title: White matter microstructural abnormalities of the cingulum bundle in youths with 22q11.2 deletion syndrome: associations with medication, neuropsychological function, and prodromal symptoms of psychosis.
abstract: BACKGROUND
  The 22q11.2 deletion syndrome (22q11.2DS) is regarded as an etiologically homogenous model for understanding neuroanatomic disruptions associated with a high risk for schizophrenia. This study utilized diffusion tensor imaging (DTI) to analyze white matter microstructure in individuals with 22q11.2DS. We focused on the cingulum bundle (CB), previously shown to be disrupted in patients with schizophrenia and associated with symptoms of psychosis.
  
  
  METHODS
  White matter microstructure was assessed in the anterior, superior, and posterior CB using the tractography algorithm in DTIStudio. Neuropsychological function, presence of prodromal symptoms of psychosis, and medication history were assessed in all participants.
  
  
  RESULTS
  Relative to controls, young adults with 22q11.2DS showed alterations in most DTI metrics of the CB. Alterations were associated with positive prodromal symptoms of psychosis. However, when individuals with 22q11.2DS were divided by usage of antipsychotics/mood stabilizers, the medicated and non-medicated groups differed significantly in axial diffusivity of the anterior CB and in fractional anisotropy of the superior CB. DTI metrics did not differ between the medicated group and the control group.
  
  
  CONCLUSIONS
  Results suggest that the microstructure of the CB is altered in individuals with 22q11.2DS, and that those alterations may underlie positive prodromal symptoms of psychosis. Our findings further provide preliminary evidence that antipsychotic/mood stabilizer usage may have a reparative effect on white matter microstructure in prodromal 22q11.2DS, independent of the potential effects of psychosis. Future studies of white matter pathology in individuals with 22q11.2DS should test for potential effects of medication on white matter microstructure.
authors: Department of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, NY, United States. Electronic address: katesw@upstate.edu.
authors: Wendy R
authors: WR
authors: Kates
authors: Department of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, NY, United States.
authors: Amy K
authors: AK
authors: Olszewski
authors: Department of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, NY, United States.
authors: Matthew H
authors: MH
authors: Gnirke
authors: Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
authors: Zora
authors: Z
authors: Kikinis
authors: Department of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, NY, United States.
authors: Joshua
authors: J
authors: Nelson
authors: Department of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, NY, United States; Department of Psychology, Syracuse University, Syracuse, NY, United States.
authors: Kevin M
authors: KM
authors: Antshel
authors: Department of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, NY, United States.
authors: Wanda
authors: W
authors: Fremont
authors: Department of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, NY, United States.
authors: Petya D
authors: PD
authors: Radoeva
authors: Department of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, NY, United States; Department of Neuroscience and Physiology, State University of New York at Upstate Medical University, Syracuse, NY, United States.
authors: Frank A
authors: FA
authors: Middleton
authors: Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; VA Boston Healthcare System, Brockton Division, Brockton, MA, United States.
authors: Martha E
authors: ME
authors: Shenton
authors: Department of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, NY, United States.
authors: Ioana L
authors: IL
authors: Coman
mesh_terms: D058165:22q11 Deletion Syndrome / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D000293:Adolescent; D000704:Analysis of Variance; D016880:Anisotropy; D014150:Antipsychotic Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology; D056324:Diffusion Tensor Imaging; D005260:Female; D007839:Functional Laterality; D006179:Gyrus Cinguli / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D009483:Neuropsychological Tests; D062706:Prodromal Symptoms; D011569:Psychiatric Status Rating Scales; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents
keywords: Antipsychotics/mood stabilizers; Cingulum bundle; Diffusion tensor imaging (DTI); Prodromal symptoms of psychosis; Schizophrenia; Velo-cardio-facial syndrome