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Genetic subtype differences in neural circuitry of food motivation in Prader-Willi syndrome

International Journal of Obesity volume 33, pages 273–283 (2009)Cite this article

Abstract

Background:

Differences in behavioral phenotypes between the two most common subtypes of Prader-Willi syndrome (PWS) (chromosome 15q deletions and maternal uniparental disomy 15 (UPD) indicate that distinct neural networks may be affected. Though both subtypes display hyperphagia, the deletion subgroup shows reduced behavioral inhibition around food, whereas those with UPD are generally more able to maintain cognitive control over food intake impulses.

Objective:

To examine the neural basis of phenotypic differences to better understand relationships between genetic subtypes and behavioral outcomes. We predicted greater food motivation circuitry activity in the deletion subtype and greater activity in higher order cognitive regions in the UPD group, especially after eating.

Design and participants:

Nine individuals with PWS due to UPD and nine individuals with PWS due to (type 2) deletion, matched for age, gender and body mass index, underwent functional magnetic resonance imaging (fMRI) while viewing food images during two food motivation states: one before (pre-meal) and one after (post-meal) eating a standardized 500 kcal meal.

Results:

Both PWS subgroups showed greater activity in response to food pre- and post-meal compared with the healthy-weight group. Compared with UPD, the deletion subtype showed increased food motivation network activation both pre- and post-meal, especially in the medial prefrontal cortex (mPFC) and amygdala. In contrast, the UPD group showed greater activation than the deletion subtype post-meal in the dorsolateral prefrontal cortex (DLPFC) and parahippocampal gyrus (PHG).

Conclusion:

These preliminary findings are the first functional neuroimaging findings to support divergent neural mechanisms associated with behavioral phenotypes in genetic subtypes of PWS. Results are discussed within the framework of genetic mechanisms such as haploinsufficiency and gene dosage effects and their differential influence on deletion and UPD subtypes, respectively.

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Acknowledgements

This study was supported by grants from the National Institutes of Health (HD041672), the Hall Family Foundation and the Heartland Genetics and Newborn Screening Collaborative (HRSA U22MC03962-02). Dr Brooks received support from NIH (NS039123, HD050534, AG029615, AG026482, AG026374 and RR015563). Dr Butler is also supported by NIH (RR019478). The Hoglund Brain Imaging Center is supported by the Hoglund Family Foundation. The authors are grateful to Sang-Pil Lee, Allan Schmitt, Muriel Williams and Pat Weber for technical assistance and Stacey Ward, Jean Reeves and Jean Guadagnino for help in project coordination.

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Authors and Affiliations

  1. Departments of Psychiatry and Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA

    L M Holsen

  2. Department of Pediatrics and Strong Center for Developmental Disabilities, University of Rochester Medical Center, Rochester, NY, USA

    J R Zarcone

  3. Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, USA

    R Chambers, W M Brooks & C R Savage

  4. Department of Psychiatry, University of Kansas Medical Center, Kansas City, KS, USA

    M G Butler & C R Savage

  5. Department of Pediatrics, Section of Medical Genetics and Molecular Medicine, Children's Mercy Hospitals and Clinics and University of Missouri Kansas City School of Medicine, Kansas City, MO, USA

    D C Bittel

  6. Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA

    W M Brooks

  7. Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    T I Thompson

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  1. L M Holsen
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Correspondence to L M Holsen.

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Holsen, L., Zarcone, J., Chambers, R. et al. Genetic subtype differences in neural circuitry of food motivation in Prader-Willi syndrome. Int J Obes 33, 273–283 (2009). https://doi.org/10.1038/ijo.2008.255

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