Cognitive dysfunction and developmental risks for severe psychopathology:
insights from sex chromosomal disorders

Social skills are crucial for adapting to an increasingly complex social world
during development. The importance of impaired social skills and its
implications for mental well-being has called for an investigation of cognitive
and neurobiological mechanisms underlying severe social dysfunctioning in
childhood. So far, our knowledge of these mechanisms is almost exclusively
derived from studies on autism spectrum disorders. However, as the autism
spectrum represents a limited sampling of the socially impaired population,
these findings may not generalize to other children with social dysfunctions. A
solution lies in a new strategy that we employ in this study, which is the
study of sex chromosomal disorders associated with severe social dysfunctioning
(Turner syndrome and Klinefelter syndrome).

1. To what degree are the type of social difficulties similar or different in
children with Klinefelter syndrome, Turner syndrome and autism?
2. Which cognitive dysfunctions are most strongly related to social
difficulties in these different clinical populations?
3. To what degree are various neural circuits underlying social information
processing differentially affected in children with Klinefelter syndrome and is
this pattern of brain organization similar or different as compared to children
with autism?

observational study, case-control study

The burden and risks for the children and parents are minimal. The requested
time investment is a total of 4.5 hours (distributed over 3 visits) for the
non-clinical control group and 6.5 hours (distributed over 3 visits) for the
clinical groups. The researchers are skilled in working with children and our
experience is that children enjoy the cognitive computer 'games'. With regard
to eyetracking, children will not notice the eyetracker (no devices are
attached) and sit behind the p.c. monitor as any other monitor. Also, saliva
collection (3 to 6 ml) will pose no significant burden as children can simply
'spit' in a tube. Also, our experience is that most of the parents are very
much interested in reporting on their child's development and receiving reports
on the results of the study.
There will be no clinical diagnostic assessments in this study. If parents wish
clincial diagnostic assessment (medical, psychological), we will refer them to
clinicians. With regard to the MRI session, other studies from the LIBC in
which children participate in MRI research give us confidence that children
will have no problems with this part of the study. Participants will be also
thoroughly screened (using standard procedures) before scanning, resulting in
negligible risks. Even though the MRI scans will not be diagnostically screened
for abnormalities, the procedure in case of unexpected findings will be
explained (in person and in writing) to parents of participants. The potential
gains and benefits from this study (see C4) far outweigh the costs.