Brain-derived neurotrophic factor, vascular alterations, and depression: The SABPA study

Abstract

Motivation Several researchers suggest that neurotrophic factors play an important role in depression. Brain-derived neurotrophic factor (BDNF) is one of the neurotrophic factors that has been investigated and it is reported that low BDNF levels occur in individuals with depression. Brain-derived neurotrophic factor has been shown to have diverse effects on the cardiovascular (CV) system, which include angiogenesis, protective effects against oxidative stress, proinflammation and regulation of vascular tone and function. Adequate levels are therefore linked to vascular protection while low levels are associated with endothelial dysfunction and vascular remodeling. The low levels observed in individuals with depression may increase the cardiovascular disease (CVD) risk. In our study population, it has already been shown that specifically the Black population has decreased BDNF levels and increased carotid intima-media thickening when compared to their white counterparts. Many studies that originated from our study population reported significant results regarding depression. They predicted that chronic depression was associated with CV changes, such as microvasculature regulation and perfusion deficits. Based on these prior results, we wanted to investigate whether BDNF associates with markers of vascular remodeling and function in Black individuals with and without moderate to severe symptoms of depression of the SABPA study population. Aim and Objectives Our aim was to investigate differences in BDNF levels as well as markers of vascular remodeling, carotid intima-media thickness (CIMT) and pulse wave velocity (PWV) in Black individuals with and without depression and whether relationships between these markers exist in each group. Methodology The study sample included 193 Black teachers (mean age of 44; 50% women) from the Dr Kenneth Kaunda Education district in the North West Province, South Africa. Depressive symptoms were obtained by the Patient Health Questionnaire-9 (PHQ-9). The recommended cut-off point of ≥10 indicated the presence of depression. For this study, individuals were grouped according to their depressive symptoms. The recommended PHQ-9 cut-off point of ≥10 indicated the presence of moderate-to-severe depression; a score below 10 indicated individuals without depression. A high-resolution ultrasound scan with CIMT images from at least two angles of the left and right common carotid artery was obtained by using a SonoSite Micromax ultrasound x system. Pulse wave velocity was obtained with the carotid-dorsalis pedis PWV using Complior SP Acquisition System (Artech-Medical, Pantin, France). Serum BDNF was measured by Quantikine Colorometric Sandwich Immunoassay, with intra-assay precision between 3.8% and 4.2% and inter-assay coefficient of variation (CV) <7.6% and 11.3%. Results and Conclusion We observed that 44% of the population had moderate to severe depressive symptoms. The groups with and without depression characteristics were similar as no statistical differences were observed in the variables under investigation. Despite this, single regression analyses indicated an inverse relationship exist between CIMT and BDNF in individuals without depression, but not in individuals with depression (non-depressive: r=-0.214; p=0.027); depressive: r=-0.030; p=0.781). After performing multiple regression analyses adjusted for age, sex, waist circumference, glucose, CRP, LDL cholesterol, MAP and GGT an independent inverse association was confirmed between CIMT and BDNF in individuals without depression (β=-0.19; p=0.026). No significant results were observed between BDNF and PWV in both groups. Based on our results, we rejected our hypotheses since we were unable to replicate earlier findings that suggested that depression was accompanied by lower levels of BDNF and higher measures of CIMT and PWV. Despite this, our results indicate the possibility that BDNF has a protective role in maintaining endothelial barrier integrity and promoting smooth muscle cell activity in individuals without depression. The absence of the expected results between BDNF, CIMT and PWV in individuals with depression may indicate that the interplay between BDNF and the vasculature could be compromised, although further investigation is required.