Erythrocyte glutathione levels as long-term predictor of transition to psychosis

Lavoie, Suzie; Berger, Maximus; Schlögelhofer, Monika; Mr, Schäfer; Rice, Simon; Sw, Kim; Hesse, Jana; McGorry, Patrick D.; Smesny, Stefan; Amminger, G. Paul

doi:10.1038/tp.2017.30

Cited by 31 publications

(17 citation statements)

References 39 publications

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“…Models for prediction of transition to psychosis involved blood-based (20,56,71), electrophysiological (57,68,72), and neuroanatomical data using white and/or gray matter volume (38,44,51) or gyrification measures (55). Clinical models were trained on prodromal positive and negative symptoms, functioning, and family risk associated with functional decline; the neurocognitive modality was based on executive functions and verbal IQ (41) or speech features (54,73).…”

Section: Effect Of Data Modalitymentioning

confidence: 99%

Individualized Diagnostic and Prognostic Models for Patients With Psychosis Risk Syndromes: A Meta-analytic View on the State of the Art

Sanfelici

Dwyer

Antonucci

et al. 2020

Biological Psychiatry

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BACKGROUND: The clinical high risk (CHR) paradigm has facilitated research into the underpinnings of help-seeking individuals at risk for developing psychosis, aiming at predicting and possibly preventing transition to the overt disorder. Statistical methods such as machine learning and Cox regression have provided the methodological basis for this research by enabling the construction of diagnostic models (i.e., distinguishing CHR individuals from healthy individuals) and prognostic models (i.e., predicting a future outcome) based on different data modalities, including clinical, neurocognitive, and neurobiological data. However, their translation to clinical practice is still hindered by the high heterogeneity of both CHR populations and methodologies applied. METHODS: We systematically reviewed the literature on diagnostic and prognostic models built on Cox regression and machine learning. Furthermore, we conducted a meta-analysis on prediction performances investigating heterogeneity of methodological approaches and data modality. RESULTS: A total of 44 articles were included, covering 3707 individuals for prognostic studies and 1052 individuals for diagnostic studies (572 CHR patients and 480 healthy control subjects). CHR patients could be classified against healthy control subjects with 78% sensitivity and 77% specificity. Across prognostic models, sensitivity reached 67% and specificity reached 78%. Machine learning models outperformed those applying Cox regression by 10% sensitivity. There was a publication bias for prognostic studies yet no other moderator effects. CONCLUSIONS: Our results may be driven by substantial clinical and methodological heterogeneity currently affecting several aspects of the CHR field and limiting the clinical implementability of the proposed models. We discuss conceptual and methodological harmonization strategies to facilitate more reliable and generalizable models for future clinical practice.

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Section: Effect Of Data Modalitymentioning

confidence: 99%

Individualized Diagnostic and Prognostic Models for Patients With Psychosis Risk Syndromes: A Meta-analytic View on the State of the Art

Sanfelici

Dwyer

Antonucci

et al. 2020

Biological Psychiatry

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“…, 2002). GSH is the major cellular redox regulator and antioxidant, protecting cells from damage induced by reactive oxygen species (Lavoie et al. , 2017), and is a neurotransmitter/modulator that binds to the N-methyl-D-aspartate receptor (Chin et al., 2006) involved in anxiety, fear, learning and memory (Janáky et al.…”

Section: Introductionmentioning

confidence: 99%

Effects of traffic noise exposure on corticosterone, glutathione and tonic immobility in chicks of a precocial bird

Flores

Penna

Wingfield

et al. 2019

Conservation Physiology

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Repeated exposure to traffic noise may be perceived as a succession of stressors, and therefore, noisy urban environments could lead to a state of chronic stress. In developing animals, glucocorticoids can have organizational effects on the hypothalamic–pituitary–adrenal axis in addition to the classic activation effects, so evaluating the effect of traffic noise during development is urgently needed. To our knowledge, to date six studies have investigated the effects of traffic noise on baseline corticosterone (CORT) and/or the stress response in birds during development; however, these studies were performed in nestling (altricial species), where confounding factors (e.g. communication between nestlings and parents) could mask the real impact of traffic noise on stress. In this study, we evaluated the effect of traffic noise (traffic noise group vs. rural noise group) on baseline levels of CORT and stress responses in chicks of a precocial bird species, the Japanese quail (Coturnix japonica). Because CORT can also decrease glutathione (GSH) levels (antioxidant and neurotransmitter/modulator), secondly by means of path analysis we investigated whether the strength of the association between CORT levels, GSH levels and tonic immobility (TI) varied in relation to treatment. We observed (i) similar baseline levels of CORT in both groups, (ii) a trend toward higher stress response in the traffic noise group (P = 0.08), (iii) similar TI duration in both groups, (iv) higher GSH levels in the traffic noise group and (v) differences in the strength and sign of the associations in relation to the treatment (traffic vs. rural). We conclude that the acoustic environment perceived during development has implications for physiology and behaviour; as more research is done on this topic, the need for sustainable urban planning will become clearer.

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“…Thus, many studies rely upon more accessible blood and cerebral spinal fluid samples to characterize the molecular underpinnings of neuropsychiatric conditions [14-23]. Although there is variability between subjects, multiple studies have reported a significant reduction of GSH in SZ in peripherally accessible tissues and fluids, such as blood [6, 18, 19, 24-29]. …”

Section: Introductionmentioning

confidence: 99%

Sulforaphane Augments Glutathione and Influences Brain Metabolites in Human Subjects: A Clinical Pilot Study

et al. 2017

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Schizophrenia and other neuropsychiatric disorders await mechanism-associated interventions. Excess oxidative stress is increasingly appreciated to participate in the pathophysiology of brain disorders, and decreases in the major antioxidant, glutathione (GSH), have been reported in multiple studies. Technical cautions regarding the estimation of oxidative stress-related changes in the brain via imaging techniques have led investigators to explore peripheral GSH as a possible pathological signature of oxidative stress-associated brain changes. In a preclinical model of GSH deficiency, we found a correlation between whole brain and peripheral GSH levels. We found that the naturally occurring isothiocyanate sulforaphane increased blood GSH levels in healthy human subjects following 7 days of daily oral administration. In parallel, we explored the potential influence of sulforaphane on brain GSH levels in the anterior cingulate cortex, hippocampus, and thalamus via 7-T magnetic resonance spectroscopy. A significant positive correlation between blood and thalamic GSH post- and pre-sulforaphane treatment ratios was observed, in addition to a consistent increase in brain GSH levels in response to treatment. This clinical pilot study suggests the value of exploring relationships between peripheral GSH and clinical/neuropsychological measures, as well as the influences sulforaphane has on functional measures that are altered in neuropsychiatric disorders.

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Erythrocyte glutathione levels as long-term predictor of transition to psychosis

Cited by 31 publications

References 39 publications

Individualized Diagnostic and Prognostic Models for Patients With Psychosis Risk Syndromes: A Meta-analytic View on the State of the Art

Individualized Diagnostic and Prognostic Models for Patients With Psychosis Risk Syndromes: A Meta-analytic View on the State of the Art

Effects of traffic noise exposure on corticosterone, glutathione and tonic immobility in chicks of a precocial bird

Sulforaphane Augments Glutathione and Influences Brain Metabolites in Human Subjects: A Clinical Pilot Study

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