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Alterations in white matter microstructure in individuals at persistent risk for psychosis

Molecular Psychiatry volume 25, pages 2441–2454 (2020)Cite this article

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Abstract

Abnormalities in brain white matter (WM) are reported in youth at-risk for psychosis. Yet, the neurodevelopmental time course of these abnormalities remains unclear. Thus, longitudinal diffusion-weighted imaging (DWI) was used to investigate WM abnormalities in youth at-risk for psychosis. A subset of individuals from the Philadelphia Neurodevelopmental Cohort (PNC) completed two DWI scans approximately 20 months apart. Youths were identified through structured interview as having subthreshold persistent psychosis risk symptoms (n = 46), and were compared to healthy typically developing participants (TD; n = 98). Analyses were conducted at voxelwise and regional levels. Nonlinear developmental patterns were examined using penalized splines within a generalized additive model. Compared to TD, youth with persistent psychosis risk symptoms had lower whole-brain WM fractional anisotropy (FA) and higher radial diffusivity (RD). Voxelwise analyses revealed clusters of significant WM abnormalities within the temporal and parietal lobes. Lower FA within the cingulum bundle of hippocampus and cerebrospinal tracts were the most robust deficits in individuals with persistent psychosis symptoms. These findings were consistent over two visits. Thus, it appears that WM abnormalities are present early in youth with persistent psychosis risk symptoms, however, there is little evidence to suggest that these features emerge in late adolescence or early adulthood. Future studies should seek to characterize WM abnormalities in younger individuals and follow individuals as subthreshold psychotic symptoms emerge.

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Acknowledgments

Thanks to the acquisition and recruitment team: Karthik Prabhakaran, Jeff Valdez, Raphael Gerraty, Marisa Riley, Jack Keefe, Elliott Yodh, Jason Blake, Prayosha Villa, R. Sean Gallagher and Rosetta Chiavacci.

Funding

This work was supported by the National Institute of Mental Health grants MH089983, MH089924, and MH087626. Additional support was provided by K01MH102609 to DRR; K23MH098130 and R01 MH107703 to TDS; R01 MH112847 to TDS and RTS; the Dowshen Program for Neuroscience at the University of Pennsylvania; and the Life Span Brain Institute (LiBI)—a collaboration between the University of Pennsylvania School of Medicine and Children’s Hospital of Philadelphia. This work was also supported by a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. The funding sources were not directly involved in study design, collection, data analysis or interpretation, nor manuscript writing.

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Authors and Affiliations

  1. Brain Behavior Laboratory, Department of Psychiatry, Neuropsychiatry Section, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    David R. Roalf, Angel Garcia de la Garza, Monica E. Calkins, Tyler M. Moore, Megan Quarmley, Kosha Ruparel, Cedric Huchuan Xia, Petra E. Rupert, Theodore D. Satterthwaite, Ruben C. Gur & Raquel E. Gur

  2. Department of Biostatistics and Epidemiology, Perelman School of Medicine, Philadelphia, PA, 19104, USA

    Russell T. Shinohara

  3. Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, 19104, USA

    Mark A. Elliott, Ruben C. Gur & Raquel E. Gur

  4. Lifespan Brain Institute (LiBI) at the University of Pennsylvania and Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA

    Ruben C. Gur & Raquel E. Gur

  5. Department of Child and Adolescent Psychiatry, Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA

    Raquel E. Gur

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  1. David R. Roalf
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Roalf, D.R., de la Garza, A.G., Rosen, A. et al. Alterations in white matter microstructure in individuals at persistent risk for psychosis. Mol Psychiatry 25, 2441–2454 (2020). https://doi.org/10.1038/s41380-019-0360-1

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