J Psychiatry Neurosci 2012;37(4):322-32
Laura M. Holsen, PhD; Elizabeth A. Lawson, MD; Justine Blum, BA; Eunice Ko, BA; Nikos Makris, MD, PhD; Pouneh K. Fazeli, MD; Anne Klibanski, MD; Jill M. Goldstein, PhD
Holsen, Ko, Goldstein — Division of Women’s Health, Department of Medicine, Brigham and Women’s Hospital, Boston; Holsen, Goldstein — Department of Psychiatry, Brigham and Women’s Hospital, Boston; Holsen, Lawson, Fazeli, Klibanski, Goldstein— Harvard Medical School, Boston; Lawson, Blum, Fazeli, Klibanski — Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston; Makris, Goldstein — Athinoula A. Martinos Center, Massachusetts General Hospital and Massachusetts Institute of Technology, Charlestown; Makris — Harvard Medical School Departments of Neurology, Psychiatry, and Radiology Services, Center for Morphometric Analysis, Massachusetts General Hospital, Charlestown, and the Department of Anatomy and Neuro biology, Boston University School of Medicine, Boston, Mass.
Background: Previous studies have provided evidence of food motivation circuitry dysfunction in individuals with anorexia nervosa. However, methodological limitations present challenges to the development of a cohesive neurobiological model of anorexia nervosa. Our goal was to investigate the neural circuitry of appetite dysregulation across states of hunger and satiety in active and weight-restored phases of anorexia nervosa using robust methodology to advance our understanding of potential neural circuitry abnormalities related to hedonic and nonhedonic state and trait.
Methods: We scanned women with active anorexia nervosa, weight-restored women with anorexia nervosa and healthy-weight controls on a 3-T Siemens magnetic resonance scanner while they viewed images of high- and low-calorie foods and objects before (premeal) and after (postmeal) eating a 400 kcal meal.
Results: We enrolled 12 women with active disease, 10 weight-restored women with anorexia nervosa and 11 controls in our study. Compared with controls, both weight-restored women and those with active disease demonstrated hypoactivity premeal in the hypothalamus, amygdala and anterior insula in response to high-calorie foods (v. objects). Postmeal, hypoactivation in the anterior insula persisted in women with active disease. Percent signal change in the anterior insula was positively correlated with food stimuli ratings and hedonic and nonhedonic appetite ratings in controls, but not women with active disease.
Limitations: Our findings are limited by a relatively small sample size, which prevented the use of an analysis of variance model and exploration of interaction effects, although our substantial effect sizes of between-group differences suggest adequate power for our statistical analysis approach. Participants taking psychotropic medications were included.
Conclusion: Our data provide evidence of potential state and trait hypoactivations in food motivation regions involved in the assessment of food’s reward value and integration of these with interoceptive signalling of one’s internal state of well-being, with important relations between brain activity and homeostatic and hedonic aspects of appetite. Our findings give novel evidence of disruption in neurobiological circuits and stress the importance of examining both state and trait characteristics in the investigation of brain phenotypes in individuals with anorexia nervosa.
Submitted Oct. 24, 2011; Revised Jan. 6, Feb. 6, 2012; Accepted Feb. 9, 2012.
Acknowledgements: L.M. Holsen and E.A. Lawson were funded by the Harvard K12 HD051959 Building Interdisciplinary Research Careers in Women’s Health Program supported by National Institutes of Health Office of Research in Women’s Health. The research was conducted with support from Harvard Catalyst | The Harvard Clin – ical and Translational Science Center (NIH Award #UL1 RR025758) and the Davis Foundation (P.K. Fazeli). We thank Daniel Donoho, Lauren Ogden and Tara Minaker for help in earlier phases of the study and David Herzog, MD, Kamryn Eddy, PhD, and Erinne Meenaghan, NP, for clinical assessment of the participants.
Competing interests: As above for L.M. Holsen, E.A. Lawson and P.K. Fazeli. None declared for J. Blum. E. Ko, N. Makris, A. Klibanski and J.M. Goldstein declare having received grant support from the National Institutes of Health through their respective insitutions.
Contributors: L.M. Holsen, E.A. Lawson, A. Klibanski and J.M. Goldstein designed the study. L.M. Holsen, E.A. Lawson, E. Ko and P.K. Fazeli acquired the data. L.M. Holsen, E.A. Lawson, J. Blum, E. Ko, N. Makris and J.M. Goldstein analyzed the data. L.M. Holsen and J.M. Goldstein wrote the article. E.A. Lawson, J. Blum, E. Ko, N.Makris, P.K. Fazeli, A. Klibanski and J.M. Goldstein reviewed the article. All authors approved its publication.
Correspondence to: L.M. Holsen, Division of Women’s Health, BC-3, 1620 Tremont St., Boston MA 02120; firstname.lastname@example.org