Objective This study was carried out to examine the efficacy of a 12-week, low intensity (one-hour-per-week of therapist contact), parent-delivered intervention for toddlers at risk for autism spectrum disorders (ASD) ages 14–24 months and their families. Method A randomized controlled trial involving 98 children and families was carried out in three different sites investigating the efficacy of a parent delivery of the Early Start Denver Model (P-ESDM) (which fosters parental use of a child-centered responsive interaction style that embeds many teaching opportunities into play) compared to community treatment as usual. Assessments were completed at baseline and 12 weeks later, immediately after the end of parent coaching sessions. Results There was no effect of group assignment on parent-child interaction characteristics or on any child outcomes. Both groups of parents improved interaction skills and both groups of children demonstrated progress. Parents receiving P-ESDM demonstrated significantly stronger working alliances with their therapists than did the community group. Children in the community group received significantly more intervention hours than those in the P-ESDM group. For the group as a whole, both younger child age at the start of intervention, and a greater number of intervention hours, were positively related to degree of improvement in children’s behavior for most variables. Conclusions Parent-implemented intervention studies for early ASD have thus far not demonstrated the large effects seen in intensive treatment studies. Evidence that both younger age and more intervention hours positively affect developmental rates has implications for clinical practice, service delivery, and public policy.

The amino acid antiporter system Xc − is important for the synthesis of glutathione (GSH) that functions to prevent lipid peroxidation and protect cells from nonapoptotic, iron-dependent death (i.e., ferroptosis). While the activity of system Xc − often positively correlates with the expression level of its light chain encoded by SLC7A11, inhibition of system Xc − activity by small molecules (e.g., erastin) causes a decrease in the intracellular GSH level, leading to ferroptotic cell death. How system Xc − is regulated during ferroptosis remains largely unknown. Here we report that activating transcription factor 3 (ATF3), a common stress sensor, can promote ferroptosis induced by erastin. ATF3 suppressed system Xc − , depleted intracellular GSH, and thereby promoted lipid peroxidation induced by erastin. ATF3 achieved this activity through binding to the SLC7A11 promoter and repressing SLC7A11 expression in a p53-independent manner. These findings thus add ATF3 to a short list of proteins that can regulate system Xc − and promote ferroptosis repressed by this antiporter.

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