Brain iron assessment in patients with First-episode schizophrenia using quantitative susceptibility mapping

Abstract

Purpose: Decreased serum ferritin level was recently found in schizophrenia. Whether the brain iron concentration in schizophrenia exists abnormality is of research significance. Quantitative susceptibility mapping (QSM) was used in this study to assess brain iron changes in the grey matter nuclei of patients with first-episode schizophrenia.

Methods: The local ethics committee approved the study, and all subjects gave written informed consent. Thirty patients with first-episode schizophrenia and 30 age and gender-matched healthy controls were included in this study. QSM and effective transverse relaxation rate (R₂*) maps were reconstructed from a three-dimensional multi-echo gradient-echo sequence. The inter-group differences of regional QSM values, R₂* values and volumes were calculated in the grey matter nuclei, including bilateral caudate nucleus, putamen, globus pallidus, substantia nigra, red nucleus, and thalamus. The diagnostic performance of QSM and R₂* was evaluated using receiver operating characteristic curve. The correlations between regional iron variations and clinical PANSS (Positive and Negative Syndrome Scale) scores were assessed using partial correlation analysis.

Results: Compared to healthy controls, patients with first-episode schizophrenia had significantly decreased QSM values (less paramagnetic) in the bilateral substantia nigra, left red nucleus and left thalamus (p < 0.05, FDR correction). QSM proved more sensitive than R₂* regarding inter-group differences. The highest diagnostic performance for first-episode schizophrenia was observed in QSM value of the left substantia nigra (area under the curve, AUC = 0.718, p = 0.004). Regional volumes of bilateral putamen and bilateral substantia nigra were increased (p < 0.05, FDR correction) in first-episode schizophrenia. However, both QSM and R₂* values did not show significant correlations with PANSS scores (p > 0.05).

Conclusion: This study reveals decreased iron concentration in grey matter nuclei of patients with first-episode schizophrenia. QSM provides superior sensitivity over R₂* in the evaluation of schizophrenia-related brain iron changes. It demonstrated that QSM may be a potential biomarker for further understanding the pathophysiological mechanism of first-episode schizophrenia.

Keywords: Brain iron; Grey matter nucleus; MRI; Quantitative susceptibility mapping; Schizophrenia.