Genetic Polymorphisms Related to Dopamine, Serotonine and BDNF Might be Specific to Particular Symptom Dimensions in Schizophrenia

Abstract

Background: Schizophrenia is held to be result of multiple small-effect genes and their interplay with environment. Several of these genes have been discovered, but their exact role in the disease is unclear. The objective of this study is to assess relationship between genetic polymorphisms and specific symptom dimensions in schizophrenia. Methods: Fifty-three outpatients with schizophrenia from the Institute of Psychiatry, Sao Paulo,Brazil, were selected. Psychopathology was evaluated through SCID-I, PANSS and neuropsychological assessment. Genotyping was performed by real-time PCR allelic discrimination. Polymorphisms HTR2A-T102C,-rs6314 and -rs1928042, HTR2C-rs6318 and -rs3813929, DRD3-rs6280, BDNF-rs6265 and COMT-rs4680 were analyzed. Associations between genetic polymorphisms and psychopathology were measured. Factor analysis was performed between psychopathological measures yielding symptom dimensions. Generalized linear models were conducted between these dimensions and positively related genetic polymorphisms; models were repeated including cofactor “refractoriness”. Results: HTR2C(rs6318) genotype CC(ser/ser) and DRD3 genotype CC(gly/gly) were related to worst cognition(p=0.01-0.03). DRD3 genotype TT(ser/ser) was associated with negative symptoms(p=0.04-0.05). BDNF genotype GA(val/met) and COMT genotype GG(val/val) were associated with positive symptoms(p=0.00-0.04). Factor analysis yielded 7 symptom dimensions: cognition was related to DRD3 and HTR2C-rs6318 (B=1.01,p=0.00;B=-0.92,p=0.04,respectively). Disorganization-catatonia was related to BDNF and HTR2C-rs6318 (B=-0.62,p=0.05;B=1.01,p=0.03,respectively). Paranoid-influence delusions were related to DRD3, HTR2C-rs6318 and HTR2A-rs1928042 (B=-1.03,p=0.00;B=-1.31,p=0.00;B=-1.04,p=0.04,respectively). Other delusions/hallucinations were related to DRD3, HTR2C-rs3813929 and BDNF (B=-1.1,p=0.01;B=-1.00,p=0.03;B=0.80,p=0.01,respectively). Negative symptoms were related to refractoriness (B=1.10,p=0.00). Dimensions hallucinations/bizarre delusion and tactile hallucinations did not correlate with any predictor. Conclusions: Our study proposes that genetic polymorphisms might be specific in determining certain symptom dimensions in schizophrenia, suggesting differential underlying physiopathological mechanisms for them.