The Emerging Clinical Neuroscience of Autism Spectrum Disorder A Review

IMPORTANCE Autism spectrum disorder (ASD) is a highly prevalent disorder, and community psychiatrists are likely to treat many individuals with ASD during their clinical practice. This clinical case challenge describes a routine evaluation of irritability and self-injury in a preschool-aged child who meets the criteria for ASD. The case also illustrates the importance of known risk factors for ASD, such as chromosomal deletion and prematurity. This clinical neuroscience article seeks to educate the clinician of current avenues of research that can inform and may already affect clinical practice for this patient, while providing a preview of research that may yield biological treatments for ASD within the next decade. OBSERVATIONS A diagnosis of ASD is defined behaviorally; therefore, many genetic and environmental risk factors, working singly or in concert, are linked to ASD. The prenatal period of brain development is particularly sensitive to risk factors such as gene mutation or drug exposure that affect brain development and circuitry formation. Currently, neuroimaging researchers can detect changes in brain connectivity of children with ASD as young as 6 months, followed by an atypical trajectory of brain development through preschool age and ongoing connectivity inefficiencies across the lifespan. Animal and cellular model systems have provided a means for defining the molecular and cellular changes associated with risk factors for ASD. The ability to connect specific treatments to particular subgroups of people with ASD is the defining hope of precision medicine initiatives. CONCLUSIONS AND RELEVANCE The advent of next-generation sequencing technology, advanced imaging techniques, and cutting-edge molecular techniques for modeling ASD has allowed researchers to define ASD risk-related biological pathways and circuits that may, for the first time, unify the effects of disparate risk factors into common neurobiological mechanisms. The path from these mechanisms to biological treatments that improve the lives of individuals with autism remains unclear, but the cumulative output of multiple lines of research suggests that subtyping by genetic risk factors may be a particularly tractable way to capitalize on individual differences amenable to specific treatments.