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

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.

Schizophrenia Increases Variability of the Central Antioxidant System: A Meta-Analysis of Variance From MRS Studies of Glutathione

“…(2) some individuals from the putative GSH-excess subgroup (or redox sufficient) may still progress to chronic or resistant stages of schizophrenia. In the context of our current observation of increased variation in GSH levels in schizophrenia, the extant literature supports the model of 'Primary GSH Deficit' (Figure 2) in some individuals with schizophrenia; this deficit may be pathoplastic and influence the treatment outcomes [e.g., treatment resistance (47)] among patients. Demonstrating bimodal distribution of GSH levels in large samples of patients in early illness stages, in conjunction with clinical and functional validation of the distributed values, will add substantial evidence to our claim regarding the existence of subgroups (16).…”

Neuroimaging in schizophrenia: A review article

“…The group led by Akira Sawa utilized a multimodal longitudinal cohort to investigate biomarkers for treatment-resistant psychosis. Their study observed reductions in hippocampal volumes and glutathione (GSH) levels in the anterior cingulate cortex in treatment resistent patients compared to responsive patients ( Yang et al, 2022 ). Interestingly, they found that a combination of multimodal biomarkers could lead to a better prediction of treatment resistance than any individual biomarker.…”

A redux of schizophrenia research in 2021

“…Prediction of antipsychotic response in schizophrenia is slowly moving from clinical and socio-demographic towards biological markers such as inflammation and resting state functional connectivity ( Enache et al, 2021 ; Mehta et al, 2021 ; Mongan et al, 2020 ; Yang et al, 2021 ). This is a first step towards identifying disease-biology-based predictive biomarkers that can subsequently help in (a) the early identification and treatment of resistant schizophrenia, (b) treatment planning and resource allocation, and (c) delivering personalized treatments ( Kraguljac et al, 2021 ).…”