated heritability of 46.3% for neuropsychiatric disorders in general [1], and of 70% for schizophrenia [2], the genomics era has proved those 19th century pioneers right, and instilled much optimism with regard to genetic tests enabling us to diagnose specific disorders, predict treatment responses to psychotropic substances and prevent side effects. And yet precisionhealth approaches are still rare in clinical psychiatry, with only few disorders – other than Huntington’s disease and 22q11 deletion syndrome – lending themselves for genetic testing. With hundreds of causal genetic variants unearthed so far, and thousands suspected to exist, it is easy to blame this on the polygenic and pleiotropic nature of genetic contributions to psychiatric disease. And yet there is more. It is also due to the fact, as famously stated by Kenneth Kendler, that “patterns of underlying genetic liability do not map well onto current DSM [Diagnostic and Statistical Manual of Mental Disorders] categories – that is, our genes seem neither to have read DSM-IV nor to particularly respect the diagnostic boundaries it established” [3]. Since that insightful remark, the DSM has moved on to its fifth edition [4], but matching its numerous disorders with findings from genetic studies has remained an ongoing challenge, and the personalized approach has remained a rather futuristic ideal in psychiatry. Which is a pity, since psychiatry once had a head start in the area of personalized medicine, long before the term had even been invented. Around the turn of the 19th century, the literature in my discipline brimmed with clinical descriptions, neuropathological findings and novel disease concepts that were readily applicable to individuals with highly specific symptoms and syndromes. I would have loved to be a doctor during that pivotal era, and browse through the freshly printed issues of scientific journals providing the exciting first descriptions of autoscopy [5], peduncular hallucinosis [6], Capgras’ syndrome [7], Alzheimer’s disease [8], dissociation [9], cryptomnesia [10], Riddoch’s phenomenon [11] and many other symptoms, syndromes and disorders, only few of which eventually made it into the DSM. Given the phenomenal richness of that innovative period, we may ask ourselves – and should in fact ask ourselves – what happened during the intervening time to make us end up with diagnostic tools such as the DSM-5, which either lump those specific clinical disorders together into broad disease categories or fail to mention them at all. The answer to that question is quite sobering. For lack of any specific therapeutic interventions, 19th century psychiatric Psychiatry is warming up to personalized medicine 2.0