Stereological Analysis of Amygdala Neuron Number in Autism

Abstract

The amygdala is one of several brain regions suspected to be pathological in autism. Previously, we found that young children with autism have a larger amygdala than typically developing children. Past qualitative observations of the autistic brain suggest increased cell density in some nuclei of the postmortem autistic amygdala. In this first, quantitative stereological study of the autistic brain, we counted and measured neurons in several amygdala subdivisions of 9 autism male brains and 10 age-matched male control brains. Cases with comorbid seizure disorder were excluded from the study. The amygdaloid complex was outlined on coronal sections then partitioned into five reliably defined subdivisions: (1) lateral nucleus, (2) basal nucleus, (3) accessory basal nucleus, (4) central nucleus, and (5) remaining nuclei. There is no difference in overall volume of the amygdala or in individual subdivisions. There are also no changes in cell size. However, there are significantly fewer neurons in the autistic amygdala overall and in its lateral nucleus. In conjunction with the findings from previous magnetic resonance imaging studies, the autistic amygdala appears to undergo an abnormal pattern of postnatal development that includes early enlargement and ultimately a reduced number of neurons. It will be important to determine in future studies whether neuron loss in the amygdala is a consistent characteristic of autism and whether cell loss occurs in other brain regions as well.

Abnormal Fear Conditioning and Amygdala Processing in an Animal Model of Autism

“…Even though the hypothesis that the amygdala might underlie abnormal fear processing in autism has been brought forward recently (Amaral et al, 2003;Schumann and Amaral, 2006), the present study is the first to show that fear memories are greatly enhanced, overly generalized to novel stimuli, and harder to extinguish in an animal model of autism. These results are in fact also consistent with some less cited autistic features such as enhanced fears and phobias originally described by Kanner (1943) and reported in some more recent studies (Muris et al, 1998;Gillott et al, 2001;Evans et al, 2005).…”

“…Both microscopic and macroscopic studies reveal alterations in the morphology of the amygdala in autism (Kemper and Bauman, 1998;Aylward et al, 1999;Sparks et al, 2002;Schumann et al, 2004;Schumann and Amaral, 2006), indicating a dysfunction in this region that might possibly contribute to the autistic pathology. The current 'amygdala theory of autism' is based on the lost capability to evaluate socioemotional information and lost drive for social interaction derived from lesioning studies in monkeys and a few functional imaging studies in humans (Baron-Cohen et al, 2000;Sweeten et al, 2002;Pelphrey et al, 2004;Bachevalier and Loveland, 2006;Schultz, 2005), which implies that a hypofunctioning amygdala underlies autism.…”

“…Several brain structures and pathways have been suggested to underlie this disorder, among them the amygdala (Bachevalier, 1994;Baron-Cohen et al, 1999;Adolphs et al, 2001), which exhibits a number of abnormalities. Whereas earlier postmortem studies on autistic patients indicated an increased number of cells with reduced cell size in the cortical, medial, and central nuclei of the amygdala (Kemper and Bauman, 1998), more recent and modern stereological counts of neurons in the amygdala revealed a reduced number of neurons, particularly in the lateral nucleus (Schumann and Amaral, 2006). The total amygdala volume is enlarged during early infancy (Sparks et al, 2002;Schumann et al, 2004), but can be reduced in adulthood (Aylward et al, 1999).…”

Neuroimaging in autism spectrum disorders: ¹H-MRS and NIRS study

“…Although we chose the left amygdala in this study, the side of the amygdala that plays a greater role in individuals with autism is not yet clear. Schumann and Amaral reported significantly fewer neurons in the bilateral amygdalae of the postmortem autistic brain (18).…”

The mouse Engrailed genes: A window into autism

“…Interestingly, an analysis of 12 MRI studies showed that by adolescence, the difference in brain volume between autistic individuals and controls was only 1 to 2 % [55]. Volumetric changes such as these likely provoked Schumann and Amaral [58] to quantitatively measure and compare the number of amygdalar neurons in post mortem autistic and control brains. Using stereological methods, they found a significant reduction in neuronal number in both the total amygdala and in the lateral nucleus of autistic individuals.…”