Autism spectrum disorders ASD) and schizophrenia SCZ) are severe neurodevelopmental disorders associated with significant social and functional impairment, causing profound disability to affected individuals. Both disorders are characterized by substantial heterogeneity in symptom presentation and severity. Further, their developmental course, responsiveness to treatment, and underlying disease processes are not well understood. Genetic and neurobiological evidence points to considerable overlap between SCZ and ASD. Moreover, an imbalance in excitatory E) and inhibitory I) cortical signaling has been identified as a possible common neurobiological disturbance across disorders. The lack of cross-diagnostic, comparative studies evaluating shared risk factors and underlying disease processes has left the field with clinical phenotypes ungrounded in basic biology. This in turn has contributed to a lack of reliable, effective treatments for many symptoms of both ASD and SCZ. The present study will address this gap by comparing behavioral and neural correlates of excitatory/inhibitory cortical signaling imbalance across adults with ASD and early-course SCZ. Using computationally- and biologically-grounded experimental paradigms and cutting-edge functional
neuroimaging techniques, we will test for E/I imbalance in the context of basic visual processing, which has been implicated in both ASD and SCZ. Furthermore, we will relate behavioral and neural markers of E/I imbalance to shared and distinct clinical symptoms across the two disorders. Importantly, the same computational principles we will test in the context of visual processing may underlie broader social and cognitive deficits across disorders, just as basic sensory processing alterations may contribute to higher-order deficits. This research will thereby contribute to improved understanding of shared and divergent neural mechanisms of ASD and SCZ, and the extent to which they map onto core clinical features. By identifying neural processes and brain regions that are aberrant in neurodevelopmental disorders, this research will lay the groundwork for more focused studies of excitatory glutamatergic) and inhibitory GABAergic) signaling, as well as longitudinal studies examining the neurodevelopmental trajectory of the underlying pathophysiology in vulnerable individuals. Clinically, this work can inform our understanding of the diagnostic heterogeneity within neurodevelopmental and psychiatric disorders. This in turn could lead to increased specificity with which diseases can be identified and understood across development, and rationally inform potential targets for psychopharmacological intervention. In sum, by combining rigorous, cross-diagnostic and interdisciplinary clinical neuroscience approaches, this study represents a vital step in closing the existing gaps in our understanding of the neuropathology underlying SCZ and ASD. Such advances may ultimately have critical impact for public health and improving the quality of life among individuals affected by severe neuropsychiatric disorders.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
