Bench and couch: genetics and psychiatry
Posted by gregdowney on July 19, 2008
Vaughn at Mind Hacks has a nice piece on recent research, reported in Nature, on psychiatric genetics: Mental illness: in with the intron crowd. The original article, Psychiatric genetics: The brains of the family, appeared in Nature on 10 July (but it’s behind a subscription wall if you want to see the original — sorry). Daniel linked to Vaughn’s article in the last Wednesday Round Up (#20), but I wanted to make a further brief comment. Vaughn does a really nice job of laying out the key issues, so I’d recommend jumping over there if this brief discussion whets your appetite.
The problem for neuropsychiatry is that genetic links to psychiatric disorders are proving difficult to clearly define. Abbott explains the situation really well:
Finding genes involved in psychiatric conditions is proving to be particularly intractable because it is still unclear whether the various diagnoses are actually separate diseases with distinct underlying genetics or whether… they will dissolve under the genetic spotlight into one biological continuum. Indeed, some researchers suggest that it would be better to abandon conventional clinical definitions and focus instead on ‘intermediate phenotypes’, quantifiable characteristics such as brain structure, wiring and function that are midway between the risk genes involved and the psychopathology displayed.
The case of DISC1
For example, as Abbott’s original article discusses, a massive translocation of genetic material between chromosome 11 to chromosome 1, first found in a member of a family with a record of juvenile delinquency in Scotland, was discovered in four generations of family members, with widely varied effects:
Of those who carried it, five had depression, six had schizophrenia or related disorders, three had adolescent conduct disorder and two had anxiety disorder. One had attempted suicide and died in a mental hospital. Several of those without the translocation had their own problems, including anxiety, minor depressive disorder and alcoholism.
The translocation affected a gene, disrupted-in-schizophrenia 1 (DISC1) that has also shown up in studies of autism and bipolar disorder, although it hasn’t always been indicated in screens for genes linked to schizophrenia. In other words, both a genetic abnormality and psychological problems ‘ran in the family’ for this set of Scottish subjects; for a previous generation of theorists, this would have been enough to demonstrate that psychological disorders were ‘genetic.’ The problem was, the pattern is far from clear, and it sure doesn’t offer any easy explanatory story about the effects of this genetic translocation, or the origins of any particular disorder. That is, disorder looks ‘genetic,’ but it’s hard to actually figure out which genes or the genetic mechanism producing disordered development.
Vaughn discusses the pitfalls of trying to link completely different ‘levels of description’ and scales of process. In genetic psychiatry, attempting to associate microscopic genetic links and neurophysiological effects (already a complex set of relations) to observable behaviour and reportable symptoms in patients (again, already themselves in complex relations) is fraught with problems. There’s no guarantee, as Vaughn puts it, that reported symptoms — the phenomenology of psychiatric disorder — have any clear link to observable neurophysiological mechanism. And there’s no guarantee that the professional tradition of psychiatry has categories to work with that actually reflect underlying disease etiology. With a new edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM V) due out in a few years (2009 for preliminary draft; 2012 for publication), some psychiatrists are convinced that the 300 disorders listed are much more fluid and variable, overlapping and interrelated, than their professional ancestors may have thought.
Research in genetic psychiatry
Abbott highlights debates within genetics and neuropsychiatry about how to pursue more in-depth understanding of genetic contributions to psychiatric disorder; are current methods inadequate even misguided, or are the studies simply too small and require more subjects (and money) to produce reliable results? The debate is not merely pragramatic. The argument highlights different understandings of psychiatric disorders themselves and the relation of symptoms to potential genetic roots.
For example, some researchers think that the genetic confusion around disorders is exacerbated by psychiatric categories that themselves conceal a large amount of variation, perhaps even a continuum of cognitive and emotional disruptions of various sorts. In other words, two people diagnosed as ‘schizophrenic’ may have very different underlying biological issues. Several researchers advocate different overall strategies for pursuing contributing genes. I don’t want to redescribe the article completely — Vaughn does too good of a job of slicing it up, and the original Abbott piece is excellent if you can get it, so go visit Vaughn or jump to Nature News (again, apologies about the subscription wall).
But what I want to highlight is the problem discussed at the end of the Abbott article and by Vaughn: since diagnosis of psychiatric disorders is so fraught with challenges, it’s hard to even get a decent subject pool for the genetic studies. That is, the professional-social-intellectual tradition of psychiatry is itself a factor affecting how the science is being pursued. This point is pretty common in critical studies of science; science is itself a social project, and it builds upon conventional understandings of research ‘problems,’ not merely empirically verified ‘facts.’
Psychiatry is a particularly tricky contributor to the neuroanthropological mix because it has this uneasy relationship to science; on the one hand, psychiatry acts like a science, investigating cases, conducting clinical trials, and the like. On the other hand, it clearly partakes in cultural meaning making processes on a number of levels; for example, psychiatric therapies involving individual-level interactions — ‘talking therapy’ — has demonstrated effects on mental disease. But it is unclear all of the social facts that contribute to the success of these methods. Because we’re more concerned with the outcomes than the processes that produce them in psychiatry, we can usually ignore exactly how therapy is working, but I think it’s important to point out that psychiatry works through society and history, not just in individuals in biographical time.
Psychiatric disorders change over time in frequency and character, and patients become differently susceptible to treatment depending upon the historical, social and cultural context. Freud’s patients don’t look like modern patients in most cases, and they were likely treatable with different techniques than contemporary sufferers because of their patterns of social interaction and resources available.
None of this is news to self-aware psychiatrists, of course, but I get nervous about it when psychiatry is brought into contemporary neuroscience discussions. For example, in several recent popular press books, I have found that the boundary between neuroscience and psychiatric findings — very different in origin and application — is sometimes glided over. The existence of mirror neurons and of ‘counter-transference,’ although both empirically derived, has been demonstrated in very different ways following different evidentiary rules and on different observational scales. Sometimes I worry that observable neurophysiological processes are too quickly labeled with familiar psychiatric terms, blunting the insight we might gain from the bench research and prematurely assuming that psychiatry-as-usual has been confirmed with neurophysiological mechanisms.
The Abbott piece highlights the difficulties of attributing phenomenological dimensions to demonstrated neurophysiological events; for example, because we find a protein that affects a particular brain area doesn’t necessarily mean that we’ve identified the neural correlate of a ‘panic attack.’ Clearly, both sorts of data, bench research and experience-based accounts from the couch, are essential, but, like some of Abbott’s researchers, I just get nervous when we bring the two together too quickly.
Abbott, Alison. 2008. Psychiatric genetics: The brains of the family. Nature 454: 154-157. doi:10.1038/454154a