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Hallucinations and Brain Morphology Across Early Adolescence: A Longitudinal Neuroimaging Study

  • Lisa R. Steenkamp
    Affiliations
    Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC Sophia Children’s Hospital, Rotterdam

    Generation R Study group, Erasmus MC, University Medical Center Rotterdam, Rotterdam
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  • Elisabet Blok
    Affiliations
    Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC Sophia Children’s Hospital, Rotterdam

    Generation R Study group, Erasmus MC, University Medical Center Rotterdam, Rotterdam
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  • Ryan L. Muetzel
    Affiliations
    Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC Sophia Children’s Hospital, Rotterdam
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  • Tonya White
    Affiliations
    Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC Sophia Children’s Hospital, Rotterdam

    Departments of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
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  • Manon H.J. Hillegers
    Affiliations
    Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC Sophia Children’s Hospital, Rotterdam
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  • Laura M.E. Blanken
    Affiliations
    Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC Sophia Children’s Hospital, Rotterdam

    Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
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  • Koen Bolhuis
    Affiliations
    Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC Sophia Children’s Hospital, Rotterdam

    Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
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  • Henning Tiemeier
    Correspondence
    Address correspondence to Henning Tiemeier, M.D., Ph.D.
    Affiliations
    Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC Sophia Children’s Hospital, Rotterdam

    Department of Social and Behavioral Science, Harvard TH Chan School of Public Health, Boston, Massachusetts
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  • Steven A. Kushner
    Affiliations
    Psychiatry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
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      Abstract

      Background

      Psychotic disorders have been widely associated with structural brain abnormalities. However, it is unclear whether brain structure predicts psychotic experiences in youth from the general population, owing to an overall paucity of studies and predominantly cross-sectional designs. Here, the authors investigated longitudinal associations between brain morphology and hallucinations from childhood to early adolescence.

      Methods

      This study was embedded in the population-based Generation R Study. Children underwent structural neuroimaging at age 10 years (N = 2042); a subsample received a second scan at age 14 years (n = 964). Hallucinations were assessed at ages 10 and 14 years and studied as a binary variable. Cross-lagged panel models and generalized linear mixed-effects models were fitted to examine longitudinal associations between brain morphology and hallucinations.

      Results

      Smaller total gray and white matter volumes and total cortical surface area at baseline were associated with a higher occurrence of hallucinations between ages 10 and 14 years. The regions associated with hallucinations were widespread, including the frontal, parietal, temporal, and occipital lobes, as well as the insula and cingulate cortex. Analyses of subcortical structures revealed that smaller baseline hippocampal volumes were longitudinally associated with hallucinations, although this association was no longer significant following adjustment for intracranial volume. No evidence for reverse temporality was observed (i.e., hallucinations predicting brain differences).

      Conclusions

      The findings from this longitudinal study suggest that global structural brain differences are associated with the development of hallucinations. These results extend findings from clinical populations and provide evidence for a neurodevelopmental vulnerability across the psychosis continuum.

      Keywords

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