Intracranial and subcortical volumes in adolescents with early-onset psychosis: A multisite mega-analysis from the ENIGMA consortium

For the ENIGMA-EOP Working Group

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = −0.39) and hippocampal (d = −0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = −0.34) and affective psychosis (d = −0.42), and early-onset schizophrenia showed lower hippocampal (d = −0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = −0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.

Original languageEnglish
Pages (from-to)373-384
Number of pages12
JournalHuman Brain Mapping
Volume43
Issue number1
Early online date5 Oct 2020
DOIs
Publication statusPublished - Jan 2022

Bibliographical note

Special Issue: The ENIGMA Consortium: the first 10 years.

Funding Information:
ENIGMA Core: U.S. National Institutes of Health grants, R01 EB015611, U54 EB020403, R01 MH116147, R01 MH117601, S10OD023696. YTOP: The Research Council of Norway (#223273, #2137000, #250358, #288083); South-Eastern Norway Regional Health Authority (#2017112); KG Jebsen Stiftelsen (#SKGJ-MED-008). Celso Arango has received funding from CIBERSAM: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, co-financed by ERDF Funds from the European Commission, ?A way of making Europe?; CIBERSAM; Instituto de Investigaci?n Sanitaria Gregorio Mara??n; Madrid Regional Government (B2017/BMD-3740 AGES-CM-2, Youth Employment Operational Program and Youth Employment Initiative); European Social Fund and EU Structural Funds; EU Seventh Framework Program under grant agreements FP7-HEALTH-2009-2.2.1-2-241909, FP7-HEALTH-2009-2.2.1-3-242114, FP7-HEALTH-2013-2.2.1-2-602478, and FP7-HEALTH-2013-2.2.1-2-603196; EU H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS), Fundaci?n Familia Alonso, Fundaci?n Alicia Koplowitz and Fundaci?n Mutua Madrile?a. Covadonga M. D?az-Caneja holds a grant from Instituto de Salud Carlos III (JR19/00024). UCLA: NIH/NIBIB U54 EB020403 (BD2K); NIMH RO3 MH105808; P50MH066286; Staglin Family/IMHRO Music Festival for Mental Health. Deakin: This project was supported by an unrestricted grant from AstraZeneca. Michael Berk is supported by a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship (1059660 and APP1156072). SCAPS: The Swedish Research Council (#521-2014-3487, #2017-00949); FORMAS (#259-2012-31). KCL-2: Netherland Organization for Scientific Research (NWO; #451-13-035 to Anne-Kathrin J. Fett and #453-11-005 to Lydia Krabbendam); NARSAD Young Investigator Award from the Brain and Behavior Foundation (#24138 to Anne-Kathrin J. Fett). KCL-1: R01MH113619. Brain and Behavior Research Foundation/NARSAD. SRI: Canadian Institutes of Health Research; Ontario Mental Health Foundation; Brain & Behavior Research Foundation/NARSAD. Oxford: MRC G0500092. MEND: NIMH R01 MH101506. UiO PSI: South-Eastern Norway Regional Health Authority grants to Bj?rn R. Rund (#2004-259, #2006-186). We thank the research team and participants at each contributing site for the opportunity to conduct this research. This work was performed on Services for sensitive data (TSD), IT-department (USIT), University of Oslo, Norway, with resources provided by UNINETT Sigma2?the National Infrastructure for High Performance Computing and Data Storage in Norway.

Funding Information:
Celso Arango: has been a consultant to or has received honoraria or grants from Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion, and Takeda; Covadonga M. Díaz‐Caneja: has received honoraria from AbbVie, Sanofi, and Exeltis; Michael Berk: was supported by an unrestricted grant from AstraZeneca; Paul M. Thompson, Neda Jahanshad: MPI of a research grant from Biogen, Inc., for work unrelated to the contents of this manuscript. Ole A. Andreassen: has received speaker's honorarium from Lundbeck, and is a consultant to HealthLytix. Bradley J. MacIntosh: received a NARSAD Independent Investigator award from the Brain Behavior Research Foundation.

Funding Information:
ENIGMA Core: U.S. National Institutes of Health grants, R01 EB015611, U54 EB020403, R01 MH116147, R01 MH117601, S10OD023696. YTOP: The Research Council of Norway (#223273, #2137000, #250358, #288083); South‐Eastern Norway Regional Health Authority (#2017112); KG Jebsen Stiftelsen (#SKGJ‐MED‐008). Celso Arango has received funding from CIBERSAM: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, co‐financed by ERDF Funds from the European Commission, “A way of making Europe”; CIBERSAM; Instituto de Investigación Sanitaria Gregorio Marañón; Madrid Regional Government (B2017/BMD‐3740 AGES‐CM‐2, Youth Employment Operational Program and Youth Employment Initiative); European Social Fund and EU Structural Funds; EU Seventh Framework Program under grant agreements FP7‐HEALTH‐2009‐2.2.1‐2‐241909, FP7‐HEALTH‐2009‐2.2.1‐3‐242114, FP7‐HEALTH‐2013‐2.2.1‐2‐602478, and FP7‐HEALTH‐2013‐2.2.1‐2‐603196; EU H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS‐2‐TRIALS), Fundación Familia Alonso, Fundación Alicia Koplowitz and Fundación Mutua Madrileña. Covadonga M. Díaz‐Caneja holds a grant from Instituto de Salud Carlos III (JR19/00024). UCLA: NIH/NIBIB U54 EB020403 (BD2K); NIMH RO3 MH105808; P50MH066286; Staglin Family/IMHRO Music Festival for Mental Health. Deakin: This project was supported by an unrestricted grant from AstraZeneca. Michael Berk is supported by a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship (1059660 and APP1156072). SCAPS: The Swedish Research Council (#521‐2014‐3487, #2017‐00949); FORMAS (#259‐2012‐31). KCL‐2: Netherland Organization for Scientific Research (NWO; #451‐13‐035 to Anne‐Kathrin J. Fett and #453‐11‐005 to Lydia Krabbendam); NARSAD Young Investigator Award from the Brain and Behavior Foundation (#24138 to Anne‐Kathrin J. Fett). KCL‐1: R01MH113619. Brain and Behavior Research Foundation/NARSAD. SRI: Canadian Institutes of Health Research; Ontario Mental Health Foundation; Brain & Behavior Research Foundation/NARSAD. Oxford: MRC G0500092. MEND: NIMH R01 MH101506. UiO PSI: South‐Eastern Norway Regional Health Authority grants to Bjørn R. Rund (#2004‐259, #2006‐186). We thank the research team and participants at each contributing site for the opportunity to conduct this research. This work was performed on Services for sensitive data (TSD), IT‐department (USIT), University of Oslo, Norway, with resources provided by UNINETT Sigma2—the National Infrastructure for High Performance Computing and Data Storage in Norway.

Publisher Copyright:
© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.

Funding

ENIGMA Core: U.S. National Institutes of Health grants, R01 EB015611, U54 EB020403, R01 MH116147, R01 MH117601, S10OD023696. YTOP: The Research Council of Norway (#223273, #2137000, #250358, #288083); South-Eastern Norway Regional Health Authority (#2017112); KG Jebsen Stiftelsen (#SKGJ-MED-008). Celso Arango has received funding from CIBERSAM: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, co-financed by ERDF Funds from the European Commission, ?A way of making Europe?; CIBERSAM; Instituto de Investigaci?n Sanitaria Gregorio Mara??n; Madrid Regional Government (B2017/BMD-3740 AGES-CM-2, Youth Employment Operational Program and Youth Employment Initiative); European Social Fund and EU Structural Funds; EU Seventh Framework Program under grant agreements FP7-HEALTH-2009-2.2.1-2-241909, FP7-HEALTH-2009-2.2.1-3-242114, FP7-HEALTH-2013-2.2.1-2-602478, and FP7-HEALTH-2013-2.2.1-2-603196; EU H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS), Fundaci?n Familia Alonso, Fundaci?n Alicia Koplowitz and Fundaci?n Mutua Madrile?a. Covadonga M. D?az-Caneja holds a grant from Instituto de Salud Carlos III (JR19/00024). UCLA: NIH/NIBIB U54 EB020403 (BD2K); NIMH RO3 MH105808; P50MH066286; Staglin Family/IMHRO Music Festival for Mental Health. Deakin: This project was supported by an unrestricted grant from AstraZeneca. Michael Berk is supported by a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship (1059660 and APP1156072). SCAPS: The Swedish Research Council (#521-2014-3487, #2017-00949); FORMAS (#259-2012-31). KCL-2: Netherland Organization for Scientific Research (NWO; #451-13-035 to Anne-Kathrin J. Fett and #453-11-005 to Lydia Krabbendam); NARSAD Young Investigator Award from the Brain and Behavior Foundation (#24138 to Anne-Kathrin J. Fett). KCL-1: R01MH113619. Brain and Behavior Research Foundation/NARSAD. SRI: Canadian Institutes of Health Research; Ontario Mental Health Foundation; Brain & Behavior Research Foundation/NARSAD. Oxford: MRC G0500092. MEND: NIMH R01 MH101506. UiO PSI: South-Eastern Norway Regional Health Authority grants to Bj?rn R. Rund (#2004-259, #2006-186). We thank the research team and participants at each contributing site for the opportunity to conduct this research. This work was performed on Services for sensitive data (TSD), IT-department (USIT), University of Oslo, Norway, with resources provided by UNINETT Sigma2?the National Infrastructure for High Performance Computing and Data Storage in Norway. Celso Arango: has been a consultant to or has received honoraria or grants from Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion, and Takeda; Covadonga M. Díaz‐Caneja: has received honoraria from AbbVie, Sanofi, and Exeltis; Michael Berk: was supported by an unrestricted grant from AstraZeneca; Paul M. Thompson, Neda Jahanshad: MPI of a research grant from Biogen, Inc., for work unrelated to the contents of this manuscript. Ole A. Andreassen: has received speaker's honorarium from Lundbeck, and is a consultant to HealthLytix. Bradley J. MacIntosh: received a NARSAD Independent Investigator award from the Brain Behavior Research Foundation. ENIGMA Core: U.S. National Institutes of Health grants, R01 EB015611, U54 EB020403, R01 MH116147, R01 MH117601, S10OD023696. YTOP: The Research Council of Norway (#223273, #2137000, #250358, #288083); South‐Eastern Norway Regional Health Authority (#2017112); KG Jebsen Stiftelsen (#SKGJ‐MED‐008). Celso Arango has received funding from CIBERSAM: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, co‐financed by ERDF Funds from the European Commission, “A way of making Europe”; CIBERSAM; Instituto de Investigación Sanitaria Gregorio Marañón; Madrid Regional Government (B2017/BMD‐3740 AGES‐CM‐2, Youth Employment Operational Program and Youth Employment Initiative); European Social Fund and EU Structural Funds; EU Seventh Framework Program under grant agreements FP7‐HEALTH‐2009‐2.2.1‐2‐241909, FP7‐HEALTH‐2009‐2.2.1‐3‐242114, FP7‐HEALTH‐2013‐2.2.1‐2‐602478, and FP7‐HEALTH‐2013‐2.2.1‐2‐603196; EU H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS‐2‐TRIALS), Fundación Familia Alonso, Fundación Alicia Koplowitz and Fundación Mutua Madrileña. Covadonga M. Díaz‐Caneja holds a grant from Instituto de Salud Carlos III (JR19/00024). UCLA: NIH/NIBIB U54 EB020403 (BD2K); NIMH RO3 MH105808; P50MH066286; Staglin Family/IMHRO Music Festival for Mental Health. Deakin: This project was supported by an unrestricted grant from AstraZeneca. Michael Berk is supported by a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship (1059660 and APP1156072). SCAPS: The Swedish Research Council (#521‐2014‐3487, #2017‐00949); FORMAS (#259‐2012‐31). KCL‐2: Netherland Organization for Scientific Research (NWO; #451‐13‐035 to Anne‐Kathrin J. Fett and #453‐11‐005 to Lydia Krabbendam); NARSAD Young Investigator Award from the Brain and Behavior Foundation (#24138 to Anne‐Kathrin J. Fett). KCL‐1: R01MH113619. Brain and Behavior Research Foundation/NARSAD. SRI: Canadian Institutes of Health Research; Ontario Mental Health Foundation; Brain & Behavior Research Foundation/NARSAD. Oxford: MRC G0500092. MEND: NIMH R01 MH101506. UiO PSI: South‐Eastern Norway Regional Health Authority grants to Bjørn R. Rund (#2004‐259, #2006‐186). We thank the research team and participants at each contributing site for the opportunity to conduct this research. This work was performed on Services for sensitive data (TSD), IT‐department (USIT), University of Oslo, Norway, with resources provided by UNINETT Sigma2—the National Infrastructure for High Performance Computing and Data Storage in Norway.

FundersFunder number
Biogen, Inc.
Fundación Familia Alonso
H2020 Program
IT-department
KG Jebsen StiftelsenMED-008
Madrid Regional GovernmentB2017/BMD‐3740 AGES‐CM‐2
UNINETT
USIT
National Institutes of HealthR01 MH117601, S10OD023696, R01 EB015611, U54 EB020403, R01 MH116147
National Institute of Mental HealthRO3 MH105808, P50MH066286, R01MH113619
National Institute of Biomedical Imaging and Bioengineering
Brain and Behavior Research Foundation24138
AstraZeneca
Schering-Plough
Fundación Mutua MadrileñaJR19/00024
Fundación Alicia Koplowitz
Sunovion
National Alliance for Research on Schizophrenia and Depression
ACADIA Pharmaceuticals
Canadian Institutes of Health Research
Medical Research CouncilG0500092, R01 MH101506, 2006-186, 2004-259
European Commission
National Health and Medical Research CouncilAPP1156072, 1059660
Svenska Forskningsrådet Formas259-2012-31
Dainippon Sumitomo Pharma
Nederlandse Organisatie voor Wetenschappelijk Onderzoek453‐11‐005, 451‐13‐035
Ontario Mental Health Foundation
Gedeon Richter
Shire
Vetenskapsrådet521-2014-3487, 2017-00949
Instituto de Salud Carlos III
Ministerio de Ciencia e Innovación
European Social Fund
Seventh Framework ProgrammeFP7‐HEALTH‐2009‐2.2.1‐2‐241909, FP7‐HEALTH‐2013‐2.2.1‐2‐602478
Universitetet i Oslo
Norges forskningsråd2137000, 223273, 288083, 250358
Helse Sør-Øst RHF2017112
Angelini Pharma
European Regional Development Fund
Innovative Medicines Initiative115916, 777394
Servier
Norges Idrettshøgskole
Instituto de Investigación Sanitaria Gregorio Marañón

    Keywords

    • adolescence
    • antipsychotics
    • brain structure
    • early-onset
    • intracranial volume
    • psychosis spectrum

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