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Neurodevelopmental Genomic Strategies in the Study of the Psychosis Spectrum

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Book cover The Neuropsychopathology of Schizophrenia

Part of the book series: Nebraska Symposium on Motivation ((NSM,volume 63))

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Abstract

Consistent with the goals of precision medicine to redefine illness mechanistically through elucidating the pathophysiology from gene action to symptoms, large-scale genomic studies have been linking genomic variation to continuous quantitative phenotypes. Such an approach can lead to early detection of pathological processes enabling early intervention. This paradigm shift is now applied in psychiatry with an increased focus in schizophrenia research on early identification of psychosis as the process emerges. Convergent approaches integrate phenotypic features with neurocognitive and neuroimaging measures in large-scale studies. Most studies have examined help-seeking youths.

This chapter highlights two additional complementary strategies to probe the underlying neurobiology of psychosis risk. The first is the study of a community-based sample of youths with no known neurogenetic syndrome. The Philadelphia Neurodevelopment Cohort is a large (about 9, 500) prospective sample of genotyped youths where converging measures of brain and behavior have been obtained. Individuals with psychosis spectrum symptoms showed aberrant brain function across neurocognitive and neuroimaging measures.

The second converging approach is the study of youths with a known genetic syndrome that confers significantly increased risk for psychosis. The 22q11.2 deletion syndrome is associated with ~25 % risk of psychosis emerging in adolescence and early adulthood. In this sample, we compared individuals with psychotic features to those without in order to establish unique characteristic that modulate psychosis risk.

Both samples underwent “deep phenotyping” and were compared to healthy participants. Both are followed longitudinally to establish intake predictors of clinical high-risk status and ultimately transition to psychosis. As importantly, factors indicative of resilience may be uncovered using these complementary strategies.

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Acknowledgments

This work was supported by the National Institutes of Health grants MH087626, MH087636, MH089983, and MH089924 and the Dowshen Neuroscience Program. I am grateful to the faculty, trainees, and research team members of the Schizophrenia Research Center and the Brain Behavior Laboratory of the Neuropsychiatry Section at Penn Medicine and the Center for Applied Genomics and the 22q and You Center at Children’s Hospital of Philadelphia. Special thanks to the research participants and their parents for their efforts.

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  1. Department of Psychiatry, Schizophrenia Research Center, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA

    Raquel E. Gur

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Correspondence to Raquel E. Gur .

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  1. Department of Psychology, University of Nebraska-Lincoln, Lincoln, Nebraska, USA

    Ming Li

  2. Department of Psychology, University of Nebraska-Lincoln, Lincoln, Nebraska, USA

    William D. Spaulding

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Gur, R.E. (2016). Neurodevelopmental Genomic Strategies in the Study of the Psychosis Spectrum. In: Li, M., Spaulding, W. (eds) The Neuropsychopathology of Schizophrenia. Nebraska Symposium on Motivation, vol 63. Springer, Cham. https://doi.org/10.1007/978-3-319-30596-7_2

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