Cortical Iron and Mesostriatal Dopamine Function in Schizophrenia: A Positron Emission Tomography and Magnetic...

Elevated postmortem iron in Brodmann areas 10-11 has recently been linked to schizophrenia. Although in vivo studies have linked subcortical iron abnormalities to disease-related striatal hyperdopaminergia, in vivo cortical iron alterations have not been previously examined. We therefore used neuroimaging to test whether cortical iron is elevated in individuals with schizophrenia and whether this correlated with mesostriatal dopamine function.

We acquired quantitative susceptibility mapping magnetic resonance imaging (MRI) to measure magnetic susceptibility (χ), a marker of iron, in 149 participants aged 18-45 (73 with schizophrenia and 76 matched healthy controls). Subsets of patients with schizophrenia underwent [18F]-DOPA PET to estimate striatal dopamine synthesis capacity (n = 39) and neuromelanin-sensitive MRI of the dopaminergic midbrain (n = 68), as neuromelanin is a byproduct of dopamine synthesis.

Primary analyses showed no significant case-control differences in χ in the whole cortex (P = .675) or Brodmann areas 10-11 (P = .537). Exploratory analyses examined χ for 360 cortical regions, correcting for multiple comparisons. Two left temporo-parieto-occipital junction regions showed significantly elevated χ in schizophrenia: the posterior temporo-parieto-occipital junction the posterior temporo-parieto-occipital junction (d = 0.752, P < .001) and the superior temporal visual area (d = 0.638, P = .034). Mean χ across these regions inversely correlated with dopamine synthesis capacity in the associative (r = -0.37, P = .048) and limbic (r = -0.34, P = .048) striatum, and with neuromelanin-sensitive MRI values in the dopaminergic midbrain (r = -0.35, P = .005), corrected for multiple comparisons.

This study provides the first in vivo evidence of elevated cortical iron in schizophrenia and links this to mesostriatal dopamine dysfunction.