Inflammatory processes in schizophrenia: A promising neuroimmunological target for the treatment of negative/cognitive symptoms and beyond

被引:188
作者
Meyer, Urs [1 ]
Schwarz, Markus J. [2 ]
Mueller, Norbert [2 ]
机构
[1] Swiss Fed Inst Technol, Physiol & Behav Lab, CH-8603 Schwerzenbach, Switzerland
[2] Univ Munich, Dept Psychiat & Psychotherapy, D-80336 Munich, Germany
关键词
Antipsychotic drugs; Astrocytes; Cyclooxygenase; Cytokines; Inflammation; Microglia; NECROSIS-FACTOR-ALPHA; INTERLEUKIN-1 RECEPTOR ANTAGONIST; PLACEBO-CONTROLLED TRIAL; TREATMENT-RESISTANT SCHIZOPHRENIA; TYROSINE-HYDROXYLASE ACTIVITY; MATERNAL IMMUNE ACTIVATION; CONTINUOUSLY ILL PATIENTS; VARIANTS CONFERRING RISK; SOLUBLE IL-6 RECEPTORS; LONG-TERM POTENTIATION;
D O I
10.1016/j.pharmthera.2011.06.003
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Emerging evidence indicates that schizophrenia is associated with activated peripheral and central inflammatory responses. Such inflammatory processes seem to be influenced by a number of environmental and genetic predisposition factors, and they may critically depend on and contribute to the progressive nature of schizophrenic disease. There is also appreciable evidence to suggest that activated inflammatory responses Gill undermine disease-relevant affective, emotional, social, and cognitive functions, so that inflammatory processes may be particularly relevant for the precipitation of negative and cognitive symptoms of schizophrenia. Recent clinical trials of anti-inflammatory pharmacotherapy in this disorder provide promising results by showing superior beneficial treatment effects when standard antipsychotic drugs are co-administered with anti-inflammatory compounds, as compared with treatment outcomes using antipsychotic drugs alone. Given the limited efficacy of currently available antipsychotic drugs to ameliorate negative and cognitive symptoms, the further exploration of inflammatory mechanisms and anti-inflammatory strategies may open fruitful new avenues for improved treatment of symptoms undermining affective, emotional, social and cognitive functions pertinent to schizophrenic disease. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:96 / 110
页数:15
相关论文
共 234 条
[91]   Relationships between interleukins, neurotransmitters and psychopathology in drug-free male schizophrenics [J].
Kim, YK ;
Kim, L ;
Lee, MS .
SCHIZOPHRENIA RESEARCH, 2000, 44 (03) :165-175
[92]   Th1, Th2 and Th3 cytokine alteration in schizophrenia [J].
Kim, YK ;
Myint, AM ;
Lee, BH ;
Han, CS ;
Lee, HJ ;
Kim, DJ ;
Leonard, BE .
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 2004, 28 (07) :1129-1134
[93]   Cytokine Changes and Tryptophan Metabolites in Medication-Naive and Medication-Free Schizophrenic Patients [J].
Kim, Yong-Ku ;
Myint, Aye-Mu ;
Verkerk, Robert ;
Scharpe, Simon ;
Steinbusch, Harry ;
Leonard, Brian .
NEUROPSYCHOBIOLOGY, 2009, 59 (02) :123-129
[94]   Diagnosing schizophrenia in the initial prodromal phase [J].
Klosterkötter, J ;
Hellmich, M ;
Steinmeyer, EM ;
Schultze-Lutter, F .
ARCHIVES OF GENERAL PSYCHIATRY, 2001, 58 (02) :158-164
[95]   sIL-6R: more than an agonist? [J].
Knuepfer, Heike ;
Preiss, Rainer .
IMMUNOLOGY AND CELL BIOLOGY, 2008, 86 (01) :87-91
[96]   Genomic organization of the mammalian Mhc [J].
Kumánovics, A ;
Takada, T ;
Lindahl, KF .
ANNUAL REVIEW OF IMMUNOLOGY, 2003, 21 :629-657
[97]  
Kunz M., 2011, REV BRAS PSIQUIATR
[98]   Adjuvant Aspirin Therapy Reduces Symptoms of Schizophrenia Spectrum Disorders: Results From a Randomized, Double-Blind, Placebo-Controlled Trial [J].
Laan, Wijnand ;
Grobbee, Diederick E. ;
Selten, Jean-Paul ;
Heijnen, Cobi J. ;
Kahn, Rene S. ;
Burger, Huibert .
JOURNAL OF CLINICAL PSYCHIATRY, 2010, 71 (05) :520-527
[99]   Human leukocyte antigen-A1 predicts a good therapeutic response to clozapine with a low risk of agranulocytosis in patients with schizophrenia [J].
Lahdelma, L ;
Ahokas, A ;
Andersson, LC ;
Suvisaari, J ;
Hovatta, I ;
Huttunen, MO ;
Koskimies, S .
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY, 2001, 21 (01) :4-7
[100]   Early signs, diagnosis and therapeutics of the prodromal phase of schizophrenia and related psychotic disorders [J].
Larson, Molly K. ;
Walker, Elaine F. ;
Compton, Michael T. .
EXPERT REVIEW OF NEUROTHERAPEUTICS, 2010, 10 (08) :1347-1359