Pronounced immunological abnormalities in unmedicated first episode as compared to chronic schizophrenia patients

Berko Milleit , Jana Hesse , Kerstin Langbein , Kristin Rödiger , Christine Milleit , Ute C. Meier , Peter Elsner , Uta-Christina Hipler , Stefan Smesny
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Abstract

There is major evidence for the involvement of immunological processes in the pathophysiology of schizophrenia. Especially alterations of T-cell function and activation of the inflammatory response system appear to be linked to schizophrenia. A mild chronic inflammation process has been proposed and repeated findings of altered serum cytokine levels led to the hypothesis of a TH2 shift or cytokine imbalance in schizophrenia. We investigated serum levels of TH1 and TH2 related cytokines and immune markers in 25 patients suffering an acute schizophrenic episode (all unmedicated, 22 neuroleptica-naïve) at different stages of disorder (18 first episode, FEP; 7 recurrent episode, REP) compared to 25 age and sex matched healthy controls.

In patients, we found an increase of the TH2 system cytokine IL-13 (p = 0.039) and a decrease of the TH1 system markers sICAM-1 (p = 0.011) and sIL-2R (p = 0.063, n. s.). Elevation of the pro-inflammatory cytokine IL-6 was not significant (p = 0.052). The effect of sIL-2R decrease was greater in the FEP subgroup (p = 0.01) of patients. We found no group differences in the other investigated immune markers: IL-4, IL-8, TNF-alpha, and Interferon-gamma, in which most readings were below the lower detection limit of the respective assay.

Our findings support the notion of a TH1/TH2 imbalance particularly in the acute manifestation phase of schizophrenia. In the long run, this may lead to the identification of cytokine patterns that are applicable as trait or state markers, may be helpful in making or ensuring diagnosis or in monitoring therapy.

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与慢性精神分裂症患者相比,未服药的首发患者明显的免疫异常
有主要证据表明免疫过程参与精神分裂症的病理生理。尤其是t细胞功能的改变和炎症反应系统的激活似乎与精神分裂症有关。轻度慢性炎症过程已被提出,反复发现血清细胞因子水平改变导致精神分裂症中TH2移位或细胞因子失衡的假设。我们研究了25例急性精神分裂症发作患者(均未用药,22例neuroleptica-naïve)不同阶段的血清TH1和TH2相关细胞因子和免疫标志物的水平(18例首发发作,FEP;7例复发(REP),与25例年龄和性别匹配的健康对照组相比。在患者中,我们发现TH2系统细胞因子IL-13增加(p = 0.039),TH1系统标志物sICAM-1 (p = 0.011)和sIL-2R (p = 0.063,n. s.)减少。促炎细胞因子IL-6升高无统计学意义(p = 0.052)。FEP亚组患者sIL-2R降低的效果更大(p = 0.01)。我们发现其他被调查的免疫标记物:IL-4、IL-8、tnf - α和干扰素- γ没有组间差异,其中大多数读数低于各自检测的下限。我们的研究结果支持TH1/TH2失衡的概念,特别是在精神分裂症的急性表现期。从长远来看,这可能会导致细胞因子模式的识别,可作为特征或状态标记,可能有助于制定或确保诊断或监测治疗。
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期刊介绍: Neurology, Psychiatry & Brain Research publishes original papers and reviews in biological psychiatry, brain research, neurology, neuropsychiatry, neuropsychoimmunology, psychopathology, psychotherapy. The journal has a focus on international and interdisciplinary basic research with clinical relevance. Translational research is particularly appreciated. Authors are allowed to submit their manuscript in their native language as supplemental data to the English version. Neurology, Psychiatry & Brain Research is related to the oldest German speaking journal in this field, the Centralblatt fur Nervenheilkunde, Psychiatrie und gerichtliche Psychopathologie, founded in 1878. The tradition and idea of previous famous editors (Alois Alzheimer and Kurt Schneider among others) was continued in modernized form with Neurology, Psychiatry & Brain Research. Centralblatt was a journal of broad scope and relevance, now Neurology, Psychiatry & Brain Research represents a journal with translational and interdisciplinary perspective, focusing on clinically oriented research in psychiatry, neurology and neighboring fields of neurosciences and psychology/psychotherapy with a preference for biologically oriented research including basic research. Preference is given for papers from newly emerging fields, like clinical psychoimmunology/neuroimmunology, and ideas.
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