Appetite-regulating Hormones and Neurocircuitry in Anorexia Nervosa

Summary

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

Top Publications

  1. pmc Oxytocin secretion is associated with severity of disordered eating psychopathology and insular cortex hypoactivation in anorexia nervosa
    Elizabeth 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
  2. pmc Nocturnal oxytocin secretion is lower in amenorrheic athletes than nonathletes and associated with bone microarchitecture and finite element analysis parameters
    Elizabeth 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
  3. pmc Postprandial oxytocin secretion is associated with severity of anxiety and depressive symptoms in anorexia nervosa
    Elizabeth A Lawson
    Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA 02114, USA
    J Clin Psychiatry 74:e451-7. 2013
  4. pmc Increased hypothalamic-pituitary-adrenal drive is associated with decreased appetite and hypoactivation of food-motivation neurocircuitry in anorexia nervosa
    Elizabeth 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
  5. pmc Oxytocin secretion is related to measures of energy homeostasis in young amenorrheic athletes
    Elizabeth 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

Research Grants

Detail Information

Publications5

  1. pmc Oxytocin secretion is associated with severity of disordered eating psychopathology and insular cortex hypoactivation in anorexia nervosa
    Elizabeth 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...
  2. pmc Nocturnal oxytocin secretion is lower in amenorrheic athletes than nonathletes and associated with bone microarchitecture and finite element analysis parameters
    Elizabeth 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...
  3. pmc Postprandial oxytocin secretion is associated with severity of anxiety and depressive symptoms in anorexia nervosa
    Elizabeth 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...
  4. pmc Increased hypothalamic-pituitary-adrenal drive is associated with decreased appetite and hypoactivation of food-motivation neurocircuitry in anorexia nervosa
    Elizabeth 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...
  5. pmc Oxytocin secretion is related to measures of energy homeostasis in young amenorrheic athletes
    Elizabeth 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...

Research Grants31

  1. Neural mechanisms underlying abnormal food reward processing in depressed women
    LAURA MCGRATH HOLSEN; Fiscal Year: 2013
    ....
  2. Hormonal Factors in the Treatment of Anorexia Nervosa
    Anne Klibanski; Fiscal Year: 2013
    ..We propose to investigate whether long-term testosterone replacement improves symptoms of anorexia nervosa. ..
  3. Comprehensive NeuroAIDS Core Center
    Kamel Khalili; Fiscal Year: 2013
    ..abstract_text> ..
  4. Reversing Corticosteroid-Induced Memory Impairment
    E Sherwood Brown; Fiscal Year: 2013
    ..The impact of lamotrigine on memory, mood, quality of life, structural imaging, and spectroscopy will be examined. ..
  5. IMPROVING THE EFFECTIVENESS OF OBESITY MANAGEMENT
    Thomas A Wadden; Fiscal Year: 2013
    ..The effects of BED will be examined, as will those of two different surgeries. ..
  6. Monoamine Contributions to Neurocircuitry in Eating Disorders
    Walter H Kaye; Fiscal Year: 2013
    ..This application will help to understand the unique puzzling symptoms in AN and BN and contribute to finding better methods for identifying effective medications in these often relapsing and sometimes chronic disorders. ..
  7. Neural Functioning of Feeding Centers in Obese Youth
    ROBERT STANLEY SHERWIN; Fiscal Year: 2013
    ....
  8. EARLY EVENTS IN ALZHEIMER PATHOGENESIS
    SUE TILTON GRIFFIN; Fiscal Year: 2013
    ..The synergy between our aims, approaches, and measures will enable us to meet our goal of defining early cellular interactions toward development of rational interventions in AD. ..
  9. Neurobiology of Anorexia and Bulimia Nervosa
    Walter H Kaye; Fiscal Year: 2013
    ..Understanding biologic vulnerabilities in AN and BN is critical for developing effective treatment interventions for these often chronic and deadly disorders. This if the first resubmission of competing renewal MH042984 ..
  10. Changes in neural response to eating after bariatric surgery: MRI results
    Thomas A Wadden; Fiscal Year: 2013
    ..In addition, we will serially measure postprandial changes in appetite-regulating hormones and examine the relationships between neural and endocrine response to food consumption. ..
  11. Hopkins Center for Eliminate Cardiovascular Health Disparities
    Lisa A Cooper; Fiscal Year: 2013
    ..abstract_text> ..
  12. The Role of PTH in the Low Bone Mass of Anorexia Nervosa
    POUNEH KHADEJEH FAZELI; Fiscal Year: 2013
    ....
  13. Reward System Responses to Food Aromas: Effects of Obesity and Alcohol Intake
    David A Kareken; Fiscal Year: 2013
    ..To accomplish these aims we will also use food aromas, which are particularly salient stimuli that convey a more immediate presence of reward than do food images. ..
  14. Neurocircuitry Underlying DBS Effects in OCD: A Window Into Mechanisms of Action
    Suzanne N Haber; Fiscal Year: 2013
    ..Results from these studies will also make important new contributions to our understanding of the basic mechanisms of DBS. ..