Genetic contributions to the etiology of anorexia nervosa: New perspectives in molecular diagnosis and treatment

Stefano Paolacci, Aysha Karim Kiani, Elena Manara, Tommaso Beccari, Maria Rachele Ceccarini, Liborio Stuppia, Pietro Chiurazzi, Laura Dalla Ragione, Matteo Bertelli, Stefano Paolacci, Aysha Karim Kiani, Elena Manara, Tommaso Beccari, Maria Rachele Ceccarini, Liborio Stuppia, Pietro Chiurazzi, Laura Dalla Ragione, Matteo Bertelli

Abstract

Background: Anorexia nervosa is a multifactorial eating disorder that manifests with self-starvation, extreme anxiety, hyperactivity, and amenorrhea. Long-term effects include organ failure, disability, and in extreme cases, even death.

Methods: Through a literature search, here we summarize what is known about the molecular etiology of anorexia nervosa and propose genetic testing for this condition.

Results: Anorexia nervosa often has a familial background and shows strong heritability. Various genetic studies along with genome-wide association studies have identified several genetic loci involved in molecular pathways that might lead to anorexia.

Conclusion: Anorexia nervosa is an eating disorder with a strong genetic component that contributes to its etiology. Various genetic approaches might help in the molecular diagnosis of this disease and in devising novel therapeutic options.

Keywords: Anorexia nervosa; Genetic test; Genetic variant.

Conflict of interest statement

The authors declare that there is no conflict of interest regarding the publication of this paper.

© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

References

    1. Abdalla, M. M. I. (2017). Central and peripheral control of food intake. Endocrine Regulations, 51(1), 52–70. 10.1515/enr-2017-0006
    1. Anand, B. , & Brobeck, J. (1951). Hypothalamic control of food intake in rats and cats. The Yale Journal of Biology and Medicine, 24(2), 123–140.
    1. Andries, A. , & Støving, R. K. (2011). Cannabinoid‐1 receptor agonists: A therapeutic option in severe, chronic anorexia nervosa? Neuropsychiatry, 1(5), 467–476. 10.2217/npy.11.50
    1. Arcelus, J. , Mitchell, A. J. , Wales, J. , & Nielsen, S. (2011). Mortality rates in patients with anorexia nervosa and other eating disorders: A meta‐analysis of 36 studies. Archives of General Psychiatry, 68(7), 724–731. 10.1001/archgenpsychiatry.2011.74
    1. Babbs, R. K. , Beierle, J. A. , Ruan, Q. T. , Kelliher, J. C. , Chen, M. M. , Feng, A. X. , … Bryant, C. D. (2019). CyFIP1 haploinsufficiency increases compulsive‐like behavior and modulates palatable food intake in mice: Dependence on CYFIP2 genetic background, parent‐of origin, and sex. G3: Genes, Genomes . Genetics, 9(9), 3009–3022. 10.1534/g3.119.400470
    1. Beck, B. (2006). Neuropeptide Y in normal eating and in genetic and dietary‐induced obesity. Philosophical Transactions of the Royal Society B: Biological Sciences, 361(1471), 1159–1185. 10.1098/rstb.2006.1855
    1. Bello, V. , Moreau, N. , Sirour, C. , Hidalgo, M. , Buisson, N. , & Darribère, T. (2015). The dystroglycan: Nestled in an adhesome during embryonic development. Developmental Biology, 401(1), 132–142. 10.1016/j.ydbio.2014.07.006
    1. Bergen, A. W. , van den Bree, M. B. M. , Yeager, M. , Welch, R. , Ganjei, J. K. , Haque, K. , … Kaye, W. H. (2003). Candidate genes for anorexia nervosa in the 1p33‐36 linkage region: Serotonin 1D and delta opioid receptor loci exhibit significant association to anorexia nervosa. Molecular Psychiatry, 8(4), 397–406. 10.1038/sj.mp.4001318
    1. Bergen, A. W. , Yeager, M. , Welch, R. A. , Haque, K. , Ganjei, J. K. , van den Bree, M. B. M. , … Kaye, W. H. (2005). Association of multiple DRD2 polymorphisms with anorexia nervosa. Neuropsychopharmacology, 30(9), 1703–1710. 10.1038/sj.npp.1300719
    1. Berry, E. M. , & Mechoulam, R. (2002). Tetrahydrocannabinol and endocannabinoids in feeding and appetite. Pharmacology and Therapeutics, 95(2), 185–190. 10.1016/S0163-7258(02)00257-7
    1. Bienvenu, T. , Lebrun, N. , Clarke, J. , Duriez, P. , Gorwood, P. , & Ramoz, N. (2019a). De novo deleterious variants that may alter the dopaminergic reward pathway are associated with anorexia nervosa. Eating and Weight Disorders, 1–8, 10.1007/s40519-019-00802-9
    1. Bienvenu, T. , Lebrun, N. , Clarke, J. , Duriez, P. , Gorwood, P. , & Ramoz, N. (2019b). Exome sequencing in a familial form of anorexia nervosa supports multigenic etiology. Journal of Neural Transmission, 126(11), 1505–1511. 10.1007/s00702-019-02056-2
    1. Brown, K. M. O. , Bujac, S. R. , Mann, E. T. , Campbell, D. A. , Stubbins, M. J. , & Blundell, J. E. (2007). Further evidence of association of OPRD1 & HTR1D polymorphisms with susceptibility to anorexia nervosa. Biological Psychiatry, 61(3), 367–373. 10.1016/j.biopsych.2006.04.007
    1. Ceccarini, M. , Tasegian, A. , Franzago, M. , Patria, F. , Albi, E. , Codini, M. , … Beccari, T. (2019). 5‐HT2AR and BDNF gene variants in eating disorders susceptibility. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 10.1002/ajmg.b.32771
    1. Chang, X. , Qu, H. , Liu, Y. , Glessner, J. , Hou, C. , Wang, F. , … Hakonarson, H. (2019). Microduplications at the 15q11.2 BP1–BP2 locus are enriched in patients with anorexia nervosa. Journal of Psychiatric Research, 113, 34–38. 10.1016/j.jpsychires.2019.01.021
    1. Chao, J. , & Nestler, E. J. (2004). Molecular neurobiology of drug addiction. Annual Review of Medicine, 55, 113–132. 10.1146/annurev.med.55.091902.103730
    1. Chen, J. , Kang, Q. , Jiang, W. , Fan, J. , Zhang, M. , Yu, S. , & Zhang, C. (2015). The 5‐HTTLPR confers susceptibility to anorexia nervosa in Han Chinese: Evidence from a case‐control and family‐based study. PLoS ONE, 10(3), e0119378 10.1371/journal.pone.0119378
    1. Clarke, T. K. , Weiss, A. R. D. , & Berrettini, W. H. (2012). The genetics of anorexia nervosa. Clinical Pharmacology and Therapeutics, 91(2), 181–188. 10.1038/clpt.2011.253
    1. Compan, V. (2017). Serotonin 4 receptors: A cornerstone in anorexia nervosa? Autism‐Open Access, 17(2), 1–6. 10.4172/2165-7890.1000207
    1. Costa, B. , Comelli, F. , Bettoni, I. , Colleoni, M. , & Giagnoni, G. (2008). The endogenous fatty acid amide, palmitoylethanolamide, has anti‐allodynic and anti‐hyperalgesic effects in a murine model of neuropathic pain: Involvement of CB1, TRPV1 and PPARγ receptors and neurotrophic factors. Pain, 139(3), 541–550. 10.1016/j.pain.2008.06.003
    1. Cui, H. , Moore, J. , Ashimi, S. S. , Mason, B. L. , Drawbridge, J. N. , Han, S. , … Lutter, M. (2013). Eating disorder predisposition is associated with ESRRA and HDAC4 mutations. Journal of Clinical Investigation, 123(11), 4706–4713. 10.1172/JCI71400
    1. Cummings, D. E. , & Overduin, J. (2007). Gastrointestinal regulation of food intake. Journal of Clinical Investigation, 117(1), 13–23. 10.1172/JCI30227
    1. Curtis, D. , Adlington, K. , & Bhui, K. S. (2019). Pursuing parity: Genetic tests for psychiatric conditions in the UK National Health Service. British Journal of Psychiatry, 214(5), 248–250. 10.1192/bjp.2019.48
    1. Czyzyk, T. A. , Romero‐Picó, A. , Pintar, J. , McKinzie, J. H. , Tschöp, M. H. , Statnick, M. A. , & Nogueiras, R. (2012). Mice lacking δ‐opioid receptors resist the development of diet‐induced obesity. FASEB Journal, 26(8), 3483–3492. 10.1096/fj.12-208041
    1. Dardennes, R. M. , Zizzari, P. , Tolle, V. , Foulon, C. , Kipman, A. , Romo, L. , … Epelbaum, J. (2007). Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with anorexia nervosa: Association with subtype, body‐mass index, severity and age of onset. Psychoneuroendocrinology, 32(2), 106–113. 10.1016/j.psyneuen.2006.11.003
    1. De Silva, A. , & Bloom, S. R. (2012). Gut hormones and appetite control: A focus on PYY and GLP‐1 as therapeutic targets in obesity. Gut and Liver, 6(1), 10–20. 10.5009/gnl.2012.6.1.10
    1. Devlin, B. , Jones, B. L. , Bacanu, S. A. , & Roeder, K. (2002). Mixture models for linkage analysis of affected sibling pairs and covariates. Genetic Epidemiology, 22(1), 52–65. 10.1002/gepi.1043
    1. Diez‐Fernandez, C. , Rüfenacht, V. , Gemperle, C. , Fingerhut, R. , & Häberle, J. (2018). Mutations and common variants in the human arginase 1 (ARG1) gene: Impact on patients, diagnostics, and protein structure considerations. Human Mutation, 39(8), 1029–1050. 10.1002/humu.23545
    1. Di Guida, F. (2017). Pharmacological effects of palmitoylethanolamide on hypertension, insulin‐resistance and obesity in murine models. 10.6093/UNINA/FEDOA/11611.
    1. Dincheva, I. , Drysdale, A. T. , Hartley, C. A. , Johnson, D. C. , Jing, D. , King, E. C. , … Lee, F. S. (2015). FAAH genetic variation enhances fronto‐amygdala function in mouse and human. Nature Communications, 6, 6395 10.1038/ncomms7395
    1. Doris, J. M. , Millar, S. A. , Idris, I. , & O’Sullivan, S. E. (2019). Genetic polymorphisms of the endocannabinoid system in obesity and diabetes. Diabetes, Obesity and Metabolism, 21(2), 382–387. 10.1111/dom.13504
    1. Fujimoto, K. , Sakata, T. , Ishimaru, T. , Etou, H. , Ookuma, K. , Kurokawa, M. , & Machidori, H. (1989). Attenuation of anorexia induced by heat or surgery during sustained administration of ginsenoside Rg1 into rat third ventricle. Psychopharmacology (Berl), 99(2), 257–260. 10.1007/BF00442819
    1. Garcion, E. , Do Thanh, X. , Bled, F. , Teissier, E. , Dehouck, M. P. , Rigault, F. , … Darcy, F. (1996). 1,25‐dihydroxyvitamin D3 regulates γ‐glutamyl transpeptidase activity in rat brain. Neuroscience Letters, 216(3), 183–186. 10.1016/0304-3940(96)87802-5
    1. Genis‐Mendoza, A. D. , Ruiz‐Ramos, D. , López‐Narvaez, M. L. , Tovilla‐Zárate, C. A. , Rosa García, A. , Cortes Meda, G. , … Nicolini, H. (2019). Genetic association analysis of 5‐HTR2A gene variants in eating disorders in a Mexican population. Brain and Behavior, 9(7), e01286 10.1002/brb3.1286
    1. Georgescu, D. , Sears, R. M. , Hommel, J. D. , Barrot, M. , Bolaños, C. A. , Marsh, D. J. , … DiLeone, R. J. (2005). The hypothalamic neuropeptide melanin‐concentrating hormone acts in the nucleus accumbens to modulate feeding behavior and forced‐swim performance. Journal of Neuroscience, 25(11), 2933–2940. 10.1523/JNEUROSCI.1714-04.2005
    1. Giollo, A. , Idolazzi, L. , Caimmi, C. , Fassio, A. , Bertoldo, F. , Dalle Grave, R. , … Gatti, D. (2017). Vitamin D levels strongly influence bone mineral density and bone turnover markers during weight gain in female patients with anorexia nervosa. International Journal of Eating Disorders, 50(9), 1041–1049. 10.1002/eat.22731
    1. Goodfellow, C. E. , & Glass, M. (2009). Anandamide receptor signal transduction. Vitamins and Hormones, 81, 79–110. 10.1016/S0083-6729(09)81004-2
    1. Gratacòs, M. , González, J. R. , Mercader, J. M. , de Cid, R. , Urretavizcaya, M. , & Estivill, X. (2007). Brain‐derived neurotrophic factor Val66Met and psychiatric disorders: Meta‐analysis of case‐control studies confirm association to substance‐related disorders, eating disorders, and schizophrenia. Biological Psychiatry, 61(7), 911–922. 10.1016/j.biopsych.2006.08.025
    1. Grice, D. E. , Halmi, K. A. , Fichter, M. M. , Strober, M. , Woodside, D. B. , Treasure, J. T. , … Berrettini, W. H. (2002). Evidence for a susceptibility gene for anorexia nervosa on chromosome 1. American Journal of Human Genetics, 70(3), 787–792. 10.1086/339250
    1. Groves, N. J. , McGrath, J. J. , & Burne, T. H. J. (2014). Vitamin D as a neurosteroid affecting the developing and adult brain. Annual Review of Nutrition, 34, 117–141. 10.1146/annurev-nutr-071813-105557
    1. Haan, J. , Kors, E. E. , & Ferrari, M. D. (2002). Familial cyclic vomiting syndrome. Cephalalgia, 22(7), 552–554. 10.1046/j.1468-2982.2002.00420.x
    1. Haleem, D. J. (2017). Improving therapeutics in anorexia nervosa with tryptophan. Life Sciences, 178, 87–93. 10.1016/j.lfs.2017.04.015
    1. Hansen, H. S. , Kleberg, K. , & Hassing, H. A. (2015). Non‐endocannabinoid N‐acylethanolamines and monoacylglycerols: old molecules new targets. In The Endocannabinoidome: The World of Endocannabinoids and Related Mediators (pp. 1–13). 10.1016/B978-0-12-420126-2.00001-8.
    1. Hao, S. , Avraham, Y. , Mechoulam, R. , & Berry, E. M. (2000). Low dose anandamide affects food intake, cognitive function, neurotransmitter and corticosterone levels in diet‐restricted mice. European Journal of Pharmacology, 392(3), 147–156. 10.1016/S0014-2999(00)00059-5
    1. Hasan, T. F. , & Hunaid, H. (2011). Anorexia nervosa: A unified neurological perspective. International Journal of Medical Sciences, 8(8), 679–703. 10.7150/ijms.8.679
    1. Hong, S.‐H. , Lee, J.‐E. , An, S.‐M. , Shin, Y. Y. , Hwang, D. Y. , Yang, S. Y. , … An, B.‐S. (2017). Effect of vitamin D3 on biosynthesis of estrogen in porcine granulosa cells via modulation of steroidogenic enzymes. Toxicological Research, 33(1), 49–54. 10.5487/TR.2017.33.1.049
    1. Ibi, M. , Sawada, H. , Nakanishi, M. , Kume, T. , Katsuki, H. , Kaneko, S. , … Akaike, A. (2001). Protective effects of 1α,25‐(OH)2D3 against the neurotoxicity of glutamate and reactive oxygen species in mesencephalic culture. Neuropharmacology, 40(6), 761–771. 10.1016/S0028-3908(01)00009-0
    1. Ishiguro, H. , Onaivi, E. S. , Horiuchi, Y. , Imai, K. , Komaki, G. , Ishikawa, T. , … Arinami, T. (2011). Functional polymorphism in the GPR55 gene is associated with anorexia nervosa. Synapse (New York, N. Y.), 65(2), 103–108. 10.1002/syn.20821
    1. Jean, A. , Laurent, L. , Bockaert, J. , Charnay, Y. , Dusticier, N. , Nieoullon, A. , … Compan, V. (2012). The nucleus accumbens 5‐HTR4‐CART pathway ties anorexia to hyperactivity. Translational Psychiatry, 2, e203 10.1038/tp.2012.131
    1. Kalueff, A. V. , Lou, Y. R. , Laaksi, I. , & Tuohimaa, P. (2004). Increased anxiety in mice lacking vitamin D receptor gene. NeuroReport, 15(8), 1271–1274. 10.1097/01.wnr.0000129370.04248.92
    1. Kaye, W. H. , Ebert, M. H. , Gwirtsman, H. E. , & Weiss, S. R. (1984). Differences in brain serotonergic metabolism between nonbulimic and bulimic patients with anorexia nervosa. American Journal of Psychiatry, 141(12), 1598–1601. 10.1176/ajp.141.12.1598
    1. Kim, K. H. , Lee, D. , Lee, H. L. , Kim, C. E. , Jung, K. , & Kang, K. S. (2018). Beneficial effects of Panax ginseng for the treatment and prevention of neurodegenerative diseases: Past findings and future directions. Journal of Ginseng Research, 42(3), 239–247. 10.1016/j.jgr.2017.03.011
    1. Klenotich, S. J. , Ho, E. V. , McMurray, M. S. , Server, C. H. , & Dulawa, S. C. (2015). Dopamine D 2/3 receptor antagonism reduces activity‐based anorexia. Translational Psychiatry, 5, e613 10.1038/tp.2015.109
    1. Klump, K. L. , Miller, K. B. , Keel, P. K. , McGue, M. , & Iacono, W. G. (2001). Genetic and environmental influences on anorexia nervosa syndromes in a population‐based twin sample. Psychological Medicine, 31(4), 737–740. 10.1017/S0033291701003725
    1. Korsching, S. , Auburger, G. , Heumann, R. , Scott, J. , & Thoenen, H. (1985). Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation. The EMBO Journal, 4(6), 1389–1393. 10.1002/j.1460-2075.1985.tb03791.x
    1. Kortegaard, L. S. , Hoerder, K. , Joergensen, J. , Gillberg, C. , & Kyvik, K. O. (2001). A preliminary population‐based twin study of self‐reported eating disorder. Psychological Medicine, 31(2), 361–365. 10.1017/S0033291701003087
    1. L’Huillier, C. , Jarbeau, M. , Achamrah, N. , Belmonte, L. , Amamou, A. , Nobis, S. , … Coëffier, M. (2019). Glutamine, but not branched‐chain amino acids, restores intestinal barrier function during activity‐based anorexia. Nutrients, 11(6), 1348 10.3390/nu11061348
    1. Leibowitz, S. F. (1990). The role of serotonin in eating disorders. Drugs, 39(Suppl 3), 33–48. 10.2165/00003495-199000393-00005
    1. Li, D. , Chang, X. , Connolly, J. J. , Tian, L. , Liu, Y. , Bhoj, E. J. , … Hakonarson, H. (2017). A genome‐wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling. Scientific Reports, 7(1), 3847 10.1038/s41598-017-01674-8
    1. Liu, J. , Garza, J. C. , Li, W. , & Lu, X. Y. (2013). Melanocortin‐4 receptor in the medial amygdala regulates emotional stress‐induced anxiety‐like behaviour, anorexia and corticosterone secretion. International Journal of Neuropsychopharmacology, 16(1), 105–120. 10.1017/S146114571100174X
    1. Lokuge, S. , Frey, B. N. , Foster, J. A. , Soares, C. N. , & Steiner, M. (2011). Depression in women: Windows of vulnerability and new insights into the link between estrogen and serotonin. Journal of Clinical Psychiatry, 72(11), e1563–e1569. 10.4088/JCP.11com07089
    1. Lombardi, L. , Blanchet, C. , Poirier, K. , Lebrun, N. , Ramoz, N. , Rose Moro, M. , … Bienvenu, T. (2019). Anorexia nervosa is associated with Neuronatin variants. Psychiatric Genetics, 29(4), 103–110. 10.1097/YPG.0000000000000224
    1. Lutter, M. , Bahl, E. , Hannah, C. , Hofammann, D. , Acevedo, S. , Cui, H. , … Michaelson, J. J. (2017). Novel and ultra‐rare damaging variants in neuropeptide signaling are associated with disordered eating behaviors. PLoS ONE, 12(8), e0181556 10.1371/journal.pone.0181556
    1. Marsh, D. J. , Weingarth, D. T. , Novi, D. E. , Chen, H. Y. , Trumbauer, M. E. , Chen, A. S. , … Qian, S. (2002). Melanin‐concentrating hormone 1 receptor‐deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Proceedings of the National Academy of Sciences of the United States of America, 99(5), 3240–3245. 10.1073/pnas.052706899
    1. Di Marzo, V. , Goparaju, S. K. , Wang, L. , Liu, J. , Bátkai, S. , Járai, Z. , … Kunos, G. (2001). Leptin‐regulated endocannabinoids are involved in maintaining food intake. Nature, 410(6830), 822–825. 10.1038/35071088
    1. Mercader, J. M. , Ribasés, M. , Gratacòs, M. , González, J. R. , Bayés, M. , de Cid, R. , … Estivill, X. (2007). Altered brain‐derived neurotrophic factor blood levels and gene variability are associated with anorexia and bulimia. Genes, Brain and Behavior, 6(8), 706–716. 10.1111/j.1601-183X.2007.00301.x
    1. Miller, G. (2017). Appetite regulation: Hormones, peptides, and neurotransmitters and their role in obesity. American Journal of Lifestyle Medicine, 13(6), 586–601. 10.1177/1559827617716376
    1. Monteleone, A. M. , Di Marzo, V. , Aveta, T. , Piscitelli, F. , Dalle Grave, R. , Scognamiglio, P. , … Maj, M. (2015). Deranged endocannabinoid responses to hedonic eating in underweight and recently weight‐restored patients with anorexia nervosa. American Journal of Clinical Nutrition, 101(2), 262–269. 10.3945/ajcn.114.096164
    1. Monteleone, P. , Bifulco, M. , Di Filippo, C. , Gazzerro, P. , Canestrelli, B. , Monteleone, F. , … Maj, M. (2009). Association of CNR1 and FAAH endocannabinoid gene polymorphisms with anorexia nervosa and bulimia nervosa: Evidence for synergistic effects. Genes, Brain and Behavior, 8(7), 728–732. 10.1111/j.1601-183X.2009.00518.x
    1. Monteleone, P. , Matias, I. , Martiadis, V. , De Petrocellis, L. , Maj, M. , & Di Marzo, V. (2005). Blood levels of the endocannabinoid anandamide are increased in anorexia nervosa and in binge‐eating disorder, but not in bulimia nervosa. Neuropsychopharmacology, 30(6), 1216–1221. 10.1038/sj.npp.1300695
    1. Moskowitz, L. , & Weiselberg, E. (2017). Anorexia nervosa/atypical anorexia nervosa. Current Problems in Pediatric and Adolescent Health Care, 47(4), 70–84. 10.1016/j.cppeds.2017.02.003
    1. Nakabayashi, K. , Komaki, G. , Tajima, A. , Ando, T. , Ishikawa, M. , Nomoto, J. , … Shirasawa, S. (2009). Identification of novel candidate loci for anorexia nervosa at 1q41 and 11q22 in Japanese by a genome‐wide association analysis with microsatellite markers. Journal of Human Genetics, 54(9), 531–537. 10.1038/jhg.2009.74
    1. Oo, T. F. , & Burke, R. E. (1997). The time course of developmental cell death in phenotypically defined dopaminergic neurons of the substantia nigra. Developmental Brain Research, 98(2), 191–196. 10.1016/S0165-3806(96)00173-3
    1. Perello, M. , & Dickson, S. L. (2015). Ghrelin signalling on food reward: A salient link between the gut and the mesolimbic system. Journal of Neuroendocrinology, 27(6), 424–434. 10.1111/jne.12236
    1. Perry, B. , & Wang, Y. (2012). Appetite regulation and weight control: The role of gut hormones. Nutrition and Diabetes, 2, e26 10.1038/nutd.2011.21
    1. Quintero, E. M. , Willis, L. M. , Zaman, V. , Lee, J. , Boger, H. A. , Tomac, A. , … Granholm, A.‐C. (2004). Glial cell line‐derived neurotrophic factor is essential for neuronal survival in the locus coeruleus‐hippocampal noradrenergic pathway. Neuroscience, 124(1), 137–146. 10.1016/j.neuroscience.2003.11.001
    1. Ribasés, M. , Gratacòs, M. , Fernández‐Aranda, F. , Bellodi, L. , Boni, C. , Anderluh, M. , … Estivill, X. (2005). Association of BDNF with restricting anorexia nervosa and minimum body mass index: A family‐based association study of eight European populations. European Journal of Human Genetics, 13(4), 428–434. 10.1038/sj.ejhg.5201351
    1. Rossman, M. D. , Thompson, B. , Frederick, M. , Maliarik, M. , Iannuzzi, M. C. , Rybicki, B. A. , … Monos, D. (2003). HLA‐DRB1*1101: A significant risk factor for sarcoidosis in blacks and whites. American Journal of Human Genetics, 73, 720–735. 10.1086/378097
    1. Rueda, D. , Navarro, B. , Martínez‐Serrano, A. , Guzmán, M. , & Galve‐Roperh, I. (2002). The endocannabinoid anandamide inhibits neuronal progenitor cell differentiation through attenuation of the Rap1/B. Journal of Biological Chemistry, 277(48), 46645–46650. 10.1074/jbc.M206590200
    1. Sabir, M. S. , Haussler, M. R. , Mallick, S. , Kaneko, I. , Lucas, D. A. , Haussler, C. A. , … Jurutka, P. W. (2018). Optimal vitamin D spurs serotonin: 1,25‐dihydroxyvitamin D represses serotonin reuptake transport (SERT) and degradation (MAO‐A) gene expression in cultured rat serotonergic neuronal cell lines. Genes and Nutrition, 13, 19 10.1186/s12263-018-0605-7
    1. Scott‐Van Zeeland, A. A. , Bloss, C. S. , Tewhey, R. , Bansal, V. , Torkamani, A. , Libiger, O. , … Schork, N. J. (2014). Evidence for the role of EPHX2 gene variants in anorexia nervosa. Molecular Psychiatry, 19(6), 724–732. 10.1038/mp.2013.91
    1. Shah, M. , & Vella, A. (2014). Effects of GLP‐1 on appetite and weight. Reviews in Endocrine and Metabolic Disorders, 15(3), 181–187. 10.1007/s11154-014-9289-5
    1. Shimada, M. , Tritos, N. A. , Lowell, B. B. , Flier, J. S. , & Maratos‐Flier, E. (1998). Mice lacking melanin‐concentrating hormone are hypophagic and lean. Nature, 396(6712), 670–674. 10.1038/25341
    1. Siegfried, Z. , Kanyas, K. , Latzer, Y. , Karni, O. , Bloch, M. , Lerer, B. , & Berry, E. M. (2004). Association study of cannabinoid receptor gene (CNR1) alleles and anorexia nervosa: Differences between restricting and bingeing/purging subtypes. American Journal of Medical Genetics, 125B(1), 126–130. 10.1002/ajmg.b.20089
    1. Sild, M. , & Booij, L. (2019). Histone deacetylase 4 (HDAC4): A new player in anorexia nervosa? Molecular Psychiatry, 24(10), 1425–1434. 10.1038/s41380-019-0366-8
    1. Södersten, P. , Nergårdh, R. , Bergh, C. , Zandian, M. , & Scheurink, A. (2008). Behavioral neuroendocrinology and treatment of anorexia nervosa. Frontiers in Neuroendocrinology, 29(4), 445–462. 10.1016/j.yfrne.2008.06.001
    1. Steiner, A. A. , & Romanovsky, A. A. (2007). Leptin: At the crossroads of energy balance and systemic inflammation. Progress in Lipid Research, 46(2), 89–107. 10.1016/j.plipres.2006.11.001
    1. Strober, M. , Freeman, R. , Lampert, C. , Diamond, J. , & Kaye, W. (2000). Controlled family study of anorexia nervosa and bulimia nervosa: Evidence of shared liability and transmission of partial syndromes. American Journal of Psychiatry, 157(3), 393–401. 10.1176/appi.ajp.157.3.393
    1. Takeuchi, S. , Yazaki, M. , Yamada, S. , Fukuyama, T. , Inui, A. , Iwasaki, Y. , & Ikeda, S. I. (2015). An adolescent case of citrin deficiency with severe anorexia mimicking anorexia nervosa. Pediatrics, 136(2), e530–e534. 10.1542/peds.2014-4172
    1. Tasegian, A. , Curcio, F. , Dalla Ragione, L. , Rossetti, F. , Cataldi, S. , Codini, M. , … Albi, E. (2016). Hypovitaminosis D3, leukopenia, and human serotonin transporter polymorphism in anorexia nervosa and bulimia nervosa. Mediators of Inflammation, 2016, 8046479 10.1155/2016/8046479
    1. Veronese, N. , Solmi, M. , Rizza, W. , Manzato, E. , Sergi, G. , Santonastaso, P. , … Correll, C. U. (2015). Vitamin D status in anorexia nervosa: A meta‐analysis. International Journal of Eating Disorders, 48(7), 803–813. 10.1002/eat.22370
    1. Wang, K. , Zhang, H. , Bloss, C. S. , Duvvuri, V. , Kaye, W. , Schork, N. J. , … Hakonarson, H. (2011). A genome‐wide association study on common SNPs and rare CNVs in anorexia nervosa. Molecular Psychiatry, 16(9), 949–959. 10.1038/mp.2010.107
    1. Watson, H. J. , Yilmaz, Z. , Thornton, L. M. , Hübel, C. , Coleman, J. R. I. , Gaspar, H. A. , … Bulik, C. M. (2019). Genome‐wide association study identifies eight risk loci and implicates metabo‐psychiatric origins for anorexia nervosa. Nature Genetics, 51(8), 1207–1214. 10.1038/s41588-019-0439-2
    1. Weiss, M. J. , Cole, D. E. C. , Ray, K. , Whyte, M. P. , Lafferty, M. A. , Mulivor, R. A. , & Harris, H. (1988). A missense mutation in the human liver/bone/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia. Proceedings of the National Academy of Sciences of the United States of America, 85(20), 7666–7669. 10.1073/pnas.85.20.7666
    1. Wirz, L. , Reuter, M. , Felten, A. , & Schwabe, L. (2018). An endocannabinoid receptor polymorphism modulates affective processing under stress. Social Cognitive and Affective Neuroscience, 13(11), 1177–1189. 10.1093/scan/nsy083
    1. Yenchitsomanus, P. T. , Sawasdee, N. , Paemanee, A. , Keskanokwong, T. , Vasuvattakul, S. , Bejrachandra, S. , … Promwong, C. (2003). Anion exchanger 1 mutations associated with distal renal tubular acidosis in the Thai population. Journal of Human Genetics, 48(9), 451–456. 10.1007/s10038-003-0059-6
    1. Yilmaz, Z. , Hardaway, A. , & Bulik, C. (2015). Genetics and epigenetics of eating disorders. Advances in Genomics and Genetics, 5, 131–150. 10.2147/agg.s55776
    1. Zipfel, S. , Giel, K. E. , Bulik, C. M. , Hay, P. , & Schmidt, U. (2015). Anorexia nervosa: Aetiology, assessment, and treatment. The Lancet Psychiatry, 2(12), 1099–1111. 10.1016/S2215-0366(15)00356-9

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner