Brain biochemistry in Williams syndrome: evidence for a role of the cerebellum in cognition?
OBJECTIVE
To determine what biochemical changes may occur in the brain in Williams syndrome (WS) and whether these changes may be related to the cognitive deficits.


BACKGROUND
WS is a rare, congenital disorder with a characteristic physical, linguistic, and behavioral phenotype with known cognitive deficits.


METHODS
We obtained 31P magnetic resonance spectra (MRS) from a region consisting of mostly frontal and parietal lobe of 14 patients with WS (age, 8 to 37 years) and 48 similarly-aged controls. 1H MRS (27 cm3) localized to the left cerebellum obtained from the WS cohort were compared with those from 16 chronological age- and sex-matched normal controls. A battery of cognitive tests were administered to all subjects undergoing 1H MRS.


RESULTS
WS brains exhibited significant biochemical abnormalities. All 31P MRS ratios containing the phosphomonoester (PME) peak were significantly altered in WS, suggesting that PME is significantly decreased. Ratios of choline-containing compounds and creatine-containing compounds to N-acetylaspartate (Cho/NA and Cre/NA) were significantly elevated in the cerebellum in WS cf. controls, whereas the ratio of Cho/Cre was not altered. This suggests a decrease in the neuronal marker N-acetylaspartate in the cerebellum. Significant correlations were found between the cerebellar ratios Cho/NA and Cre/NA and the ability of all subjects at various neuropsychological tests, including Verbal and Performance IQ, British Picture Vocabulary Scale, Ravens Progressive Matrices, and Inspection Time.


CONCLUSIONS
The correlations can be interpreted in two ways: 1) Our sampling of cerebellar biochemistry reflects a measure of "global" cerebral biochemistry and is unrelated to cerebellar function, or 2) The relations indicate that cerebellar neuronal integrity is a requirement (on a developmental time scale or in real-time) for ability on a variety of cognitive tests.
Rae
C
C
MRC Biochemical and Clinical Magnetic Resonance Unit, John Radcliffe Hospital, Oxford, UK.
Karmiloff-Smith
A
A
Lee
M A
MA
Dixon
R M
RM
Grant
J
J
Blamire
A M
AM
Thompson
C H
CH
Styles
P
P
Radda
G K
GK
D000255:Adenosine Triphosphate / Q000032:analysis; D000293:Adolescent; D000328:Adult; D001923:Brain Chemistry; D002531:Cerebellum / Q000737:chemistry / Q000502:physiology*; D002648:Child; D003071:Cognition / Q000502:physiology*; D004983:Ethanolamines / Q000032:analysis; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry; D005994:Glycerophosphates / Q000032:analysis; D006600:Hexosephosphates / Q000032:analysis; D006801:Humans; D007295:Inositol Phosphates / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000737:chemistry; D010725:Phosphocreatine / Q000032:analysis; D010761:Phosphorus Radioisotopes; D010767:Phosphorylcholine / Q000032:analysis; D010768:Phosphoserine / Q000032:analysis; D011522:Protons; D011877:Radionuclide Imaging; D018980:Williams Syndrome / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*
D004983:Ethanolamines; D005994:Glycerophosphates; D006600:Hexosephosphates; D007295:Inositol Phosphates; D010761:Phosphorus Radioisotopes; D011522:Protons; D010725:Phosphocreatine; D010767:Phosphorylcholine; C002647:inositol 1-phosphate; D010768:Phosphoserine; C005448:phosphorylethanolamine; D000255:Adenosine Triphosphate; C029620:alpha-glycerophosphoric acid