Association between serum metal levels and risks of depression and anxiety in college students: A cross-sectional study

Background  Various metals in environment and diet are related to depression and anxiety.However, the relationships of serum metal element levels with depression, anxiety, and neurotransmitter levels are not clear.

Objective  This study aims to analyze the associations of serum metal element levels with depression and anxiety scale scores as well as serum neurotransmitter levels in college students.

Methods  A total of 86 college students, recruited from a medical university in Hebei Province in December 2017, were asked to fill in a general information questionnaire, the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder (GAD-7). Fasting venous blood was collected, and serum was separated by centrifugation. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect 11 metals in serum. ELISA was employed to measure cortisol (CORT), dopamine (DA), and 5-hydroxytryptamine (5-HT) levels in serum. LASSO was used to screen the metal elements related to the scores of PHQ-9 and GAD-7 as well as the levels of neurotransmitters. Then the associations of screened metal elements with the scores of PHQ-9 and GAD-7 and the levels of neurotransmitters were analyzed by multiple linear regression after adjusting for confounding factors. The false positive rate caused by multiple hypothesis tests was adjusted by false discovery rate (FDR).

Results  Depression or anxiety were found in 10.465% or 5.814% of the participants, respectively. The results of LASSO analysis showed that cobalt (Co), arsenic (As), selenium (Se), molybdenum (Mo), and cadmium (Cd) levels were related with PHQ-9 score, respectively; As and lead (Pb) levels were related with GAD-7 score, respectively; Co level was related with CORT level; Cd level was related with DA level; Mo, Cd, stannum (Sn), and antimony (Sb) levels were related with 5-HT level, respectively. The results of multiple linear regression analysis indicated that, after adjusting for age, sex, and body mass index (BMI), for each 10 μg·L^-1 increment in serum metal levels, Cd was positively associated with PHQ-9 score (b: 2.180, 95% CI: 1.220-3.140); As was positively associated with PHQ-9 score (b: 0.010, 95% CI: 0.001-0.020); Se was positively associated with PHQ-9 score (b: 0.010, 95% CI: 0.001-0.010); Co was positively associated with PHQ-9 score (b: 0.930, 95% CI: 0.410-1.460) and negatively associated with CORT level (b: -2.990, 95% CI: -5.690 - -0.330); Mo was positively associated with PHQ-9 score (b: 0.190, 95% CI: 0.030-0.340) and negatively associated with 5-HT level (b: 0.980, 95% CI: 0.230-1.730), respectively (P_FDR < 0.05).

Conclusion  A certain proportion of college students experience depression and anxiety in the study. The levels of Cd, Co, As, Se, and Mo in serum are significantly correlated with PHQ-9 score. However, no significant association between serum metal levels and GAD-7 score is found. Co level in serum is negatively associated with CORT level. Mo level in serum is positively associated with 5-HT level. The findings indicate that serum metal levels are associated with depression in college students.