Association of Prefrontal Myo-Inositol with White Matter Microstructure changes in Early Psychosis
Poster No:
380
Submission Type:
Abstract Submission
Authors:
Tommaso Pavan1, Pascal Steullet2, Yasser Alemán-Gómez3, Raoul Jenni2, Martin Cleusix2, Luis Alameda4, Kim Do2, Philippe Conus5, Patric Hagmann3, Daniella Dwir2, Paul Klauser2, Ileana Jelescu1
Institutions:
1Department of Radiology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Vaud, 2Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and UNIL, Lausanne, Vaud, 3Lausanne University Hospital and University of Lausanne (CHUV-UNIL), Lausanne, Vaud, 4Service of General Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Vaud, 5Service of General Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland, Lausanne, Vaud
First Author:
Tommaso Pavan
Department of Radiology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL)
Lausanne, Vaud
Department of Radiology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL)
Lausanne, Vaud
Co-Author(s):
Pascal Steullet
Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and UNIL
Lausanne, Vaud
Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and UNIL
Lausanne, Vaud
Yasser Alemán-Gómez
Lausanne University Hospital and University of Lausanne (CHUV-UNIL)
Lausanne, Vaud
Lausanne University Hospital and University of Lausanne (CHUV-UNIL)
Lausanne, Vaud
Raoul Jenni
Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and UNIL
Lausanne, Vaud
Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and UNIL
Lausanne, Vaud
Martin Cleusix
Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and UNIL
Lausanne, Vaud
Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and UNIL
Lausanne, Vaud
Kim Do
Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and UNIL
Lausanne, Vaud
Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and UNIL
Lausanne, Vaud
Philippe Conus
Service of General Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland
Lausanne, Vaud
Service of General Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland
Lausanne, Vaud
Daniella Dwir
Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and UNIL
Lausanne, Vaud
Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and UNIL
Lausanne, Vaud
Paul Klauser
Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and UNIL
Lausanne, Vaud
Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and UNIL
Lausanne, Vaud
Ileana Jelescu
Department of Radiology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL)
Lausanne, Vaud
Department of Radiology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL)
Lausanne, Vaud
Introduction:
Recent research highlights the key role of white matter (WM) in early psychosis (EP) and schizophrenia (SZ), reporting volumetric and structural changes across the brain of people suffering from psychosis (Kelly, 2018). In this work, we aim to investigate the neuroinflammation hypothesis in SZ, believed to produce WM alterations following inflammation dysregulation (Wijtenburg & Rowland, 2023). Thus, we tested the association between four functional metabolites quantified in the medial prefrontal cortex (mPFC) using Magnetic Resonance Spectroscopy (MRS), and possibly involved in neuroinflammation: myo-Inositol (myo-Ins), total Choline (tCho), Glutamate (Glu) and Glutathione (GSH), and WM microstructure estimates obtained from Diffusion Kurtosis Imaging (DKI) and from a biophysical model of WM providing compartment-specific microstructure features (WM tract integrity - Watson, WMTI-W; Jespersen, 2018).
Methods:
Diffusion MRI and single-voxel MRS data were acquired for 23 EP patients (25±5 y/o) and 41 healthy controls (HC) (25±5 y/o). dMRI: Diffusion-weighted images were acquired using a PGSE-EPI sequence (TE/TR = 0.144/6.1s, 2-mm isotropic resolution, 15 b-values, range 0-8000 s/mm2, Cartesian q-space coverage totaling 129 images). After standard preprocessing (Ades-Aron, 2018), diffusion and kurtosis scalar maps (axial, mean, radial diffusivity and kurtosis, and fractional anisotropy (MD, AD, RD, FA, MK, AK, RK) were estimated from data with b≤2500 s/mm2. The WMTI-W model parameters (axonal water fraction f, intra-axonal diffusivity Da, extra-axonal parallel and perpendicular diffusivities De,//, De,⊥, and fiber orientation coherence c2) were computed using an in-house Python script. MRS: Metabolite concentrations were quantified as described in Xin et al. (2016). Statistics: MRS metabolite relationships with the voxel-wise dMRI metrics in the WM skeleton were investigated via FSL's Tract-Based Spatial Statistics (TBSS), correcting for age and sex.
Results:
Myo-Inositol showed the widest association with the dMRI metrics across the WM. It was negatively associated with diffusivities AD, RD, MD (Fig. 1A), positively with RK, MK (p<0.0005, Fig. 1C) and the slope of the association differed between EP and HC (MD, MK p<0.00045, Fig. 1B, C). Similarly, myo-Ins was positively associated with the axonal water fraction, f (p<0.0001, Fig. 1E), and negatively with the parallel extra-axonal diffusivity, De,// (p<0.0001, Fig. 1G). Both slopes differed from HC (f, De,//: p<0.00016, Fig. 1F, H). Total Choline had the second largest number of significant association clusters. MD and De,// (p<0.0001, Fig. 2A,B) showed a small cluster of negative associations with tCho concentrations in EP, both slopes differed from HC (p<0.00028, Fig. 2B,D). Glutamate showed less associations with WM microstructure. The only cluster larger than 20 voxels revealed lower AK (p<0.0001) with higher Glu in EP. GSH: No significant clusters were found. Combined: When testing each metabolite while co-varying for the others, myo-Ins suppressed the other metabolite associations, implying that the effect observed is common to all metabolites and is most pronounced with myo-Ins.
Conclusions:
We mainly observed a negative association in diffusivities (MD, De,//) paired with a positive association in cellularity metrics (MK, f) to myo-Ins and tCho in EP. Myo-Ins has three main roles, as constituent of the lipids (phosphoglycerides) in biomembranes, as regulator of the cellular volume via osmolytic action and as intracellular second messenger system. Similarly, tCho is utilised for phospholipids synthesis and strongly correlates with cell density indicating a role as membrane and myelin marker (Rae. 2014). In light of this, our results suggest the association of myo-Ins and tCho to dMRI metrics may be driven by membrane density, reflecting localized cellular density, which may increase with inflammation.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity
Novel Imaging Acquisition Methods:
Diffusion MRI
MR Spectroscopy
Keywords:
Astrocyte
Demyelinating
MR SPECTROSCOPY
Myelin
Psychiatric
Psychiatric Disorders
Schizophrenia
White Matter
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - psychosis
1|2Indicates the priority used for review
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Provide references using APA citation style.
Jespersen, S. N., Olesen, J. L., Hansen, B., & Shemesh, N. (2017). Diffusion time dependence of microstructural parameters in fixed spinal cord. NeuroImage, 182, 329–342. https://doi.org/10.1016/j.neuroimage.2017.08.039
Kelly, S., Jahanshad, N., Zalesky, A., Kochunov, P., Agartz, I., Alloza, C., Andreassen, O. A., Arango, C., Banaj, N., Bouix, S., Bousman, C. A., Brouwer, R. M., Bruggemann, J., Bustillo, J., Cahn, W., Calhoun, V., Cannon, D., Carr, V., Catts, S., & Chen, J. (2017). Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group. Molecular Psychiatry, 23(5), 1261–1269. https://doi.org/10.1038/mp.2017.170
Rae, C. D. (2013). A Guide to the Metabolic Pathways and Function of Metabolites Observed in Human Brain 1H Magnetic Resonance Spectra. Neurochemical Research, 39(1), 1–36. https://doi.org/10.1007/s11064-013-1199-5
Wijtenburg, S. A., & Rowland, L. M. (2023). Schizophrenia spectrum disorders. Advances in Magnetic Resonance Technology and Applications, 469–487. https://doi.org/10.1016/b978-0-323-91771-1.00008-3
Xin, L., Ralf Mekle, Fournier, M., Baumann, P. S., Ferrari, C., Alameda, L., Jenni, R., Lu, H., Schaller, B., Cuenod, M., Philippe Conus, Gruetter, R., & Q, K. (2016). Genetic Polymorphism Associated Prefrontal Glutathione and Its Coupling With Brain Glutamate and Peripheral Redox Status in Early Psychosis. 42(5), 1185–1196. https://doi.org/10.1093/schbul/sbw038