ABSTRACT
Objective: To test the hypothesis that genetic variations of cannabinoid receptors contribute to the pathophysiology of cognitive deficits in schizophrenia. Methods: In this genetic association case-control study, cannabinoid receptor polymorphisms CNR1 rs12720071 and CNR2 rs2229579 were tested for association with neurocognitive performance in 69 patients with schizophrenia and 45 healthy controls. Neurocognition was assessed by the Brief Assessment of Cognition in Schizophrenia (BACS). Results: We found a consistent association between CNR1 rs12720071 polymorphism and the cognitive performance of patients in several cognitive domains. Patients with C/C polymorphism presented significantly worse performance in motor speed, verbal fluency, attention/processing speed and reasoning/problem solving. Conclusion: Although limited, our data support the hypothesis that CNR1 variations may be associated with the pathogenesis of cognitive deficits of schizophrenia.
ABSTRACT
OBJECTIVE: Schizophrenia is a psychiatric disorder whose mechanisms have remained only partially elucidated. The current proposals regarding its biological basis, such as the dopaminergic hypothesis, do not fully explain the diversity of its symptoms, indicating that other processes may be involved. This paper aims to review evidence supporting the involvement of the endocannabinoid system (ECS), a neurotransmitter group that is the target of Cannabis sativa compounds, in this disorder. METHODS: A systematic review of original papers, published in English, indexed in PubMed up to April, 2012. RESULTS: Most studies employed genetics and histological, neuroimaging or neurochemical methods - either in vivo or post-mortem - to investigate whether components of the ECS are compromised in patients. Overall, the data show changes in cannabinoid receptors in certain brain regions as well as altered levels in endocannabinoid levels in cerebrospinal fluid and/or blood. CONCLUSIONS: Although a dysfunction of the ECS has been described, results are not entirely consistent across studies. Further data are warrant to better define a role of this system in schizophrenia.
OBJETIVO: A esquizofrenia é um transtorno psiquiátrico cujos mecanismos permanecem apenas parcialmente elucidados. As atuais propostas relativas à base biológica, tais como a hipótese dopaminérgica, não explicam por completo a diversidade de seus sintomas, o que indica que outros processos podem estar envolvidos. Este artigo tem como objetivo revisar indícios que sustentem o envolvimento do sistema endocanabinoide (SECB), um grupo de neurotransmissoresalvo dos compostos da Cannabis sativa, nesse transtorno. MÉTODOS: Revisão sistemática dos artigos originais, publicados em inglês e indexados no PubMed até abril de 2012. RESULTADOS: A maioria dos estudos empregou métodos neuroquímicos ou de neuroimagem genéticos e histológicos - tanto in vivo quanto post-mortem - para investigar se os componentes do SECB estão comprometidos nos pacientes. De modo geral, os dados mostram mudanças nos receptores canabinoides em determinadas regiões cerebrais, bem como a alteração dos níveis de endocanabinoides no líquido cefalorraquidiano e/ou no sangue. CONCLUSÕES: Ainda que a disfunção do SECB tenha sido descrita, os resultados dos estudos não são totalmente consistentes. São necessários mais dados para definir melhor o papel desse sistema na esquizofrenia.