title: Deviant trajectories of cortical maturation in 22q11.2 deletion syndrome (22q11DS): a cross-sectional and longitudinal study.
abstract: 22q11.2 deletion syndrome (22q11DS) is associated with an increased susceptibility to develop schizophrenia. Despite a large body of literature documenting abnormal brain structure in 22q11DS, cerebral changes associated with brain maturation in 22q11DS remained largely unexplored. To map cortical maturation from childhood to adulthood in 22q11.2 deletion syndrome, we used cerebral MRI from 59 patients with 22q11DS, aged 6 to 40, and 80 typically developing controls; three year follow-up assessments were also available for 32 patients and 31 matched controls. Cross-sectional cortical thickness trajectories during childhood and adolescence were approximated in age bins. Repeated-measures were also conducted with the longitudinal data. Within the group of patients with 22q11DS, exploratory measures of cortical thickness differences related to COMT polymorphism, IQ, and schizophrenia were also conducted. We observed deviant trajectories of cortical thickness changes with age in patients with 22q11DS. In affected preadolescents, larger prefrontal thickness was observed compared to age-matched controls. Afterward, we observed greater cortical loss in 22q11DS with a convergence of cortical thickness values by the end of adolescence. No compelling evidence for an effect of COMT polymorphism on cortical maturation was observed. Within 22q11DS, significant differences in cortical thickness were related to cognitive level in children and adolescents, and to schizophrenia in adults. Deviant trajectories of cortical thickness from childhood to adulthood provide strong in vivo cues for a defect in the programmed synaptic elimination, which in turn may explain the susceptibility of patients with 22q11DS to develop psychosis.
authors.affiliation: Service Médico-Pédagogique, Department of Psychiatry, Geneva Faculty of Medicine, CH-1211 Geneva 8, Switzerland. marie.schaer@unige.ch
authors.forename: Marie
authors.initials: M
authors.lastname: Schaer
authors.forename: Martin
authors.initials: M
authors.lastname: Debbané
authors.forename: Meritxell
authors.initials: M
authors.lastname: Bach Cuadra
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Ottet
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Glaser
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Thiran
authors.forename: Stephan
authors.initials: S
authors.lastname: Eliez
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000704:Analysis of Variance; D001931:Brain Mapping; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000473:pathology*; D002648:Child; D003430:Cross-Sectional Studies; D004062:DiGeorge Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology* / Q000523:psychology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007360:Intelligence / Q000235:genetics; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008715:Methionine / Q000235:genetics; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics; D012559:Schizophrenia / Q000209:etiology / Q000235:genetics; D014633:Valine / Q000235:genetics; D055815:Young Adult
chemical_list: D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine