Beyond IQ: executive function deficits and their relation to functional, clinical, and neuroimaging outcomes in 3q29 deletion syndrome.
Rebecca M Pollak, Esra Sefik, Katrina Aberizk, Kuaikuai Duan, Roberto Espana, Ryan M Guest, Adam E Goldman-Yassen, Katrina Goines, Derek M Novacek, Celine A Saulnier, Cheryl Klaiman, Stormi Pulver, Joseph F Cubells, T Lindsey Burrell, Sarah Shultz, Elaine F Walker, Melissa M Murphy, Jennifer G Mulle
Author Information
Rebecca M Pollak: Center for Advanced Biotechnology and Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA. ORCID
Esra Sefik: Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA.
Katrina Aberizk: Department of Psychology, Emory University, Atlanta, GA, USA.
Kuaikuai Duan: Marcus Autism Center, Children's Healthcare of Atlanta & Emory University School of Medicine, Atlanta, GA, USA.
Roberto Espana: Department of Psychology, Emory University, Atlanta, GA, USA.
Ryan M Guest: Department of Psychology, Emory University, Atlanta, GA, USA.
Adam E Goldman-Yassen: Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA.
Katrina Goines: Department of Psychology, Emory University, Atlanta, GA, USA.
Derek M Novacek: Desert Pacific Mental Illness Research, Education, and Clinical Center, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
Celine A Saulnier: Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
Cheryl Klaiman: Marcus Autism Center, Children's Healthcare of Atlanta & Emory University School of Medicine, Atlanta, GA, USA.
Stormi Pulver: Marcus Autism Center, Children's Healthcare of Atlanta & Emory University School of Medicine, Atlanta, GA, USA.
Joseph F Cubells: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
T Lindsey Burrell: Atlanta Children's Center, Atlanta, GA, USA.
Sarah Shultz: Marcus Autism Center, Children's Healthcare of Atlanta & Emory University School of Medicine, Atlanta, GA, USA.
Elaine F Walker: Department of Psychology, Emory University, Atlanta, GA, USA.
Melissa M Murphy: Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
Jennifer G Mulle: Center for Advanced Biotechnology and Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA.
BACKGROUND: 3q29 deletion syndrome (3q29del) is a rare (~1:30 000) genomic disorder associated with a wide array of neurodevelopmental and psychiatric phenotypes. Prior work by our team identified clinically significant executive function (EF) deficits in 47% of individuals with 3q29del; however, the nuances of EF in this population have not been described. METHODS: We used the Behavior Rating Inventory of Executive Function (BRIEF) to perform the first in-depth assessment of real-world EF in a cohort of 32 individuals with 3q29del (62.5% male, mean age = 14.5 ± 8.3 years). All participants were also evaluated with gold-standard neuropsychiatric and cognitive assessments. High-resolution structural magnetic resonance imaging was performed on a subset of participants ( = 24). RESULTS: We found global deficits in EF; individuals with 3q29del scored higher than the population mean on the BRIEF global executive composite (GEC) and all subscales. In total, 81.3% of study subjects ( = 26) scored in the clinical range on at least one BRIEF subscale. BRIEF GEC scores were higher among 3q29del participants with a diagnosis of attention deficit/hyperactivity disorder (ADHD), and BRIEF GEC scores were associated with schizophrenia spectrum symptoms as measured by the Structured Interview for Psychosis-Risk Syndromes. BRIEF GEC scores were not associated with cognitive ability. The BRIEF-2 ADHD form accurately (sensitivity = 86.7%) classified individuals with 3q29del based on ADHD diagnosis status. BRIEF GEC scores were correlated with cerebellar white matter and subregional cerebellar cortex volumes. CONCLUSIONS: Together, these data expand our understanding of the phenotypic spectrum of 3q29del and identify EF as a core feature linked to both psychiatric and neuroanatomical features of the syndrome.
