Delayed Development of Neurons in Networks Involved with Stereotypic Behaviors and Reward in Autism

Background:

Autism signs include lower-order repetitive motor behaviors, intense circumscribed patterns of interests, and higher-order rituals and compulsions that occur regularly and interfere with daily functioning (Gabriels et al., 2005). Several studies have implicated the role of basal ganglia and frontostriatal circuitry in the pathophysiology of autism, especially in repetitive and stereotyped behaviors. Increased volume of the basal ganglia was reported in several MRI studies (Herbert et al., 2003; Hollander et al., 2005; Langen et al., 2007; Sears et al., 1999). However, the nature of cellular changes in the basal ganglia is unknown.

Objectives:

We suggest that the application of sensitive, unbiased morphometric methods may reveal cellular developmental changes in the striatum that contribute to the restricted repetitive and stereotyped behavior in autistic subjects. The presence of changes in the nucleus accumbens could be an indicator of the abnormal function of the reward system. We hypothesize also that changes in the reward system may amplify repetitive and stereotyped behaviors in early childhood.

Methods:

To test this hypothesis, we examined the caudate nucleus, putamen and globus pallidus, contributing to restricted repetitive and stereotyped behaviors, and the nucleus accumbens, which is a component of the reward system, in the brains of 14 subjects diagnosed with idiopathic autism and of 14 age-matched controls. The Cavalieri method was applied to evaluate the volume of the examined structures; the fractionator method, to estimate the number of neurons; and a nucleator, to estimate the volume of neurons and nuclei.

Results:

Our study showed a significantly smaller size of neurons in the caudate, putamen, and globus pallidus in the brains of autistic children 4 - 8 years of age. This suggests a developmental delay in the growth of neurons, which may contribute to the dysfunction of all components of the basal ganglia network. The significant developmental delay of neuron growth in the nucleus accumbens suggests that the reward system is also affected.

Conclusions:

Our results provide new evidence that developmental abnormalities in the striatal circuitry contribute to repetitive and stereotyped behaviors and that developmental changes in the nucleus accumbens may enhance engagement in rituals and stereotyped behavior.