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Temporal Lobe Anatomy and Psychiatric Symptoms in Velocardiofacial Syndrome (22q11.2 Deletion Syndrome)

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ABSTRACT

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. J. Am. Acad. Child Adolesc. Psychiatry, 2006;45(5):000-000.

Section snippets

Participants

Herein, we report on 80 children between the ages of 9 and 15 years. The age-matched sample for these analyses consisted of 47 children with VCFS (22 males, mean age, 11.7 [SD = 2.1]; mean IQ, 71.2 [SD = 12.3]), 18 unaffected children (12 males, mean age, 11.5 [SD = 2.0]; mean IQ, 90.3 [SD = 12.1]), and 15 unaffected siblings (five males, mean age, 11.5 [SD = 1.8]; mean IQ, 102.4 [SD = 12.7]).

Families of children with VCFS were recruited through advertisements in the VCFS Educational Foundation

Relationship Between Whole Brain Volume and Regions of Interest

Whole brain volume was significantly smaller in children with VCFS relative to controls (F 1,78 = 5.1; p =.03; η2 = 0.06). In addition, whole brain volume was significantly correlated with hippocampus, amygdala, and prefrontal cortex volumes in both study groups (data not shown). Whole brain was also associated with prefrontal cortex/hippocampus and prefrontal cortex/amygdala ratios in both study groups (data not shown). Accordingly, we covaried for whole brain volume for all neuroanatomic

DISCUSSION

This study demonstrated that volumes of mesial temporal lobe structures are altered in children and adolescents with VCFS and that alterations in amygdala volume are associated with more psychiatric symptoms in children with this genetic disorder. Comparable to a previous study of mesial temporal lobe structures in VCFS (Eliez et al., 2001), participants with VCFS exhibited smaller hippocampal volumes that were proportionate to overall reductions in whole brain volume. In contrast to previous

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    This research was supported by National Institutes of Health awards MH64824 and MH65481 to Dr. Kates. In addition, the authors are grateful to Robert J. Shprintzen, Ph.D., Anne Marie Higgins, N.P., and the children and families who participated.

    Disclosure: Dr. Fremont is funded by Pfizer as part of a multisitestudy of the effectiveness of Zoloft to treat posttraumatic stress disorderin children. The other authors have no financial relationships to disclose.

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