Brain network informed subject community detection in early-onset schizophrenia

Zhi Yang, Yong Xu, Ting Xu, Colin Weir Hoy, Daniel A. Handwerker, Gang Chen, Georg Franz Josef Northoff, Xi Nian Zuo, Peter A. Bandettini

研究成果: 雜誌貢獻文章

30 引文 (Scopus)

摘要

Early-onset schizophrenia (EOS) offers a unique opportunity to study pathophysiological mechanisms and development of schizophrenia. Using 26 drug-naïve, first-episode EOS patients and 25 age-and gender-matched control subjects, we examined intrinsic connectivity network (ICN) deficits underlying EOS. Due to the emerging inconsistency between behavior-based psychiatric disease classification system and the underlying brain dysfunctions, we applied a fully data-driven approach to investigate whether the subjects can be grouped into highly homogeneous communities according to the characteristics of their ICNs. The resultant subject communities and the representative characteristics of ICNs were then associated with the clinical diagnosis and multivariate symptom patterns. A default mode ICN was statistically absent in EOS patients. Another frontotemporal ICN further distinguished EOS patients with predominantly negative symptoms. Connectivity patterns of this second network for the EOS patients with predominantly positive symptom were highly similar to typically developing controls. Our post-hoc functional connectivity modeling confirmed that connectivity strength in this frontotemporal circuit was significantly modulated by relative severity of positive and negative syndromes in EOS. This study presents a novel subtype discovery approach based on brain networks and proposes complex links between brain networks and symptom patterns in EOS.
原文英語
期刊Scientific Reports
4
DOIs
出版狀態已發佈 - 2014
對外發佈Yes

指紋

Schizophrenia
Brain
Psychiatry
Pharmaceutical Preparations

引用此文

Yang, Z., Xu, Y., Xu, T., Hoy, C. W., Handwerker, D. A., Chen, G., ... Bandettini, P. A. (2014). Brain network informed subject community detection in early-onset schizophrenia. Scientific Reports, 4. https://doi.org/10.1038/srep05549

Brain network informed subject community detection in early-onset schizophrenia. / Yang, Zhi; Xu, Yong; Xu, Ting; Hoy, Colin Weir; Handwerker, Daniel A.; Chen, Gang; Northoff, Georg Franz Josef; Zuo, Xi Nian; Bandettini, Peter A.

於: Scientific Reports, 卷 4, 2014.

研究成果: 雜誌貢獻文章

Yang, Z, Xu, Y, Xu, T, Hoy, CW, Handwerker, DA, Chen, G, Northoff, GFJ, Zuo, XN & Bandettini, PA 2014, 'Brain network informed subject community detection in early-onset schizophrenia', Scientific Reports, 卷 4. https://doi.org/10.1038/srep05549
Yang, Zhi ; Xu, Yong ; Xu, Ting ; Hoy, Colin Weir ; Handwerker, Daniel A. ; Chen, Gang ; Northoff, Georg Franz Josef ; Zuo, Xi Nian ; Bandettini, Peter A. / Brain network informed subject community detection in early-onset schizophrenia. 於: Scientific Reports. 2014 ; 卷 4.
@article{ae13d90ebd834d24a746df15e5c9a942,
title = "Brain network informed subject community detection in early-onset schizophrenia",
abstract = "Early-onset schizophrenia (EOS) offers a unique opportunity to study pathophysiological mechanisms and development of schizophrenia. Using 26 drug-na{\"i}ve, first-episode EOS patients and 25 age-and gender-matched control subjects, we examined intrinsic connectivity network (ICN) deficits underlying EOS. Due to the emerging inconsistency between behavior-based psychiatric disease classification system and the underlying brain dysfunctions, we applied a fully data-driven approach to investigate whether the subjects can be grouped into highly homogeneous communities according to the characteristics of their ICNs. The resultant subject communities and the representative characteristics of ICNs were then associated with the clinical diagnosis and multivariate symptom patterns. A default mode ICN was statistically absent in EOS patients. Another frontotemporal ICN further distinguished EOS patients with predominantly negative symptoms. Connectivity patterns of this second network for the EOS patients with predominantly positive symptom were highly similar to typically developing controls. Our post-hoc functional connectivity modeling confirmed that connectivity strength in this frontotemporal circuit was significantly modulated by relative severity of positive and negative syndromes in EOS. This study presents a novel subtype discovery approach based on brain networks and proposes complex links between brain networks and symptom patterns in EOS.",
keywords = "adolescent, brain mapping, case control study, child, female, frontal lobe, human, male, multivariate analysis, nerve cell network, pathophysiology, reproducibility, Schizophrenia, Childhood, temporal lobe, Adolescent, Brain Mapping, Case-Control Studies, Child, Female, Frontal Lobe, Humans, Male, Multivariate Analysis, Nerve Net, Reproducibility of Results, Temporal Lobe",
author = "Zhi Yang and Yong Xu and Ting Xu and Hoy, {Colin Weir} and Handwerker, {Daniel A.} and Gang Chen and Northoff, {Georg Franz Josef} and Zuo, {Xi Nian} and Bandettini, {Peter A.}",
note = "Cited By :5 Export Date: 11 May 2016 Correspondence Address: Xu, Y.; Key Laboratory of Behavioral Science and Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; email: xuyongsmu@vip.163.com References: Vyas, N.S., Hadjulis, M., Vourdas, A., Byrne, P., Frangou, S., The maudsley early onset schizophrenia study. Predictors of psychosocial outcome at 4-year followup (2007) Eur. Child Adoles. Psy., 16, pp. 465-470; Rabinowitz, J., Levine, S.Z., Hafner, H., A population based elaboration of the role of age of onset on the course of schizophrenia (2006) Schizophrenia Research, 88 (1-3), pp. 96-101. , DOI 10.1016/j.schres.2006.07.007, PII S0920996406003203; Frazier, J.A., Alaghband-Rad, J., Jacobsen, L., Lenane, M.C., Hamburger, S., Albus, K., Smith, A., Rapoport, J.L., Pubertal development and onset of psychosis in childhood onset schizophrenia (1997) Psychiatry Research, 70 (1), pp. 1-7. , DOI 10.1016/S0165-1781(97)03062-X, PII S016517819703062X; Hollis, C., Adult outcomes of child-and adolescent-onset schizophrenia: Diagnostic stability and predictive validity (2000) Am. J. Psychiat., 157, pp. 1652-1659; Vyas, N.S., Kumra, S., Puri, B.K., What insights can we gain from studying earlyonset schizophrenia? the neurodevelopmental pathway and beyond (2010) Expert Rev. Neurother., 10, pp. 1243-1247; Frazier, J.A., Giedd, J.N., Hamburger, S.D., Albus, K.E., Kassen, D., Vaituzis, A.C., Rajapakse, J.C., Rapoport, J.L., Brain anatomic magnetic resonance imaging in childhood-onset schizophrenia (1996) Archives of General Psychiatry, 53 (7), pp. 617-624; Rapoport, J.L., Gogtay, N., Brain neuroplasticity in healthy, hyperactive and psychotic children: Insights from neuroimaging (2008) Neuropsychopharmacology, 33 (1), pp. 181-197. , DOI 10.1038/sj.npp.1301553, PII 1301553; Thompson, P.M., Vidal, C., Giedd, J.N., Gochman, P., Blumenthal, J., Nicolson, R., Toga, A.W., Rapoport, J.L., Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia (2001) Proceedings of the National Academy of Sciences of the United States of America, 98 (20), pp. 11650-11655. , DOI 10.1073/pnas.201243998; Greicius, M., Resting-state functional connectivity in neuropsychiatric disorders (2008) Curr. Opin. Neurol., 21, pp. 424-430; Lynall, M.E., Functional connectivity and brain networks in schizophrenia (2010) J. Neurosci., 30, pp. 9477-9487; Schmitt, A., Hasan, A., Gruber, O., Falkai, P., Schizophrenia as a disorder of disconnectivity (2011) Eur. Arch. Psy. Clin. N., 261, pp. 150-154; Kapur, S., Phillips, A.G., Insel, T.R., Why has it taken so long for biological psychiatry to develop clinical tests and what to do about it? (2012) Mol Psychiatr, 17, pp. 1174-1179; Insel, T., Research domain criteria (RDoC): Toward a new classification framework for research on mental disorders (2010) Am. J. Psychiat., 167, pp. 748-751; Yang, Z., LaConte, S., Weng, X., Hu, X., Ranking and averaging independent component analysis by reproducibility (RAICAR) (2008) Human Brain Mapping, 29 (6), pp. 711-725. , DOI 10.1002/hbm.20432; Yang, Z., Generalized RAICAR: Discover homogeneous subject (sub)groups by reproducibility of their intrinsic connectivity networks (2012) Neuroimage, 63, pp. 403-414; Yang, Z., Connectivity trajectory across lifespan differentiates the precuneus from the default network (2014) Neuroimage, 89, pp. 45-56; Zapala, M.A., Schork, N.J., Statistical properties of multivariate distance matrix regression for high-dimensional data analysis (2012) Front. Genet., 3, p. 190; Seiferth, N.Y., Neuronal correlates of facial emotion discrimination in early onset schizophrenia (2009) Neuropsychopharmacol, 34, pp. 477-487; Rapoport, J.L., Giedd, J.N., Blumenthal, J., Hamburger, S., Jeffries, N., Fernandez, T., Nicolson, R., Evans, A., Progressive cortical change during adolescence in childhood-onset schizophrenia: A longitudinal magnetic resonance imaging study (1999) Archives of General Psychiatry, 56 (7), pp. 649-654. , DOI 10.1001/archpsyc.56.7.649; Jacobsen, L.K., Giedd, J.N., Berquin, P.C., Krain, A.L., Hamburger, S.D., Kumra, S., Rapoport, J.L., Quantitative morphology of the cerebellum and fourth ventricle in childhood-onset schizophrenia (1997) American Journal of Psychiatry, 154 (12), pp. 1663-1669; Marquardt, R.K., Levitt, J.G., Blanton, R.E., Caplan, R., Asarnow, R., Siddarth, P., Fadale, D., Toga, A.W., Abnormal development of the anterior cingulate in childhood-onset schizophrenia: A preliminary quantitative MRI study (2005) Psychiatry Research - Neuroimaging, 138 (3), pp. 221-233. , DOI 10.1016/j.pscychresns.2005.01.001; Hagmann, P., Mapping the structural core of human cerebral cortex (2008) PLoS Biol, 6, pp. e159; Van Den Heuvel, M.P., Sporns, O., Rich-club organization of the human connectome (2011) J. Neurosci., 31, pp. 15775-15786; Sporns, O., The human connectome: A complex network (2011) Ann. N. Y. Acad. Sci., 1224, pp. 109-125; Greicius, M.D., Krasnow, B., Reiss, A.L., Menon, V., Functional connectivity in the resting brain: A network analysis of the default mode hypothesis (2003) Proceedings of the National Academy of Sciences of the United States of America, 100 (1), pp. 253-258. , DOI 10.1073/pnas.0135058100; Raichle, M.E., MacLeod, A.M., Snyder, A.Z., Powers, W.J., Gusnard, D.A., Shulman, G.L., A default mode of brain function (2001) Proceedings of the National Academy of Sciences of the United States of America, 98 (2), pp. 676-682. , DOI 10.1073/pnas.98.2.676; Cavanna, A.E., The precuneus and consciousness (2007) CNS Spectrums, 12 (7), pp. 545-552; Wallentin, M., Weed, E., Ostergaard, L., Mouridsen, K., Roepstorff, A., Accessing the mental space - Spatial working memory processes for language and vision overlap in precuneus (2008) Human Brain Mapping, 29 (5), pp. 524-532. , DOI 10.1002/hbm.20413; Buckner, R.L., Andrews-Hanna, J.R., Schacter, D.L., The brain's default network: Anatomy, function, and relevance to disease (2008) Annals of the New York Academy of Sciences, 1124, pp. 1-38. , DOI 10.1196/annals.1440.011, The Year in Cognitive Neuroscience 2008; Whitfield-Gabrieli, S., Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia (2009) Proc. Natl. Acad. Sci. U. S. A., 106, pp. 1279-1284; Kuhn, S., Gallinat, J., Resting-state brain activity in schizophrenia and major depression: A quantitative meta-analysis (2013) Schizophr. Bull., 39, pp. 358-365; Mitchell, R.L.C., Elliott, R., Woodruff, P.W.R., FMRI and cognitive dysfunction in schizophrenia (2001) Trends in Cognitive Sciences, 5 (2), pp. 71-81. , DOI 10.1016/S1364-6613(00)01599-0, PII S1364661300015990; Puri, B.K., Progressive structural brain changes in schizophrenia (2010) Expert Rev. Neurother., 10, pp. 33-42; Flaum, M., Symptom dimensions and brain morphology in schizophrenia and related psychotic disorders (1995) J. Psychiatr. Res., 29, pp. 261-276; Antonova, E., Sharma, T., Morris, R., Kumari, V., The relationship between brain structure and neurocognition in schizophrenia: A selective review (2004) Schizophrenia Research, 70 (2-3), pp. 117-145. , DOI 10.1016/j.schres.2003.12.002, PII S0920996404000027; Young, A.H., A magnetic resonance imaging study of schizophrenia: Brain structure and clinical symptoms (1991) Br. J. Psychiat., 158, pp. 158-164; Roberts, G.W., Schizophrenia: A neuropathological perspective (1991) Br. J. Psychiat., 158, pp. 8-17; Woodruff, P.W.R., Wright, I.C., Shuriquie, N., Russouw, H., Rushe, T., Howard, R.J., Graves, M., Murray, R.M., Structural brain abnormalities in male schizophrenics reflect fronto-temporal dissociation (1997) Psychological Medicine, 27 (6), pp. 1257-1266. , DOI 10.1017/S0033291797005229; Giedd, J.N., Jeffries, N.O., Blumenthal, J., Castellanos, F.X., Vaituzis, A.C., Fernandez, T., Hamburger, S.D., Rapoport, J.L., Childhood-onset schizophrenia: Progressive brain changes during adolescence (1999) Biological Psychiatry, 46 (7), pp. 892-898. , DOI 10.1016/S0006-3223(99)00072-4, PII S0006322399000724; Jacobson, S., Structural and functional brain correlates of subclinical psychotic symptoms in 11-13 year old school children (2010) Neuroimage, 49, pp. 1875-1885; Jacobson McEwen, S., Resting-state connectivity deficits associated with impaired inhibitory control in non-treatment-seeking adolescents with psychotic symptoms (2014) Acta Psychiatr. Scand., 129, pp. 134-142; Yung, A.R., McGorry, P.O., The prodromal phase of first-episode psychosis: Past and current conceptualizations (1996) Schizophrenia Bulletin, 22 (2), pp. 353-370; Yung, A.R., McGorry, P.D., McFarlane, C.A., Jackson, H.J., Patton, G.C., Rakkar, A., Monitoring and care of young people at incipient risk of psychosis (1996) Schizophrenia Bulletin, 22 (2), pp. 283-303; Ziauddeen, H., Dibben, C., Kipps, C., Hodges, J.R., McKenna, P.J., Negative schizophrenic symptoms and the frontal lobe syndrome: One and the same? (2011) Eur. Arch. Psy. Clin. N., 261, pp. 59-67; Peralta, V., Psychometric properties of the positive and negative syndrome scale (PANSS) in schizophrenia (1994) Psychiatry Research, 53 (1), pp. 31-40. , DOI 10.1016/0165-1781(94)90093-0; Lancon, C., Auquier, P., Nayt, G., Reine, G., Stability of the five-factor structure of the Positive and Negative Syndrome Scale (PANSS) (2000) Schizophrenia Research, 42 (3), pp. 231-239. , DOI 10.1016/S0920-9964(99)00129-2, PII S0920996499001292; Borsook, D., Becerra, L., Fava, M., Use of functional imaging across clinical phases in CNS drug development (2013) Transl. Psychiatry., 3, pp. e282; Emsley, R., Rabinowitz, J., Torreman, M., Schooler, N., Kapala, L., Davidson, M., McGory, P., The factor structure for the Positive and Negative Syndrome Scale (PANSS) in recent-onset psychosis (2003) Schizophrenia Research, 61 (1), pp. 47-57. , DOI 10.1016/S0920-9964(02)00302-X; Andrews, G., Brugha, T., Thase, M.E., Duffy, F.F., Rucci, P., Slade, T., Dimensionality and the category of major depressive episode (2007) International Journal of Methods in Psychiatric Research, 16 (SUPPL. 1), pp. S41-S51. , DOI 10.1002/mpr.216; Miller, J., What is the probability of replicating a statistically significant effect? (2009) Psychon. B. Rev., 16, pp. 617-640; (2000) Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR, , Amercian Psychiatric Association American Psychiatric Publishing, Inc; Kay, S.R., Fiszbein, A., Opler, L.A., The positive and negative syndrome scale (PANSS) for schizophrenia (1987) Schizophrenia Bulletin, 13 (2), pp. 261-276; Zuo, X.N., Toward reliable characterization of functional homogeneity in the human brain: Preprocessing, scan duration, imaging resolution and computational space (2013) Neuroimage, 65, pp. 374-386; Friston, K.J., Williams, S., Howard, R., Frackowiak, R.S., Turner, R., Movementrelated effects in fMRI time-series (1996) Magn. Reson. Med., 35, pp. 346-355; Patriat, R., The effect of resting condition on resting-state fMRI reliability and consistency: A comparison between resting with eyes open, closed, and fixated (2013) Neuroimage, 78, pp. 463-473; Beckmann, C.F., Smith, S.M., Probabilistic independent component analysis for functional magnetic resonance imaging (2004) IEEE Trans. Med. Imaging, 23, pp. 137-152; Palla, G., Derenyi, I., Farkas, I., Vicsek, T., Uncovering the overlapping community structure of complex networks in nature and society (2005) Nature, 435 (7043), pp. 814-818. , DOI 10.1038/nature03607; Luce, R.D., Perry, A.D., A method of matrix analysis of group structure (1949) Psychometrika, 14, pp. 95-116",
year = "2014",
doi = "10.1038/srep05549",
language = "English",
volume = "4",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Brain network informed subject community detection in early-onset schizophrenia

AU - Yang, Zhi

AU - Xu, Yong

AU - Xu, Ting

AU - Hoy, Colin Weir

AU - Handwerker, Daniel A.

AU - Chen, Gang

AU - Northoff, Georg Franz Josef

AU - Zuo, Xi Nian

AU - Bandettini, Peter A.

N1 - Cited By :5 Export Date: 11 May 2016 Correspondence Address: Xu, Y.; Key Laboratory of Behavioral Science and Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; email: xuyongsmu@vip.163.com References: Vyas, N.S., Hadjulis, M., Vourdas, A., Byrne, P., Frangou, S., The maudsley early onset schizophrenia study. Predictors of psychosocial outcome at 4-year followup (2007) Eur. Child Adoles. Psy., 16, pp. 465-470; Rabinowitz, J., Levine, S.Z., Hafner, H., A population based elaboration of the role of age of onset on the course of schizophrenia (2006) Schizophrenia Research, 88 (1-3), pp. 96-101. , DOI 10.1016/j.schres.2006.07.007, PII S0920996406003203; Frazier, J.A., Alaghband-Rad, J., Jacobsen, L., Lenane, M.C., Hamburger, S., Albus, K., Smith, A., Rapoport, J.L., Pubertal development and onset of psychosis in childhood onset schizophrenia (1997) Psychiatry Research, 70 (1), pp. 1-7. , DOI 10.1016/S0165-1781(97)03062-X, PII S016517819703062X; Hollis, C., Adult outcomes of child-and adolescent-onset schizophrenia: Diagnostic stability and predictive validity (2000) Am. J. Psychiat., 157, pp. 1652-1659; Vyas, N.S., Kumra, S., Puri, B.K., What insights can we gain from studying earlyonset schizophrenia? the neurodevelopmental pathway and beyond (2010) Expert Rev. Neurother., 10, pp. 1243-1247; Frazier, J.A., Giedd, J.N., Hamburger, S.D., Albus, K.E., Kassen, D., Vaituzis, A.C., Rajapakse, J.C., Rapoport, J.L., Brain anatomic magnetic resonance imaging in childhood-onset schizophrenia (1996) Archives of General Psychiatry, 53 (7), pp. 617-624; Rapoport, J.L., Gogtay, N., Brain neuroplasticity in healthy, hyperactive and psychotic children: Insights from neuroimaging (2008) Neuropsychopharmacology, 33 (1), pp. 181-197. , DOI 10.1038/sj.npp.1301553, PII 1301553; Thompson, P.M., Vidal, C., Giedd, J.N., Gochman, P., Blumenthal, J., Nicolson, R., Toga, A.W., Rapoport, J.L., Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia (2001) Proceedings of the National Academy of Sciences of the United States of America, 98 (20), pp. 11650-11655. , DOI 10.1073/pnas.201243998; Greicius, M., Resting-state functional connectivity in neuropsychiatric disorders (2008) Curr. Opin. Neurol., 21, pp. 424-430; Lynall, M.E., Functional connectivity and brain networks in schizophrenia (2010) J. Neurosci., 30, pp. 9477-9487; Schmitt, A., Hasan, A., Gruber, O., Falkai, P., Schizophrenia as a disorder of disconnectivity (2011) Eur. Arch. Psy. Clin. N., 261, pp. 150-154; Kapur, S., Phillips, A.G., Insel, T.R., Why has it taken so long for biological psychiatry to develop clinical tests and what to do about it? (2012) Mol Psychiatr, 17, pp. 1174-1179; Insel, T., Research domain criteria (RDoC): Toward a new classification framework for research on mental disorders (2010) Am. J. Psychiat., 167, pp. 748-751; Yang, Z., LaConte, S., Weng, X., Hu, X., Ranking and averaging independent component analysis by reproducibility (RAICAR) (2008) Human Brain Mapping, 29 (6), pp. 711-725. , DOI 10.1002/hbm.20432; Yang, Z., Generalized RAICAR: Discover homogeneous subject (sub)groups by reproducibility of their intrinsic connectivity networks (2012) Neuroimage, 63, pp. 403-414; Yang, Z., Connectivity trajectory across lifespan differentiates the precuneus from the default network (2014) Neuroimage, 89, pp. 45-56; Zapala, M.A., Schork, N.J., Statistical properties of multivariate distance matrix regression for high-dimensional data analysis (2012) Front. Genet., 3, p. 190; Seiferth, N.Y., Neuronal correlates of facial emotion discrimination in early onset schizophrenia (2009) Neuropsychopharmacol, 34, pp. 477-487; Rapoport, J.L., Giedd, J.N., Blumenthal, J., Hamburger, S., Jeffries, N., Fernandez, T., Nicolson, R., Evans, A., Progressive cortical change during adolescence in childhood-onset schizophrenia: A longitudinal magnetic resonance imaging study (1999) Archives of General Psychiatry, 56 (7), pp. 649-654. , DOI 10.1001/archpsyc.56.7.649; Jacobsen, L.K., Giedd, J.N., Berquin, P.C., Krain, A.L., Hamburger, S.D., Kumra, S., Rapoport, J.L., Quantitative morphology of the cerebellum and fourth ventricle in childhood-onset schizophrenia (1997) American Journal of Psychiatry, 154 (12), pp. 1663-1669; Marquardt, R.K., Levitt, J.G., Blanton, R.E., Caplan, R., Asarnow, R., Siddarth, P., Fadale, D., Toga, A.W., Abnormal development of the anterior cingulate in childhood-onset schizophrenia: A preliminary quantitative MRI study (2005) Psychiatry Research - Neuroimaging, 138 (3), pp. 221-233. , DOI 10.1016/j.pscychresns.2005.01.001; Hagmann, P., Mapping the structural core of human cerebral cortex (2008) PLoS Biol, 6, pp. e159; Van Den Heuvel, M.P., Sporns, O., Rich-club organization of the human connectome (2011) J. Neurosci., 31, pp. 15775-15786; Sporns, O., The human connectome: A complex network (2011) Ann. N. Y. Acad. Sci., 1224, pp. 109-125; Greicius, M.D., Krasnow, B., Reiss, A.L., Menon, V., Functional connectivity in the resting brain: A network analysis of the default mode hypothesis (2003) Proceedings of the National Academy of Sciences of the United States of America, 100 (1), pp. 253-258. , DOI 10.1073/pnas.0135058100; Raichle, M.E., MacLeod, A.M., Snyder, A.Z., Powers, W.J., Gusnard, D.A., Shulman, G.L., A default mode of brain function (2001) Proceedings of the National Academy of Sciences of the United States of America, 98 (2), pp. 676-682. , DOI 10.1073/pnas.98.2.676; Cavanna, A.E., The precuneus and consciousness (2007) CNS Spectrums, 12 (7), pp. 545-552; Wallentin, M., Weed, E., Ostergaard, L., Mouridsen, K., Roepstorff, A., Accessing the mental space - Spatial working memory processes for language and vision overlap in precuneus (2008) Human Brain Mapping, 29 (5), pp. 524-532. , DOI 10.1002/hbm.20413; Buckner, R.L., Andrews-Hanna, J.R., Schacter, D.L., The brain's default network: Anatomy, function, and relevance to disease (2008) Annals of the New York Academy of Sciences, 1124, pp. 1-38. , DOI 10.1196/annals.1440.011, The Year in Cognitive Neuroscience 2008; Whitfield-Gabrieli, S., Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia (2009) Proc. Natl. Acad. Sci. U. S. A., 106, pp. 1279-1284; Kuhn, S., Gallinat, J., Resting-state brain activity in schizophrenia and major depression: A quantitative meta-analysis (2013) Schizophr. Bull., 39, pp. 358-365; Mitchell, R.L.C., Elliott, R., Woodruff, P.W.R., FMRI and cognitive dysfunction in schizophrenia (2001) Trends in Cognitive Sciences, 5 (2), pp. 71-81. , DOI 10.1016/S1364-6613(00)01599-0, PII S1364661300015990; Puri, B.K., Progressive structural brain changes in schizophrenia (2010) Expert Rev. Neurother., 10, pp. 33-42; Flaum, M., Symptom dimensions and brain morphology in schizophrenia and related psychotic disorders (1995) J. Psychiatr. Res., 29, pp. 261-276; Antonova, E., Sharma, T., Morris, R., Kumari, V., The relationship between brain structure and neurocognition in schizophrenia: A selective review (2004) Schizophrenia Research, 70 (2-3), pp. 117-145. , DOI 10.1016/j.schres.2003.12.002, PII S0920996404000027; Young, A.H., A magnetic resonance imaging study of schizophrenia: Brain structure and clinical symptoms (1991) Br. J. Psychiat., 158, pp. 158-164; Roberts, G.W., Schizophrenia: A neuropathological perspective (1991) Br. J. Psychiat., 158, pp. 8-17; Woodruff, P.W.R., Wright, I.C., Shuriquie, N., Russouw, H., Rushe, T., Howard, R.J., Graves, M., Murray, R.M., Structural brain abnormalities in male schizophrenics reflect fronto-temporal dissociation (1997) Psychological Medicine, 27 (6), pp. 1257-1266. , DOI 10.1017/S0033291797005229; Giedd, J.N., Jeffries, N.O., Blumenthal, J., Castellanos, F.X., Vaituzis, A.C., Fernandez, T., Hamburger, S.D., Rapoport, J.L., Childhood-onset schizophrenia: Progressive brain changes during adolescence (1999) Biological Psychiatry, 46 (7), pp. 892-898. , DOI 10.1016/S0006-3223(99)00072-4, PII S0006322399000724; Jacobson, S., Structural and functional brain correlates of subclinical psychotic symptoms in 11-13 year old school children (2010) Neuroimage, 49, pp. 1875-1885; Jacobson McEwen, S., Resting-state connectivity deficits associated with impaired inhibitory control in non-treatment-seeking adolescents with psychotic symptoms (2014) Acta Psychiatr. Scand., 129, pp. 134-142; Yung, A.R., McGorry, P.O., The prodromal phase of first-episode psychosis: Past and current conceptualizations (1996) Schizophrenia Bulletin, 22 (2), pp. 353-370; Yung, A.R., McGorry, P.D., McFarlane, C.A., Jackson, H.J., Patton, G.C., Rakkar, A., Monitoring and care of young people at incipient risk of psychosis (1996) Schizophrenia Bulletin, 22 (2), pp. 283-303; Ziauddeen, H., Dibben, C., Kipps, C., Hodges, J.R., McKenna, P.J., Negative schizophrenic symptoms and the frontal lobe syndrome: One and the same? (2011) Eur. Arch. Psy. Clin. N., 261, pp. 59-67; Peralta, V., Psychometric properties of the positive and negative syndrome scale (PANSS) in schizophrenia (1994) Psychiatry Research, 53 (1), pp. 31-40. , DOI 10.1016/0165-1781(94)90093-0; Lancon, C., Auquier, P., Nayt, G., Reine, G., Stability of the five-factor structure of the Positive and Negative Syndrome Scale (PANSS) (2000) Schizophrenia Research, 42 (3), pp. 231-239. , DOI 10.1016/S0920-9964(99)00129-2, PII S0920996499001292; Borsook, D., Becerra, L., Fava, M., Use of functional imaging across clinical phases in CNS drug development (2013) Transl. Psychiatry., 3, pp. e282; Emsley, R., Rabinowitz, J., Torreman, M., Schooler, N., Kapala, L., Davidson, M., McGory, P., The factor structure for the Positive and Negative Syndrome Scale (PANSS) in recent-onset psychosis (2003) Schizophrenia Research, 61 (1), pp. 47-57. , DOI 10.1016/S0920-9964(02)00302-X; Andrews, G., Brugha, T., Thase, M.E., Duffy, F.F., Rucci, P., Slade, T., Dimensionality and the category of major depressive episode (2007) International Journal of Methods in Psychiatric Research, 16 (SUPPL. 1), pp. S41-S51. , DOI 10.1002/mpr.216; Miller, J., What is the probability of replicating a statistically significant effect? (2009) Psychon. B. Rev., 16, pp. 617-640; (2000) Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR, , Amercian Psychiatric Association American Psychiatric Publishing, Inc; Kay, S.R., Fiszbein, A., Opler, L.A., The positive and negative syndrome scale (PANSS) for schizophrenia (1987) Schizophrenia Bulletin, 13 (2), pp. 261-276; Zuo, X.N., Toward reliable characterization of functional homogeneity in the human brain: Preprocessing, scan duration, imaging resolution and computational space (2013) Neuroimage, 65, pp. 374-386; Friston, K.J., Williams, S., Howard, R., Frackowiak, R.S., Turner, R., Movementrelated effects in fMRI time-series (1996) Magn. Reson. Med., 35, pp. 346-355; Patriat, R., The effect of resting condition on resting-state fMRI reliability and consistency: A comparison between resting with eyes open, closed, and fixated (2013) Neuroimage, 78, pp. 463-473; Beckmann, C.F., Smith, S.M., Probabilistic independent component analysis for functional magnetic resonance imaging (2004) IEEE Trans. Med. Imaging, 23, pp. 137-152; Palla, G., Derenyi, I., Farkas, I., Vicsek, T., Uncovering the overlapping community structure of complex networks in nature and society (2005) Nature, 435 (7043), pp. 814-818. , DOI 10.1038/nature03607; Luce, R.D., Perry, A.D., A method of matrix analysis of group structure (1949) Psychometrika, 14, pp. 95-116

PY - 2014

Y1 - 2014

N2 - Early-onset schizophrenia (EOS) offers a unique opportunity to study pathophysiological mechanisms and development of schizophrenia. Using 26 drug-naïve, first-episode EOS patients and 25 age-and gender-matched control subjects, we examined intrinsic connectivity network (ICN) deficits underlying EOS. Due to the emerging inconsistency between behavior-based psychiatric disease classification system and the underlying brain dysfunctions, we applied a fully data-driven approach to investigate whether the subjects can be grouped into highly homogeneous communities according to the characteristics of their ICNs. The resultant subject communities and the representative characteristics of ICNs were then associated with the clinical diagnosis and multivariate symptom patterns. A default mode ICN was statistically absent in EOS patients. Another frontotemporal ICN further distinguished EOS patients with predominantly negative symptoms. Connectivity patterns of this second network for the EOS patients with predominantly positive symptom were highly similar to typically developing controls. Our post-hoc functional connectivity modeling confirmed that connectivity strength in this frontotemporal circuit was significantly modulated by relative severity of positive and negative syndromes in EOS. This study presents a novel subtype discovery approach based on brain networks and proposes complex links between brain networks and symptom patterns in EOS.

AB - Early-onset schizophrenia (EOS) offers a unique opportunity to study pathophysiological mechanisms and development of schizophrenia. Using 26 drug-naïve, first-episode EOS patients and 25 age-and gender-matched control subjects, we examined intrinsic connectivity network (ICN) deficits underlying EOS. Due to the emerging inconsistency between behavior-based psychiatric disease classification system and the underlying brain dysfunctions, we applied a fully data-driven approach to investigate whether the subjects can be grouped into highly homogeneous communities according to the characteristics of their ICNs. The resultant subject communities and the representative characteristics of ICNs were then associated with the clinical diagnosis and multivariate symptom patterns. A default mode ICN was statistically absent in EOS patients. Another frontotemporal ICN further distinguished EOS patients with predominantly negative symptoms. Connectivity patterns of this second network for the EOS patients with predominantly positive symptom were highly similar to typically developing controls. Our post-hoc functional connectivity modeling confirmed that connectivity strength in this frontotemporal circuit was significantly modulated by relative severity of positive and negative syndromes in EOS. This study presents a novel subtype discovery approach based on brain networks and proposes complex links between brain networks and symptom patterns in EOS.

KW - adolescent

KW - brain mapping

KW - case control study

KW - child

KW - female

KW - frontal lobe

KW - human

KW - male

KW - multivariate analysis

KW - nerve cell network

KW - pathophysiology

KW - reproducibility

KW - Schizophrenia, Childhood

KW - temporal lobe

KW - Adolescent

KW - Brain Mapping

KW - Case-Control Studies

KW - Child

KW - Female

KW - Frontal Lobe

KW - Humans

KW - Male

KW - Multivariate Analysis

KW - Nerve Net

KW - Reproducibility of Results

KW - Temporal Lobe

U2 - 10.1038/srep05549

DO - 10.1038/srep05549

M3 - Article

C2 - 24989351

VL - 4

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

ER -