The neurobiology of autism.
Improving clinical tests are allowing us to more precisely classify autism spectrum disorders and diagnose them at earlier ages. This raises the possibility of earlier and potentially more effective therapeutic interventions. To fully capitalize on this opportunity, however, will require better understanding of the neurobiological changes underlying this devastating group of developmental disorders. It is becoming clear that the normal trajectory of neurodevelopment is altered in autism, with aberrations in brain growth, neuronal patterning and cortical connectivity. Changes to the structure and function of synapses and dendrites have also been strongly implicated in the pathology of autism by morphological, genetic and animal modeling studies. Finally, environmental factors are likely to interact with the underlying genetic profile, and foster the clinical heterogeneity seen in autism spectrum disorders. In this review we attempt to link the molecular pathways altered in autism to the neurodevelopmental and clinical changes that characterize the disease. We focus on signaling molecules such as neurotrophin, Reelin, PTEN and hepatocyte growth factor, neurotransmitters such as serotonin and glutamate, and synaptic proteins such as neurexin, SHANK and neuroligin. We also discuss evidence implicating oxidative stress, neuroglial activation and neuroimmunity in autism.
Pardo
Carlos A
CA
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287. USA. cpardo@jhmi.edu
Eberhart
Charles G
CG
D001321:Autistic Disorder / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001921:Brain / Q000002:abnormalities* / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D009421:Nervous System Malformations / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology; D000091042:Reelin Protein; D015398:Signal Transduction / Q000235:genetics