Associations of cerebrospinal fluid metal ion profiles with depressive symptoms in active smokers: a cross-sectional network analysis.

Background: Smokers are more likely to report depressive symptoms, on the other hand, individuals with depression are also more likely to initiate smoking. In a recent study, higher CSF concentration of magnesium, zinc, iron, lead, lithium, and aluminum were reported among active smokers. This study investigated whether the disruption of central metal homeostasis in active smokers is associated with self-reports of depressive symptoms. Methods: CSF samples from 161 Chinese male patients who underwent anterior cruciate ligament reconstruction surgical operation following knee joint injuries were obtained. Among the 161 male patients, 57 male patients were active smokers while 104 patients reported never engaged in any form of smoking. Depressive symptoms were measured via Beck Depression Inventory (BDI) self-reports. CSF concentrations of 8 metal ions were quantified by atomic absorption spectrophotometry. Group comparisons, correlation analyses, mixed graphical model network analyses, and moderation models were performed to examine associations among smoking, CSF metal ions, and depressive symptoms. Results: Active smokers had higher BDI total scores and higher CSF concentrations of magnesium, zinc, iron, lead, lithium, and aluminum than non-smokers. Higher BDI total scores were associated with higher CSF concentration of zinc, iron, lead, and aluminum. Network analysis revealed iron, zinc, and lead ranked the highest in terms of strength, expected influence, and closeness among the 8 metal ions. With iron as an important association node among the three in the metal ion network observed, simultaneously significantly associated with BDI total scores. Further analyses revealed smoking was positively associated with depressive symptoms, and the interaction between smoking and iron significantly predicted BDI total scores. Additional analyses revealed that concentrations of iron in CSF also significantly interacted with zinc and lead. Conclusions: Iron is an important associated node that connects various other metal ions to self-reports of depressive symptoms. This finding shed light upon the interrelationships among smoking status, depressive symptoms, and metal ions in CSF, providing partial evidence supporting the relevance of central metal dysregulation to the smoking-depressive symptoms among male smokers.