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Association Between Amygdala Volume and Anxiety Level: Magnetic Resonance Imaging (MRI) Study in Autistic Children

Department of Pediatrics, University of California, Irvine, Irvine, CA; jjuranek{at}uci.edu

Pauline A. Filipek, MD

Department of Pediatrics, University of California, Irvine, Irvine, CA; Divisions of Child Neurology, University of California, Irvine, Irvine, CA

Gholam R. Berenji, MD

Charlotte Modahl, PhD

Department of Pediatrics, University of California, Irvine, Irvine, CA

Kathryn Osann, PhD

Department of Medicine, University of California, Irvine, Irvine, CA

M. Anne Spence, PhD

Department of Pediatrics, University of California, Irvine, Irvine, CA; Divisions of Human Genetics, College of Medicine, University of California, Irvine, Irvine, CA

Our objective was to evaluate brain-behavior relationships between amygdala volume and anxious/depressed scores on the Child Behavior Checklist in a well-characterized population of autistic children. Volumes for the amygdala, hippocampus, and whole brain were obtained from three-dimensional magnetic resonance images (MRIs) captured from 42 children who met the criteria for autistic disorder. Anxious/depressed symptoms were assessed in these children by the Anxious/Depressed subscale of the Child Behavior Checklist. To investigate the association between anxious/depressed scores on the Child Behavior Checklist and amygdala volume, data were analyzed using linear regression methods with Pearson correlation coefficients. A multivariate model was used to adjust for potential covariates associated with amygdala volume, including age at MRI and total brain size. We found that anxious/depressed symptoms were significantly correlated with increased total amygdala volume (r = .386, P = .012) and right amygdala volume (r = .469, P = .002). The correlation between anxious/depressed symptoms and left amygdala volume did not reach statistical significance (r = .249, P = .112). Child Behavior Checklist anxious/depressed scores were found to be a significant predictor of amygdala total (P = .014) and right amygdala (P = .002) volumes. In conclusion, we have identified a significant brain-behavior relationship between amygdala volume and anxious/depressed scores on the Child Behavior Checklist in our autistic cohort. This specific relationship has not been reported in autism. However, the existing literature on human psychiatry and behavior supports our reported evidence for a neurobiologic relationship between symptoms of anxiety and depression with amygdala structure and function. Our results highlight the importance of characterizing comorbid psychiatric symptomatology in autism. The abundance of inconsistent findings in the published literature on autism might reflect differences between study populations regarding age at MRI, level of impairment within autistic subjects, and underlying anxiety level in the selected study groups.

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