Hilâl Cerit1, Kara Christensen2, Priyanka Moondra2, Anne Klibanski3, Jill M Goldstein4, Laura M Holsen5. 1. Division of Women's Health, Department of Medicine, Brigham and Women's Hospital, BC-3 1620 Tremont Street, Boston, MA 02120, USA; Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. 2. Division of Women's Health, Department of Medicine, Brigham and Women's Hospital, BC-3 1620 Tremont Street, Boston, MA 02120, USA. 3. Harvard Medical School, Boston, MA, USA; Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. 4. Division of Women's Health, Department of Medicine, Brigham and Women's Hospital, BC-3 1620 Tremont Street, Boston, MA 02120, USA; Harvard Medical School, Boston, MA, USA; Division of Psychiatric Neuroscience, Athinoula A. Martinos Center, Boston, MA, USA; Departments of Psychiatry, Obstetrics and Gynecology, Neurology, and Medicine - Cardiology, Massachusetts General Hospital, Boston, MA, USA. 5. Division of Women's Health, Department of Medicine, Brigham and Women's Hospital, BC-3 1620 Tremont Street, Boston, MA 02120, USA; Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: lholsen@bwh.harvard.edu.
Abstract
BACKGROUND: The neurobiological mechanisms involved in divergent appetitive phenotypes in major depressive disorder (MDD) are not well understood, although recent data suggest disruption in mesolimbic reward circuitry. Ghrelin, an orexigenic hormone, has been shown to modulate the reward circuitry. We aimed to investigate the relationship between acylated ghrelin levels and the neural response to food stimuli in individuals with hyperphagic and hypophagic MDD in remission. METHODS: Women with hyperphagic MDD (n = 10), hypophagic MDD (n = 18), and healthy controls (HC; n = 18) underwent fMRI scanning during which they viewed images of food. The fMRI session was followed by a standardized meal, appetite ratings, and serial blood draws. RESULTS: In individuals with hyperphagic MDD, greater change in acylated ghrelin in response to a meal was associated with increased BOLD response to high-calorie food in the bilateral ventral tegmental area and left hypothalamus. In contrast, negative associations were observed between acylated ghrelin AUC and BOLD activity in the right hypothalamus in the hypophagic MDD group. LIMITATIONS: Unbalanced group sizes with a relatively small sample in the hyperphagic MDD group. CONCLUSIONS: In the absence of differences in absolute ghrelin levels between the hyperphagic MDD and HC groups, results in hyperphagic MDD might suggest a ghrelinergic signaling mechanism for increased appetite during an MDD episode in this group. Our findings shed light on interactions between appetite hormones and mesolimbic circuitry which could contribute to development of therapeutic targets for opposing appetite phenotypes in depression.
BACKGROUND: The neurobiological mechanisms involved in divergent appetitive phenotypes in major depressive disorder (MDD) are not well understood, although recent data suggest disruption in mesolimbic reward circuitry. Ghrelin, an orexigenic hormone, has been shown to modulate the reward circuitry. We aimed to investigate the relationship between acylated ghrelin levels and the neural response to food stimuli in individuals with hyperphagic and hypophagic MDD in remission. METHODS:Women with hyperphagic MDD (n = 10), hypophagic MDD (n = 18), and healthy controls (HC; n = 18) underwent fMRI scanning during which they viewed images of food. The fMRI session was followed by a standardized meal, appetite ratings, and serial blood draws. RESULTS: In individuals with hyperphagic MDD, greater change in acylated ghrelin in response to a meal was associated with increased BOLD response to high-calorie food in the bilateral ventral tegmental area and left hypothalamus. In contrast, negative associations were observed between acylated ghrelin AUC and BOLD activity in the right hypothalamus in the hypophagic MDD group. LIMITATIONS: Unbalanced group sizes with a relatively small sample in the hyperphagic MDD group. CONCLUSIONS: In the absence of differences in absolute ghrelin levels between the hyperphagic MDD and HC groups, results in hyperphagic MDD might suggest a ghrelinergic signaling mechanism for increased appetite during an MDD episode in this group. Our findings shed light on interactions between appetite hormones and mesolimbic circuitry which could contribute to development of therapeutic targets for opposing appetite phenotypes in depression.
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