Objectives: In order to assess whether lower neuron numbers in the amygdala of autistic adults may also be the product of irregular development, we extended our original stereological analysis, counting neurons in the amygdala using an expanded dataset with a greater focus on childhood.
Methods: We used the optical fractionator technique to estimate neuron number in Nissl-stained sections from a postmortem sample of autistic and control cases between 2-44 years of age. Data were divided into three age classes, child, adolescent, and adult, including at least 6 cases per class. A 2-way ANOVA and pairwise comparisons were used to assess the influence of age class and diagnosis on neuron number. Additionally, neuron numbers in each diagnostic group were regressed against subjects’ numeric age, testing for the possibility of a linear, quadratic, or cubic relationship between variables.
Results: Children with autism exhibited a slightly higher mean number of neurons in the lateral nucleus than typically developing children, but this relationship was reversed in adolescence and adulthood. The 2-Way ANOVA approached significance. The main effect of age class did not reach significance, but the main effect of diagnosis and the interaction of age class and diagnosis approached significance. Specifically, pairwise comparisons indicated that the number of neurons in the lateral nuclei of autistic children was significantly greater than in autistic adults (p = 0.037) and nearly significantly greater than in autistic adolescents (p = 0.059). In pairwise comparisons of diagnostic categories within discrete age classes, adults, but not children or adolescents, with autism exhibited significantly fewer neurons in the lateral nucleus compared with control cases (p = 0.035). No age differences were evident in the control sample. Reinforcing these trends, the relationship between numeric age and neuron number in autism was best described by a negative linear regression line (p = 0.067). Neuron number in control cases was not closely related to numeric age (p > 0.50 for all lines).
Conclusions: In our sample, autistic children exhibited approximately the same number of neurons in the lateral nucleus as control children, statistically, although autistic adults exhibited significantly lower numbers. This is presumably due to an age-related decrease in neuron number in autism, rather than age-related changes in control cases. These preliminary findings suggest that autistic individuals are not born with a deficit of amygdala neurons, but may experience greater rates of neuron loss through development than do typically developing individuals. The low availability of tissue in young age classes clearly limits statistical power in this and related developmental analyses, but our findings highlight the importance of assessing variation at the earliest stages of autistic neuropathology.