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.

A esquizofrenia é uma doença psiquiátrica na qual as alterações do conteúdo do pensamento são uma característica marcante. A ruptura do fluxo normal de pensamentos, ou “Alteração Formal do Pensamento” (AFP) é acessada através da forma e conteúdo da fala do paciente. Alterações de fala e linguagem em esquizofrênicos eram consideradas como consequentes à ruptura de seus sistemas conceituais e processos associativos relacionados à psicose. Esta visão alterou-se pelo aumento nas evidências de comprometimento primário da linguagem na esquizofrenia, especialmente em seus aspectos semânticos, discursivos e pragmáticos. A esquizofrenia é atualmente considerada por alguns autores como uma “doença humana específica relacionada à linguagem”, ou “logopatia”. Os correlatos neuroanatômicos e genéticos do prejuízo linguístico nestes pacientes estão sendo investigados. Estes esforços podem levar à maior compreensão da fisiopatologia desta grave doença mental. Nesta revisão, apresentamos conceitos atuais sobre AFP e sua diferenciação das anormalidades linguísticas primárias na esquizofrenia.

Schizophrenia is a psychiatric illness in which disorders of thought content are a prominent feature. The disruption of normal flow of thought, or “Formal Thought Disorder” (FTD), has been traditionally assessed through the content and form of patients’ speech, and speech abnormalities in schizophrenia were considered as a by-product of the disruption in conceptual structures and associative processes related to psychosis. This view has been changed due to increasing evidence that language per se is impaired in schizophrenia, especially its semantic, discursive, and pragmatic aspects. Schizophrenia is currently considered by some authors as a “language related human specific disease” or “logopathy”, and the neuroanatomical and genetic correlates of the language impairment in these patients are under investigation. Such efforts may lead to a better understanding about the pathophysiology of this devastating mental disease. We present some current concepts related to FTD as opposed to primary neurolinguistic abnormalities in schizophrenia.