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Unique functional neuroimaging signatures of genetic versus clinical high risk for psychosis.
Schleifer, Charles H; Chang, Sarah E; Amir, Carolyn M; O'Hora, Kathleen P; Fung, Hoki; Kang, Jee Won D; Kushan-Wells, Leila; Daly, Eileen; Di Fabio, Fabio; Frascarelli, Marianna; Gudbrandsen, Maria; Kates, Wendy R; Murphy, Declan; Addington, Jean; Anticevic, Alan; Cadenhead, Kristin S; Cannon, Tyrone D; Cornblatt, Barbara A; Keshavan, Matcheri; Mathalon, Daniel H; Perkins, Diana O; Stone, William; Walker, Elaine; Woods, Scott W; Uddin, Lucina Q; Kumar, Kuldeep; Hoftman, Gil D; Bearden, Carrie E.
Afiliação
  • Schleifer CH; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
  • Chang SE; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
  • Amir CM; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
  • O'Hora KP; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
  • Fung H; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
  • Kang JWD; Department of Psychology, University of California, Los Angeles, CA, USA.
  • Kushan-Wells L; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
  • Daly E; Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, London, UK.
  • Di Fabio F; Department of Human Neurosciences, Sapienza University, Rome, Italy.
  • Frascarelli M; Department of Human Neurosciences, Sapienza University, Rome, Italy.
  • 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.
  • Kates WR; Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA.
  • Murphy D; Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, London, UK.
  • Addington J; Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
  • Anticevic A; Departments of Psychology and Psychiatry, Yale University, New Haven, CT, USA.
  • Cadenhead KS; Department of Psychiatry, University of California, San Diego, CA, USA.
  • Cannon TD; Departments of Psychology and Psychiatry, Yale University, New Haven, CT, USA.
  • Cornblatt BA; Department of Psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
  • Keshavan M; Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
  • Mathalon DH; Department of Psychiatry, University of California, and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
  • Perkins DO; Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
  • Stone W; Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
  • Walker E; Department of Psychology, Emory University, Atlanta, GA, USA.
  • Woods SW; Departments of Psychology and Psychiatry, Yale University, New Haven, CT, USA.
  • Uddin LQ; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
  • Kumar K; Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal, Canada.
  • Hoftman GD; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
  • 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.
Biol Psychiatry ; 2024 Aug 22.
Article em En | MEDLINE | ID: mdl-39181389
ABSTRACT

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:

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:

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:

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.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article