👤 Claudia L Treviño

Autistic youth experience high rates of emotion dysregulation, which can significantly impact functioning and quality of life. Despite its clinical significance, emotion dysregulation remains understudied and misunderstood, with few validated measures for use in autistic youth. This study aimed to further validate the Emotion Dysregulation Inventory (EDI) and explore its utility in understanding emotion dysregulation, its relationship with autism symptoms, and its associations with treatment-relevant factors. Caregivers of autistic youth aged 6-11, recruited through the SPARK initiative, completed questionnaires on child behaviors, emotions, and experiences. A total of 320 families were included, with oversampling of minoritized racial and ethnic backgrounds. Structural equation modeling was used to confirm the EDI's two-factor structure and measurement invariance across diverse groups. Latent profile analysis (LPA) and the R3STEP procedure were used to identify subgroups based on emotion dysregulation and autism symptom severity and examine associations with child and family factors. The EDI demonstrated robust psychometric properties, with measurement invariance supporting its use across diverse racial and ethnic groups, as well as for youth with or without a history of language disorder. LPA identified three phenotypic subgroups, each showing meaningful associations with child and family characteristics, including behavioral problems, parental stress, and sleep disturbances. This study contributes to our understanding of emotion dysregulation in autism by supporting the EDI's validity in diverse samples and highlighting associations with autism symptoms, comorbidities, and other challenges. Integrating emotion dysregulation into clinical conceptualizations can improve the quality of care for autistic youth. Show less

Exocytosis of the acrosome (the acrosome reaction) relies on cAMP production, assembly of a proteinaceous fusion machinery, calcium influx from the extracellular medium, and mobilization from inositol 1,4,5-trisphosphate-sensitive intracellular stores. Addition of cAMP to human sperm suspensions bypasses some of these requirements and elicits exocytosis in a protein kinase A- and extracellular calcium-independent manner. The relevant cAMP target is Epac, a guanine nucleotide exchange factor for the small GTPase Rap. We show here that a soluble adenylyl cyclase synthesizes the cAMP required for the acrosome reaction. Epac stimulates the exchange of GDP for GTP on Rap1, upstream of a phospholipase C. The Epac-selective cAMP analogue 8-pCPT-2'-O-Me-cAMP induces a phospholipase C-dependent calcium mobilization in human sperm suspensions. In addition, our studies identify a novel connection between cAMP and Rab3A, a secretory granule-associated protein, revealing that the latter functions downstream of soluble adenylyl cyclase/cAMP/Epac but not of Rap1. Challenging sperm with calcium or 8-pCPT-2'-O-Me-cAMP boosts the exchange of GDP for GTP on Rab3A. Recombinant Epac does not release GDP from Rab3A in vitro, suggesting that the Rab3A-GEF activation by cAMP/Epac in vivo is indirect. We propose that Epac sits at a critical point during the exocytotic cascade after which the pathway splits into two limbs, one that assembles the fusion machinery into place and another that elicits intracellular calcium release. Show less