International Meeting for Autism Research: Sex-Related Brain Differences and Heterogeneity in the Autism Spectrum

Sex-Related Brain Differences and Heterogeneity in the Autism Spectrum

Friday, May 21, 2010
Franklin Hall B Level 4 (Philadelphia Marriott Downtown)
2:00 PM
K. A. Loveland , Dept. of Psychiatry & Behavioral Sciences, University of Texas Medical School at Houston, Houston, TX
L. Cirilli , Yerkes National Primate Research Centre, Emory University, Atlanta
D. A. Pearson , Dept. of Psychiatry & Behavioral Sciences, University of Texas Medical School at Houston, Houston, TX
J. Bachevalier , Yerkes National Primate Research Centre, Emory University, Atlanta
Background: Autism is a neurodevelopmental disorder characterized by social-cognitive differences affecting many areas of functioning. Autism is also highly heterogeneous with a complex genetic and neural basis. Medial temporal lobe structures including amygdala and hippocampus have been identified by imaging, histopathologic, neurologic and neuropsychologic studies as among those affected in Autism Spectrum Disorders (ASD). Research has also linked these structures to the central social cognitive differences of ASD. However, they have not been well studied with respect to other characteristics, such as sex, IQ and changes with age, that may help to explain some of the heterogeneity in ASD.

Objectives: As part of a study of fronto-limbic brain structures and development in ASD, we collected structural Magnetic Resonance Imaging on children and adolescents aged 7 – 18 with (n=58; 49 males) and without (n=52; 38 males) ASD.  Regions of Interest (ROIs) for the present study included amygdala, hippocampus, and regions of the corpus callosum, along with anterior commissure length (AC), Total Brain Volume and Total Brain Surface Area. We examined differences between the two groups in volumes of medial temporal lobe structures, as well as other non-MTL structures and also whether any differences in MTL structure volumes were related to participants’ sex, chronological age (CA), verbal or nonverbal IQ (VIQ, NVIQ).

Methods: Participants were grouped using ADI-R and ADOS and stratified by age and IQ. sMRI was collected using a GE 1.5T MR scanner with a thin-slice (0.7 mm) T1-weighted 3D SPGR brain (temporal lobe) sequence. ROIs were traced and volumes calculated using ImageJ software (NIH). All ROI dependent measures except Total Brain Volume with and without ventricles were expressed as a ratio of ROI volume to Total Brain Volume. Group differences were examined using ANCOVA with sex, CA, VIQ and NVIQ as covariates.

Results: Total brain volume differed by sex, F(1,103)=10.67, p=.001, but not by diagnostic group, CA or IQ. With effects of CA, VIQ and NVIQ controlled, both right and left amygdala volumes for ASD females were higher than those of males, whereas volumes for non-ASD females were lower than those of males [Group x Sex: F(1,103)=8.39, p=.005]. Total brain surface area of females was also greater than that of males within the ASD group, but this difference was not present in the non-ASD group [Group x Sex, F(1,103)= 7.26, p=.008].  A statistically significant difference in volume between the ASD and non-ASD groups was found in left but not right hippocampus. In both groups, amygdala and hippocampus volumes (bilaterally) and regions of the posterior corpus callosum were positively associated with CA, whereas total brain surface area, total brain volume, and anterior corpus callosum were not. Bilaterally, hippocampus volumes were positively associated with NVIQ, whereas amygdala volumes were not associated with VIQ or NVIQ.          

Conclusions: Males and females with ASD may differ in brain structures in ways not characteristic of similar persons without ASD. Sex-related differences in brain development deserve further exploration in ASD because they may reveal sources of heterogeneity of developmental course and also have implications for treatments.

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