CEREBROVASCULAR DYSFUNCTION AND DEPRESSIVE SYMPTOMS IN PRE-CLINICAL MODELS: INSIGHTS FROM A SCOPING REVIEW

While existing literature supports associations between cerebrovascular dysfunction and the emergence of depression and depressive symptoms, relatively little is known about underlying mechanistic pathways that may explain potential relationships. As such, an integrated understanding of these relationships in pre-clinical models could provide insight into the nature of the relationship, basic mechanistic linkages and areas in which additional investment should be targeted. This scoping review was conducted in MEDLINE, EMBASE and Scopus to outline the relationship between depressive symptoms and cerebrovascular dysfunction in pre-clinical animal models with additional focus on the areas above. From 3438 articles initially identified, 15 studies met the inclusion criteria and were included in the review. All studies reported a positive association between the severity of markers for cerebrovascular dysfunction and that for depressive symptoms in rodent models and this spanned all models for either pathology. Specific mechanistic links between the two such as chronic inflammation, elevated vascular oxidant stress, and altered serotonergic signaling were highlighted. Notably, almost all studies addressed outcomes in male animals, with a near complete lack of data from females, and there was little consistency in terms of how cerebrovascular dysfunction was assessed. Across nearly all studies was a lack of clarity for any "cause and effect" relationship between depressive symptoms and cerebrovascular dysfunction. At this time, it is reasonable to conclude that a correlative relationship clearly exists between the two and future investigation will be required to parse out more specific aspects to this relationship.