This study demonstrates for the first time that infants with classical CAH due to 21-hydroxylase deficiency have significantly lower plasma epinephrine levels than controls, indicating that impaired adrenomedullary function may occur during fetal development and be present from birth. A longitudinal study of adrenomedullary function in CAH patients from infancy through early childhood is warranted.

Chronic stress can be challenging, lead to maladaptive coping strategies, and cause negative mental and physical health outcomes. Early-life adversity exposes developing young to physical or psychological experiences that risks surpassing their capacity to effectively cope, thereby impacting their lifetime physical and mental wellbeing. Sensitivity to stressful events, like social isolation, has the potential to magnify stress-coping. Chronic stress through social defeat is an established paradigm that models adverse early-life experiences and can trigger enduring alterations in behavioral and neural phenotypes. To assess the degree to which stress resilience and sensitivity stemming from early-life chronic stress impact sociability, we exposed male prairie voles to chronic social defeat stress (CSDS) during adolescence. We simultaneously exposed subjects to either social isolation (CSDS+Isol) or group housing (CSDS+Soc) during this crucial time of development. On PND41, all subjects underwent a social approach test to examine the immediate impact of isolation, CSDS, or their combined effects on sociability. Unlike the CSDS+Isol group which primarily displayed social avoidance, the CSDS+Soc group was split by individuals exhibiting susceptible or resilient stress phenotypes. Notably, the Control+Soc and CSDS+Soc animals and their cage-mates significantly gained body weight between PND31 and PND40, whereas the Control+Isol and CSDS+Isol animals did not. These results suggest that the effects of early-life stress may be mitigated by having access to social support. Vasopressin, oxytocin, and opioids and their receptors (avpr1a, oxtr, oprk1, oprm1, and oprd1) are known to modulate social and stress-coping behaviors in the lateral septum (LS). Therefore, we did an mRNA expression analysis with RT-qPCR of the avpr1a, oxtr, oprk1, oprm1, and oprd1 genes to show that isolation and CSDS, or their collective influence, can potentially differentially bias sensitivity of the LS to early-life stressors. Collectively, our study supports the impact and dimensionality of early-life adversity because the type (isolation vs. CSDS), duration (acute vs. chronic), and combination (isolation + CSDS) of stressors can dynamically alter behavioral and neural outcomes.

Although much has been written on the topic of social behavior, many terms referring to different aspects of social behavior have become inappropriately conflated and the specific mechanisms governing them remains unclear. It is therefore critical that we disentangle the prosocial and antisocial elements associated with different forms of social behavior to fully understand the social brain. The lateral septum (LS) mediates social behaviors, emotional processes, and stress responses necessary for individuals to navigate day-to-day social interactions. The LS is particularly important in general and selective prosocial behavior (monogamy) but its role in how these two behavioral domains intersect is unclear. Here, we investigate the effects of chemogenetic-mediated LS activation on social responses in male prairie voles when they are 1) sex-naïve and generally affiliative and 2) after they become pair-bonded and display selective aggression. Amplifying neural activity in the LS augments same-sex social approach behaviors. Despite partner preference formation remaining unaltered, LS activation in pair-bonded males leads to reduced selective aggression while increasing social affiliative behaviors. These results suggest that LS activation alters behavior within certain social contexts, by increasing sex-naïve affiliative behaviors and reducing pair bonding-induced selective aggression with same-sex conspecifics, but not altering bonding with opposite-sex individuals.

Although much has been written on the topic of social behavior, many terms referring to different aspects of social behavior have become inappropriately conflated and the specific mechanisms governing them remains unclear. It is therefore critical that we disentangle the pro- and anti-social elements associated with different forms of social behavior to fully understand the social brain. The lateral septum (LS) mediates social behaviors, emotional processes, and stress responses necessary for individuals to navigate day-to-day social interactions. The LS is particularly important in general and selective prosocial behavior (monogamy) but its role in how these two behavioral domains intersect is unclear. Here, we investigate the effects of chemogenetic-mediated LS activation on social responses in male prairie voles when they are 1) sex-naïve and generally affiliative and 2) after they become pair-bonded and display selective aggression. Amplifying neural activity in the LS augments same-sex social approach behaviors. Despite partner preference formation remaining unaltered, LS activation in pair-bonded males leads to reduced selective aggression while increasing social affiliative behaviors. These results suggest that LS activation alters behavior within certain social contexts, by increasing sex-naïve affiliative behaviors and reducing pair bonding-induced selective aggression with same-sex conspecifics, but not altering bonding with opposite-sex individuals.