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    The additive impact of cardio-metabolic disorders and psychiatric illnesses on accelerated brain aging.

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    Author
    Ryan, Meghann C
    Hong, 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
    Show allShow less

    Date
    2022-02-03
    Journal
    Human Brain Mapping
    Publisher
    Wiley-Blackwell
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1002/hbm.25769
    Abstract
    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
    MRI
    UK 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/10713/17971
    ae974a485f413a2113503eed53cd6c53
    10.1002/hbm.25769
    Scopus Count
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