The neurobiology of autism: new pieces of the puzzle

Abstract

The neurobiologic basis of autism is reviewed, with discussion of evidence from genetic, magnetic resonance imaging, neuropathology, and functional neuroimaging studies. Although autism is a behaviorally valid syndrome, it is remarkably heterogeneous and involves multiple developmental domains as well as a wide range of cognitive, language, and socioemotional functioning. Although multiple etiologies are implicated, recent advances have identified common themes in pathophysiology. Genetic factors play a primary role, based on evidence from family studies, identification of putative genes using genome-wide linkage analyses, and comorbidities with known genetic mutations. The RELN gene, which codes for an extracellular protein guiding neuronal migration, has been implicated in autism. Numerous neuropathologic changes have been described, including macroencephaly, acceleration and then deceleration in brain growth, increased neuronal packing and decreased cell size in the limbic system, and decreased Purkinje cell number in the cerebellum. Abnormalities in organization of the cortical minicolumn, representing the fundamental subunit of vertical cortical organization, may underlie the pathology of autism and result in altered thalamocortical connections, cortical disinhibition, and dysfunction of the arousal-modulating system of the brain. The role of acquired factors is speculative, with insufficient evidence to link the measles-mumps-rubella (MMR) vaccine with autism or to change immunization practices.