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Polygenic risk for schizophrenia, transition and cortical gyrification: a high-risk study

Published online by Cambridge University Press:  25 October 2017

E. Neilson ,
C. Bois ,
T.-K. Clarke ,
L. Hall ,
E. C. Johnstone ,
D. G. C. Owens ,
H. C. Whalley ,
A. M. McIntosh  and
S. M. Lawrie
E. Neilson*
Affiliation:
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Kennedy Tower, Edinburgh, UK
C. Bois
Affiliation:
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Kennedy Tower, Edinburgh, UK
T.-K. Clarke
Affiliation:
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Kennedy Tower, Edinburgh, UK
L. Hall
Affiliation:
International Centre for Life, Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, UK
E. C. Johnstone
Affiliation:
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Kennedy Tower, Edinburgh, UK
D. G. C. Owens
Affiliation:
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Kennedy Tower, Edinburgh, UK
H. C. Whalley
Affiliation:
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Kennedy Tower, Edinburgh, UK
A. M. McIntosh
Affiliation:
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Kennedy Tower, Edinburgh, UK
S. M. Lawrie
Affiliation:
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Kennedy Tower, Edinburgh, UK
*
Author for correspondence: E Neilson, E-mail: [email protected]
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Abstract

Background

Schizophrenia is a highly heritable disorder, linked to several structural abnormalities of the brain. More specifically, previous findings have suggested that increased gyrification in frontal and temporal regions are implicated in the pathogenesis of schizophrenia.

Methods

The current study included participants at high familial risk of schizophrenia who remained well (n = 31), who developed sub-diagnostic symptoms (n = 28) and who developed schizophrenia (n = 9) as well as healthy controls (HC) (n = 16). We first tested whether individuals at high familial risk of schizophrenia carried an increased burden of trait-associated alleles using polygenic risk score analysis. We then assessed the extent to which polygenic risk was associated with gyral folding in the frontal and temporal lobes.

Results

We found that individuals at high familial risk of schizophrenia who developed schizophrenia carried a significantly greater burden of risk-conferring variants for the disorder compared to those at high risk (HR) who developed sub-diagnostic symptoms or remained well and HC. Furthermore, within the HR cohort, there was a significant and positive association between schizophrenia polygenic risk score and bilateral frontal gyrification.

Conclusions

These results suggest that polygenic risk for schizophrenia impacts upon early neurodevelopment to confer greater gyral folding in adulthood and an increased risk of developing the disorder.

Keywords

Familial high riskpolygenic risk scoresstructural MRI
Type
Original Articles
Information
Psychological Medicine , Volume 48 , Issue 9 , July 2018 , pp. 1532 - 1539
Copyright
Copyright © Cambridge University Press 2017 

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