Kuang Dan, Wei Hongkai, Qin Wei
Severe Psychiatric Ward, Shaoxing Seventh People's Hospital (Affiliated Mental Health Center, Medical College of Shaoxing University), Shaoxing, Zhejiang, China.
Psychiatry Department, Daizhuang Hospital in Shandong Province, Jining, Shandong, China.
Front Psychiatry. 2025 Aug 14;16:1618147. doi: 10.3389/fpsyt.2025.1618147. eCollection 2025.
Executive dysfunction is a widespread and complex manifestation in schizophrenia, significantly impairing patients' cognitive and functional outcomes. Despite extensive research, specific biomarkers associated with this dysfunction remain unidentified. Serum ceruloplasmin (Cp), a copper-binding protein involved in iron metabolism and oxidative stress regulation, has recently been implicated in neurological conditions. This study aims to investigate the relationship between reduced serum Cp levels and executive dysfunction in hospitalized schizophrenia patients, providing insights into potential biomarkers and therapeutic targets.
A total of 95 schizophrenia inpatients treated at Shaoxing Seventh People's Hospital from January 2023 to December 2024 were enrolled. Patients were divided into two subgroups based on serum Cp concentrations: 48 patients with reduced Cp levels (SC1 group, Cp < 200 mg/L) and 47 patients with normal Cp levels (SC2 group, 200-600 mg/L). Additionally, 42 age- and gender-matched healthy individuals served as the control group. Blood samples were collected for Cp measurement using an automated biochemical analyzer. The severity of psychiatric symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS), while the Tower of London (TOL) test was employed to evaluate executive function. Statistical analyses included one-way ANOVA and Spearman's correlation to examine group differences and relationships between Cp levels and cognitive performance.
Significant differences in serum Cp levels were observed among the SC1, SC2, and control groups (P < 0.01). Executive function, assessed via the TOL test, showed no significant difference between the SC1 and SC2 groups (P > 0.05); however, both groups exhibited significantly impaired performance compared to the control group (P < 0.001). A strong positive correlation was identified between Cp levels and TOL performance in the SC1 group (r = 0.890, P < 0.001), particularly in simpler and moderately complex tasks.
Based on the existing evidence of widespread cognitive impairment in schizophrenia patients, this study delves deeper into its potential causes. We found that regardless of whether schizophrenia patients had normal or low serum ceruloplasmin (CP) levels, their executive function was significantly lower than that of healthy individuals. Furthermore, a correlation analysis showed a significant link between CP levels and executive dysfunction in schizophrenia patients with decreased CP levels. Our study suggests that low CP levels may aggravate executive dysfunction, indicating that CP deficiency might be a biological marker of executive dysfunction in schizophrenia.
执行功能障碍是精神分裂症中一种广泛且复杂的表现，严重损害患者的认知和功能结局。尽管进行了广泛研究，但与这种功能障碍相关的特定生物标志物仍未确定。血清铜蓝蛋白（Cp）是一种参与铁代谢和氧化应激调节的铜结合蛋白，最近被认为与神经疾病有关。本研究旨在探讨住院精神分裂症患者血清Cp水平降低与执行功能障碍之间的关系，为潜在的生物标志物和治疗靶点提供见解。
纳入2023年1月至2024年12月在绍兴市第七人民医院治疗的95例精神分裂症住院患者。根据血清Cp浓度将患者分为两个亚组：48例Cp水平降低的患者（SC1组，Cp<200mg/L）和47例Cp水平正常的患者（SC2组，200 - 600mg/L）。另外，42名年龄和性别匹配的健康个体作为对照组。使用自动生化分析仪采集血样进行Cp测量。使用阳性和阴性症状量表（PANSS）评估精神症状的严重程度，同时采用伦敦塔（TOL）测试评估执行功能。统计分析包括单因素方差分析和Spearman相关性分析，以检验组间差异以及Cp水平与认知表现之间的关系。
SC1组、SC2组和对照组之间血清Cp水平存在显著差异（P<0.01）。通过TOL测试评估的执行功能在SC1组和SC2组之间无显著差异（P>0.05）；然而，与对照组相比，两组的表现均显著受损（P<0.001）。在SC1组中，Cp水平与TOL表现之间存在强正相关（r = 0.890，P<0.001），特别是在较简单和中等复杂的任务中。
基于精神分裂症患者广泛存在认知障碍的现有证据，本研究更深入地探究了其潜在原因。我们发现，无论精神分裂症患者的血清铜蓝蛋白（CP）水平正常还是偏低，其执行功能均显著低于健康个体。此外，相关性分析表明，CP水平降低的精神分裂症患者中，CP水平与执行功能障碍之间存在显著关联。我们的研究表明，低CP水平可能会加重执行功能障碍，这表明CP缺乏可能是精神分裂症执行功能障碍的一个生物学标志物。
