Linking Systems-Level Redox Measurements of Oxidative Stress to Psychiatric Symptomology

Description

Inflammation and oxidative stress (OxSt) appear to have important links to mental health disorders, yet there is no simple generally-accepted measurement to quantify OxSt. Previously, a redox-based iridium-reducing capacity assay (Ir-RCA) that involves a 1-hour sample incubation to generate an end-point optical measurement showed a promising relationship to clinical assessments of schizophrenia symptom severity and responses to stressors or interventions. Here, we report the dimensionality of the Ir-RCA can be increased by: measuring the decay of the optical signal during the 1-hour assay incubation; and characterizing this time series using simple curve-fitting models to extract quantifiable signal metrics. We evaluated this approach using serum samples from a cross-sectional clinical study with a subpopulation of persons diagnosed with schizophrenia and sensitive to gluten but without Celiac’s disease (N=38). This subgroup is known to be immune system dysregulated and have prominent negative symptoms (e.g., anhedonia or asociality). Replicate serum measurements spaced weeks apart showed intra-class correlation coefficients for most metrics to exceed 0.8 which indicates these metrics are reliable measures of stable features of the sample. Numerous correlations were observed between various subjective clinical symptom assessments and objectively-measured Ir-RCA metrics. We believe this work is important because it demonstrates that redox-based measurements can provide valuable pathophysiological information especially relevant for detecting immune system and redox dysregulations. Potentially, such redox measurements could provide movable targets for disease management that extend beyond mental health. Also, the electronic format of such measurements may eventually enable such redox-measurements to be integrated into emerging digital phenotyping approaches.

Categories

Funders

• Defense Threat Reduction Agency

  Office of the Secretary of Defense

  Fort Belvoir

  Grant ID: HDTRA1-19-0021
• Gordon and Betty Moore Foundation

  Palo Alto

  Grant ID: 11395
• National Institute of Mental Health

  National Institutes of Health

  Bethesda

  Grant ID: R01MH113617

Licence