Temporal lobe anatomy and psychiatric symptoms in velocardiofacial syndrome (22q11.2 deletion syndrome)

Objective: To investigate the association between mesial temporal lobe morphology, ratios of prefrontal cortex to amygdala and hippocampus volumes, and psychiatric symptomatology in children and adolescents with velocardiofacial syndrome (VCFS). Method: Scores on behavioral rating scales and volumetric measures of the amygdala, hippocampus, and prefrontal cortex based on high-resolution magnetic resonance imaging were compared among 47 children with VCFS, 15 of their siblings, and 18 community controls. Results: After covarying for whole brain volume, children with VCFS exhibited 11% greater volume of the left amygdala (p = .002) and 8% greater volume of the right amygdala (p = .01). Children with VCFS exhibited smaller volumes of the hippocampus, but not disproportionately to reductions in whole brain volume. Children with VCFS exhibited smaller volumetric ratios of prefrontal and orbitofrontal cortex to amygdala, but not prefrontal cortex to hippocampus. For children with VCFS, but not for the comparison sample, larger volumes of the amygdala and smaller ratios of prefrontal cortex to amygdala were associated with higher scores on the Internalizing, Externalizing, Anxiety, and Aggression scales of the Child Behavior Checklist and on the parent version of the Young Mania Rating Scale. Conclusions: These findings suggest that the prefrontal cortex-amygdala circuit that underlies emotional processing is disrupted in children with VCFS and may be an important neurobiological substrate of psychiatric disorder in these children.