Anorexia Risk

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As with all risk factors, these do not cause Anorexia: they add an element of risk and may act in synergy with other risk factors or susceptibility genes. Their risk promoting ability may be increased or decreased by these other factors. These risk factors, and the genes, form the components of a puzzle, whose assembly will one day alow us to see the whole picture

Environmental risk factors and medical conditions associated with Anorexia

Ongoing clinical trails, worldwide, can be interrogated at ClinicalTrials.Gov a service of the US National Institutes of Health

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Eating disorders from NIMH

 Eating disorder referral center Gliadin antibodies as a potential cause of schizophrenia

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Genes

Genome wide association @ Genome.gov ADRB1 ADORA1 AKAP6 CALM1 CDH9 CDH10 CRH CRHR1 CSRP2BP FAM155A FREQ GABRA4 GABRP GAD2 GLP2R GNAS GRIA1 GRIN2B GRM5 HTR5A IGFBP2 KCNN3 LRP2 NSF NTNG1 NTSR1 OPRD1 PAH POMC PPARGC1A QDPR RGS10 SLC6A2 SLC6A3 SLC18A1 SSBP2 UCP1 VGLL4 ZNF804B Wang et al, 2010 Pinheiro et al, 2010 Wang et al, 2011

Phenotypic traits DRD3 GRK5 GRM5 HCRTR1 INS KCNN3 TACR1 Root et al, 2011

ADIPOQ AGRP AVPR1A BDNF CCK CLOCK CNR1 CNTN5 COMT DRD2 ESR1 ESR2 FAAH GHRL GPR55 GOAT GRIN2B HTR1D HTR2A HTR2C IGF2 KCNN3 MAOA NGF NTRK2 NTRK3 OPRD1 RETN SLC6A2 SLC6A4 TNF TPH2 UCP2 UCP3

Gwas : Pinheiro et al, 2010

Anorexia all: ADRB1 FREQ GABRA4 GAD2 GLP2R GRIA1 GRIN2B HTR5A KCNN3 PAH QDPR RGS10 SLC18A1 SLC6A3

Anorexia with no binge eating ADORA1 ADRB1 CRH CRHR1 FREQ GLP2R GRIA1 KCNN3 NSF NTSR1 PAH PPARGC1A RGS10 SLC18A1 SLC18A2 SLC6A2 SLC6A3 UCP1

Restricting Anorexia : ADRB1 CALM1 CRH FREQ GABRP GLP2R GNAS IGFBP2 KCNN3 PAH POMC QDPR RGS10 SLC18A1 SLC18A2 SLC6A2 SLC6A4 UCP1
Kegg pathway analysis of anorexia genes

Genes needing KEGG mapping EPHX2 FTO GRIA3 OLIG2 CLEC5A LOC136242 TSHZ1 SYTL5 ESRRA HDAC4 (SOX2OT PPP3CA CUL3 FAM124B SPATA13)

Risk Factors

Infectious agents

Autoimmunity

  • Antibodies against alpha-Melanocyte stimulating hormone , Oxytocin T, and Vasopressin Fettisov et al, 2005
  • ACTH antibodies Wheatland, 2005
  • Autoantibodies against alpha -MSH, ACTH, and Luteinising Hormone Releasing Hormone in anorexia and bulimia nervosa patients. Fettisov et al, 2002

Prenatal factors and Birth related

  • In utero exposure to chickenpox or rubella during the 6th month of pregnancy associated with anorexia in the offspring Favaro et al, 2011
  • Exposure to diethylstilbestrol in utero Gustavson et al, 1991
  • In the UK the season of birth of eating disorders patients peaks in May. In younger patients peak season of birth peaks in March Rezaul et al, 1996
  • A higher environmental temperature at the point of assumed conception was more likely to be found in restrictive anorexics than in anorexics of the binge-purge subtype Waller et al, 2002
  • But: No difference in season of birth at the equator Willoughby et al, 2005
  • Eating disorder patients appear to be more frequently conceived during the transitional stages of the ovulatory pattern due to seasonal preovulatory overripeness ovopathy and less frequently at the ovulatory peaks due to seasonal optimally ripened oocytes Jongbloet et al, 2005
  • Associated with obstetric complications Verdoux and Sutter, 2002
    • Including maternal anemia , diabetes mellitus , preeclampsia , placental infarction, neonatal cardiac problems , and hyporeactivity associated with the later development of anorexia in the offspring.Favaro et al, 2006
  • In the UK an excess of anorexia births was observed from March to June and a deficit from September to October, suggesting an environmental influence Disanto et al, 2011
Dietary factors and environmental

Association with other diseases

  • Familial association between eating disorders and major depression. Logue et al, 1989 Wade et al, 2000
  • Xerosis, lanugo-like body hair, telogen effluvium, carotenoderma, acne, hyperpigmentation, seborrheic dermatitis, acrocyanosis, perniosis, petechiae, livedo reticularis, interdigital intertrigo, paronychia, generalized pruritus, acquired striae distensae, slower wound healing, prurigo pigmentosa, edema, linear erythema craquele, acral coldness, pellagra, scurvy, and acrodermatitis enteropathica as a consequence of anorexia Strumia, 2005
  • A significant association between eating disorders and substance use disorders Baker et al, 2010
  • Associated with coeliac disease Snyder et al, 2008
  • A feature of dermatomyositis Maugars et al, 1996
  • A feauture of Hyperparathyroidism causd by increased decretion of parathyroid hormone Tonini et al, 2004
  • Common in the aged Constans 2003
  • Anorexia is a risk factor for osteoporosis Rivera-Gallardo et al, 2005

Biochemistry

  • Low or normal serum Thyroid stimulating hormone concentration is common during fasting and in patients with anorexia nervosa.Matsubayashi et al, 1988
  • Starvation-induced serum estrogen and triiodothyronine deficits Buehren et al, 2011
  • Higher levels of cortisol and Peptide YY are associated with disordered eating Lawson et al, 2011
  • High serum glutamine levels Nakazato et al, 2010
  • Low IGF1 and free testeosterone levels in women Brick et al, 2010 Polli et al, 2008
  • Binge purge patients had higher serum adiponectin levels compared with restrictive anorexia patients , and hyperactive patients had higher serum leptin and lower serum resistin levels compared with Nonhyperactive anorexia patients.Nogueira et al, 2010
  • Elevated serum levels of Macrophage inhibitory cytokine-1 Dostálová et al, 2010
  • Low serum apelin levels Ziora et al, 2010
  • Increased nocturnal melatonin levels Ostrowska et al, 2010
  • Reduced amylin levls Wojcik et al, 2010
  • Elevated cortisol levels Lawson et al, 2009
  • Reduced serum BDNF levels, restored by recovery Ehrlich et al, 2009
  • Reduced serum levels of fibroblast growth factor FGF21 Dostálová et al, 2008
  • Increased levels of FGF23 coupled with low levels of 1,25-dihydroxyvitamin D in binge purge patients Otani et al, 2008
  • Elevated serum alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) levels Fong et al, 2008
  • Reduced serum levels of S100B Holtkamp et al, 2008
  • Mean serum levels of estradiol (E2) , IGF-I, triiodothyronin (T3) and leptin were significantly lower in anorexia. Serum levels of osteoprotegerin (OPG) were significantly higher in anorexia and negatively correlated with body mass index (BMI), E2, IGF-I or leptin.Ohwada et al, 2007
  • High serum levels of obestatin and ghrelin Nakahara et al, 2008
  • Higher salivary cortisol levels, someties without circadian rhythm dos Santos et al, 2007
  • serum levels of total cholesterol , low-density lipoprotein cholesterol, high-density lipoprotein cholesterol,, ketone bodies, apolipoprotein (apo)-A1, APOB, APOC2, APOC3, APOE, and cholesterol ester transfer protein (CETP) activity were significantly higher in anorexia nervosa patients.Ohwada et al, 2006
  • Low serum leptin levels Holtkamp et al, 2006
  • Low serum levels of complement component C3 Flierl et al, 2011
Others
  • Increased risk in adopted children Holden, 1991
  • A symbiotically close mother-daughter relationship with elements of aggression was noted in anorexicx children. In the fathers, the autoritarian-dominant type predominated.Bonenberger and Klosinski 1988
  • Lower family cohesion, expressiveness, and organization were significantly associated with greater eating disorder risk Lower independence was significantly associated with increased eating disorder risk, but to a lesser degree (p < .05). Greater conflict and control were significantly associated with greater eating disorder risk Felker and Stevers, 1994
  • Children of alcoholic parents are more at risk of developing eating disorders Chandy et al, 1994
  • Women with a history of anorexia nervosa of the binge/purge subtype reported higher levels of loneliness, shyness and feelings of inferiority in adolescence Troop and Bifulco, 2002
  • Elevated anxiety and eating-related obsessionality may increase the risk for the development of anorexia and nonremission Yackobovitch-Gavan et al, 2009
  • Eating disorders are more common in females in early adolescence de Castro and Goldstein, 1995
  • with a sex ratio of 9 to 1 Bocheareau et al, 1999.
  • A genetic contribution of about 44% Rutherford et al, 1993
  • No association with urbanisation.Van Son et al, 2006
  • Eating disorder subjects were, on average, shorter than control subjects Favaro et al, 2007
  • The risk of developing anorexia is higher in female twins than in male twins (production of an intrauterine risk factor ?) Procopio and Marriott.2007
  • A consequence of high-altitude headache Serrano-Dueñas 2005

 

 

 

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