中国临床心理学杂志

Functional Connectivity of the Frontostriato-thalamic Circuit Correlates with Positive Symptoms in Schizophrenia

作者：HUANG Xiao-jun Mwansisya Tumbwene PU Wei-dan LIU Hai-hong LV Dong-sheng XUE Zhi-min LIU Zhe-ning

单位：1. Mental Health Institute of Second Xiangya Hospital Central South University Changsha 410011 China 2. Aga Khan University P. O Box125 Dar es salaam Tanzania 3. Medical Psychological Institute Second Xiangya Hospital Central South University Changsha 410011 China 4. Mental Health Center of Xiangya Hospital Central South University Changsha 410008 China 5. State Key Laboratory of Medical Genetics Central South University Changsha 410006 China

关键词：Functional connectivity analysis Positive symptoms Resting-state Schizophrenia Striatum

分类号：R395.1

出版年,卷(期):页码：2017,25(5):793-799

摘要：

目的：探讨纹状体的功能连接和精神分裂症临床症状的关系。方法：运用基于体素的功能连接分析法来识别精神分裂症患者纹状体与其他脑区功能连接的异常，入组对象为70位精神分裂症患者和60位年龄、性别相匹配的健康对照。结果：与健康对照比较，我们发现患者的左侧尾状核与左侧额中回、左侧额上回以及左侧丘脑，右侧尾状核与右侧额中回、左右两侧丘脑，右侧壳核与右侧楔叶均表现为功能连接减弱。相关分析发现，左侧尾状核和左侧额中回的功能连接强度与患者阳性症状量表的幻觉评分成负相关，右侧尾状核与右侧丘脑的功能连接强度与患者阳性症状量表的怪异行为呈正相关。结论：结果显示精神分裂症患者额叶-纹状体-丘脑环路静息态功能连接存在异常。并且此环路中的左侧尾状核与左侧额中回以及右侧尾状核与右侧丘脑的功能连接异常可能分别为精神分裂症患者幻觉和怪异行为的神经生物学基础。

Objective: To explore the relationship between the functional connectivity of the striatum and clinical symp-toms of schizophrenia. Methods: Voxel-based resting-state functional connectivity analyses were performed to identify the functional connectivity of the striatal regions in whole brain in 70 schizophrenia patients and 60 age-and sex-matched healthy controls. Results: We found the functional connectivity between the left caudate(CAU) and left middle frontal gyrus (MFG), left superior frontal gyrus(SFG) and left thalamus(THA), right CAU and right MFG, left THA and right THA, and right putamen(PUT) and right cuneus(CUN) to be significantly decreased in the schizophrenia patient group compared to the healthy controls. Moreover, the functional connectivity between the left CAU and MFG was found to be negatively associat-ed with hallucinations in patient group. Moreover, a positive correlation was found between bizarre behavior and the func-tional connectivity of the CAU with THA. Conclusion: These findings demonstrate resting-state functional abnormalities of the frontal-striatal-thalamic(FST) circuit in schizophrenia. Moreover, the significantly altered functional connectivity be-tween the left CAU and left MFG and between the right CAU and right THA in the FST circuit may be the underlying neu-ro-substrates, respectively, for the hallucinations and bizarre behaviors observed in schizophrenia patients.

基金项目：

国家自然科学基金项目“精神病性症状脑有效连接与多巴胺相关基因的关联研究”（项目编号：81471362）

作者简介：

参考文献：

1 Schmitt GJ, Meisenzahl EM, Frodl T, et al. Increase of striatal dopamine transmission in first episode drug-naive schizophrenic patients as demonstrated by[(123)I]IBZM SPECT. Psychiatry Res, 2009, 173(3):183-189
2 Siever LJ, Davis KL. The pathophysiology of schizophrenia disorders:perspectives from the spectrum. Am J Psychiatry, 2004, 161(3):398-413
3 Biswal B, Yetkin FZ, Haughton VM, et al. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Neuron, 1997, 19(3):591-611
4 Breiter HC, Gollub RL, Weisskoff RM, et al. Acute effects of cocaine on human brain activity and emotion. J Neurosci, 2001, 21:RC159
5 Knutson B, Adams CM, Fong GW, et al. Anticipation of increasing monetary reward selectively recruits nucleus accumbens. Magn Reson Med, 1995, 34(4):537-541
6 Chudasama Y, Robbins TW. Functions of frontostriatal systems in cognition:comparative neuropsychopharmacological studies in rats, monkeys and humans. Biol Psychol, 2006, 73 (1):19-38
7 Graybiel AM. The basal ganglia:learning new tricks and loving it. Curr Opin Neurobiol, 2005, 15(6):638-644
8 Rogers RD, Andrews TC, Grasby PM, et al. Contrasting cortical and subcortical activations produced by attentional-set shifting and reversal learning in humans. J Cogn Neurosci, 2000, 12(1):142-162
9 Berridge KC, Robinson TE. What is the role of dopamine in reward:hedonic impact, reward learning, or incentive salience? Brain Res Brain Res Rev, 1998, 28(3):309-369
10 Robbins TW, Everitt BJ. Neurobehavioural mechanisms of reward and motivation. Curr Opin Curr Opin Neurobiol, 1996, 6(2):228-236
11 Wise RA. Neuroleptics and operant-behavior:the anhedoniahypothesis. Behavioral and brain sciences, 1982, 5:39-53
12 Akil M, Brewer GJ. Psychiatric and behavioral abnormalities in Wilson's disease. Adv Neurol, 1995, 65:171-178
13 Oder W, Grimm G, Kollegger H, et al. Neurological and neuropsychiatric spectrum of Wilson's disease:aprospective study of 45 cases. J Neurol, 1991, 238(5):281-287
14 Cedarbaum JM, Schleifer LS. Drugs for Parkinson's disease, spasticity, and acute muscle spasms. Goodman and Gilman's the Pharmacological Basis of Therapeutics, 1990. 479-480
15 Kulik AV, Wilbur R. Delirium and stereotypy from anticholinergic antiparkinson drugs. Prog Neuropsychopharmacol Biol Psychiatry, 1982, 6(1):75-82
16 Carlsson A, Waters N, Carlsson ML. Neurotransmitter interactions in schizophrenia——therapeutic implications. Biol Psychiatry, 1999, 46(10):1388-1395
17 Sesack SR, Carr DB. Selective prefrontal cortex inputs to dopamine cells:implications for schizophrenia. Physiol Behav, 2002, 77(4-5):513-517
18 Goldstein RZ, Volkow ND. Drug addiction and its underlying neurobiological basis:neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry, 2002, 159 (10):1642-1652
19 Sheline YI, Price JL, Yan Z. Resting-state functional MRI indepression unmasks increased connectivity between networks via the dorsalnexus. Proceedings of the National Academy of Sciences, 2010, 107(24):11020-11025
20 Fox MD, Greicius M. Clinical applications of resting state functional connectivity. Front Syst Neurosci, 2010, 4:19
21 Tzourio-Mazoyer N, Landeau B, Papathanassiou D. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI singlesubject brain. Neuroimage, 2002, 15(3):273-289
22 First MB, Spitzer, RL, Gibbon, M, et al. Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition (SCID-I/P). New York(NY):Biometrics Research Department:New York State Psychiatric Institute, 1996
23 Annett M. A classification of hand preference by association analysis. Br J Psychol, 1970, 61(3):303-321
24 Andreasen NC. The Scale for the Assessment of Positive Symptoms in Schizophrenia. Iowa:The University of Iowa, 1984a
25 Andreasen NC. The Scale for the Assessment of Negative Symptoms in Schizophrenia. Iowa:The University of Iowa, 1984b
26 Andreasen NC. Scale for the Assessment of Negative Symptoms. Iowa City:University of Iowa, 1983
27 Lewdorowicz M, Yoffe Y, Zuberek J, et al. Chemical synthesis and binding activity of the trypanosomatid cap-4 structure. RNA, 2004, 10:1469-1478
28 Chepenik LG, Raffo M, Hampson M, et al. Functional connectivity between ventral prefrontal cortex and amygdala at low frequency in the resting state in bipolar disorder. Psychiatry Psychiatry Research-Neuroimaging, 2010, 182(3):207-210
29 Öngür D, Lundy M, Greenhouse I, et al. Default mode network abnormalities in bipolar disorder and schizophrenia. Psychiatry Research-Neuroimaging, 2010, 183(1):59-68
30 Weinberger DR, Radulescu E. Finding the Elusive Psychiatric "Lesion" With 21st-Century Neuroanatomy:A Note of Caution. Am J Psychiatry, 2016, 173:27-33
31 Howes OD, Kapur S. The dopamine hypothesis of schizophrenia:version Ⅲ——the final common pathway. Schizophr Bull, 2009, 35(3):549-562
32 Fusar-Poli P, Howes OD, Allen P, et al. Abnormal frontostriatal interactions in people with prodromal signs of psychosis:a multimodal imaging study. Arch Gen Psychiatry, 2010, 67(7):683-691
33 Howes OD, Montgomery AJ, Asselin MC, et al. Elevated striatal dopamine function linked to prodromal signs of schizophrenia. Arch Gen Psychiatry, 2009, 66(1):13-20
34 Kegeles LS, Abi-Dargham A, Frankle WG, et al. Increased synaptic dopamine function in associative regions of the striatum in schizophrenia. Arch Gen Psychiatry, 2010, 67(3):231-239
35 Agid O, Mamo D, Ginovart N, et al. Striatal vs extrastriatal dopamine D2 receptors in antipsychotic response——a double-blind PET study in schizophrenia. Neuropsychopharmacology, 2007, 32(6):1209-1215
36 Dandash O, Fornito A, Lee J, et al. Altered striatal functional connectivity in subjects with an at-risk mental state for psychosis. Schizophr Bull, 2014, 40(4):904-913
37 Teng S, Lu CF, Wang PS, et al. Altered resting-state functional connectivity of striatal-thalamic circuit in bipolar disorder. PLoS One, 2014, 9(5):e96422
38 Haznedar MM, Roversi F, Pallanti S, et al. Fronto-thalamostriatal gray and white matter volumes and anisotropy of their connections in bipolar spectrum illnesses. Bipolar Disorders, 2009, 11(1):11-18
39 Sussmann JE, Lymer GKS, McKirdy J, et al. White matter abnormalities in bipolar disorder and schizophrenia detected using diffusion tensor magnetic resonance imaging. Biological Psychiatry, 2005, 57(7):733-742
40 Carlsson A. The current status of the dopamine hypothesis of schizophrenia. Neuropsychopharmacology, 1988, 1(3):179-186
41 Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci, 1986, 9:357-381
42 Andreasen NC, O'Leary DS, Cizadlo T, et al. Schizophrenia and cognitive dysmetria:a positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry. Proc Natl Acad Sci USA, 1996, 93(18):9985-9990
43 Meyer-Lindenberg A, Miletich RS, Kohn PD, et al. Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia. Nat Neurosci, 2002, 5(3):267-271
44 Bernacer J, Prensa L, Gimenez-Amaya JM. Distribution of GABAergic interneurons and dopaminergic cells in the functional territories of the human striatum. PLoS One, 2012, 7 (1):e30504
45 Menon V, Anagnoson RT, Glover GH, et al. Functional magnetic resonance imaging evidence for disrupted basal ganglia function in schizophrenia. Am J Psychiatry, 2001, 158(4):646-649
46 Simpson EH, Kellendonk C, Kandel E. A possible role for the striatum in the pathogenesis of the cognitive symptoms of schizophrenia. Neuron, 2010, 65(5):585-596
47 Howes OD, Montgomery AJ, Asselin MC, et al. Molecular imaging studies of the striatal dopaminergic system in psychosis and predictions for the prodromal phase of psychosis. Br J Psychiatry Suppl, 2007, 51:s13-18

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