Genetic and epigenetic signatures associated with plasma oxytocin levels in children and adolescents with autism spectrum disorder.

Oxytocin (OT), the brain's most abundant neuropeptide, plays an important role in social salience and motivation. Clinical trials of the efficacy of OT in autism spectrum disorder (ASD) have reported mixed results due in part to ASD's complex etiology. We investigated whether genetic and epigenetic variation contribute to variable endogenous OT levels that modulate sensitivity to OT therapy. To carry out this analysis, we integrated genome-wide profiles of DNA-methylation, transcriptional activity, and genetic variation with plasma OT levels in 290 participants with ASD enrolled in a randomized controlled trial of OT. Our analysis identified genetic variants with novel association with plasma OT, several of which reside in known ASD risk genes. We also show subtle but statistically significant association of plasma OT levels with peripheral transcriptional activity and DNA-methylation profiles across several annotated gene sets. These findings broaden our understanding of the effects of the peripheral oxytocin system and provide novel genetic candidates for future studies to decode the complex etiology of ASD and its interaction with OT signaling and OT-based interventions. LAY SUMMARY: Oxytocin (OT) is an abundant chemical produced by neurons that plays an important role in social interaction and motivation. We investigated whether genetic and epigenetic factors contribute to variable OT levels in the blood. To this, we integrated genetic, gene expression, and non-DNA regulated (epigenetic) signatures with blood OT levels in 290 participants with autism enrolled in an OT clinical trial. We identified genetic association with plasma OT, several of which reside in known autism risk genes. We also show statistically significant association of plasma OT levels with gene expression and epigenetic across several gene pathways. These findings broaden our understanding of the factors that influence OT levels in the blood for future studies to decode the complex presentation of autism and its interaction with OT and OT-based treatment.

Medical Etiologies of Secondary Psychosis in Children and Adolescents.

This is an updated review of child and adolescent somatic disorders associated with psychosis/psychotic symptoms, organized into neurologic, infectious, genetic, inborn errors of metabolism, autoimmune, rheumatologic, endocrine, nutritional, metabolic, and iatrogenic categories. When possible clinical manifestations or types of psychotic symptoms and proposed neuropathogenesis causing the neuropsychiatric symptoms are included. In some cases, the psychiatric symptoms may be the first presentation of the disease. The authors hope that this review will aid child and adolescent psychiatrists in considering alternative etiologies of youth presenting with psychosis and encourage appropriate physical examination, history, and further work-up when suspected.

Anti-N-Methyl d-Aspartate Receptor Encephalitis and Electroconvulsive Therapy: Literature Review and Future Directions.

Despite the majority of patients with anti-N-methyl d-aspartate receptor (NMDAR) antibody encephalitis presenting with catatonic symptoms, the literature has not focused on well-known treatments for catatonia, such as electroconvulsive therapy (ECT). The authors review the literature identifying case reports that document the effective use of ECT for anti-NMDAR encephalitis. They also identify gaps in the literature regarding use and documentation of ECT and review possible mechanisms of action for ECT. The authors propose identifying catatonia as a syndrome with multiple potential causes (including anti-NMDAR encephalitis) and suggest a standardized treatment approach using evidence-based catatonia treatments such as ECT and benzodiazepines.