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Aim: To search for genetic variants associated with premorbid personality in patients with schizophrenia., Material and Methods: The sample included 272 men diagnosed with schizophrenia or schizoaffective disorder. Patients were divided into 3 groups based on premorbid personality difficulties: mild (group 1, n=110), moderate (group 2, n=113), marked (group 3, n=49). The following polymorphisms were genotyped: 5-HTR2A (T102C), 5-HTTLPR, BDNF (Val66Met), CRP (-717A>G)., Results: A significant increase in the frequency of the CC (5-HTR2A T102C), LL (5-HTTLPR) and Met/Met (BDNF Val66Met) genotypes was identified in group 3 compared to group 1. Frequencies of CC and LL genotypes were significantly higher in group 2 compared to group 1 as well. The differences between group 2 and group 3 were found only for the Met/Met genotype. There were no between-group differences in the frequencies of CRP (-717A>G) genotypes., Conclusion: 5-HTR2A (T102C), 5-HTTLPR, BDNF (Val66Met) polymorphisms previously reported to modify schizophrenia course are also associated with premorbid personality in schizophrenic patients.

We explored the association of brain-derived neurotrophic factor (BDNF) and serotonin transporter genes with neurophysiological characteristics of the early stages of verbal information processing in the brain in the groups of patients with schizophrenia and schizophrenia spectrum disorders and healthy people. It has been shown that Val66Met and 5-HTTLPR polymorphisms are associated with P100 and N170 during the passive reading of single words written in Russian presented with different occurrence frequency. The healthy carriers of the ValVal genotype (BDN F Val66Met) allele or the SS (5-HTTLPR) genotype performed the task better compared to those with an Met or an L allele. The differences were significant in healthy people and observed as a trend in thepatients.

The 5-HTTLPR SLC6A4 and catechol-o-methyltransferase (COMT) Val158Met polymorphisms are reported to be associated with processing of facial expressions in general population. Impaired recognition of facial expressions that is characteristic of schizophrenia negatively impacts on the social adaptation of the patients. To search for molecular mechanisms of this deficit, we studied main and epistatic effects of 5-HTTLPR and Val158Met polymorphisms on the facial emotion recognition in patients with schizophrenia (n=299) and healthy controls (n=232). The 5-HTTLPR polymorphism was associated with the emotion recognition in patients. The ll-homozygotes recognized facial emotions significantly better compared to those with an s-allele (F=8.00; p=0.005). Although the recognition of facial emotions was correlated with negative symptoms, verbal learning and trait anxiety, these variables did not significantly modified the association. In both groups, no effect of the COMT on the recognition of facial emotions was found.

We studied the relationship between genes of serotonin transporter and brain-derived neurotrophic factor and parameters of AEP N100 wave to a non-significant stimulus in patients with endogenous mental diseases. In patients with endogenous psychoses, a significant effect of BDNF Val66Met marker on N100 wave amplitude was revealed: the mean N100 amplitude was higher in carriers of Val/Val genotype compared to Val/Met genotype carriers. The effect of the 5-HTTLPR marker on the wave amplitude was less pronounced (tendency): the SS genotype was associated with higher N100 amplitude.

A number of studies have reported an association between 5-HTTLPR, a polymorphism of the serotonin transporter gene, and the development of depressive states in response to a variety of distal and proximal stressors. We report here studies of the effects of the 5-HTTLPR polymorphism on the probability that an individual will develop mental maladaptation in 224 close relatives of patients with severe chronic mental disorders - schizophrenia and schizoaffective and affective psychoses. The ss genotype of the serotonin transporter gene contributes to the formation predominantly of manifestations of distress, reflected by increases on the hypochondriasis scale of the MMPI scale of factors such as the extent of the autonomic component of anxiety reactions and increased attention to own health, as well as increases in sensitivity. At the same time, the ss genotype was less likely to influence the appearance of depression and anxiety, as determined on the depression scale. These tendencies were more marked in males than females. Furthermore, males with the ss genotype were characterized by some increase in tension, suspicion, detachment, and attention difficulty (on the paranoia and schizophrenia scales). These data can be regarded as supporting the role of the short allele of the serotonin transporter gene in enhancing and modulating psychopathological reactions to chronic stress situations in relatives of mental patients.