Abstract
White matter (WM) abnormalities are commonly reported in schizophrenia but whether these arise from the axon or myelin compartments or both is not known. In addition, the relationship between WM abnormalities and cognitive function is not fully explored in this condition. We recruited 39 individuals with schizophrenia spectrum disorders and 37 healthy comparison subjects. All participants underwent MRI scanning at 4 Tesla to collect data in the prefrontal white matter on magnetization transfer ratio (MTR) and diffusion tensor spectroscopy (DTS) which provide information on myelin and axon compartments, respectively. We also collected Matrics Composite Cognitive Battery (MCCB) and Stroop cognitive data. We found an elevated N-acetylaspartate (NAA) apparent diffusion coefficient in schizophrenia in this cohort as in our previous work; we also observed poorer performance on both the MCCB composite and the Stroop in schizophrenia patients compared to controls. The MTR measure was correlated with the MCCB composite (r = 0.363, p = 0.032) and Stroop scores (r = 0.387, p = 0.029) in healthy individuals but not in schizophrenia. Since this is the first exploration of the relationship between these WM and cognitive measures, we consider our analyses exploratory and did not adjust for multiple comparisons; the findings are not statistically significant if adjusted for multiple comparisons. These findings indicate that WM integrity is associated with cognitive function in healthy individuals but this relationship breaks down in patients with schizophrenia.
Highlights
Several lines of evidence implicate white matter (WM) abnormalities in the pathophysiology of schizophrenia (SZ)
We used Magnetization Transfer Ratio (MTR) and Diffusion Tensor Spectroscopy (DTS) to quantify white matter abnormalities in a group of SZ patients and matched healthy controls and we correlated these results with performance in neurocognitive tests
We found reduced cognitive scores based on the Matrics Composite Cognitive Battery (MCCB) composite and the Stroop test in people with SZ, as well as significantly elevated NAA apparent diffusion coefficient (ADC)
Summary
Several lines of evidence implicate white matter (WM) abnormalities in the pathophysiology of schizophrenia (SZ). Diffusion tensor imaging (DTI) is an MRI modality which measures in vivo water molecule diffusion and provides noninvasive information on integrity of the myelinated axon pathways within WM. DTI research has provided significant insights into WM abnormalities in brain disorders such as schizophrenia, it cannot currently resolve signals from axon and myelin compartments since water molecules exist in both intracellular and extracellular spaces and there is exchange between these. To provide compartment-specific information on WM integrity in the human brain, we recently implemented Magnetization Transfer Ratio (MTR) and Diffusion Tensor Spectroscopy (DTS) approaches [7], and we reported abnormalities in schizophrenia [8] and bipolar disorder [9] using these techniques. MTR is an MRI modality that provides information on brain myelin content. NAA is only intraneuronal [10] and it has been proposed that NAA diffusion can help us understand microstructure within neurons [11]
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