Reduced Brain Iron and Striatal Hyperdopaminergia in Schizophrenia: A Quantitative Susceptibility Mapping MRI and PET Study
Luke Vano, Robert A. McCutcheon, Jan Sedlacik, Stephen J. Kaar, Grazia Rutigliano, Giovanna Nordio, Valeria Finelli, Leigh Townsend, Alaine Berry, Ben Statton, Amir Fazlollahi, Mattia Veronese, Seth C. Hopkins, Kenneth S. Koblan, Ian Everall, Oliver Howes
Abstract
OBJECTIVE: Neuroimaging studies have independently associated schizophrenia with low iron and elevated dopamine synthesis. While preclinical research demonstrates that midbrain iron deficiency leads to striatal hyperdopaminergia, this relationship has not been studied in schizophrenia. The authors conducted a case-control study to examine differences in tissue magnetic susceptibility, a marker of brain iron, and correlated these with striatal dopamine synthesis capacity. METHODS: . RESULTS: , independent of mean diffusivity and NM-MRI contrast-to-noise ratios (r=-0.44). In both analyses, the strongest effects were observed in the ventral SN-VTA. CONCLUSIONS: These findings suggest that lower levels of non-neuromelanin-bound iron in the SN-VTA contribute to striatal hyperdopaminergia in schizophrenia. Further investigation is warranted to understand the role of low iron in schizophrenia and its potential as a treatment target.