Biological markers of intellectual disability in tuberous sclerosis.
BACKGROUND
Intellectual disability (ID) is highly prevalent in tuberous sclerosis (TS). Putative neurobiological risk factors include indices of cortical tuber (CT) load and epilepsy. We have used univariate and multivariate analyses, including both CT and epilepsy measures as predictors, in an attempt to clarify the pattern of cross-sectional associations between these variables and ID in TS.


METHODS
Forty-eight children, adolescents and young adults with TS were identified through regional specialist clinics. All subjects underwent thorough history taking and examination, and had brain magnetic resonance imaging (MRI) scans. The number and regional distribution of CTs was recorded. Subjects were assigned to one of nine ordered intellectual quotient (IQ) categories (range 130) using age-appropriate tests of intelligence.


RESULTS
On univariate analyses, ID was significantly associated with both a history of infantile spasm (IS) (Z=-2.49, p=0.01) and total CT count (Spearman's rho=-0.30, p=0.04). When controlling for total CT count, the presence of CTs in frontal (regression coefficient=-2.43, p=0.02) and temporal (regression coefficient=-1.60, p=0.02) lobes was significantly associated with ID. In multivariate analyses the association between IS and ID was rendered insignificant by the inclusion of the presence of CTs in temporal and frontal lobes, both of which remained associated (p=0.05 and p=0.06 respectively) with ID.


CONCLUSIONS
The presence of CTs in specific brain regions as opposed to a history of IS was associated with ID in TS. The significance of these findings is discussed in relation to previous work in TS, and the neural basis of intelligence.
Raznahan
Armin
A
Department of Child and Adolescent Psychiatry, Institute of Psychiatry, King's College London, UK. armin.raznahan@iop.kcl.ac.uk
Higgins
Nicholas P
NP
Griffiths
Paul D
PD
Humphrey
Ayla
A
Yates
John R W
JR
Bolton
Patrick F
PF
D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis*; D007360:Intelligence / Q000502:physiology; D007361:Intelligence Tests; D008297:Male; D013036:Spasms, Infantile / Q000175:diagnosis*; D013223:Statistics as Topic; D013702:Temporal Lobe / Q000473:pathology; D014402:Tuberous Sclerosis / Q000175:diagnosis*