ObjectivesBrain-derived neurotrophic factor (BDNF) may be involved in the pathogenesis of bipolar disorder (BD). The functional BDNF Val66Met polymorphism (rs6265) is associated with secretion of BDNF. The current study aimed to explore the correlation between changes of plasma BDNF and cognitive function after 12 week of treatment, considering the influence of the BDNF val66Met polymorphism. The correlation of changes of plasma BDNF with quality of life (QOL) was explored.MethodsFirst diagnosed patients with BD were recruited. Symptom severity, plasma BDNF levels were examined during weeks 0, 1, 2, 4, 8, and 12. QOL, Wisconsin Card Sorting Test (WCST) and the Conners’ Continuous Performance Test (CPT) were assessed at baseline and endpoint. The genotype of the BDNF Val66Met polymorphism was determined. The change of cognitive function and QOL measures over 12 weeks were reduced by factor analysis. Pearson's correlation was used to investigate the association between change of plasma BDNF levels with cognitive function and QOL.ResultsFive hundred and forty-one BP patients were recruited. Three hundred and fifty-five (65.6%) patients completed the 12-week follow-up. A significant negative correlation was found between changes of plasma BDNF level with factor 1 (WCST) (r = −0.25, P < 0.001). After further stratification according to subtypes of BD and the BDNF genotypes, above significant correlation was found only in those with BP-I and the BDNF Val66Met Val/Met genotype (r = −0.54, P < 0.008).ConclusionWe conclude that changes in plasma BDNF significantly correlated with changes in WCST in patients with BD; such correlation is moderated by the BDNF Val66Met polymorphism and subtype of BD.Disclosure of interestThe author has not supplied his declaration of competing interest.