A normative chart for cognitive development in a genetically selected population.


Journal

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
ISSN: 1740-634X
Titre abrégé: Neuropsychopharmacology
Pays: England
ID NLM: 8904907

Informations de publication

Date de publication:
06 2022
Historique:
received: 14 07 2020
accepted: 30 01 2021
revised: 12 01 2021
pubmed: 31 3 2021
medline: 21 5 2022
entrez: 30 3 2021
Statut: ppublish

Résumé

Certain pathogenic genetic variants impact neurodevelopment and cause deviations from typical cognitive trajectories. Understanding variant-specific cognitive trajectories is clinically important for informed monitoring and identifying patients at risk for comorbid conditions. Here, we demonstrate a variant-specific normative chart for cognitive development for individuals with 22q11.2 deletion syndrome (22q11DS). We used IQ data from 1365 individuals with 22q11DS to construct variant-specific normative charts for cognitive development (Full Scale, Verbal, and Performance IQ). This allowed us to calculate Z-scores for each IQ datapoint. Then, we calculated the change between first and last available IQ assessments (delta Z-IQ-scores) for each individual with longitudinal IQ data (n = 708). We subsequently investigated whether using the variant-specific IQ-Z-scores would decrease required sample size to detect an effect with schizophrenia risk, as compared to standard IQ-scores. The mean Z-IQ-scores for FSIQ, VIQ, and PIQ were close to 0, indicating that participants had IQ-scores as predicted by the normative chart. The mean delta-Z-IQ-scores were equally close to 0, demonstrating a good fit of the normative chart and indicating that, as a group, individuals with 22q11DS show a decline in IQ-scores as they grow into adulthood. Using variant-specific IQ-Z-scores resulted in 30% decrease of required sample size, as compared to the standard IQ-based approach, to detect the association between IQ-decline and schizophrenia (p < 0.01). Our findings suggest that using variant-specific normative IQ data significantly reduces required sample size in a research context, and may facilitate a more clinically informative interpretation of IQ data. This approach allows identification of individuals that deviate from their expected, variant-specific, trajectory. This group may be at increased risk for comorbid conditions, such as schizophrenia in the case of 22q11DS.

Identifiants

pubmed: 33782512
doi: 10.1038/s41386-021-00988-6
pii: 10.1038/s41386-021-00988-6
pmc: PMC9117666
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1379-1386

Subventions

Organisme : NIMH NIH HHS
ID : U01 MH119736
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH119758
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH119738
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD105352
Pays : United States
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R01 MH085953
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH119740
Pays : United States

Informations de copyright

© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.

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Auteurs

Ania M Fiksinski (AM)

Wilhelmina Children's Hospital & University Medical Center Utrecht, Brain Center, Utrecht, The Netherlands. a.m.fiksinski@umcutrecht.nl.
Centre for Addiction and Mental Health, Toronto, ON, Canada. a.m.fiksinski@umcutrecht.nl.
The Dalglish Family 22q Clinic for 22q11.2 Deletion Syndrome, Toronto General Hospital, University Health Network, Toronto, ON, Canada. a.m.fiksinski@umcutrecht.nl.
Department of Psychiatry and Neuropsychology, Division of Mental Health, MHeNS, Maastricht University, Maastricht, The Netherlands. a.m.fiksinski@umcutrecht.nl.

Carrie E Bearden (CE)

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

Anne S Bassett (AS)

The Dalglish Family 22q Clinic, Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Canada.
Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Canada.
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.

René S Kahn (RS)

Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Janneke R Zinkstok (JR)

Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.

Stephen R Hooper (SR)

Department of Allied Health Sciences, School of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, United States of America.

Wanda Tempelaar (W)

Centre for Addiction and Mental Health, Toronto, ON, Canada.
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

Donna McDonald-McGinn (D)

Division of Human Genetics, 22q and You Center, Clinical Genetics Center, and Section of Genetic Counseling, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Department of Pediatrics, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.

Ann Swillen (A)

Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium.
Department of Human Genetics KU Leuven, Leuven, Belgium.

Beverly Emanuel (B)

Division of Human Genetics, 22q and You Center, Clinical Genetics Center, and Section of Genetic Counseling, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Bernice Morrow (B)

Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.

Raquel Gur (R)

Department of Psychiatry and Lifespan Brain Institute, Penn Medicine-CHOP, University of Pennsylvania, Philadelphia, PA, USA.

Eva Chow (E)

Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Canada.
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

Marianne van den Bree (M)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.

Joris Vermeesch (J)

Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium.

Stephen Warren (S)

Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.

Michael Owen (M)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.

Therese van Amelsvoort (T)

Department of Psychiatry and Neuropsychology, Division of Mental Health, MHeNS, Maastricht University, Maastricht, The Netherlands.

Stephan Eliez (S)

Developmental Imaging and Psychopathology, Department of Psychiatry, University of Geneva, Geneva, Switzerland.

Doron Gothelf (D)

The Child Psychiatry Division, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel.
Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.

Celso Arango (C)

Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, School of Medicine, Universidad Complutense, Madrid, Spain.

Wendy Kates (W)

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

Tony Simon (T)

MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California Davis, Sacramento, CA, USA.

Kieran Murphy (K)

Department of Psychiatry, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.

Gabriela Repetto (G)

Centro de Genética y Genómica, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile.

Damian Heine Suner (DH)

Genomics of Health Group and Molecular Diagnostics and Clinical Genetics Unit (UDMGC), Health Research Institute of the Balearic Islands (IdISBa), Hospital Universitari Son Espases, Palma de Mallorca, Spain.

Stefano Vicari (S)

Department of Life Sciences and Public Health, Catholic University; Child and Adolescent Psychiatry Unit, Bambino Gesù Children's Hospital, IRCSS, Rome, Italy.

Joseph Cubells (J)

Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
Emory Autism Center, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.

Marco Armando (M)

Developmental Imaging and Psychopathology, Department of Psychiatry, University of Geneva, Geneva, Switzerland.

Nicole Philip (N)

Département de Génétique Médicale, APHM, CHU Timone Enfants, Marseille, France.
Aix Marseille Université, MMG, INSERM, Marseille, France.

Linda Campbell (L)

School of Psychology, University of Newcastle, Newcastle, Australia.

Sixto Garcia-Minaur (S)

Institute of Medical and Molecular Genetics (INGEMM), La Paz University Hospital, Madrid, Spain.

Maude Schneider (M)

Developmental Imaging and Psychopathology, Department of Psychiatry, University of Geneva, Geneva, Switzerland.

Vandana Shashi (V)

Division of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.

Jacob Vorstman (J)

Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Psychiatry, The Hospital for Sick Children, Toronto, Ontario, Canada.

Elemi J Breetvelt (EJ)

Department of Psychiatry, The Hospital for Sick Children, Toronto, Ontario, Canada.

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