Neurofilament Light Chain Is a Novel Biomarker for Major Depression and Related Executive Dysfunction

Abstract

Background Evidence suggests that major depressive disorder is related to neuroaxonal injury and that neurofilament light chain (NfL) is a biomarker of neuroaxonal injury. In addition, proinflammatory cytokines have been reported to be associated with major depression and neuroaxonal injury. Methods Forty patients with major depression and 40 age- and sex-matched healthy control subjects were enrolled for the measurement of NfL and proinflammatory cytokines and assessment of executive function. General linear models were used to examine the association between NfL levels, proinflammatory cytokine levels, and executive function. Results Patients with major depressive disorder exhibited significantly higher NfL levels (p = 0.007) than the control subjects. NfL levels were positively related to log-transformed levels of tumor necrosis factor (TNF)-α (p = 0.004). Higher levels of NfL (p = 0.002) and TNF-α (p = 0.013) were associated with greater deficits in executive function. Discussion NfL was a novel biomarker for major depressive disorder and related executive dysfunction. Further studies are necessary to elucidate the role of NfL in the pathophysiology of major depression and related cognitive impairment.

The physio-affective phenome of major depression is strongly associated with biomarkers of astroglial and neuronal projection toxicity which in turn are associated with peripheral inflammation, insulin resistance and lowered calcium

“…The first major finding of the present study is that serum levels of PDGFR, NF-L, GFAP, and P-tau-217 are higher in MDD patients than in controls. These results expand those of prior papers demonstrating that serum levels of NF-L are higher in MDD and treatment-resistant depression (Chen et al, 2022; Domingues et al, 2019; Jakobsson et al, 2014; Rathbone et al, 2018; Spanier et al, 2019). Other research indicates that the mean CSF and serum concentration of NF-L is higher in individuals with bipolar disorder and other mental illnesses compared to healthy controls (Isgren et al, 2017; Spanier et al, 2019; Tauil et al, 2021).…”

Combining Glial Fibrillary Acidic Protein and Neurofilament Light Chain for the Diagnosis of Major Depressive Disorder

“…Serum levels of GFAP and NFL are significantly higher in patients than in healthy individuals. It is consistent with the fact that astrocyte activation and structural axonal damage coexist in the brains of patients with MDD, 29,30 CT, 31,32 or AD. 33,34 GFAP is released by activated astrocytes after brain inflammation, 35 while NFL is from axonal damage and correlated with neurodegeneration.…”

The 2022 Lady Estelle Wolfson lectureship on neurofilaments

“…Higher Nf concentrations are observed with neurodegeneration. It is, therefore, interesting to note that there is a small increase in Nf concentrations in Depression (Bavato et al, 2021; Chen, Liu, et al, 2021; Zhao et al, 2020), Schizophrenia (Bavato et al, 2021; Rodrigues‐Amorim et al, 2020) and with Psychosis (Katisko et al, 2019). Future research will need to investigate how much of this is due to neuro‐axonal loss or potential side effects of treatments.…”