Inflammation and the two-hit hypothesis of schizophrenia

Abstract

The high societal and individual cost of schizophrenia necessitates finding better, more effective treatment, diagnosis, and prevention strategies. One of the obstacles in this endeavor is the diverse set of etiologies that comprises schizophrenia. A substantial body of evidence has grown over the last few decades to suggest that schizophrenia is a heterogeneous syndrome with overlapping symptoms and etiologies. At the same time, an increasing number of clinical, epidemiological, and experimental studies have shown links between schizophrenia and inflammatory conditions. In this review, we analyze the literature on inflammation and schizophrenia, with a particular focus on comorbidity, biomarkers, and environmental insults. We then identify several mechanisms by which inflammation could influence the development of schizophrenia via the two-hit hypothesis. Lastly, we note the relevance of these findings to clinical applications in the diagnosis, prevention, and treatment of schizophrenia.

Meta-analyses of 10 polymorphisms associated with the risk of schizophrenia

“…Environment and genetic factors play significant roles in SCZ (3)(4)(5). Environmental factors, including redox imbalance (4), inflammation (6) or obstetrical complications (7), have been reported to be associated with SCZ. Family, twin and adoption studies have shown that the genetic components increased the risk of SCZ (8,9).…”

Nonsteroidal Anti-inflammatory Drugs and 5-HT3Serotonin Receptor Antagonists as Innovative Antipsychotic Augmentation Treatments for Schizophrenia

“…Inflammatory markers have been identified in plasma as well as brain before and during the onset of psychotic symptoms in schizophrenia [3][4][5] ; if these contribute to the disease process, then anti-inflammatory treatments may attenuate the severity of schizophrenia. 6 5-HT 3 receptors are widely distributed in the brain, including in limbic and frontal cortical areas.…”

Serum gamma-glutamyltransferase is associated with future risk of psychosis - A prospective cohort study

“…Emerging evidence also suggests that inflammatory processes may be involved in the etiopathogenesis of psychosis. (Feigenson et al, 2014) We therefore hypothesized that GGT will be linked to the development of psychosis. In this context, we aimed to assess the association of GGT with risk of psychosis, using a population-based cohort of 2,341 men free from any apparent mental illness at baseline from eastern Finland.…”

“…Over the last few decades, emerging evidence suggests that chronic inflammatory processes (Benros et al, 2011;Feigenson et al, 2014) as well as oxidative stress (Owe-Larsson et al, 2011) may be involved in the pathogenesis of psychotic disorders. Whether GGT has a direct role in the pathogenesis or may just be a marker of underlying pathology, is not clear.…”