Poster No:
506
Submission Type:
Abstract Submission
Authors:
Julia Schulz1, Melissa Thalhammer1, Moritz Bonhoeffer1, Viktor Neumaier1, Yifan Mayr2, Igor Yakushev2, Felix Brandl3, Christian Sorg1
Institutions:
1Department of Neuroradiology, School of Medicine, Technical University of Munich (TUM), Munich, Bavaria, 2Department of Nuclear Medicine, School of Medicine, Technical University of Munich (TUM), Munich, Bavaria, 3Department of Psychiatry, School of Medicine, Technical University of Munich (TUM), Munich, Germany
First Author:
Julia Schulz
Department of Neuroradiology, School of Medicine, Technical University of Munich (TUM)
Munich, Bavaria
Co-Author(s):
Melissa Thalhammer
Department of Neuroradiology, School of Medicine, Technical University of Munich (TUM)
Munich, Bavaria
Moritz Bonhoeffer
Department of Neuroradiology, School of Medicine, Technical University of Munich (TUM)
Munich, Bavaria
Viktor Neumaier
Department of Neuroradiology, School of Medicine, Technical University of Munich (TUM)
Munich, Bavaria
Yifan Mayr
Department of Nuclear Medicine, School of Medicine, Technical University of Munich (TUM)
Munich, Bavaria
Igor Yakushev
Department of Nuclear Medicine, School of Medicine, Technical University of Munich (TUM)
Munich, Bavaria
Felix Brandl
Department of Psychiatry, School of Medicine, Technical University of Munich (TUM)
Munich, Germany
Christian Sorg
Department of Neuroradiology, School of Medicine, Technical University of Munich (TUM)
Munich, Bavaria
Introduction:
Schizophrenia is a severe psychiatric disorder affecting approximately 1% of the global population. It is characterized by positive, negative, and cognitive symptoms that frequently follow a chronic course of psychotic episodes and phases of remission of psychotic symptoms (McCutcheon, 2020). The dopamine hypothesis remains a leading model of schizophrenia's pathophysiology, postulating that elevated dopamine levels in subcortical and limbic structures contribute to positive symptoms (Avram, 2019; Fusar-Poli & Meyer-Lindenberg, 2013; Howes & Kapur, 2009). Neuromelanin-sensitive (NM-) MRI emerged as a promising tool to quantify long-term dopamine metabolism in the substantia nigra pars compacta and ventral tegmental area (Cassidy, 2019; Schulz, 2022). Recent meta-analyses suggest elevated neuromelanin levels in the substantia nigra in schizophrenia, particularly in patients with severe psychotic symptoms (Wieland, 2021). However, the relationship of neuromelanin levels in substantia nigra and ventral tegmental area with distinct disease states (i.e., psychosis vs. psychotic remission) in schizophrenia remains elusive.
Methods:
We acquired a longitudinal dataset including 20 healthy controls and 25 patients with schizophrenia during psychosis, along with 17 follow-up scans for controls and 19 for patients in remission. The outcome measure, neuromelanin MRI contrast-to-noise ratio (CNR), was calculated as the ratio of signal intensity in neuromelanin-rich regions to that of a reference region (crus cerebri).The images were processed using the toolbox developed by Wengler et al. (Wengler, 2020). Preprocessing steps included motion correction, spatial normalization, and smoothing. A CNR map for each ROI was generated as the signal difference in NM-MRI signal intensity from the signal intensity in the crus cerebri. To evaluate the effects of group and time, we employed a general linear model with group and session as factors. Pairwise comparisons were conducted using Tukey's post hoc test.
Results:
In the whole substantia nigra, there was a significant effect of group (F = 8.10, p = 0.006), with schizophrenia patients in psychosis (SCZ-01) exhibiting higher CNR compared to healthy controls (HC-01, p = 0.004), and patients in remission (SCZ-02) showing higher CNR compared to controls at follow-up (HC-02, p = 0.05). Similar results were observed for the pars compacta subregion of substantia nigra, with higher CNR in SCZ-01 compared to HC-01 (p = 0.04). In the ventral tegmental area, group effects approached significance (F = 3.64, p = 0.06). Across all regions, no significant effects of session or group-by-session interactions were observed.
Conclusions:
We could replicate the findings of higher neuromelanin levels in the substantia nigra during psychosis in schizophrenia compared to healthy controls. Interestingly, our results suggest that neuromelanin levels remain stable across disease stages, with no significant differences between psychosis and psychotic remission in schizophrenia. This implies that midbrain dopaminergic dysfunction in schizophrenia is persistent throughout the course of the illness, rather than fluctuating with disease state, at least not within our period of observation, since neuromelanin changes only in the long term. These findings highlight the potential of NM-MRI as a non-invasive biomarker for schizophrenia, relevant to both psychosis and psychotic remission.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Novel Imaging Acquisition Methods:
Imaging Methods Other 2
Keywords:
Dopamine
MRI
Psychiatric Disorders
Schizophrenia
Other - Neuromelanin
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Resting state
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Patients
Was this research conducted in the United States?
No
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Yes
Were any animal research approved by the relevant IACUC or other animal research panel?
NOTE: Any animal studies without IACUC approval will be automatically rejected.
Not applicable
Please indicate which methods were used in your research:
Structural MRI
Other, Please specify
-
Neuromelanin-sensitive imaging
For human MRI, what field strength scanner do you use?
3.0T
Which processing packages did you use for your study?
SPM
Other, Please list
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ANTS
Provide references using APA citation style.
1. Avram, M., Brandl, F., Cabello, J., Leucht, C., Scherr, M., Mustafa, M., Leucht, S., Ziegler, S., & Sorg, C. (2019). Reduced striatal dopamine synthesis capacity in patients with schizophrenia during remission of positive symptoms. Brain, 142(6), 1813–1826. https://doi.org/10.1093/brain/awz093
2. Cassidy, C. M., Zucca, F. A., Girgis, R. R., Baker, S. C., Weinstein, J. J., Sharp, M. E., Bellei, C., Valmadre, A., Vanegas, N., Kegeles, L. S., Brucato, G., Kang, U. J., Sulzer, D., Zecca, L., Abi-Dargham, A., & Horga, G. (2019). Neuromelanin-sensitive MRI as a noninvasive proxy measure of dopamine function in the human brain. Proceedings of the National Academy of Sciences, 116(11), 5108–5117. https://doi.org/10.1073/pnas.1807983116
3. Fusar-Poli, P., & Meyer-Lindenberg, A. (2013). Striatal Presynaptic Dopamine in Schizophrenia, Part II: Meta-Analysis of [18F/11C]-DOPA PET Studies. Schizophrenia Bulletin, 39(1), 33–42. https://doi.org/10.1093/schbul/sbr180
4. Howes, O. D., & Kapur, S. (2009). The Dopamine Hypothesis of Schizophrenia: Version III--The Final Common Pathway. Schizophrenia Bulletin, 35(3), 549–562. https://doi.org/10.1093/schbul/sbp006
5. McCutcheon, R. A., Krystal, J. H., & Howes, O. D. (2020). Dopamine and glutamate in schizophrenia: Biology, symptoms and treatment. World Psychiatry, 19(1), 15–33. https://doi.org/10.1002/wps.20693
6. Schulz, J., Zimmermann, J., Sorg, C., Menegaux, A., & Brandl, F. (2022). Magnetic resonance imaging of the dopamine system in schizophrenia – A scoping review. Frontiers in Psychiatry, 13, 925476. https://doi.org/10.3389/fpsyt.2022.925476
7. Wengler, K., He, X., Abi-Dargham, A., & Horga, G. (2020). Reproducibility assessment of neuromelanin-sensitive magnetic resonance imaging protocols for region-of-interest and voxelwise analyses. NeuroImage, 208, 116457. https://doi.org/10.1016/j.neuroimage.2019.116457
8. Wieland, L., Fromm, S., Hetzer, S., Schlagenhauf, F., & Kaminski, J. (2021). Neuromelanin-Sensitive Magnetic Resonance Imaging in Schizophrenia: A Meta-Analysis of Case-Control Studies. Frontiers in Psychiatry, 12, 770282. https://doi.org/10.3389/fpsyt.2021.770282
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