title: Functional and effective frontotemporal connectivity and genetic risk for schizophrenia.
abstract: BACKGROUND
  Functional neuroimaging and electrophysiologic studies have found disturbed frontotemporal interaction in schizophrenia. We sought to determine whether abnormalities of frontotemporal connectivity are trait markers of genetic risk for schizophrenia.
  
  
  METHODS
  We investigated 64 schizophrenia patients, 79 of their clinically unaffected siblings, and 88 unrelated normal controls with an auditory oddball electroencephalogram (EEG) evoked potential paradigm. We measured: 1) frontotemporal event-related EEG-coherence (i.e. a measure of functional connectivity); and 2) we performed structural equation modeling of the effective connectivity between the frontal P300 and temporoparietal P300-amplitude.
  
  
  RESULTS
  Schizophrenic patients and their siblings showed a reduction of frontotemporal coherence. At peak activation during the P300 time-window, a negative ("inhibitory") frontotemporal path coefficient was found in normal controls, whereas a positive coefficient was seen in schizophrenic patients with siblings being intermediate. Intra-class correlations between sib-pairs and relative risk estimates of the applied connectivity measures were non-significant. Topographic correlation matrix analyses suggested that the altered functional and effective frontotemporal connectivity indirectly reflect regional abnormalities of increased activation variance.
  
  
  CONCLUSIONS
  Impaired interaction of the frontotemporal macro-circuit indirectly reflects genetically determined abnormalities of frontal and temporoparietal microcircuits. The reasons why frontotemporal connectivity appears to be a poor predictor of genetic risk for schizophrenia are discussed.
authors.affiliation: Clinical Brain Disorders Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Georg
authors.initials: G
authors.lastname: Winterer
authors.forename: Richard
authors.initials: R
authors.lastname: Coppola
authors.forename: Michael F
authors.initials: MF
authors.lastname: Egan
authors.forename: Terry E
authors.initials: TE
authors.lastname: Goldberg
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
mesh_terms: D000328:Adult; D004569:Electroencephalography; D018913:Event-Related Potentials, P300 / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*; D035781:Siblings; D013702:Temporal Lobe / Q000503:physiopathology*