Effect of serum antioxidants on cognitive dysfunction in first-episode and drug-naïve patients with major depressive disorder.

BACKGROUND

Cognitive dysfunction is a persistent and difficult-to-treat symptom of major depressive disorder (MDD) and is receiving increasing attention. A balanced state of oxidative stress sustained by antioxidants is essential for normal functioning of brain, including learning capacity, emotional regulation, and cognitive function. The correlation between cognition and oxidative stress may also be altered in patients with mental disorders. This study aimed to explore the relationship between serum antioxidant levels and cognitive dysfunction in patients with MDD.

METHODS

We collected and matched cognitive performance data using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB), serum antioxidants, and demographic and clinical characteristics of 105 first-episode drug-naïve patients with MDD and 53 healthy controls (HC) from February 2022 to October 2023, and then analyzed the differences between the two groups. HamiltonDepressionScale-17 and Young Mania Rating Scale (YMRS) were used to evaluate the clinical symptoms of the participants with MDD. Serum antioxidants, including albumin (ALB), uric acid (UA), and superoxide dismutase (SOD) were used to detect the level of oxidative stress in participants and its correlation with cognitive function. We then used a threshold for cognitive dysfunction of 1.5 standard deviations below the mean of the standard score to divide the participants with MDD into two groups to detect the relevant elements of the five different domains of cognitive dysfunction in MDD.

RESULTS

ALB levels were significantly lower in the MDD group (p = 0.001) after adjusting for years of education. The performance in all five domains of cognitive function was significantly worse in the MDD group than in the HC group (p < 0.001). Speed of processing (SOP) in the MDD group correlated with ALB (r = 0.261, p = 0.008), and UA (r = 0.295, p = 0.002) levels. We also explored the correlation between the attention/vigilance (AV) domain and the UA (r = 0.239, p = 0.015). YMRS score was risk factor of impairment of SOP domain in patients with MDD. Yet UA was a protective factor against SOP impairment, with a 0.006-fold reduction in the risk of SOP impairment for each 1-unit increase in UA.

CONCLUSIONS

As serum antioxidants, ALB and UA may serve as biomarkers of cognitive function in patients with MDD. Our findings contribute to the understanding of the potential ability of serum antioxidants to predict cognitive decline in patients with MDD.