RESUMO
OBJECTIVE: The dopaminergic system plays an important role in the prefrontal cortex (PFC) and is believed to mediate cognitive dysfunction (CD) in bipolar disorder (BD). The enzyme catechol-O-methyltransferase (COMT) is involved in the catabolism of dopamine in the PFC, and an association between COMT single nucleotide polymorphisms (SNPs) and BD has been reported. COMT SNPs have also been associated with executive and working memory performance in healthy subjects, patients with schizophrenia, and euthymic BD patients. The objective of this study was to investigate the association between COMT SNPs and acute CD during BD mood episodes. METHODS: Seventy-two symptomatic, medication-free subjects with bipolar I disorder (BD-I) and 76 healthy controls were evaluated using neuropsychological tests, and genotyped for COMT SNPs rs4680 and rs165599. RESULTS: Patients undergoing mania and mixed episodes carrying the COMT allele G had better performance on executive function, memory, verbal fluency, and intelligence tests. Moreover, an interaction was detected between the COMT allele G and the Young Mania Rating Scale in BD CD. CONCLUSIONS: Allele G from COMT SNPs rs4680 and rs165599 may represent reliable state-dependent predictors of global CD during manic and mixed episodes in BD. Further studies in larger samples are necessary to confirm these findings.
Assuntos
Transtorno Bipolar/genética , Catecol O-Metiltransferase/genética , Transtornos Cognitivos/genética , Adulto , Alelos , Atenção , Transtorno Bipolar/complicações , Transtorno Bipolar/metabolismo , Estudos de Casos e Controles , Catecol O-Metiltransferase/metabolismo , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/metabolismo , Dopamina/metabolismo , Função Executiva , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Testes de Inteligência , Masculino , Memória , Testes Neuropsicológicos , Fenótipo , Polimorfismo de Nucleotídeo Único , Córtex Pré-Frontal/metabolismoRESUMO
INTRODUCTION: Creativity is a complex human ability influenced by affective and cognitive components but little is known about its underlying neurobiology. Bipolar Disorder (BD) is highly prevalent among creative individuals. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophic factor, and has been implicated in the pathophysiology of BD. In contrast to the better functioning of the BDNF polymorphism (Val(66)Met) Val allele, the Met allele decreases BDNF transport and has been associated with worsened performance on several cognitive domains in euthymic BD subjects and controls. We hypothesized that the Val allele is associated with increased creativity in bipolar disorder. MATERIALS AND METHODS: Sixty-six subjects with BD (41 in manic and 25 in depressive episodes) and 78 healthy volunteers were genotyped for BDNF Val(66)Met and tested for creativity using the Barrow Welsh Art Scale (BWAS) and neuropsychological tests. RESULTS: Manic patients with the Val allele (Met-) had higher BWAS scores than Met+ carriers. This relationship was not observed among patients in depressive episodes or among control subjects. BDNF Met allele status showed no association with cognitive function in any of the groups. CONCLUSION: As postulated, these findings suggest that the better functioning allele of BDNF may selectively facilitate creative thinking in subjects with manic episodes, but not in controls or depressives. Further studies exploring the role of BDNF in the neurobiology of creativity in BD and in euthymic phases are warranted.