Causal associations between iron levels in subcortical brain regions and psychiatric disorders: a Mendelian randomization study.

IF 6.2 1区医学 Q1 PSYCHIATRY Translational Psychiatry Pub Date : 2025-01-22 DOI:10.1038/s41398-025-03231-8

Wei Du, Biqiu Tang, Senhao Liu, Wenjing Zhang, Su Lui

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Abstract

Despite observational studies linking brain iron levels to psychiatric disorders, the exact causal relationship remains poorly understood. This study aims to examine the relationship between iron levels in specific subcortical brain regions and the risk of psychiatric disorders. Utilizing two-sample Mendelian randomization (MR) analysis, this study investigates the causal associations between iron level changes in 16 subcortical nuclei and eight major psychiatric disorders, including schizophrenia (SCZ), major depressive disorder (MDD), autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder, bipolar disorder, anxiety disorders, obsessive-compulsive disorder, and insomnia. The genetic instrumental variables linked to iron levels and psychiatric disorders were derived from the genome-wide association studies data of the UK Biobank Brain Imaging and Psychiatric Genomics Consortium. Bidirectional causal estimation was primarily obtained using the inverse variance weighting (IVW) method. Iron levels in the left substantia nigra showed a negative association with the risk of MDD (OR_IVW = 0.94, 95% CI = 0.91-0.97, p < 0.001) and trends with risk of SCZ (OR_IVW = 0.90, 95% CI = 0.82-0.98, p = 0.020). Conversely, iron levels in the left putamen were positively associated with the risk of ASD (OR_IVW = 1.11, 95% CI = 1.04-1.19, p = 0.002). Additionally, several bidirectional trends were observed between subcortical iron levels and the risk for psychiatric disorders. Lower iron levels in the left substantia nigra may increase the risk of MDD, and potentially increase the risk of SCZ, indicating a potential shared pathogenic mechanism. Higher iron levels in the left putamen may lead to the development of ASD. The observed bidirectional trends between subcortical iron levels and psychiatric disorders, indicate the importance of the underlying biomechanical interactions between brain iron regulation and these disorders.

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脑皮层下铁水平与精神疾病之间的因果关系：一项孟德尔随机研究。

尽管观察性研究将脑铁水平与精神疾病联系起来，但确切的因果关系仍然知之甚少。本研究旨在研究大脑皮层下特定区域的铁水平与精神疾病风险之间的关系。本研究利用双样本孟德尔随机化（MR）分析，探讨了16个皮质下核铁水平变化与8种主要精神疾病的因果关系，包括精神分裂症（SCZ）、重度抑郁症（MDD）、自闭症谱系障碍（ASD）、注意力缺陷/多动障碍、双相情感障碍、焦虑障碍、强迫症和失眠。与铁水平和精神疾病相关的遗传工具变量来自英国生物银行脑成像和精神基因组学联盟的全基因组关联研究数据。双向因果估计主要采用逆方差加权法（IVW）。左侧黑质铁水平与MDD风险呈负相关（ORIVW = 0.94, 95% CI = 0.91-0.97, p IVW = 0.90, 95% CI = 0.82-0.98, p = 0.020）。相反，左壳核中的铁水平与ASD的风险呈正相关（ORIVW = 1.11, 95% CI = 1.04-1.19, p = 0.002）。此外，在皮质下铁水平和精神疾病风险之间观察到几个双向趋势。左侧黑质铁含量较低可能增加MDD的风险，并可能增加SCZ的风险，表明可能存在共同的致病机制。高铁水平的左壳核可能导致ASD的发展。观察到的皮质下铁水平与精神疾病之间的双向趋势，表明脑铁调节与这些疾病之间潜在的生物力学相互作用的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Psychiatry PSYCHIATRY-

CiteScore

11.50

自引率

2.90%

发文量

484

审稿时长

23 weeks

期刊介绍： Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.