Secondary analysis of neurotransmitter metabolism and cognitive function in first-diagnosed, drug-naïve adult patients with major depressive disorder.

Background & Aims: Growing evidence suggests that neurotransmitters may be associated with cognitive decline in MDD. This study primarily investigated the differences in cognitive functions between MDD patients and healthy controls, and explored the potential association between neurotransmitters and cognitive function of MDD patients.

Methods: This cross-sectional study enrolled 87 first-diagnosed and drug-naïve patients with MDD and 50 healthy controls. Neurotransmitters (glutamine, glutamic acid, γ-2Aminobutiric acid, kainate, vanillylmandelic acid (VMA), 3-methoxy 4-hydroxyphenyl ethylene glycol (MHPG), noradrenaline (NE), homovanillic acid, dihydroxy-phenyl acetic acid (DOPAC), dopamine (DA), tryptophane, kynurenine, 5-HT, 5-hydroxyindoleacetic acid) were measured using LC-MS/MS and cognitive functions were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Then associative analyses with adjustment (female, age, BMI, education) by multiple linear regression between neurotransmitters and cognitive functions especially in MDD patients were performed.

Results: MDD patients had lower RBANS scores in immediate memory, delayed memory and RBANS scores after adjustment. Neurotransmitters were associated with the cognitive levels of MDD patients after adjustment: DOPAC and DOPAC/DA had positive association with immediate memory score; DOPAC, DOPAC/DA and (VMA+MHPG)/NE were positively associated with attention score; NE was negatively associated with language score; DOPAC/DA was positively associated with both delayed memory and RBANS scores.

Conclusion: Patients had greater cognitive impairment especially in memory. Furthermore, plasma neurotransmitter may be related to MDD and play an important role in cognitive impairment in MDD, especially in memory and attention.