Relationship between whole blood omega-3 fatty acid levels and dorsal cingulate gray matter volume: Sex differences and implications for impulse control

During adolescence, the prefrontal cortex (PFC) undergoes substantial structural development, including cortical thinning, a process associated with improvements in behavioral control. The cingulate cortex is among the regions recruited in response inhibition and mounting evidence suggests cingulate function may be sensitive to availability of an essential dietary nutrient, omega-3 fatty acids (N3; i.e. EPA + DHA). Our primary aim was to investigate the relationship between a biomarker of omega-3 fatty acids -- percent of whole blood fatty acids as EPA + DHA (N3 Index) -- and cingulate morphology, in typically developing adolescent males (n = 29) and females (n = 33). Voxel-based morphometry (VBM) was used to quantify gray matter volume (GMV) in the dorsal region of the cingulate (dCC). Impulse control was assessed via caregiver report (BRIEF) and Go/No-Go task performance. We predicted that greater N3 Index in adolescents would be associated with less dCC GMV and better impulse control. Results revealed that N3 Index was inversely related to GMV in males, but not in females. Furthermore, males with less right dCC GMV exhibited better caregiver-rated impulse control. A simple mediation model revealed that, in males, N3 Index may indirectly impact impulse control through its association with right dCC GMV. Findings suggest a sex-specific link between levels of N3 and dCC structural development, with adolescent males more impacted by lower N3 levels than females. Identifying factors such as omega-3 fatty acid levels, which may modulate the neurodevelopment of response inhibition, is critical for understanding typical and atypical developmental trajectories associated with this core executive function.