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.

Project Narrative Psychotic Spectrum Disorders (PSD) are severe mental syndromes associated with significant lifelong impairment and high prevalence. In this proposal we aim to employ non-invasive imaging technologies to test that deficiency in brain iron, an essential element for brain functioning, is a feature of PSD. The results of this study may provide new targets for treatments aimed at alleviating psychotic symptoms and cognitive dysfunction in PSD patients.