A Meta-Analysis of the Corpus Callosum in Autism

Background: Several previous MRI studies have reported reductions in corpus callosum (CC) total area and several of its sub-regions in individuals with autism , supporting the aberrant connectivity hypothesis. However, studies have differed concerning the presence (3 of 10 studies report null findings), magnitude, and/or sub-region contributing to CC reductions.

Objectives: The primary aim of the present study was to meta-analytically determine the significance and magnitude of reduction in CC total, regional, and Witelson subdivision area measures in patients with autism. The secondary aim was to examine possible moderators of total CC effects.

Methods: PubMed/Medline and PsycInfo databases were searched to identify MRI studies examining corpus callosum area in autism. Ten studies contributed data from 253 patients with autism (Mean age=14.58, SD=6.00) and 250 healthy controls (M age=14.47, sd=5.31). Of these ten studies, eight reported area measurements for corpus callosum sub-regions (anterior, mid/body, and posterior) with six studies reporting area for Witelson subdivisions. Fixed and random effects meta-analytic procedures were used to quantify autism versus healthy control differences in total and sub-region CC area measurements. Demographics and study characteristics were also coded and examined as moderators of total CC area reductions. Funnel plots and fail-safe N were used to examine possible study sampling bias.

Results: Total CC area was reduced in autism and the magnitude of the reduction was medium (Weighted Mean d=.48, 95% CI=.30-.66). All sub-regions showed reductions in size with the magnitude of the effect decreasing caudally (anterior d=.49, mid/body d=.43, posterior d=.37). Witelson sub-division 3 (rostral body) showed the largest effect, indicating greatest reduction in the region containing pre-/supplementary motor neurons. Funnel plots and fail-safe N indicated minimal, if any, bias in study sampling. Older participants and greater magnet strength produced larger discrepancies in total CC area between individuals with autism and healthy controls.

Conclusions: CC reductions are present in autism and support the aberrant connectivity hypothesis. Future diffusion tensor imaging studies examining specific fiber tracts connecting the hemispheres via the corpus callosum are needed to identify the cortical regions most affected by CC area reductions. Future research should also model the variance in CC area/volume to identify possible autism sub-groups.