Overlapping brain correlates of superior cognition among children at genetic risk for Alzheimer’s disease and/or major depressive disorder

Petrican, Raluca ORCID: https://orcid.org/0000-0002-1363-5553, Paine, Amy L. ORCID: https://orcid.org/0000-0002-9025-3719, Escott-Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483 and Shelton, Katherine H. ORCID: https://orcid.org/0000-0002-1311-5291 2023. Overlapping brain correlates of superior cognition among children at genetic risk for Alzheimer’s disease and/or major depressive disorder. Scientific Reports 13 (1) , p. 984. 10.1038/s41598-023-28057-6

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Abstract

Early life adversity (ELA) tends to accelerate neurobiological ageing, which, in turn, is thought to heighten vulnerability to both major depressive disorder (MDD) and Alzheimer’s disease (AD). The two conditions are putatively related, with MDD representing either a risk factor or early symptom of AD. Given the substantial environmental susceptibility of both disorders, timely identification of their neurocognitive markers could facilitate interventions to prevent clinical onset. To this end, we analysed multimodal data from the Adolescent Brain and Cognitive Development study (ages 9–10 years). To disentangle genetic from correlated genetic-environmental influences, while also probing gene-adversity interactions, we compared adoptees, a group generally exposed to substantial ELA, with children raised by their biological families via genetic risk scores (GRS) from genome-wide association studies. AD and MDD GRSs predicted overlapping and widespread neurodevelopmental alterations associated with superior fluid cognition. Specifically, among adoptees only, greater AD GRS were related to accelerated structural maturation (i.e., cortical thinning) and higher MDD GRS were linked to delayed functional neurodevelopment, as reflected in compensatory brain activation on an inhibitory control task. Our study identifies compensatory mechanisms linked to MDD risk and highlights the potential cognitive benefits of accelerated maturation linked to AD vulnerability in late childhood.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Psychology
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Nature Research
Date of First Compliant Deposit:	20 January 2023
Date of Acceptance:	12 January 2023
Last Modified:	05 Jan 2024 07:53
URI:	https://orca.cardiff.ac.uk/id/eprint/156126

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