Wilkinson, ID, Mahmood, T, Yasmin, SF et al. (11 more authors) (2022) In memory of Professor Iain Wilkinson: cognitive and neuroimaging endophenotypes in a consanguineous schizophrenia multiplex family. Psychological Medicine. PII S0033291721005250. ISSN 0033-2917
Abstract
Background
Schizophrenia endophenotypes may help elucidate functional effects of genetic risk variants in multiply affected consanguineous families that segregate recessive risk alleles of large effect size. We studied the association between a schizophrenia risk locus involving a 6.1Mb homozygous region on chromosome 13q22–31 in a consanguineous multiplex family and cognitive functioning, haemodynamic response and white matter integrity using neuroimaging.
Methods
We performed CANTAB neuropsychological testing on four affected family members (all homozygous for the risk locus), ten unaffected family members (seven homozygous and three heterozygous) and ten healthy volunteers, and tested neuronal responses on fMRI during an n-back working memory task, and white matter integrity on diffusion tensor imaging (DTI) on four affected and six unaffected family members (four homozygous and two heterozygous) and three healthy volunteers. For cognitive comparisons we used a linear mixed model (Kruskal–Wallis) test, followed by posthoc Dunn's pairwise tests with a Bonferroni adjustment. For fMRI analysis, we counted voxels exceeding the p < 0.05 corrected threshold. DTI analysis was observational.
Results
Family members with schizophrenia and unaffected family members homozygous for the risk haplotype showed attention (p < 0.01) and working memory deficits (p < 0.01) compared with healthy controls; a neural activation laterality bias towards the right prefrontal cortex (voxels reaching p < 0.05, corrected) and observed lower fractional anisotropy in the anterior cingulate cortex and left dorsolateral prefrontal cortex.
Conclusions
In this family, homozygosity at the 13q risk locus was associated with impaired cognition, white matter integrity, and altered laterality of neural activation.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s), 2022. Published by Cambridge University Press. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited. |
Keywords: | Cognition; connectivity; consanguinity; endophenotypes; fractional anisotropy; schizophrenia |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Health Sciences (Leeds) > Academic Unit of Psychiatry and Behavioural Sciences (Leeds) |
Funding Information: | Funder Grant number MRC (Medical Research Council) MR/J004391/1 Wellcome Trust NOT GIVEN Qatar National Research Fund NPRP7-1174-3 302 |
Depositing User: | Symplectic Publications |
Date Deposited: | 21 Feb 2022 07:55 |
Last Modified: | 04 Mar 2022 15:55 |
Status: | Published online |
Publisher: | Cambridge University Press |
Identification Number: | 10.1017/S0033291721005250 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:183741 |