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.
BackgroundDespite the increasing pervasiveness of mobile computational technologies, knowledge about psychiatric patients’ preferences regarding the design and utility of mobile applications is very poor. This paper reports on a pilot-study that involved 120 psychiatric patients in the development of a mobile application (app) that is being used for data entry into the Signature Project data bank at the Institut universitaire en santé mentale de Montréal (IUSMM), Canada. Participants were invited to comment on the ‘look and feel’ of the Signature App. Their input also extended the procedures for data collection. These suggestions may contribute to increased mental health literacy and empowerment of persons with mental illness receiving services at the IUSMM.MethodsParticipants were recruited to fill out a questionnaire on a tablet computer while waiting at the Emergency Room (ER, n = 40), Psychotic Disorders outpatient clinic (n = 40) or Anxiety and Mood Disorders outpatient clinic (n = 40) of IUSMM. Nine patients from each of these sub-groups participated in a focus group to review the results and to discuss how the design and use of the Signature App could be improved to better meet the needs of patients.ResultsThis study (n = 120) indicated that psychiatric patients are clearly capable of using a tablet computer to fill out questionnaires for quantitative data entry, and that they enjoyed this experience. Results from the focus groups (n = 27) highlight that the app could also be used by patients to communicate some personal and contextual qualitative information. This would support a holistic and person-centered approach, especially at the ER where people acutely need to describe their recent history and receive emotional support.ConclusionsThis pilot-study has confirmed the necessity of involving patients not only in the testing of a new mobile application, but also as active contributors in the entire research and development process of a person-centered information and communication technology infrastructure. The input of participants was essential in designing the Signature Project computational procedure and making use of the app a positive and empowering experience. Participants also gave critical feedback remarks that went beyond the initial scope of the pilot-study, for example they suggested the addition of a client-clinician component.
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