Tuesday, May 27, 2008

it could happen to you

Mr G, a gentleman in his sixties with an engaging manner and a professional degree, had never set foot in a psychiatric unit until today.  Bald and avuncular, with a rich white beard and a mischievous wink, he had a bit of a drinking problem and some deep-buried scars from his time in Vietnam.  But nothing else really, none of the 'meat' of inpatient psychiatry (schizophrenia, schizoaffective, bipolar disorder) that we spend our time handling.

Someone somewhere thought two antidepressants and some Antabuse would be good for him.  In a week or two he had changed his personality entirely, wandered into moving traffic, threatened the police who came to the scene, and attempted to seduce the psychiatry resident who admitted him - nothing anyone who knew him could have believed.  Indeed his family members called daily, frantic for understanding, unable to comprehend how their loved one had been replaced by a stranger.  In short, he had had a manic and psychotic episode.

But what is 'psychotic,' other than a term used loosely by the ignorant to describe the behavior of those who irritate them?  Psychosis is a mental state characterized by the impairment of reality testing.  Any society typically has a consensus about what is 'real' and what isn't.  (Judgements about this may differ between societies, but that's a different treatise.)  People suffering from psychosis have fallen off this bandwagon and have very different ideas about what is 'real' from the man on the street.  But there's a method to the madness: psychosis typically involves several specific, bizarre modes of thought. Auditory hallucinations (usually voices), delusions (fixed false beliefs), and paranoia (the pervasive and unshakable feeling that unknowable dangers lurk) are hallmarks of the syndrome.  Though each patient is unique, themes quickly emerge, and anyone who has spent more than a week or two on an inpatient psychiatric unit will begin to recognize the patterns.

Psychosis, clearly, is not a torture reserved for the unlucky few born to its ravages, like cystic fibrosis or a Thalidomide deformity.  I suspect it may be an alternative mode of function that lies buried in each of us, more deeply for some than for others.  It can be precipitated in otherwise mentally healthy people by pregnancy, medical illness, or - as in Mr G's case - merely the wrong combination of medications.  An unlucky few have the problem of chronic or recurrent psychosis.  This is the disease schizophrenia, a disorder with its peak onset in the normally promising and productive years of early adulthood.

Some are doubtless more susceptible than others; as with every human trait, psychotic tendencies lie along a continuum.  Mr G had always been a bit up-and-down in his moods, and while another person might have been able to tolerate the double-antidepressant regimen, for Mr G it magnified his normal highs and lows into an off-the-charts manic spike that came, as extreme mood disorders sometimes can, with the booster benefit of psychotic symptoms.

But what is this psychosis then, what is it for?  Why does its potential lie buried somewhere in so many of us?  What purpose does it serve?  Some have argued that it is a byproduct of the development of social complexity in the human brain  (see for example, Burns JK).
Unfortunately, this particular argument (and related ones) suffer from a lack of specificity and a paucity of evidence.  They certainly sound reasonable; but the logic boils down to this: Schizophrenia is a complex behavioral disorder - social and creative endeavors require complex processing and behavior - schizophrenics have difficulty with social functioning - ergo, these modules are related.

I don't doubt that schizophrenia (and psychosis more generally) are related to social functioning, given how important social functioning is to humans - almost everything we think or do is related to social functioning, broadly defined.  But that makes the hypothesis that 'schizophrenia is related to social functioning' so broad as to be useless. 
Another line of reasoning jumps off the intriguing finding that artistic inclinations and schizophrenia are often found in the same families (see Horrobin DF), and posits that schizophrenia is merely the other face of the coin of creativity.   This one is slightly more specific (creativity being less of a blanket term than 'social function') and can claim at least some circumstantial evidence to its credit.  

Dr Horrobin also does a nice job of suggesting a biochemical basis, though I am in general skeptical of papers that claim to pinpoint individual biochemical factors or pathways as causative of psychiatric diseases.  Psychiatric illnesses are complex states of the person as a whole, and doubtless they affect and are affected by many, many biochemical pathways (most of which, as we are discovering, interact with each other anyway).  Generally I'd say that trying to pinpoint a single gene, factor, or pathway in the pathogenesis of psychiatric disease is sort of like blaming global warming on a carbon dioxide spike in Juneau in the summer of 1998.  Sure, they're related; but there are a bunch of other factors involved, and who knows which way the causal arrow goes anyway.

In any case, those optimistic scientists who have persisted in trying to pinpoint single specific causes of psychiatric diseases are indeed finding out that the problem is significantly larger than one might have guessed back in the flushed and heady days of the one-disease-one-gene school of thought (Iwamoto and Kato).

I don't doubt that we'll make some interesting progress on this problem once as we develop better tools to manage and investigate complexity in biology.  The ever-growing computational power that's available to us makes it feasible to look at complex interactions in a way that was impossible twenty years ago.  It's going to be an interesting next couple of decades.

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