Genomes and Genes
Appetite-regulating Hormones and Neurocircuitry in Anorexia Nervosa
Principal Investigator: ELIZABETH AUSTEN LAWSON
Abstract: DESCRIPTION (provided by applicant): Project Summary/Abstract This project takes a novel, multidisciplinary approach to understanding endocrine factors and neurocircuitry underlying appetite and eating behavior in anorexia nervosa (AN). AN, characterized by self-induced starvation, is associated with medical complications, depression, and the highest mortality of any psychiatric disease. Treatment strategies have been ineffective. Hormones involved in eating behavior are abnormal in AN, and brain regions in these pathways can now be examined with dynamic paradigms using functional MRI (fMRI). AN is also associated with testosterone (T) deficiency, and preliminary data indicates that physiologic replacement leads to an increase in body mass index (BMI). Studies in animals and humans implicate T in feeding behavior. Moreover, pilot data demonstrate hypoactivation by fMRI in brain regions implicated in T deficiency in response to a food-related paradigm, suggesting that T may influence eating behavior through direct effects on the brain, and has therapeutic potential in AN. The goal of this application is to investigate the hypothesis that the AN phenotype is characterized by abnormalities in hormones and neurocircuitry involved in food motivation and reward, and that T administration improves outcomes by modulating these pathways. 60 women with AN and 20 controls aged 20-30 will be studied. During a single visit, subjects will undergo measurement of BMI;a fasting blood draw for hormone levels (eg, ghrelin, PYY);assessment of appetite, mood and disordered eating psychopathology;and fMRI with visual food and non-food stimuli. After consumption of a standardized mixed meal, appetite and mood will be reassessed, serial blood samples will be obtained for hormone levels, and fMRI will be repeated. Of the 60 AN who participate in the cross-sectional visit, 40 AN with relative T deficiency will be randomized in a double-blind design to receive low-dose transdermal T (300mcg qd), and will return to repeat the above procedures at 4 weeks and 6 months. Dr. Lawson is an Instructor in Medicine at Harvard Medical School (HMS) and Assistant in Medicine at Massachusetts General Hospital (MGH). She is on staff in the Neuroendocrine Unit at MGH and devotes the majority of her time to clinical research. Her expertise in studying hormonal abnormalities in AN and established collaboration investigating the neurocircuitry of appetite positions her to lead the proposed project. She completed her Masters of Medical Science through HMS and Massachusetts Institute of Technology (MIT) in June, and plans to expand her training to include advanced statistics, neuroanatomy and neuroimaging technology. She is well-supported by MGH and has full access to Neuroendocrine Unit, Clinical Research Center and Harvard Catalyst resources. Her co-mentors, Drs. Anne Klibanski and Jill Goldstein, are well-funded and invested in the direction of Dr. Lawson's research. This project will support Dr. Lawson's training in clinical research, with the ultimate goal of becoming an independent investigator with an expertise in combining neuroendocrinology and neuroimaging technology to better understand pathophysiology of disease.
Funding Period: 2011-07-06 - 2016-06-30
more information: NIH RePORT
- Oxytocin secretion is associated with severity of disordered eating psychopathology and insular cortex hypoactivation in anorexia nervosaElizabeth A Lawson
Neuroendocrine Unit, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, USA
J Clin Endocrinol Metab 97:E1898-908. 2012..The relationships between oxytocin, food-motivation neurocircuitry, and disordered eating psychopathology have not been investigated in humans...
- Nocturnal oxytocin secretion is lower in amenorrheic athletes than nonathletes and associated with bone microarchitecture and finite element analysis parametersElizabeth A Lawson
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
Eur J Endocrinol 168:457-64. 2013..We therefore investigated oxytocin secretion and its association with bone microarchitecture and strength in young female athletes...
- Postprandial oxytocin secretion is associated with severity of anxiety and depressive symptoms in anorexia nervosaElizabeth A Lawson
Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA 02114, USA
J Clin Psychiatry 74:e451-7. 2013..A meal may represent a significant source of stress in patients with disordered eating. We therefore investigated the association between postprandial oxytocin secretion and symptoms of anxiety and depression in anorexia nervosa...
- Increased hypothalamic-pituitary-adrenal drive is associated with decreased appetite and hypoactivation of food-motivation neurocircuitry in anorexia nervosaElizabeth A Lawson
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Bulfinch 457 D, Boston, Massachusetts 02114, USA
Eur J Endocrinol 169:639-47. 2013..We investigated the relationship between HPA activity, appetite, and food-motivation neurocircuitry hypoactivation in AN...
- Oxytocin secretion is related to measures of energy homeostasis in young amenorrheic athletesElizabeth A Lawson
Neuroendocrine Unit E A L, K E A, M S, D A M, H C, M M, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, and Pediatric Endocrine Unit M M, Massachusetts General Hospital for Children and Harvard Medical School, Boston Massachusetts 02114 and Division of Sports Medicine K E A, Department of Orthopedics, Boston Children s Hospital and Harvard Medical School, Boston Massachusetts 02115
J Clin Endocrinol Metab 99:E881-5. 2014..Whether oxytocin is associated with measures of energy homeostasis in athletes is unknown...
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