Variation of Circulating Brain-Derived Neurotrophic Factor (BDNF) in Depression: Relationships with Inflammatory Indices, Metabolic Status and Patients’ Clinical Features

Abstract

This study seeks to offer a contribution to the method of subtyping major depressed patients by exploring the possible relationships between circulating brain-derived neurotrophic factor (BDNF), different peripheral inflammatory/metabolic markers in the blood and clinical characteristics. Thirty-nine patients, thoroughly diagnosed according to the DSM-5 criteria, underwent a comprehensive set of evaluations encompassing structured interviews, rating scales and a panel of blood tests. Correlation and comparison analyses were carried out by means of non-parametric statistical tests. Concurrently, a principal component analysis was performed to explain biochemical variance. The findings of our research unveiled that leukocyte counts, their ratios and other inflammatory parameters are positively correlated with depression scores. Moreover, we found variations within the BDNF pools of depressed patients. Specifically, higher levels of platelet-poor plasma BDNF (PPP-BDNF) were correlated with augmented inflammatory markers in patients showing specific episode characteristics, whereas reduced platelet BDNF (PLT-BDNF) provided a better indication of the changes that were linked to a diagnosis of long-term depression. Our findings suggest that PPP-BDNF and PLT-BDNF might differentiate depression conditions. They also imply usefulness in appraising peripheral biomarker profiles in patients for a deeper characterization of major depressive episodes. At the same time, it is plausible that they might constitute novel avenues for developing more tailored therapeutic strategies for patients with MDs.

Plasma and Platelet Brain-Derived Neurotrophic Factor (BDNF) Levels in Bipolar Disorder Patients with Post-Traumatic Stress Disorder (PTSD) or in a Major Depressive Episode Compared to Healthy Controls

“…Our result showing nonsignificant PPP-BDNF levels in patients vs. controls still requires attention. The BDNF values reported in the investigations conducted until now have been quite variable between the different studies [ 34 , 41 , 65 , 67 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. The influence of many parameters can affect plasma BDNF measures [ 67 ]: different procedures in blood withdrawal, plasma separation and handling, centrifugation, temperature and plasma acidification may all impact final plasma BDNF results [ 42 , 65 , 85 , 86 ].…”

“…In the present study, most of these aspects were controlled and have been carefully considered, preventing our results from being affected by these critical points. It is, however, always possible that BDNF amounts in PPP, obtained by two different centrifugation steps, are not fully identical to the plasmatic ones [ 42 , 67 ], and they could reflect alterations in inflammatory components or pathways, as observed in different cohorts of depressed patients [ 42 , 80 , 84 ]. Substantially, plasmatic BDNF may rather be a state marker related to the presence of peculiar proinflammatory paths activated in different clinical presentations, including production and release by the endothelium, smooth musculature and activated lymphomonocytes [ 42 ], as well as the intrinsic variability in extracellular BDNF as a modulator of the allostatic response to stress and its dynamics [ 42 ].…”

“…Very few studies have investigated BDNF contents inside platelets of psychiatric patients. In addition, both basic and clinical studies from the literature were conducted, adopting different procedures of platelet lysis and homogenization [ 29 , 45 , 80 , 84 , 95 , 96 ]. Most authors normalized BDNF values obtained in platelet lysates with respect to platelet counts measured by flow cytometry in the PRP.…”

“…The PLT-BDNF counterpart appears rather under the influence of lifetime mood-related parameters. In a previous work, we reported that PLT-BDNF was reduced in patients with a major depressive disorder with respect to those with a diagnosis of BD-I, being also negatively correlated with HAM-D scores [ 84 ], thus entailing that both lifetime and current depression seem to exert a kind of “hierarchical” impact on this parameter. This would also explain the lack of variance in PLT-BDNF in PTSD symptomatic bipolar patients with respect to controls, even if this parameter displayed mean and mean rank values higher than depressed patients but lower than controls, without attaining the statistical significance in both cases.…”

“…For PPP and platelet preparation, vacutainer tubes were always centrifuged at the Biochemistry Laboratory within 30 min of withdrawal. All centrifugations were performed at room temperature (RT), 22–25 °C, as previously described [ 45 , 84 ]. The first centrifugation was conducted at low speed, 150–200× g , for 15 min, in order to separate the platelet-rich plasma (PRP) from the other cellular elements.…”