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Genome-Transcriptome-Functional Connectivity-Cognition Link Differentiates Schizophrenia From Bipolar Disorder.
Chen, Jiayu; Fu, Zening; Bustillo, Juan R; Perrone-Bizzozero, Nora I; Lin, Dongdong; Canive, Jose; Pearlson, Godfrey D; Stephen, Julia M; Mayer, Andrew R; Potkin, Steven G; van Erp, Theo G M; Kochunov, Peter; Elliot Hong, L; Adhikari, Bhim M; Andreassen, Ole A; Agartz, Ingrid; Westlye, Lars T; Sui, Jing; Du, Yuhui; Macciardi, Fabio; Hanlon, Faith M; Jung, Rex E; Turner, Jessica A; Liu, Jingyu; Calhoun, Vince D.
Affiliation
  • Chen J; Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, and Emory University, Atlanta, GA, USA.
  • Fu Z; Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, and Emory University, Atlanta, GA, USA.
  • Bustillo JR; Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.
  • Perrone-Bizzozero NI; Department of Psychiatry and Behavioral Sciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.
  • Lin D; Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.
  • Canive J; Department of Psychiatry and Behavioral Sciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.
  • Pearlson GD; Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, and Emory University, Atlanta, GA, USA.
  • Stephen JM; Department of Psychiatry and Behavioral Sciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.
  • Mayer AR; Olin Neuropsychiatry Research Center, Institute of Living, Hartford, CT, USA.
  • Potkin SG; Department of Psychiatry and Neuroscience, Yale University, New Haven, CT, USA.
  • van Erp TGM; The Mind Research Network, Albuquerque, NM, USA.
  • Kochunov P; The Mind Research Network, Albuquerque, NM, USA.
  • Elliot Hong L; Department of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine, CA, USA.
  • Adhikari BM; Department of Psychiatry and Human Behavior, Clinical Translational Neuroscience Laboratory, School of Medicine, University of California, Irvine, CA, USA.
  • Andreassen OA; Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, USA.
  • Agartz I; Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, USA.
  • Westlye LT; Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, USA.
  • Sui J; Division of Mental Health and Addiction, Norwegian Centre for Mental Disorders Research (NORMENT), Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Du Y; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
  • Macciardi F; Division of Mental Health and Addiction, Norwegian Centre for Mental Disorders Research (NORMENT), Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Hanlon FM; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
  • Jung RE; Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.
  • Turner JA; Division of Mental Health and Addiction, Norwegian Centre for Mental Disorders Research (NORMENT), Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Liu J; Department of Psychology, University of Oslo, Oslo, Norway.
  • Calhoun VD; Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, and Emory University, Atlanta, GA, USA.
Schizophr Bull ; 48(6): 1306-1317, 2022 11 18.
Article in En | MEDLINE | ID: mdl-35988022
ABSTRACT
BACKGROUND AND

HYPOTHESIS:

Schizophrenia (SZ) and bipolar disorder (BD) share genetic risk factors, yet patients display differential levels of cognitive impairment. We hypothesized a genome-transcriptome-functional connectivity (frontoparietal)-cognition pathway linked to SZ-versus-BD differences, and conducted a multiscale study to delineate this pathway. STUDY DESIGNS Large genome-wide studies provided single nucleotide polymorphisms (SNPs) conferring more risk for SZ than BD, and we identified their regulated genes, namely SZ-biased SNPs and genes. We then (a) computed the polygenic risk score for SZ (PRSSZ) of SZ-biased SNPs and examined its associations with imaging-based frontoparietal functional connectivity (FC) and cognitive performances; (b) examined the spatial correlation between ex vivo postmortem expressions of SZ-biased genes and in vivo, SZ-related FC disruptions across frontoparietal regions; (c) investigated SZ-versus-BD differences in frontoparietal FC; and (d) assessed the associations of frontoparietal FC with cognitive performances. STUDY

RESULTS:

PRSSZ of SZ-biased SNPs was significantly associated with frontoparietal FC and working memory test scores. SZ-biased genes' expressions significantly correlated with SZ-versus-BD differences in FC across frontoparietal regions. SZ patients showed more reductions in frontoparietal FC than BD patients compared to controls. Frontoparietal FC was significantly associated with test scores of multiple cognitive domains including working memory, and with the composite scores of all cognitive domains.

CONCLUSIONS:

Collectively, these multiscale findings support the hypothesis that SZ-biased genetic risk, through transcriptome regulation, is linked to frontoparietal dysconnectivity, which in turn contributes to differential cognitive deficits in SZ-versus BD, suggesting that potential biomarkers for more precise patient stratification and treatment.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Schizophrenia / Bipolar Disorder / Cognition Disorders Type of study: Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Journal: Schizophr Bull Year: 2022 Type: Article Affiliation country: United States
Fulltext
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Schizophrenia / Bipolar Disorder / Cognition Disorders Type of study: Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Journal: Schizophr Bull Year: 2022 Type: Article Affiliation country: United States