Association of PIP4K2A Polymorphisms with Alcohol Use Disorder

Background: Alcohol use disorder (AUD) not only influences individuals and families but also has a lasting social impact on communities at the national level. Dopaminergic neurotransmission is involved in excessive alcohol consumption. Phosphatidylinositol-5-phosphate-4-kinase type 2 α (PIP4K2A) plays an important role in the regulation of ascending dopamine pathways. In this study; we determined possible associations between nine polymorphisms in PIP4K2A and AUD in Russian men. Methods: 279 Russian men with AUD were investigated. The control group consisted of 222 healthy men from the general Russian population. Genotyping of DNA samples for nine polymorphic variants of PIP4K2A was carried out by the Applied Biosystems™ QuantStudio™ 5 Real-Time PCR System with use of the TaqMan1 Validated SNP Genotyping Assay (Applied Biosystems; CIIIA). Results: Carriage of the PIP4K2A rs2230469*TT/T genotype/allele was a relative risk factor for developing AUD in men (p = 0.026 and p = 0.0084 accordingly). Moreover; men with AUD had a higher frequency of PIP4K2A rs746203*T allele (p = 0.023) compared to healthy men. Conclusions: For the first time; we demonstrated different PIP4K2A polymorphisms to be associated with AUD presumably due to dopamine system modulation resulting from regulation of the lateral habenula

Investigating the potential role of BDNF and PRL genotypes on antidepressant response in depression patients:A prospective inception cohort study in treatment-free patients

Background: Brain-derived neurotrophic factor (BDNF) is associated with response to antidepressant drugs in mood and anxiety disorders. Prolactin (PRL) is a pituitary hormone with behavioural effects, acting as a neurotrophic factor within the brain and may be involved in antidepressant response. Objectives: To investigate the relationship between BDNF and PRL genotypes with antidepressant drug response. Methods: Prospective inception cohort of 186 Russian treatment-free participants (28 men and 158 women) between 18 and 70 years clinically diagnosed with depressive disorder who initiated antidepressant medication. DNA polymorphisms were genotyped for PRL rs1341239, BDNF rs6265 and rs7124442. Primary outcome was measured by differences in Hamilton Depression Rating Scale (Delta HAM-D) scores between baseline/week two, week two/week four, and baseline/week four. Linear regression and independent t-test determined the significance between polymorphisms and Delta HAM-D. Results: Comparisons between genotypes did not reveal any significant differences in scores during the first two weeks of treatment. In the latter two weeks, BDNF rs7124442 homozygous C patients responded significantly worse in comparison to homozygous T patients during this period. Further analysis within women and in postmenopausal women found a similar comparison between alleles. Limitations: Study lasted four weeks, which may be considered short to associate genuine antidepressant effects. Conclusions: Patients taking tricylic antidepressants were noted to have a significant improvement in Delta HAM-D compared to patients taking SSRIs. Homozygous C BDNF rs712442 patients were found to respond significantly worse in the last two weeks of treatment

Association of Polymorphisms of Serotonin Transporter (5HTTLPR) and 5-HT2C Receptor Genes with Criminal Behavior in Russian Criminal Offenders

Background: Human aggression is a heterogeneous behavior with biological, psychological, and social backgrounds. As the biological mechanisms that regulate aggression are components of both reward-seeking and adversity-fleeing behavior, these phenomena are difficult to disentangle into separate neurochemical processes. Nevertheless, evidence exists linking some forms of ag

Serum Levels of S100B Protein and Myelin Basic Protein as a Potential Biomarkers of Recurrent Depressive Disorders

Nowadays, nervous tissue damage proteins in serum are considered promising drug targets and biomarkers of Mood Disorders. In a cross-sectional naturalistic study, the S100B, MBP and GFAP levels in the blood serum were compared between two diagnostic groups (patients with Depressive Episode (DE, n = 28) and patients with Recurrent Depressive Disorder (RDD, n = 21)), and healthy controls (n = 25). The diagnostic value of serum markers was assessed by ROC analysis. In the DE group, we did not find changed levels of S100B, MBP and GFAP compared with controls. In the RDD group, we found decreased S100B level (p = 0.011) and increased MBP level (p = 0.015) in comparison to those in healthy controls. Provided ROC analysis indicates that MBP contributes to the development of a DE (AUC = 0.676; 95%Cl 0.525–0.826; p = 0.028), and S100B and MBP have a significant effect on the development of RDD (AUC = 0.732; 95%Cl 0.560–0.903; p = 0.013 and AUC = 0.712; 95%Cl 0.557–0.867; p = 0.015, correspondingly). The study of serum markers of nervous tissue damage in patients with a current DE indicates signs of disintegration of structural and functional relationships, dysfunction of gliotransmission, and impaired secretion of neurospecific proteins. Modified functions of astrocytes and oligodendrocytes are implicated in the pathophysiology of RDD

Association of Polymorphisms of Serotonin Transporter (5HTTLPR) and 5-HT2C Receptor Genes with Criminal Behavior in Russian Criminal Offenders

BACKGROUND: Human aggression is a heterogeneous behavior with biological, psychological, and social backgrounds. As the biological mechanisms that regulate aggression are components of both reward-seeking and adversity-fleeing behavior, these phenomena are difficult to disentangle into separate neurochemical processes. Nevertheless, evidence exists linking some forms of aggression to aberrant serotonergic neurotransmission. We determined possible associations between 6 serotonergic neurotransmission-related gene variants and severe criminal offenses. METHODS: Male Russian prisoners who were convicted for murder (n = 117) or theft (n = 77) were genotyped for variants of the serotonin transporter (5HTTLPR), tryptophan hydroxylase, tryptophan-2,3-dioxygenase, or type 2C (5-HT2C) receptor genes and compared with general-population male controls (n = 161). Prisoners were psychologically phenotyped using the Buss-Durkee Hostility Inventory and the Beck Depression Inventory. RESULTS: No differences were found between murderers and thieves either concerning genotypes or concerning psychological measures. Comparison of polymorphism distribution between groups of prisoners and controls revealed highly significant associations of 5HTTLPR and 5-HTR2C (rs6318) gene polymorphisms with being convicted for criminal behavior. CONCLUSIONS: The lack of biological differences between the 2 groups of prisoners indicates that the studied 5HT-related genes do not differentiate between the types of crimes committed