Neuropsychiatric and neurocognitive assessment in this group of young individuals with 22q11DS supports the potential utility of prospective longitudinal studies in the context of understanding liability to schizophrenia. The clinical evaluation indicated that one 22q11DS participant had threshold features of schizophrenia, but over half of the participants with 22q11DS had significant prodromal symptoms in the SIPS interview, as has been described by other centers [Rockers and others 2009
; Stoddard and others 2010
]. Notably, this is a young sample where schizophrenia type disorder may still be evolving and longitudinal follow-up is needed to ascertain the course of psychotic symptoms in this population. The application of the SIPS in individuals with developmental disabilities requires special consideration. On the one hand, some disorganization or negative symptoms, such as deficits in “ideational richness”, are evident in many individuals with 22q11DS and may not be interpretable as “prodromal” symptoms in individuals with significant developmental disabilities. On the other hand, 38% of 22q participants did not exhibit significant negative or disorganized symptoms; it is possible that those without such features have a low likelihood of developing a psychotic illness. Longitudinal follow-up will inform the predictive validity of apparently significant negative and disorganized symptoms in the 22q population.
The computerized neurocognitive battery (CNB) was well tolerated by all participants, even as young as 8 years, and provided rapid assessment of several neurocognitive domains in 1.5 hours. Another advantage of the CNB is that data collection and scoring are automated and immediately available for data validation and analysis. Results with the CNB of the 22q11DS participants showed a similar neurocognitive profile to that described by others with this population using standard pencil-and-paper tasks. However, the computerized testing permits separate evaluation of accuracy and speed of performance and our study revealed that the deficits are not equal across these aspects of performance. The accuracy of the 22q11DS group overall was lower than individuals with schizophrenia. A number of CNB domains showed lower accuracy scores by the 22q11DS group than have been reported by other 22q11DS centers using traditional measures: attention [Campbell and others 2006
; Gothelf and others 2007
], working memory [Campbell and others 2006
; Eliez and others 2001
], face memory [Andersson and others 2008
], and visuospatial processing [Antshel and others 2008
; Kates and others 2007
; Moss and others 1999
; Niklasson and others 2002
]. Test procedures and comparison groups are potential sources of variability. Other significant areas of deficit found in this study include verbal reasoning and list memory. Additionally, the 22q11DS group had significantly lower performance in emotion recognition when compared to all
of the other groups, which has also been described by other centers [Campbell and others 2006
]. Our study found less pronounced difficulty in abstract reasoning compared to another study using the Modified Card Sorting Test [Rockers and others 2009
]. Similarly, the deficit in accuracy of verbal memory was less profound than that reported by another group [Campbell and others 2006
; Majerus and others 2007
In contrast to impaired accuracy, individuals with 22q11DS were less impaired in speed than patients with schizophrenia. The reduction in speed in schizophrenia has been previously described by us [Gur and others 2001a
]. As with accuracy, the profile of performance of patients with 22q11DS parallels that of the other patient and risk groups. This finding further supports the utility of the neurocognitive profile in characterizing genetically informative populations thereby rendering potential biomarkers.
The study has several limitations. Most importantly, the sample size is too small to examine the relation between neuropsychiatric and neurocognitive measures in the 22q11DS group. The experience gained from this effort has guided modifications in the CNB for younger participants with 22q11DS. For example, there was some difficulty with completion of the Letter-N-Back practice, resulting in missing data in the Working Memory task in the 22q11DS group. This task may be more developmentally appropriate and user-friendly as a 0-back and 1-back task. Additionally, very young participants in first or second grade may not be able to read sufficiently to complete word memory and verbal reasoning tasks. Interestingly, the 22q11DS group over the age of 12 performed as well as comparison groups, with exception of low risk/healthy controls, in verbal memory. This is all the more exceptional as the 22q11 group had an average of 9.7 (SD 2.6) years of completed education versus mean 11.3–13.5 in the comparison groups. Studies to date of neurocognitive processing in 22q11DS have used IQ assessment and matching. This study utilized the WRAT as an estimate of IQ and judgment of participants’ ability to perform verbal tasks and participants had no mental retardation. As our focus is on brain behavior relations as part of large-scale genomic studies, we employed common research procedures across groups. With larger samples, IQ measures clinically available will enable comparison with data obtained in other research centers that assess IQ.