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.