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Polygenic risk of psychosis and ventral striatal activation during reward processing in healthy adolescents

JAMA psychiatry, 73, 852-861, 2016


Status: Published

Citations:

Cite: [bibtex]


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Abstract: Importance: Psychotic disorders are characterized by attenuated activity in the brain’s valuation system in key reward processing areas, such as the ventral striatum (VS), as measured with functional magnetic resonance imaging.
Objective: To examine whether common risk variants for psychosis are associated with individual variation in the VS.
Design, Setting, and Participants: A cross-sectional study of a large cohort of adolescents from the IMAGEN study (a European multicenter study of reinforcement sensitivity in adolescents) was performed from March 1, 2008, through December 31, 2011. Data analysis was conducted from October 1, 2015, to January 9, 2016. Polygenic risk profile scores (RPSs) for psychosis were generated for 1841 healthy adolescents. Sample size and characteristics varied across regression analyses, depending on mutual information available (N = 1524-1836).
Main Outcomes and Measures: Reward-related brain function was assessed with blood oxygen level dependency (BOLD) in the VS using the monetary incentive delay (MID) task, distinguishing reward anticipation and receipt. Behavioral impulsivity, IQ, MID task performance, and VS BOLD were regressed against psychosis RPS at 4 progressive P thresholds (P < .01, P < .05, P < .10, and P < .50 for RPS models 1-4, respectively).
Results: In a sample of 1841 healthy adolescents (mean age, 14.5 years; 906 boys and 935 girls), we replicated an association between increasing psychosis RPS and reduced IQ (matrix reasoning: corrected P = .003 for RPS model 2, 0.4% variance explained), supporting the validity of the psychosis RPS models. We also found a nominally significant association between increased psychosis RPS and reduced MID task performance (uncorrected P = .03 for RPS model 4, 0.2% variance explained). Our main finding was a positive association between psychosis RPS and VS BOLD during reward anticipation at all 4 psychosis RPS models and for 2 P thresholds for reward receipt (RPS models 1 and 3), correcting for the familywise error rate (0.8%-1.9% variance explained).
Conclusions and Relevance: These findings support an association between psychosis RPS and VS BOLD in adolescents. Genetic risk for psychosis may shape an individual’s response to rewarding stimuli.



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Joshua Bongard - Department of Computer Science, Associate Professor

Bongard's work focuses on understanding the general nature of cognition, regardless of whether it is found in humans, animals or robots. This unique approach focuses on the role that morphology and evolution plays in cognition. Addressing these questions has taken him into the fields of biology, psychology, engineering and computer science.


  • Stacks Image 525371
    Josh Bongard, Victor Zykov, Hod Lipson. Resilient Machines Through
    Continuous Self-Modeling.
    Science 314, 1118 (2006). [Journal Page]
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    Joey Anetsberger and Josh Bongard. Robots can ground crowd-proposed symbols by forming theories of group mind. Proceedings of the Artificial Life Conference 2016. [Link to Proceedings]
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    Sam Kriegman, Nick Cheney, and Josh Bongard. How morphological development can guide evolution. arXiv 2017. [arXiv]


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Chris Danforth -Department of Mathematics and Statistics, Flint Professor of Mathematical, Natural, and Technical Sciences

Danforth is an applied mathematician interested in modeling a variety of physical, biological, and social phenomenon. He has applied principles of chaos theory to improve weather forecasts as a member of the Mathematics and Climate Research Network, and developed a real-time remote sensor of global happiness using messages from Twitter: the Hedonometer. Danforth co-runs the Computational Story Lab with Peter Dodds, and helps run UVM's reading group on complexity.

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    Peter Sheridan Dodds , Kameron Decker Harris, Isabel M. Kloumann, Catherine A. Bliss, Christopher M. Danforth. Temporal Patterns of Happiness and Information in a Global Social Network: Hedonometrics and Twitter. PLoS ONE 2011. [Journal Page].
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    Lewis Mitchell , Morgan R. Frank, Kameron Decker Harris, Peter Sheridan Dodds, Christopher M. Danforth. The Geography of Happiness: Connecting Twitter Sentiment and Expression, Demographics, and Objective Characteristics of Place. PLoS ONE 2013. [Journal Page].
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    Andrew G Reece and Christopher M Danforth. Instagram photos reveal predictive markers of depression. EPJ Data Science 2017. [Journal Page].


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Laurent Hébert-Dufresne - Assistant Professor, Computer Science

Laurent studies the interaction of structure and dynamics. His research involves network theory, statistical physics and nonlinear dynamics along with their applications in epidemiology, ecology, biology, and sociology. Recent projects include comparing complex networks of different nature, the coevolution of human behavior and infectious diseases, understanding the role of forest shape in determining stability of tropical forests, as well as the impact of echo chambers in political discussions.

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Paul Hines - School of Engineering, Associate Professor

Hines' work broadly focuses on finding ways to make electric energy more reliable, more affordable, with less environmental impact. Particular topics of interest include understanding the mechanisms by which small problems in the power grid become large blackouts, identifying and mitigating the stresses caused by large amounts of electric vehicle charging, and quantifying the impact of high penetrations of wind/solar on electricity systems.

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    Mert Korkali, Jason G. Veneman, Brian F. Tivnan, James P. Bagrow & Paul D. H. Hines. Reducing Cascading Failure Risk by Increasing Infrastructure Network Interdependence. Scientific Reports volume 7, Article number: 44499 (2017. [Journal Page]
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    Pooya Rezaei, Paul D. H. Hines, Margaret J. Eppstein. Estimating Cascading Failure Risk With Random Chemistry. IEEE Transactions on Power Systems ( Volume: 30, Issue: 5, Sept. 2015 ). [Journal Page]


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James Bagrow - Assistant Professor, Department of Mathematics and Statistics

Bagrow's interests include: Complex Networks (community detection, social modeling and human dynamics, statistical phenomena, graph similarity and isomorphism), Statistical Physics (non-equilibrium methods, phase transitions, percolation, interacting particle systems, spin glasses), and Optimization(glassy techniques such as simulated/quantum annealing, (non-gradient) minimization of noisy objective functions).

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    Y.-Y. Ahn, J. P. Bagrow and S. Lehmann. Link communities reveal multiscale complexity in networks. Nature, 466: 761-764 (2010). [Journal Page].
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    M. R. Frank, J. R. Williams, L. Mitchell, J. P. Bagrow, P. S. Dodds, C. M. Danforth. Constructing a taxonomy of fine-grained human movement and activity motifs through social media. In preparation. (2015). [Journal Page].
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    J. P. Bagrow and L. Mitchell. The quoter model: a paradigmatic model of the social flow of written information. To appear, Chaos (2018). [Journal Page].