Altered Peripheral Immune Profiles in First-Episode, Drug-Free Patients With Schizophrenia: Response to Antipsychotic Medications

Abstract

Previous research has demonstrated aberrations in the levels of inflammatory cytokines in patients with schizophrenia (SCZ), but most of the respective studies have tested a narrow set of inflammatory cytokines. Here, we aimed to analyze broad immune profiles in the peripheral blood of the first-episode drug-free (FEDF) patients with SCZ at baseline and after an 8-week treatment with atypical antipsychotics. Serum samples from 24 FEDF patients with SCZ and 25 healthy control (HC) subjects were tested using Luminex multiplex analysis for 30 cytokines, chemokines, and growth factors. Multiple comparison tests demonstrated that interleukin-2 (IL-2), IL-4, interferon-gamma (IFN-γ), monokine induced by IFN-γ, and granulocyte colony-stimulating factor (G-CSF) levels were significantly increased, whereas those of the epidermal growth factor were significantly decreased in the FEDF patients with SCZ. Moreover, the levels of the 6 dysregulated cytokines as well as those of 12 additional soluble factors in FEDF patients with SCZ were significantly decreased after 8 weeks of antipsychotic treatment. Furthermore, the transcription of G-CSF and IFN-γ was significantly increased in FEDF patients with SCZ when compared with controls, and G-CSF and IFN-γ mRNA levels were highly correlated with their respective protein concentrations. Receiver operating characteristic curves showed that G-CSF and IFN-γ had good performance in differentiating between FEDF patients with SCZ and HC subjects. Taken together, our data revealed that FEDF patients with SCZ were accompanied by a unique pattern of immune profile, and antipsychotic medications seemed to suppress the immune function in these patients, which could be used to develop novel targets for the diagnosis and treatment of SCZ.

Potential Inflammatory Biomarker in Patients with Attention Deficit Hyperactivity Disorder

“…At this point, prenatal exposure to inflammation may restrain brain development resulting from structural changes in the volume of gray matter that can cause permanent neural circuits to fail to mature or bring neuroendocrine changes, thus elevating the risk of ADHD [ 95 ]. In addition, the interaction of the HPA axis with a chronic increase in cytokine signals in the immune system during developmental processes is associated with the pathogenesis of ADHD [ 96 ]. However, these serological changes in inflammatory cytokines tend to wane or become reversed along with advances in the age of ADHD patients.…”

The Interrelation between Interleukin-2 and Schizophrenia

“…Extensive studies have been carried out on the change of the IL-2 level in patients with schizophrenia. However, the results of these studies vary largely, with some studies showing an increase in the level of IL-2 in in patients with schizophrenia [ 12 , 13 , 14 ], while some found a decrease [ 60 , 61 ] or no change [ 62 ]. There seems to be no generally accepted explanation for this inconsistency, and many possible reasons could contribute to it that may be related to race, disease time, disease process, disease severity and the selection of control.…”

“…Interleukin-2 (IL-2) is a growth factor regulating the autocrine of T-cells (regulatory T, Treg) that plays a role in the immune response [ 11 ]. A large number of studies have shown that IL-2 levels are different in patients with schizophrenia when compared with the healthy control group [ 12 , 13 , 14 ]. This difference is thought to be related to inflammation.…”

Potential Inflammatory Biomarker in Patients with Attention Deficit Hyperactivity Disorder

“…At this point, prenatal exposure to inflammation may restrain brain development resulting from structural changes in the volume of gray matter that can cause permanent neural circuits to fail to mature or bring neuroendocrine changes, thus elevating the risk of ADHD [95]. Also, interaction of the HPA axis with chronic increase of cytokine signals in the immune system during developmental processes is associated with the pathogenesis of ADHD [96]. However, these serological changes of inflammatory cytokines tend to wane or become reversed along with advances in age of ADHD patients.…”