The Diagnostic Value of the Combination of Serum Brain-Derived Neurotrophic Factor and Insulin-Like Growth Factor-1 for Major Depressive Disorder Diagnosis and Treatment Efficacy.

Alexandra S Troyan,Oleg A Levada

doi:10.3389/fpsyt.2020.00800

Abstract

BackgroundLast decades of psychiatric investigations have been marked by a search for biological markers that can clarify etiology and pathogenesis, confirm the diagnosis, screen individuals at risk, define the severity, and predict the course of mental disorders. In our study, we aimed to evaluate if BDNF and IGF-1 serum concentrations separately and in combination might be used as biomarkers for major depressive disorder (MDD) diagnosis and treatment efficacy and to evaluate the relationships among those proteins and clinical parameters of MDD.MethodsForty-one MDD patients (according to DSM-5) and 32 healthy controls (HC) were included in this study. BDNF and IGF-1 serum concentrations, psychopathological (MADRS, CGI) and neuropsychological parameters (PDQ-5, RAVLT, TMT-B, DSST), functioning according to Sheehan Disability Scale were analyzed in all subjects at admission and 30 MDD patients after 8 weeks of vortioxetine treatment. Correlational analyses were performed to explore relationships between BDNF and IGF-1 and clinical characteristics. AUC-ROCs were calculated to determine if the value of serum BDNF and IGF-1 levels could serve for MDD diagnosis.ResultsMDD patients had significantly lower serum BDNF (727.6 ± 87.9 pg/ml vs. 853.0 ± 93.9 pg/ml) and higher serum IGF-1 levels (289.15 ± 125.3 ng/ml vs. 170.2 ± 58.2 ng/ml) compared to HC. Significant correlations were obtained between BDNF levels and MDD status, depressive episode (DE) severity, precipitating factors, executive functions disruption (TMT-B, RAVLT immediate recall scores) and all subdomains of functioning. As for IGF-1, correlations were found between IGF-1 level and MDD status, DE severity, number and duration of DE, parameters of subjective and objective cognitive functioning (PDQ-5, RAVLT, TMT-B, DSST scores), and all subdomains of functioning. The associations between IGF-1 concentrations and cognitive tests’ performance were stronger than those of BDNF. Separately both BDNF and IGF-1 demonstrated good discriminating ability for MDD diagnosis with AUC of 0.840 and 0.824, respectively. However, the combination of those neurotrophins had excellent diagnostic power to discriminate MDD patients from HC, providing an AUC of 0.916. Vortioxetine treatment significantly increased BDNF and attenuated IGF-1 serum concentrations, improved all psychopathological and neuropsychological parameters and functioning.ConclusionsThe combination of IGF-1 and BDNF might be considered as a diagnostic combination for MDD.

Highlights

The last decades of psychiatric investigations have been marked by a search for biological markers that can clarify etiology and pathogenesis, confirm a diagnosis, screen individuals at risk, define the severity, and predict the course of mental disorders [1,2,3]
The number of people with predisposing factors was higher in major depressive disorder (MDD) patients, only the presence of precipitating factors significantly differed MDD patients from healthy controls (HC)
As for insulinlike growth factor-1 (IGF-1), positive correlations were found between IGF-1 level and MDD status (r = 0.50, p < 0.01), number (r = 0.43, p < 0.01) and duration of depressive episode (DE) (r = 0.37, p < 0.01), Clinical Global Impression Severity (CGI-S) score (r = 0.45, p < 0.01), Perceived Deficit Questionnaire-5 (PDQ-5) score (r = 0.43, p < 0.01), Montgomery-Asberg depression rating scale (MADRS) score (r = 0.46, p < 0.01), Trail Making Test B (TMT-B) score (r = 0.55, p < 0.01) and all subdomains of functioning and negative associations between IGF-1 and the performance of Rey Auditory Verbal Learning Test (RAVLT) and Digit Symbol Substitution Test (DSST) tests

Summary

Introduction

The last decades of psychiatric investigations have been marked by a search for biological markers that can clarify etiology and pathogenesis, confirm a diagnosis, screen individuals at risk, define the severity, and predict the course of mental disorders [1,2,3]. With respect to major depressive disorder (MDD), abnormal neuroplasticity in cerebral regions, responsible for emotional and cognitive processing, is considered to be one of the key pathogenic mechanisms [4, 5] that potentially have a biomarker value. It is associated with alterations in the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), neurotrophin-3, neurotrophin-4/5, nerve growth factor, insulin-like growth factor (IGF-1), etc. We aimed to evaluate if BDNF and IGF-1 serum concentrations separately and in combination might be used as biomarkers for major depressive disorder (MDD) diagnosis and treatment efficacy and to evaluate the relationships among those proteins and clinical parameters of MDD

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Conclusion