Obiettivo
This project aims to identify psychosocial and genetic risk factors for anorexia, bulimia and obesity, and correlate these with neuroimaging and neuropsychological. We will create an aetiological model, for use as tool for improving prevention and treatment of these disorders. We will examine environment by measuring psychosocial and endogenous risk factors such as childhood obesity, sexual abuse, personality and psychopathology. We will examine the human genome for genetic risk factors in large, well-characterised European samples. We will examine the brain by performing firm and PET neuroimaging to explore neuroanatomical and neurochemical correlates, and neuropsychological to reveal cognitive factors which trigger and prolong these disorders. Finally we will model interactions between psychopathology, genes, culture, gender and psychosocial risk.
We have created an aetiological model of anorexia nervosa (AN) and bulimia nervosa (BN), based on genes, environment and function of the brain. Patients who develop eating disorder have a set of identified environmental risk factors together with genetic vulnerability which together lead to the illness. In addition, there are characteristic traits such as childhood perfectionism, cognitive inflexibility, and dieting behaviour which result from the actions of both genes and environment. We identified genetic risk factors, including BDNF which appears common to both disorders, and MCR4, which is a risk factor for BN. Thus, AN and BN appear to differ for some factors (BN for example having genetic risk factors in common with obesity) and have common risks for others (such as cognitive inflexibility and many environmental risk factors). These risks manifest themselves though specific abnormalities in neural process which can be viewed by neuroimaging. Specific results: Twin population analysis: Dieting is associated with many unhealthy behaviours at the age 14, but at this early risk age mood problems are a better predictor of future eating disorder symptoms than dieting. Predictors of obesity at age 14 were early puberty, daily TV watching, self-reported unpopularity among peers, sleeping disturbances (boys) and reduced daily outdoor activities.
Many ED related traits are heritable. Functional magnetic resonance imaging: We found that medial prefrontal cortex response to symptom provoking stimuli is a common feature of anorexia and bulimia nervosa and common with obsessive-compulsive and addictive disorders; it is present even after long-term recovery from anorexia nervosa and may a trait vulnerability; prefrontal reaction is specifically associated with food; Decreased response to food in the anterior and lateral prefrontal cortex is specific to bulimia nervosa; Lateral and apical prefrontal involvement differentiates recovered people from chronic patients and is associated with a good outcome. Neuropsychology: A battery of neuropsychological tests of mental flexibility was used, and uncovered four factors: simple alteration, mental flexibility, preservation and semantic shifting. The AN group showed global impairment on three of four factors, compared to healthy controls, while BN had impairment in selected areas that present a cognitive set shifting dysfunction. Our findings suggest that cognitive inflexibility may present an important manifestation of biological substrate of AN and BN and may add to the broader phenotypic definition for future genetic studies. Risk factors: Nearly all risk factors previously found were replicated in this study using a within-family design corroborating that these risk factors are non-shared in nature. The occurrence of major depressive episodes was significantly more common in the pre-onset period of AN patients. Temperament and character has also been investigated and patients were high in harm avoidance, persistence, and self-transcendence, and low in novelty seeking, self-directedness and cooperativeness. They did not differ in reward dependence. Furthermore, being low in self-directedness predicted strongly the comorbid presence of a personality disorder in these patients with AN.
Cross cultural variation and gender. We found that during childhood, the number of time that meals were eaten together as a family was significantly greater in the Spanish sample and access to snacks was less restricted than in the UK. Furthermore, parents in Spain were less likely to have strict rules about food or use food as a punishment or reward. The results of this study indicate that there are cross-cultural differences in childhood eating patterns and parental attitudes to food in people with an ED. There are few gender differences in personality and psychological traits in eating disorders. However, higher premorbid obesity and overweight are more common antecedent factors in males. Does dieting trigger and eating disorder. The completed statistical analyses confirmed the initial trend apparent in the preliminary evaluations, showing that inpatient treatment for weight reduction is not followed by a significant rise in the incidence of eating disorders. Genetic analysis: We have analysed 13 different genes in the project Serotonin receptor 5-HT2A, Catechol-O-methyltransferase, Agouti related protein, Serotonin transporter 5-HTT, gherkin, melanocortin 4 receptor, 5-HT1D, 5-HT1B, Muscarinic receptor M3, Delta opioid receptor, BDNF, Orexin peptide gene, 5-HT2A, DRD4, DRD2, UCP2 with a total of approximately 30 polymorphisms. One of these genes, BDNF, was highly significant across all samples and a paper is in preparation. We have also finished collecting data and performed preliminary analysis for gene environment interaction. Two associations are significant DRD4 VNTR polymorphisms allele 7 and harm avoidance, and DRD4 VNTR polymorphism allele 7 and reward dependence.
Campo scientifico (EuroSciVoc)
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: Il Vocabolario Scientifico Europeo.
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: Il Vocabolario Scientifico Europeo.
- scienze mediche e della salute medicina clinica psichiatria disturbo ossessivo compulsivo
- scienze naturali scienze biologiche biochimica biomolecole proteine
- ingegneria e tecnologia ingegneria medica diagnostica per immagini risonanza magnetica per immagini
- scienze naturali scienze biologiche genetica genomi
- scienze mediche e della salute scienze della salute nutrizione obesità
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Meccanismo di finanziamento (o «Tipo di azione») all’interno di un programma con caratteristiche comuni. Specifica: l’ambito di ciò che viene finanziato; il tasso di rimborso; i criteri di valutazione specifici per qualificarsi per il finanziamento; l’uso di forme semplificate di costi come gli importi forfettari.
Coordinatore
WC2R 2LS LONDON
Regno Unito
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