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.

Plasma malondialdehyde (MDA) levels were raised in Friedreich's ataxia (FRDA) patients. These levels correlated with increasing age and disease duration, suggesting lipid peroxidation increased with disease progression. Using fibroblasts from FRDA patients we observed that GSH levels and aconitase activities were normal, suggesting their antioxidant status was unchanged. When exposed to various agents to increase free radical generation we observed that intracellular superoxide generation induced by paraquat caused enhanced oxidative damage. This correlated with the size of the GAA1 expansion, suggesting decreased frataxin levels may render the cells more vulnerable to mild oxidative stress. More severe oxidative stress induced by hydrogen peroxide caused increased cell death in FRDA fibroblasts but was not significantly different from control cells. We propose that abnormal respiratory chain function and iron accumulation may lead to a progressive increase in oxidative damage, but increased sensitivity to free radicals may not require detectable respiratory chain dysfunction.

Cognitive dysfunction is a well recognized symptom of schizophrenia, as well as patients having poor insight into their illness. The subjective scale to investigate cognition in schizophrenia (SSTICS) is one of several scales that have been developed to study subjective cognitive dysfunction and has been compared to patients’ objective cognitive level. A literature search was performed using PubMed, psychINFO, Web of Science, and cross-referencing to find 26 articles which used 14 different subjective cognitive dysfunction scales to investigate the relationship between subjective and objective measures of cognition in schizophrenia. Although the majority of studies using the SSTICS found significant correlations between subjective and objective measures of cognition, the findings from the other scales were less clear. From this review, the issue of whether or not schizophrenic patients have good cognitive insight remains unsure. However, due to the heterogeneous nature of the study designs and their outcome measures, continued work in this area with consistency on these points is necessary; on the path to better provide management options for a very debilitating component of this illness.

There appear to be two peaks of incidence of Obsessive Compulsive Disorder (OCD), one with a pre-adolescent onset and another in early adulthood. As new cases are added, the cumulative prevalence of OCD increases, but the great majority of cases have an onset in youth. The notion that early onset OCD represents a unique developmental subtype of the disorder has been considered by many researchers based on several specific age-related factors. Ascertainment and early intervention in affected youth is critical to abbreviate the functional impairments associated with untreated illness. In this paper we review the clinical, familial and translational biomarker correlates seen in early onset OCD that support the notion of a developmental subtype and discuss implications for research and treatment aimed at this cohort. The importance of cognitive, academic and social development tasks of childhood and adolescence, illness-specific and familial factors, and immune-mediated inflammatory factors are discussed, with their implications for management.