Childhood neglect is associated with reduced corpus callosum area.

BACKGROUND: Childhood abuse has been associated with abnormalities in brain development, particularly corpus callosum (CC) morphology. The impact of neglect has not been assessed, though it is the most prevalent form of childhood maltreatment. METHODS: Regional CC area was measured from magnetic resonance imaging scans in 26 boys and 25 girls admitted for psychiatric evaluation (28 with abuse or neglect) and compared with CC area in 115 healthy control subjects. Data were analyzed by multivariate analysis of covariance, with age and midsagittal area as covariates. RESULTS: Total CC area of the abused/neglected patients was 17% smaller than in control subjects (p =.0001) and 11% smaller than in psychiatric patients who had not been abused or neglected (contrast group; p =.01). Control subjects and the contrast group did not differ in total CC area. Neglect was the strongest experiential factor and was associated with a 15%-18% reduction in CC regions 3, 4, 5, and 7 (all p <.02). In contrast, sexual abuse seemed to be the strongest factor associated with reduced CC size in girls. CONCLUSIONS: These data are consistent with animal research that demonstrated reduced CC size in nursery-reared compared with semi-naturally reared primates. Early experience might also affect the development of the human CC.

Allelic variation within the putative autism spectrum disorder risk gene homeobox A1 and cerebellar maturation in typically developing children and adolescents.

Homeobox A1 (HOXA1) has been proposed as a candidate gene for autism spectrum disorder (ASD) as it regulates embryological patterning of hind-brain structures implicated in autism neurobiology. In line with this notion, a nonsynonymous single nucleotide polymorphism within a highly conserved domain of HOXA1--A218G (rs10951154)--has been linked to both ASD risk, and cross-sectional differences in superior posterior lobar cerebellar anatomy in late adulthood. Despite evidence for early onset and developmentally dynamic cerebellar involvement in ASD, little is known of the relationship between A218G genotype and maturation of the cerebellum over early development. We addressed this issue using 296 longitudinally acquired structural magnetic resonance imaging brain scans from 116 healthy individuals between 5 and 23 years of age. Mixed models were used to compare the relationship between age and semi-automated measures of cerebellar volume in A-homozygotes (AA) and carriers of the G allele (Gcar). Total cerebellar volume increased between ages of 5 and 23 years in both groups. However, this was accelerated in the Gcar relative to the AA group (Genotype-by-age interaction term, P = 0.03), and driven by genotype-dependent differences in the rate of bilateral superior posterior lobar volume change with age (P = 0.002). Resultantly, although superior posterior lobar volume did not differ significantly between genotype groups at age 5 (P = 0.9), by age 23 it was 12% greater in Gcar than AA (P = 0.002). Our results suggest that common genetic variation within this putative ASD risk gene has the capacity to modify the development of cerebellar systems implicated in ASD neurobiology.