title: Abnormal relationships between the neural response to high- and low-calorie foods and endogenous acylated ghrelin in women with active and weight-recovered anorexia nervosa.
abstract: Evidence contributing to the understanding of neurobiological mechanisms underlying appetite dysregulation in anorexia nervosa draws heavily on separate lines of research into neuroendocrine and neural circuitry functioning. In particular, studies consistently cite elevated ghrelin and abnormal activation patterns in homeostatic (hypothalamus) and hedonic (striatum, amygdala, insula) regions governing appetite. The current preliminary study examined the interaction of these systems, based on research demonstrating associations between circulating ghrelin levels and activity in these regions in healthy individuals. In a cross-sectional design, we studied 13 women with active anorexia nervosa (AN), 9 women weight-recovered from AN (AN-WR), and 12 healthy-weight control women using a food cue functional magnetic resonance imaging paradigm, with assessment of fasting levels of acylated ghrelin. Healthy-weight control women exhibited significant positive associations between fasting acylated ghrelin and activity in the right amygdala, hippocampus, insula, and orbitofrontal cortex in response to high-calorie foods, associations which were absent in the AN and AN-WR groups. Women with AN-WR demonstrated a negative relationship between ghrelin and activity in the left hippocampus in response to high-calorie foods, while women with AN showed a positive association between ghrelin and activity in the right orbitofrontal cortex in response to low-calorie foods. Findings suggest a breakdown in the interaction between ghrelin signaling and neural activity in relation to reward responsivity in AN, a phenomenon that may be further characterized using pharmacogenetic studies.
authors.affiliation: Division of Women׳s Health, Department of Medicine, Boston, MA, USA; Department of Psychiatry, Brigham & Women׳s Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: lholsen@partners.org.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Holsen
authors.affiliation: Harvard Medical School, Boston, MA, USA; Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Lawson
authors.affiliation: Division of Women׳s Health, Department of Medicine, Boston, MA, USA.
authors.forename: Kara
authors.initials: K
authors.lastname: Christensen
authors.affiliation: Harvard Medical School, Boston, MA, USA; Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Klibanski
authors.affiliation: Division of Women׳s Health, Department of Medicine, Boston, MA, USA; Department of Psychiatry, Brigham & Women׳s Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Athinoula A. Martinos Center, Massachusetts General Hospital and Massachusetts Institute of Technology, Charlestown, MA, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Goldstein
mesh_terms: D000215:Acylation; D000328:Adult; D000679:Amygdala / Q000503:physiopathology; D000856:Anorexia Nervosa / Q000378:metabolism* / Q000503:physiopathology*; D001066:Appetite; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology*; D003342:Corpus Striatum / Q000503:physiopathology; D003430:Cross-Sectional Studies; D002149:Energy Intake; D005260:Female; D005518:Food Preferences; D054439:Ghrelin / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000503:physiopathology; D012201:Reward; D015398:Signal Transduction; D015430:Weight Gain; D055815:Young Adult
chemical_list: D054439:Ghrelin
keywords: Appetite; Eating disorders; Hormones; Reward; fMRI