Inflammation in psychotic disorders: A population-based study

Abstract

We investigated inflammatory markers in psychotic disorders and their association with metabolic comorbidity, antipsychotic medication, smoking, alcohol use, physical condition, and mood. From the population-based Finnish Health 2000 study, we identified all persons with schizophrenia (n = 45), other nonaffective psychosis (ONAP) (n = 57), affective psychosis (n = 37) and chose controls matched by age, sex, and region of residence. We found that persons with schizophrenia had significantly higher sIL-2Rα, IL-1RA and C-reactive protein (CRP), persons with ONAP significantly higher IL-1RA and CRP and persons with affective psychosis almost significantly higher TNF-α compared to their matched controls. Current antipsychotic use was associated with elevated IL-1RA and CRP. After taking metabolic and lifestyle-related variables that associated with inflammatory markers into account, only antipsychotic medication remained associated with elevated IL-1RA and TNF-α which are markers related to the activation of innate immune system. CRP was influenced by both antipsychotic medication and nonaffective psychosis. sIL-2Rα, a marker of T-cell activation, was associated with depressive symptoms, schizophrenia, and affective psychosis. We conclude that in persons with psychotic disorders, activation of mononuclear phagocyte system was mostly related to metabolic comorbidity and antipsychotic medication use, whereas T-cell activation had a more direct relationship with both psychotic disorders and depressive symptoms.

Introduction

Inflammation and immunity may be involved in the etiology and pathogenesis of schizophrenia and major mood disorders (Ganguli et al., 1994, Miller et al., 2009, Drexhage et al., 2010). There is evidence of both proinflammatory activation of the innate immune system and an activation of the T-cells of the adaptive immune system in both schizophrenia and bipolar disorder (Drexhage et al., 2010). This activation is reflected in alterations in circulating inflammatory cytokines (Potvin et al., 2008, Brietzke et al., 2009, Miller et al., 2009).

Elevated cytokine levels might lead to psychiatric symptoms through several mechanisms. Cytokines are involved in neuronal cell survival (de Araujo et al., 2009), neural stem cell renewal, differentiation and brain repair (Bauer, 2009), and in monoamine neurotransmitter metabolism (Miller et al., 2009). Some cytokines have stressor-like effects on CNS, including changes in tryptophan metabolism, hypothalamo–pituitary–adrenocortical axis, and brain-derived neurotrophic factor expression (Dantzer et al., 2008, Miller et al., 2009).

However, elevated cytokine levels might also reflect general medical comorbidity and lifestyle-related factors in psychotic disorders. Schizophrenia and other psychotic disorders are associated with high prevalence of type 2 diabetes (Suvisaari et al., 2008), metabolic syndrome (Suvisaari et al., 2007), and obesity (Saarni et al., 2009), all diseases in which inflammation has a key role (Pradhan et al., 2001, Hajer et al., 2008). Lifestyle-related factors that could be related to the association between psychotic disorders and both inflammation and medical comorbidity include smoking (Sopori, 2002), alcohol use (Cook, 1998), and poor physical condition and low muscle strength (Schrager et al., 2007, Ruiz et al., 2008).

The objectives of the current study were to investigate the role of inflammation in different psychotic disorders, and its association with metabolic comorbidity, antipsychotic medication, smoking and alcohol use, physical fitness, and mood in a general population-based sample of people with psychotic disorders and matched controls. We analyzed five cytokines or cytokine receptors most strongly associated with schizophrenia in a recent meta-analysis (Potvin et al., 2008): tumor necrosis factor alpha (TNF-α), interleukin-1 receptor antagonist (IL-1RA), interleukin-2 (IL-2) and its soluble receptor's alpha subunit (sIL-2Rα), and interleukin-6 (IL-6), and sensitive C-reactive protein (CRP) as another inflammatory marker.