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Serotonin type 2A receptors (5-HTR2A) have long been implicated in schizophrenia pathology. A decreased number of these receptors were found in postmortem brain studies of schizophrenic patients as well as in experiments using neuroimaging techniques. Molecular genetic studies revealed that the T102C polymorphism of the 5-HTR2A gene is associated with schizophrenia, with the CC genotype frequency being higher in patients compared to healthy controls. However the association was not confirmed in all studies. We carried out a replication study, which aimed at searching for association between this polymorphism and schizophrenia in a large samples of patients (n=919), their psychiatrically well first-degree relatives (n=330) and screened controls (n=500). The C allele and the CT+CC genotype frequencies were significantly higher in patients than in controls (chi2=5.1; df=1; p=0.02; OR 1.2, 95% CI 1.0-1.4) and chi2=5.4; df=1; p=0.02; OR 1.4, 95% CI 1.1-1.8 respectively). In a family-based study, the transmission disequilibrium test (TDT) and the family-based association test (FBAT) did not show a preferential transmission of any allele. In conclusion, our replication study provides further evidence for association between the 5-HTR2A receptor T102C polymorphism and schizophrenia.

To clarify nosologic differences between schizoaffective psychosis (SAP) and attack-like progressive schizophrenia at molecular-genetic level, the genetic polymorphism of serotonin receptor type 2A (5HTR2A), serotonin transporter (5-HTTLRP), and brain-derived neurotrophic factor (BDNF) was studied in 563 patients with schizophrenia (mean age 37.7+/-14.4 years, age at disease onset 26.7+/-11.4 years), and 171 patients with SAP (mean age 30.7+/-11.6 years, age at disease onset 24.9+/-8.5 years). The control group consisted of 536 psychiatrically well subjects. Clinical symptoms and personal features were evaluated as well. By comparison with schizophrenic patients, those with SAP were featured by subtle negative symptoms and personality changes that supported the evidence that SAP is a disorder with a favorable outcome. Molecular-genetic studies revealed higher frequencies of S allele and SS genotype (5-HTTLPR polymorphism), which are thought to be associated with depression and depressive symptoms, and higher frequency of BDNF genotypes, containing Met allele, in combination with 5-HTTLRP genotypes containing L allele, in patients with SAP as compared to the schizophrenic group. C allele and CC genotype (T102C 5-HTR2A polymorphism) frequencies were higher in both groups of patients vs. controls. In conclusion, the results confirm the concept considering SAP an independent nosologic category.

Polymorphic marker Ser9Gly of dopamine receptor D3 gene is considered perspective for associative studies of schizophrenia. Allele and genotype frequency of this polymorphism were studied in different ethnic groups of schizophrenic patients as well as the attempts have been made to reveal an association with clinical presentations of the disease. However, the results are inconsistent. The present study aimed at investigating Ser9Gly DRD3 gene polymorphism in Russian sample of schizophrenic patients. One hundred and fifty patients with ICD-10 diagnosis of schizophrenia (broad definition), 69 male and 81 female, aged 34.8+/-13.87 years, age at disease onset 24.3+/-9 years, have been examined. Control group consisted of 150 healthy subjects without family history of schizophrenia, 60 male and 90 female, aged 32.7+/-13.5 years. No between-group differences have been found for Ser9Gly DRD3 allele and genotype frequencies. However, a frequency of homozygous genotype Gly/Gly was significantly higher in female patients, comparing to female controls (p=0.038 Yate's corrected, OR 9. CI 0.95% 1.0-79.5). A role of sex-dependent association between Ser9Gly DRD3 polymorphism and schizophrenia is discussed.