The uneven landscape of cognitive domains in 22q11.2 deletion syndrome: A large consortium study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background 22q11.2 deletion syndrome (22q11DS) is strongly associated with aberrant neurodevelopment, including decreased cognitive functioning and schizophrenia spectrum disorders (SSDs). While the different core domains of IQ have distinct clinical ramifications, their collective profile has not been well-characterized in 22q11DS. Here, in the largest 22q11DS sample to date, we elucidate the overall IQ profile, including Verbal and Performance IQ (VIQ and PIQ), Processing Speed (PS), and Working Memory (WM), including associations with developmental stage and SSDs. Methods We included 1,328 individuals with 22q11DS from the International Brain and Behavior Consortium. We derived an overall IQ profile using VIQ, PIQ, PS, and WM scores at initial assessment, from age-appropriate Wechsler scales. Using both cross-sectional and longitudinal IQ data from a subset ( n = 496; 37.35%) of individuals, we examined IQ profiles across three age groups and compared profiles between individuals with and without SSDs. Results IQ profiles in 22q11DS exhibited differences between IQ domains ( p < 0.001), ranked from relatively strongest to weakest: PS > WM > VIQ > PIQ. This profile was similar across age groups, with scores highest in children, lower in adolescents, and lowest in adults. Individuals without SSDs had higher IQ scores than those with SSDs ( p < 0.001), with no significant domain-specific effects. Conclusions The results indicate a tendency toward a characteristic IQ profile in 22q11DS, regardless of SSD status. A clinical implication of these divergent IQ domains, in particular the relative weakness in PIQ, is that functional expectations are likely to be overestimated. The domain-specific differences across age-groups highlight the need for repeated and comprehensive cognitive assessments in this high-risk population, and may suggest differing underlying mechanisms that require further investigation.
Source: Psychological Medicine
Authors: Ania M. Fiksinski, Rielle Wierenga, Donna McDonald-McGinn, Anne S. Bassett, Carrie E. Bearden, Bernice Morrow, Beverly Emanuel, Raquel E. Gur, Ann Swillen, Stephen R. Hooper, Eva W.C. Chow, Marianne B.M. van den Bree, Joris R. Vermeesch, Michael J. Owen, Stephan Eliez, Doron Gothelf, Celso Arango, Wendy R. Kates, Tony Simon, Kieran C. Murphy, Declan Murphy, Gabriela M. Repetto, Jaume Morey Canyelles, Stefano Vicari, Joseph Cubells, Nicole Philip, Linda Campbell, Covadonga M. Díaz-Caneja, Maude Schneider, Vandana Shashi, Marco Armando, Elemi J. Breetvelt, Henriette de Veye, Therese van Amelsvoort, Jacob Vorstman
Institutions: University Medical Center Utrecht, Maastricht University, Children's Hospital of Philadelphia, University of Pennsylvania, Centre for Addiction and Mental Health, University of Toronto, Toronto General Hospital, Albert Einstein College of Medicine, KU Leuven, University of North Carolina at Chapel Hill, Cardiff University, University of Geneva, Tel Aviv University, Sheba Medical Center, Hospital General Universitario Gregorio Marañón, SUNY Upstate Medical University, University of California, Davis, Beaumont Hospital, King's College London, Universidad del Desarrollo, Clínica Alemana, Hospital Universitario Son Espases, Bambino Gesù Children's Hospital, Emory University, Aix-Marseille Université, Hôpital de la Timone, University of Newcastle Australia, Duke University, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Leiden University Medical Center, Great Ormond Street Hospital, Hospital for Sick Children, Maastricht University Medical Centre
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,550
Funders: McLaughlin Centre, University of Toronto, Fundación Alicia Koplowitz, Wellcome Trust, International Seafood Sustainability Foundation, European Commission, Fonds Wetenschappelijk Onderzoek, Ministerio de Ciencia e Innovación, Hospital for Sick Children, Centro de Investigación Biomédica en Red de Salud Mental, National Institutes of Health, Horizon 2020 Framework Programme, HORIZON EUROPE Framework Programme, Canadian Institutes of Health Research, Medical Research Council, Instituto de Salud Carlos III, European Regional Development Fund, National Institute of Mental Health, NextGenerationEU
Awards: G1033681661, G1108105839, Neurobiological basis of dysconnectivity in a genetic risk model of psychosis, G1671053229, G1716692930, G1871873595, G1973349908, G2017605187, G2157603779, G2170376007, G2274687562, G2439142437, G2572068296, G2641609363, G2724637306, G2811660202, G2892701942, G3341568521, G3498118121, G3560035619, G3572747598, G3629701755, G3764841371, G3920792168, 3/9 Dissecting the effects of genomic variants on neurobehavioral dimensions in CNVs enriched for neuropsychiatric disorders, G4461667574, Estudio integral de variación genética y molecular de una cohorte española de trastornos del espectro autista y diseño de algoritmos de diagnóstico genético y de biotipos terapéuticos. Cohorte ESTEA., G5543596241, G5547416247, G5701184066, Psychiatric Ratings using Intermediate Stratified Markers 2, G5982772783, G5983053349, G6067885870, G6081615879, Intellectual Disability and Mental Health: Assessing Genomic Impact on Neurodevelopment (IMAGINE), G6262202302, Autism Innovative Medicine Studies – 2 – Trials, G6550514894, G6701618956, G6972650492, G6979406599, G7050644217, G7070498705, G7094983079, G7336256237, Enfoque integral y translacional para el diagnóstico genético de TEA: Caracterización clínica, G7636808386, G7870769612, Intellectual Disability and Mental Health: Assessing Genomic Impact on Neurodevelopment (IMAGINE), 5/9: Dissecting the effects of genomic variants on neurobehavioral dimensions in CNVs enriched for neuropsychiatric disorders, G8351277590, G842865865, G8494123976, G8563726104, G8726972595, IMAGINE-2: Stratifying Genomic Causes of Intellectual Disability by Mental Health Outcomes in Childhood and Adolescence, G8950770007, G9000011481, G9000141350
OpenAlex ID: W7213866522