Cigarette Smoking, Insomnia and Depression Linked by CSF Metal Ion Levels

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A new analysis suggests raise levels of zinc, iron, lead and aluminum—linked to cigarette use—is positively correlated with insomnia.

Levels of cerebrospinal fluid (CSF) metal ions indicate a physiological association between cigarette smoking and risk of depression and insomnia, according to new findings.

In research from a team of China investigators, the CSF levels of multiple metal ions in a population of male participants showed raised counts of elements like magnesium and zinc—common among current smokers—are linked to measures of depression like the Beck Depression Inventory (BDI) and insomnia like the Pittsburgh Sleep Quality Index (PSQI).

Led by Yuying Li, of the Wenzhou Medical College Affiliated Third Hospital in China, investigators sought to determine links between cigarette smoking and neuropsychiatric burdens including anxiety, depression and insomnia via CSF metal ion levels. As they noted, previous laboratory-level analyses have associated ions including aluminum, manganese, and zinc with these conditions, and cigarette smoke is known to cause accumulation of such metals quickly in users.

“However, no study has been published yet that uses CSF metal ions to investigate the relationship between active smoking and emotional dysfunction and sleep disorder,” they wrote.

Due to smoking prevalence being very low among women in China, Li and colleagues’ analysis included 178 male pariticpants recruited from September 2014 - January 2016. Among participants, 64 (30.3%) were active smokers. Investigators recorded sociodemographic data including age, years of education and body mass index (BMI). They also included patient-reported clinical data relevant to the analysis.

Investigators conducted patient questionnaires including PSQI, BDI, the Self-Rating Anxiety Scale (SRAS), and the Fagerstrom Test for Nicotine Dependence (FTND) to interpret insomnia status, depression, anxiety and nicotine dependence, respectively, in each patient.

At the time of recruitment, each male patient was undergoing anterior cruciate ligament (ACL) reconstructive surgery; because of this, they had underwent a lumbar puncture that allowed for a CSF sample extraction. Investigators assessed for levels of magnesium, zinc, iron, lead, lithium, copper, manganese and aluminum.

Investigators observed significantly greater higher scores for BMI (25.7 vs 24.37; P = .01) BDI (3.65 vs 2.15; P <.001), and PSQI (4.53 vs 2.79; P <.001) among active smokers than nonsmokers—indicating greater obesity, depression and insomnia rates, respectively. Smokers also had significantly greater CSF levels of magnesium, zinc, iron, lead, lithium and aluminum (P < .002).

Using a Spearman’s correlations assessment, investigators interpreted a positive correlation between zinc, iron, lead and aluminum, depression per BDI (P <.01). They additionally observed a positive correlation between metal ions including zinc and lead, and sleep quality per PSQI (P <.05).

Though the trial was limited by potentially confounding health associated with ACL injury patients, as well as the exclusivity of male participants, the team concluded their findings were promising enough to warrant future assessment.

“Cigarette smoking was associated with depression and insomnia, as shown by higher BDI and PSQI scores,” they wrote. “Significantly higher magnesium, zinc, iron, lead, lithium, and aluminum CSF levels were found in active smokers than in nonsmokers. Furthermore, CSF aluminum played a mediating role in the relationship between smoking and depression, which further confirmed its neurotoxicity.”

The study, “Metal ions in cerebrospinal fluid: Associations with anxiety, depression, and insomnia among cigarette smokers,” was published online in CNS Neuroscience & Therapeutics.