Redox and Immune Signaling in Schizophrenia: New Therapeutic Potential

Abstract

Redox biology and immune signaling play major roles in the body, including in brain function. A rapidly growing literature also suggests that redox and immune abnormalities are implicated in neuropsychiatric conditions such as schizophrenia, bipolar disorder, autism, and epilepsy. In this article we review this literature, its implications for the pathophysiology of schizophrenia, and the potential for development of novel treatment interventions targeting redox and immune signaling. Redox biology and immune signaling in the brain are complex and not fully understood; in addition, there are discrepancies in the literature, especially in patient-oriented studies. Nevertheless, it is clear that abnormalities arise in schizophrenia from an interaction between genetic and environmental factors during sensitive periods of brain development and these abnormalities disrupt local circuits and long-range connectivity. Interventions that correct these abnormalities may be effective in normalizing brain function in psychotic disorders, especially in early phases of illness.

Sleep, mood disorders, and the ketogenic diet: potential therapeutic targets for bipolar disorder and schizophrenia

“…This oxidative stress can also result in mitochondrial dysfunction, another potential factor in bipolar disorder ( 5 , 6 ). Redox homeostasis is crucial not only for containing tissue damage over time but also for maintaining appropriate signaling in specific biochemical pathways ( 81 ). Redox dysregulation is also notably regarded as a pivotal environmental risk factor in the neurodevelopmental context of schizophrenia ( 7 ).…”

“…Moreover, prolonged oxidative stress in the circuitry of neurotransmitters, e.g., parvalbumin interneurons in GABAergic circuits, have been identified in schizophrenia and bipolar disorder ( 84 – 86 ). This implies that redox dysregulation can be regarded as a notable environmental risk factor for neuronal dysfunction in psychiatric diseases which may relate to psychotic symptoms ( 5 , 7 , 81 ).…”

Neuroinflammation and schizophrenia – is there a link?

“…Consequently, the review by Dwir et al. (2023) underscores redox and immune signaling as critical therapeutic targets in schizophrenia ( 46 ).…”

“…Williams et al (2022) identified a significant correlation between genetically determined IL-6 levels and gray matter volumes in the frontotemporal cortex of schizophrenia patients (45). Consequently, the review by Dwir et al (2023) underscores redox and immune signaling as critical therapeutic targets in schizophrenia (46).…”

Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescents

“…Adolescence is a highly metabolically demanding period [ 18 ], rendering the brain potentially sensitive to the imbalance between antioxidant capacity and reactive oxygen species (ROS) leading to oxidative stress (OxS) [ 19 ]. Preclinical findings indicate increased vulnerability of the brain to redox dysregulation during peripuberty, compared to later developmental stages [ 20 , 21 ].…”