Influence of BDNF rs10835210 on right parahippocampal volume and its related cognitive function in first- and multiple-episode bipolar disorder

The brain-derived neurotrophic factor (BDNF) polymorphism rs10835210 has been implicated in bipolar disorder, but its effects on brain morphology and cognition remain unclear. A total of 43 first-episode mania patients (FEM), 110 multiple-episode mania patients (MEM) and 80 healthy controls were enrolled in our study. We investigated the impact of BDNF rs10835210 on hippocampal and parahippocampal volumes, and also the Cambridge Neuropsychological Test Automated Battery. We found a significant interaction between BDNF genotype and diagnosis affecting the volume of the right parahippocampus as well as cognitive measures of memory and attention functions. Specifically, risk A allele carriers exhibited reduced right parahippocampal volumes in both FEM (p < 0.001) and MEM (p = 0.044) groups; however, the risk A allele was associated with declines in memory and attention functions exclusively in FEM patients (p < 0.05). Furthermore, we demonstrated that lower right parahippocampal volume was correlated with worse attention function in A allele carriers among FEM (r = 0.341, p = 0.025). This is the first study to demonstrate that BDNF rs10835210 is linked to right parahippocampal volume reductions across illness stages and to parahippocampus-dependent cognitive deficits specifically in FEM. These findings highlight rs10835210 as a candidate marker of neuroimaging alterations and early cognitive dysfunction in bipolar disorder.