Tear fluid biomarkers in major depressive disorder: Potential of spectral methods in biomarker discovery

Abstract

Spectroscopic methods represent a group of analytical methods that demonstrate high potential in providing clinically relevant diagnostic information, such as biochemical, functional or structural changes of macromolecular complexes that might occur due to pathological processes or therapeutic intervention. Although application of these methods in the field of psychiatric research is still relatively recent, the preliminary results show that they have the capacity to detect subtle neurobiological abnormalities in major depressive disorder (MDD). Methods of mass spectrometry (MALDI-TOF MS), zymography, synchronous fluorescence spectroscopy (SFS), circular dichroism (CD) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy and atomic force microscopy (AFM) were used to analyze the human tear fluid of subjects with MDD. Using MALDI-TOF MS, two diagnostically significant peaks (3747 and 16 411 m/z) were identified with an AUC value of 0.89 and 0.92 in tear fluid of subjects with MDD vs controls, respectively. We also identified various forms of matrix metalloproteinase 9 in subjects with MDD using zymography and synchronous fluorescence spectra (SFS) showed a significant increase in fluorescence intensity at 280 nm. CD spectra were redshifted in tear fluid of subjects with MDD vs healthy controls. FTIR spectroscopy showed changes in the positions of peaks for amide A, I, II in tear fluid of subjects with MDD vs controls. Moreover, atomic force microscopy (AFM) showed different pattern in the crystal structures of tear fluid components in subjects with MDD. SFS, CD, FTIR spectroscopy, AFM and MALDI-TOF MS confirmed, that the human tear fluid proteome could be helpful in discriminating between the group of subjects with MDD and healthy controls. These preliminary findings suggest that spectral methods could represent a useful tool in clinical psychiatry, especially in establishing differential diagnosis, monitoring illness progression and the effect of psychiatric treatment.

Keywords: Diagnostics; MALDI-TOF; Major depressive disorder; Mass spectrometry; Tear fluid.