Lateralized white matter integrity changes across the lifespan in major depression: AES-SDM meta-analysis

This meta-analysis examined white matter fractional anisotropy (FA) differences across the lifespan to better understand underlying neurobiological mechanisms of major depressive disorder (MDD). Using anisotropic effect size-based–signed differential mapping (AES-SDM), the study meta-analyzed 67 whole-brain FA voxel-based analysis (VBA) and tract-based spatial statistics (TBSS) studies. The sample included 3620 individuals with MDD and 3764 age-matched healthy controls, ranging from adolescence to older adulthood. AES-SDM uses anisotropic kernels combined with random-effects models and permutation tests to perform robust neuroimaging meta-analysis. Between-group analyses uncovered a lateralization effect: Adolescent and adult MDD were associated with left-hemisphere abnormalities, while older adult MDD was associated with right-hemisphere abnormalities. Specifically, MDD was associated with lower left anterior thalamic projection, left pons, left corticospinal projection, and left cingulum FA in adolescents; lower left optic radiation, left striatum, left cingulum, and left inferior longitudinal fasciculus FA in adults; and lower right anterior thalamic projection, right fronto-occipital fasciculus, right striatum, right superior longitudinal fasciculus, and left inferior longitudinal fasciculus FA in older adults. The laterality seen in the current data and previous research could potentially serve as biomarkers to improve diagnostic accuracy. It is recommended that future white matter MDD primary studies include more adolescents and older adults.