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Accelerated cortical thinning and volume reduction over time in young people at high genetic risk for bipolar disorder

Published online by Cambridge University Press:  07 September 2020

G. Roberts Open the ORCID record for G. Roberts [Opens in a new window] ,
R. Lenroot ,
B. Overs ,
J. Fullerton ,
V. Leung ,
K. Ridgway ,
A. Stuart ,
A. Frankland ,
F. Levy  and
D. Hadzi-Pavlovic
...Show all authors
G. Roberts
Affiliation:
School of Psychiatry, University of New South Wales, Randwick, NSW, Australia Black Dog Institute, Prince of Wales Hospital, Randwick, NSW, Australia
R. Lenroot
Affiliation:
School of Psychiatry, University of New South Wales, Randwick, NSW, Australia Neuroscience Research Australia, Sydney, NSW, Australia School of Medicine, University of New Mexico, Albuquerque, New Mexico
B. Overs
Affiliation:
Neuroscience Research Australia, Sydney, NSW, Australia
J. Fullerton
Affiliation:
Neuroscience Research Australia, Sydney, NSW, Australia School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
V. Leung
Affiliation:
School of Psychiatry, University of New South Wales, Randwick, NSW, Australia Black Dog Institute, Prince of Wales Hospital, Randwick, NSW, Australia
K. Ridgway
Affiliation:
School of Psychiatry, University of New South Wales, Randwick, NSW, Australia Black Dog Institute, Prince of Wales Hospital, Randwick, NSW, Australia
A. Stuart
Affiliation:
School of Psychiatry, University of New South Wales, Randwick, NSW, Australia Black Dog Institute, Prince of Wales Hospital, Randwick, NSW, Australia
A. Frankland
Affiliation:
School of Psychiatry, University of New South Wales, Randwick, NSW, Australia Black Dog Institute, Prince of Wales Hospital, Randwick, NSW, Australia
F. Levy
Affiliation:
School of Psychiatry, University of New South Wales, Randwick, NSW, Australia Prince of Wales Hospital, Randwick, NSW, Australia
D. Hadzi-Pavlovic
Affiliation:
School of Psychiatry, University of New South Wales, Randwick, NSW, Australia Black Dog Institute, Prince of Wales Hospital, Randwick, NSW, Australia
M. Breakspear
Affiliation:
School of psychology, University of Newcastle, Callaghan, NSW, Australia
P. B. Mitchell*
Affiliation:
School of Psychiatry, University of New South Wales, Randwick, NSW, Australia Black Dog Institute, Prince of Wales Hospital, Randwick, NSW, Australia Prince of Wales Hospital, Randwick, NSW, Australia
*
Author for correspondence: P. B. Mitchell, E-mail: phil.mitchell@unsw.edu.au
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Abstract

Background

Bipolar disorder (BD) is a familial psychiatric disorder associated with frontotemporal and subcortical brain abnormalities. It is unclear whether such abnormalities are present in relatives without BD, and little is known about structural brain trajectories in those at risk.

Method

Neuroimaging was conducted at baseline and at 2-year follow-up interval in 90 high-risk individuals with a first-degree BD relative (HR), and 56 participants with no family history of mental illness who could have non-BD diagnoses. All 146 subjects were aged 12–30 years at baseline. We examined longitudinal change in gray and white matter volume, cortical thickness, and surface area in the frontotemporal cortex and subcortical regions.

Results

Compared to controls, HR participants showed accelerated cortical thinning and volume reduction in right lateralised frontal regions, including the inferior frontal gyrus, lateral orbitofrontal cortex, frontal pole and rostral middle frontal gyrus. Independent of time, the HR group had greater cortical thickness in the left caudal anterior cingulate cortex, larger volume in the right medial orbitofrontal cortex and greater area of right accumbens, compared to controls. This pattern was evident even in those without the new onset of psychopathology during the inter-scan interval.

Conclusions

This study suggests that differences previously observed in BD are developing prior to the onset of the disorder. The pattern of pathological acceleration of cortical thinning is likely consistent with a disturbance of molecular mechanisms responsible for normal cortical thinning. We also demonstrate that neuroanatomical differences in HR individuals may be progressive in some regions and stable in others.

Keywords

Bipolar disordergenetic risklongitudinalstructural MRI
Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 7 , May 2022 , pp. 1344 - 1355
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Copyright
Copyright © The Author(s) 2020. Published by Cambridge University Press

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