Converging evidence suggests that schizophrenia (SZ) with primary, enduring negative symptoms (i.e., Deficit SZ (DSZ)) represents a distinct entity within the SZ spectrum while the neurobiological underpinnings remain undetermined. In the largest dataset of DSZ and Non-Deficit (NDSZ), we conducted a meta-analysis of data from 1560 individuals (168 DSZ, 373 NDSZ, 1019 Healthy Controls (HC)) and a mega-analysis of a subsampled data from 944 individuals (115 DSZ, 254 NDSZ, 575 HC) collected across 9 worldwide research centers of the ENIGMA SZ Working Group (8 in the mega-analysis), to clarify whether they differ in terms of cortical morphology. In the meta-analysis, sites computed effect sizes for differences in cortical thickness and surface area between SZ and control groups using a harmonized pipeline. In the mega-analysis, cortical values of individuals with schizophrenia and control participants were analyzed across sites using mixed-model ANCOVAs. The meta-analysis of cortical thickness showed a converging pattern of widespread thinner cortex in fronto-parietal regions of the left hemisphere in both DSZ and NDSZ, when compared to HC. However, DSZ have more pronounced thickness abnormalities than NDSZ, mostly involving the right fronto-parietal cortices. As for surface area, NDSZ showed differences in fronto-parietal-temporo-occipital cortices as compared to HC, and in temporo-occipital cortices as compared to DSZ. Although DSZ and NDSZ show widespread overlapping regions of thinner cortex as compared to HC, cortical thinning seems to better typify DSZ, being more extensive and bilateral, while surface area alterations are more evident in NDSZ. Our findings demonstrate for the first time that DSZ and NDSZ are characterized by different neuroimaging phenotypes, supporting a nosological distinction between DSZ and NDSZ and point toward the separate disease hypothesis.

Biomedical Network Research Centre on Mental Health Instituto de Salud Carlos 3 Madrid Spain

Brain Behavior Unit Department of Psychiatry and Mental Health University of Cape Town Cape Town South Africa

CARE National Institute of Mental Health Klecany Czech Republic

Center for Addiction and Mental Health Campbell Family Mental Health Research Institute Toronto ON Canada

Center for the Neurobiology of Learning and Memory University of California Irvine Irvine CA USA

Child and Adolescence Neuropsychiatry Unit Bambino Gesù Children's Hospital IRCCS Rome Italy

Clinical Translational Neuroscience Laboratory Department of Psychiatry and Human Behavior University of California Irvine Irvine CA USA

Department of Biomedical Engineering Johns Hopkins University School of Medicine Baltimore MD USA

Department of child and adolescent psychiatry TU Dresden Dresden Saxony Germany

Department of Genetic Medicine Johns Hopkins University School of Medicine Baltimore Baltimore MD USA

Department of Mental Health Johns Hopkins Bloomberg School of Public Health Baltimore MD USA

Department of Neuroscience Johns Hopkins University School of Medicine Baltimore MD USA

Department of Pharmacology Johns Hopkins University School of Medicine Baltimore MD USA

Department of Psychiatry and Behavioral Health Wexner Medical Center The Ohio State University Columbus OH USA

Department of Psychiatry and Behavioral Sciences University of California San Francisco CA USA

Department of Psychiatry and Mental Health Neuroscience Institute University of Cape Town Cape Town South Africa

Department of Psychiatry and Mental Health University of Cape Town Cape Town Western Cape South Africa

Department of Psychiatry and Mental Health Valkenberg Psychiatric Hospital Cape Town Western Cape South Africa

Department of Psychiatry Johns Hopkins University School of Medicine Baltimore MD USA

Department of Psychiatry University of California Irvine Newfoundland NJ NJ 07435 USA

Department of Psychiatry University of Toronto Temerty Faculty of Medicine Toronto ON Canada

Department of Psychiatry University of Toronto Toronto ON Canada

Department of Psychological Medicine Institute of Psychiatry Psychology and Neurology King's College London London UK

Division of Psychiatry University of Edinburgh Edinburg EH10 5HF UK

FIMDAG Sisters Hospitallers Research Foundation Barcelona Spain

Hospital Benito Menni CASM Barcelona Spain

Imaging Genetics Center Mark and Mary Stevens Neuroimaging and Informatics Institute Keck School of Medicine University of Southern California Marina del Rey CA USA

Imaging of mood and anxiety related disorders Barcelona 08036 Spain

Kimel Family Lab Centre for Addiction and Mental Health Toronto ON Canada

Medicina University of Barcelona Barcelona 08036 Spain

Menninger Department of Psychiatry and Behavioral Sciences Baylor College of Medicine Houston TX USA

Neuropsychiatry Laboratory Department of Clinical Neuroscience and Neurorehabilitation IRCCS Santa Lucia Foundation Rome Italy

Psichiatry and Neuroscience University of New Mexico Albuquerque NM USA

Psychiatry and Human Behavior University of California Irvine Orange CA 92868 USA

Psychosis Studies Institute of Psychiatry Psychology and Neurology King's College London London UK

SAMRC Unit on Risk and Resilience in Mental Disorders Department of Psychiatry and Neuroscience Institute University of Cape Town Cape Town South Africa

San Francisco VA Health Care System San Francisco CA USA

Section for Experimental Psychopathology and Neuroimaging Department of General Psychiatry Heidelberg University Heidelberg Baden Wuerttemberg Germany

West Region Institute of Mental Health National Healthcare Group Singapore Singapore

Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore

See more in PubMed

Kirkpatrick B, Buchanan RW, Ross DE, Carpenter WT., Jr A separate disease within the syndrome of schizophrenia. Arch Gen Psychiatry. 2001;58:165–71. doi: 10.1001/archpsyc.58.2.165. PubMed DOI

Carpenter WT, Jr, Heinrichs DW, Wagman AM. Deficit and nondeficit forms of schizophrenia: the concept. Am J Psychiatry. 1988;145:578–83. doi: 10.1176/ajp.145.5.578. PubMed DOI

Kirkpatrick B, Mucci A, Galderisi S. Primary, Enduring Negative Symptoms: An Update on Research. Schizophr Bull. 2017;43:730–6. doi: 10.1093/schbul/sbx064. PubMed DOI PMC

Voineskos AN, Foussias G, Lerch J, Felsky D, Remington G, Rajji TK, et al. Neuroimaging evidence for the deficit subtype of schizophrenia. JAMA Psychiatry. 2013;70:472–80. doi: 10.1001/jamapsychiatry.2013.786. PubMed DOI

López-Díaz Á, Lara I, Lahera G. Is the Prevalence of the Deficit Syndrome in Schizophrenia Higher than Estimated? Results of a Meta-Analysis. Psychiatry Investig. 2018;15:94–8. doi: 10.4306/pi.2018.15.1.94. PubMed DOI PMC

Strauss GP, Harrow M, Grossman LS, Rosen C. Periods of recovery in deficit syndrome schizophrenia: a 20-year multi-follow-up longitudinal study. Schizophr Bull. 2010;36:788–99. doi: 10.1093/schbul/sbn167. PubMed DOI PMC

Albayrak Y, Akyol ES, Beyazyüz M, Baykal S, Kuloglu M. Neurological soft signs might be endophenotype candidates for patients with deficit syndrome schizophrenia. Neuropsychiatr Dis Treat. 2015;11:2825–31. doi: 10.2147/NDT.S91170. PubMed DOI PMC

Bora E, Binnur Akdede B, Alptekin K. Neurocognitive impairment in deficit and non-deficit schizophrenia: a meta-analysis. Psychol Med. 2017;47:2401–13. doi: 10.1017/S0033291717000952. PubMed DOI

Boutros NN, Mucci A, Vignapiano A, Galderisi S. Electrophysiological aberrations associated with negative symptoms in schizophrenia. Curr Top Behav Neurosci. 2014;21:129–56. doi: 10.1007/7854_2014_303. PubMed DOI

Goldsmith DR, Haroon E, Miller AH, Strauss GP, Buckley PF, Miller BJ. TNF-α and IL-6 are associated with the deficit syndrome and negative symptoms in patients with chronic schizophrenia. Schizophr Res. 2018;199:281–4. doi: 10.1016/j.schres.2018.02.048. PubMed DOI PMC

Mucci A, Merlotti E, Üçok A, Aleman A, Galderisi S. Primary and persistent negative symptoms: Concepts, assessments and neurobiological bases. Schizophr Res. 2017;186:19–28. doi: 10.1016/j.schres.2016.05.014. PubMed DOI

Wheeler AL, Wessa M, Szeszko PR, Foussias G, Chakravarty MM, Lerch JP, et al. Further neuroimaging evidence for the deficit subtype of schizophrenia: a cortical connectomics analysis. JAMA Psychiatry. 2015;72:446–55. doi: 10.1001/jamapsychiatry.2014.3020. PubMed DOI

Downs J, Dean H, Lechler S, Sears N, Patel R, Shetty H, et al. Negative Symptoms in Early-Onset Psychosis and Their Association With Antipsychotic Treatment Failure. Schizophr Bull. 2019;45:69–79. doi: 10.1093/schbul/sbx197. PubMed DOI PMC

Peralta V, Moreno-Izco L, Sanchez-Torres A, García de Jalón E, Campos MS, Cuesta MJ. Characterization of the deficit syndrome in drug-naive schizophrenia patients: the role of spontaneous movement disorders and neurological soft signs. Schizophr Bull. 2014;40:214–24. doi: 10.1093/schbul/sbs152. PubMed DOI PMC

Arango C, Buchanan RW, Kirkpatrick B, Carpenter WT. The deficit syndrome in schizophrenia: implications for the treatment of negative symptoms. Eur Psychiatry. 2004;19:21–6. doi: 10.1016/j.eurpsy.2003.10.004. PubMed DOI

Miyamoto S, Miyake N, Jarskog LF, Fleischhacker WW, Lieberman JA. Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents. Mol Psychiatry. 2012;17:1206–27. doi: 10.1038/mp.2012.47. PubMed DOI

Kirkpatrick B, Gürbüz Oflezer Ö, Delice Arslan M, Hack G, Fernandez-Egea E. An Early Developmental Marker of Deficit versus Nondeficit Schizophrenia. Schizophr Bull. 2019;45:1331–5. doi: 10.1093/schbul/sbz024. PubMed DOI PMC

Kirkpatrick B, Galderisi S. Deficit schizophrenia: an update. World Psychiatry. 2008;7:143–7. doi: 10.1002/j.2051-5545.2008.tb00181.x. PubMed DOI PMC

López-Díaz Á, Menéndez-Sampil C, Pérez-Romero A, Palermo-Zeballos FJ, Valdés-Florido MJ. Characterization of deficit schizophrenia and reliability of the bidimensional model of its negative symptomatology. Nord J Psychiatry. 2020;74:400–6. doi: 10.1080/08039488.2020.1736151. PubMed DOI

Ahmed AO, Strauss GP, Buchanan RW, Kirkpatrick B, Carpenter WT. Schizophrenia heterogeneity revisited: Clinical, cognitive, and psychosocial correlates of statistically-derived negative symptoms subgroups. J Psychiatr Res. 2018;97:8–15. doi: 10.1016/j.jpsychires.2017.11.004. PubMed DOI

Cohen AS, Docherty NM. Deficit versus negative syndrome in schizophrenia: prediction of attentional impairment. Schizophr Bull. 2004;30:827–35. doi: 10.1093/oxfordjournals.schbul.a007135. PubMed DOI

Cascella NG, Testa SM, Meyer SM, Rao VA, Diaz-Asper CM, Pearlson GD, et al. Neuropsychological impairment in deficit vs. non-deficit schizophrenia. J Psychiatr Res. 2008;42:930–7. doi: 10.1016/j.jpsychires.2007.10.002. PubMed DOI

Farkas M, Polgár P, Kelemen O, Réthelyi J, Bitter I, Myers CE, et al. Associative learning in deficit and nondeficit schizophrenia. Neuroreport. 2008;19:55–8. doi: 10.1097/WNR.0b013e3282f2dff6. PubMed DOI

Polgár P, Réthelyi JM, Bálint S, Komlósi S, Czobor P, Bitter I. Executive function in deficit schizophrenia: what do the dimensions of the Wisconsin Card Sorting Test tell us? Schizophr Res. 2010;122:85–93. doi: 10.1016/j.schres.2010.06.007. PubMed DOI

Spalletta G, Pasini A, De Angelis F, Troisi A. Patients with deficit, nondeficit, and negative symptom schizophrenia: do they differ during episodes of acute psychotic decompensation? Schizophr Res. 1997;24:341–8. doi: 10.1016/S0920-9964(96)00124-7. PubMed DOI

Yu M, Tang X, Wang X, Zhang X, Zhang X, Sha W, et al. Neurocognitive Impairments in Deficit and Non-Deficit Schizophrenia and Their Relationships with Symptom Dimensions and Other Clinical Variables. PLoS ONE. 2015;10:e0138357. doi: 10.1371/journal.pone.0138357. PubMed DOI PMC

Takayanagi Y, Sasabayashi D, Takahashi T, Komori Y, Furuichi A, Kido M, et al. Altered brain gyrification in deficit and non-deficit schizophrenia. Psychol Med. 2019;49:573–80. doi: 10.1017/S0033291718001228. PubMed DOI

Spalletta G, De Rossi P, Piras F, Iorio M, Dacquino C, Scanu F, et al. Brain white matter microstructure in deficit and non-deficit subtypes of schizophrenia. Psychiatry Res. 2015;231:252–61. doi: 10.1016/j.pscychresns.2014.12.006. PubMed DOI

Cascella NG, Fieldstone SC, Rao VA, Pearlson GD, Sawa A, Schretlen DJ. Gray-matter abnormalities in deficit schizophrenia. Schizophr Res. 2010;120:63–70. doi: 10.1016/j.schres.2010.03.039. PubMed DOI

Fischer BA, Keller WR, Arango C, Pearlson GD, McMahon RP, Meyer WA, et al. Cortical structural abnormalities in deficit versus nondeficit schizophrenia. Schizophr Res. 2012;136:51–4. doi: 10.1016/j.schres.2012.01.030. PubMed DOI PMC

Takayanagi M, Wentz J, Takayanagi Y, Schretlen DJ, Ceyhan E, Wang L, et al. Reduced anterior cingulate gray matter volume and thickness in subjects with deficit schizophrenia. Schizophr Res. 2013;150:484–90. doi: 10.1016/j.schres.2013.07.036. PubMed DOI PMC

De Rossi P, Dacquino C, Piras F, Caltagirone C, Spalletta G. Left nucleus accumbens atrophy in deficit schizophrenia: A preliminary study. Psychiatry Res Neuroimaging. 2016;254:48–55. doi: 10.1016/j.pscychresns.2016.06.004. PubMed DOI

Galderisi S, Quarantelli M, Volpe U, Mucci A, Cassano GB, Invernizzi G, et al. Patterns of structural MRI abnormalities in deficit and nondeficit schizophrenia. Schizophr Bull. 2008;34:393–401. doi: 10.1093/schbul/sbm097. PubMed DOI PMC

Quarantelli M, Larobina M, Volpe U, Amati G, Tedeschi E, Ciarmiello A, et al. Stereotaxy-based regional brain volumetry applied to segmented MRI: validation and results in deficit and nondeficit schizophrenia. Neuroimage. 2002;17:373–84. doi: 10.1006/nimg.2002.1157. PubMed DOI

Chen CH, Fiecas M, Gutiérrez ED, Panizzon MS, Eyler LT, Vuoksimaa E, et al. Genetic topography of brain morphology. Proc Natl Acad Sci USA. 2013;110:17089–94. doi: 10.1073/pnas.1308091110. PubMed DOI PMC

Rakic P. Evolution of the neocortex: a perspective from developmental biology. Nat Rev Neurosci. 2009;10:724–35. doi: 10.1038/nrn2719. PubMed DOI PMC

Panizzon MS, Fennema-Notestine C, Eyler LT, Jernigan TL, Prom-Wormley E, Neale M, et al. Distinct genetic influences on cortical surface area and cortical thickness. Cereb Cortex. 2009;19:2728–35. doi: 10.1093/cercor/bhp026. PubMed DOI PMC

Winkler AM, Kochunov P, Blangero J, Almasy L, Zilles K, Fox PT, et al. Cortical thickness or grey matter volume? The importance of selecting the phenotype for imaging genetics studies. Neuroimage. 2010;53:1135–46. doi: 10.1016/j.neuroimage.2009.12.028. PubMed DOI PMC

Grasby KL, Jahanshad N, Painter JN, Colodro-Conde L, Bralten J, Hibar DP, et al. The genetic architecture of the human cerebral cortex. Science. 2020;367:eaay6690. doi: 10.1126/science.aay6690. PubMed DOI PMC

Weinberger DR. Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry. 1987;44:660–9. doi: 10.1001/archpsyc.1987.01800190080012. PubMed DOI

Rimol LM, Nesvåg R, Hagler DJ, Jr, Bergmann O, Fennema-Notestine C, Hartberg CB, et al. Cortical volume, surface area, and thickness in schizophrenia and bipolar disorder. Biol Psychiatry. 2012;71:552–60. doi: 10.1016/j.biopsych.2011.11.026. PubMed DOI

van Erp TGM, Walton E, Hibar DP, Schmaal L, Jiang W, Glahn DC, et al. Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium. Biol Psychiatry. 2018;84:644–54. doi: 10.1016/j.biopsych.2018.04.023. PubMed DOI PMC

Xie T, Zhang X, Tang X, Zhang H, Yu M, Gong G, et al. Mapping Convergent and Divergent Cortical Thinning Patterns in Patients With Deficit and Nondeficit Schizophrenia. Schizophr Bull. 2019;45:211–21. doi: 10.1093/schbul/sbx178. PubMed DOI PMC

Burke DL, Ensor J, Riley RD. Meta-analysis using individual participant data: one-stage and two-stage approaches, and why they may differ. Stat Med. 2017;36:855–75. doi: 10.1002/sim.7141. PubMed DOI PMC

Stewart LA, Tierney JF. To IPD or not to IPD? Advantages and disadvantages of systematic reviews using individual patient data. Eval Health Prof. 2002;25:76–97. doi: 10.1177/0163278702025001006. PubMed DOI

Zugman A, Harrewijn A, Cardinale EM, Zwiebel H, Freitag GF, Werwath KE, et al. Mega-analysis methods in ENIGMA: The experience of the generalized anxiety disorder working group. Hum Brain Mapp. 2022;43:255–77. doi: 10.1002/hbm.25096. PubMed DOI PMC

Boedhoe PS, Schmaal L, Abe Y, Ameis SH, Arnold PD, Batistuzzo MC, et al. Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta- and Mega-Analysis. Am J Psychiatry. 2017;174:60–9. doi: 10.1176/appi.ajp.2016.16020201. PubMed DOI PMC

Boedhoe PSW, Schmaal L, Abe Y, Alonso P, Ameis SH, Anticevic A, et al. Cortical Abnormalities Associated With Pediatric and Adult Obsessive-Compulsive Disorder: Findings From the ENIGMA Obsessive-Compulsive Disorder Working Group. Am J Psychiatry. 2018;175:453–62. doi: 10.1176/appi.ajp.2017.17050485. PubMed DOI PMC

Radua J, Vieta E, Shinohara R, Kochunov P, Quidé Y, Green MJ, et al. Increased power by harmonizing structural MRI site differences with the ComBat batch adjustment method in ENIGMA. Neuroimage. 2020;218:116956. doi: 10.1016/j.neuroimage.2020.116956. PubMed DOI PMC

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., text rev. Washington, DC: American Psychiatric Association; 2000.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.

World Health Organization. ICD-10: international statistical classification of diseases and related health problems: tenth revision, 2nd ed., World Health Organization; 2004.

First MB, Spitzer RL, Gibbon M, & Williams JBW. Structured clinical interview for DSM-IV-TR axis I disorders, research version, patient edition. (SCID-I/P) New York: Biometrics Research, New York State Psychiatric Institute; 2002.

First M, Williams J, Karg R, Spitzer R. Structured Clinical Interview for DSM‐5 (SCID-5 for DSM-5) Arlington. American Psychiatric Association; 2017.

Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13:261–76. doi: 10.1093/schbul/13.2.261. PubMed DOI

Sivera R, Delingette H, Lorenzi M, Pennec X, Ayache N. A model of brain morphological changes related to aging and Alzheimer’s disease from cross-sectional assessments. Neuroimage. 2019;198:255–70. doi: 10.1016/j.neuroimage.2019.05.040. PubMed DOI

Kirkpatrick B, Buchanan RW, Breier A, Carpenter WT., Jr Case identification and stability of the deficit syndrome of schizophrenia. Psychiatry Res. 1993;47:47–56. doi: 10.1016/0165-1781(93)90054-K. PubMed DOI

Goetz RR, Corcoran C, Yale S, Stanford AD, Kimhy D, Amador X, et al. Validity of a ‘proxy’ for the deficit syndrome derived from the Positive And Negative Syndrome Scale (PANSS) Schizophr Res. 2007;93:169–77. doi: 10.1016/j.schres.2007.02.018. PubMed DOI PMC

Kirkpatrick B, Tek C, Allardyce J, Morrison G, McCreadie RG. Summer birth and deficit schizophrenia in Dumfries and Galloway, southwestern Scotland. Am J Psychiatry. 2002;159:1382–7. doi: 10.1176/appi.ajp.159.8.1382. PubMed DOI

Subotnik KL, Nuechterlein KH, Ventura J, Green MF, Hwang SS. Prediction of the deficit syndrome from initial deficit symptoms in the early course of schizophrenia. Psychiatry Res. 1998;80:53–9. doi: 10.1016/S0165-1781(98)00052-3. PubMed DOI

Kirkpatrick B, Amador XF, Flaum M, Yale SA, Gorman JM, Carpenter WT, Jr, et al. The deficit syndrome in the DSM-IV Field Trial: I. Alcohol and other drug abuse. Schizophr Res. 1996;20:69–77. doi: 10.1016/0920-9964(95)00102-6. PubMed DOI

Desikan RS, Ségonne F, Fischl B, Quinn BT, Dickerson BC, Blacker D, et al. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage. 2006;31:968–80. doi: 10.1016/j.neuroimage.2006.01.021. PubMed DOI

van Erp TG, Hibar DP, Rasmussen JM, Glahn DC, Pearlson GD, Andreassen OA, et al. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium. Mol Psychiatry. 2016;21:547–53. doi: 10.1038/mp.2015.63. PubMed DOI PMC

Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, Toga AW. Mapping cortical change across the human life span. Nat Neurosci. 2003;6:309–15. doi: 10.1038/nn1008. PubMed DOI

Borenstein M. Software for Publication Bias. In: Publication Bias in Meta‐Analysis: Prevention, Assessment and Adjustments. 2005:193–220.

Rakic P. A small step for the cell, a giant leap for mankind: a hypothesis of neocortical expansion during evolution. Trends Neurosci. 1995;18:383–8. doi: 10.1016/0166-2236(95)93934-P. PubMed DOI

Wierenga LM, Langen M, Oranje B, Durston S. Unique developmental trajectories of cortical thickness and surface area. Neuroimage. 2014;87:120–6. doi: 10.1016/j.neuroimage.2013.11.010. PubMed DOI

Pontious A, Kowalczyk T, Englund C, Hevner RF. Role of intermediate progenitor cells in cerebral cortex development. Dev Neurosci. 2008;30:24–32. doi: 10.1159/000109848. PubMed DOI

Birnbaum R, Weinberger DR. Genetic insights into the neurodevelopmental origins of schizophrenia. Nat Rev Neurosci. 2017;18:727–40. doi: 10.1038/nrn.2017.125. PubMed DOI

Yildiz M, Borgwardt SJ, Berger GE. Parietal lobes in schizophrenia: do they matter? Schizophr Res Treat. 2011;2011:581686. PubMed PMC

Spence SA, Brooks DJ, Hirsch SR, Liddle PF, Meehan J, Grasby PM. A PET study of voluntary movement in schizophrenic patients experiencing passivity phenomena (delusions of alien control) Brain. 1997;120:1997–2011. doi: 10.1093/brain/120.11.1997. PubMed DOI

Yang YL, Joshi AA, Joshi SH, Baker LA, Narr KL, Raine A, et al. Genetic and environmental influences on cortical thickness among 14-year-old twins. Neuroreport. 2012;23:702–6. doi: 10.1097/WNR.0b013e328355a62a. PubMed DOI PMC

Antonova E, Sharma T, Morris R, Kumari V. The relationship between brain structure and neurocognition in schizophrenia: a selective review. Schizophr Res. 2004;70:117–45. doi: 10.1016/j.schres.2003.12.002. PubMed DOI

Jonides J, Schumacher EH, Smith EE, Koeppe RA, Awh E, Reuter-Lorenz PA, et al. The role of parietal cortex in verbal working memory. J Neurosci. 1998;18:5026–34. doi: 10.1523/JNEUROSCI.18-13-05026.1998. PubMed DOI PMC

Rushworth MFS, Ellison A, Walsh V. Complementary localization and lateralization of orienting and motor attention (vol 4, pg 656, 2001) Nat Neurosci. 2001;4:959–959. doi: 10.1038/88492. PubMed DOI

Thoenissen D, Zilles K, Toni I. Differential involvement of parietal and precentral regions in movement preparation and motor intention. J Neurosci. 2002;22:9024–34. doi: 10.1523/JNEUROSCI.22-20-09024.2002. PubMed DOI PMC

Gottlieb J. From thought to action: the parietal cortex as a bridge between perception, action, and cognition. Neuron. 2007;53:9–16. doi: 10.1016/j.neuron.2006.12.009. PubMed DOI

Buckner RL, Wheeler ME. The cognitive neuroscience of remembering. Nat Rev Neurosci. 2001;2:624–34. doi: 10.1038/35090048. PubMed DOI

Bor D, Seth AK. Consciousness and the prefrontal parietal network: insights from attention, working memory, and chunking. Front Psychol. 2012;3:63. doi: 10.3389/fpsyg.2012.00063. PubMed DOI PMC

Lou HC, Changeux JP, Rosenstand A. Towards a cognitive neuroscience of self-awareness. Neurosci Biobehav Rev. 2017;83:765–73. doi: 10.1016/j.neubiorev.2016.04.004. PubMed DOI

Cuffel BJ, Alford J, Fischer EP, Owen RR. Awareness of illness in schizophrenia and outpatient treatment adherence. J Nerv Ment Dis. 1996;184:653–9. doi: 10.1097/00005053-199611000-00001. PubMed DOI

Fett AK, Viechtbauer W, Dominguez MD, Penn DL, van Os J, Krabbendam L. The relationship between neurocognition and social cognition with functional outcomes in schizophrenia: a meta-analysis. Neurosci Biobehav Rev. 2011;35:573–88. doi: 10.1016/j.neubiorev.2010.07.001. PubMed DOI

Green MF, Olivier B, Crawley JN, Penn DL, Silverstein S. Social cognition in schizophrenia: recommendations from the measurement and treatment research to improve cognition in schizophrenia new approaches conference. Schizophr Bull. 2005;31:882–7. doi: 10.1093/schbul/sbi049. PubMed DOI

Schwartz RC. The relationship between insight, illness and treatment outcome in schizophrenia. Psychiatr Q. 1998;69:1–22. doi: 10.1023/A:1022141322657. PubMed DOI

Hartikainen KM. Emotion-Attention Interaction in the Right Hemisphere. Brain Sci. 2021;11:1006. doi: 10.3390/brainsci11081006. PubMed DOI PMC

Mitchell RL, Crow TJ. Right hemisphere language functions and schizophrenia: the forgotten hemisphere? Brain. 2005;128:963–78. doi: 10.1093/brain/awh466. PubMed DOI

Blom SSAH, Aarts H, Semin GR. Lateralization of facial emotion processing and facial mimicry. Laterality. 2020;25:259–74. doi: 10.1080/1357650X.2019.1657127. PubMed DOI

Parola A, Brasso C, Morese R, Rocca P, Bosco FM. Understanding communicative intentions in schizophrenia using an error analysis approach (vol 7, 12, 2021) Npj Schizophr. 2021;7:12. doi: 10.1038/s41537-021-00142-7. PubMed DOI PMC

Snelleksz M, Rossell SL, Gibbons A, Nithianantharajah J, Dean B. Evidence that the frontal pole has a significant role in the pathophysiology of schizophrenia. Psychiat Res. 2022;317:114850. doi: 10.1016/j.psychres.2022.114850. PubMed DOI

Salvador R, Suckling J, Coleman MR, Pickard JD, Menon D, Bullmore ET. Neurophysiological architecture of functional magnetic resonance images of human brain. Cereb Cortex. 2005;15:1332–42. doi: 10.1093/cercor/bhi016. PubMed DOI

Hunter R, Barry S. Negative symptoms and psychosocial functioning in schizophrenia: Neglected but important targets for treatment. Eur Psychiat. 2012;27:432–6. doi: 10.1016/j.eurpsy.2011.02.015. PubMed DOI

Allen P, Moore H, Corcoran CM, Gilleen J, Kozhuharova P, Reichenberg A, et al. Emerging Temporal Lobe Dysfunction in People at Clinical High Risk for Psychosis. Front Psychiatry. 2019;10:298. doi: 10.3389/fpsyt.2019.00298. PubMed DOI PMC

Borgwardt SJ, McGuire PK, Aston J, Gschwandtner U, Pflüger MO, Stieglitz RD, et al. Reductions in frontal, temporal and parietal volume associated with the onset of psychosis. Schizophr Res. 2008;106:108–14. doi: 10.1016/j.schres.2008.08.007. PubMed DOI

Tohid H, Faizan M, Faizan U. Alterations of the occipital lobe in schizophrenia. Neurosci (Riyadh) 2015;20:213–24. PubMed PMC

Vanes LD, Mouchlianitis E, Patel K, Barry E, Wong K, Thomas M, et al. Neural correlates of positive and negative symptoms through the illness course: an fMRI study in early psychosis and chronic schizophrenia. Sci Rep. 2019;9:14444. doi: 10.1038/s41598-019-51023-0. PubMed DOI PMC

Hogstrom LJ, Westlye LT, Walhovd KB, Fjell AM. The structure of the cerebral cortex across adult life: age-related patterns of surface area, thickness, and gyrification. Cereb Cortex. 2013;23:2521–30. doi: 10.1093/cercor/bhs231. PubMed DOI

Bush G, Luu P, Posner MI. Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci. 2000;4:215–22. doi: 10.1016/S1364-6613(00)01483-2. PubMed DOI

Davis KD, Taylor KS, Hutchison WD, Dostrovsky JO, McAndrews MP, Richter EO, et al. Human anterior cingulate cortex neurons encode cognitive and emotional demands. J Neurosci. 2005;25:8402–6. doi: 10.1523/JNEUROSCI.2315-05.2005. PubMed DOI PMC

Horne CM, Sahni A, Pang SW, Vanes LD, Szentgyorgyi T, Averbeck B, et al. The role of cognitive control in the positive symptoms of psychosis. Neuroimage Clin. 2022;34:103004. doi: 10.1016/j.nicl.2022.103004. PubMed DOI PMC

Kirkpatrick B, Buchanan RW, McKenney PD, Alphs LD, Carpenter WT., Jr The Schedule for the Deficit syndrome: an instrument for research in schizophrenia. Psychiatry Res. 1989;30:119–23. doi: 10.1016/0165-1781(89)90153-4. PubMed DOI

Fervaha G, Agid O, Foussias G, Siddiqui I, Takeuchi H, Remington G. Neurocognitive impairment in the deficit subtype of schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2016;266:397–407. doi: 10.1007/s00406-015-0629-6. PubMed DOI

Messias E, Kirkpatrick B, Bromet E, Ross D, Buchanan RW, Carpenter WT, Jr, et al. Summer birth and deficit schizophrenia: a pooled analysis from 6 countries. Arch Gen Psychiatry. 2004;61:985–9. doi: 10.1001/archpsyc.61.10.985. PubMed DOI

Schmaal L, Hibar DP, Sämann PG, Hall GB, Baune BT, Jahanshad N, et al. Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group. Mol Psychiatry. 2017;22:900–9. doi: 10.1038/mp.2016.60. PubMed DOI PMC

Neurostructural subgroup in 4291 individuals with schizophrenia identified using the subtype and stage inference algorithm

Two neurostructural subtypes: results of machine learning on brain images from 4,291 individuals with schizophrenia