To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Decline in cognitive functioning precedes the first psychotic episode in the course of schizophrenia and is considered a hallmark symptom of the disorder. Given the low incidence of schizophrenia, it remains a challenge to investigate whether cognitive decline coincides with disease-related changes in brain structure, such as white matter abnormalities. The 22q11.2 deletion syndrome (22q11DS) is an appealing model in this context, as 25% of patients develop psychosis. Furthermore, we recently showed that cognitive decline also precedes the onset of psychosis in individuals with 22q11DS. Here, we investigate whether the early cognitive decline in patients with 22q11DS is associated with alterations in white matter microstructure.
We compared the fractional anisotropy (FA) of white matter in 22q11DS patients with cognitive decline [n = 16; −18.34 (15.8) VIQ percentile points over 6.80 (2.39) years] to 22q11DS patients without cognitive decline [n = 18; 17.71 (20.17) VIQ percentile points over 5.27 (2.03) years] by applying an atlas-based approach to diffusion-weighted imaging data.
FA was significantly increased (p < 0.05, FDR) in 22q11DS patients with a cognitive decline in the bilateral superior longitudinal fasciculus, the bilateral cingulum bundle, all subcomponents of the left internal capsule and the left superior frontal-occipital fasciculus as compared with 22q11DS patients without cognitive decline.
Within 22q11DS, the early cognitive decline is associated with microstructural differences in white matter. At the mean age of 17.8 years, these changes are reflected in increased FA in several tracts. We hypothesize that similar brain alterations associated with cognitive decline take place early in the trajectory of schizophrenia.
People with 22q11.2 deletion syndrome (velo-cardio-facial syndrome) have
a 30-fold risk of developing schizophrenia. In the general population the
schizophrenia phenotype includes a cognitive deficit and a decline in
academic performance preceding the first episode of psychosis in a
subgroup of patients. Findings of cross-sectional studies suggest that
cognitive abilities may decline over time in some children with 22q11.2
deletion syndrome. If confirmed longitudinally, this could indicate that
one or more genes within 22q11.2 are involved in cognitive decline.
To assess longitudinally the change in IQ scores in children with 22q11.2
Sixty-nine children with the syndrome were cognitively assessed two or
three times at set ages 5.5 years, 7.5 years and 9.5 years.
A mean significant decline of 9.7 Full Scale IQ points was found between
ages 5.5 years and 9.5 years. In addition to the overall relative decline
that occurred when results were scored according to age-specific IQ
norms, in 10 out of a group of 29 children an absolute decrease in
cognitive raw scores was found between ages 7.5 years and 9.5 years. The
decline was not associated with a change in behavioural measures.
The finding of cognitive decline can be only partly explained as the
result of ‘growing into deficit’; about a third of 29 children showed an
absolute loss of cognitive faculties. The results underline the
importance of early psychiatric screening in this population and indicate
that further study of the genes at the 22q11.2 locus may be relevant to
understanding the genetic basis of early cognitive deterioration.
Email your librarian or administrator to recommend adding this to your organisation's collection.