Genetics of Psychiatric Conditions

The Cross-Disorder Group of the Psychiatric Genomic Consortium has done it again!

Who are they?  Oh, some really smart psychiatric research scientists following on a hunch:  they think it is better to say there is no such thing as bipolar disorder or schizophrenia, per se, but that we have clusters of disorders, dysfunctions across different domains (such as cognitive processing, perception, emotion regulation, executive function, working memory, fear-response to external stimuli, and so forth).  They study genetics in huge studies involving the DNA of tens of thousands of subjects.

So, whats their discovery?

Well, they have published two respected articles now, in the recent year, with the last released just now, in respected journals (Lancet, Nature Genetics), that show something amazing–the genetics of psychiatric symptoms cuts across diagnoses.  Huh?  It means there is no genetic proof of something called bipolar or schizophrenia as a specific entity.  Rather, there are lots of genetic alterations of DNA (any of,  sequence and structure and repeats and copies) and each does something different to the brain.

Specifics?

Their data shows that maybe 20-25% of the contribution to either bipolar or schizophrenia is SNP variants (i.e. variants of sequence) and the rest is environmental, gene-enviroment interaction, (and psychosocial constructs, I would add).  Other studies in the past suggest up to 80%, but that is now being questioned.  Also, the shared genetic variations between diagnosis is great.  Particularly, schizophrenia and bipolar have a lot in common, but also–to a lesser extent–bipolar or schizophrenia and depression,  and ADHD and depression.  Unexpectedly, schizophrenia and autism was not linked, nor was bipolar and ADHD.

Conclusion?

Well, this completely agrees with everything I have been reading these past years, and decidedly so.  I was a bit taken aback about the lack of correlation between schizophrenia and autism–since they look so similar–and ADHD and bipolar–also similar.  It goes to show that what’s under the hood is totally different even if the outside looks the same.

They offered a neat metaphor worth remembering.  A person is like a house.  As it falls down ,the shape of the collapse is unique, depending on which beams and posts fail.   From the outside different houses collapse differently, while on the inside some of the same beams and posts make have broken.  This was explained in an interview with Psychiatric News, Sept 20, 2013, with Bruce Cuthbert, PhD, the head of the RDoc (Research Domain Criteria)–the new challenger to the DSM5.  I like the bridge metaphor better, which is the same, a bridge slows falls as the girders fail, and some of the same girders break between different bridges.

In either case, you fix the house (or bridge) by fixing the correct beam (girder).  In the future, psychiatric treatment, hopefully, will use a better blueprint:  we could fix selected girders and not give every broken bridge the same remedy (i.e. all schizophrenia gets antipsychotics only).

This new model also explains why so many folks with psychiatric conditions end up on complex drug cocktails.  Many girders/beams fail or weaken, but each medicine only treats one (or a few) domains (i.e. girders/beams).

The abstract of the last article here and February article here

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