In the central nervous system, the neuropeptide oxytocin stimulates neural networks that regulate social behaviors, including social attachment, aggression, and complex social cognition. Perturbations in oxytocin and/or oxytocin receptor expression results in social behavioral deficits and are associated with a number of psychopathologies including autism spectrum disorder, schizophrenia, anxiety, and depression. In rodent models of autism spectrum disorder, oxytocin is effective at improving social behavior. However, limited translatability between animal models and human physiology has hindered successful translation of these findings into human therapeutics. Oxytocin variant-induced cellular signaling pathways and G-protein coupling have largely been investigated in HEK and CHO heterologous expression systems; however, cellular context is crucial, and these profiles likely differ from intact neurons. This project assessed oxytocin variants in in vitro human-derived neuron-like SH-SY5Y cells that endogenously express the oxytocin receptor. Results demonstrated that the naturally occurring oxytocin variants Leu⁸-OT, Pro⁸-OT and Val³-Pro⁸-OT activated intracellular signaling pathways and promoted neuronal differentiation-associated responses, including calcium mobilization, membrane hyperpolarization, and neurite outgrowth in a concentration-dependent manner. Knowledge of how oxytocin variants alter cellular structure and function has the potential to both identify mechanisms that produce social dysfunction and to inform the development of therapeutic agents.

Introduction: Seizure disorders are a common comorbidity of pregnancy, leading to increased maternal and neonatal complications. In particular, we sought to identify the impact of seizure disorders on severe maternal morbidity (SMM) and hypertensive disorders of pregnancy in a contemporary cohort. Methods: Retrospective cohort study using the National Inpatient Sample (NIS) database from 2017 to 2021 through Healthcare Cost and Utilization Project (HCUP)/Agency for Healthcare and Research Quality (AHRQ), utilizing delivery admissions. Pregnant patients with seizure disorder were identified by International Classification of Diseases (ICD)‐10 codes. We assessed the prevalence of seizure disorders in pregnancy and compared baseline characteristics of those with a seizure disorder to those without a seizure disorder using weighted sampling per the NIS guidelines. Our primary outcome was a composite of SMM as defined by the Centers for Disease Control. Secondary outcomes were hypertensive disorders of pregnancy, hemorrhage, cesarean delivery, maternal death, and maternal length of stay. Statistical analyses were performed with survey weights and included Student's t ‐test, χ ² analysis, and linear and logistic regression to control for confounders. A sensitivity analysis was performed among only subjects with HDP to assess adverse outcomes in this population. Results: Over a 5‐year period, more than 16 million subjects were included, of which a total of 83,050 (0.5%) pregnant patients had an ICD‐10 diagnosis for seizure disorder at the time of delivery. The prevalence increased from 2017 to 2021 (0.45% to 0.54%, p < 0.001). Patients with an ICD‐10 code for seizure disorder were more likely to use tobacco and have ICD‐10 or CMR code for obesity, diabetes mellitus, and hypertension. Those with a seizure disorder were more likely to experience the composite SMM, hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, eclampsia, hemorrhage, cesarean delivery, maternal death, and longer length of stay than those without a seizure disorder during their delivery hospitalization. In the adjusted analyses, seizure disorder was associated with SMM (adjusted odds ratio [aOR], 2.16; 95% confidence interval [CI], 2.03–2.30) and maternal death (aOR, 6.30; 95% CI, 3.07–12.942). Having a seizure disorder was also associated with hemorrhage, cesarean, severe forms of hypertensive disorders of pregnancy, and increased length of stay. SMM remained elevated in the seizure disorder population in the sensitivity analysis. Conclusion: Seizure disorder in pregnancy increased in prevalence from 2017 to 2021 and is associated with risk factors such as obesity, tobacco use, diabetes mellitus, and hypertension. These patients are more likely to experience SMM, death, and severe forms of hypertensive disorders of pregnancy than pregnant patients without a seizure disorder.