The Biochemical Basis of Autistic Behavior and Pathology

Autism and autism spectrum disorders (ASD) are diseases which are characterized by physical (neurological function and pathology) and behavioral (social interaction) abnormalities that are most commonly diagnosed in children (predominately males) between the ages of 2 and 10 years. Autism is a neurodevelopmental disorder. In autism the Central Nervous System (CNS) cells preferentially affected are the GABAergic Purkinje neurons of the cerebellum. However unlike classical neurodegenerative diseases, in autism, progressive decline is uncommon and there is a concomitant superimposition of neuronal hypersensitivity. This apparent contradiction can be best explained by metabolic abnormalities which have differing effects on specific cell types. Identifying the root of these pleiotropic events has been a topic of intense investigation. From a biochemical perspective, the preponderance of evidence implicates the breakdown of mitochondrial function. From a genetics perspective, genetic mutations targeting mitochondrial function collectively account for more than 10% of all cases, by far the largest single site genetic contribution. However, despite the evidence implicating impaired mitochondrial function, the extramitochondrial biochemical implications and consequences of an impaired mitochondrial system have not been thoroughly investigated. The following chapter outlines the causes and implications of mitochondrial impairment in autism.