Influence of 5-HT1A and 5-HTTLPR genetic variants on the schizophrenia symptoms and occurrence of treatment-resistant schizophrenia

Abstract

Tea Terzić,1 Matej Kastelic,2 Vita Dolžan,2 Blanka Kores Plesničar11Ljubljana University Psychiatric Hospital, Ljubljana, Slovenia; 2Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaAbstract: This study aimed to explore the influence of two genetic polymorphisms of the 5-hydroxytryptamine 1A receptor (5-HT1A) and solute carrier family 6, member 4 (SLC6A4) genes on the clinical symptoms and treatment resistance in Slovenian patients with schizophrenia. A total of 138 patients with schizophrenia were evaluated using the Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, Clinical Global Impression, and Global Assessment of Functioning. Based on the selected criteria, 94 patients were included in the treatment-responsive and 44 in the treatment-resistant group. All subjects and 94 controls were genotyped for the 5-HT1A rs6295 and 5-HTTLPR polymorphisms. There were no statistically significant differences in the frequencies of these polymorphisms between the patients with schizophrenia and the control group and between the treatment-resistant and treatment-responsive group of schizophrenia patients. Polymorphisms rs6295 and 5-HTTLPR had an influence on the Global Assessment of Functioning scale score, while 5-HTTLPR also had an influence on the total score of the negative subscale within the Positive and Negative Syndrome Scale. Although we found no effect on progression toward the treatment-resistant schizophrenia, our data suggest that the rs6295 and 5-HTTLPR polymorphisms can influence some clinical symptoms in schizophrenia.Keywords: genetic polymorphisms, serotonergic system, antipsychotics, SLC6A4, serotonergic receptor