치료 저항성 조현병 환자와 치료 반응성 조현병 환자간의 CRP를 포함한 염증 표지자 비교
Comparison of Inflammatory Markers Including C-Reactive Protein between Treatment Resistant Schizophrenia and Non-Treatment Resistant Schizophrenia
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objectives：The present study is to investigate inflammatory markers and associated clinical factors between treatment resistant schizophrenia and non-treatment resistant schizophrenia. Methods：Of the 116 schizophrenia subjects who were hospitalized for acute symptomatic treatment, 19 patients (16%) were treated with clozapine as a treatment resistant schizophrenia(TRS) and 97 patients(84%) were treated with other atypical antipsychotics as a non-treatment resistant schizophrenia(Non-TRS). Various inflammatory markers including C-reactive protein(CRP) and clinical factors were retrospectively evaluated with electrical medical records. Results：There were significant differences between two groups in disease duration( p =0.015), number of admission ( p =0.003), Clinical Global Impression( p ＜0.001) but other demographic and clinical variables including previous antipsychotics use did not show significant differences. In terms of hematologic profiles, TRS group demonstrated higher CRP level( p =0.006), lower neutrophil count( p =0.012), and lower hemoglobin level( p =0.003) compared with non-TRS group. Body mass index was significantly correlated with CRP(r=0.318, p =0.001). Conclusion：The elevated level of serum CRP in TRS suggests that treatment resistance in schizophrenia may be associated with inflammatory response. However, retrospective study design and small number of subjects could limit this interpretation.
Abstract
Objectives：The present study is to investigate inflammatory markers and associated clinical factors between treatment resistant schizophrenia and non-treatment resistant schizophrenia. Methods：Of the 116 schizophrenia subjects who were hospitalized for acute symptomatic treatment, 19 patients (16%) were treated with clozapine as a treatment resistant schizophrenia(TRS) and 97 patients(84%) were treated with other atypical antipsychotics as a non-treatment resistant schizophrenia(Non-TRS). Various inflammatory markers including C-reactive protein(CRP) and clinical factors were retrospectively evaluated with electrical medical records. Results：There were significant differences between two groups in disease duration( p =0.015), number of admission ( p =0.003), Clinical Global Impression( p ＜0.001) but other demographic and clinical variables including previous antipsychotics use did not show significant differences. In terms of hematologic profiles, TRS group demonstrated higher CRP level( p =0.006), lower neutrophil count( p =0.012), and lower hemoglobin level( p =0.003) compared with non-TRS group. Body mass index was significantly correlated with CRP(r=0.318, p =0.001). Conclusion：The elevated level of serum CRP in TRS suggests that treatment resistance in schizophrenia may be associated with inflammatory response. However, retrospective study design and small number of subjects could limit this interpretation.
참고문헌 (53)
- Suvisaari J, "Inflammation in psychotic disorders : a population-based study", Psychiatry Res, 189, pp.305~311 (2011)
- Singh B, "Role of C-reactive protein in schizophrenia : an overview", Psychiatry Res, 216, pp.277~285 (2014)
- Müller N, "Immunology of schizophrenia", J Neuroimmunomodulation, 21, pp.109~116 (2014)
- Müller N, "Inflammation in schizophrenia", Adv Protein Chem Struct Biol, pp.49~68 (2012)
- Fineberg AM, "Inflammatory cytokines and neurological and neurocognitive alterations in the course of schizophrenia", Biol Psychiatry, 73, pp.951~966 (2013)
- Kinney DK, "A unifying hypothesis of schizophrenia:abnormal immune system development may help explain roles of prenatal hazards, post-pubertal onset, stress, genes, climate, infections, and brain dysfunction", Med Hypotheses, 74, pp.555~563 (2010)
- Nitta M, "Adjunctive use of nonsteroidal antiinflammatory drugs for schizophrenia : a meta-analytic investigation of randomized controlled trials", Schizophr Bull, 39, pp.1230~1241 (2013)
- Müller N, "Beneficial antipsychotic effects of celecoxib add-on therapy compared to risperidone alone in schizophrenia", Am J Psychiatry, 159, pp.1029~1034 (2002)
- Dickerson F, "C-reactive protein is elevated in schizophrenia", Psychiatry Res, 143, pp.198~202 (2013)
- Fond G, "C-Reactive Protein as a peripheral biomarker in schizophrenia. An updated systematic review", Front Psychiatry, 9, pp.392~ (2018)
- Zahorec R, "Ratio of neutrophil to lymphocyte countsrapid and simple parameter of systemic inflammation and stress in critically ill", Bratisl Lek Listy, 102, pp.5~14 (2001)
- Özdin S, "Neutrophil", lymphocyte, platelet, lymphocyte ratios in different stages of schizophrenia, pp.Psychiatry Res, 2019[DOI]
- Bustan Y, "Elevated neutrophil to lymphocyte ratio in non-affective psychotic adolescent inpatients : evidence for early association between inflammation and psychosis", Psychiatry Res, 262, pp.149~153 (2018)
- Kennedy JL, "The social and economic burden of treatment-resistant schizophrenia : a systematic literature review", Int Clin Psychopharmacol, 29, pp.63~76 (2014)
- 김의태, "치료 저항성 조현병의 이해와 치료", 신경정신의학, 57(3), pp.230~234 (2018), 대한신경정신의학회[DOI]
- Seeman P, "Antipsychotic drugs : direct correlation between clinical potency and presynaptic action on dopamine neurons", Science, 188, pp.1217~1219 (1975)
- -DOPA PET imaging study, "Am J Psychiatry", 2011, 1311~1317
- Strawbridge R, "Inflammation and clinical response to treatment in depression : a meta-analysis", Eur Neuropsychopharmacol, 25, pp.1532~1543 (2015)
- Uher R, "An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline", Am J Psychiatry, 171, pp.1278~1286 (2014)
- Chamberlain SR, "Treatment-resistant depression and peripheral C-reactive protein", Br J Psychiatry, 214, pp.11~19 (2019)
- Maes M, "Increased serum interleukin-8and interleukin-10 in schizophrenic patients resistant to treatment with neuroleptics and the stimulatory effects of clozapine on serum leukemia inhibitory factor receptor", Psychiatry Res, 54, pp.281~291 (2002)
- Lin A, "T he i nflammatory response system i n treatment-resistant schizophrenia : increased serum interleukin-6", Psychiatry Res, 32, pp.9~15 (1998)
- Zhang XY, "Cortisol and cytokines in chronic and treatment-resistant patients with schizophrenia : association with psychopathology and response to antipsychotics", Neuropsychopharmacology, 30, pp.1532~ (2005)
- Maes M, "Effects of atypical antipsychotics on the inflammatory response system in schizophrenic patients resistant to treatment with typical neuroleptics", Eur Neuropsychopharmacol, 10, pp.119~124 (2000)
- Horsdal HT, "C-reactive protein levels and treatment resistance in schizophrenia-A Danish population-based cohort study", Hum Psychopharmacol, 32, pp.e2632~ (2017)
- Guy W, "Clinical global impression", J Assessment manual for Psychopharmacology, pp.217~222 (1976)
- Busner J, "The clinical global impressions scale : applying a research tool in clinical practice", Psychiatry, 4, pp.28~ (2007)
- Pearson TA, "Markers of inflammation and cardiovascular disease : application to clinical and public health practice : a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association", Circulation, 107, pp.499~511 (2003)
- Woods SW, "Chlorpromazine equivalent doses for the newer atypical antipsychotics", J Clin Psychiatry, 64, pp.663~667 (2003)
- Wener MH, "The influence of age, sex, and race on the upper reference limit of serum C-reactive protein concentration", J Rheumatol, 27, pp.2351~2359 (2000)
- Wannamethee SG, "Associations between cigarette smoking, pipe", cigar smoking, and smoking cessation, and haemostatic and inflammatory markers for cardiovascular disease, 2005, pp.26, 1765~1773
- Park HS, "Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-α and IL-6", Diabetes Res Clin Pract, 69, pp.29~35 (2005)
- Fan X, "Elevated serum levels of C-reactive protein are associated with more severe psychopathology in a subgroup of patients with schizophrenia", Psychiatry Res, 149, pp.267~271 (2007)
- Frydecka D, "Interleukin-6: the missing element of the neurocognitive deterioration in schizophrenia? The focus on genetic underpinnings, cognitive impairment and clinical manifestation", Eur Arch Psychiatry Clin Neurosci, 265, pp.449~459 (2015)
- Haroon E, "Conceptual convergence : increased inflammation is associated with increased basal ganglia glutamate in patients with major depression", Mol Psychiatry, 21, pp.1351~ (2016)
- Tilleux S, "Neuroinflammation and regulation of glial glutamate uptake in neurological disorders", J Neurosci Res, 85, pp.2059~2070 (2007)
- Ida T, "Cytokine-induced enhancement of calcium-dependent glutamate release from astrocytes mediated by nitric oxide", Neurosci Lett, 432, pp.232~236 (2008)
- Sanacora G, "Towards a glutamate hypothesis of depression : an emerging frontier of neuropsychopharmacology for mood disorders", Neuropharmacology, 62, pp.63~77 (2012)
- Mouchlianitis E, "Treatment-resistant schizophrenia patients show elevated anterior cingulate cortex glutamate compared to treatment-responsive", Schizophr Bull, 42, pp.744~752 (2016)
- Duncan GE, "Metabolic mapping of the rat brain after subanesthetic doses of ketamine : potential relevance to schizophrenia", Brain Res, 787, pp.181~190 (1998)
- Joshi I, "Coincident activation of metabotropic glutamate receptors and NMDA receptors(NMDARs)downregulates perisynaptic", extrasynaptic NMDARs and enhances high-fidelity neurotransmission at the developing calyx of Held synapse, 2007, pp.27, 9989~9999
- Veerman SR, "Memantine augmentation in clozapine-refractory schizophrenia:a randomized, double-blind, placebo-controlled crossover study", Psychol Med, 46, pp.1909~1921 (2016)
- Yuen EY, "Homeostatic regulation of glutamatergic transmission by dopamine D4 receptors", Proc Natl Acad Sci USA, 107, pp.22308~22313 (2010)
- Tanahashi S, "Clozapine, but not haloperidol, enhances glial D-serine and L-glutamate release in rat frontal cortex and primary cultured astrocytes", Br J Pharmacol, 165, pp.1543~1555 (2012)
- Bliss TV, "A synaptic model of memory : long-term potentiation in the hippocampus", Nature, 361, pp.31~ (1993)
- Hefner G, "Inflammation and psychotropic drugs : the relationship between C-reactive protein and antipsychotic drug levels", Psychopharmacology, 233, pp.1695~1705 (2016)
- Fernandes BS, "C-reactive protein is increased in schizophrenia but is not altered by antipsychotics : metaanalysis and implications", Mol Psychiatry, 21, pp.554~ (2016)
- Löffler S, "Clozapine therapy raises serum concentrations of high sensitive C-reactive protein in schizophrenic patients", Int Clin Psychopharmacol, 25, pp.101~106 (2010)
- Ali I, "Prevalence of Anemia among Schizophrenic Patients in Palestine", PMPJ, 7, pp.6~ (2017)
- Rettenbacher MA, "Neutropenia induced by second generation antipsychotics : a prospective investigation", Pharmacopsychiatry, 43, pp.41~44 (2010)
- Alvir JM, "Clozapine-induced agranulocytosis--incidence and risk factors in the United States", N Engl J Med, 329, pp.162~167 (1993)
- 김계환, "조현병 및 조현정동장애 입원환자에서 혈청 염증표지자와 정신병적 증상과의 관련성", 생물정신의학, 19(4), pp.193~198 (2012), 대한생물정신의학회
- Ridker PM, "C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women", Circulation, 107, pp.391~397 (2003)