title: Structural abnormalities in cortical volume, thickness, and surface area in 22q11.2 microdeletion syndrome: Relationship with psychotic symptoms.
abstract: BACKGROUND
  22q11.2 deletion syndrome (22q11DS) represents one of the largest known genetic risk factors for psychosis, yet the neurobiological mechanisms underlying symptom development are not well understood. Here we conducted a cross-sectional study of 22q11DS to decompose cortical volume into its constituent parts, cortical thickness (CT) and surface area (SA), which are believed to have distinct neurodevelopmental origins.
  
  
  METHODS
  High-resolution T1-weighted scans were collected on 65 participants (31 22q11DS, 34 demographically comparable typically developing controls, 10-25 years old). Measures of cortical volume, CT, and SA were extracted from regions of interest using the FreeSurfer image analysis suite. Group differences and age-related trajectories in these structures, as well as their association with psychotic symptomatology, were assessed.
  
  
  RESULTS
  Relative to controls, 22q11DS participants showed bilateral volumetric reductions in the inferior temporal cortex, fusiform gyrus, anterior cingulate, superior parietal cortex, and cuneus, which were driven by decreased SA in these regions. 22q11DS participants also had increased volumes, driven by increased CT, in bilateral insula regions. 22q11DS youth had increased CT in frontal regions, particularly middle frontal and medial orbitofrontal cortices. A pattern of age-associated cortical thinning was observed in typically developing controls in brain regions associated with visual and sensory information-processing (i.e., left pericalcarine cortex and fusiform gyrus, right lingual and postcentral cortices). However, this relationship was disrupted in 22q11DS participants. Finally, correlational analyses revealed that increased CT in right medial orbitofrontal cortex was associated with increased positive symptom severity in 22q11DS.
  
  
  CONCLUSIONS
  Differential disruptions of CT and SA in distinct cortical regions in 22q11DS may indicate abnormalities in distinct developmental neural processes. Further, neuroanatomic abnormalities in medial frontal brain structures disproportionately affected in idiopathic schizophrenia were associated with psychotic symptom severity in 22q11DS youth, suggesting that disrupted biological processes in these cortical regions may underlie development of psychotic symptoms, both in 22q11DS and in the broader population.
authors.affiliation: Department of Psychology, University of California, 1285 Franz Hall, Box 951563, Los Angeles, CA 90095-1563, USA ; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, 760 Westwood Plaza, Los Angeles, CA 90095, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Jalbrzikowski
authors.forename: Rachel
authors.initials: R
authors.lastname: Jonas
authors.forename: Damla
authors.initials: D
authors.lastname: Senturk
authors.forename: Arati
authors.initials: A
authors.lastname: Patel
authors.forename: Carolyn
authors.initials: C
authors.lastname: Chow
authors.forename: Michael F
authors.initials: MF
authors.lastname: Green
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Bearden
keywords: 22q11DS, 22q11.2 deletion syndrome; ANCOVA, analysis of covariance; CNV, copy number variation; CT, cortical thickness; Copy number variation; MRI, magnetic resonance imaging; Psychosis; SA, surface area; SIPS, Structured Interview for Prodromal Syndromes; Schizophrenia; Structural magnetic resonance imaging; Velocardiofacial syndrome