Squitti Rosanna, Rongioletti Mauro, Fostinelli Silvia, Severino Altea, Bonvicini Cristian, Geviti Andrea, Martinelli Alessandra, Tura Giovanni Battista, Ghidoni Roberta
Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia 25125, Italy; Department of Laboratory Science, Research and Development Division, Ospedale Isola Tiberina Gemelli Isola, Rome, Italy.
Department of Laboratory Science, Research and Development Division, Ospedale Isola Tiberina Gemelli Isola, Rome, Italy.
J Trace Elem Med Biol. 2024 Dec;86:127532. doi: 10.1016/j.jtemb.2024.127532. Epub 2024 Sep 14.
Meta-analyses show increased copper (Cu) levels in major depression disorder. However, the association of Cu biomarkers with clinical classification in other mental health disorders has not been fully explored.
To this aim, we compared an extensive panel of Cu biomarkers, composed of Cu, ceruloplasmin (Cp) Cp activity, Cp specific activity, Cu not bound to ceruloplasmin (non-Cp Cu, also known as 'free' copper) in 171 consecutive patients affected by psychiatric disorders and in 61 healthy controls (HC) using MANOVA adjusting for the effect of sex and age, and studied their association with the clinical scale outcomes at psychiatric examination, namely Global Assessment of Functioning, Clinical Global Impression, and Brief Psychiatric Rating Scale.
individuals with psychiatric disorders were classified as 109 patients affected by mood spectrum disorders (MSD), 20 patients with schizophrenia spectrum disorders (SSD), and 42 with personality disorders (PD). Cu and non-Cp Cu were increased in psychiatric individuals than in HC, which also differed among the patients stratified per the clinical classification, being higher in the MSD individuals. The analysis stratified for sex revealed that women from the patient group, and specifically from the MSD group, had increased levels of Cu and non-Cp Cu than healthy women, while no difference was revealed in men. A logistic regression model considering the effect of sex and age revealed that non-Cp Cu could explain 26 % increased odds of having MSD per µmol/L unit increase (OR = 1.26; p = 0.0008; 95 % CI 1.099-1.436), that reached 40 % when considering only women. This result was driven by non-Cp Cu that correctly classified 64.1 % MSD (70 % in women) individuals vs. HC in a decision tree model, with values higher than 2.1 µmol/L which could distinguish the majority of MSD patients (86.3 % MSD vs. 13.7 % HC in women). None of the biological variables under study correlated with outcomes of the clinical scales, substances, or alcohol abuse.
Current results suggest mild Cu toxicity in women with MSD, as revealed by a value of non-Cp Cu higher than 2.1 µmol/L, which can be further investigated to assess its potential diagnostic accuracy in bigger and longitudinal cohorts.
荟萃分析显示，重度抑郁症患者体内铜（Cu）水平升高。然而，铜生物标志物与其他精神健康障碍临床分类之间的关联尚未得到充分探索。
为此，我们比较了大量的铜生物标志物，包括铜、铜蓝蛋白（Cp）、Cp活性、Cp比活性、未与铜蓝蛋白结合的铜（非Cp铜，也称为“游离”铜），这些标志物来自171例连续的精神疾病患者和61名健康对照者（HC），使用多变量方差分析（MANOVA）来调整性别和年龄的影响，并研究它们与精神检查时临床量表结果的关联，即功能总体评定量表、临床总体印象量表和简明精神病评定量表。
精神疾病患者被分为109例受情绪谱系障碍（MSD）影响的患者、20例精神分裂症谱系障碍（SSD）患者和42例人格障碍（PD）患者。精神疾病患者体内的铜和非Cp铜含量高于健康对照者，且根据临床分类分层的患者之间也存在差异，MSD患者体内的含量更高。按性别分层分析显示，患者组中的女性，特别是MSD组中的女性，其铜和非Cp铜水平高于健康女性，而男性之间未发现差异。考虑性别和年龄影响的逻辑回归模型显示，非Cp铜每增加1 μmol/L，患MSD的几率增加26%（OR = 1.26；p = 0.0008；95% CI 1.099 - 1.436），仅考虑女性时这一比例达到40%。这一结果是由非Cp铜驱动的，在决策树模型中，非Cp铜能正确分类64.1%的MSD患者（女性中为70%）与健康对照者，其值高于2.1 μmol/L时可区分大多数MSD患者（女性中86.3%的MSD患者与13.7%的健康对照者）。所研究的生物学变量均与临床量表、物质或酒精滥用的结果无关。
目前的结果表明，MSD女性存在轻度铜中毒，表现为非Cp铜值高于2.1 μmol/L，这可在更大规模的纵向队列中进一步研究，以评估其潜在的诊断准确性。
