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Longitudinal changes in brain metabolites in healthy controls and patients with first episode psychosis: a 7-Tesla MRS study

Molecular Psychiatry volume 28, pages 2018–2029 (2023)Cite this article

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Abstract

Seven Tesla magnetic resonance spectroscopy (7T MRS) offers a precise measurement of metabolic levels in the human brain via a non-invasive approach. Studying longitudinal changes in brain metabolites could help evaluate the characteristics of disease over time. This approach may also shed light on how the age of study participants and duration of illness may influence these metabolites. This study used 7T MRS to investigate longitudinal patterns of brain metabolites in young adulthood in both healthy controls and patients. A four-year longitudinal cohort with 38 patients with first episode psychosis (onset within 2 years) and 48 healthy controls was used to examine 10 brain metabolites in 5 brain regions associated with the pathophysiology of psychosis in a comprehensive manner. Both patients and controls were found to have significant longitudinal reductions in glutamate in the anterior cingulate cortex (ACC). Only patients were found to have a significant decrease over time in γ-aminobutyric acid, N-acetyl aspartate, myo-inositol, total choline, and total creatine in the ACC. Together we highlight the ACC with dynamic changes in several metabolites in early-stage psychosis, in contrast to the other 4 brain regions that also are known to play roles in psychosis. Meanwhile, glutathione was uniquely found to have a near zero annual percentage change in both patients and controls in all 5 brain regions during a four-year follow-up in young adulthood. Given that a reduction of the glutathione in the ACC has been reported as a feature of treatment-refractory psychosis, this observation further supports the potential of glutathione as a biomarker for this subset of patients with psychosis.

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Fig. 1: Magnetic Resonance Spectroscopy (MRS) voxel localizations and representative spectra.
Fig. 2: Boxplots of the Annual Percentage Change (APC) in brain metabolites in the Anterior Cingulate Cortex (ACC).
Fig. 3: Boxplots of the Annual Percentage Change (APC) in glutathione.

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Acknowledgements

This study is supported by The National Institute of Mental Health Grants MH-092443 (to AS), MH-094268 (to AS), MH-105660 (to AS), and MH-107730 (to AS); foundation grants from Stanley (to AS), RUSK/S-R (to AS), and a NARSAD young investigator award from the Brain and Behavior Research Foundation (to AS, KY). Study recruitment was in part funded by Mitsubishi Tanabe Pharma Corporation, Japan. LP acknowledges support from the Tanna Schulich Chair of Neuroscience and Mental Health. The authors thank Yukiko Lema for suggestions, for formatting the figures and for her role in research management, and thank Dr. Melissa A Landek-Salgado for scientific and English editions.

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Authors and Affiliations

  1. Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Min Wang & Peter B. Barker

  2. College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China

    Min Wang

  3. F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA

    Peter B. Barker

  4. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Nicola G. Cascella, Jennifer M. Coughlin, Gerald Nestadt, Frederick C. Nucifora Jr, Thomas W. Sedlak, Alexandra Kelly, Akira Sawa & Kun Yang

  5. Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, USA

    Laurent Younes & Donald Geman

  6. Robarts Research Institution, University of Western Ontario, London, ON, Canada

    Lena Palaniyappan

  7. Department of Psychiatry, University of Western Ontario, London, ON, Canada

    Lena Palaniyappan

  8. Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, QC, Canada

    Lena Palaniyappan

  9. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Akira Sawa

  10. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA

    Akira Sawa

  11. Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Akira Sawa

  12. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Akira Sawa

  13. Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA

    Akira Sawa

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  1. Min Wang
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Contributions

The current research was designed by AS, PBB, and KY. The analytic pipeline was designed by KY, LY, and DG. The data was analyzed by MW and KY. Analysis results interpretation were assisted by NGC and LP. Clinical recruitment is supervised by AS. Study participants were recruited and/or interviewed by NGC, JMC, GN, FCN, TWS, and AK. The manuscript was drafted by MW, KY, AS and PBB. All authors contributed to the discussion of the results and have approved the final manuscript to be published.

Corresponding authors

Correspondence to Peter B. Barker, Akira Sawa or Kun Yang.

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Competing interests

LP receives book royalties from Oxford University Press and income from the SPMM MRCPsych course. LP has received investigator-initiated educational grants from Otsuka, Janssen, and Sunovion Canada and speaker fees from Otsuka and Janssen Canada, and the Canadian Psychiatric Association. The original recruitment of study participants was partly funded by Mitsubishi Tanabe Pharma Corporation. However, this company is not involved in this specific study.

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Wang, M., Barker, P.B., Cascella, N.G. et al. Longitudinal changes in brain metabolites in healthy controls and patients with first episode psychosis: a 7-Tesla MRS study. Mol Psychiatry 28, 2018–2029 (2023). https://doi.org/10.1038/s41380-023-01969-5

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