SLC6A3, HTR2C and HTR6 Gene Polymorphisms and the Risk of Haloperidol-Induced Parkinsonism.

Antipsychotic-induced parkinsonism (AIP) is the most common type of extrapyramidal side effect (EPS), caused by the blockage of dopamine receptors. Since dopamine availability might influence the AIP risk, the dopamine transporter (DAT) and serotonin receptors (5-HTRs), which modulate the dopamine release, may be also involved in the AIP development. As some of the individual differences in the susceptibility to AIP might be due to the genetic background, this study aimed to examine the associations of SLC6A3, HTR2C and HTR6 gene polymorphisms with AIP in haloperidol-treated schizophrenia patients. The Extrapyramidal Symptom Rating Scale (ESRS) was used to evaluate AIP as a separate entity. Genotyping was performed using a PCR, following the extraction of blood DNA. The results revealed significant associations between HTR6 rs1805054 polymorphism and haloperidol-induced tremor and rigidity. Additionally, the findings indicated a combined effect of HTR6 T and SLC6A3 9R alleles on AIP, with their combination associated with significantly lower scores of ESRS subscale II for parkinsonism, ESRS-based tremor or hyperkinesia and ESRS subscales VI and VIII. These genetic predictors of AIP could be helpful in better understanding its pathophysiology, recognizing the individuals at risk of developing AIP and offering personalized therapeutic strategies for the patients suffering from this EPS.

HTR1A, HTR1B, HTR2A, HTR2C and HTR6 Gene Polymorphisms and Extrapyramidal Side Effects in Haloperidol-Treated Patients with Schizophrenia.

Schizophrenia is a serious, chronic psychiatric disorder requiring lifelong treatment. Extrapyramidal side effects (EPS) are common adverse reactions to antipsychotic medications. In addition to the dopaminergic system, serotonergic mechanisms, including serotonin (5-HT) receptors, might be involved in EPS development. This study aimed to examine molecular associations of HTR1A, HTR1B, HTR2A, HTR2C and HTR6 gene polymorphisms with acute EPS in 229 male schizophrenia patients, following two weeks of haloperidol monotherapy. The Simpson-Angus Rating Scale for Extrapyramidal Side Effects (SAS), Barnes Akathisia Rating Scale (BARS) and Extrapyramidal Symptom Rating Scale (ESRS) were used to evaluate EPS severity. Genotyping was performed using real-time PCR, following extraction of blood DNA. Significant acute EPS appeared in 48.03% of schizophrenia patients. For the rs13212041 HTR1B gene polymorphism, affecting microRNA regulation of HTR1B gene expression, a higher frequency of TT carriers was found among haloperidol-treated patients with akathisia when compared to the group without akathisia symptoms. In comparison to C-allele carriers, patients carrying the TT genotype had higher akathisia severity, as determined by the SAS, BARS and ESRS scales. These molecular findings suggest potential involvement of 5-HT1B receptors in akathisia development following haloperidol treatment, as well as possible epigenetic mechanisms of serotonergic modulation associated with antipsychotic-induced EPS.

The association between HTR1B gene rs13212041 polymorphism and onset of alcohol abuse.

BACKGROUND: Alcohol dependence displays a wide variety of clinical phenotypes. Various typology classifications of alcoholism include age of onset of alcohol abuse as one of the major phenotypic features. Serotonergic changes have been associated with alcoholism, while serotonin receptors type 1B (5-HT1B) play an important role in regulating serotonergic neurotransmission. The rs13212041 polymorphism modulates the expression of HTR1B gene coding for 5-HT1B receptor. This study examined the association of platelet serotonin (5-HT) and HTR1B gene with the onset of alcohol abuse in alcohol-dependent subjects. MATERIALS AND METHODS: Determination of platelet 5-HT concentration and genotyping of rs13212041 HTR1B gene polymorphism were performed in 613 alcohol-dependent patients, subdivided according to early/late onset (before/after 25 years of age) of alcohol abuse. RESULTS: Alcohol-dependent individuals with CC genotype were more frequent in the group with early onset of alcohol abuse compared to carriers of T allele. Besides HTR1B genotype, age and gender, but not platelet 5-HT, were major variables associated with the onset of alcohol abuse. Platelet 5-HT concentration was not significantly different between patients with early and late onset of alcohol abuse, or patients carrying various HTR1B genotypes. Although we observed no influence of co-variables such as age, gender, or somatic and psychiatric comorbidities, platelet 5-HT concentration was significantly affected by smoking. CONCLUSION: These findings support potential involvement of 5-HT1B receptors in the onset of alcohol abuse and development of alcohol dependence. Additionally, the results of our study emphasize the importance of controlling for smoking status, as one of the significant confounding factors influencing platelet 5-HT concentration.