[en] The identification of the cerebral substrates of psychoses such as schizophrenia and bipolar disorder is likely hampered by its biological heterogeneity, which may contribute to the low replication of results in the field. In this study we aimed to replicate in a completely new sample and supplement the results of a previous study with additional data on this topic. In the aforementioned study we identified a schizophrenia cluster characterized by high mean cortical curvature and low cortical thickness, subcortical hypometabolism and progressive negative symptoms. Here, we have used magnetic resonance images from 61 schizophrenia and 28 bipolar patients, as well as 51 healthy controls and a cluster analysis to search for possible subgroups primarily characterized by cerebral structural data. Diffusion tensor imaging (fractional anisotropy, FA), cognition, clinical data and electroencephalographic (EEG) modulation during a P300 task were used to validate the possible clusters. Two clusters of patients were identified. The first cluster (29 schizophrenia and 18 bipolar patients) showed decreased cortical thickness and area values, as well as lower subcortical volumes and higher cortical curvature in some regions, as compared to the second cluster. This first cluster also showed decreased FA in frontal lobe connections and worse cognitive performance. Although this cluster also showed longer illness duration, there were first episode patients in both clusters and treatment doses and types were not different between clusters. Both clusters of patients showed decreased EEG task-related modulation. In conclusion, our data give additional support to a distinct biologically based cluster encompassing schizophrenia and bipolar disorder patients with cortical and subcortical alterations, hampered cortical connectivity and lower cognitive performance.
Disciplines :
Psychiatry
Author, co-author :
Planchuelo-Gómez, Álvaro; Imaging Processing Laboratory, University of Valladolid, Paseo de Belén, 15, 47011 Valladolid, Spain
Lubeiro, Alba; Psychiatry Department, School of Medicine, University of Valladolid, Av. Ramón y Cajal, 7, 47005 Valladolid, Spain
Nunez Novo, Pablo ; Biomedical Engineering Group, University of Valladolid, Paseo de Belén, 15, 47011 Valladolid, Spain
Gomez-Pilar, Javier; Biomedical Engineering Group, University of Valladolid, Paseo de Belén, 15, 47011 Valladolid, Spain, Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain
de Luis-García, Rodrigo; Imaging Processing Laboratory, University of Valladolid, Paseo de Belén, 15, 47011 Valladolid, Spain
Del Valle, Pilar; Psychiatry Department, School of Medicine, University of Valladolid, Av. Ramón y Cajal, 7, 47005 Valladolid, Spain, Psychiatry Service, Clinical Hospital of Valladolid, Ramón y Cajal, 3, 47003 Valladolid, Spain
Martín-Santiago, Óscar; Psychiatry Department, School of Medicine, University of Valladolid, Av. Ramón y Cajal, 7, 47005 Valladolid, Spain, Psychiatry Service, Clinical Hospital of Valladolid, Ramón y Cajal, 3, 47003 Valladolid, Spain
Pérez-Escudero, Adela; Psychiatry Department, School of Medicine, University of Valladolid, Av. Ramón y Cajal, 7, 47005 Valladolid, Spain, Psychiatry Service, Clinical Hospital of Valladolid, Ramón y Cajal, 3, 47003 Valladolid, Spain
Molina, Vicente; Psychiatry Department, School of Medicine, University of Valladolid, Av. Ramón y Cajal, 7, 47005 Valladolid, Spain, Psychiatry Service, Clinical Hospital of Valladolid, Ramón y Cajal, 3, 47003 Valladolid, Spain, Neurosciences Institute of Castilla y León (INCYL), Pintor Fernando Gallego, 1, 37007, University of Salamanca, Spain. Electronic address: vicente.molina@uva.es
Language :
English
Title :
Identificacion of MRI-based psychosis subtypes: Replication and refinement.
Publication date :
08 June 2020
Journal title :
Progress in Neuro-Psychopharmacology and Biological Psychiatry
ISCIII - Instituto de Salud Carlos III JCYL - Junta de Castilla y León ESF - European Social Fund
Funding text :
This work was supported by the Instituto Carlos III ( PI15/00299 and PI 18/00178 ), the Gerencia Regional de Salud de Castilla y León ( GRS 1721/A/18 and GRS 1933/A/19 ) and the Consejería de Educación de la Junta de Castilla y León ( VA05P17 grant).This work was supported by the Instituto Carlos III (PI15/00299 and PI 18/00178), the Gerencia Regional de Salud de Castilla y Le?n (GRS 1721/A/18 and GRS 1933/A/19) and the Consejer?a de Educaci?n de la Junta de Castilla y Le?n (VA05P17 grant).?PG was supported by the Junta de Castilla y Le?n (Spain) and the European Social Fund (ID: 376062, Base de Datos Nacional de Subvenciones). PNN was in receipt of a predoctoral scholarship ?Ayuda para contratos predoctorales para la Formaci?n de Profesorado Universitario (FPU)? grant from the ?Ministerio de Educaci?n, Cultura y Deporte? (FPU17/00850). JGP was supported by 'CIBER de Bioingenier?a, Biomateriales y Nanomedicina (CIBER-BBN)' through 'Instituto de Salud Carlos III' co-funded with FEDER fundsÁPG was supported by the Junta de Castilla y León (Spain) and the European Social Fund (ID: 376062 , Base de Datos Nacional de Subvenciones). PNN was in receipt of a predoctoral scholarship ‘ Ayuda para contratos predoctorales para la Formación de Profesorado Universitario (FPU) ’ grant from the ‘ Ministerio de Educación, Cultura y Deporte ’ ( FPU17/00850 ). JGP was supported by ' CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) ' through 'Instituto de Salud Carlos III' co-funded with FEDER funds
Adachi, Y., Osada, T., Sporns, O., Watanabe, T., Matsui, T., Miyamoto, K., Miyashita, Y., Functional connectivity between anatomically unconnected areas is shaped by collective network-level effects in the macaque cortex. Cereb. Cortex 22 (2012), 1586–1592.
Arnedo, J., Svrakic, D.M., Del Val, C., Romero-Zaliz, R., Hernández-Cuervo, H., Fanous, A.H., Pato, M.T., Pato, C.N., de Erausquin, G.A., Cloninger, C.R., Zwir, I., Uncovering the hidden risk architecture of the schizophrenias: confirmation in three independent genome-wide association studies. Am. J. Psychiatry 172 (2015), 139–153.
Bachiller, A., Díez, A., Suazo, V., Domínguez, C., Ayuso, M., Hornero, R., Poza, J., Molina, V., Decreased spectral entropy modulation in patients with schizophrenia during a P300 task. Eur. Arch. Psychiatry Clin. Neurosci. 264 (2014), 533–543.
Bachiller, A., Lubeiro, A., Díez, Á., Suazo, V., Domínguez, C., Blanco, J.A., Ayuso, M., Hornero, R., Poza, J., Molina, V., Decreased entropy modulation of EEG response to novelty and relevance in schizophrenia during a P300 task. Eur. Arch. Psychiatry Clin. Neurosci. 265 (2015), 525–535.
Benjamini, Y., Hochberg, Y., Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B 57 (1995), 289–300.
Brugger, S.P., Howes, O.D., Heterogeneity and homogeneity of regional brain structure in schizophrenia: a meta-analysis. JAMA Psychiatr. 74 (2017), 1104–1111.
Buchsbaum, M.S., Shihabuddin, L., Brickman, A.M., Miozzo, R., Prikryl, R., Shaw, R., Davis, K., Caudate and putamen volumes in good and poor outcome patients with schizophrenia. Schizophr. Res. 64 (2003), 53–62.
Chakos, M.H., Lieberman, J.A., Bilder, R.M., Borenstein, M., Lerner, G., Bogerts, B., Wu, H., Kinon, B., Ashtari, M., Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs. Am. J. Psychiatry 151 (1994), 1430–1436.
Clementz, B.A., Sweeney, J.A., Hamm, J.P., Ivleva, E.I., Ethridge, L.E., Pearlson, G.D., Keshavan, M.S., Tamminga, C.A., Identification of distinct psychosis biotypes using brain-based biomarkers. Am. J. Psychiatry 173 (2016), 373–384.
Dale, A.M., Fischl, B., Sereno, M.I., Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage 9 (1999), 179–194.
DeLisi, L.E., Holcomb, H.H., Cohen, R.M., Pickar, D., Carpenter, W., Morihisa, J.M., King, A.C., Kessler, R., Buchsbaum, M.S., Positron emission tomography in schizophrenic patients with and without neuroleptic medication. J Cereb Bloow Flow Metab 5 (1985), 201–206.
Desikan, R.S., Ségonne, F., Fischl, B., Quinn, B.T., Dickerson, B.C., Blacker, D., Buckner, R.L., Dale, A.M., Maguire, R.P., Hyman, B.T., Albert, M.S., Killiany, R.J., An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 31 (2006), 968–980.
Díez, A., Suazo, V., Casado, P., Martín-Loeches, M., Perea, M.V., Molina, V., Frontal gamma noise power and cognitive domains in schizophrenia. Psychiatry Res. 221 (2014), 104–113.
Doucet, G.E., Moser, D.A., Luber, M.J., Leibu, E., Frangou, S., Baseline brain structural and functional predictors of clinical outcome in the early course of schizophrenia. Mol. Psychiatry, 2018, 10.1038/s41380-018-0269-0.
Dwyer, D.B., Cabral, C., Kambeitz-Ilankovic, L., Sanfelici, R., Kambeitz, J., Calhoun, V., Falkai, P., Pantelis, C., Meisenzahl, E., Koutsouleris, N., Brain subtyping enhances the neuroanatomical discrimination of schizophrenia. Schizophr. Bull. 44 (2018), 1060–1069.
Fuentes Durá, I., Romero Peris, M., Dasí Vivó, C., Ruiz Ruiz, J.C., Short form of the WAIS-III for use with patients with schizophrenia. Psicothema 22 (2010), 202–207.
Gomez-Pilar, J., de Luis-García, R., Lubeiro, A., de la Red, H., Poza, J., Núñez, P., Hornero, R., Molina, V., Relations between structural and EEG-based graph metrics in healthy controls and schizophrenia patients. Hum. Brain Mapp. 39 (2018), 3152–3165.
Gomez-Pilar, J., de Luis-García, R., Lubeiro, A., de Uribe, N., Poza, J., Núñez, P., Ayuso, M., Hornero, R., Molina, V., Deficits of entropy modulation in schizophrenia are predicted by functional connectivity strength in the theta band and structural clustering. Neuroimage Clin. 18 (2018), 382–389.
Gould, I.C., Shepherd, A.M., Laurens, K.R., Cairns, M.J., Carr, V.J., Green, M.J., Multivariate neuroanatomical classification of cognitive subtypes in schizophrenia: a support vector machine learning approach. Neuroimage Clin 6 (2014), 229–236.
Guo, S., Palaniyappan, L., Liddle, P.F., Feng, J., Dynamic cerebral reorganization in the pathophysiology of schizophrenia: a MRI-derived cortical thickness study. Psychol. Med. 46 (2016), 2201–2214.
Hanford, L.C., Pinnock, F., Hall, G.B., Heinrichs, R.W., Cortical thickness correlates of cognitive performance in cognitively-matched individuals with and without schizophrenia. Brain Cogn. 132 (2019), 129–137.
Ivleva, E.I., Clementz, B.A., Dutcher, A.M., Arnold, S.J.M., Jeon-Slaughter, H., Aslan, S., Witte, B., Poudyal, G., Lu, H., Meda, S.A., Pearlson, G.D., Sweeney, J.A., Keshavan, M.S., Tamminga, C.A., Brain structure biomarkers in the psychosis biotypes: findings from the bipolar-schizophrenia network for intermediate phenotypes. Biol. Psychiatry 82 (2017), 26–39.
Kay, S.R., Fiszbein, A., Opler, L.A., The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr. Bull. 13 (1987), 261–276.
Kelly, S., Jahanshad, N., Zalesky, A., Kochunov, P., Agartz, I., Alloza, C., Andreassen, O.A., Arango, C., Banaj, N., Bouix, S., Bousman, C.A., Brouwer, R.M., Bruggemann, J., Bustillo, J., Cahn, W., Calhoun, V., Cannon, D., Carr, V., Catts, S., Chen, J., Chen, J.-X., Chen, X., Chiapponi, C., Cho, K.K., Ciullo, V., Corvin, A.S., Crespo-Facorro, B., Cropley, V., De Rossi, P., Diaz-Caneja, C.M., Dickie, E.W., Ehrlich, S., Fan, F.-M., Faskowitz, J., Fatouros-Bergman, H., Flyckt, L., Ford, J.M., Fouche, J.-P., Fukunaga, M., Gill, M., Glahn, D.C., Gollub, R., Goudzwaard, E.D., Guo, H., Gur, R.E., Gur, R.C., Gurholt, T.P., Hashimoto, R., Hatton, S.N., Henskens, F.A., Hibar, D.P., Hickie, I.B., Hong, L.E., Horacek, J., Howells, F.M., Hulshoff Pol, H.E., Hyde, C.L., Isaev, D., Jablensky, A., Jansen, P.R., Janssen, J., Jönsson, E.G., Jung, L.A., Kahn, R.S., Kikinis, Z., Liu, K., Klauser, P., Knöchel, C., Kubicki, M., Lagopoulos, J., Langen, C., Lawrie, S., Lenroot, R.K., Lim, K.O., Lopez-Jaramillo, C., Lyall, A., Magnotta, V., Mandl, R.C.W., Mathalon, D.H., McCarley, R.W., McCarthy-Jones, S., McDonald, C., McEwen, S., McIntosh, A., Melicher, T., Mesholam-Gately, R.I., Michie, P.T., Mowry, B., Mueller, B.A., Newell, D.T., O'Donnell, P., Oertel-Knöchel, V., Oestreich, L., Paciga, S.A., Pantelis, C., Pasternak, O., Pearlson, G., Pellicano, G.R., Pereira, A., Pineda Zapata, J., Piras, F., Potkin, S.G., Preda, A., Rasser, P.E., Roalf, D.R., Roiz, R., Roos, A., Rotenberg, D., Satterthwaite, T.D., Savadjiev, P., Schall, U., Scott, R.J., Seal, M.L., Seidman, L.J., Shannon Weickert, C., Whelan, C.D., Shenton, M.E., Kwon, J.S., Spalletta, G., Spaniel, F., Sprooten, E., Stäblein, M., Stein, D.J., Sundram, S., Tan, Y., Tan, S., Tang, S., Temmingh, H.S., Westlye, L.T., Tønnesen, S., Tordesillas-Gutierrez, D., Doan, N.T., Vaidya, J., van Haren, N.E.M., Vargas, C.D., Vecchio, D., Velakoulis, D., Voineskos, A., Voyvodic, J.Q., Wang, Z., Wan, P., Wei, D., Weickert, T.W., Whalley, H., White, T., Whitford, T.J., Wojcik, J.D., Xiang, H., Xie, Z., Yamamori, H., Yang, F., Yao, N., Zhang, G., Zhao, J., van Erp, T.G.M., Turner, J., Thompson, P.M., Donohoe, G., Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA schizophrenia DTI working group. Mol. Psychiatry 23 (2018), 1261–1269, 10.1038/mp.2017.170.
Le Bihan, D., Mangin, J.F., Poupon, C., Clark, C.A., Pappata, S., Molko, N., Chabriat, H., Diffusion tensor imaging: concepts and applications. J. Magn. Reson. Imaging 13 (2001), 534–546.
Lichtenstein, P., Yip, B.H., Björk, C., Pawitan, Y., Cannon, T.D., Sullivan, P.F., Hultman, C.M., Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373 (2009), 234–239.
Lubeiro, A., Rueda, C., Hernández, J.A., Sanz, J., Sarramea, F., Molina, V., Identification of two clusters within schizophrenia with different structural, functional and clinical characteristics. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 64 (2016), 79–86.
Lubeiro, A., de Luis-García, R., Rodríguez, M., Álvarez, A., de la Red, H., Molina, V., Biological and cognitive correlates of cortical curvature in schizophrenia. Psychiatry Res. Neuroimaging 270 (2017), 68–75.
MacQueen, J., Some methods for classification and analysis of multivariate observations. Proc Fifth Berkeley Symp Math Stat. Prob 1 (1967), 281–297.
Molina Rodríguez, V., Montz Andrée, R., Pérez Castejón, M.J., Capdevila García, E., Carreras Delgado, J.L., Rubia Vila, F.J., SPECT study of regional cerebral perfusion in neuroleptic-resistant schizophrenic patients who responded or did not respond to clozapine. Am. J. Psychiatry 153 (1996), 1343–1346.
Molina, V., Hernández, J.A., Sanz, J., Paniagua, J.C., Hernández, A.I., Martín, C., Matías, J., Calama, J., Bote, B., Subcortical and cortical gray matter differences between Kraepelinian and non-Kraepelinian schizophrenia patients identified using voxel-based morphometry. Psychiatry Res. 184 (2010), 16–22.
Molina, V., Taboada, D., Aragüés, M., Hernández, J.A., Sanz-Fuentenebro, J., Greater clinical and cognitive improvement with clozapine and risperidone associated with a thinner cortex at baseline in first-episode schizophrenia. Schizophr. Res. 158 (2014), 223–229.
Molina, V., Lubeiro, A., Soto, O., Rodríguez, M., Álvarez, A., Hernández, R., de Luis-García, R., Alterations in prefrontal connectivity in schizophrenia assessed using diffusion magnetic resonance imaging. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 76 (2017), 107–115.
Molina, V., Bachiller, A., Gomez-Pilar, J., Lubeiro, A., Hornero, H., Cea-Cañas, B., Valcárcel, C., Haidar, M.K., Poza, J., Deficit of entropy modulation of the EEG in schizophrenia associated to cognitive performance and symptoms. A replication study. Schizophr. Res. 195 (2018), 334–342.
Padmanabhan, J.L., Tandon, N., Haller, C.S., Mathew, I.T., Eack, S.M., Clementz, B.A., Pearlson, G.D., Sweeney, J.A., Tamminga, C.A., Keshavan, M.S., Correlations between brain structure and symptom dimensions of psychosis in schizophrenia, schizoaffective, and psychotic bipolar I disorders. Schizophr. Bull. 41 (2015), 154–162.
Pan, Y., Pu, W., Chen, X., Huang, X., Cai, Y., Tao, H., Xue, Z., Mackinley, M., Limongi, R., Liu, Z., Palaniyappan, L., Morphological Profiling of Schizophrenia. 2020, Cluster Analysis of MRI-Based Cortical Thickness Data. Schizophr. Bull, 10.1093/schbul/sbz112.
Penadés, R., Pujol, N., Catalán, R., Masana, G., García-Rizo, C., Bargalló, N., González-Rodríguez, A., Vidal-Piñeiro, D., Bernardo, M., Junqué, C., Cortical thickness in regions of frontal and temporal lobes is associated with responsiveness to cognitive remediation therapy in schizophrenia. Schizophr. Res. 171 (2016), 110–116.
Rousseeuw, P.J., Silhouettes: a graphical aid to the interpretation and validation of cluster analysis. J. Comput. Appl. Math. 20 (1987), 53–65.
Scheeringa, R., Fries, P., Petersson, K.M., Oostenveld, R., Grothe, I., Norris, D.G., Hagoort, P., Bastiaansen, M.C., Neuronal dynamics underlying high- and low-frequency EEG oscillations contribute independently to the human BOLD signal. Neuron 69 (2011), 572–583.
Segarra, N., Bernardo, M., Gutierrez, F., Justicia, A., Fernandez-Egea, E., Allas, M., Safont, G., Contreras, F., Gascon, J., Soler-Insa, P.A., Menchon, J.M., Junque, C., Keefe, R.S., Spanish validation of the brief assessment in cognition in schizophrenia (BACS) in patients with schizophrenia and healthy controls. Eur Psychiatr. 26 (2011), 69–73.
Severiano, A., Carriço, J.A., Robinson, D.A., Ramirez, M., Pinto, F.R., Evaluation of Jackknife and bootstrap for defining confidence intervals for pairwise agreement measures. PLoS One, 6, 2011, e19539.
Shabab, S., Mulsant, B.H., Levesque, M.L., Calarco, N., Nazeri, A., Wheeler, A.L., Foussias, G., Rajji, T.K., Voineskos, A.N., Brain structure, cognition, and brain age in schizophrenia, bipolar disorder, and healthy controls. Neuropsychopharmacology 44 (2019), 898–906.
Smith, R.E., Tournier, J.-D., Calamante, F., Connelly, A., Anatomically-constrained tractography: improved diffusion MRI streamlines tractography through effective use of anatomical information. Neuroimage 62 (2012), 1924–1938.
Sprooten, E., Papmeyer, M., Smyth, A.M., Vincenz, D., Honold, S., Conlon, G.A., Moorhead, T.W., Job, D., Whalley, H.C., Hall, J., McIntosh, A.M., Owens, D.C., Johnstone, E.C., Lawrie, S.M., Cortical thickness in first-episode schizophrenia patients and individuals at high familial risk: a cross-sectional comparison. Schizophr. Res. 151 (2013), 259–264.
Sun, D., Ching, C.R.K., Lin, A., Forsyth, J.K., Kushan, L., Vajdi, A., Jalbrzikowski, M., Hansen, L., Villalon-Reina, J.E., Qu, X., Jonas, R.K., van Amelsvoort, T., Bakker, G., Kates, W.R., Antshel, K.M., Fremont, W., Campbell, L.E., McCabe, K.L., Daly, E., Gudbrandsen, M., Murphy, C.M., Murphy, D., Craig, M., Vorstman, J., Fiksinski, A., Koops, S., Ruparel, K., Roalf, D.R., Gur, R.E., Schmitt, J.E., Simon, T.J., Goodrich-Hunsaker, N.J., Durdle, C.A., Bassett, A.S., Chow, E.W.C., Butcher, N.J., Vila-Rodriguez, F., Doherty, J., Cunningham, A., van den Bree, M.B.M., Linden, D.E.J., Moss, H., Owen, M.J., Murphy, K.C., McDonald-McGinn, D.M., Emanuel, B., van Erp, T.G.M., Turner, J.A., Thompson, P.M., Bearden, C.E., Large-scale mapping of cortical alterations in 22q11.2 deletion syndrome: Convergence with idiopathic psychosis and effects of deletion size. Mol. Psychiatry, 2018, 10.1038/s41380-018-0078-5.
Sun, H., Lui, S., Yao, L., Deng, W., Xiao, Y., Zhang, W., Huang, X., Hu, J., Bi, F., Li, T., Sweeney, J.A., Gong, Q., Two patterns of White matter abnormalities in medication-naive patients with first-episode schizophrenia revealed by diffusion tensor imaging and cluster analysis. JAMA Psychiatry 72 (2015), 678–686.
Thorndike, R.L., Who belongs in the family?. Psychometrika 18 (1953), 267–276.
Tournier, J.-D., Smith, R., Raffelt, D., Tabbara, R., Dhollander, T., Pietsch, M., Christiaens, D., Jeurissen, B., Yeh, C.-H., Connelly, A., MRtrix3: a fast, flexible and open software framework for medical image processing and visualisation. Neuroimage, 202, 2019, 116137, 10.1101/551739.
Vázquez-Bourgon, J., Roiz-Santiañez, R., Papiol, S., Ferro, A., Varela-Gómez, N., Fañanás, L., Crespo-Facorro, B., Variations in disrupted-in-schizophrenia 1 gene modulate long-term longitudinal differences in cortical thickness in patients with a first-episode of psychosis. Brain Imaging Behav 10 (2016), 629–635.
Wannan, C.M.J., Cropley, V.L., Chakravarty, M.M., Bousman, C., Ganella, E.P., Bruggemann, J.M., Weickert, T.W., Weickert, C.S., Everall, I., McGorry, P., Velakoulis, D., Wood, S.J., Bartholomeusz, C.F., Pantelis, C., Zalesky, A., Evidence for network-based cortical thickness reductions in schizophrenia. Am. J. Psychiatry 176 (2019), 552–563.
Wheeler, A.L., Wessa, M., Szeszko, P.R., Foussias, G., Chakravarty, M.M., Lerch, J.P., DeRosse, P., Remington, G., Mulsant, B.H., Linke, J., Malhotra, A.K., Voineskos, A.N., Further neuroimaging evidence for the deficit subtype of schizophrenia: a cortical connectomics analysis. JAMA Psychiatr. 72 (2015), 446–455.
Wolfers, T., Doan, N.T., Kaufmann, T., Alnæs, D., Moberget, T., Agartz, I., Buitelaar, J.K., Ueland, T., Melle, I., Franke, B., Andreassen, O.A., Beckmann, C.F., Westlye, L.T., Marquand, A.F., Mapping the heterogeneous phenotype of schizophrenia and bipolar disorder using normative models., 75, 2018, 1146–1155.
Yasuda, Y., Okada, N., Nemoto, K., Fukunaga, M., Yamamori, H., Ohi, K., Koshiyama, D., Kudo, N., Shiino, T., Morita, S., Morita, K., Azechi, H., Fujimoto, M., Miura, K., Watanabe, Y., Kasai, K., Hashimoto, R., Brain morphological and functional features in cognitive subgroups of schizophrenia. Psychiatry Clin. Neurosci., 2019, 10.1111/pcn.12963.
