Abstract
Background: Since the neurotrophic hypothesis of depression was formulated, conflicting results have been reported regarding the role of growth factor proteins in depressed patients, including whether there are state or trait alterations found in patients compared to controls and whether they represent predictors of treatment response. Recently it has been hypothesized that heterogeneity of findings within this literature might be partly explained by participants' history of treatment-resistant depression. This study aimed to investigate the role of growth factor proteins in patients with treatment-resistant depression (TRD) undergoing an inpatient intervention.Methods: Blood samples were collected from 36 patients with TRD and 36 matched controls. Patients were assessed both at admission and discharge from a specialist inpatient program. We examined serum biomarker differences between patients and non-depressed matched controls, longitudinal changes after inpatient treatment and relationship to clinical outcomes. Additionally, the influence of potential covariates on biomarker levels were assessed.Results: Patients displayed lower serum levels of brain-derived neurotrophic factor (OR = 0.025; 95% CI = 0.001, 0.500) and vascular endothelial growth factor-C (VEGFC; OR = 0.083, 95% CI = 0.008, 0.839) as well as higher angiopoietin-1 receptor (Tie2; OR = 2.651, 95% CI = 1.325, 5.303) compared to controls. Patients were stratified into responders (56%) and non-responders (44%). Lower VEGFD levels at admission predicted subsequent non-response (OR = 4.817, 95% CI = 1.247, 11.674). During treatment, non-responders showed a decrease in VEGF and VEGFC levels, while responders showed no significant changes.Conclusion: TRD patients demonstrate a deficit of peripheral growth factors and our results suggest that markers of the VEGF family might decline over time in chronically depressed patients in spite of multidisciplinary treatment. The action of angiogenic proteins may play an important role in the pathophysiology of TRD, and pending comprehensive investigation may provide important insights for the future of precision psychiatry.
Highlights
Major Depressive Disorder (MDD) is considered the leading cause of disability worldwide [1]
Evidence for a role of growth factors in the pathophysiology of depression has come from clinical studies mainly investigating brain derived neurotrophic factor (BDNF), a neurotrophin involved in processes of neuronal maturation, synapse formation and synaptic plasticity [3], and vascular endothelial growth factor (VEGF or VEGFA), an angiogenic factor possessing neurotrophic and neuroprotective properties [6, 7]
Alongside the well-researched BDNF and VEGF, we considered six growth factors that play a role in neurogenesis and maintenance of neural connections but have never been investigated in treatment-resistant depression (TRD); due to the scant evidence in our possession surrounding their role in depression, these comparisons were exploratory in nature
Summary
Major Depressive Disorder (MDD) is considered the leading cause of disability worldwide [1]. Evidence for a role of growth factors in the pathophysiology of depression has come from clinical studies mainly investigating brain derived neurotrophic factor (BDNF), a neurotrophin involved in processes of neuronal maturation, synapse formation and synaptic plasticity [3], and vascular endothelial growth factor (VEGF or VEGFA), an angiogenic factor possessing neurotrophic and neuroprotective properties [6, 7]. Since the neurotrophic hypothesis of depression was formulated, conflicting results have been reported regarding the role of growth factor proteins in depressed patients, including whether there are state or trait alterations found in patients compared to controls and whether they represent predictors of treatment response. This study aimed to investigate the role of growth factor proteins in patients with treatment-resistant depression (TRD) undergoing an inpatient intervention
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
