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

Kun Yang, Luisa Longo, Zui Narita, Nicola Cascella, Frederick C. Nucifora Jr., Jennifer M. Coughlin, Gerald Nestadt, Thomas W. Sedlak, Marina Mihaljevic, Min Wang, Anshel Kenkare, Anisha Nagpal, Mehk Sethi, Alexandra Kelly, Pasquale Di Carlo, Vidyulata Kamath, Andreia Faria, Peter Barker, Akira Sawa
doi: https://doi.org/10.1101/2021.05.03.442450
Kun Yang
aDepartments of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Luisa Longo
aDepartments of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Zui Narita
aDepartments of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Nicola Cascella
aDepartments of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Frederick C. Nucifora Jr.
aDepartments of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Jennifer M. Coughlin
aDepartments of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Gerald Nestadt
aDepartments of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Thomas W. Sedlak
aDepartments of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Marina Mihaljevic
aDepartments of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Min Wang
eDepartments of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Anshel Kenkare
aDepartments of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Anisha Nagpal
gDepartment of Public Health Studies, Johns Hopkins University Zanvyl Krieger School of Arts and Sciences, Baltimore, MD 21218, USA
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Mehk Sethi
hDepartment of Applied Math and Statistics, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA
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Alexandra Kelly
aDepartments of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Pasquale Di Carlo
aDepartments of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Vidyulata Kamath
aDepartments of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Andreia Faria
eDepartments of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Peter Barker
eDepartments of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
jF. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205, USA
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Akira Sawa
aDepartments of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
bDepartments of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
cDepartments of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
dDepartments of Genetic Medicine, and Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
fDepartment of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA
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  • For correspondence: asawa1@jhmi.edu
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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 138 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 significant reduction in the volumes of the hippocampus (HP) and superior frontal gyrus (SFG), and a significant 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 trait 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.

Competing Interest Statement

The authors have declared no competing interest.

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Posted May 04, 2021.
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A multimodal study of a first episode psychosis cohort: potential markers of antipsychotic treatment resistance
Kun Yang, Luisa Longo, Zui Narita, Nicola Cascella, Frederick C. Nucifora Jr., Jennifer M. Coughlin, Gerald Nestadt, Thomas W. Sedlak, Marina Mihaljevic, Min Wang, Anshel Kenkare, Anisha Nagpal, Mehk Sethi, Alexandra Kelly, Pasquale Di Carlo, Vidyulata Kamath, Andreia Faria, Peter Barker, Akira Sawa
bioRxiv 2021.05.03.442450; doi: https://doi.org/10.1101/2021.05.03.442450
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A multimodal study of a first episode psychosis cohort: potential markers of antipsychotic treatment resistance
Kun Yang, Luisa Longo, Zui Narita, Nicola Cascella, Frederick C. Nucifora Jr., Jennifer M. Coughlin, Gerald Nestadt, Thomas W. Sedlak, Marina Mihaljevic, Min Wang, Anshel Kenkare, Anisha Nagpal, Mehk Sethi, Alexandra Kelly, Pasquale Di Carlo, Vidyulata Kamath, Andreia Faria, Peter Barker, Akira Sawa
bioRxiv 2021.05.03.442450; doi: https://doi.org/10.1101/2021.05.03.442450

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