Abstract
Structural and functional abnormalities were reported in the brain of patients with adolescent-onset schizophrenia (AOS). However, evidence of abnormal functional connectivity of the brain in AOS patients is limited. Thus, we analyzed the resting-state functional magnetic resonance scans of 48 drug-naive AOS patients and 31 healthy controls to determine their functional connectivity strength (FCS) and examined if FCS abnormalities were correlated with clinical characteristics. Compared with healthy controls, AOS patients showed significantly increased FCS in the left cerebellum VI and right inferior frontal gyrus/insula. A positive correlation was observed between FCS values in the right inferior frontal gyrus/insula and general psychopathology scores of positive and negative syndrome scale. Results suggest that functional connectivity pattern is disrupted in drug-naive AOS patients. The FCS values in this abnormal region have potential for evaluating the disease severity.
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References
Kumra S, Oberstar JV, Sikich L, Findling RL, McClellan JM, Vinogradov S, Charles Schulz S (2008) Efficacy and tolerability of second-generation antipsychotics in children and adolescents with schizophrenia. Schizophr Bull 34(1):60–71
Pina-Camacho L, Parellada M, Kyriakopoulos M (2016) Autism spectrum disorder and schizophrenia: boundaries and uncertainties. BJPsych Adv 22(5):316–324
Paus T, Keshavan M, Giedd JN (2008) Why do many psychiatric disorders emerge during adolescence? Nat Rev Neurosci 9(12):947–957
Zhang Y, Zheng J, Fan X, Guo X, Guo W, Yang G, Chen H, Zhao J, Lv L (2015) Dysfunctional resting-state connectivities of brain regions with structural deficits in drug-naive first-episode schizophrenia adolescents. Schizophr Res 168(1–2):353–359
Kyriakopoulos M, Dima D, Roiser JP, Corrigall R, Barker GJ, Frangou S (2012) Abnormal functional activation and connectivity in the working memory network in early-onset schizophrenia. J Am Acad Child Adolesc Psychiatry 51 (9):911–920 e912
White T, Schmidt M, Kim DI, Calhoun VD (2011) Disrupted functional brain connectivity during verbal working memory in children and adolescents with schizophrenia. Cereb Cortex 21(3):510–518
Tang J, Liao Y, Song M, Gao JH, Zhou B, Tan C, Liu T, Tang Y, Chen J, Chen X (2013) Aberrant default mode functional connectivity in early onset schizophrenia. PLoS One 8(7):e71061
Wang X, Xia M, Lai Y, Dai Z, Cao Q, Cheng Z, Han X, Yang L, Yuan Y, Zhang Y, Li K, Ma H, Shi C, Hong N, Szeszko P, Yu X, He Y (2014) Disrupted resting-state functional connectivity in minimally treated chronic schizophrenia. Schizophr Res 156(2–3):150–156
Meyer-Lindenberg AS, Olsen RK, Kohn PD, Brown T, Egan MF, Weinberger DR, Berman KF (2005) Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia. Arch Gen Psychiatry 62(4):379–386
Guo W, Song Y, Liu F, Zhang Z, Zhang J, Yu M, Liu J, Xiao C, Liu G, Zhao J (2015) Dissociation of functional and anatomical brain abnormalities in unaffected siblings of schizophrenia patients. Clin Neurophysiol 126(5):927–932
Guo W, Liu F, Xiao C, Liu J, Yu M, Zhang Z, Zhang J, Zhao J (2015) Increased short-range and long-range functional connectivity in first-episode, medication-naive schizophrenia at rest. Schizophr Res 166(1–3):144–150
Guo W, Liu F, Xiao C, Yu M, Zhang Z, Liu J, Zhang J, Zhao J (2015) Increased causal connectivity related to anatomical alterations as potential endophenotypes for schizophrenia. Medicine 94(42):0000000000001493
Lynall ME, Bassett DS, Kerwin R, McKenna PJ, Kitzbichler M, Muller U, Bullmore E (2010) Functional connectivity and brain networks in schizophrenia. J Neurosci 30(28):9477–9487
Yu Q, Allen EA, Sui J, Arbabshirani MR, Pearlson G, Calhoun VD (2012) Brain connectivity networks in schizophrenia underlying resting state functional magnetic resonance imaging. Curr Top Med Chem 12(21):2415–2425
van den Heuvel MP, Pol HEH (2010) Exploring the brain network: a review on resting-state fMRI functional connectivity. Eur Neuropsychopharm 20(8):519–534
Joel SE, Caffo BS, Zijl PCM, Pekar JJ (2011) On the relationship between seed-based and ICA-based measures of functional connectivity. Magn Reson Med 66(3):644–657
Reijneveld JC, Ponten SC, Berendse HW, Stam CJ (2007) The application of graph theoretical analysis to complex networks in the brain. Clin Neurophysiol 118(11):2317–2331
Xia M, He Y (2011) Magnetic resonance imaging and graph theoretical analysis of complex brain networks in neuropsychiatric disorders. Brain Connect 1(5):349–365
Liang X, Zou Q, He Y, Yang Y (2013) Coupling of functional connectivity and regional cerebral blood flow reveals a physiological basis for network hubs of the human brain. Proc Natl Acad Sci USA 110(5):1929–1934
Harrison JE (2005) Orthodontic clinical trials III: reporting of ethical issues associated with clinical trials published in three orthodontic journals between 1989 and 1998. J Orthod 32(2):115–121
Chao-Gan Y, Yu-Feng Z (2010) DPARSF: a MATLAB toolbox for “pipeline” data analysis of resting-state fMRI. Front Syst Neurosci 4:13
Henseler I, Falkai P, Gruber O (2010) Disturbed functional connectivity within brain networks subserving domain-specific subcomponents of working memory in schizophrenia: relation to performance and clinical symptoms. J Psychiatr Res 44(6):364–372
Biswal B, Yetkin FZ, Haughton VM, Hyde JS (1995) Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med 34(4):537–541
Lowe MJ, Mock BJ, Sorenson JA (1998) Functional connectivity in single and multislice echoplanar imaging using resting-state fluctuations. Neuroimage 7(2):119–132
Su QJ, Yao DP, Jiang ML, Liu F, Jiang JJ, Xu CX, Dai Y, Yu MY, Long LL, Li HZ, Liu JR, Zhang ZK, Zhang J, Xiao CQ, Guo WB (2015) Increased functional connectivity strength of right inferior temporal gyrus in first-episode, drug-naive somatization disorder. Aust Nz J Psychiatry 49(1):74–81
Liu F, Zhu C, Wang Y, Guo W, Li M, Wang W, Long Z, Meng Y, Cui Q, Zeng L, Gong Q, Zhang W, Chen H (2015) Disrupted cortical hubs in functional brain networks in social anxiety disorder. Clin Neurophysiol 126(9):1711–1716
Power JD, Barnes KA, Snyder AZ, Schlaggar BL, Petersen SE (2012) Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage 59(3):2142–2154
Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, Mazoyer B, Joliot M (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15(1):273–289
Andreasen NC, Pierson R (2008) The role of the cerebellum in schizophrenia. Biol Psychiatry 64(2):81–88
Grodd W, Hulsmann E, Lotze M, Wildgruber D, Erb M (2001) Sensorimotor mapping of the human cerebellum: fMRI evidence of somatotopic organization. Hum Brain Mapp 13(2):55–73
Glickstein M, Doron K (2008) Cerebellum: connections and functions. Cerebellum 7(4):589–594
Ho BC, Mola C, Andreasen NC (2004) Cerebellar dysfunction in neuroleptic naive schizophrenia patients: clinical, cognitive, and neuroanatomic correlates of cerebellar neurologic signs. Biol Psychiatry 55(12):1146–1153
Paradiso S, Andreasen NC, Crespo-Facorro B, O’Leary DS, Watkins GL, Boles Ponto LL, Hichwa RD (2003) Emotions in unmedicated patients with schizophrenia during evaluation with positron emission tomography. Am J Psychiatry 160(10):1775–1783
Takahashi H, Koeda M, Oda K, Matsuda T, Matsushima E, Matsuura M, Asai K, Okubo Y (2004) An fMRI study of differential neural response to affective pictures in schizophrenia. Neuroimage 22(3):1247–1254
Wilke M, Kaufmann C, Grabner A, Putz B, Wetter TC, Auer DP (2001) Gray matter-changes and correlates of disease severity in schizophrenia: a statistical parametric mapping study. Neuroimage 13(5):814–824
Wang H, Guo W, Liu F, Wang G, Lyu H, Wu R, Chen J, Wang S, Li L, Zhao J (2016) Patients with first-episode, drug-naive schizophrenia and subjects at ultra-high risk of psychosis shared increased cerebellar-default mode network connectivity at rest. Sci Rep 6. doi:10.1038/srep26124
Nopoulos PC, Ceilley JW, Gailis EA, Andreasen NC (1999) An MRI study of cerebellar vermis morphology in patients with schizophrenia: evidence in support of the cognitive dysmetria concept. Biol Psychiatry 46(5):703–711
Liegeois F, Morgan AT, Connelly A, Vargha-Khadem F (2011) Endophenotypes of FOXP2: dysfunction within the human articulatory network. Eur J Paediatr Neurol 15(4):283–288
Aron AR, Robbins TW, Poldrack RA (2004) Inhibition and the right inferior frontal cortex. Trends Cogn Sci 8(4):170–177
Hirshorn EA, Thompson-Schill SL (2006) Role of the left inferior frontal gyrus in covert word retrieval: neural correlates of switching during verbal fluency. Neuropsychologia 44(12):2547–2557
Iwashiro N, Suga M, Takano Y, Inoue H, Natsubori T, Satomura Y, Koike S, Yahata N, Murakami M, Katsura M, Gonoi W, Sasaki H, Takao H, Abe O, Kasai K, Yamasue H (2012) Localized gray matter volume reductions in the pars triangularis of the inferior frontal gyrus in individuals at clinical high-risk for psychosis and first episode for schizophrenia. Schizophr Res 137(1–3):124–131
Wang S, Wang G, Lv H, Wu R, Zhao J, Guo W (2016) Abnormal regional homogeneity as potential imaging biomarker for psychosis risk syndrome: a resting-state fMRI study and support vector machine analysis. Sci Rep 6. doi:10.1038/srep27619
Onitsuka T, Shenton ME, Salisbury DF, Dickey CC, Kasai K, Toner SK, Frumin M, Kikinis R, Jolesz FA, McCarley RW (2004) Middle and inferior temporal gyrus gray matter volume abnormalities in chronic schizophrenia: an MRI study. Am J Psychiatry 161(9):1603–1611
Wylie KP, Tregellas JR (2010) The role of the insula in schizophrenia. Schizophr Res 123(2–3):93–104
Kim JJ, Andreasen NC, O’Leary DS, Wiser AK, Ponto LL, Watkins GL, Hichwa RD (1999) Direct comparison of the neural substrates of recognition memory for words and faces. Brain 122(Pt 6):1069–1083
Kim J-J, Youn T, Lee JM, Kim IY, Kim SI, Kwon JS (2003) Morphometric abnormality of the insula in schizophrenia: a comparison with obsessive–compulsive disorder and normal control using MRI. Schizophr Res 60(2–3):191–198
Crespo-Facorro B, Kim J-J, Andreasen NC, O’Leary DS, Bockholt HJ, Magnotta V (2000) Insular cortex abnormalities in schizophrenia: a structural magnetic resonance imaging study of first-episode patients. Schizophr Res 46(1):35–43
Acknowledgements
We thank Yi He (Chengdu FX Biotechnology Co., Ltd.) for assistance in the methodological preparation.
Author contribution
Authors SW, WG, and JZ designed the study. Author SW wrote the protocol and the first draft of the manuscript. Authors SW, YZ, and LL collected the original imaging data. Authors SW, YZ, WG, and RW managed and analyzed the imaging data. Authors SW, LL, and XF undertook the statistical analysis and managed the literature searches. All authors contributed to and have approved the final manuscript.
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This study was supported by grants from the National Natural Science Foundation of China (Grant Nos. 81260210, 81571310, 81630033 and 81361120396), the National Key Basic Research Program (2016YFC1307104), and the Natural Science Foundation of Guangxi Province for Distinguished Young Scientists (Grant No. 2014GXNSFGA118010).
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We declare no conflict of interests (both financial and personal) related to the present study.
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S. Wang and Y. Zhan contributed equally to this work.
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Wang, S., Zhan, Y., Zhang, Y. et al. Abnormal functional connectivity strength in patients with adolescent-onset schizophrenia: a resting-state fMRI study. Eur Child Adolesc Psychiatry 26, 839–845 (2017). https://doi.org/10.1007/s00787-017-0958-2
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DOI: https://doi.org/10.1007/s00787-017-0958-2