The additive impact of cardio-metabolic disorders and psychiatric illnesses on accelerated brain aging.
Author
Ryan, Meghann CHong, L Elliot
Hatch, Kathryn S
Gao, Si
Chen, Shuo
Haerian, Krystl
Wang, Jingtao
Goldwaser, Eric L
Du, Xiaoming
Adhikari, Bhim M
Bruce, Heather
Hare, Stephanie
Kvarta, Mark D
Jahanshad, Neda
Nichols, Thomas E
Thompson, Paul M
Kochunov, Peter
Date
2022-02-03Journal
Human Brain MappingPublisher
Wiley-BlackwellType
Article
Metadata
Show full item recordAbstract
Severe mental illnesses (SMI) including major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia spectrum disorder (SSD) elevate accelerated brain aging risks. Cardio-metabolic disorders (CMD) are common comorbidities in SMI and negatively impact brain health. We validated a linear quantile regression index (QRI) approach against the machine learning "BrainAge" index in an independent SSD cohort (N = 206). We tested the direct and additive effects of SMI and CMD effects on accelerated brain aging in the N = 1,618 (604 M/1,014 F, average age = 63.53 ± 7.38) subjects with SMI and N = 11,849 (5,719 M/6,130 F; 64.42 ± 7.38) controls from the UK Biobank. Subjects were subdivided based on diagnostic status: SMI+/CMD+ (N = 665), SMI+/CMD- (N = 964), SMI-/CMD+ (N = 3,765), SMI-/CMD- (N = 8,083). SMI (F = 40.47, p = 2.06 × 10-10 ) and CMD (F = 24.69, p = 6.82 × 10-7 ) significantly, independently impacted whole-brain QRI in SMI+. SSD had the largest effect (Cohen's d = 1.42) then BD (d = 0.55), and MDD (d = 0.15). Hypertension had a significant effect on SMI+ (d = 0.19) and SMI- (d = 0.14). SMI effects were direct, independent of MD, and remained significant after correcting for effects of antipsychotic medications. Whole-brain QRI was significantly (p < 10-16 ) associated with the volume of white matter hyperintensities (WMH). However, WMH did not show significant association with SMI and was driven by CMD, chiefly hypertension (p < 10-16 ). We used a simple and robust index, QRI, the demonstrate additive effect of SMI and CMD on accelerated brain aging. We showed a greater effect of psychiatric illnesses on QRI compared to cardio-metabolic illness. Our findings suggest that subjects with SMI should be among the targets for interventions to protect against age-related cognitive decline.Rights/Terms
© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.Keyword
MRIUK Biobank
accelerated brain aging
cardio-metabolic disorders
quantile regression index
severe mental illness
Identifier to cite or link to this item
http://hdl.handle.net/10713/17971ae974a485f413a2113503eed53cd6c53
10.1002/hbm.25769
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