Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells. We also show that targeted adeno-associated virus-mediated suppression of claudin-5 in the mouse brain results in localized BBB disruption and behavioural changes. Using an inducible 'knockdown' mouse model, we further link claudin-5 suppression with psychosis through a distinct behavioural phenotype showing impairments in learning and memory, anxiety-like behaviour and sensorimotor gating. In addition, these animals develop seizures and die after 3-4 weeks of claudin-5 suppression, reinforcing the crucial role of claudin-5 in normal neurological function. Finally, we show that anti-psychotic medications dose-dependently increase claudin-5 expression in vitro and in vivo while aberrant, discontinuous expression of claudin − 5 in the brains of schizophrenic patients post mortem was observed compared to age-matched controls. Together, these data suggest that BBB disruption may be a modifying factor in the development of schizophrenia and that drugs directly targeting the BBB may offer new therapeutic opportunities for treating this disorder.

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Academic and corporate interest in ethical leadership, corporate social responsibility (CSR), and firm performance has attracted a lot of attention in recent years. In fact, many research papers and journal special issues have been focused on these three domains. In this context, this paper conducts a systematic review on the concepts of ethical leadership and CSR and their impact on firm performance. 114 papers published over a period of 58 years (1958–2016) were selected and analyzed according to descriptive and content perspectives to propose a conceptual framework and define a future research agenda. In fact, the main results allow us to derive six main propositions representing possible areas of investigation to direct research on the topic. More in details, the body of literature highlights that financial factors are the main barriers affecting the adoption of CSR practices. On the contrary, internal and external environment was found to represent a critical success factor in the adoption of CSR practices. Finally, the results highlight that personal values have impact on ethical leadership that in turn has direct positive impact on CSR and direct and indirect impact on firm performance.

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