In Vivo 7-Tesla MRI Investigation of Brain Iron and Its Metabolic Correlates in Chronic Schizophrenia

Abstract

Brain iron is central to dopaminergic neurotransmission, a key component in schizophrenia pathology. Iron can also generate oxidative stress, which is one proposed mechanism for gray matter volume reduction in schizophrenia. The role of brain iron in schizophrenia and its potential link to oxidative stress has not been previously examined. In this study, we used 7-Tesla MRI quantitative susceptibility mapping (QSM), magnetic resonance spectroscopy (MRS), and structural T1 imaging in 12 individuals with chronic schizophrenia and 14 healthy age-matched controls. In schizophrenia, there were higher QSM values in bilateral putamen and higher concentrations of phosphocreatine and lactate in caudal anterior cingulate cortex (caCC). Network-based correlation analysis of QSM across corticostriatal pathways as well as the correlation between QSM, MRS, and volume, showed distinct patterns between groups. This study introduces increased iron in the putamen in schizophrenia in addition to network-wide disturbances of iron and metabolic status.

Alterations in subcortical magnetic susceptibility and disease-specific relationship with brain volume in major depressive disorder and schizophrenia

“…Earlier studies on MDD using QSM reported high magnetic susceptibility in the putamen, hippocampus, and thalamus, which is not in agreement with the current results [22]. Further, prior research reported a decrease in magnetic susceptibility in the globus pallidus, left putamen, and left thalamus of rst-episode schizophrenia patients [24] and observed high magnetic susceptibility bilaterally in the putamen of chronic schizophrenia patients [25]. These discrepancies were probably caused by differences in QSM analysis methods used by earlier studies.…”

“…In addition, only a few studies on psychiatric disorders examine the relationship between structural subcortical volume changes and magnetic susceptibility; however, research indicates a negative correlation between volume and magnetic susceptibility in the hippocampus in schizophrenia patients [25]. In neurological studies using amyloid-beta (Aβ) PET, subcortical Aβ is associated with changes in the surface morphology of speci c brain regions, and a high Aβ is associated with poor cognitive function and small hippocampal volume in cognitively normal individuals [26].…”

Alterations in subcortical magnetic susceptibility and disease-specific relationship with brain volume in major depressive disorder and schizophrenia

“…Earlier studies on MDD using QSM reported high magnetic susceptibility in the putamen, hippocampus, and thalamus, which is not in agreement with the current results [ 28 ]. Further, prior research reported a decrease in magnetic susceptibility in the globus pallidus, left putamen, and left thalamus of first-episode schizophrenia patients [ 30 ] and observed high magnetic susceptibility bilaterally in the putamen of chronic schizophrenia patients [ 31 ]. The reason for these differences may be that previous study was not an atlas-based analysis using MNI, but a manual ROI analysis [ 28 , 30 , 31 ].…”

“…In addition, only a few studies on psychiatric disorders examine the relationship between structural subcortical volume changes and magnetic susceptibility; however, research indicates a negative correlation between volume and magnetic susceptibility in the hippocampus in schizophrenia patients [ 31 ]. Increased magnetization rates are not solely determined by iron deposition; a reduction in diamagnetic myelin also contributes to this increase.…”

Recommended implementation of quantitative susceptibility mapping for clinical research in the brain: A consensus of the ISMRM electro‐magnetic tissue properties study group

“…33,34 The latter has proven valuable for presurgical mapping of deep gray nuclei targets in deep brain stimulation. 30,[35][36][37][38][39] QSM is also utilized to study imbalances in neurotransmitter levels or metabolism in psychiatric disorders such as psychosis 40,41 and depression 42,43 and to investigate neural mechanisms through which alcohol affects the brain. [44][45][46] An important feature of QSM, when compared to, for example, R 1 or R 2 relaxometry, is that its results may be less independent of field strength and scanner manufacturer when a consistent reconstruction QSM pipeline is used.…”