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

铁缺乏及其与精神病谱系障碍症状和认知的关系

• 批准号: 10595270
• 负责人: MARIANA LAZAR
• 金额: $ 69.13万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10595270
• 关键词: Address; Adolescence; Adult; Affect; Anemia; Aphasia; Area; Biological; Blood; Brain; Brain imaging; Chronic; Cognition; Cognitive; Cognitive deficits; Corpus striatum structure; Data; Delusions; Development; Diagnosis; Diagnostic; Diet; Disease; Disease Outcome; Elements; Emotions; Etiology; Future; Globus Pallidus; Goals; Hallucinations; Health; High Prevalence; Histologic; Homeostasis; Image; Imaging technology; Impaired cognition; Impairment; Incidence; Individual; Interview; Iron; Knowledge; Life; Light; Literature; MATRICS Consensus Cognitive Battery; Magnetic Resonance Imaging; Magnetism; Maintenance; Measures; Modeling; Myelin; Neurobehavioral Manifestations; Neurotransmitters; Oligodendroglia; Outcome; Pathogenesis; Pathway interactions; Patients; Perception; Pharmaceutical Preparations; Play; Population; Process; Protons; Psyche structure; Psychoses; Relaxation; Research; Role; Schizoaffective Disorders; Schizophrenia; Serotonergic System; Structure; Symptoms; Syndrome; System; T2 weighted imaging; Testing; Thalamic structure; Work; brain abnormalities; brain tissue; cognitive ability; cognitive function; cognitive performance; cost estimate; critical developmental period; disability; dopamine system; dysmyelination; efficacy evaluation; functional outcomes; gray matter; histological studies; imaging study; improved; in vivo; in vivo imaging; infancy; insight; iron deficiency; iron metabolism; myelination; neuromechanism; non-invasive imaging; novel; peripheral blood; prenatal; psychotic; psychotic symptoms; remediation; timeline; treatment strategy; white matter; young adult

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.

项目摘要 精神病谱系障碍（Psychotic spectrum disorders，PSD）是一种严重的致残性精神综合征，发病率较高.尽管 尽管在治疗疾病方面取得了进展，但目前的药物治疗并不是在所有患者中都成功， 认知缺陷，这在预测功能结果方面具有重要意义。因此，新的治疗目标是 这是推动该领域向前发展的关键。 铁代谢缺陷已被认为是一种潜在的机制，并得到了更高水平的研究结果的支持。 从出生前开始，在不同发育阶段受铁缺乏影响的个体中PSD的发病率 从婴儿期到成年期然而，在大脑水平上对铁含量的评估仍然非常罕见， 这代表了目前对疾病理解的一个关键差距，特别是考虑到最近的 强调铁在青春期多巴胺能系统发育中作用的文献， 青年期是PSD出现的关键发展时期。 在本申请中，我们建议通过进行多参数MRI研究来解决文献中的这一空白 以检测PSD中几种皮质下结构的铁含量是否降低。我们还将测试 脑铁减少与症状增加和认知能力下降有关。评估铁 脑水平的铁含量是必需的，因为脑组织铁可能在检测到贫血之前被耗尽，因此， 缺乏可能不能通过血液中铁的典型评估来反映。 PSD患者脑铁缺乏的确认应促进进一步的研究，重点是更好地了解 脑铁稳态如何影响PSD以及铁缺乏如何影响相关系统和过程 在这些疾病中受到影响。如果成功，这项研究可能最终导致治疗策略， 可以有助于改善PSD症状，并且可以提供评估这种治疗的功效的方法。 治疗。