Neurocognitive correlates of polygenic risk for bipolar disorder among youth with and without bipolar disorder.

Autor: Jiang X; Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada., Zai C; Department of Psychiatry, University of Toronto, Toronto, Canada; Centre for Addiction and Mental Health, Toronto, ON, Canada., Mio M; Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, Canada., Dimick MK; Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, Canada., Sultan AA; Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, Canada., Young LT; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Centre for Addiction and Mental Health, Toronto, ON, Canada., Goldstein BI; Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada. Electronic address: benjamin.goldstein@camh.ca.
Jazyk: angličtina
Zdroj: Journal of affective disorders [J Affect Disord] 2025 Jan 15; Vol. 369, pp. 845-853. Date of Electronic Publication: 2024 Oct 18.
DOI: 10.1016/j.jad.2024.10.047
Abstrakt: Introduction: There is well-established evidence of reduced neurocognitive performance in adults and youth with bipolar disorder (BD). However, little is known about the polygenic underpinnings of neurocognition in individuals with BD, particularly in youth. The current study aimed to examine the association between polygenic risk score for BD (BD-PRS) and neurocognition among youth with BD and healthy controls (HC).
Methods: 129 youth of European ancestry (72 BD, 57 HC), ages 13-20 years, were included. Six neurocognitive tasks within the Cambridge Neuropsychological Test Automated Battery were assessed. General linear models were used to examine the association between BD-PRS and neurocognitive composite scores, controlling for age, sex, IQ, and two genetic principal components.
Results: In the overall sample, higher BD-PRS was associated with significantly poorer affective processing (β = -0.25, p = 0.01), decision-making (β = -0.23, p = 0.02), and sustained attention (β = -0.28, p = 0.002). Secondary analyses revealed that higher BD-PRS was associated with significantly poorer sustained attention within the BD group (β = -0.27, p = 0.04), and with significantly poorer affective processing within the HC group (β = -0.29, p = 0.04).
Limitations: Cross-sectional design. Modest sample size may have reduced power to detect smaller effect sizes.
Conclusion: The current study found that higher BD-PRS generated based on adult GWAS was associated with poorer neurocognitive performance in youth with BD and HC. Future longitudinal studies incorporating repeated neurocognitive assessments would further inform whether the associations of BD-PRS with neurocognition vary from youth to adulthood, and whether BD-PRS is associated with differential neurodevelopmental trajectories in individuals with and without BD.
Competing Interests: Declaration of competing interest Dr. Clement C. Zai receives an honorarium for a Medscape review on bipolar disorder genetics. Dr. Mikaela K. Dimick is the recipient of a Postdoctoral Award from the Canadian Institutes of Health Research. Dr. Benjamin I. Goldstein acknowledges his position as RBC Investments Chair in Children's Mental Health and Developmental Psychopathology at CAMH, a joint Hospital-University Chair between the University of Toronto, CAMH, and the CAMH Foundation. All other authors report no actual or potential conflict of interests.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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