Macrophage Migration Inhibitory Factor in Major Depressive Disorder: A Multilevel Pilot Study

Abstract

Macrophage migration inhibitory factor (MIF) is a controversially discussed inflammatory marker in major depressive disorder (MDD). While some studies show an association of high MIF protein levels with depression, animal models have yielded conflicting results. Thus, it remains elusive as to whether MIF plays an anti- or pro-depressive role. Therefore, we aimed to examine the potential of MIF at the genetic, expression and protein levels as a risk factor and biomarker to diagnose, monitor, or predict the course of MDD. Patients with a current major depressive episode (n = 66 with, and n = 63 without, prior medication) and remitted patients (n = 39) were compared with healthy controls (n = 61). Currently depressed patients provided a second blood sample after three weeks of therapy. Depression severity was assessed by self-evaluation and clinician rating scales. We genotyped for three MIF polymorphisms and analyzed peripheral MIF expression and serum levels. The absence of minor allele homozygous individuals in the large group of 96 female patients compared with 10–16% in female controls suggests a protective effect for MDD, which was not observed in the male group. There were no significant group differences of protein and expression levels, however, both showed predictive potential for the course of depression severity in some subgroups. While MIF protein levels, but not MIF expression, decreased during treatment, they were not associated with changes in depression severity. This project is the first to investigate three biological levels of MIF in depression. The data hint toward a genetic effect in women, but do not provide robust evidence for the utility of MIF as a biomarker for the diagnosis or monitoring of MDD. The observed predictive potential requires further analysis, emphasizing future attention to confounding factors such as sex and premedication.

Epigenetic and Genetic Mechanisms Underlying Cardiovascular Diseases and Neurodevelopmental Disorders

“…This result was later confirmed in two studies of Chinese populations (37,38). In inflammatory diseases, MIF -173 was found to be a disease severity marker for male multiple sclerosis patients (56), while the minor homozygous genotype for both the 974 CATT repeat and the -173G/C polymorphism were reported to protect female patients from major depressive disorder (57). However, another study showed that the MIF -173C allele is a susceptibility factor for depression in type 2 diabetes patients (58).…”

Impact of the MIF -173G/C variant on cardiovascular disease risk: a meta-analysis of 9,047 participants

“…This result was later confirmed in two studies of Chinese populations ( 37 , 38 ). In inflammatory diseases, MIF -173 was found to be a disease severity marker for male multiple sclerosis patients ( 56 ), while the minor homozygous genotype for both the 974 CATT repeat and the -173G/C polymorphism were reported to protect female patients from major depressive disorder ( 57 ). However, another study showed that the MIF -173C allele is a susceptibility factor for depression in type 2 diabetes patients ( 58 ).…”

Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression

“…The study was conducted utilizing samples and data from the CeraBiDe (“Ceramide-associated Biomarkers in Depression”) study [ 80 , 81 , 82 , 83 , 84 ]. Recruitment took place between 01/2014 and 01/2017, adhering to the ethical principles outlined in the sixth revision of the Declaration of Helsinki (Seoul 2008) and the International Conference on Harmonization Guidelines for Good Clinical Practice (1996) and had received approval from the Ethics Committee of the Medical Faculty of the Friedrich-Alexander University Erlangen-Nürnberg (FAU, ID 148_13 B, 17 July 2013).…”

“…The cycling conditions for all three genes included an initial denaturation step at 95 °C for 2 min, followed by 50 cycles of amplification (3 s denaturation at 95 °C, 20 s annealing and amplification at 60 °C), and a cooling step at 40 °C for 30 s. A melting profile was incorporated to verify product specificity. The expression levels of reference genes beta-actin ( ACTB ), ornithine decarboxylase 1 ( ODC1 ), and beta-2-microglobulin ( B2M ) were determined in a multiplex qPCR using double fluorescently labeled probes, as previously described [ 84 ]. Quantification cycles were determined using the “Abs Quant/2nd Derivative Max” analysis method provided by the LightCycler Software.…”