Global Brain Flexibility During Working Memory is reduced in a High Genetic Risk Group for Schizophrenia

Stavros I Dimitriadis; Thomas Lancaster; Gavin Perry; Katherine Tansey; Derek K Jones; Krish D Singh; Stanley  Zammit; George Davey Smith; Jeremy Hall; Michael C O'Donovan; Michael J Owen; David E Linden

doi:10.1016/j.bpsc.2021.01.007

Global Brain Flexibility During Working Memory is reduced in a High Genetic Risk Group for Schizophrenia

Stavros I Dimitriadis^*
, Thomas Lancaster
, Gavin Perry
, Katherine Tansey
, Derek K Jones
, Krish D Singh
, Stanley Zammit
, George Davey Smith
, Jeremy Hall
, Michael C O'Donovan
, Michael J Owen
, David E Linden

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

12 Citations (Scopus)

224 Downloads (Pure)

Abstract

Altered functional brain connectivity has been proposed as an intermediate phenotype between genetic risk loci and clinical expression of schizophrenia. Genetic high-risk groups of healthy subjects are particularly suited for the investigation of this proposition because they can be tested in the absence of medication or other secondary effects of schizophrenia.

Original language	English
Pages (from-to)	1176-1184
Number of pages	9
Journal	Biological Psychiatry
Volume	6
Issue number	12
Early online date	29 Jan 2021
DOIs	https://doi.org/10.1016/j.bpsc.2021.01.007
Publication status	Published - Dec 2021

Bibliographical note

Funding Information:
This work was supported by the Medical Research Council, United Kingdom (Grant No. MR/K004360/1 [to DEL]; Behavioural and Neurophysiological Effects of Schizophrenia Risk Genes: A Multi-locus, Pathway Based Approach), the MRC/Engineering and Physical Sciences Research Council?funded UK MEG Partnership Grant (Grant No. MR/K005464/1 [to KDS]), the MRC Centre for Neuropsychiatric Genetics and Genomics, United Kingdom (Grant No. MR/L010305/1 [to KDS]), a Marie Curie COFUND EU-UK Research Fellowship (to SID), a Wellcome Trust New Investigator Award and Wellcome Trust Strategic Award (Grant No. 104943/Z/14/Z [to DKJ]), and the National Institute for Health Research Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol (to SZ and GDS). GDS works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (Grant No. MC_UU_00011/1 [to GDS]). The UK Medical Research Council and Wellcome (Grant No. 102215/2/13/2) and the University of Bristol provided core support for Avon Longitudinal Study of Parents and Children. Genome-wide association studies data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. DEL, KDS, DKJ, SZ, GDS, MJO, MCO, and JH designed research; GP and SID performed experiments; SID designed analysis pipeline and analyzed data; TML and KET contributed to data analysis; SID wrote the paper; and all of the authors discussed the results and made critical revisions to the manuscript. We are grateful to Professor Peter Holmans for comments on the manuscript. We are extremely grateful to all the families who took part in this study; the midwives for their help in recruiting them; and the whole Avon Longitudinal Study of Parents and Children team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. The authors report no biomedical financial interests or potential conflicts of interest.

Funding Information:
This work was supported by the Medical Research Council, United Kingdom (Grant No. MR/K004360/1 [to DEL] ; Behavioural and Neurophysiological Effects of Schizophrenia Risk Genes: A Multi-locus, Pathway Based Approach), the MRC/Engineering and Physical Sciences Research Council–funded UK MEG Partnership Grant (Grant No. MR/K005464/1 [to KDS]), the MRC Centre for Neuropsychiatric Genetics and Genomics, United Kingdom (Grant No. MR/L010305/1 [to KDS] ), a Marie Curie COFUND EU-UK Research Fellowship (to SID), a Wellcome Trust New Investigator Award and Wellcome Trust Strategic Award (Grant No. 104943/Z/14/Z [to DKJ]), and the National Institute for Health Research Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol (to SZ and GDS). GDS works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (Grant No. MC_UU_00011/1 [to GDS] ). The UK Medical Research Council and Wellcome (Grant No. 102215/2/13/2) and the University of Bristol provided core support for Avon Longitudinal Study of Parents and Children. Genome-wide association studies data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe.

Publisher Copyright:
© 2021

Keywords

population study
genetics
imaging
schizophrenia
brain flexibility
temporal modularity

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10.1016/j.bpsc.2021.01.007

Full-text PDF (author’s accepted manuscript)
This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Elsevier at https://doi.org/10.1016/j.bpsc.2021.01.007 . Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 882 KBLicence: CC BY-NC-ND

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IEU: MRC Integrative Epidemiology Unit Quinquennial renewal
Gaunt, L. F. (Principal Investigator) & Davey Smith, G. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research

Cite this

@article{8ef0ebf596dc47db9292d490f8556fa4,

title = "Global Brain Flexibility During Working Memory is reduced in a High Genetic Risk Group for Schizophrenia",

abstract = "Altered functional brain connectivity has been proposed as an intermediate phenotype between genetic risk loci and clinical expression of schizophrenia. Genetic high-risk groups of healthy subjects are particularly suited for the investigation of this proposition because they can be tested in the absence of medication or other secondary effects of schizophrenia.",

keywords = "population study, genetics, imaging, schizophrenia, brain flexibility, temporal modularity",

author = "Dimitriadis, \{Stavros I\} and Thomas Lancaster and Gavin Perry and Katherine Tansey and Jones, \{Derek K\} and Singh, \{Krish D\} and Stanley Zammit and \{Davey Smith\}, George and Jeremy Hall and O'Donovan, \{Michael C\} and Owen, \{Michael J\} and Linden, \{David E\}",

note = "Funding Information: This work was supported by the Medical Research Council, United Kingdom (Grant No. MR/K004360/1 [to DEL]; Behavioural and Neurophysiological Effects of Schizophrenia Risk Genes: A Multi-locus, Pathway Based Approach), the MRC/Engineering and Physical Sciences Research Council?funded UK MEG Partnership Grant (Grant No. MR/K005464/1 [to KDS]), the MRC Centre for Neuropsychiatric Genetics and Genomics, United Kingdom (Grant No. MR/L010305/1 [to KDS]), a Marie Curie COFUND EU-UK Research Fellowship (to SID), a Wellcome Trust New Investigator Award and Wellcome Trust Strategic Award (Grant No. 104943/Z/14/Z [to DKJ]), and the National Institute for Health Research Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol (to SZ and GDS). GDS works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (Grant No. MC\_UU\_00011/1 [to GDS]). The UK Medical Research Council and Wellcome (Grant No. 102215/2/13/2) and the University of Bristol provided core support for Avon Longitudinal Study of Parents and Children. Genome-wide association studies data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. DEL, KDS, DKJ, SZ, GDS, MJO, MCO, and JH designed research; GP and SID performed experiments; SID designed analysis pipeline and analyzed data; TML and KET contributed to data analysis; SID wrote the paper; and all of the authors discussed the results and made critical revisions to the manuscript. We are grateful to Professor Peter Holmans for comments on the manuscript. We are extremely grateful to all the families who took part in this study; the midwives for their help in recruiting them; and the whole Avon Longitudinal Study of Parents and Children team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. The authors report no biomedical financial interests or potential conflicts of interest. Funding Information: This work was supported by the Medical Research Council, United Kingdom (Grant No. MR/K004360/1 [to DEL] ; Behavioural and Neurophysiological Effects of Schizophrenia Risk Genes: A Multi-locus, Pathway Based Approach), the MRC/Engineering and Physical Sciences Research Council–funded UK MEG Partnership Grant (Grant No. MR/K005464/1 [to KDS]), the MRC Centre for Neuropsychiatric Genetics and Genomics, United Kingdom (Grant No. MR/L010305/1 [to KDS] ), a Marie Curie COFUND EU-UK Research Fellowship (to SID), a Wellcome Trust New Investigator Award and Wellcome Trust Strategic Award (Grant No. 104943/Z/14/Z [to DKJ]), and the National Institute for Health Research Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol (to SZ and GDS). GDS works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (Grant No. MC\_UU\_00011/1 [to GDS] ). The UK Medical Research Council and Wellcome (Grant No. 102215/2/13/2) and the University of Bristol provided core support for Avon Longitudinal Study of Parents and Children. Genome-wide association studies data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = dec,

doi = "10.1016/j.bpsc.2021.01.007",

language = "English",

volume = "6",

pages = "1176--1184",

journal = "Biological Psychiatry",

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AU - Dimitriadis, Stavros I

AU - Lancaster, Thomas

AU - Perry, Gavin

AU - Tansey, Katherine

AU - Jones, Derek K

AU - Singh, Krish D

AU - Zammit, Stanley

AU - Davey Smith, George

AU - Hall, Jeremy

AU - O'Donovan, Michael C

AU - Owen, Michael J

AU - Linden, David E

N1 - Funding Information: This work was supported by the Medical Research Council, United Kingdom (Grant No. MR/K004360/1 [to DEL]; Behavioural and Neurophysiological Effects of Schizophrenia Risk Genes: A Multi-locus, Pathway Based Approach), the MRC/Engineering and Physical Sciences Research Council?funded UK MEG Partnership Grant (Grant No. MR/K005464/1 [to KDS]), the MRC Centre for Neuropsychiatric Genetics and Genomics, United Kingdom (Grant No. MR/L010305/1 [to KDS]), a Marie Curie COFUND EU-UK Research Fellowship (to SID), a Wellcome Trust New Investigator Award and Wellcome Trust Strategic Award (Grant No. 104943/Z/14/Z [to DKJ]), and the National Institute for Health Research Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol (to SZ and GDS). GDS works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (Grant No. MC_UU_00011/1 [to GDS]). The UK Medical Research Council and Wellcome (Grant No. 102215/2/13/2) and the University of Bristol provided core support for Avon Longitudinal Study of Parents and Children. Genome-wide association studies data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. DEL, KDS, DKJ, SZ, GDS, MJO, MCO, and JH designed research; GP and SID performed experiments; SID designed analysis pipeline and analyzed data; TML and KET contributed to data analysis; SID wrote the paper; and all of the authors discussed the results and made critical revisions to the manuscript. We are grateful to Professor Peter Holmans for comments on the manuscript. We are extremely grateful to all the families who took part in this study; the midwives for their help in recruiting them; and the whole Avon Longitudinal Study of Parents and Children team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. The authors report no biomedical financial interests or potential conflicts of interest. Funding Information: This work was supported by the Medical Research Council, United Kingdom (Grant No. MR/K004360/1 [to DEL] ; Behavioural and Neurophysiological Effects of Schizophrenia Risk Genes: A Multi-locus, Pathway Based Approach), the MRC/Engineering and Physical Sciences Research Council–funded UK MEG Partnership Grant (Grant No. MR/K005464/1 [to KDS]), the MRC Centre for Neuropsychiatric Genetics and Genomics, United Kingdom (Grant No. MR/L010305/1 [to KDS] ), a Marie Curie COFUND EU-UK Research Fellowship (to SID), a Wellcome Trust New Investigator Award and Wellcome Trust Strategic Award (Grant No. 104943/Z/14/Z [to DKJ]), and the National Institute for Health Research Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol (to SZ and GDS). GDS works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (Grant No. MC_UU_00011/1 [to GDS] ). The UK Medical Research Council and Wellcome (Grant No. 102215/2/13/2) and the University of Bristol provided core support for Avon Longitudinal Study of Parents and Children. Genome-wide association studies data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. Publisher Copyright: © 2021

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AB - Altered functional brain connectivity has been proposed as an intermediate phenotype between genetic risk loci and clinical expression of schizophrenia. Genetic high-risk groups of healthy subjects are particularly suited for the investigation of this proposition because they can be tested in the absence of medication or other secondary effects of schizophrenia.

KW - population study

KW - genetics

KW - imaging

KW - schizophrenia

KW - brain flexibility

KW - temporal modularity

U2 - 10.1016/j.bpsc.2021.01.007

DO - 10.1016/j.bpsc.2021.01.007

M3 - Article (Academic Journal)

C2 - 33524599

SN - 0006-3223

VL - 6

SP - 1176

EP - 1184

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 12

ER -

Global Brain Flexibility During Working Memory is reduced in a High Genetic Risk Group for Schizophrenia

Abstract

Bibliographical note

Keywords

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Projects

IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

Cite this