title: Semi-metric analysis of the functional brain network: Relationship with familial risk for psychotic disorder.
abstract: BACKGROUND
  Dysconnectivity in schizophrenia can be understood in terms of dysfunctional integration of a distributed network of brain regions. Here we propose a new methodology to analyze complex networks based on semi-metric behavior, whereby higher levels of semi-metricity may represent a higher level of redundancy and dispersed communication. It was hypothesized that individuals with (increased risk for) psychotic disorder would have more semi-metric paths compared to controls and that this would be associated with symptoms.
  
  
  METHODS
  Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 unaffected siblings and 72 controls. Semi-metric percentages (SMP) at the whole brain, hemispheric and lobar level were the dependent variables in a multilevel random regression analysis to investigate group differences. SMP was further examined in relation to symptomatology (i.e., psychotic/cognitive symptoms).
  
  
  RESULTS
  At the whole brain and hemispheric level, patients had a significantly higher SMP compared to siblings and controls, with no difference between the latter. In the combined sibling and control group, individuals with high schizotypy had intermediate SMP values in the left hemisphere with respect to patients and individuals with low schizotypy. Exploratory analyses in patients revealed higher SMP in 12 out of 42 lobar divisions compared to controls, of which some were associated with worse PANSS symptomatology (i.e., positive symptoms, excitement and emotional distress) and worse cognitive performance on attention and emotion processing tasks. In the combined group of patients and controls, working memory, attention and social cognition were associated with higher SMP.
  
  
  CONCLUSIONS
  The results are suggestive of more dispersed network communication in patients with psychotic disorder, with some evidence for trait-based network alterations in high-schizotypy individuals. Dispersed communication may contribute to the clinical phenotype in psychotic disorder. In addition, higher SMP may contribute to neuro- and social cognition, independent of psychosis risk.
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, EURON, Maastricht University Medical Centre, PO Box 616 (Vijv1), 6200 MD Maastricht, The Netherlands; Faculty of Psychology and Educational Sciences, Open University of the Netherlands, Heerlen, The Netherlands.
authors.forename: Sanne
authors.initials: S
authors.lastname: Peeters
authors.affiliation: Behavioral and Clinical Neuroscience Institute, Department of Psychiatry, University of Cambridge, United Kingdom.
authors.forename: Tiago
authors.initials: T
authors.lastname: Simas
authors.affiliation: Behavioral and Clinical Neuroscience Institute, Department of Psychiatry, University of Cambridge, United Kingdom; Cambridge and Peterborough Foundation NHS Trust. Cambridge, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Suckling
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, EURON, Maastricht University Medical Centre, PO Box 616 (Vijv1), 6200 MD Maastricht, The Netherlands.
authors.forename: Ed
authors.initials: E
authors.lastname: Gronenschild
authors.affiliation: Behavioral and Clinical Neuroscience Institute, Department of Psychiatry, University of Cambridge, United Kingdom.
authors.forename: Ameera
authors.initials: A
authors.lastname: Patel
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, EURON, Maastricht University Medical Centre, PO Box 616 (Vijv1), 6200 MD Maastricht, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Habets
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, EURON, Maastricht University Medical Centre, PO Box 616 (Vijv1), 6200 MD Maastricht, The Netherlands; King's College London, King's Health Partners, Department of Psychosis Studies Institute of Psychiatry, London, United Kingdom.
authors.forename: Jim
authors.initials: J
authors.lastname: van Os
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, EURON, Maastricht University Medical Centre, PO Box 616 (Vijv1), 6200 MD Maastricht, The Netherlands; Institute for Mental Health Care Eindhoven (GGzE), Eindhoven, The Netherlands.
authors.forename: Machteld
authors.initials: M
authors.lastname: Marcelis
mesh_terms: D000328:Adult; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods*; D003627:Data Interpretation, Statistical; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011618:Psychotic Disorders / Q000235:genetics* / Q000503:physiopathology*; D012307:Risk Factors; D035781:Siblings; D055815:Young Adult
keywords: Functional brain network; Graph theory; Psychotic disorder; Resting-state fMRI; Semi-metric percentage; Unaffected siblings