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（PSD）是使患病率很高的严重精神综合症禁用严重的精神综合症。尽管 治疗疾病的进展，当前药物在所有患者中均未成功，也不解决 认知缺陷，这对于预测功能结果很重要。因此，新的治疗目标是 向前推动领域至关重要。 已经提出了铁代谢的缺陷作为潜在机制，由较高的发现支持 从产前生活中，在不同发育阶段受铁缺乏症影响的个体的PSD发病率 和婴儿期至成年。但是，对大脑水平的铁含量的评估仍然极为罕见， 这代表了当前对疾病的理解的关键差距，特别是鉴于最近 文献强调了铁在青春期期间铁中铁的作用 年轻成年，这是PSD出现的关键发展时期。 在此应用中，我们建议通过进行多参数MRI研究来解决文献中的这一差距 为了测试PSD中几种皮层结构的铁含量是否降低。我们还将测试是否 脑铁的伴侣随着症状增加和认知能力降低而降低。评估铁 在大脑水平上的含量是必不可少的，因为在检测到贫血之前，脑组织铁可能会耗尽 缺陷可能不会通过对血液中铁的典型评估反映。 确认PSD中脑铁缺乏症应促进进一步的研究，重点是更好地理解 脑铁稳态如何影响PSD以及铁缺陷如何影响相关的系统和过程 已知在这些疾病中受到影响。如果成功，该研究最终可能会导致治疗策略 可能有助于改善PSD症状，并可以提供驴的功效的手段 治疗。