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A multimodal study of a first episode psychosis cohort: potential markers of antipsychotic treatment resistance

Molecular Psychiatry volume 27, pages 1184–1191 (2022)Cite this article

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Abstract

Treatment resistant (TR) psychosis is considered to be a significant cause of disability and functional impairment. Numerous efforts have been made to identify the clinical predictors of TR. However, the exploration of molecular and biological markers is still at an early stage. To understand the TR condition and identify potential molecular and biological markers, we analyzed demographic information, clinical data, structural brain imaging data, and molecular brain imaging data in 7 Tesla magnetic resonance spectroscopy from a first episode psychosis cohort that includes 136 patients. Age, gender, race, smoking status, duration of illness, and antipsychotic dosages were controlled in the analyses. We found that TR patients had a younger age at onset, more hospitalizations, more severe negative symptoms, a reduction in the volumes of the hippocampus (HP) and superior frontal gyrus (SFG), and a reduction in glutathione (GSH) levels in the anterior cingulate cortex (ACC), when compared to non-TR patients. The combination of multiple markers provided a better classification between TR and non-TR patients compared to any individual marker. Our study shows that ACC-GSH, HP and SFG volumes, and age at onset, could potentially be biomarkers for TR diagnosis, while hospitalization and negative symptoms could be used to evaluate the progression of the disease. Multimodal cohorts are essential in obtaining a comprehensive understanding of brain disorders.

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Fig. 1: Box plots of glutathione (GSH) levels (water reference) in treatment resistant (TR) and non-TR patients.
Fig. 2: Classification models of treatment resistant (TR) and non-TR patients.

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Acknowledgements

This study is supported by the National Institutes 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 Brain and Behavior Research Foundation (to AS, KY). The original recruitment of study participants was partly funded by the Mitsubishi Tanabe Pharma Corporation. The authors thank Drs. Brian Caffo for kindly contributing to scientific discussions and feedback related to this work. The authors appreciate Ms. Yukiko Lema for research management and manuscript organization, and thank Dr. Melissa A Landek-Salgado for critical reading of the manuscript.

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Author notes

  1. Luisa Longo & Pasquale Di Carlo

    Present address: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy

  2. Min Wang

    Present address: College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China

  3. These authors contributed equally: Kun Yang, Luisa Longo.

Authors and Affiliations

  1. Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Kun Yang, Luisa Longo, Zui Narita, Nicola Cascella, Frederick C. Nucifora Jr, Jennifer M. Coughlin, Gerald Nestadt, Thomas W. Sedlak, Marina Mihaljevic, Anshel Kenkare, Alexandra Kelly, Vidyulata Kamath & Akira Sawa

  2. Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Min Wang, Andreia Faria & Peter Barker

  3. Department of Public Health Studies, Johns Hopkins University Zanvyl Krieger School of Arts and Sciences, Baltimore, MD, 21218, USA

    Anisha Nagpal

  4. Department of Applied Math and Statistics, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, 21218, USA

    Mehk Sethi

  5. Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA

    Pasquale Di Carlo

  6. F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, 21205, USA

    Peter Barker

  7. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Akira Sawa

  8. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA

    Akira Sawa

  9. Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Akira Sawa

  10. Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, 21205, USA

    Akira Sawa

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  1. Kun Yang
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Contributions

The current research was designed by AS. The analytic pipeline was designed by KY. The data were analyzed by KY, LL, ZN, AN, MS, and PDC. Data analysis and interpretation regarding clinical scales were assisted by NC and MM. Data analysis and interpretation regarding smell test were assisted by VK. Data analysis and interpretation regarding 7 T MRS data were assisted by MW and PB. Data analysis and interpretation regarding brain volume data were assisted by AF. Study participants were recruited and/or interviewed by NC, FCN, JMC, GN, TWS, AK (Kenkare), and AK (Kelly). The manuscript was drafted by KY, LL, and AS. All authors contributed to the discussion of the results and have approved the final manuscript to be published.

Corresponding author

Correspondence to Akira Sawa.

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Competing interests

The authors declare no competing interests. As noted in the acknowledgement section, 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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Yang, K., Longo, L., Narita, Z. et al. A multimodal study of a first episode psychosis cohort: potential markers of antipsychotic treatment resistance. Mol Psychiatry 27, 1184–1191 (2022). https://doi.org/10.1038/s41380-021-01331-7

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