Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia?

Schizophrenia continues to be an illness with poor outcome. Most mechanistic changes occur many years before the first episode of schizophrenia; these are not reversible after the illness onset. A developmental mechanism that is still modifiable in adult life may center on intracortical glutathione (GSH). A large body of pre-clinical data has suggested the possibility of notable GSH-deficit in a subgroup of patients with schizophrenia. Nevertheless, studies of intracortical GSH are not conclusive in this regard. In this review, we highlight the recent ultra-high field magnetic resonance spectroscopic studies linking GSH to critical outcome measures across various stages of schizophrenia. We discuss the methodological steps required to conclusively establish or refute the persistence of GSH-deficit subtype and clarify the role of the central antioxidant system in disrupting the brain structure and connectivity in the early stages of schizophrenia. We propose in-vivo GSH quantification for patient selection in forthcoming antioxidant trials in psychosis. This review offers directions for a promising non-dopaminergic early intervention approach in schizophrenia.

Progressive changes in descriptive discourse in First Episode of Schizophrenia: A longitudinal computational semantics study

Computational semantics, a branch of computational linguistics, involves automated meaning analysis that relies on how words occur together in natural language. This offers a promising tool to study schizophrenia. At present, we do not know if these word level choices in speech are sensitive to illness stage (i.e. acute untreated vs. stable established state), track cognitive deficits in major domains (e.g. cognitive control, processing speed) and relate to established dimensions of formal thought disorder. Here we study samples of descriptive discourse in patients with untreated first episode of schizophrenia (x̅ 2.8 days of lifetime daily dose exposure) and healthy subjects (246 samples of 1-minute speech; n=82, FES=46, HC=36) using a co-occurrence based vector embedding of words. We obtained six-month follow-up data in a subsample (99 speech samples, n=33, FES=20, HC=13). At baseline, the evidence for higher semantic similarity during descriptive discourse in FES was substantial, compared to null difference ( Bayes Factor =6 for full description; 32 for 10-words window). Moreover, the was a linear increase in semantic similarity with time in FES compared to HC (Bayes Factor= 6). Higher semantic similarity related to lower Stroop performance (accuracy and interference, response time), and was present irrespective of the severity of clinically ascertained thought disorder. Automated analysis of non-intrusive 1-minute speech samples provides a window on cognitive control deficits, role functioning and tracks latent progression in schizophrenia.

Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia?

Schizophrenia continues to be an illness with poor outcome. Most mechanistic changes occur many years before the first episode of schizophrenia; these are not reversible after the illness onset. A developmental mechanism that is still modifiable in adult life may center on intracortical glutathione (GSH). A large body of pre-clinical data has suggested the possibility of notable GSH-deficit in a subgroup of patients with schizophrenia. Nevertheless, studies of intracortical GSH are not conclusive in this regard. In this review, we highlight the recent ultra-high field magnetic resonance spectroscopic studies linking GSH to critical outcome measures across various stages of schizophrenia. We discuss the methodological steps required to conclusively establish or refute the persistence of GSH-deficit subtype and clarify the role of the central antioxidant system in disrupting the brain structure and connectivity in the early stages of schizophrenia. We propose in-vivo GSH quantification for patient selection in forthcoming antioxidant trials in psychosis. This review offers directions for a promising non-dopaminergic early intervention approach in schizophrenia.

Monoamine Oxidase as a Potential Biomarker of the Efficacy of Treatment of Mental Disorders

The review summarizes the results of our own studies and published data on the biological markers of psychiatric disorders, with special emphasis on the activity of platelet monoamine oxidase. Pharmacotherapy studies in patients with the mixed anxiety-depressive disorder and first episode of schizophrenia have shown that the activity of platelet monoamine oxidase could serve as a potential biomarker of the efficacy of therapeutic interventions in these diseases.