Objective: To assess the relationship between cognitive function, a proposed schizophrenia endophenotype, and two genetic polymorphisms related to dopamine function, catechol-O-methyl transferase (COMT) Val158Met and dopamine receptor 3 (DRD3) Ser9Gly. Methods: Fifty-eight outpatients with schizophrenia/schizoaffective disorder and 88 healthy controls underwent neurocognitive testing and genotyping. Analyses of covariance (ANCOVAs) using age, sex, and years of education as covariates compared cognitive performance for the proposed genotypes in patients and controls. ANCOVAs also tested for the epistatic effect of COMT and DRD3 genotype combinations on cognitive performance. Results: For executive functioning, COMT Val/Val patients performed in a similar range as controls (30.70-33.26 vs. 35.53-35.67), but as COMT Met allele frequency increased, executive functioning worsened. COMT Met/Met patients carrying the DRD3 Ser/Ser genotype performed poorest (16.184 vs. 27.388-31.824). Scores of carriers of this COMT/DRD3 combination significantly differed from all DRD3 Gly/Gly combinations (p < 0.05), from COMT Val/Met DRD3 Ser/Gly (p = 0.02), and from COMT Val/Val DRD3 Ser/Ser (p = 0.01) in patients. It also differed significantly from all control scores (p < 0.001). Conclusion: Combined genetic polymorphisms related to dopamine neurotransmission might influence executive function in schizophrenia. Looking at the effects of multiple genes on a single disease trait (epistasis) provides a comprehensive and more reliable way to determine genetic effects on endophenotypes.

RESUMO OBJETIVO O Transtorno de déficit de atenção e hiperatividade (TDAH) é um transtorno do neurodesenvolvimento que causa importantes prejuízos em várias áreas do funcionamento humano, resultando em pior qualidade de vida (QoL). Entretanto, são escassos os estudos que se utilizam de escalas válidas para documentar, objetivamente, os prejuízos na QoL de adultos com TDAH nunca tratados. O presente estudo teve por objetivos avaliar QoL numa amostra clínica de adultos com TDAH virgens de tratamento comparando com grupo controle saudável (GC) e investigar a relação entre QoL e gravidade de sintomas. MÉTODO Foram utilizadas para classificação de gravidade de sintomas a escala Auto-relato de sintomas TDAH em adultos, ASRS e como medida de QoL a WHOQOL-BREF em uma amostra de 46 adultos com TDAH com média de idade de 29,3 anos, que nunca receberam tratamento; estes foram comparados com 28 voluntários saudáveis - GC, com média de idade de 28,7 anos). RESULTADOS Observou-se QoL significativamente pior no grupo TDAH comparado ao GC (p<0,001). A gravidade de sintomas de hiperatividade (mas não os de desatenção) correlacionou negativamente com escores da escala de QoL (p<0,05). CONCLUSÃO O uso de um instrumento genérico de QoL como a WHOQOL-BREF, permite a detecção de baixa QoL em adultos com TDAH comparado ao GC e destaca a importância que deve ser atribuída a prejuízos na QoL durante o planejamento e monitoramento de estratégias de tratamento para esta população.

OBJECTIVE Attention-Deficit and Hyperactivity Disorder is a neurodevelopmental condition that causes substantial deficits in several aspects of human function, resulting in a poor quality of life. However, studies using valid reports to objectively document Quality of Life impairment in never-treated adults with Hyperactivity Disorder Self-Report Scale have, to date, been scarce. The aim of this study was to assess Quality of Life in a clinical sample of treatment-naïve adults with Attention-Deficit and Hyperactivity Disorder in comparison to a healthy control group, and to investigate the relationship between Quality of Life and symptom severity ratings. METHOD Symptom severity ratings (assessed using the Attention-Deficit and Hyperactivity Disorder Self-Report Scale) and quality of life measurements using the World Health Organization Quality of Life scale (through WHOQOL-BREF) were obtained from a sample of 46 treatment-naïve adults with Attention-Deficit and Hyperactivity Disorder (mean age=29.3 years) and a group of 28 healthy controls (mean age=28.7 years). RESULTS Quality of Life was significantly worse in the Attention-deficit and Hyperactivity Disorder group compared to the healthy controls. The severity of symptoms of hyperactivity (but not of inattention) was negatively correlated with quality of life. CONCLUSION The use of a generic Quality of Life tool such as the WHOQOL-BREF allows the detection of lower Quality of Life, vs. healthy controls, in adult Attention-Deficit and Hyperactivity Disorder patients, and highlights the relevance of Quality of Life impairment when planning and monitoring treatment strategies for such a population.