Multi-omics of human plasma reveals molecular features of dysregulated inflammation and accelerated aging in schizophrenia

Abstract

Schizophrenia is a devastating psychiatric illness that detrimentally affects a significant portion of the worldwide population. Aging of schizophrenia patients is associated with reduced longevity, but the potential biological factors associated with aging in this population have not yet been investigated in a global manner. To address this gap in knowledge, the present study assesses proteomics and metabolomics profiles in the plasma of subjects afflicted with schizophrenia compared to non-psychiatric control patients over six decades of life. Global, unbiased analyses of circulating blood plasma can provide knowledge of prominently dysregulated molecular pathways and their association with schizophrenia, as well as features of aging and gender in this disease. The resulting data compiled in this study represent a compendium of molecular changes associated with schizophrenia over the human lifetime. Supporting the clinical finding of schizophrenia’s association with more rapid aging, both schizophrenia diagnosis and age significantly influenced the plasma proteome in subjects assayed. Schizophrenia was broadly associated with prominent dysregulation of inflammatory and metabolic system components. Proteome changes demonstrated increased abundance of biomarkers for risk of physiologic comorbidities of schizophrenia, especially in younger individuals. These findings advance our understanding of the molecular etiology of schizophrenia and its associated comorbidities throughout the aging process.

Schizophrenia as metabolic disease. What are the causes?

“…The metabolic profile of SZ showed accelerated ageing and inflammatory response. These data are supported by proteomic studies ( Campeau et al 2022 ). An experimental study examined the metabolic profiles of chronically hospitalised SZ candidates and showed lower glutamate and urea cycle metabolism (Okamoto et al 2021 ).…”

Current State of Fluid Lipid Biomarkers for Personalized Diagnostics and Therapeutics in Schizophrenia Spectrum Disorders and Related Psychoses: A Narrative Review

“…This integrative approach may also interpret new connections between tissue types, including relationships between CSF and blood lipid levels, not seen by chance or simple associations, leading to the discovery of new biomarkers and therapeutics. Although the integration of lipidomics datasets is still in its infancy, some of the analyses reported here have applied integrative strategies and demonstrated new functional relationships of lipids with proteins, metabolic pathways, and gene expression, previously unknown in psychiatric conditions ( 78 , 100 , 102 ).…”

“…In a recent study, Campeau et al . ( 100 ) performed a multi-omics analysis of plasma samples from individuals with SCZ and healthy controls (aged 28–74 years) to examine age- and disease-related effects on various proteins and metabolites. The majority of altered metabolites between SCZ and healthy controls were classified as lipids.…”

The Host-Microbiome Response to Hyperbaric Oxygen Therapy in Ulcerative Colitis Patients

“…Fifty micrograms of peptide was dried down and labeled using TMT10plex Isobaric Labeling reagents (catalog #90406) as described in Campeau et al. 49 Labeled peptides were subsequently dried down, desalted, and fractionated using high pH reverse phase fractionation (Thermo Ultimate 3000 HPLC off-line fraction collector and c18 column, 37 s per well, 96 wells total). After fractionation samples were concatenated into 24 samples.…”