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.

APA Citation

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.; and Kochunov, Peter, "The additive impact of cardio-metabolic disorders and psychiatric illnesses on accelerated brain aging" (2022). GW Authored Works. Paper 279.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/279

Department

Clinical Research and Leadership