A dopamine receptor D2 genetic polymorphism associated with transition to mental disorders in a cohort of individuals with at-risk mental state for psychosis

• Published in: Revista brasileira de psiquiatria Vol. 45; no. 3; pp. 268 - 273
• Main Authors: Marques, Julia Hatagami, Talib, Leda Leme, Hortêncio, Lucas, Andrade, Julio Cesar, Alves, Tania Maria, Serpa, Mauricio Henriques, Yamamoto, Guilherme Lopes, van de Bilt, Martinus Theodorus, Rössler, Wulf, Gattaz, Wagner Farid, Loch, Alexandre Andrade
• Format: Journal Article
• Language: English
• Published: Brazil Associação Brasileira de Psiquiatria 2023; Associação Brasileira de Psiquiatria (ABP)
• Subjects: attenuated psychosis; Brief Communication; clinical high risk; Dopamine; flip-flop; PSYCHIATRY; schizophrenia; rs6277; DRD2; dopamine; C957T; UHR; attenuated psychosis; Dopamine; schizophrenia; flip-flop; clinical high risk
• DOI: 10.47626/1516-4446-2023-3044
• ISSN: 1516-4446; 1809-452X

We aimed to test the association of 45 single nucleotide polymorphisms (SNPs) and transition to psychiatric disorders in a cohort of individuals with at-risk mental state for psychosis (UHR). Through general population screening, 88 non-help-seeking UHR subjects and 130 healthy control individuals were genotyped for 45 SNPs related to psychosis. They were followed up for a mean of 2.5 years, and conversion to psychotic and to general psychiatric disorders was assessed. Genotype frequencies between controls, converters and non-converters were analyzed. There were no differences in sociodemographics between controls and UHR. Also, UHR converters and non-converters had no differences in their baseline symptoms scores. The rs6277, a dopamine receptor D2 gene (DRD2) SNP, was significantly related to UHR who transitioned to psychosis (p<0.001) and to UHR who transitioned to any psychiatric disorders (p=0.001), when compared to UHR who did not transition. The rs6277 T allele was related to psychiatric morbidity in a dose-response fashion, being significantly more frequent in UHR-converters than UHR-non-converters and control subjects (p=0.003). Our findings suggest that rs6277 could potentially constitute a genetic marker of transition to psychiatric disorders in subjects with at risk mental states, warranting further investigation with larger samples.