No abstract

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.

The predictive relation between attachment and mother, teacher, and self-reported psychopathology was examined for a diverse socioeconomic status French Canadian sample of 96 children. Attachment classifications were assigned on the basis of reunion behavior with mother when the children were approximately 6 years old, and child problem behavior was assessed 2 years later using the Child Behavior Checklist (mother report), the Social Behavior Questionaire (teacher report), and the Dominic Questionnaire (child self-report). Results indicated that both insecure/ambivalent and insecure/controlling children children were rated higher than secure children on a composite measure of externalizing problems. Concerning internalizing problems, only the controlling group was significantly higher on both a composite adult (teacher and mother) and self-report measure of internalizing problems. Analyses of clinical cutoff scores showed that only the controlling group had a significantly greater likelihood of overall problem behavior than other children.