title: Structural Brain Network Disturbances in the Psychosis Spectrum.
abstract: BACKGROUND
  Individuals with subclinical psychotic symptoms provide a unique window on the pathophysiology of psychotic experiences as these individuals are free of confounders such as hospitalization, negative and cognitive symptoms and medication use. Brain network disturbances of white matter connections are thought to play a central role in the pathophysiology of psychosis. Based on the structural network disconnection hypothesis in schizophrenia, we expect less and weaker connections, and altered brain network organization in individuals with clinical and those with subclinical psychotic symptoms.
  
  
  METHODS
  We used diffusion tensor imaging to study 35 patients with a psychotic disorder, 35 subjects with subclinical psychotic symptoms, and 36 healthy controls. The structural brain network was analyzed on 3 levels: connection density, white matter microstructure (fractional anisotropy, mean diffusivity, and magnetic transfer ratio), and network organization. Network organization was studied with minimum spanning tree analysis, a method to reconstruct a backbone of structural highways in the brain.
  
  
  RESULTS
  Decreased fractional anisotropy and increased mean diffusivity was found in both groups with psychotic symptoms, while their network topology showed decreased overlap with a healthy reference network. Decreased centrality was found in several brain regions, including parietal hubs and language areas, in both groups with psychotic symptoms. Deviation of network characteristics was more apparent in clinical subjects than in subclinical subjects.
  
  
  CONCLUSIONS
  Weaker connections and decreased centrality of parietal hubs characterize the structural brain network in subjects with psychotic symptoms. These differences are more notable in clinical than in subclinical subjects with psychotic experiences.
authors.affiliation: Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Psychiatry, Brain Center Rudolf Magnus, Utrecht, The Netherlands; E.vanDellen@umcutrecht.nl.
authors.forename: Edwin
authors.initials: E
authors.lastname: van Dellen
authors.affiliation: Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Psychiatry, Brain Center Rudolf Magnus, Utrecht, The Netherlands;
authors.forename: Marc M
authors.initials: MM
authors.lastname: Bohlken
authors.affiliation: Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Psychiatry, Brain Center Rudolf Magnus, Utrecht, The Netherlands;
authors.forename: Laurijn
authors.initials: L
authors.lastname: Draaisma
authors.affiliation: Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands;
authors.forename: Prejaas K
authors.initials: PK
authors.lastname: Tewarie
authors.affiliation: Center for Mindfulness, University of Massachusetts School of Medicine, Shrewsbury, MA;
authors.forename: Remko
authors.initials: R
authors.lastname: van Lutterveld
authors.affiliation: Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Psychiatry, Brain Center Rudolf Magnus, Utrecht, The Netherlands;
authors.forename: René
authors.initials: R
authors.lastname: Mandl
authors.affiliation: Department of Clinical Neurophysiology and MEG Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Cornelis J
authors.initials: CJ
authors.lastname: Stam
authors.affiliation: Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Psychiatry, Brain Center Rudolf Magnus, Utrecht, The Netherlands;
authors.forename: Iris E
authors.initials: IE
authors.lastname: Sommer
mesh_terms: D000328:Adult; D000368:Aged; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000473:pathology*; D010296:Parietal Lobe / Q000473:pathology*; D011618:Psychotic Disorders / Q000473:pathology*; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
keywords: brain networks; diffusion tensor imaging; fractional anisotropy; hubs; minimum spanning tree; psychosis continuum