title: The hippocampi of children with chromosome 22q11.2 deletion syndrome have localized anterior alterations that predict severity of anxiety.
abstract: Individuals with 22q11.2 deletion syndrome (22q11.2DS) have an elevated risk for schizophrenia, which increases with history of childhood anxiety. Altered hippocampal morphology is a common neuroanatomical feature of 22q11.2DS and idiopathic schizophrenia. Relating hippocampal structure in children with 22q11.2DS to anxiety and impaired cognitive ability could lead to hippocampus-based characterization of psychosis-proneness in this at-risk population.
  
  
  
  We measured hippocampal volume using a semiautomated approach on MRIs collected from typically developing children and children with 22q11.2DS. We then analyzed hippocampal morphology with Localized Components Analysis. We tested the modulating roles of diagnostic group, hippocampal volume, sex and age on local hippocampal shape components. Lastly, volume and shape components were tested as covariates of IQ and anxiety.
  
  
  
  We included 48 typically developing children and 69 children with 22q11.2DS in our study. Hippocampal volume was reduced bilaterally in children with 22q11.2DS, and these children showed greater variation in the shape of the anterior hippocampus than typically developing children. Children with 22q11.2DS had greater inward deformation of the anterior hippocampus than typically developing children. Greater inward deformation of the anterior hippocampus was associated with greater severity of anxiety, specifically fear of physical injury, within the 22q11.2DS group.
  
  
  
  Shape alterations are not specific to hippocampal subfields.
  
  
  
  Alterations in the structure of the anterior hippocampus likely affect function and may impact limbic circuitry. We suggest these alterations potentially contribute to anxiety symptoms in individuals with 22q11.2DS through modulatory pathways. Altered hippocampal morphology may be uniquely linked to anxiety risk factors for schizophrenia, which could be a powerful neuroanatomical marker of schizophrenia risk and hence protection.
authors.affiliation: From the Department of Neurology, University of California, Davis (Scott); Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California, Davis (Goodrich-Hunsaker, Kalish, Lee, Hunsaker, Schumann, Simon); and Pennington Biomedical Research Center, Louisiana State University (Carmichael).
authors.forename: Julia A
authors.initials: JA
authors.lastname: Scott
authors.affiliation: From the Department of Neurology, University of California, Davis (Scott); Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California, Davis (Goodrich-Hunsaker, Kalish, Lee, Hunsaker, Schumann, Simon); and Pennington Biomedical Research Center, Louisiana State University (Carmichael).
authors.forename: Naomi
authors.initials: N
authors.lastname: Goodrich-Hunsaker
authors.affiliation: From the Department of Neurology, University of California, Davis (Scott); Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California, Davis (Goodrich-Hunsaker, Kalish, Lee, Hunsaker, Schumann, Simon); and Pennington Biomedical Research Center, Louisiana State University (Carmichael).
authors.forename: Kristopher
authors.initials: K
authors.lastname: Kalish
authors.affiliation: From the Department of Neurology, University of California, Davis (Scott); Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California, Davis (Goodrich-Hunsaker, Kalish, Lee, Hunsaker, Schumann, Simon); and Pennington Biomedical Research Center, Louisiana State University (Carmichael).
authors.forename: Aaron
authors.initials: A
authors.lastname: Lee
authors.affiliation: From the Department of Neurology, University of California, Davis (Scott); Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California, Davis (Goodrich-Hunsaker, Kalish, Lee, Hunsaker, Schumann, Simon); and Pennington Biomedical Research Center, Louisiana State University (Carmichael).
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hunsaker
authors.affiliation: From the Department of Neurology, University of California, Davis (Scott); Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California, Davis (Goodrich-Hunsaker, Kalish, Lee, Hunsaker, Schumann, Simon); and Pennington Biomedical Research Center, Louisiana State University (Carmichael).
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Schumann
authors.affiliation: From the Department of Neurology, University of California, Davis (Scott); Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California, Davis (Goodrich-Hunsaker, Kalish, Lee, Hunsaker, Schumann, Simon); and Pennington Biomedical Research Center, Louisiana State University (Carmichael).
authors.forename: Owen T
authors.initials: OT
authors.lastname: Carmichael
authors.affiliation: From the Department of Neurology, University of California, Davis (Scott); Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California, Davis (Goodrich-Hunsaker, Kalish, Lee, Hunsaker, Schumann, Simon); and Pennington Biomedical Research Center, Louisiana State University (Carmichael).
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Simon
mesh_terms: D000293:Adolescent; D001007:Anxiety / Q000000981:diagnostic imaging*; D002648:Child; D004062:DiGeorge Syndrome / Q000000981:diagnostic imaging* / Q000523:psychology*; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging* / Q000254:growth & development; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007360:Intelligence; D007361:Intelligence Tests; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D011379:Prognosis; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D012727:Sex Characteristics