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Biological markers of intellectual disability in tuberous sclerosis

Published online by Cambridge University Press:  05 March 2007

ARMIN RAZNAHAN ,
NICHOLAS P. HIGGINS ,
PAUL D. GRIFFITHS ,
AYLA HUMPHREY ,
JOHN R. W. YATES  and
PATRICK F. BOLTON
ARMIN RAZNAHAN*
Affiliation:
Department of Child and Adolescent Psychiatry, Institute of Psychiatry, King's College London, UK
NICHOLAS P. HIGGINS
Affiliation:
Addenbrooke's Hospital Neuroradiology Department, University of Cambridge, UK
PAUL D. GRIFFITHS
Affiliation:
Section of Academic Radiology, University of Sheffield, UK
AYLA HUMPHREY
Affiliation:
Section of Developmental Psychiatry, University of Cambridge, UK
JOHN R. W. YATES
Affiliation:
Department of Medical Genetics, University of Cambridge, UK
PATRICK F. BOLTON
Affiliation:
Department of Child and Adolescent Psychiatry, Institute of Psychiatry, King's College London, UK Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
*
*Address for correspondence: Dr Armin Raznahan, Clinical Research Worker, Institute of Psychiatry, Department of Child and Adolescent Psychiatry, PO85, 16 De Crespigny Park, LondonSE5 8AF, UK. (Email: [email protected])
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Abstract

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.

Method

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 <25 to >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 ρ=−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.

Type
Original Article
Information
Psychological Medicine , Volume 37 , Issue 9 , September 2007 , pp. 1293 - 1304
Copyright
Copyright © Cambridge University Press 2007

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