Schizophrenia is a severe mental disorder with an unclear pathophysiology. Increased expression of the immune gene C4 has been linked to a greater risk of developing schizophrenia; however, it is not known whether C4 plays a causative role in this brain disorder. Using confocal imaging and whole-cell electrophysiology, we demonstrate that overexpression of C4 in mouse prefrontal cortex neurons leads to perturbations in dendritic spine development and hypoconnectivity, which mirror neuropathologies found in schizophrenia patients. We find evidence that microglia-mediated synaptic engulfment is enhanced with increased expression of C4. We also show that C4-dependent circuit dysfunction in the frontal cortex leads to decreased social interactions in juvenile and adult mice. These results demonstrate that increased expression of the schizophrenia-associated gene C4 causes aberrant circuit wiring in the developing prefrontal cortex and leads to deficits in juvenile and adult social behavior, suggesting that altered C4 expression contributes directly to schizophrenia pathogenesis.
Children with autism spectrum disorders (ASD) face pervasive challenges in symbolic and social play development. The Integrated Play Groups (IPG) model provides intensive guidance for children with ASD to participate with typical peers in mutually engaging experiences in natural settings. This study examined the effects of a 12-week IPG intervention on the symbolic and social play of 48 children with ASD using a repeated measures design. The findings revealed significant gains in symbolic and social play that generalized to unsupported play with unfamiliar peers. Consistent with prior studies, the outcomes provide robust and compelling evidence that further validate the efficacy of the IPG model. Theoretical and practical implications for maximizing children's developmental potential and social inclusion in play are discussed.
This study examined how parenting style at 9 months predicts growth in infant social engagement (i.e., social smiling) between 9 and 18 months during a free-play interaction in infants at high (HR-infants) and low (LR-infants) familial risk for Autism Spectrum Disorder (ASD). Results indicated that across all infants, higher levels of maternal responsiveness were concurrently associated with higher levels of social smiling, while higher levels of maternal directiveness predicted slower growth in social smiling. When accounting for maternal directiveness, which was higher in mothers of HR-infants, HR-infants exhibited greater growth in social smiling than LR-infants. Overall, each parenting style appears to make a unique contribution to the development of social engagement in infants at high- and low-risk for ASD.
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