title: Default mode network connectivity as a function of familial and environmental risk for psychotic disorder.
abstract: BACKGROUND
  Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder.
  
  
  METHODS
  Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology.
  
  
  RESULTS
  There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity.
  
  
  CONCLUSIONS
  Increased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network "connectivity at rest" intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure.
authors: Dept. of Psychiatry and Psychology, School for Mental Health and Neuroscience, EURON, Maastricht University Medical Center, Maastricht, The Netherlands.
authors: Sanne C T
authors: SC
authors: Peeters
authors: Dept. of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, University of Maastricht, Maastricht, The Netherlands.
authors: Vincent
authors: V
authors: van de Ven
authors: Dept. of Psychiatry and Psychology, School for Mental Health and Neuroscience, EURON, Maastricht University Medical Center, Maastricht, The Netherlands.
authors: Ed H B M
authors: EH
authors: Gronenschild
authors: Behavioral and Clinical Neuroscience Institute, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors: Ameera X
authors: AX
authors: Patel
authors: Dept. of Psychiatry and Psychology, School for Mental Health and Neuroscience, EURON, Maastricht University Medical Center, Maastricht, The Netherlands.
authors: Petra
authors: P
authors: Habets
authors: Dept. of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, University of Maastricht, Maastricht, The Netherlands.
authors: Rainer
authors: R
authors: Goebel
authors: Dept. of Psychiatry and Psychology, School for Mental Health and Neuroscience, EURON, Maastricht University Medical Center, Maastricht, The Netherlands; King's College London, King's Health Partners, Department of Psychosis Studies Institute of Psychiatry, London, United Kingdom.
authors: Jim
authors: J
authors: van Os
authors: Dept. of Psychiatry and Psychology, School for Mental Health and Neuroscience, EURON, Maastricht University Medical Center, Maastricht, The Netherlands; Institute for Mental Health Care Eindhoven (GGzE), Eindhoven, The Netherlands.
authors: Machteld
authors: M
authors: Marcelis
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology*; D011618:Psychotic Disorders / Q000503:physiopathology*; D012306:Risk; D012559:Schizophrenia / Q000175:diagnosis / Q000503:physiopathology; D035781:Siblings