title: Graph Metrics of Structural Brain Networks in Individuals with Schizophrenia and Healthy Controls: Group Differences, Relationships with Intelligence, and Genetics.
abstract: OBJECTIVE
  One of the most prominent features of schizophrenia is relatively lower general cognitive ability (GCA). An emerging approach to understanding the roots of variation in GCA relies on network properties of the brain. In this multi-center study, we determined global characteristics of brain networks using graph theory and related these to GCA in healthy controls and individuals with schizophrenia.
  
  
  METHODS
  Participants (N=116 controls, 80 patients with schizophrenia) were recruited from four sites. GCA was represented by the first principal component of a large battery of neurocognitive tests. Graph metrics were derived from diffusion-weighted imaging.
  
  
  RESULTS
  The global metrics of longer characteristic path length and reduced overall connectivity predicted lower GCA across groups, and group differences were noted for both variables. Measures of clustering, efficiency, and modularity did not differ across groups or predict GCA. Follow-up analyses investigated three topological types of connectivity--connections among high degree "rich club" nodes, "feeder" connections to these rich club nodes, and "local" connections not involving the rich club. Rich club and local connectivity predicted performance across groups. In a subsample (N=101 controls, 56 patients), a genetic measure reflecting mutation load, based on rare copy number deletions, was associated with longer characteristic path length.
  
  
  CONCLUSIONS
  Results highlight the importance of characteristic path lengths and rich club connectivity for GCA and provide no evidence for group differences in the relationships between graph metrics and GCA.
authors.affiliation: 1Department of Psychology,University of New Mexico,Albuquerque,New Mexico.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Yeo
authors.affiliation: 1Department of Psychology,University of New Mexico,Albuquerque,New Mexico.
authors.forename: Sephira G
authors.initials: SG
authors.lastname: Ryman
authors.affiliation: 3Department of Psychiatry,Brain Center Rudolph Magnus,University Medical Center Utrecht,Netherlands.
authors.forename: Martijn P
authors.initials: MP
authors.lastname: van den Heuvel
authors.affiliation: 3Department of Psychiatry,Brain Center Rudolph Magnus,University Medical Center Utrecht,Netherlands.
authors.forename: Marcel A
authors.initials: MA
authors.lastname: de Reus
authors.affiliation: 1Department of Psychology,University of New Mexico,Albuquerque,New Mexico.
authors.forename: Rex E
authors.initials: RE
authors.lastname: Jung
authors.affiliation: 1Department of Psychology,University of New Mexico,Albuquerque,New Mexico.
authors.forename: Jessica
authors.initials: J
authors.lastname: Pommy
authors.affiliation: 1Department of Psychology,University of New Mexico,Albuquerque,New Mexico.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Mayer
authors.affiliation: 5MGH/MIT/HMS Martinos Center for Biomedical Imaging,Massachusetts General Hospital,Charlestown,Massachusetts.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehrlich
authors.affiliation: 8Department of Psychiatry,University of Minnesota,Minneapolis,Minnesota.
authors.forename: S Charles
authors.initials: SC
authors.lastname: Schulz
authors.affiliation: 9Department of Molecular Biology,Cell Biology and Biochemistry,Laboratory for Molecular Medicine,Brown University,Providence,Rhode Island.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Morrow
authors.affiliation: 10Psychiatric Neuroimaging and Athinoula A. Martinos Center for Biomedical Imaging Massachusetts General Hospital,Charlestown,Massachusetts.
authors.forename: Dara
authors.initials: D
authors.lastname: Manoach
authors.affiliation: 11Department of Psychiatry,Carver College of Medicine,University of Iowa,Iowa City,Iowa.
authors.forename: Beng-Choon
authors.initials: BC
authors.lastname: Ho
authors.affiliation: 8Department of Psychiatry,University of Minnesota,Minneapolis,Minnesota.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Sponheim
authors.affiliation: 2The Mind Research Network,Albuquerque,New Mexico.
authors.forename: Vince D
authors.initials: VD
authors.lastname: Calhoun
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007360:Intelligence / Q000502:physiology*; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications / Q000235:genetics / Q000473:pathology; D055815:Young Adult
keywords: Brain; Cognitive; Connectivity; Copy number variation; Graph theory; White matter