Is T‐helper type 2 shift schizophrenia‐specific? Primary results from a comparison of related psychiatric disorders and healthy controls

Abstract

Aim: An imbalance between T-helper type 1 (Th1) and type 2 (Th2) cytokines has been implicated in schizophrenia, although empirical evidence is rare. The aim of this study was to examine if a Th1/Th2 imbalance occurs in schizophrenia and schizophrenia-related disorder.Methods: Twenty-six subjects with schizophrenia, 26 subjects with schizophrenia-related disorders, and 26 healthy controls were recruited. The Human Th1/Th2 Cytokine Cytometric Bead Array Kit-II was utilized to assess serum Th1/Th2 cytokines and ratios simultaneously. MANOVA was used to detect differences among the three diagnostic groups in distinct Th1/ Th2 cytokines/ratios. Pearson/Spearman correlations were used to examine the relationships between distinct Th1/Th2 cytokines/ratios and clinical/ psychopathological data in schizophrenia.Results: Interferon (IFN)-g/interleukin (IL)-4, IFN-g/ IL-10, IL-2/IL-4, and tumor necrosis factor (TNF)-a/IL-4 ratios were significantly decreased in schizophrenia, but not in schizophrenia-related disorders compared to healthy controls. IFN-g/IL-4 and IFN-g/ IL-10 in schizophrenia subjects positively correlated with age, but not in schizophrenia-related disorder subjects or in healthy controls. Conclusion:A clear Th2 shift was observed in schizophrenia, but not in schizophrenia-related disorders. The Th2 shift in schizophrenia appeared to be an aberrant developmental phenomenon.

Inflammation in Schizophrenia: Cytokine Levels and Their Relationships to Demographic and Clinical Variables

“…Our findings of elevated levels of TNF-α and IL-6 in schizophrenia are consistent with some studies, (15, 20–29, 35–39, 44, 47–62), but not others (20, 21, 23, 26, 30–45, 63–68, 78–81). We did not find a significant difference in IFN-γ levels between schizophrenia and HC groups, similar to several published studies (38, 67, 78–81). Only one study that reported lower IFN-γ levels in persons with schizophrenia than in HCs had more than 50 subjects in each group, but had limited generalizability as all the study participants were men and smoked fewer than 5 cigarettes per day (44).…”

“…IFN-γ is involved in lymphocyte activation and the kynurenine pathway of tryptophan metabolism, which may link inflammatory processes with glutamatergic and dopaminergic systems. Nine studies of IFN-γ reported lower levels (24, 44, 69–75), four found higher levels (29, 37, 76, 77), and six showed no difference in levels (38, 67, 78–81). …”

“…Normal aging affects CNS regeneration and repair processes, including dysregulation of TNF-α and IL-6 (82). TNF-α, IL-6 and IFN-γ blood levels have been shown to vary with age in healthy samples (24, 61, 81, 83), though findings in schizophrenia are mixed; with only one study of TNF-α levels(81), tree studies of IL-6 (24, 61, 81, 83), and one study of IFN-γ (15, 21, 39, 44, 45, 47, 52, 55) finding significant correlations between age and cytokine levels only in persons with schizophrenia. Although these findings are somewhat suggestive of a stronger correlation of age with cytokine levels in persons with schizophrenia than healthy comparison subjects, none of these studies directly compared the magnitude and direction of the correlations between those groups.…”

Kynurenines in CNS disease: regulation by inflammatory cytokines

“…Since IDO and KMO expression appear to be positively regulated by similar mechanisms, it would be interesting to determine whether KMO expression is similarly inhibited by IL-4 and/or IL-13, and whether such inhibition leads to overproduction of central KYNA. Such a hypothesis might be relevant to a role of cytokine-mediated KP dysregulation in schizophrenia, since a recent study of 26 schizophrenic patients and 26 control subjects found that the ratios of serum IFN-γ/IL-4, IFN-γ/IL-10, IL-2/IL-4, and TNF-α/IL-4 were significantly reduced in schizophrenic patients compared to controls (Chiang et al, 2013). These data support an emerging, though controversial hypothesis which proposes that schizophrenia is associated with a subtle shift from the production of Th1 cytokines, such as IFN-γ, IL-2, and TNF-α, toward the production of Th2 cytokines, such as IL-4, IL-10, and IL-6 [reviewed in Muller et al (2012)].…”

Assessment the Serum Level of IL6, IL10 versus Neuregulin 1 among Schizophrenic Patients in Iraq

“…Results are highly agreeable with a large bulk of studies with variable respects to the clinical stage of the disease and status of medical treatment or associated other parameters, among these Potvin et al, (19) later psychiatric assessments ,they concluded that higher levels of the systemic inflammatory marker IL-6 in childhood are associated with an increased risk of developing schizophrenia in young adulthood. Chiang et al, (20) found that the IL6 level in schizophrenic patient, and control subjects were not significantly distinguishable P= 0.93. On the other hand serum IL10 showed only a marginal and statistically insignificant increase P=0.74, in cases with schizophrenia mean 322.3pg/ml when compared to both healthy and relative groups (mean 310.8 and 302.5 pg/ml) respectively P=0.74.…”