Integration of the Cortical Haemodynamic Response Measured by Functional Near-Infrared Spectroscopy and Amino Acid Analysis to Aid in the Diagnosis of Major Depressive Disorder.

Hai Ning Wee,Jean-Paul Kovalik,Samantha K. Ong,Man Si Cheng,Tong Boon Tang,Herbert Schwarz,Syeda F. Husain,Cyrus S. Ho,Jianhong Ching

doi:10.3390/diagnostics11111978

Abstract

Background: Major depressive disorder (MDD) is a debilitating condition with a high disease burden and medical comorbidities. There are currently few to no validated biomarkers to guide the diagnosis and treatment of MDD. In the present study, we evaluated the differences between MDD patients and healthy controls (HCs) in terms of cortical haemodynamic responses during a verbal fluency test (VFT) using functional near-infrared spectroscopy (fNIRS) and serum amino acid profiles, and ascertained if these parameters were correlated with clinical characteristics. Methods: Twenty-five (25) patients with MDD and 25 age-, gender-, and ethnicity-matched HCs were recruited for the study. Real-time monitoring of the haemodynamic response during completion of a VFT was quantified using a 52-channel NIRS system. Serum samples were analysed and quantified by liquid chromatography-mass spectrometry for amino acid profiling. Receiver-operating characteristic (ROC) curves were used to classify potential candidate biomarkers. Results: The MDD patients had lower prefrontal and temporal activation during completion of the VFT than HCs. The MDD patients had lower mean concentrations of oxy-Hb in the left orbitofrontal cortex (OFC), and lower serum histidine levels. When the oxy-haemoglobin response was combined with the histidine concentration, the sensitivity and specificity of results improved significantly from 66.7% to 73.3% and from 65.0% to 90.0% respectively, as compared to results based only on the NIRS response. Conclusions: These findings demonstrate the use of combination biomarkers to aid in the diagnosis of MDD. This technique could be a useful approach to detect MDD with greater precision, but additional studies are required to validate the methodology.

Highlights

Introduction conditions of the Creative CommonsMajor depressive disorder (MDD) is a debilitating condition with increasing prevalence and a devastating socioeconomic impact worldwide [1,2]
As compared with healthy controls (HCs), patients performed worse in the verbal fluency test (VFT) (F1,44 = 4.769, p = 0.034; g = −0.603, 95% CI from −1.176 to −0.031) and had markedly higher HAMD scores (F1,45 = 436.541, p < 0.001; g = 6.000, 95% CI 4.7–7.3)
Lower activation in the frontotemporal cortices may suggest a regression in physiological function. functional near-infrared spectroscopy (fNIRS) and fMRI studies found that MDD patients in remission exhibited reduced cerebral responses and functional abnormalities in the left prefrontal cortex (PFC), suggesting that dysfunction in the frontal lobe may be a specific trait marker for depression [58,73]

Summary

Introduction

Major depressive disorder (MDD) is a debilitating condition with increasing prevalence and a devastating socioeconomic impact worldwide [1,2] It is characterised by depressed mood, anhedonia, disturbed sleep and appetite, and anxiety. A greater understanding of the background pathophysiology of the disorder, alongside with a reliable and defined diagnostic approach will provide clinicians with defined guidelines to better tailor treatment plans according to the best possible evidence regarding the effectiveness and tolerability of each drug for each patient. This warrants the development of diagnostic and therapeutic technologies in the field of psychiatry

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