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Neuropsychiatric disorders are common in 22q11.2 Deletion Syndrome (22q11DS) with about 25% of affected individuals developing schizophrenia spectrum disorders by young adulthood. Longitudinal evaluation of psychosis spectrum features and neurocognition can establish developmental trajectories and impact on functional outcome.
157 youth with 22q11DS were assessed longitudinally for psychopathology focusing on psychosis spectrum symptoms, neurocognitive performance and global functioning. We contrasted the pattern of positive and negative psychosis spectrum symptoms and neurocognitive performance differentiating those with more prominent Psychosis Spectrum symptoms (PS+) to those without prominent psychosis symptoms (PS−).
We identified differences in the trajectories of psychosis symptoms and neurocognitive performance between the groups. The PS+ group showed age associated increase in symptom severity, especially negative symptoms and general nonspecific symptoms. Correspondingly, their level of functioning was worse and deteriorated more steeply than the PS− group. Neurocognitive performance was generally comparable in PS+ and PS− groups and demonstrated a similar age-related trajectory. However, worsening executive functioning distinguished the PS+ group from PS− counterparts. Notably, of the three executive function measures examined, only working memory showed a significant difference between the groups in rate of change. Finally, structural equation modeling showed that neurocognitive decline drove the clinical change.
Youth with 22q11DS and more prominent psychosis features show worsening of symptoms and functional decline driven by neurocognitive decline, most related to executive functions and specifically working memory. The results underscore the importance of working memory in the developmental progression of psychosis.
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.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.