title: Event-related fMRI of word classification and successful word recognition in subjects at genetically enhanced risk of schizophrenia.
abstract: BACKGROUND
  Verbal declarative memory is a core deficit in schizophrenia patients, seen to a lesser extent in unaffected biological relatives. Neuroimaging studies suggest volumetric differences and aberrant function in prefrontal and temporal regions in schizophrenia patients compared to controls. These deficits are also reflected in the small number of similar investigations in unaffected biological relatives. However, it is unclear the extent to which dysfunction is genetically mediated or a feature of the established illness.
  
  
  METHODS
  Event-related blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to measure brain activation in 68 biological relatives of schizophrenia patients (of whom 27 experienced transient or isolated psychotic symptoms) and 21 controls during verbal classification and recognition.
  
  
  RESULTS
  During word classification, the high-risk group showed a greater response relative to controls in the right inferior frontal gyrus. During correct recognition (relative to correct rejection), the high-risk group showed significantly greater response relative to controls in the right cerebellum. When the high-risk group was split into those with (HR+) and without (HR-) psychotic symptoms, the increased response in the right inferior frontal gyrus was only seen when the HR+ were compared to controls. The greater cerebellar response was seen when both HR groups were compared to controls.
  
  
  CONCLUSIONS
  Activation increases in the right inferior frontal gyrus and cerebellum in high-risk subjects compared to controls during a relatively low-load memory task are likely to represent compensation for genetically mediated abnormalities. This is consistent with a leftward shift of the inverted 'U' load-response model of cognitive function in schizophrenia.
authors.affiliation: Division of Psychiatry, University of Edinburgh, UK.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Whyte
authors.forename: Heather C
authors.initials: HC
authors.lastname: Whalley
authors.forename: Enrico
authors.initials: E
authors.lastname: Simonotto
authors.forename: Susanna
authors.initials: S
authors.lastname: Flett
authors.forename: Richard
authors.initials: R
authors.lastname: Shillcock
authors.forename: Ian
authors.initials: I
authors.lastname: Marshall
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Goddard
authors.forename: Eve C
authors.initials: EC
authors.lastname: Johnstone
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Lawrie
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D002531:Cerebellum / Q000033:anatomy & histology / Q000378:metabolism; D005071:Evoked Potentials / Q000502:physiology*; D005625:Frontal Lobe / Q000033:anatomy & histology / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D010100:Oxygen / Q000097:blood; D021641:Recognition, Psychology; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis* / Q000235:genetics*; D012660:Semantics; D014825:Vocabulary
chemical_list: D010100:Oxygen