Association between brain similarity to severe mental illnesses and comorbid cerebral, physical, and cognitive impairments
Yizhou Ma,
Mark D. Kvarta,
Bhim M. Adhikari,
Joshua Chiappelli,
Xiaoming Du,
Andrew van der Vaart,
Eric L. Goldwaser,
Heather Bruce,
Kathryn S. Hatch,
Si Gao,
Ann Summerfelt,
Neda Jahanshad,
Paul M. Thompson,
Thomas E. Nichols,
L. Elliot Hong,
Peter Kochunov
Affiliations
Yizhou Ma
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA; Corresponding author: Phone: (410) 402-6027, Fax: (410) 402-6077
Mark D. Kvarta
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
Bhim M. Adhikari
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
Joshua Chiappelli
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
Xiaoming Du
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
Andrew van der Vaart
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
Eric L. Goldwaser
Department of Psychiatry, Weill Cornell Medical College/New York-Presbyterian Hospital, New York, NY, USA
Heather Bruce
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
Kathryn S. Hatch
School of Medicine, University of California, San Diego, CA, USA
Si Gao
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
Ann Summerfelt
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
Neda Jahanshad
Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, CA, USA
Paul M. Thompson
Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, CA, USA
Thomas E. Nichols
Big Data Science Institute, Department of Statistics, University of Oxford, Oxford, UK.
L. Elliot Hong
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
Peter Kochunov
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
Severe mental illnesses (SMIs) are often associated with compromised brain health, physical comorbidities, and cognitive deficits, but it is incompletely understood whether these comorbidities are intrinsic to SMI pathophysiology or secondary to having SMIs. We tested the hypothesis that cerebral, cardiometabolic, and cognitive impairments commonly observed in SMIs can be observed in non-psychiatric individuals with SMI-like brain patterns of deviation as seen on magnetic resonance imaging. 22,883 participants free of common neuropsychiatric conditions from the UK Biobank (age = 63.4 ± 7.5 years, range = 45–82 years, 50.9% female) were split into discovery and replication samples. The regional vulnerability index (RVI) was used to quantify each participant's respective brain similarity to meta-analytical patterns of schizophrenia spectrum disorder, bipolar disorder, and major depressive disorder in gray matter thickness, subcortical gray matter volume, and white matter integrity. Cluster analysis revealed five clusters with distinct RVI profiles. Compared with a cluster with no RVI elevation, a cluster with RVI elevation across all SMIs and brain structures showed significantly higher volume of white matter hyperintensities (Cohen's d = 0.59, pFDR < 10−16), poorer cardiovascular (Cohen's d = 0.30, pFDR < 10−16) and metabolic (Cohen's d = 0.12, pFDR = 1.3 × 10−4) health, and slower speed of information processing (|Cohen's d| = 0.11-0.17, pFDR = 1.6 × 10−3-4.6 × 10−8). This cluster also had significantly higher level of C-reactive protein and alcohol use (Cohen's d = 0.11 and 0.28, pFDR = 4.1 × 10−3 and 1.1 × 10−11). Three other clusters with respective RVI elevation in gray matter thickness, subcortical gray matter volume, and white matter integrity showed intermediate level of white matter hyperintensities, cardiometabolic health, and alcohol use. Our results suggest that cerebral, physical, and cognitive impairments in SMIs may be partly intrinsic via shared pathophysiological pathways with SMI-related brain anatomical changes.
