Development and Psychopathology



A multilevel analysis of cognitive dysfunction and psychopathology associated with chromosome 22q11.2 deletion syndrome in children


TONY J.  SIMON  a1 c1 , JOEL P.  BISH  a2 , CARRIE E.  BEARDEN  a3 , LIJUN  DING  a2 , SAMANTHA  FERRANTE  a2 , VY  NGUYEN  a1 , JAMES C.  GEE  a4 , DONNA M.  McDONALD–McGINN  a2 , ELAINE H.  ZACKAI  a2 a4 and BEVERLY S.  EMANUEL  a2 a4
a1 University of California, Davis
a2 Children's Hospital of Philadelphia
a3 University of California, Los Angeles
a4 University of Pennsylvania

Article author query
simon tj   [PubMed][Google Scholar] 
bish jp   [PubMed][Google Scholar] 
bearden ce   [PubMed][Google Scholar] 
ding l   [PubMed][Google Scholar] 
ferrante s   [PubMed][Google Scholar] 
nguyen v   [PubMed][Google Scholar] 
gee jc   [PubMed][Google Scholar] 
mcdonaldmcginn dm   [PubMed][Google Scholar] 
zackai eh   [PubMed][Google Scholar] 
emanuel bs   [PubMed][Google Scholar] 

Abstract

We present a multilevel approach to developing potential explanations of cognitive impairments and psychopathologies common to individuals with chromosome 22q11.2 deletion syndrome. Results presented support our hypothesis of posterior parietal dysfunction as a central determinant of characteristic visuospatial and numerical cognitive impairments. Converging data suggest that brain development anomalies, primarily tissue reductions in the posterior brain and changes to the corpus callosum, may affect parietal connectivity. Further findings indicate that dysfunction in “frontal” attention systems may explain some executive cognition impairments observed in affected children, and that there may be links between these domains of cognitive function and some of the serious psychiatric conditions, such as attention-deficit/hyperactivity disorder, autism, and schizophrenia, that have elevated incidence rates in the syndrome. Linking the neural structure and the cognitive processing levels in this way enabled us to develop an elaborate structure/function mapping hypothesis for the impairments that are observed. We show also, that in the case of the catechol-O-methyltransferase gene, a fairly direct relationship between gene expression, cognitive function, and psychopathology exists in the affected population. Beyond that, we introduce the idea that variation in other genes may further explain the phenotypic variation in cognitive function and possibly the anomalies in brain development. a


Correspondence:
c1 Address correspondence and reprint requests to: Tony J. Simon, M.I.N.D. Institute, University of California, Davis, 2825 50th Street, Sacramento, CA 95817; E-mail: tjsimon@ucdavis.edu.


Footnotes

a We thank the children and families that participated in our studies and the staff of the 22q and You Center at the Children's Hospital of Philadelphia. This work was supported by grants from the NIH (R01HD42974 and R01HD46159) and the Philadelphia Foundation to T.J.S., Grant PO1DC02027 to B.S.E., and Grant M01-RR00240 to the Children's Hospital of Philadelphia.