The neuropathology of the autism spectrum disorders: what have we learned?

Abstract

Autism is a behaviourally defined disorder, initially described by Kanner in 1943. By definition, symptoms are manifested by 36 months of age and are characterized by delayed and disordered language, impaired social interaction, abnormal responses to sensory stimuli, events and objects, poor eye contact, an insistence on sameness, an unusual capacity for rote memory, repetitive and stereotypic behaviour and a normal physical appearance. Relatively few neuropathological studies have been performed on the brains of autistic subjects. Of those reported, abnormalities have been described in the cerebral cortex, the brainstem, the limbic system and the cerebellum. Although those with the disorder present with a specific set of core characteristics, each individual patient is somewhat different from another. Thus, it should not be surprising that the brains of these subjects should show a wide range of abnormalities. However, it is important to delineate the anatomic features, which are common to all cases, regardless of age, sex and IQ, in order to begin to understand the central neurobiological profile of this disorder. The results of our systematic studies indicate that the anatomic features that are consistently abnormal in all cases include reduced numbers of Purkinje cells in the cerebellum, and small tightly packed neurons in the entorhinal cortex and in the medially placed nuclei of the amygdala. It is known that the limbic system is important for learning and memory, and that the amygdala plays a role in emotion and behaviour. Research in the cerebellum indicates that this structure is important as a modulator of a variety of brain functions and impacts on language processing, anticipatory and motor planning, mental imagery and timed sequencing. Defining the differences and similarities in brain anatomy in autism and correlating these observations with detailed clinical descriptions of the patient may allow us greater insight into the underlying neurobiology of this disorder.