Serum insulin-like growth factor-1 as a potential marker for MDD diagnosis, its clinical characteristics, and treatment efficacy validation: data from an open-label vortioxetine study

Abstract

Background: IGF-1 is an essential neurotrophin produced peripherally and in the brain. Impairments in the brain IGF-1 concentrations might be responsible for some aspects of major depressive disorder (MDD) pathogenesis, whereas peripheral IGF-1 could have the marker value. We aimed: 1) to compare serum IGF-1 levels in MDD patients and healthy controls (HC); 2) to elucidate possible associations between changes in IGF-1 expression and crucial characteristics of the current depressive episode, MDD course; 3) to evaluate IGF-1 dynamics after 8 weeksv ortioxetine treatment. Methods: Seventy-eight MDD patients (according to DSM-5) and 47 HC were enrolled. Serum IGF-1, psychopathological (MADRS, CGI) and neuropsychological parameters (PDQ-5, RAVLT, TMT-B, DSST) were analyzed in all subjects at admission and 48 patients after 8 weeks`vortioxetine treatment. AUC-ROCs were calculated to determine if the value of serum IGF-1 could separate MDD patients from HC. Multiple regression models were performed to explore relationships between IGF-1 and depressive episode's symptoms. Results: MDD patients had significantly higher serum IGF-1 levels than HC (228 (183-312) ng/ml vs 153 (129-186) ng/ml, p < 0.0001). IGF-1 had a good diagnostic value for predicting MDD in the whole sample with AUC of 0.820 (p < 0.0001). For a cutoff of 178.00 ng/ml, the sensitivity and specificity were 83 and 71%, respectively, and the number needed to misdiagnose was 5, indicating that only 1 of 5 tests give an invalid result. Among MADRS items, only reported sadness, inner tension, and concentration difficulties were significantly positively associated with serum IGF-1 concentrations. Vortioxetine treatment significantly attenuated IGF-1 levels and improved all psychopathological, neuropsychological parameters.

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

“…The reported here correlations between IGF-1 level and severity, number, and duration of DE, subjective and objective cognitive functioning (PDQ-5, RAVLT subtests, TMT-B, DSST), all subdomains of functioning are in line with our previous results (23). Nevertheless, here we pointed out that the associations for IGF-1 concentrations and the level of performance of cognitive tests were stronger than those for BDNF levels.…”

“…According to our recent systematized data, there are discrepancies in IGF-1 levels in MDD patients across the studies, although the majority demonstrate higher levels of peripheral IGF-1 compared to healthy controls (HC) (8). The elevation of peripheral total IGF-1 concentrations and its decline after antidepressants`treatment were established in several studies in MDD patients (21)(22)(23), moreover, it was reported that only patients in remission had attenuated IGF-1 concentrations following treatment (21,22). The enhancement of the peripheral IGF-1 expression in MDD may be a compensatory mechanism in response to its brain synthesis decrease (24) or diminished neurotrophin bioavailability due to the hyposensitivity of IGF-1 receptors under the neuroinflammatory stress (25).…”

Effects of Antidepressant Treatment on Neurotrophic Factors (BDNF and IGF-1) in Patients with Major Depressive Disorder (MDD)

“…Four studies of IGF-1 met the search criteria and were included in the present review. In a study conducted in a group of patients carrying the clinical diagnosis of MDD ( n = 41) and a control group ( n = 32), vortioxetine was given for 8 weeks [ 45 ]. Serum IGF-1 levels were determined at baseline (T0) and after 8 weeks of treatment (T1).…”

“…Similar results were reported by Levada et al (2020). The vortioxetine treatment assessed in their study ( n = 48) markedly decreased IGF-1 levels, which correlated with an improvement in clinical symptoms and cognitive function ( p < 0.0001) [ 45 ]. Results of the research concerning IFG-1 levels is presented in Table 2 .…”

“…There is evidence of a modulating effect of antidepressants on depression via the neurotrophins in preclinical and clinical models of depression; however, the results are conflicting; therefore, the therapeutic role of antidepressants cannot be clearly stated [ 21 , 22 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. The pharmacotherapy of depression most frequently used in clinical practice is based on the use of drugs that increase the level of monoamines.…”