The basic helix-loop-helix transcription factor, neurogenin-1 is known to regulate neural development and neurite outgrowth. As such, it makes for a particularly interesting point to begin to understand mental illness and its complex developmental origins. The recent paper by Ho et al., “Basic helix–loop–helix transcription factor NEUROG1 and schizophrenia: Effects on illness susceptibility, MRI brain morphometry and cognitive abilities ” [doi: 10.1016/l.schres.2008.08.009] makes for a very interesting read since this gene resides in the midst of the chromosome 5q31 region – which has been a risk hotspot in a number of previous linkage studies – and – two snps in NEUROG1 (the C-allele of rs2344484 and the G-allele of rs8192558) have also been associated with the disorder.
The authors report that in a sample of 392 patients and 226 control subjects, the major alleles of rs2344484 and rs8192558 were more prevalent among patients. Furthermore, some of the participants underwent structural MR brain imaging which allowed the research team to examine where in the brain such genetic risk might arise from. Interestingly, the team found that both patients and control subjects who carried the C-allele of rs2344484 showed somewhat smaller volumes of grey matter. For example, in Table 3 there were 145 CC,CT individuals with an average of 662 cubic centimeters of grey matter while the 28 participants with the TT genotype showed an average volume of 682 cu.cm. This allele was also found to be associated with poorer cognitive abilities in these C-carrier participants.
As pointed out by the research team, NEUROG1 is expressed early in the development of the human brain and is implicated in the differentiation of cortical progenitor cells and of glutamatergic excitatory cells in deep layers of the cortex. Thus, the role of variation in a transcription factor – a gene that regulates the expression of other genes – in the risk of schizophrenia can be very early and with very broadly effects on the neocortex.
How to treat such an early deficit? Would be interesting to discuss further. My own 23andMe profile shows a CT heterozygote which places me within the higher risk, but more common genotypic pool. Hmmm. What to make of that?