Prevalence, symptoms, and treatment of depression suggest that major depressive disorders (MDD) present sex differences. Social stress-induced neurovascular pathology is associated with depressive symptoms in male mice; however, this association is unclear in females. Here, we report that chronic social and subchronic variable stress promotes blood-brain barrier (BBB) alterations in mood-related brain regions of female mice. Targeted disruption of the BBB in the female prefrontal cortex (PFC) induces anxiety- and depression-like behaviours. By comparing the endothelium cell-specific transcriptomic profiling of the mouse male and female PFC, we identify several pathways and genes involved in maladaptive stress responses and resilience to stress. Furthermore, we confirm that the BBB in the PFC of stressed female mice is leaky. Then, we identify circulating vascular biomarkers of chronic stress, such as soluble E-selectin. Similar changes in circulating soluble E-selectin, BBB gene expression and morphology can be found in blood serum and postmortem brain samples from women diagnosed with MDD. Altogether, we propose that BBB dysfunction plays an important role in modulating stress responses in female mice and possibly MDD.

Lombardy was the epicenter of the Covid-19 outbreak in Italy, and in March 2020 the rapid escalation in cases prompted the Italian Government to decree a mandatory lockdown and to introduce safety practices in mental health services. The general objective of the study is to evaluate the early impact of the Covid-19 emergency and quarantine on the well-being and work practices of mental health service personnel and professionals. Data were collected through an online survey of workers and professionals working with people with mental health problems in Lombardy in several outpatient and inpatient services. Their socio-demographic characteristics, professional background, description of working conditions during lockdown and psychological distress levels were collected. All analyses were performed on a sample of 241. Approximately, 31% of the participants obtained a severe score in at least one of the burnout dimensions, 11.6% showed moderate or severe levels of anxiety, and 6.6% had a moderate or severe level of depression. Different work conditions and patterns of distress were found for outpatient service workers and inpatient service workers. The overall impact of the Covid-19 emergency on mental health workers’ level of distress was mild, although a significant number of workers experienced severe levels of depersonalization and anxiety. More research is needed to assess specific predictive factors.

These findings represent the first stage of a research program aimed at reducing use of seclusion and restraint in psychiatric settings. They underscore the importance of evaluating a variety of factors, including perceptions of safety and violence, when examining reasons for use of these controversial interventions.

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