DISEASES of the psyche have always been slippery things. Schizophrenia, bipolar disorder, major depression and a host of others have no visible markers in the brain. Their symptoms overlap sufficiently that diagnoses may differ between medical practitioners, or even vary over time when given by a single practitioner. In this they are unlike neurological diseases. These either leave organic traces in the brain that, though not always accessible before a patient’s death, are characteristic of the condition in question, or cause recognisable perturbations of things such as electroencephalograms.
The impulse to categorise, though, is enormous—as witness the ever greater number of conditions identified in successive editions of the Diagnostic and Statistical Manual of Mental Disorders, published by the American Psychiatric Association. That is because diagnosis and treatment go hand in hand. But if diagnostic categories are misconceived then treatment may be misapplied. In this context a paper published recently in Science, by a group calling itself the Brainstorm Consortium, is helpful. The consortium has brought together many research groups who work on various psychiatric diseases, as well as on neurological diseases, and has run their collective data through the wringer.
In particular, the consortium’s researchers have looked at what are known as genome-wide association studies, or GWASs. In these, thousands of genomes are searched in order to identify places where differences between people’s DNA seem associated with the presence or absence of particular diseases or symptoms. Past GWASs, comparing pairs of diseases, have shown overlapping genetic involvement in some psychiatric illnesses. But, by pooling the work of so many groups, the Brainstorm Consortium was able to go beyond this and cross-correlate the putative genetic underpinnings of 25 psychiatric and neurological problems. In all, the consortium looked at 265,218 cases of different brain disorders and 784,643 healthy volunteers who acted as controls.
Of the 25 conditions in question, ten are conventionally classified as psychiatric. Besides schizophrenia, bipolar disorder and major depression, these include obsessive-compulsive disorder, anorexia nervosa and Tourette’s syndrome. Neurological problems, the remaining 15 conditions, include Alzheimer’s disease, Parkinson’s disease, various forms of epilepsy, strokes and migraines.
There were many underlying genetic correlations between pairs of psychiatric disorders. Assuming these are in part causative of disease, such overlaps go a long way to explaining the slippery nature of psychiatric diagnosis, by providing a genetic explanation for shared symptoms.
There were also, however, observable patterns in the data that might help refine the process of classification. Major depression has at least some positive genetic correlation with each of the other nine conditions. Schizophrenia, bipolar disorder, anxiety disorders and attention-deficit hyperactivity disorder (ADHD) are strongly correlated with one another, as well as with major depression. Anorexia nervosa, obsessive-compulsive disorder and schizophrenia also cluster, as do Tourette’s syndrome and obsessive-compulsive disorder. The only psychiatric illness that showed no significant correlation with the others was post-traumatic-stress disorder.
Such clustering was absent from most neurological disorders. In particular, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and epilepsy all stood independent from each other. Nor, with the exception of migraine, which clustered with Tourette’s, major depression and ADHD, did neurological disorders show much correlation with psychiatric ones. This study therefore confirms genetically the idea that the set of diseases dealt with by psychiatry is indeed distinct from that dealt with by neurology and explains why psychiatric disease is a hydra-headed monster that is difficult to pin down.
Going from the sorts of GWASs on which the consortium relied to an underlying understanding of psychiatric illness will, though, be a long haul. The genetic differences picked out are often things called single-nucleotide polymorphisms (SNPs), which are places in the genome where a lone pair of bases, the chemical letters in which genetic messages are written, can vary between individuals. Frequently, such SNPs are not even in the bits of the genome that directly encode proteins. Rather, they are in what was once called junk DNA, because its function was unknown.
Recent research suggests that much of the junk serves to regulate when genes are translated into proteins, and how much protein is thus produced. That, in turn, determines how cells grow and what sorts of cell they turn into. With luck, analysing the genetic patterns exposed by studies such as this will eventually point out where to look in the brain’s microanatomy to find whatever miswiring is causing psychiatric disease. For, though that may not be visible at the moment, even the psyche must somehow be manifested physically in the brain and its debilitations must thus be recognisable. When that moment of understanding occurs psychiatry will truly have taken a great leap forward.