Friday, April 1, 2011

No Bipolar Genie Yet?

With all the advances in genetic research over the past two decades researchers had been very confident of identifying the gene or genes responsible for bipolar disorder and other mental illnesses thought to have a strong genetic link.

Yet the search has proved to be more elusive than Aladdin's famous Genie. Even the white coated researchers are getting discouraged by the complexity of their task, as suggested in two recent scientific articles. Searching for Genetic Risk for Schizophrenia and Bipolar Disorder.The missing genes: what happened to the heritability of psychiatric disorders?

In the first article the authors explain that:
"Ten years ago it was widely expected that the genetic basis of common disease would be resolved by genome-wide association studies (GWAS), large-scale studies in which the entire genome is covered by genetic markers. However, the bulk of heritable variance remains unexplained."

And in the second article:
"Less than 2% of the 80–90% heritability of major psychiatric disease, for example, schizophrenia and manic-depressive illness is attributable to genes identified by linkage and association. Where is the missing heritability?"

Where is that Missing Heritabliity?
Its a great question and of coarse and the easy quick think answer is that genetics is more complex than we realized at the outset of the genome project, and given enough time and resources scientist's will find the genetic markers of all psychopathology? Or will they? Is the very nature of 'affective disorder' far more systemic and inter-relational  than simple linear 'this causes that' thinking can possibly identify?

In the the article that prompted my words here; "Where’s the Bipolar Gene?By CANDIDA FINK, MD,
The author writes:
Reading these comments from researchers can be a bit deflating – the excitement about identifying the genes that cause bipolar disorder seems to be losing some steam in the face of the complexity of the process, technical limitations, and costs of the necessary research techniques. But I think it’s way too early to be discouraged. Like all scientific exploration, this process often ends up opening up more doors and asking more questions than it answers, at least in its initial stages – that’s the nature of research. It’s always more complicated and expensive than we anticipate.

Even before understanding the genetics of brain variations such as mental illness, studies of typical brain development and behavior have shown that there are few linear or straightforward connections between singe genes and behavior or emotions. The old genetics we learned in high school about peas and eye color don’t work in this area. We have only just begun this journey to understand the science of ourselves.

I am confident that ongoing research will ultimately provide us with valuable information about people at risk for mental illness and the how environmental factors act upon these genetically based vulnerabilities. In the longer term, we will know significantly more about the evolution of these conditions and maybe even how to reduce risk of developing full blown conditions. In a more short-term way, the genetic work helps scientists identify more specific molecular pathways related to illness, even if these are not simple cause-and-effect relationships, that point us toward new and hopefully more targeted and effective treatments strategies.

Hmm! Maybe.
I went back three generations looking for genetic evidence of mental illness in my family background and was unable to find it. My four boys are grown men now with no examples of maladjustment beyond the 'normal' vices.
Perhaps any genetic predisposition is in the sensitivity of the organism to environmental conditions, such as the response of the autonomic nervous system to instinctive threat, or what neuroscience calls, 'neuroception.'

As I described in a recent post: Bipolar: Family & the Gen Affect
The theories & concepts pointed to above combine to show how common perception may contain more mis-perception than true understanding & awareness, so much so that we may be barking up the wrong tree in a belief that 'affective disorders' like bipolar, are in fact an 'illness.'
Indeed how much is our preference for linear cause and effect thinking, instinctively rather than intelligently driven, such as our assumption that the brain alone is responsible for affective disorders.

Perhaps there is a little too much differentiation in science circles, with not enough holistic integration across the many areas of research, as was pointed out in Allan Schore's excellent book Affect Regulation and the Origin of the Self: The Neurobiology of Emotional Development. He brings together thousands of scientific papers to show a more complete picture of human development, including the probable genesis of affective disorders, than any one particular line of inquiry possibly can. 

Just as the writer Candida Fink, MD suggests; "these are not simple cause-and-effect relationships," and just like the wish that conjured Aladdin's genie, are we perhaps wishing for technology to solve a problem stimulated by the instinctual energies of affect/emotion, prompted by denial?  

In research that seeks a more complete picture neuroscience is beginning to glimpse the complexity of human development and interaction, coining the term 'affective states' to describe the systemic reactivity of each moment we live. The view of mental illness as disease includes such systemic reactivity, born of fear and the need for objective thinking to distance the mind from sensations of the body and the overwhelming power of affect/emotion.