title: Anatomical distance affects functional connectivity in patients with schizophrenia and their siblings.
abstract: BACKGROUND
  The efficiency of human brain depends on the integrity of both long- and short-range connections, but the long-range connections need to be "penalized" to reduce overall wiring costs. This principle, termed as the anatomical distance function (ADF), refers to the presence of an inverse relationship between anatomical distance and connectivity. A crucial developmental feature that occurs in normal adolescence is the weakening of ADF, which is characterized by a selective strengthening of long-distance connections. Schizophrenia is associated with widespread dysconnectivity that is linked to aberrant cortical development.
  
  
  METHODS
  We studied the ADF in adults with schizophrenia (n = 28), their age-matched siblings (n = 28), and healthy controls (n = 60). We investigated the proportional abnormalities in the long-range connections involving interhemispheric, subcortical, frontal, and salience network regions and localized the connections showing most significant changes in schizophrenia. The groups were discriminated on the basis of short- and long-range connectivity using a machine-learning algorithm.
  
  
  RESULTS
  Both patients and their siblings showed abnormally pronounced ADF. This was associated with a disproportionate reduction in the number of long-range connections, affecting the subcortical, interhemispheric, and the salience network connections. The abnormalities in long-range connections had superior ability to accurately identify group membership.
  
  
  CONCLUSIONS
  A crucial organizing principle of the brain architecture that becomes apparent during normal adolescence is disturbed in schizophrenia. While siblings show some evidence of compensating for this deficit, patients lack putative compensatory changes. Age-related shift in ADF provides an explanatory framework for the developmental emergence of widespread dysconnectivity that is influenced by genetic risk in schizophrenia.
authors.affiliation: *To whom correspondence should be addressed; Department of Computer Science, University of Warwick, Coventry CV4 7AL, UK; tel: 00447799572480; fax: 00442476523193. jianfeng64@gmail.com.
authors.forename: Shuixia
authors.initials: S
authors.lastname: Guo
authors.forename: Lena
authors.initials: L
authors.lastname: Palaniyappan
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Zhening
authors.initials: Z
authors.lastname: Liu
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Xue
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Feng
mesh_terms: D000328:Adult; D000465:Algorithms; D001185:Artificial Intelligence; D001921:Brain / Q000254:growth & development / Q000503:physiopathology*; D063132:Connectome / Q000295:instrumentation / Q000379:methods*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000254:growth & development / Q000503:physiopathology*; D012559:Schizophrenia / Q000145:classification / Q000209:etiology / Q000503:physiopathology*; D035781:Siblings
keywords: anatomical distance; functional connectivity; genetic risk; salience network; schizophrenia; wiring cost