title: Altered language network activity in young people at familial high-risk for schizophrenia.
abstract: BACKGROUND
  Abnormalities in language and language neural circuitry are observed in schizophrenia (SZ). Similar, but less pronounced language deficits are also seen in young first-degree relatives of people with SZ, who are at higher familial risk (FHR) for the disorder than the general population. The neural underpinnings of these deficits in people with FHR are unclear.
  
  
  METHODS
  Participants were 43 people with FHR and 32 comparable controls. fMRI scans were collected while participants viewed associated and unrelated word pairs, and performed a lexical decision task. fMRI analyses conducted in SPM8 examined group differences in the modulation of hemodynamic activity by semantic association.
  
  
  RESULTS
  There were no group differences in demographics, IQ or behavioral semantic priming, but FHR participants had more schizotypal traits than controls. Controls exhibited the expected suppression of hemodynamic activity to associated versus unrelated word pairs. Compared to controls, FHR participants showed an opposite pattern of hemodynamic modulation to associated versus unrelated word pairs, in the left inferior frontal gyrus (IFG), right superior and middle temporal gyrus (STG) and the left cerebellum. Group differences in activation were significant, FWE-corrected for multiple comparisons (p<0.05). Activity within the IFG during the unrelated condition predicted schizotypal symptoms in FHR participants.
  
  
  CONCLUSIONS
  FHR for SZ is associated with abnormally increased neural activity to semantic associates within an inferior frontal/temporal network. This might increase the risk of developing unusual ideas, perceptions and disorganized language that characterize schizotypal traits, potentially predicting which individuals are at greater risk to develop a psychotic disorder.
authors.affiliation: Harvard Medical School, Boston, MA, USA; Massachusetts Mental Health Center Division of Public Psychiatry, Boston, MA, USA; Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. Electronic address: hthermen@bidmc.harvard.edu.
authors.forename: H W
authors.initials: HW
authors.lastname: Thermenos
authors.forename: S
authors.initials: S
authors.lastname: Whitfield-Gabrieli
authors.forename: L J
authors.initials: LJ
authors.lastname: Seidman
authors.forename: G
authors.initials: G
authors.lastname: Kuperberg
authors.forename: R J
authors.initials: RJ
authors.lastname: Juelich
authors.forename: S
authors.initials: S
authors.lastname: Divatia
authors.forename: C
authors.initials: C
authors.lastname: Riley
authors.forename: G A
authors.initials: GA
authors.lastname: Jabbar
authors.forename: M E
authors.initials: ME
authors.lastname: Shenton
authors.forename: M
authors.initials: M
authors.lastname: Kubicki
authors.forename: T
authors.initials: T
authors.lastname: Manschreck
authors.forename: M S
authors.initials: MS
authors.lastname: Keshavan
authors.forename: L E
authors.initials: LE
authors.lastname: DeLisi
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000098:blood supply / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007802:Language; D007807:Language Tests; D016014:Linear Models; D008297:Male; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011930:Reaction Time; D012559:Schizophrenia / Q000473:pathology* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D012660:Semantics; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: Functional MRI; Genetics; High-risk; Language; Schizophrenia; Semantic priming