title: Proline and COMT status affect visual connectivity in children with 22q11.2 deletion syndrome.
abstract: BACKGROUND
  Individuals with the 22q11.2 deletion syndrome (22q11DS) are at increased risk for schizophrenia and Autism Spectrum Disorders (ASDs). Given the prevalence of visual processing deficits in these three disorders, a causal relationship between genes in the deleted region of chromosome 22 and visual processing is likely. Therefore, 22q11DS may represent a unique model to understand the neurobiology of visual processing deficits related with ASD and psychosis.
  
  
  METHODS
  We measured Event-Related Potentials (ERPs) during a texture segregation task in 58 children with 22q11DS and 100 age-matched controls. The C1 component was used to index afferent activity of visual cortex area V1; the texture negativity wave provided a measure for the integrity of recurrent connections in the visual cortical system. COMT genotype and plasma proline levels were assessed in 22q11DS individuals.
  
  
  RESULTS
  Children with 22q11DS showed enhanced feedforward activity starting from 70 ms after visual presentation. ERP activity related to visual feedback activity was reduced in the 22q11DS group, which was seen as less texture negativity around 150 ms post presentation. Within the 22q11DS group we further demonstrated an association between high plasma proline levels and aberrant feedback/feedforward ratios, which was moderated by the COMT(158) genotype.
  
  
  CONCLUSIONS
  These findings confirm the presence of early visual processing deficits in 22q11DS. We discuss these in terms of dysfunctional synaptic plasticity in early visual processing areas, possibly associated with deviant dopaminergic and glutamatergic transmission. As such, our findings may serve as a promising biomarker related to the development of schizophrenia among 22q11DS individuals.
authors: Rudolf Magnus Institute of Neuroscience, Department of Child and Adolescent Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands. M.J.C.M.Magnee@umcutrecht.nl
authors: Maurice J C M
authors: MJ
authors: Magnée
authors: Victor A F
authors: VA
authors: Lamme
authors: Monique G M
authors: MG
authors: de Sain-van der Velden
authors: Jacob A S
authors: JA
authors: Vorstman
authors: Chantal
authors: C
authors: Kemner
mesh_terms: D058165:22q11 Deletion Syndrome / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D000293:Adolescent; D001519:Behavior / Q000502:physiology; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D004192:Discrimination, Psychological / Q000502:physiology; D005071:Evoked Potentials / Q000235:genetics / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011392:Proline / Q000097:blood*; D014793:Visual Cortex / Q000503:physiopathology*; D014796:Visual Perception / Q000235:genetics / Q000502:physiology; D055815:Young Adult
chemical_list: D011392:Proline; D002394:Catechol O-Methyltransferase