title: Temporal lobe volume abnormalities precede the prodrome: a study of children presenting antecedents of schizophrenia.
abstract: Distributed abnormalities of gray matter (GM) and white matter (WM) volume characterize individuals experiencing their first episode of schizophrenia. Regions of abnormality are present already, albeit less extensively, during the prodromal phase of illness. This study aimed to determine whether putatively at-risk children, aged 9-12 years, who present multiple antecedents of schizophrenia (ASz), display GM and WM volume abnormalities relative to typically developing (TD) children presenting no antecedents. Structural magnetic resonance images were acquired for 20 ASz children and 20 TD children matched on age, sex, and IQ. Whole-brain differences in GM and WM volume were determined using voxel-based morphometry. Relative to the TD group, ASz children showed significantly decreased GM volume in the right middle temporal gyrus (MTG) and increased GM volume in the left superior-middle temporal gyri (P < 0.05, cluster correction). WM volume was significantly increased in ASz children relative to TD children in a cluster encompassing the left inferior parietal lobe, occipital lobe, and superior temporal gyrus. Post-hoc analyses indicated that these abnormalities were not limited to ASz children who self-reported auditory hallucinations on questionnaire. Our findings suggest that children aged 9-12 years who present multiple ASz are characterized by abnormalities of GM and WM volume in the temporal lobes, comprising a subset of the regions affected in first-episode schizophrenia and in the prodromal phase of illness. These preliminary findings indicate that structural brain abnormalities associated with schizophrenia may be detected in putatively at-risk, preprodromal children. Prospective studies following the brain development of at-risk children are needed.
authors.affiliation: To whom correspondence should be addressed; Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Box P023, De Crespigny Park, London, SE5 8AF; tel: +44 20 7848 5678, fax: +44 (0)20 7848 0754, e-mail: alexis.cullen@kcl.ac.uk.
authors.forename: Alexis E
authors.initials: AE
authors.lastname: Cullen
authors.forename: Stéphane A
authors.initials: SA
authors.lastname: De Brito
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Gregory
authors.forename: Robin M
authors.initials: RM
authors.lastname: Murray
authors.forename: Steven C R
authors.initials: SC
authors.lastname: Williams
authors.forename: Sheilagh
authors.initials: S
authors.lastname: Hodgins
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Laurens
mesh_terms: D015415:Biomarkers; D001921:Brain / Q000473:pathology*; D002648:Child; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D008297:Male; D062706:Prodromal Symptoms; D012306:Risk; D012559:Schizophrenia / Q000473:pathology*; D013702:Temporal Lobe / Q000473:pathology*
chemical_list: D015415:Biomarkers
keywords: MRI; VBM; biomarkers; brain structure; high risk; psychosis