The impact of BDNF Val66Met polymorphism on cognition in Bipolar Disorder: A review

Abstract

Background Converging lines of evidence suggest that Brain-Derived Neurotrophic Factor (BDNF) may play a central role in the pathogenesis of Bipolar Disorder (BD), thus representing a valid biomarker of the disease. A common genetic variation in the BDNF gene, the Val66Met, is associated with reduced maturation and secretion of BDNF and therefore it has been related to specific mood, cognitive and neuroanatomical alterations in BD. However, so far, only a handful of studies have investigated the association between Val66Met polymorphism and cognitive functioning in BD. Methods We performed a bibliographic search on PUBMED of all genetic studies investigating Val66Met modulation on cognitive performances in BD subjects. The inclusion criteria were met by nine studies, including a total amount of 897 BD subjects and 803 healthy controls. Results From the analysis of the existing literature emerged that a) Val allele in BD adults, but not in BD adolescents, was associated with better performances in selective cognitive domains including executive functions, verbal learning and memory; b) Met allele may negatively modulate the association between childhood trauma and performances in memory, verbal ability and verbal fluency tasks; c) Met allele may also negatively regulate structural abnormalities in cognitive cerebral structures; d) Val/Met carriers showed greater improvements in cognitive functions compared to Val/Val and Met/Met carriers. Limitations Few genetic studies exploring the impact of Val66Met on cognition in BD. Conclusions Val66Met polymorphism likely modulates cognitive functions in BD patients with complex gene-environment interactions and through potential modulations of cerebral structures. Further and larger genetic studies are required in order to detect association between BDNF polymorphism, BDNF levels, brain abnormalities and cognition in BD.