A recent review of the COMT genotype Met/VAL SNP on psychiatric phenotypes of schizophrenia, bipolar mood disorder and schizoaffective disorder seems to suggest that the SNP’s effcet mya be more of modifying the symptoms (with Val conferring positive symptom susceptibility and MET negative symptom susceptibility) of psychosis and mania, rather than conferring susceptibility to the diseases per se. Also the association, in European populations primarily, would be between both psychosis and mania (schizoaffcetive) present rather than juts a simple diagnosis of schizophrenia or bipolarity.
The narrowing of COMT linkages to the combination of Mania and Psychosis loks like a step forward and the distinction between symptom modifying effects and the distinction between symptoms based on their being positive (additions of functionality) or negative (deletion of functionality) seems to be a step in the right direction.
This differential effect of having a Met or Val allele on symptom type (positive and negative) is also inline with the inverted U model of dopamine levels that suggests that there is a range of dopamine levels that is good for the body(brain) and beyond either end there are deleterious effects. It could be that while a Met allele confers protective advantage for positive symptoms, it is an aggravator for negative symptoms. Depending on dopamine environmental levels, the person having Met allele may or may not show the symptoms of mania/ scizophrenia.
I am also intrigued by the BDNF met/val allele effect on anxiety susceptibility and forced to think whether there too the effect may be that of symptom modification rather than susceptibility?