Children with chromosome 22q11 deletion syndrome (22q11DS), a common neurodevelopmental disorder, have a remarkably high risk (25-40%) of developing schizophrenia and other psychotic disorders in late adolescence/adulthood. The psychotic disorders are preceded by neurocognitive deficits in childhood that are similar to that seen in individuals with schizophrenia. Based on recent research in neuroplasticity, we hypothesize that these deficits may be remediable by therapeutic cognitive interventions. We will conduct a pilot study, the aims of which are to adapt a neurocognitive and social cognitive training program specifically for children with 22q11DS, to assess feasibility and to gather preliminary data for a subsequent randomized controlled trial to evaluate the efficacy of cognitive remediation in mitigating the cognitive and social deficits in these individuals. Our approach is two-pronged, consisting of a computer-based training program designed to improve neurocognition through visual and auditory tasks, and a small-group intervention designed to improve social cognition. These approaches have been effective in adults with cognitive deficits and with schizophrenia and we now seek to adapt them to children with 22q11DS, who have exceptional needs due to their young age and high risk of psychosis. An open-labeled, randomized study will be performed, involving 18 children with 22q11DS and 18 control subjects, ages 12-17 years. The participants will undergo sequential computerized neurocognitive and social cognitive training for the duration of one year, with assessments of these domains before and after the interventions. Data collected from this pilot project will be used for a larger scale evaluation of the efficacy of cognitive remediation in individuals with 22q11DS. The proposed research is highly innovative, since there are no current treatments for the cognitive deficits in 22q11DS;additionally the combined neurocognitive and social cognitive approach in children with 22q11DS is novel. We believe that the development of a cognitive remediation program explicitly for children with 22q11DS is significant, since it would have the potential to mitigate the cognitive deficits that are an integral part of the childhood problems and may in the future be effective in modifying the cognitive decline associated with the onset of psychosis.

Public Health Relevance

The purpose of this project is to adapt a cognitive remediation program that is uniquely suited for children with 22q11.2 deletion syndrome, to test its feasibility and to gather preliminary data for a future study designed to examine efficacy of such cognitive intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Planning Grant (R34)
Project #
5R34MH091314-02
Application #
8288079
Study Section
Interventions Committee for Disorders Involving Children and Their Families (ITVC)
Program Officer
Wagner, Ann
Project Start
2011-07-01
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
2
Fiscal Year
2012
Total Cost
$235,116
Indirect Cost
$71,841
Name
Duke University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Vorstman, Jacob A S; Breetvelt, Elemi J; Duijff, Sasja N et al. (2015) Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome. JAMA Psychiatry 72:377-85
Schneider, Maude; Debbané, Martin; Bassett, Anne S et al. (2014) Psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome: results from the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome. Am J Psychiatry 171:627-39
Harrell, Waverly; Eack, Shaun; Hooper, Stephen R et al. (2013) Feasibility and preliminary efficacy data from a computerized cognitive intervention in children with chromosome 22q11.2 deletion syndrome. Res Dev Disabil 34:2606-13