Autism Spectrum Disorders: Multiple Routes to, and Multiple Consequences of, Abnormal Synaptic Function and Connectivity
Carroll L., BRAEUTIGAM S., DAWES J., Krsnik Z., Kostovic I., Coutinho E., Horton C., Dewing J., Gomez-Nicola D., Menassa DA.
Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders of genetic and environmental aetiologies. Some ASD cases are syndromic: associated with clinically defined patterns of somatic abnormalities and a neurobehavioural phenotype (e.g. Fragile X syndrome). Many cases, however, are idiopathic or non-syndromic. Such disorders present themselves during the early postnatal period when language, speech and personality start to develop. ASDs manifest by deficits in social communication and interaction, restricted and repetitive patterns of behaviour across multiple contexts, sensory abnormalities across multiple modalities and comorbidities, such as epilepsy amongst many others. ASDs are disorders of connectivity, as synaptic dysfunction is common to both syndromic and idiopathic forms. Whilst multiple theories have been proposed, particularly in idiopathic ASDs, none address why certain brain areas (e.g. frontotemporal) appear more vulnerable than others or identify factors that may affect phenotypic specificity. In this hypothesis article, we identify possible routes leading to, and the consequences of, altered connectivity and review the evidence of central and peripheral synaptic dysfunction in ASDs. We postulate that phenotypic specificity could arise from aberrant experience-dependent plasticity mechanisms in frontal brain areas and peripheral sensory networks and propose why the vulnerability of these areas could be part of a model to unify pre-existing pathophysiological theories.