Extrahypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance.

Oxytocin increases the salience of both positive and negative social contexts and it is thought that these diverse actions on behavior are mediated in part through circuit-specific action. This hypothesis is based primarily on manipulations of oxytocin receptor function, leaving open the question of whether different populations of oxytocin neurons mediate different effects on behavior. Here we inhibited oxytocin synthesis in a stress-sensitive population of oxytocin neurons specifically within the medioventral bed nucleus of the stria terminalis (BNSTmv). Oxytocin knockdown prevented social stress-induced increases in social vigilance and decreases in social approach. Viral tracing of BNSTmv oxytocin neurons revealed fibers in regions controlling defensive behaviors, including lateral hypothalamus, anterior hypothalamus, and anteromedial BNST (BNSTam). Oxytocin infusion into BNSTam in stress naïve mice increased social vigilance and reduced social approach. These results show that a population of extrahypothalamic oxytocin neurons plays a key role in controlling stress-induced social anxiety behaviors.

Oxytocin receptor behavioral effects and cell types in the bed nucleus of the stria terminalis.

Oxytocin is a neuropeptide that can produce anxiolytic effects and promote social approach. However, emerging evidence shows that under some conditions, oxytocin can instead induce anxiety-related behaviors. These diverse effects of oxytocin appear to be mediated by circuit-specific actions. Recent data showed that inhibition of oxytocin receptors (OTRs) in the bed nucleus of the stria terminalis (BNST) was sufficient to increase social approach and decrease social vigilance in female California mice (Peromyscus californicus) exposed to social defeat stress. As a member of the G-protein coupled receptor family, OTRs can induce distinct downstream pathways by coupling to different G-protein isoforms. We show that infusion of carbetocin, a biased OTR-Gq agonist, in the BNST reduced social approach in both female and male California mice. In both females and males, carbetocin also increased social vigilance. To gain insight into cell types that could be mediating this effect, we analyzed previously published single-cell RNAseq data from the BNST and nucleus accumbens (NAc). In the NAc, we and others showed that OTR activation promotes social approach behaviors. In the BNST, Oxtr was expressed in over 40 cell types, that span both posterior and anterior subregions of the BNST. The majority of Oxtr-expressing neurons were GABAergic. In the anterior regions of BNST targeted in our carbetocin experiments, Cyp26b1-expressing neurons had high average Oxtr expression. In the NAc, most Oxtr+ cells were D1 dopamine receptor-expressing neurons and interneurons. These differences in Oxtr cell type distribution may help explain how activation of OTR in BNST versus NAc can have different effects on social approach and social vigilance.

Relationship of health-related social needs and hospital readmissions in patients following a hospitalization for atrial fibrillation.

Atrial fibrillation (AF) has a high economic burden on the healthcare system with rehospitalizations as the most significant contributing factor necessitating an understanding of aspects related to hospitalizations to minimize economic costs and improve patient outcomes. Our study aims to assess whether all-cause 30-day hospital readmission following AF-specific hospitalization is associated with health-related social needs (HRSN) using the Nationwide Readmissions Database (NRD). All hospitalization data were abstracted from the 2015-2019 NRD, including hospitalizations for patients at least 18 years of age with a primary discharge diagnosis of AF. For each hospitalization, we identified secondary diagnoses for five HRSN domains including employment, family, housing, psychosocial, and socioeconomic status. Primary outcomes included all-cause 30-day readmission rates. Secondary outcomes included all-cause 90-day readmissions and diagnosis on readmissions. An estimated 1,807,460 index hospitalizations in the United States included a primary discharge diagnosis of AF. Of these, 97.3 % included a diagnosis in only one HRSN domain with the most frequently diagnosed HRSN domain being housing (54.5 %) followed by socioeconomic (29.4 %), family (10.0 %), employment (6.1 %), and psychosocial (2.8 %). Index hospitalizations that included any HRSN diagnosis had 2.2-times greater unadjusted odds of all-cause 30-day readmission (95 % CI: 2.1 to 2.3-times greater, p < .001). Index hospitalizations that included an HRSN diagnosis were associated with higher rates of 90-day readmission due to conduction disorder and COPD. In conclusion, there is a significant association between HRSN and hospital readmissions in patients with AF. Further research is required to explain the true nature of this relationship with a specific emphasis on housing insecurity.