title: Neuroanatomical correlates of Klinefelter syndrome studied in relation to the neuropsychological profile.
abstract: Brain imaging in Klinefelter syndrome (47, XXY) (KS), a genetic disorder characterized by the presence of an extra X chromosome, may contribute to understanding the relationship between gene expression, brain structure, and subsequent cognitive disabilities and psychiatric disorders. We conducted the largest to date voxel-based morphometry study of 65 KS subjects and 65 controls matched for age and education and correlated these data to neuropsychological test scores. The KS patients had significantly smaller total brain volume (TBV), total gray matter volume (GMV) and total white matter volume (WMV) compared to controls, whereas no volumetric difference in cerebral spinal fluid (CSF) was found. There were no differences in TBV, GMV, WMV or CSF between testosterone treated KS (T-KS) and untreated KS (U-KS) patients. Compared to controls, KS patients had significantly decreased GMV bilaterally in insula, putamen, caudate, hippocampus, amygdala, temporal pole and frontal inferior orbita. Additionally, the right parahippocampal region and cerebellar volumes were reduced in KS patients. KS patients had significantly larger volumes in right postcentral gyrus, precuneus and parietal regions. Multivariate classification analysis discriminated KS patients from controls with 96.9% (p < 0.001) accuracy. Regression analyses, however, revealed no significant association between GMV differences and cognitive and psychological factors within the KS patients and controls or the groups combined. These results show that although gene dosage effect of having and extra X-chromosome may lead to large scale alterations of brain morphometry and extended cognitive disabilities no simple correspondence links these measures.
authors.affiliation: Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, 8000 Aarhus C, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Skakkebæk
authors.forename: Claus Højbjerg
authors.initials: CH
authors.lastname: Gravholt
authors.forename: Peter Mondrup
authors.initials: PM
authors.lastname: Rasmussen
authors.forename: Anders
authors.initials: A
authors.lastname: Bojesen
authors.forename: Jens Søndergaard
authors.initials: JS
authors.lastname: Jensen
authors.forename: Jens
authors.initials: J
authors.lastname: Fedder
authors.forename: Peter
authors.initials: P
authors.lastname: Laurberg
authors.forename: Jens Michael
authors.initials: JM
authors.lastname: Hertz
authors.forename: John Rosendahl
authors.initials: JR
authors.lastname: Ostergaard
authors.forename: Anders Degn
authors.initials: AD
authors.lastname: Pedersen
authors.forename: Mikkel
authors.initials: M
authors.lastname: Wallentin
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000175:diagnosis* / Q000209:etiology*; D003718:Denmark; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D007713:Klinefelter Syndrome / Q000150:complications* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D025341:Principal Component Analysis; D011569:Psychiatric Status Rating Scales; D055815:Young Adult
keywords: Cognition; Klinefelter syndrome; MRI; Mental disorders; Personality