Psychosis-proneness correlates with expression levels of dopaminergic genes.

Psychosis-proneness or schizotypy is a personality organisation mirroring individual risk for schizophrenia-development. Believed to be a fully dimensional construct sharing considerable geno- and phenotypal variance with clinical schizophrenia, it has become an increasingly promising tool for basic psychosis-research. Although many studies show genetic commonalities between schizotypy and schizophrenia, changes in regulation of gene expression have never been examined in schizotypy before. We therefore extracted RNA from the blood, a valid surrogate for brain tissue, of a large sample of 67 healthy male volunteers and correlated the activities of all genes relevant for dopaminergic neurotransmission with the positive schizotypy-scale of the O-LIFE. We found significant negative correlations regarding the expression of the genes COMT, MAOB, DRD4, DRD5 and FOS, indicating that increased schizotypy coincides with higher levels of dopaminergic dysregulation on the mRNA-level. Considering the advantages of this method, we suggest that it be applied more often in fundamental psychosis-research.

5-HTTLPR S-allele: a genetic plasticity factor regarding the effects of life events on personality?

The S-allele of the 5-HTTLPR has been identified as a genetic vulnerability factor, being associated with an increased risk for affective disorders and/or maladaptive traits (e.g. neuroticism), especially after exposition to negative life-events (LEs). Alternatively, it has been hypothesized that this genetic risk factor might constitute a genetic plasticity factor. That is, S-allele carriers are not only vulnerable to the negative effects of a preponderance of stressful LEs but also disproportionally benefit from a preponderance of positive environmental influences. We tested this hypothesis in 357 subjects who were genotyped for the 5-HTTLPR and provided self-reports of neuroticism, life-satisfaction and LEs. Results showed a relatively increased number of positive LEss to be associated with reduced neuroticism (men: ß = -0.501, P < 0.05, women: ß = -0.369, P < 0.005) and increased life satisfaction (ß = 0.494, P < 0.001) within SS-homozygotes. Within SL-heterozygotes, similar tendencies were found. No associations were detected in LL-homozygotes. Extreme Group comparisons revealed a genotype × LE interaction (F(2,198) = 5.593, P < 0.005), with SS-homozygotes having experienced predominantly positive LEs exhibiting reduced neuroticism (women: F(1,34) = 4.764, P < 0.05; men: F(1,17) = 2.092, P = 0.17), and increased life satisfaction (F(1,53) = 4.057, P < 0.05), as compared to LL-homozygotes having experienced predominantly positive LEs. Our data support the idea that the S-allele of the 5-HTTLPR is associated with an overall increased reactivity to environmental influences, be they positive or negative in nature. These findings constitute a promising add-on to earlier data and support the plasticity hypothesis.