The Number of Genomic Copies at the 16p11.2 Locus Modulates Language, Verbal Memory, and Inhibition

• Published in: Biological psychiatry (1969) Vol. 80; no. 2; pp. 129 - 139
• Main Authors: Hippolyte, Loyse, Maillard, Anne M, Rodriguez-Herreros, Borja, Pain, Aurélie, Martin-Brevet, Sandra, Ferrari, Carina, Conus, Philippe, Macé, Aurélien, Hadjikhani, Nouchine, Metspalu, Andres, Reigo, Anu, Kolk, Anneli, Männik, Katrin, Barker, Mandy, Isidor, Bertrand, Le Caignec, Cédric, Mignot, Cyril, Schneider, Laurence, Mottron, Laurent, Keren, Boris, David, Albert, Doco-Fenzy, Martine, Gérard, Marion, Bernier, Raphael, Goin-Kochel, Robin P, Hanson, Ellen, Green Snyder, LeeAnne, Ramus, Franck, Beckmann, Jacques S, Draganski, Bogdan, Reymond, Alexandre, Jacquemont, Sébastien
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-07-2016
• Subjects: 16p11.2; Adolescent; Adult; ASD; Autistic Disorder - diagnostic imaging; Autistic Disorder - genetics; Autistic Disorder - physiopathology; Child; Child, Preschool; Chromosome Deletion; Chromosome Disorders - diagnostic imaging; Chromosome Disorders - genetics; Chromosome Disorders - physiopathology; Chromosome Duplication - genetics; Chromosomes, Human, Pair 16 - genetics; Cognitive Dysfunction - diagnostic imaging; Cognitive Dysfunction - genetics; Cognitive Dysfunction - physiopathology; Copy number variation; DNA Copy Number Variations - genetics; Executive Function - physiology; Female; Heterozygote; Humans; Inhibition; Intellectual Disability - diagnostic imaging; Intellectual Disability - genetics; Intellectual Disability - physiopathology; Intelligence - genetics; Language; Male; Memory; Memory - physiology; Middle Aged; Motor Skills - physiology; Pedigree; Psychiatric/Mental Health; Young Adult; ASD; Copy number variation; Inhibition; Language; Memory; 16p11.2
• DOI: 10.1016/j.biopsych.2015.10.021
• EISSN: 1873-2402
• ISSN: 0006-3223

AbstractBackgroundDeletions and duplications of the 16p11.2 BP4-BP5 locus are prevalent copy number variations (CNVs), highly associated with autism spectrum disorder and schizophrenia. Beyond language and global cognition, neuropsychological assessments of these two CNVs have not yet been reported. MethodsThis study investigates the relationship between the number of genomic copies at the 16p11.2 locus and cognitive domains assessed in 62 deletion carriers, 44 duplication carriers, and 71 intrafamilial control subjects. ResultsIQ is decreased in deletion and duplication carriers, but we demonstrate contrasting cognitive profiles in these reciprocal CNVs. Deletion carriers present with severe impairments of phonology and of inhibition skills beyond what is expected for their IQ level. In contrast, for verbal memory and phonology, the data may suggest that duplication carriers outperform intrafamilial control subjects with the same IQ level. This finding is reminiscent of special isolated skills as well as contrasting language performance observed in autism spectrum disorder. Some domains, such as visuospatial and working memory, are unaffected by the 16p11.2 locus beyond the effect of decreased IQ. Neuroimaging analyses reveal that measures of inhibition covary with neuroanatomic structures previously identified as sensitive to 16p11.2 CNVs. ConclusionsThe simultaneous study of reciprocal CNVs suggests that the 16p11.2 genomic locus modulates specific cognitive skills according to the number of genomic copies. Further research is warranted to replicate these findings and elucidate the molecular mechanisms modulating these cognitive performances.