LAUSR

In this issue, Braun et al. [3] report a study in which they took four independent blood samples from patients with psychotic disorders, including schizophrenia (n = 140), schizoaffective disorder (n = 43), bipolar disorder (n = 34), and depression (n = 52) with psychotic symptoms, and measured levels of immunoglobulin M (IgM) and the cytokines IL-6, tumor necrosis factor-α, neopterin, transforming growth factor-β1, and soluble cluster of differentiation 14 (sCD14). In a subgroup of 20–30% of the patients, they noted unusual behavior of the inflammatory response system, as quantified through IgM levels, that appeared to be associated with the pathogenesis of schizophrenia (p < 0.0001). They also report that the variation in concordance for schizophrenia of monozygotic twins could in part be “explained” by chronically elevated IgM levels (accounting for 24.54% of the observed phenotypic variance; p = 0.043), suggesting that monozygotic twins who are concordant for schizophrenia may possess a less “robust” variant of the inflammatory response system. This paper suggests a way for the early identification of the patients with schizophrenia for whom the inflammatory response system may be a target for therapeutic intervention [3]. Cerebrospinal fluid (CSF) is a more appropriate sampling substrate than blood because it more closely reflects brain functions. In this issue, Johansson et al. [4] report measuring CSF biomarkers of microglia activation, including monocyte chemoattractant protein-1, chitinase 3-like protein 1 (YKL-40), and sCD14, in 17 pairs of twins, including those with schizophrenia or bipolar disorder and those who were not affected by these disorders. They found higher CSF levels of sCD14 in the subjects with schizophrenia or bipolar disorder compared to their unaffected co-twins. sCD14 is produced in the central nervous system by activated macrophages triggered by the immune system, Editorial: Multiple lines of evidence suggest that abnormalities in the brain–immune system play a key role in the pathogenesis of psychotic disorders [1]. Accumulating data suggest that changes in the function of the immune system, particularly an increase in inflammation, can negatively impact virtually every aspect of brain function, including neurogenesis, synaptic remodeling, neuronal excitability, metabolic support, and even the response to medication [1]. The best-documented and most reproducible findings are increases in peripheral blood levels of interleukin-6 (IL6) and C-reactive protein (CRP) in patients with psychotic disorders. Although the precise mechanisms underlying the inflammatory response in these patients are unknown, it has been reported that there is increased activation of fundamental inflammatory signaling molecules and pathways [1]. Therefore, appropriate compounds which promote or regulate certain elements of immune system function may prevent the onset of psychotic disorders. Blood IL-6 and high-sensitivity CRP (hsCRP) levels have been observed to be significantly higher in schizophrenia patients (n = 151) than in healthy controls (n = 194) [2]. Interestingly, the levels of both IL-6 and hsCRP in that study were associated with the insidious onset of the psychosis, the duration of the illness, and a chronic schizophrenia course with deterioration. These results suggest that elevated blood levels of IL-6 may serve as an inflammatory biomarker of deterioration in schizophrenia [2].