Eating disorders

IDA NILSSON TEAM

Research

The research of our team is focused on the eating disorders anorexia nervosa (AN). AN is a severe psychiatric disorder characterized by restriction of energy intake leading to a significantly low body weight, an intense fear of weight gain, and a distorted experience of one’s own body weight or shape. The course of AN can be prolonged and may lead to enduring disability, in particular for the individuals with the often called severe and enduring AN. With a 10% mortality, AN is among the most lethal of all psychiatric disorders. Unfortunately, there is still no evidence-based pharmacological treatment for AN, and the optimal treatment, psychological as well as pharmaceutical, is debated. 

One central and unexplained feature of AN is the paradoxical response to negative energy balance. While most people cannot lose a few kilos, these individuals stay in an emaciated and starved condition commonly for many years. Even after therapeutic renourishment, their bodies commonly revert to what appears to be a negative set point, i.e. the inverse of happens for obese individuals. AN genome-wide association studies have yielded significant negative single-nucleotide-based genetic correlations with BMI and other anthropometric measures, which seems to indicate a genetic predisposition for a lower body weight set point in AN. However, we do not understand the (neuro)biological underpinnings of such a set point nor the mechanisms explaining the contradictory response to underweight in AN. 

The overall goal of our group is to understand the molecular mechanisms involved in food intake in general, and in the elective starvation of AN in particular. Our main hypothesis involves dysregulated hypothalamic circuits. Upon defining the neurobiological mechanisms and molecular players involved in the paradoxical response to underweight in AN, will we be able to find new pharmacological targets, as well as vulnerability markers. Pharmacological therapy, preventing the continued starvation and the loss of weight after recovery, could be combined with the today most commonly used treatment for AN; psycho- and nutritional therapy. Finally, extending the understanding of the neurobiology of AN will reduce the stigma surrounding AN, thus promoting early treatment and reduced mortality.

 

Selected publications

Nilsson IAK, Millischer V, Göteson A, Hübel C, Thornton LM, Bulik CM, Schalling M, Landén. Aberrant inflammatory profile in acute but not recovered anorexia nervosa. Brain Behav Immun. 2020 May 7: S0889-1591(20)30253-1. doi: 10.1016/j.bbi.2020.05.024. Online ahead of print.

D'Addario C, Zaplatic E, Giunti E, Pucci M, Micioni Di Bonaventura MV, Scherma M, Dainese E, Maccarone M, Nilsson IA, Cifani C, Fadda P. Epigenetic regulation of the cannabinoid receptor CB1 in an activity-based rat model of anorexia nervosa. Int J Eat Disord. 2020 May;53(5):432-446.

Kong L, Nilsson IAK, Brismar K, Gissler M, Lavebratt C. Associations of different types of maternal diabetes and body mass index with offspring psychiatric disorders. JAMA Network Open. 2020 Feb 5. 

V Florent, M Baroncini, P Jissendi-Tchofo, R Lopes, M Vanhoutte, S. Rasika, J-P Pruvo, J Vignau, J E Johansen, M Pigeyre, S G Bouret, I AK Nilsson#, Vincent Prevot#. Hypothalamic structural and functional imbalances in anorexia nervosa. Neuroendocrinology. 2019 Sep 5. #directed the work together

Nilsson IAK, Millischer V, Danylaité Karrenbauer V, Jureus A, Salehi A, Norring C, von Hausswolff-Juhlin Y, Schalling M, Blennow K, Bulik CM, Zetterberg H, Landén M. Plasma neurofilament light chain concentration is increased in anorexia nervosa. Transl Psych. 2019 Aug 1.

Kong L, Nilsson IAK, Gissler M, Lavebratt C. Associations of Maternal Diabetes and Body Mass Index With Offspring Birth Weight and Prematurity. JAMA Pediatrics. 2019 February 25.

Nilsson IAK. The anx/anx mouse – a valuable resource in anorexia nervosa research. Frontiers in Neuroscience. 2019 Feb 5.

Schaumberg K, Welch E, Breithaupt L, Hübel C, Baker JH, Munn-Chernoff MA, Yilmaz Z, Ehrlich S, Mustelin L, Ghaderi A, Hardaway AJ, Bulik-Sullivan EC, Hedman AM, Jangmo A, Nilsson IAK, Wiklund C, Yao S, Seidel M, Bulik CM. The Science Behind the Academy for Eating Disorders' Nine Truths About Eating Disorders. Eur Eat Disord Rev. 2017 Nov;25(6):432-450. 

Bergström U, Lindfors C, Svedberg M, Johansen JE, Häggkvist J, Schalling M, Wibom R, Katz A, Nilsson IAK. Reduced metabolism in the hypothalamus of the anorectic anx/anx mouse. J Endocrinol. 2017 Apr;233(1):15-24. 

Charlotte Lindfors, Abram Katz, Lars Selander, Jeanette E Johansen, Giulia Marconi, Martin Schalling, Tomas Hökfelt, Per-Olof Berggren, Sergei Zaitsev, Ida AK Nilsson. Glucose intolerance and pancreatic β-cell dysfunction in the anorectic anx/anx mouse. American Journal of Physiology – Endocrinology and Metabolism. Am J Physiol Endocrinol Metab. 2015 Aug 15;309(4):E418-27.

Ida AK Nilsson, Charlotte Lindfors, Tomas Hökfelt, Martin Schalling, Jeanette E Johansen. Anorexia and hypothalamic degeneration. Anorexia, Vol 92, VH, UK: Academic Press, Elsevier, New York, 2013, pp. 27-60. (Invited author)

Lindfors C, Nilsson IA, Garcia-Roves PM, Zuberi AR, Karimi M, Donahue LR, Roopenian DC, Mulder J, Uhlén M, Ekström TJ, Davisson MT, Hökfelt TG, Schalling M, Johansen JE. Hypothalamic mitochondrial dysfunction associated with anorexia in the anx/anx mouse. Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):18108-13.

Nilsson IA, Thams S, Lindfors C, Bergstrand A, Cullheim S, Hökfelt T, Johansen JE. Evidence of hypothalamic degeneration in the anorectic anx/anx mouse. Glia. 2011 Jan;59(1):45-57.

Hökfelt T, Stanic D, Sanford SD, Gatlin JC, Nilsson I, Paratcha G, Ledda F, Fetissov S, Lindfors C, Herzog H, Johansen JE, Ubink R, Pfenninger KH. NPY and its involvement in axon guidance, neurogenesis, and feeding. Nutrition. 2008 Sep;24(9):860-8.

Nilsson I, Lindfors C, Fetissov SO, Hökfelt T, Johansen JE. Aberrant agouti-related protein system in the hypothalamus of the anx/anx mouse is associated with activation of microglia. J Comp Neurol. 2008 Mar 1;507(1):1128-40.

Johansen JE, Fetissov SO, Bergström U, Nilsson I, Faÿ C, Ranscht B, Hökfelt T, Schalling M. Evidence for hypothalamic dysregulation in mouse models of anorexia as well as in humans. Physiol Behav. 2007 Sep 10;92(1-2):278-82. 

Nilsson I, Johansen JE, Schalling M, Hökfelt T, Fetissov SO. Maturation of the hypothalamic arcuate agouti-related protein system during postnatal development in the mouse. Brain Res Dev Brain Res. 2005 Mar 31;155(2):147-54.