LRFN5 and OLFM4 as novel potential biomarkers for major depressive disorder: a pilot study

Abstract

Evidences have shown that both LRFN5 and OLFM4 can regulate neural development and synaptic function. Recent genome-wide association studies on major depressive disorder (MDD) have implicated LRFN5 and OLFM4, but their expressions and roles in MDD are still completely unclear. Here, we examined serum concentrations of LRFN5 and OLFM4 in 99 drug-naive MDD patients, 90 drug-treatment MDD patients, and 81 healthy controls (HCs) using ELISA methods. The results showed that both LRFN5 and OLFM4 levels were considerably higher in MDD patients compared to HCs, and were significantly lower in drug-treatment MDD patients than in drug-naive MDD patients. However, there were no significant differences between MDD patients who received a single antidepressant and a combination of antidepressants. Pearson correlation analysis showed that they were associated with the clinical data, including Hamilton Depression Scale score, age, duration of illness, fasting blood glucose, serum lipids, and hepatic, renal, or thyroid function. Moreover, these two molecules both yielded fairly excellent diagnostic performance in diagnosing MDD. In addition, a combination of LRFN5 and OLFM4 demonstrated a better diagnostic effectiveness, with an area under curve of 0.974 in the training set and 0.975 in the testing set. Taken together, our data suggest that LRFN5 and OLFM4 may be implicated in the pathophysiology of MDD and the combination of LRFN5 and OLFM4 may offer a diagnostic biomarker panel for MDD.

Fig. 1. Concentrations of LRFN5 and OLFM4 in HCs and MDD groups.

A, B Compared to HCs, MDD patients had significantly higher levels of LRFN5 (A) and OLFM4 (B). Data are presented as mean ± S.D. HCs healthy controls, MDD major depressive disorder.

Fig. 2. Effects of medication and sex on LRFN5 and OLFM4 levels.

A effects of medication on LRFN5 level, antidepressants treatment could significantly decrease the level of LRFN5; B effects of medication on OLFM4 level, antidepressants treatment could significantly decrease the level of OLFM4; C sex had no significant impact on LRFN5 level; D sex had no significant impact on OLFM4 level. Data are presented as mean ± S.D. DN-MDD drug-naive major depressive disorder, DT-MDD drug-treatment major depressive disorder, HCs healthy controls, M male, F female.

Fig. 3. Correlation between LRFN5 and OLFM4.

LRFN5 level was significantly positively correlated with OLFM4 level in serum.

Fig. 4. Correlations between LRFN5/OLFM4 and other variables.

The blue and red lines represented negative and positive correlations, respectively. The thicker the line, the stronger the correlation between variables. ALT alanine aminotransferase, AST aspartate aminotransferase, duration duration of illness, HAMD Hamilton Depression Scale, urea urea nitrogen.

Fig. 5. Effects of different treatment modalities on LRFN5 and OLFM4 levels.

A effects of single antidepressant vs. combined antidepressants on LRFN5 and OLFM4 levels; B there was no sex-specific difference in LRFN5 and OLFM4 levels in patients receiving single antidepressant; C compared to male patients, female patients receiving combined antidepressants had a significantly lower level of LRFN5 and a similar level of OLFM4; D among the patients receiving single antidepressant, the levels of LRFN5 and OLFM4 were similar between patients receiving selective serotonin reuptake inhibitor (SSRI) and patients receiving other antidepressants. Data are presented as mean ± S.D.

Fig. 6. Diagnostic performances of LRFN5 and OLFM4 in diagnosing MDD.

A area under the receiver operating characteristic curve (AUC) value of LRFN5 in diagnosing MDD patients; B AUC value of OLFM4 in diagnosing MDD patients; C AUC value of the combination of LRFN5 and OLFM4 in diagnosing MDD patients in training set; D AUC value of the combination of LRFN5 and OLFM4 in diagnosing MDD patients in testing set.