Bcl-2 Polymorphism Influences Gray Matter Volume in the Ventral Striatum in Healthy Humans

Background: Bcl-2 is a major regulator of neural plasticity and cellular resilience. A single nucleotide polymorphism (SNP) in the Bcl-2 gene, Bcl-2 rs956572, significantly modulates the expression of Bcl-2 protein and cellular vulnerability to apoptosis. We tested the hypothesis that this SNP would modulate gray matter (GM) volume in the limbic-cortical-striatal-pallidal-thalamic circuitry that plays major roles in mood regulation. Methods: Forty-seven healthy subjects participated in this study (30 A carriers, 17 G homozygotes). Neuromorphometric differences between G homozygotes and A carriers were investigated using optimized voxel-based morphometry (VBM). Statistical significance was set at p<.05, corrected for multiple comparisons. Results: A carriers showed less GM volume than G homozygotes in the left ventral striatum (p(corrected)<.05). Conclusions: Genetic variation in the Bcl-2 gene modulates GM volume in areas known to play key roles in the neurobiology of reward processes and emotion regulation and in the pathophysiology of mood disorders. Thus, the findings from the current study are noteworthy insofar as they converge with preclinical findings that Bcl-2 functions to enhance neuronal viability and might indirectly extend this evidence to humans.