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, 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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1184-1191
Number of pages8
JournalMolecular psychiatry
Issue number2
StatePublished - Feb 2022

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Molecular Biology


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