Unique functional neuroimaging signatures of genetic versus clinical high risk for psychosis.

22q11.2 deletion syndrome brain signal variability clinical high risk functional connectivity neuromaps psychosis

Journal

Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264

Informations de publication

Date de publication:
22 Aug 2024
Historique:
received: 09 04 2024
revised: 05 08 2024
accepted: 08 08 2024
medline: 26 8 2024
pubmed: 26 8 2024
entrez: 24 8 2024
Statut: aheadofprint

Résumé

22q11.2 Deletion Syndrome (22qDel) is a copy number variant (CNV) associated with psychosis and other neurodevelopmental disorders. Adolescents at clinical high risk for psychosis (CHR) are identified based on the presence of subthreshold psychosis symptoms. Whether common neural substrates underlie these distinct high-risk populations is unknown. We compared functional brain measures in 22qDel and CHR cohorts and mapped results to biological pathways. We analyzed two large multi-site cohorts with resting-state functional MRI (rs-fMRI): 1) 22qDel (n=164, 47% female) and typically developing (TD) controls (n=134, 56% female); 2) CHR individuals (n=244, 41% female) and TD controls (n=151, 46% female) from the North American Prodrome Longitudinal Study-2. We computed global brain connectivity (GBC), local connectivity (LC), and brain signal variability (BSV) across cortical regions, testing case-control differences for 22qDel and CHR separately. Group difference maps were related to published brain maps using autocorrelation-preserving permutation. BSV, LC, and GBC are significantly disrupted in 22qDel compared with TD controls (False Discovery Rate q<0.05). Spatial maps of BSV and LC differences are highly correlated with each other, unlike GBC. In CHR, only LC is significantly altered versus controls, with a different spatial pattern compared to 22qDel. Group differences map onto biological gradients, with 22qDel effects strongest in regions with high predicted blood flow and metabolism. 22qDel and CHR exhibit divergent effects on fMRI temporal variability and multi-scale functional connectivity. In 22qDel, strong and convergent disruptions in BSV and LC not seen in CHR individuals suggest distinct functional brain alterations.

Sections du résumé

BACKGROUND BACKGROUND
22q11.2 Deletion Syndrome (22qDel) is a copy number variant (CNV) associated with psychosis and other neurodevelopmental disorders. Adolescents at clinical high risk for psychosis (CHR) are identified based on the presence of subthreshold psychosis symptoms. Whether common neural substrates underlie these distinct high-risk populations is unknown. We compared functional brain measures in 22qDel and CHR cohorts and mapped results to biological pathways.
METHODS METHODS
We analyzed two large multi-site cohorts with resting-state functional MRI (rs-fMRI): 1) 22qDel (n=164, 47% female) and typically developing (TD) controls (n=134, 56% female); 2) CHR individuals (n=244, 41% female) and TD controls (n=151, 46% female) from the North American Prodrome Longitudinal Study-2. We computed global brain connectivity (GBC), local connectivity (LC), and brain signal variability (BSV) across cortical regions, testing case-control differences for 22qDel and CHR separately. Group difference maps were related to published brain maps using autocorrelation-preserving permutation.
RESULTS RESULTS
BSV, LC, and GBC are significantly disrupted in 22qDel compared with TD controls (False Discovery Rate q<0.05). Spatial maps of BSV and LC differences are highly correlated with each other, unlike GBC. In CHR, only LC is significantly altered versus controls, with a different spatial pattern compared to 22qDel. Group differences map onto biological gradients, with 22qDel effects strongest in regions with high predicted blood flow and metabolism.
CONCLUSION CONCLUSIONS
22qDel and CHR exhibit divergent effects on fMRI temporal variability and multi-scale functional connectivity. In 22qDel, strong and convergent disruptions in BSV and LC not seen in CHR individuals suggest distinct functional brain alterations.

Identifiants

DOI: 10.1016/j.biopsych.2024.08.010 PMID: 39181389
pubmed: 39181389
pii: S0006-3223(24)01538-5
doi: 10.1016/j.biopsych.2024.08.010
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Charles H Schleifer (CH)

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.

Sarah E Chang (SE)

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.

Carolyn M Amir (CM)

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.

Kathleen P O'Hora (KP)

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.

Hoki Fung (H)

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.

Jee Won D Kang (JWD)

Department of Psychology, University of California, Los Angeles, CA, USA.

Leila Kushan-Wells (L)

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.

Eileen Daly (E)

Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, London, UK.

Fabio Di Fabio (F)

Department of Human Neurosciences, Sapienza University, Rome, Italy.

Marianna Frascarelli (M)

Department of Human Neurosciences, Sapienza University, Rome, Italy.

Maria Gudbrandsen (M)

Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, London, UK; Centre for Psychological Research (CREW), School of Psychology, University of Roehampton, London, UK.

Wendy R Kates (WR)

Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA.

Declan Murphy (D)

Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, London, UK.

Jean Addington (J)

Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.

Alan Anticevic (A)

Departments of Psychology and Psychiatry, Yale University, New Haven, CT, USA.

Kristin S Cadenhead (KS)

Department of Psychiatry, University of California, San Diego, CA, USA.

Tyrone D Cannon (TD)

Departments of Psychology and Psychiatry, Yale University, New Haven, CT, USA.

Barbara A Cornblatt (BA)

Department of Psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.

Matcheri Keshavan (M)

Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

Daniel H Mathalon (DH)

Department of Psychiatry, University of California, and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.

Diana O Perkins (DO)

Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.

William Stone (W)

Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

Elaine Walker (E)

Department of Psychology, Emory University, Atlanta, GA, USA.

Scott W Woods (SW)

Departments of Psychology and Psychiatry, Yale University, New Haven, CT, USA.

Lucina Q Uddin (LQ)

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.

Kuldeep Kumar (K)

Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal, Canada.

Gil D Hoftman (GD)

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.

Carrie E Bearden (CE)

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA; Department of Psychology, University of California, Los Angeles, CA, USA. Electronic address: cbearden@mednet.ucla.edu.

Classifications MeSH