Variation of circulating levels of BDNF neurotrophin in depression: correlations with symptom severity, metabolic status and inflammatory indices

Background: Major depression is a chronic, debilitating syndrome and a heterogeneous disorder both in the transverse that in the longitudinal course. Recent studies show how Major Depression can be considered as a systemic pathology, and there is a large literature on the neuroanatomical, neurophysiological and neuroendrocrinological correlates of this illness, although no laboratory test has been sufficiently sensitive and specific as a diagnostic tool for the disorder so far. Numerous studies indicate, in depression, in addition to neurotransmitters and neuroendocrine markers, the involvement of the inflammatory response and, more generally, of the immune system, energy/redox metabolism and and the system of neurotrophins, in particular of the Brain-Derived Neurotrophic Factor (BDNF). Aims: aims of the study were to evaluate the peripheral, bloodstream counterpart of BDNF in Major Depressive Episode through its measurement in plasma and platelet samples obtained from a well-defined group of patients; to search possible correlations with patients’ clinical symptoms and results at routine laboratory tests, these last including the main blood metabolic, cellular and inflammation parameters. Methods: All subjects participating to the study were recruited from inpatient or outpatient healthcare settings with a major depressive episode in a contest of a diagnosis of MDD, BD-I, BD-II according to DSM-5. The sample was evaluated by clinical and biochemical assessments. Clinical evaluations were assessed with psychiatric rating scales: HAM-D, YMRS, CGI-s, GAF. About Biochemical assessments: a sample of peripheral venous blood was withdrawn from each recruited patient and then processed to obtain separate platelets and platelet-poor plasma (PPP). Then free mature BDNF was determined in patients’ platelet cytosolic fractions and plasma by means of an enzyme immunoassay method (sandwich ELISA). To evaluate inflammation indices and hematochemical parameters: a sample of blood was also collected and sent to the laboratory of Cisanello Hospital. All data obtained by clinical and laboratory evaluations were organized in database and used for statistical analyses. Results: Patients present mostly a Major depressive episode “with anxious distress” specifier (79.4%) in the context of a diagnosis of BD-II. They had particularly severe depressive symptoms (HAM-D scale≥ 17), a mild manic component, with relevant impairment. White blood cell counts and ratios were found positively correlated to depression scores, while CRP was slightly raised in patients without correlating with symptom severity. There is a negative correlation between intra-platelet mature free BDNF levels and more severe symptoms of depression (HAM-D scores), while plasma BDNF (PPP-BDNF) revealing a more complex profile, with a link with the presence of a mild inflammatory condition, together a tendency to increase in depressed patients with suicide attempts. Conclusions: The results of this study allow to believe that plasma and platelet neurotrophin levels are distinct components that might underlie peculiar networks related to inflammation, symptom presentation and severity of symptoms. These results encourage the search of other inflammatory mediators that could better explain the here observed relation between plasma BDNF variations and white blood cell indices, with the aim at applying these patterns as predictive biological indices of tendency to relapse, severity of depressive episode or responsiveness to drugs