Iron deficits and their relationship with symptoms and cognition in Psychotic Spectrum Disorders

项目摘要 精神病谱系障碍(PSD)是一种发病率较高的严重精神障碍。尽管 治疗这些疾病的进展，目前的药物并不是对所有患者都有效，而且没有解决 认知缺陷，这在预测功能结果方面很重要。因此，新的治疗目标是 在推动这一领域向前发展方面至关重要。 铁代谢缺陷被认为是一种潜在的机制，这得到了更高水平的研究结果的支持 出生前不同发育阶段受缺铁影响的PSD发生率 从婴儿期到成年期。然而，对大脑水平的铁含量的评估仍然非常罕见， 这代表着目前对这些障碍的理解存在严重差距，特别是考虑到最近的 文献强调铁在青春期和青春期多巴胺能系统发育中的作用 青壮年，PSD出现的关键发育期。 在这一应用中，我们建议通过进行多参数磁共振研究来解决文献中的这一差距 检测PSD患者几种皮质下结构的铁含量是否降低。我们还将测试 大脑铁含量降低与症状增加和认知能力下降有关。评估铁质 大脑水平的含量是必不可少的，因为在检测到贫血之前，脑组织铁可能就会耗尽，因此， 对血液中铁的典型评估可能不会反映出缺陷症。 对PSD患者脑铁缺乏的确认应该会促进进一步的研究，重点是更好地了解 PSD患者脑铁稳态如何受到影响以及铁缺乏如何影响相关系统和过程 已知在这些疾病中受到影响。如果成功，这项研究最终可能导致治疗策略 可能有助于改善PSD症状，并可能提供评估这种 治疗。

Project Summary Psychotic spectrum disorders (PSD) are disabling severe mental syndromes with high prevalence. Despite progress in treating the disorders, current medications are not successful in all patients and do not address cognitive deficits, which are significant in predicting functional outcome. Thus, new treatment targets are essential in moving the field forward. Deficits in iron metabolism have been proposed as a potential mechanism, supported by findings of higher incidence of PSD in individuals affected by iron deficiency at different developmental stages, from prenatal life and infancy to adulthood. However, assessments of the iron content at brain level remain extremely rare, which represents a critical gap in the current understanding of the disorders, particularly in light of recent literature highlighting the role of iron in the development of the dopaminergic system during adolescence and young adulthood, a critical developmental period for the emergence of PSD. In this application, we propose to address this gap in literature by conducting a multi-parametric MRI study to test whether iron content of several subcortical structures is decreased in PSD. We will also test whether decreased brain iron associates with increased symptoms and decreased cognitive ability. Assessing iron content at brain level is essential since brain tissue iron may be depleted before anemia is detected, and thus, deficits may not be reflected by typical assessments of iron in blood. Confirmation of brain iron deficits in PSD should promote further studies focused on better understanding of how brain iron homeostasis is affected in PSD and how iron deficits impact related systems and processes known to be affected in these disorders. If successful, the study may ultimately lead to treatment strategies that may contribute to amelioration of PSD symptoms and may provide means to asses the efficacy of such treatments.