健康人群和慢性精神分裂症病人前脉冲抑制的影响因素

doi:10.3969/j.issn.1006-7795.2017.02.007

摘要/Abstract

摘要： 目的本研究以健康人群和慢性精神分裂症病人为研究对象，初步探索两者前脉冲抑制（prepulse inhibition，PPI）的影响因素。方法对50名健康成人（健康组）和75名精神分裂症病人（病人组）进行了PPI测试和认知测试。认知测试采用重复神经心理测查系统（Repeatable Battery for the Assessment of Neuropsychological Status，RBANS）和Stroop色词测验，并用阳性和阴性症状量表（Positive and Negative Syndrome Scale，PANSS）评定病人精神症状。结果 1）与健康组相比，病人组PPI抑制率降低（9.4%±29.3% vs 31.7%±26.2%，P<0.001）;病人组RBANS总分及其5因子分数、Stroop颜色和词语干扰时间[（370.0±48.5），（55.5±15.5），（79.7±15.8），（77.9±12.3），（91.8±12.2），（65.3±18.3），（7.6±6.9）s，（24.5±12.9）s]与健康组的差异存在统计学意义（P<0.05）。2）健康人群PPI的影响因素分析：单因素分析显示，健康组性别（P<0.05）、吸烟量（r=0.29，P<0.05）、RBANS总分（r=0.30，P<0.05）、注意因子得分（r=0.29，P<0.05）对PPI抑制率的影响具有统计学意义;多因素岭回归分析显示，健康组岭参数k=2.95模型稳定，R²=0.33，PPI抑制率受到性别、吸烟量、RBANS总分、注意因子分的影响（P<0.05）。3）慢性精神分裂症病人PPI的影响因素分析：单因素分析显示，病人组吸烟量（r=0.23，P<0.05）、复发次数（>3次 vs≤3次，P<0.05）对PPI抑制率的影响差异具有统计学意义;多因素岭回归分析显示，病人组岭参数k=2.58模型稳定，R²=0.26，PPI抑制率受到性别、吸烟量和复发次数的影响（P<0.05）。结论 PPI抑制率是反映感觉门控功能的指标，健康人群和慢性精神分裂症病人PPI的影响因素不尽相同。女性、吸烟可能是精神分裂症病人感觉门控的保护性因素，而发病次数过多可能对精神分裂症病人感觉门控功能有损害。

关键词: 精神分裂症, 前脉冲抑制, 认知功能, 岭回归

Abstract: Objective To study the prepulse inhibition (PPI) and its related factors among healthy people and patients with chronic schizophrenia. Methods The PPI and cognitive performance (repeatable battery for the assessment of neuropsychological status (RBANS) and Stroop Color-world test) were tested in 50 healthy people (HP)and 75 chronic schizophrenia patients (SCZ). Positive and negative syndrome scale (PANSS) was used to evaluate the psychotic symptoms of patients. Results (1) Compared with HP, SCZ showed decreased PPI% (9.4%±29.3% vs 31.7%±26.2%,P<0.001), and the difference between two groups was found in cognitive performance (RBANS scores and its scores of all items in RBANS, Stroop color and word time). (2) Related factors of PPI% in healthy people:univariate analysis in PPI% showed that gender (male vs female, P<0.05), smoking (r=0.29,P<0.05), RBANS scores (r=0.30,P<0.05) and attention item scores (r=0.29,P<0.05) on the impact of the PPI% were statistically significant. Furthermore, multivariate ridge regression showed the same results as well as univariate analysis (ridge parameter k=2.95, adjusted R²=0.33, P<0.05). (3) Related factors of PPI% in people with chronic schizophrenia:PPI% was significantly correlated with smoking (r=0.23,P<0.05), relapses (>3 times vs≤3 times, P<0.05) in univariate analysis. And mutlivariate ridge regression showed the significantly related factors of PPI% in schizophrenia patients were gender, smoking and relapses (ridge parameter k=2.58, adjusted R²=0.26, P<0.05). Conclusion PPI% is an indicator of sensory gating, and its related factors may be different for different groups. Female and smoking may be protective factors for sensory gating in schizophrenia, more recurrence may be destroy the sensory gating function of patients with schizophrenia.

Key words: schizophrenia, prepulse inhibition, cognitive function, ridge regression

中图分类号:

R749.3

范玉, 杨宁波, 田晴, 朱秀强, 王传跃. 健康人群和慢性精神分裂症病人前脉冲抑制的影响因素[J]. 首都医科大学学报, 2017, 38(2): 178-185.

Fan Yu, Yang Ningbo, Tian Qing, Zhu Xiuqiang, Wang Chuanyue. Prepulse inhibition and the related factors among healthy people and patients with chronic schizophrenia[J]. Journal of Capital Medical University, 2017, 38(2): 178-185.

参考文献

[1] Braff D L, Geyer M A, Swerdlow N R. Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies[J]. Psychopharmacology (Berl), 2001,156(2-3):234-258.
[2] Braff D L, Geyer M A, Light G A, et al. Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia[J]. Schizophr Res, 2001,49(1-2):171-178.
[3] Kumari V, Soni W, Mathew V M, et al. Prepulse inhibition of the startle response in men with schizophrenia: effects of age of onset of illness, symptoms, and medication[J]. Arch Gen Psychiatry, 2000,57(6):609-614.
[4] Cadenhead K S. Startle reactivity and prepulse inhibition in prodromal and early psychosis: effects of age, antipsychotics, tobacco and cannabis in a vulnerable population[J]. Psychiatry Res, 2011,188(2):208-216.
[5] Green M F, Butler P D, Chen Y, et al. Perception measurement in clinical trials of schizophrenia: promising paradigms from CNTRICS[J]. Schizophr Bull, 2009,35(1):163-181.
[6] Butler P D, Chen Y, Ford J M, et al. Perceptual measurement in schizophrenia: promising electrophysiology and neuroimaging paradigms from CNTRICS[J]. Schizophr Bull, 2012,38(1):81-91.
[7] Swerdlow N R, Light G A, Sprock J, et al. Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS[J]. Schizophr Res, 2014,152(2-3):503-512.
[8] American Psychiatric Association. Diagnostic and Statistic Manual of Mental Disorders[M]. Washington D C: American Psychiatric Press, Inc., 2000
[9] 张保华, 谭云龙, 张五芳, 等. 重复性成套神经心理状态测验的信度、效度分析[J]. 中国心理卫生杂志, 2008,22(12):865-869.
[10] 刘海燕, 陈俊, 张积家. Stroop效应在精神病理学研究中的论证[J]. 2007,7(5):382-386.
[11] Braff D L. Prepulse inhibition of the startle reflex: a window on the brain in schizophrenia[J]. Curr Top Behav Neurosci, 2010,4:349-371.
[12] 何晓群. 应用回归分析 [M]. 4版. 北京:中国人民大学出版社, 2015.
[13] Cule E, De Iorio M. Ridge regression in prediction problems: automatic choice of the ridge parameter[J]. Genet Epidemiol, 2013,37(7):704-714.
[14] Braff D, Stone C, Callaway E, et al. Prestimulus effects on human startle reflex in normals and schizophrenics[J]. Psychophysiology, 1978,15(4):339-343.
[15] Braff D L, Swerdlow N R, Geyer M A. Symptom correlates of prepulse inhibition deficits in male schizophrenic patients[J]. Am J Psychiatry, 1999,156(4):596-602.
[16] 王志仁, 谭云龙, 杨甫德, 等. 慢性精神分裂症男性病人听觉刺激惊跳反射的初步研究[J]. 中华精神科杂志, 2010,43(3):135-139.
[17] Weike A I, Bauer U, Hamm A O. Effective neuroleptic medication removes prepulse inhibition deficits in schizophrenia patients[J]. Biol Psychiatry, 2000,47(1):61-70.
[18] Rahman Q, Kumari V, Wilson G D. Sexual orientation-related differences in prepulse inhibition of the human startle response[J]. Behav Neurosci, 2003,117(5):1096-1102.
[19] Swerdlow N R, Auerbach P, Monroe S M, et al. Men are more inhibited than women by weak prepulses[J]. Biol Psychiatry, 1993,34(4):253-260.
[20] Kumari V, Aasen I, Sharma T. Sex differences in prepulse inhibition deficits in chronic schizophrenia[J]. Schizophr Res, 2004,69(2-3):219-235.
[21] van den Buuse M, Mingon R L, Gogos A. Chronic estrogen and progesterone treatment inhibits ketamine-induced disruption of prepulse inhibition in rats[J]. Neurosci Lett, 2015,607:72-76.
[22] Labouesse M A, Langhans W, Meyer U. Effects of selective estrogen receptor alpha and beta modulators on prepulse inhibition in male mice[J]. Psychopharmacology (Berl), 2015,232(16):2981-2994.
[23] Curzon P, Kim D J, Decker M W. Effect of nicotine, lobeline, and mecamylamine on sensory gating in the rat[J]. Pharmacol Biochem Behav, 1994,49(4):877-882.
[24] Hong L E, Wonodi I, Lewis J, et al. Nicotine effect on prepulse inhibition and prepulse facilitation in schizophrenia patients[J]. Neuropsychopharmacology, 2008,33(9):2167-2174.
[25] Olincy A, Freedman R. Nicotinic mechanisms in the treatment of psychotic disorders: a focus on the alpha7 nicotinic receptor[J]. Handb Exp Pharmacol, 2012(213):211-232.
[26] Winterer G, Gallinat J, Brinkmeyer J, et al. Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study[J]. Neuropharmacology, 2013,64:197-204.
[27] Azzopardi E, Typlt M, Jenkins B, et al. Sensorimotor gating and spatial learning in alpha7-nicotinic receptor knockout mice[J]. Genes Brain Behav, 2013,12(4):414-423.
[28] Kumari V, Soni W, Sharma T. Normalization of information processing deficits in schizophrenia with clozapine[J]. Am J Psychiatry, 1999,156(7):1046-1051.
[29] Mackeprang T, Kristiansen K T, Glenthoj B Y. Effects of antipsychotics on prepulse inhibition of the startle response in drug-naive schizophrenic patients[J]. Biol Psychiatry, 2002,52(9):863-873.
[30] Weike A I, Bauer U, Hamm A O. Effective neuroleptic medication removes prepulse inhibition deficits in schizophrenia patients[J]. Biol Psychiatry, 2000,47(1):61-70.
[31] During S, Glenthoj B Y, Andersen G S, et al. Effects of dopamine D2/D3 blockade on human sensory and sensorimotor gating in initially antipsychotic-naive, first-episode schizophrenia patients[J]. Neuropsychopharmacology, 2014,39(13):3000-3008.
[32] Csomor P A, Preller K H, Geyer M A, et al. Influence of aripiprazole, risperidone, and amisulpride on sensory and sensorimotor gating in healthy 'low and high gating’ humans and relation to psychometry[J]. Neuropsychopharmacology, 2014,39(10):2485-2496.
[33] 王红星, 陈兴时, 张明岛. 精神分裂症感觉运动门控及惊跳反射弱刺激抑制的研究[J]. 中华精神科杂志, 2005,38(1):55-58.
[34] Steckler T, Inglis W, Winn P, et al. The pedunculopontine tegmental nucleus: a role in cognitive processes?[J]. Brain Res Brain Res Rev, 1994,19(3):298-318.
[35] Lang P J, Simons R F, Balaban M. Attention and Orienting: Sensory and Motivational Processes[M]. New York, USA: Taylor & Francis, 2013.
[36] Blumenthal T D. Prepulse inhibition of the startle eyeblink as an indicator of temporal summation[J]. Percept Psychophys, 1995,57(4):487-494.
[37] Li L, Du Y, Li N, et al. Top-down modulation of prepulse inhibition of the startle reflex in humans and rats[J]. Neurosci Biobehav Rev, 2009,33(8):1157-1167.
[38] Dawson M E, Hazlett E A, Filion D L, et al. Attention and schizophrenia: impaired modulation of the startle reflex[J]. J Abnorm Psychol, 1993,102(4):633-641.
[39] Ramirez-Moreno D F, Sejnowski T J. A computational model for the modulation of the prepulse inhibition of the acoustic startle reflex[J]. Biol Cybern, 2012,106(3):169-176.
[40] Scholes K E, Martin-Iverson M T. Relationships between prepulse inhibition and cognition are mediated by attentional processes[J]. Behav Brain Res, 2009,205(2):456-467.
[41] Karper L P, Freeman G K, Grillon C, et al. Preliminary evidence of an association between sensorimotor gating and distractibility in psychosis[J]. J Neuropsychiatry Clin Neurosci, 1996,8(1):60-66.