MRI Indices of Cortical Development in Young People with Psychotic Experiences: Influence of Genetic Risk and Persistence of Symptoms

Leon Fonville, Mark Drakesmith, Stanley Zammit, Glyn H Lewis, Derek K. Jones, Anthony S. David

Research output: Contribution to journalArticle (Academic Journal)peer-review

14 Citations (Scopus)
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Background: Psychotic experiences (PEs) are considered part of an extended psychosis phenotype and are associated with an elevated risk of developing a psychotic disorder. Risk of transition increases with persistence of PEs, and this is thought to be modulated by genetic and environmental factors. However, it is unclear if persistence is associated with progressive schizophrenia-like disturbances in neuroanatomy.
Methods: We examined cortical morphometry in 247 young adults, from a population-based cohort, assessed for the presence of PEs at ages 18 and 20. We then incorporated a polygenic risk score for schizophrenia (PRS) to elucidate the effects of high genetic risk. Finally, we used atlas-based tractography data to examine the underlying white matter.
Results: Individuals with persisting PEs showed reductions in gyrification (local gyrification index: lGI) in the left temporal gyrus as well as atypical associations with brain volume (TBV) in the left occipital and right prefrontal gyri. No main effect was found for the PRS, but interaction effects with PEs were identified in the orbitofrontal, parietal, and temporal regions. Examination of underlying white matter did not provide strong evidence of further disturbances.
Conclusions: Disturbances in lGI were similar to schizophrenia but findings were mostly limited to persistent PEs. These could reflect subtle changes that worsen with impending psychosis or reflect an early vulnerability associated with the persistence of PEs. The lack of clear differences in underlying white matter suggest our findings reflect early disturbances in cortical expansion rather than progressive changes in brain structure leading up to a psychotic disorder.
Original languageEnglish
Article numbersbx195
Pages (from-to)169-179
Number of pages11
JournalSchizophrenia Bulletin
Issue number1
Early online date29 Jan 2018
Publication statusPublished - 1 Jan 2019


  • Psychotic experiences
  • psychosis
  • polygenic risk
  • magnetic resonance imaging
  • gyrification


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  • NIHR BRC Mental Health

    Gunnell, D. J.


    Project: Research, Parent

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