Amygdala Neuron Number in ASD Is Increased at Pediatric Ages but Decreased By Adulthood

Background: The amygdala is a complex cluster of nuclei located in the rostral portion of the temporal lobe. It plays a prominent role in modulating socioemotional processing, yet little is known about the postnatal neuronal development of this structure in humans. Structural and functional imaging studies have demonstrated an altered age-related growth trajectory and activation of the amygdala across the lifespan in individuals with autism. However, the cellular substrates that underlie this aberrant growth and function are not well understood.

Objectives: Our goal was to quantify the number of mature neurons within subregions of the amygdala in both typical development and autism across the lifespan. We also examine the number of immature neurons within the basal complex of the amygdala using immunohistochemistry as a function of both age and diagnosis.

Methods: We performed a stereological analysis of neuron number and size in subregions of the amygdala utilizing postmortem tissue from 50 human brains (28 Autism, 22 Typical; ages: 2-48 years old) representing the largest study of its kind to date. Additionally, we performed immunohistochemistry for B-cell lymphoma 2 (bcl-2) to examine the number of immature neurons within the basal complex of the amygdala.

Results: The ANOVA analyses demonstrate a significant main effect of diagnosis for lateral nucleus mature neuron number (F(1,39) = 5.24, p < .05), and significant interactions between age and diagnosis for the total amygdala (F(2,41) = 5.69, p < .01), basal nucleus (F(2,41) = 7.13, p < .01), accessory basal nucleus (F(2,41) = 6.85, p < .01), and central nucleus (F(2,39) = 4.23, p < .05). Post hoc comparisons show that within the pediatric group, individuals with autism have more mature neurons than neurotypical individuals in the basal and central nuclei. In adult cases, individuals with autism have significantly fewer mature neurons relative to neurotypical adults in the total amygdala and in the lateral, basal, and accessory basal nuclei. Preliminary examination of immature neurons shows significant age-related reductions of bcl-2 immunoreactive neurons in the basal complex of the amygdala.

Conclusions: These findings provide the first evidence of the normal pattern of lifelong neuronal development and maturation in the postnatal human amygdala. Furthermore, we demonstrate that these typical processes are disrupted in autism, resulting in an age-related loss of neurons across amygdala nuclei in adults with autism. Our results implicate altered neuronal maturation of the amygdala at early ages in autism with potential subsequent degeneration of this structure in adulthood.