Ray Arti, Tomo Sojit, Yadav Dharmveer, Banerjee Mithu, Sharma Praveen, Sharma Shailja, Nebhinani Naresh, Birdi Amandeep, Pawar Harshita, Janu Vikas Chandra
Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.
Department of Psychiatry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.
Biol Trace Elem Res. 2025 Jun 18. doi: 10.1007/s12011-025-04701-2.
The presence of hazardous heavy metals (HMs) in the environment is well established, and numerous studies have explored their involvement in brain-related disorders. However, their potential impact on neuroinflammation, disease severity, and cognitive function in schizophrenia (SZ) remains largely unexplored. Therefore, this study aimed to investigate the potential pathophysiological role of environmental HMs in SZ. A total of 40 SZ patients and 40 healthy controls (HCs) were recruited from AIIMS Jodhpur, India. Blood samples were analyzed for lead (Pb), cadmium (Cd), arsenic (As), aluminium (Al), and TNF-α using atomic absorption spectroscopy and ELISA, while TNF-α gene expression was quantified using RT-qPCR. Patients exhibited notably elevated concentrations of Cd and Pb while decreased levels of As with median (IQR), 0.9 (0.40-1.72); 1.11 (0.59-1.26); and 0.73 (0.46-0.89) compared to HCs with median (IQR), 0.75 (0.46-1.06); 0.11 (0.04-0.18); and 0.92 (0.65-1.60) respectively. A significant positive relationship between TNF-α gene expression and blood As (ρ = 0.33, p < 0.05) and a negative association between Pb and Al (ρ = -0.34; p < 0.05) were reported in the patient group. Cognitive focus test scores were significantly lower in patients than in controls (p < 0.001). Cd levels negatively correlated with Stroop Word, Stroop Color, Color-Word, and Stroop Total scores (ρ = - 0.28, - 0.36, - 0.28, - 0.33), indicating cognitive dysfunction. Additionally, PANSS score correlated negatively with Stroop Word (ρ = - 0.36) and Stroop Total (ρ = - 0.35), while PANSS Total scores showed negative correlations with Stroop Total (ρ = - 0.33) and Stroop Color (ρ = - 0.34), linking higher disease severity to poorer cognitive performance. In conclusion, these findings provide novel insights into SZ pathophysiology, highlighting the neurotoxic impact of heavy metals on TNF-α regulation, neuroinflammation, and cognition. The relationship between cognitive function with Cd and disease severity underscores the importance of early intervention and environmental risk mitigation to protect brain function and overall health.
环境中有害重金属（HMs）的存在已得到充分证实，众多研究探讨了它们与脑相关疾病的关联。然而，它们对精神分裂症（SZ）的神经炎症、疾病严重程度和认知功能的潜在影响在很大程度上仍未得到探索。因此，本研究旨在调查环境HMs在SZ中的潜在病理生理作用。从印度焦特布尔全印医学科学研究所招募了40例SZ患者和40名健康对照（HCs）。使用原子吸收光谱法和酶联免疫吸附测定法分析血样中的铅（Pb）、镉（Cd）、砷（As）、铝（Al）和肿瘤坏死因子-α（TNF-α），同时使用逆转录定量聚合酶链反应（RT-qPCR）对TNF-α基因表达进行定量。与HCs相比，患者的Cd和Pb浓度显著升高，而As水平降低，患者的中位数（四分位间距）分别为0.9（0.40 - 1.72）；1.11（0.59 - 1.26）；0.73（0.46 - 0.89），HCs的中位数（四分位间距）分别为0.75（0.46 - 1.06）；0.11（0.04 - 0.18）；0.92（0.65 - 1.60）。在患者组中，报告了TNF-α基因表达与血As之间存在显著正相关（ρ = 0.33，p < 0.05），以及Pb与Al之间存在负相关（ρ = -0.34；p < 0.05）。患者的认知聚焦测试得分显著低于对照组（p < 0.001）。Cd水平与Stroop单词、Stroop颜色、颜色 - 单词和Stroop总分呈负相关（ρ = -0.28， - 0.36， - 0.28， - 0.33），表明存在认知功能障碍。此外，阳性和阴性症状量表（PANSS）得分与Stroop单词（ρ = -0.36）和Stroop总分（ρ = -0.35）呈负相关，而PANSS总分与Stroop总分（ρ = -0.33）和Stroop颜色（ρ = -0.34）呈负相关，将更高的疾病严重程度与较差的认知表现联系起来。总之，这些发现为SZ病理生理学提供了新的见解，突出了重金属对TNF-α调节、神经炎症和认知的神经毒性影响。认知功能与Cd之间以及与疾病严重程度之间的关系强调了早期干预和减轻环境风险以保护脑功能和整体健康的重要性。
