Introduction Hyperprolactinaemia, a common adverse effect of antipsychotic drugs, is primarily linked to blockade of dopamine D2 receptors in the pituitary gland. Certain antipsychotic drugs, such as, for example risperidone and paliperidone, are more likely to induce hyperprolactinaemia compared to others. This effect is probably caused by a relatively high blood/brain concentration ratio, a consequence of being a substrate of P‐glycoprotein. Genetic variants of P‐glycoprotein with changed functional activity might influence the potential of risperidone and paliperidone to cause hyperprolactinaemia as the altered blood/brain concentration ratio would lead to a reduced therapeutic drug level within essential brain areas making dose adaptations necessary. This increases exposure of dopamine D2 receptors within the pituitary gland. Aims To investigate possible associations between MDR1/ABCB1 gene polymorphisms and antipsychotic drug‐induced hyperprolactinaemia in Russian patients with schizophrenia and to determine possible differences between risperidone/paliperidone and other antipsychotics. Methods In total, 446 patients with schizophrenia were included from 3 psychiatric hospitals in Siberia. Blood samples were obtained in a cross‐sectional study design for DNA extraction and prolactin measurement. Associations between hyperprolactinaemia and 8 MDR1/ABCB1 gene‐polymorphisms were assessed using logistic regression analysis accounting for covariates. The analysis was repeated in a patient subgroup using risperidone or paliperidone. Results We did not observe an association between any of the 8 single nucleotide polymorphisms and the prevalence of antipsychotic‐induced hyperprolactinaemia in the total patient population. However, in the risperidone/paliperidone subgroup, the single nucleotide polymorphism rs2032582 (G2677T) was found to be negatively associated with risperidone/paliperidone‐induced hyperprolactinaemia. Conclusion This study revealed a significant association between the ABCB1 gene polymorphism rs2032582 (G2677T) and risperidone/paliperidone‐induced hyperprolactinaemia.

Background: Antipsychotic-induced metabolic syndrome (MetS) is a multifactorial disease with a genetic predisposition. Serotonin and its receptors are involved in antipsychotic-drug-induced metabolic disorders. The present study investigated the association of nine polymorphisms in the four 5-hydroxytryptamine receptor (HTR) genes HTR1A, HTR2A, HTR3A, and HTR2C and the gene encoding for the serotonin transporter SLC6A4 with MetS in patients with schizophrenia. Methods: A set of nine single-nucleotide polymorphisms of genes of the serotonergic system was investigated in a population of 475 patients from several Siberian regions (Russia) with a clinical diagnosis of schizophrenia. Genotyping was performed and the results were analyzed using chi-square tests. Results: Polymorphic variant rs521018 (HTR2C) was associated with higher body mass index in patients receiving long-term antipsychotic therapy, but not with drug-induced metabolic syndrome. Rs1150226 (HTR3A) was also associated but did not meet Hardy–Weinberg equilibrium. Conclusions: Our results indicate that allelic variants of HTR2C genes may have consequences on metabolic parameters. MetS may have too complex a mechanistic background to be studied without dissecting the syndrome into its individual (causal) components.

Major depressive disorder has become a prominent cause of disability, as lifetime prevalence has increased to ~15% in the Western world. Pharmacological effects of serotonin (5-hydroxytryptamine, 5-HT) are mediated through 5-hydroxytryptamine receptor (5-HTR) binding. Serotonin regulation of amygdala activity is attained through activation of three 5-HT2 family receptor subtypes, 5-HT2A, 5-HT2B, and 5-HT2C. Specifically, HT2A and the HT2C receptors have similar gross cerebral distribution and function, with higher constitutive activity found in HT2C than in HT2A. We investigated the possible association of 5-HTR gene polymorphisms to specific and non-specific antidepressant treatment responses in treatment-free patients in Siberia. 156 patients, aged between 18–70 years and clinically diagnosed with depressive disorders, were treated with antidepressants for 4 weeks. Patients were genotyped for a subset of 29 SNPs from the following 5-HT Receptor genes: HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B and HTR6. Primary outcome was measured by differences in Hamilton Depression Rating Scale (ΔHAM‐D 17) scores between baseline/week two, week two/week four and baseline/week four. Univariate linear regression was initially conducted to determine the 5-HTR SNPs to be studied within the multiple linear regression. Multiple linear regression analyses over the three time periods were conducted for ΔHAM‐D 17 with independent factors including: age, gender, depression diagnosis, antidepressant treatment and selected 5-HTR SNPs. We found improved ∆HAM-D 17 in patients taking tricyclic antidepressants (0–4 weeks: B = 4.85, p = 0.0002; 0–2 weeks: B = 3.58, p = 0.002) compared to patients taking SSRIs. Over the course of study, significant associations between 5-HT receptors SNPs and antidepressant response were not identified.

Purpose: Metabolic syndrome (MetS) is characterized by abdominal obesity, hyperglycaemia, dyslipidaemia and hypertension. FTO gene has been implicated in the pathogenesis of obesity, but the available scientific data concerning their relationship to antipsychotic drug-induced obesity and metabolic syndrome is still incomplete and inconsistent, which indicates that continuing the investigation of this gene’s role is necessary. Patients and Methods: In the present study, 517 patients with schizophrenia underwent antipsychotic drug treatment, and two groups were identified: patients with MetS and without MetS. Genotyping of 6 SNPs in the FTO gene was performed, and the results analyzed using R-programme. Results: We performed a statistical analysis to identify possible associations of the frequencies of genotypes and alleles of the studied polymorphisms with the presence of metabolic syndrome in schizophrenia patients, with the presence of abdominal obesity, and with an increased body mass index. The rs7185735 polymorphism did not meet the Hardy-Weinberg criterion and was excluded. After correcting for differences in age, gender and duration of illnesses, none of the variants was shown to be related to metabolic syndrome or abdominal obesity, but rs9939609, rs1421085, rs3751812 and rs8050136 were associated with body mass index. Conclusion: The present study provides additional support for these SNP’s roles as a pharmacogenetic biomarker that may become useful in the framework of the personalized medicine approach.

Background: Previous studies have linked muscarinic M4 receptors (CHRM4) to schizophrenia. Specifically, the rs2067482 polymorphism was found to be highly associated with this disease. Purpose: To test whether rs2067482 and rs72910092 are potential risk factors for schizophrenia and/or pharmacogenetic markers for antipsychotic-induced tardive dyskinesia. Patients and Methods: We genotyped DNA of 449 patients with schizophrenia and 134 healthy controls for rs2067482 and rs72910092 polymorphisms of the CHRM4 gene with the use of the MassARRAY^® System by Agena Bioscience. Mann–Whitney test was used to compare qualitative traits and χ² test was used for categorical traits. Results: The frequency of genotypes and alleles of rs72910092 did not differ between patients with schizophrenia and control subjects. We did not reveal any statistical differences for both rs2067482 and rs72910092 between schizophrenia patients with and without tardive dyskinesia. The frequency of the C allele of the polymorphic variant rs2067482 was significantly higher in healthy persons compared to patients with schizophrenia (OR=0.51, 95% CI [0.33– 0.80]; p=0.003). Accordingly, the CC genotype was found significantly more often in healthy persons compared to patients with schizophrenia (OR=0.49, 95% CI [0.31– 0.80]; p=0.010). Conclusion: Our study found the presence of the minor allele (T) of rs2067482 variant being associated with schizophrenia. We argue that the association of rs2067482 with schizophrenia may be via its regulatory effect on some other gene with protein kinase C and casein Kknase substrate in neurons 3 (PACSIN3) as a possible candidate. Neither rs2067482 nor rs72910092 is associated with tardive dyskinesia.

Background: Many antidepressants are substrates of P‐glycoprotein, an efflux transporter in the blood‐brain‐barrier encoded by the ABCB1 gene. Genetic variations might influence the transport rate of antidepressants and hence their pharmacological effects. This study investigates the influence of eight polymorphisms in the ABCB1 gene on antidepressant treatment response.Method: 152 patients were included from psychiatric departments of the Mental Health Research Institute in Tomsk. The difference in Hamilton‐Depression‐Rating‐Scale (HAMD‐17)‐scores between baseline and week two, week two and four, and baseline and week four was used to estimate timing of improvement of depression. Associations between the ABCB1 gene‐polymorphisms and reduction in HAMD‐17 score were assessed using independent t‐test and multiple linear regression.Results: Tricyclic antidepressants were associated with a higher reduction of HAMD‐17 score when compared to SSRIs. The SNP rs2235040 A‐allele had a significant positive influence on the ΔHAMD‐17_(0→2W) score but a significant negative influence on the ΔHAMD‐17_(2→4W) score. The rs4148739 G‐allele had a significant negative influence on the ΔHAMD‐17_(0→2W) score but a significant positive influence on the ΔHAMD‐17_(2→4W) score. The SNP rs2235015 T‐allele is significant negatively related to the ΔHAMD‐17_(2→4W) score.Conclusion: ABCB1 Genetic variations appear to affect speed but not magnitude of antidepressant drug response.