Title

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

Authors

Meghann C. Ryan, Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
L Elliot Hong, Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Kathryn S. Hatch, Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Si Gao, Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Shuo Chen, Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Krystl Haerian, Department of Clinical Research and Leadership, School of Medicine and Health Sciences, George Washington University, Washington, District of Columbia, USA.
Jingtao Wang, Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Eric L. Goldwaser, Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Xiaoming Du, Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Bhim M. Adhikari, Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Heather Bruce, Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Stephanie Hare, Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Mark D. Kvarta, Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Neda Jahanshad, Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Los Angeles, California, USA.
Thomas E. Nichols, Nuffield Department of Population Health of the University of Oxford, Oxford, UK.
Paul M. Thompson, Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Los Angeles, California, USA.
Peter Kochunov, Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Document Type

Journal Article

Publication Date

4-15-2022

Journal

Human brain mapping

Volume

43

Issue

6

DOI

10.1002/hbm.25769

Keywords

MRI; UK Biobank; accelerated brain aging; cardio-metabolic disorders; quantile regression index; severe mental illness

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 ) and CMD (F = 24.69, p = 6.82 × 10 ) 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 ) 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 ). 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.

Department

Clinical Research and Leadership

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