Age-dependent subcortical iron accumulation in chronic schizophrenia: findings from a quantitative susceptibility mapping study

Abnormal brain iron levels are implicated in several neuropsychiatric illnesses, including schizophrenia spectrum disorders (SSD). However, current evidence on subcortical iron changes in chronic SSD remains limited, with the majority of studies conducted in early psychosis. We recruited 20 chronic SSD patients and 19 healthy controls from the Centre for Addiction & Mental Health (CAMH) in Toronto, Canada. Participants underwent quantitative susceptibility mapping (QSM) with a 3T MRI to estimate brain iron levels. Magnetic susceptibility was significantly elevated in the left hippocampus (d_adj = 1.108, p_FDR = 0.02) and nearing significance in the left putamen (d_adj = 0.86, p_FDR = 0.068) of SSD patients compared to controls, while accounting for age and sex. Interestingly, there was a significant, positive age-by-illness effect in the aforementioned areas, indicating a stronger age-related iron accumulation in SSD (L-putamen: β = 0.0006, p = 0.01; L-hippocampus: β = 0.0005, p = 0.001). We demonstrate elevated subcortical magnetic susceptibility, likely corresponding to elevated iron, in chronic SSD and a more pronounced age-related iron deposition associated with the illness. In conclusion, the expected age-related accumulation of subcortical iron levels appears to be disrupted in SSD and should be considered as a confounding factor in future analyses.