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

L. M. Holsen, J. R. Zarcone, R. Chambers, M. G. Butler, D. C. Bittel, W. M. Brooks, T. I. Thompson, C. R. Savage

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)273-283
Number of pages11
JournalInternational Journal of Obesity
Volume33
Issue number2
DOIs
StatePublished - Feb 20 2009

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Prader-Willi Syndrome
Meals
Motivation
Food
Eating
Prefrontal Cortex
Behavioral Genetics
Phenotype
Haploinsufficiency
Hyperphagia
Chromosome Deletion
Parahippocampal Gyrus
Functional Neuroimaging
Gene Dosage
Trisomy mosaicism Chromosome 15
Amygdala
Body Mass Index
Mothers
Magnetic Resonance Imaging
Weights and Measures

Keywords

  • Brain activity
  • FMRI
  • Genetic phenotypes
  • Hyperphagia
  • Prader-Willi syndrome

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Genetic subtype differences in neural circuitry of food motivation in Prader-Willi syndrome. / Holsen, L. M.; Zarcone, J. R.; Chambers, R.; Butler, M. G.; Bittel, D. C.; Brooks, W. M.; Thompson, T. I.; Savage, C. R.

In: International Journal of Obesity, Vol. 33, No. 2, 20.02.2009, p. 273-283.

Research output: Contribution to journalArticle

Holsen, LM, Zarcone, JR, Chambers, R, Butler, MG, Bittel, DC, Brooks, WM, Thompson, TI & Savage, CR 2009, 'Genetic subtype differences in neural circuitry of food motivation in Prader-Willi syndrome', International Journal of Obesity, vol. 33, no. 2, pp. 273-283. https://doi.org/10.1038/ijo.2008.255
Holsen, L. M. ; Zarcone, J. R. ; Chambers, R. ; Butler, M. G. ; Bittel, D. C. ; Brooks, W. M. ; Thompson, T. I. ; Savage, C. R. / Genetic subtype differences in neural circuitry of food motivation in Prader-Willi syndrome. In: International Journal of Obesity. 2009 ; Vol. 33, No. 2. pp. 273-283.
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