Amygdala Enlargement in Toddlers with Autism Related to Severity of Social and Communication Impairments

Background: Autism is a heterogeneous neurodevelopmental disorder of unknown etiology marked by social, emotional and communication impairments. The amygdala has long been a site of intense interest in the search for neuropathology in individuals with autism, given its well established role in the production and recognition of emotions and modulatory role in social behavior. Previous studies suggest that the amygdala undergoes an abnormal growth trajectory in individuals with autism that includes a period of early overgrowth, followed by diminished growth at older ages, which parallels an abnormal cortical growth trajectory albeit extends to a later age. However, this pattern is not well characterized, particularly at young ages when the symptoms of autism first become apparent.

Objectives: To 1) measure amygdala volume in toddlers with autism compared to age- and gender-matched, typically developing children and 2) evaluate potential relationships between amygdala size and the severity of behavioral impairments.

Methods: Eighty nine toddlers (n= 66 males, 23 females) participated between the ages of 18-60 months as part of an ongoing longitudinal MRI study. We measured amygdala volume on each toddler’s MRI scan taken closest to 3 years of age using previously published tracing methods (Schumann et al., 2004). Each child then returned at ~5 years of age for a final clinical evaluation, which included the ADOS, ADI-R, and IQ exam.

Results: Toddlers at 3 years of age who later received a confirmed diagnosis of autism (32 males, 9 females) compared to typically developing toddlers (28 males, 11 females) had a larger right (p<.01) and left (p<.05) amygdala volume, when gender and age at MRI were considered covariates. When each gender was analyzed separately, and covaried for age at MRI scan, autistic males had a significantly larger right amygdala volume (p<.05) and autistic females had a significantly larger left (p<.01) and right (p<.01) amygdala volume compared to age- and gender-matched typical toddlers. Correlation analyses revealed a significant relationship of amygdala volume with the severity of social and communication impairments on the ADI-R and in toddlers with an autism spectrum disorder. In males, but not females, with autism, right (r=.51, p<.01) and left (r=.55, p<.01) amygdala volume was correlated with the ADI-R Social scores. Also in males, but not females, with autism, there was a significant negative correlation of Vineland Communication score and right (r=.41, p<.05) and left (r=.37, p<.05) amygdala volume.Conclusions: This study provides further evidence that the amygdala undergoes an abnormal growth trajectory in children with autism, and that the overgrowth begins at least by three years of age, often before the diagnosis is typically given. In toddlers who eventually receive a diagnosis of autism, the degree of amygdala enlargement at three years of age is associated with the severity of their social and communication impairments at five years of age. However, males and females differed in their neuropathological and behavioral profiles, where females more robustly differed from typical in amygdala volume and males showed a significant relationship of amygdala size with the severity of their social and communication impairments.