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Ida Nilsson Team

The neurobiology of anorexia nervosa

About

Anorexia nervosa (AN) has the highest mortality rate of all psychiatric disorders. Chronicity and relapse rates are at present unacceptably high, underscoring the need for improved treatments. A puzzling part of the disorder is the paradoxical response to negative energy balance, leading to continued loss of body weight and consequent low energy stores. Under normal circumstances, upon losing weight, hormones and other signals from adipose tissue and gut instruct the brain to activate neuronal circuits to increase appetite and reduce energy expenditure, thus restoring energy stores and ensuring survival. Despite the development of these intricate systems of energy homeostasis, individuals with AN reside in a state of persistent severe starvation, emaciation, and negative energy balance. Recent genetic data support a biologically underpinned lower body weight set point in individuals with or at risk of AN. The energy homeostatic mechanisms are centered in the hypothalamus, especially in the Arc neurons. The overarching hypothesis of the work in our team is that the Arc neurons are untuned in AN, in particular the communication with the surrounding microglia, and that this explains the continued starvation and low body weight in this patient group. We explore this hypothesis by studying preclinical models, clinical samples and patient-derived stem cell models. By defining the molecular mechanisms of food intake and weight regulation in the anorectic state, we hope to identify targets for drug development aiming for sustainable renourishment and weight gain, which are crucial in the initial critical phase of treatment and for long-term recovery.

Team Leader

Ida AK Nilsson

Education and positions:

2021 Associate Professor in Neuroscience, KI

2016-2022 Assistant Professor, MMK, KI

2012-2016 Postdoctoral position, MMK, KI

2011-2012 Postdoctoral position supported by Swedish Brain Foundation, at INSERM, Lille (FR) and MMK, KI

2010 PhD in Medical Science, MMK, KI

2004 Master in Nutrition, Stockholm University

Team members

Jingjing Xu, PhD student, jingjing.xu@ki.se

Wilma Brogren, Master student, wilma.brogren@hotmail.com

Barbara Eramo, visiting PhD student, barbara.eramo@uniroma1.it

Alumni

Ulrika Bergström

Charlotte Lindfors

Chiara Camoglio

Judit Ozsvar

Elizabeta Zaplatic

Vincent Millischer

Consortia and networks

Psychiatric Genomics Consortium Eating Disorders (PGC-ED)

Funding

Swedish Brain Foundation, Stockholm County Council, Sten & Birgitta Westerberg

Prizes and awards

NARSAD Young Investigator 2013 & 2014

PhD theses from the lab

Molecular studies of hypothalamic food intake regulating systems and central myelination in two anorectic mouse models. Ulrika Bergström, 2016.

Appetite control – genetic, immunological and neurobiological aspects. Charlotte Lindfors, 2017.

Selected publications

Plasma concentrations of short-chain fatty acids in active and recovered anorexia nervosa. Xu J, Landberg R, Lavebratt C, Bulik CM, Landén M, Nilsson IAK. Nutrients, 2022 Dec 9;14(24):5247.

Exploring the mechanisms of recovery in anorexia nervosa through a translational approach: from original ecological measurements in human to brain tissue analyses in mouse. Duriez P, Nilsson IAK, Le Thuc O, Alexandre D, Chartrel N, Rovere C, Chauveau C, Gorwood P, Tolle V, Viltart O. Nutrients, 2021 Aug 13;13(8):2786.

Functional aspects of GRK3 deficiency in brain immune activation and psychosis. Sellgren CM, Imbeault S, Larsson MK, Oliveros A, Nilsson IAK, Gracias J, Codeluppi S, Bhat M, Tufvesson-Alm M, Orhan F, Kegel ME, Faka A, Svedberg M, Powell SB, Caldwell S, Kamenski ME, Goiny M, Svensson CI, Schalling M, Hökfelt T, Schwieler L, Cervenka S, Choi D, Landén M, Engberg G, Erhardt S. Mol Psych, 2021 Nov;26(11):6820-6832.

Serum profiling of anorexia nervosa: a 1H NMR-based metabolomics study. Salehi AM, Nilsson IAK, Figueira J, Juréus A, Thornton LM, Abdulkarim I, Pålsson E, Bulik CM, Landén M. Eur J Neuropsychopharmacology, 2021 Aug:49:1-10.

Aberrant inflammatory profile in acute but not recovered anorexia nervosa. Nilsson IAK, Millischer V, Göteson A, Hübel C, Thornton LM, Bulik CM, Schalling M, Landén M. Brain, Behavior and Immunity, 2020 Aug:88:718-724.

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

Associations of different types of maternal diabetes and body mass index with offspring psychiatric disorders. Kong L, Nilsson IAK, Brismar K, Gissler M, Lavebratt C. JAMA Network Open. 2020 Feb 5;3(2):e1920787.

Hypothalamic structural and functional imbalances in anorexia nervosa. 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. Neuroendocrinology 2020 110(6):552-562.

Plasma neurofilament light chain concentration is increased in anorexia nervosa. 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. Transl Psych. 2019 Aug 1;9(1):180.

Effects of maternal diabetes and body mass index on offspring birth weight and prematurity.  Kong L, Nilsson IAK, Gissler M, Lavebratt C. JAMA Pediatrics. 2019 Apr 1;173(4):371-378.

Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa.  Duncan L, Yilmaz Z, Walters R, Goldstein J, Antilla V, Bulik-Sullivan B, Ripke S, Adan R….. Nilsson IAK,…. Thornton L, Hinney A, Daly M, Sullivan P, Zeggini E, Breen G, Bulik C. Genome-Wide. Am J Psychiatry. 2017 Sep 1;174(9):850-858.

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

Glucose intolerance and pancreatic β-cell dysfunction in the anorectic anx/anx mouse. Lindfors C, Katz A, Selander L, Johansen JE, Marconi G, Schalling M, Hökfelt T, Berggren PO, Zaitsev S, Nilsson IAK. Am J Physiol Endocrinol Metab. 2015 Aug 15;309(4):E418-27.

Hypothalamic mitochondrial dysfunction associated with anorexia. Lindfors C#, Nilsson IAK#, Garcia-Roves PM, Zuberi AR, Karimi M, Donahue LR, Roopenian DC, Mulder J, Uhlén M, Ekström T, Davisson MT, Hökfelt T, Schalling M, Johansen JE. PNAS, 2011; 108:18108-13. #shared first author

About CMM

The Center for Molecular Medicine (CMM) is a foundation instituted by the Stockholm County Council (Region Stockholm). CMM is at the heart of a close partnership with the Karolinska University Hospital and Karolinska Institutet, fueling advancements in biomedical and clinical research.

Contact

Center for Molecular Medicine Foundation, org. nr. 815201-3689

Karolinska University Hospital L8:05

Visionsgatan 18

171 76 Stockholm, Sweden

communication@cmm.se

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