Archive for the ‘ZNF804A’ Category

Pillow talk

Her: Why haven’t you asked me to try that one thing that you really want to try, but haven’t tried yet?

Him: It’s not something you can just “do” Honey. It takes time to learn. You know how I always overestimate how difficult it will be to learn something new? and then my prefrontal cortex – hippocampal connections go and mediate a rapid-fire one shot kind of learning?

Her: Awwww, don’t be embarrassed Dear. I am glad you are an ZNF804A  rs1344706 heterozygote. If I had to choose between too quickly or going on and on for hours … well, let’s just say, my favorite part is always the hugging afterwards. Mmmmkay?

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We all have social networks.  Your friends and family are a network of relationships.  The neural networks in your brain that carry out computations involved in social interactions are another type of “social network”.  These two networks are obviously related – in so far as your ability to self-reference and understand your own internal thoughts and feelings predicts how well you can understand and predict the internal thoughts and feelings of others – and thus how extensive your network of friends and family is likely to be.  The structure of your brain networks may even be related to how many friends you have on facebook.

According to Lencz and colleagues, there is a genetic association between the T-allele of rs1344706 and the structure and connectivity of the neural networks that carry out self-referential processing in the brain … in the so-called “default mode network” that is associated with “stimulus independent” mental activity and with social cognition such as when you are attributing mental states to others.

Interestingly, the T-allele of this SNP – residing in the zinc finger protein 804A gene – has been previously associated with schizophrenia (SZ).

From Lencz and colleagues:

“To our knowledge, this is also the first study to identify a genetic correlate of multiple brain regional GM volumes comprising the default mode network.”

The default mode network comprises regions that show synchronized activity at ‘resting’ baseline, in the absence of specific stimulation (Raichle et al, 2001). Ongoing work has implicated this network in the development of self-referential thought (Spreng and Grady, 2010), which has been specifically implicated in the developmental psychopathology of SZ (Nelson et al, 2009).

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Example of a Genome-wide Scan for Quantitative...
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A recent summary statement from the Cross-Disorder Phenotype Group of the Psychiatric GWAS Consortium [doi 10.1192/bjp.bp.108.063156] highlights the recent convergence of GWAS findings in bipolar disorder (ANK3 & CACNA1C) and schizophrenia (ZNF804A).  They also suggest that, “the most useful biological categories and/or dimensional definitions and measures are still unknown” and that “there may be overlap in the genetic susceptibility across disorders” and furthermore, “The notion that there is a gene for one of more psychiatric disorders is inappropriate and unhelpful“.

As someone whose been covering the more granular details of genes and brain function, it is reassuring to hear that the genome experts at 10,000 feet find that the evidence suggests that DSM-based diagnostics do not always jibe with basic brain biology.

How to interpret past psychiatric genetic data and how to move forward to make sense of the waves of new data (the PGC will have more than 80,000 participants each with more than 500,000 genotypes on record by end of 2009)?   Jeebus help us!

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Ataxin 1Image via Wikipedia The recent SNP association report, “Identification of loci associated with schizophrenia by genomewide association and follow-up (doi:10.1038/ng.201) by O’Donovan et. al, – an analysis of more than 370,000 Affymetrix SNPs on a population of 479 affected individuals – finds strong evidence for c in the zinc finger protein 804A (ZNF804A). One clue to the otherwise inscrutable history of this gene may lie in the findings of a yeast 2-hybrid screen where ataxin-1 was used as a bait. Mutations in ATXN1 can give rise to Spinocerebellar Ataxia, a degenerative condition of the cerebellum and spinal cord. Such profound developmental deficits, even if weakly expressed would be consistent with the many cognitive difficulties experienced by patients with schizophrenia.

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