André B. Negrão

Etiologia dos transtornos alimentares: aspectos biológicos, psicológicos e sócio-culturais

Eating disorders have a multifactorial etiology, composed by genetic predisposition, sociocultural factors, and biological and psychological vulnerabilities. Among the predisposing factors, emphasis is given to a history of eating and/or mood disorders, personality traits, patterns of family interaction, alterations in brain monoamines and sociocultural overvalued drive for thinness. Dieting is the most frequently event present at the onset of an eating disorder. Nevertheless, dieting itself is not sufficient to precipitate an eating disorder. An interaction among risk factors and other precipitating events is necessary. Finally, the chronic or transitory course of an eating disorder is related to the persistence of distorted cognitions, to the occurrence of significant vital events, and to starvation-induced psychobiological alterations.

Marked suppression of gastric ulcerogenesis and intestinal responses to stress by a novel class of drugs.

When exposed to prolonged stress, rats develop gastric ulceration, enhanced colon motility with depletion of its mucin content and signs of physiological and behavioral arousal. In this model, we tested whether antidepressants (fluoxetine and bupropion), anxiolytics (diazepam and buspirone) or the novel nonpeptide corticotropin-releasing hormone (CRH) type-1 receptor (CRH-R1) antagonist, antalarmin, modify these responses. Fluoxetine, bupropion, diazepam and antalarmin all suppressed stress-induced gastric ulceration in male Sprague–Dawley rats exposed to four hours of plain immobilization. Antalarmin produced the most pronounced anti-ulcer effect and additionally suppressed the stress-induced colonic hypermotility, mucin depletion, autonomic hyperarousal and struggling behavior. Intraperitoneal CRH administration reproduced the intestinal but not the gastric responses to stress while vagotomy antagonized the stress-induced gastric ulceration but not the intestinal responses. We conclude that brain CRH-R1 and vagal pathways are essential for gastric ulceration to occur in response to stress and that peripheral CRH-R1 mediates colonic hypermotility and mucin depletion in this model. Nonpeptide CRH-R1 antagonists may therefore be prophylactic against stress ulcer in the critically ill and therapeutic for other pathogenetically related gastrointestinal disorders such as peptic ulcer disease and irritable bowel syndrome.

Leptina: o diálogo entre adipócitos e neurônios

The discovery of leptin led to a renewed interest in the study of enegy homeostasis. It is now recognized that white adipose tissue is the major site of leptin synthesis. After it is secreted into the bloodstream leptin binds itself to specific receptors in the brain, providing the central nervous system with a satiety signal that reflects the amount of energy stored as fat. Acting through receptors that transduce a signal by the JAK/STAT pathway, leptin modifies the expression and activity of hypothalamic peptides that regulate appetite and energy expenditure. In addition, leptin signals nutritional status to other physiological systems and modulates the function of several target glands. More recently, recombinant leptin was successfully given to an obese patient with leptin deficiency due to a mutation in the ob gene. On the other hand, the effects of recombinant leptin in the only study with obese patients and increased levels of circulating leptin were less impressive. Here we review the complexity of leptin actions with a focus on its integrative role as a signal of nutritional status for the organism.

Distribution and heritability of diurnal preference (chronotype) in a rural Brazilian family-based cohort, the Baependi study

Diurnal preference (chronotype) is a useful instrument for studying circadian biology in humans. It harbours trait-like dimensions relating to circadian period and sleep homeostasis, but also has ontogenetic components (morningness increases with age). We used the Morningness-Eveningness questionnaire (MEQ) in the Baependi study, a family-based cohort study based in a small town in Minas Gerais, Brazil. The population is highly admixed and has a cohesive and conservative lifestyle. 825 individuals (497 female) aged 18–89 years (average ± SD = 46.4 ± 16.3) and belonging to 112 different families participated in this study. The average MEQ score was 63.5 ± 11.2 with a significant (P < 0.0001) linear increase with age. Morningness was significantly (P < 0.0001) higher in the rural (70.2 ± 9.8) than in the municipal zone (62.6 ± 11.1), and was also significantly (P = 0.025) higher in male (64.6 ± 10.9) than in female (62.8 ± 11.2) participants. Thus, in spite of universal access to electricity, the Baependi population was strongly shifted towards morningness, particularly in the rural zone. Heritability of MEQ score was 0.48 when adjusted for sex and age, or 0.38 when adjusted for sex, age, and residential zone. The reported MEQ score heritability is more akin to those of previous twin studies than previous family studies.

Emergent Oscillations in Mathematical Model of the Human Menstrual Cycle

BACKGROUNDnThe aim of this study was to develop a mathematical model of the hypothalamo-pituitary-gonadal axis that would reflect available data in humans.nnnMETHODSnA model of hormonal relationships at the early follicular and midluteal phases of the human menstrual cycle is proposed.nnnFINDINGSnTwo distinct temporal patterns of oscillatory behavior have been demonstrated for both pituitary and gonadal steroids in the early follicular phase: first, rapid oscillations in gonadotropin releasing hormone, follicle stimulating hormone and luteinizing hormone (Q approximate to 1 hour) that were an immediate consequence of the programmed equations. Second, there were slower, undulating, emergent rhythms in luteinizing hormone and follicle stimulating hormone, and also in estrogen, having oscillatory periods of 2-12 hours. There was also a longer-period (Q2-3 days) emergent rhythm in progesterone. In the mid-luteal phase, estrogen and progesterone rhythms were correlated, and all hormones showed an approximately 6-hour periodicity.nnnCONCLUSIONSnTo our knowledge, the oscillatory behavior of peripheral sex steroids in the follicular phase has not been previously noted.

Mood Changes after Maximal Exercise Testing in Subjects with Symptoms of Exercise Dependence

Considering exercise has positive and negative reinforcing properties, the mood states of sedentary, nonexercise-dependent and exercise-dependent volunteers were compared after maximal exercise testing. Mood status was evaluated by the Beck Depression Inventory, Trait-State Anxiety Inventory, and Profile of Mood States (POMS). No differences were detected before the test or after it, indicating little possibility of positive reinforcement. However, a significant reduction in the POMS Tension-Anxiety scores was observed in both exerciser groups (greater in the exercise-dependent group) but not in the sedentary group. Only in the exercise-dependent group were significant reductions in Anger and Total Mood Disorders scores observed compared with their pre-exercise scores. These data suggest that exercising has stronger negative reinforcement properties for exercise-dependent volunteers and is a factor which could increase the odds of their becoming dependent on exercise.

Nutritional aspects of eating episodes followed by vomiting in Brazilian patients with bulimia nervosa

Background. The clinical aspects of bulimia nervosa (BN) are similar in countries with different sociocultural backgrounds, but less is known about dietary composition in patients from developing countries. Little is also known about the role that nutritional aspects may play in behaviours aimed at counteracting the effects of binge eating. Objectives. To describe the daily energy intake and eating behaviour of BN patients in Brazil and compare the dietary patterns of the patients who terminated eating episodes by vomiting and those patients who did not. Methods. Thirty patients from an eating disorders programme in a university-affiliated hospital completed a 14-day dietetic diary; the data were analysed using nutritional software. Results. Mean age and BMI of the patients were respectively 27.2±9.6 years and 25.5±6.7 Kg/m2. The patients in the vomiting subgroup ate more irregularly and consumed a more variable number of meals per day than those in the non-vomiting subgroup. The daily energy intake of the patients as a whole was 2,202kcal, with a macronutrient composition of 53% carbohydrates, 31% fats and 17% proteins. The mean energy intake of the eating episodes followed by vomiting was 1,331kcal with a macronutrient profile of 51% carbohydrates, 36% fat and 14% protein. Intake and eating patterns were characterised by between- and within- individual variability, and so no significant differences were found in the subgroup comparisons. Foods with a high energy density were preferred during the eating episodes followed by vomiting. Conclusions. The results indicate that patients who vomit have a more irregular and variable eating pattern than those who do not vomit, but their daily nutrient content is comparable.

Amerindian (but not African or European) ancestry is significantly associated with diurnal preference within an admixed Brazilian population

ABSTRACT Significant questions remain unanswered regarding the genetic versus environmental contributions to racial/ethnic differences in sleep and circadian rhythms. We addressed this question by investigating the association between diurnal preference, using the morningness–eveningness questionnaire (MEQ), and genetic ancestry within the Baependi Heart Study cohort, a highly admixed Brazilian population based in a rural town. Analysis was performed using measures of ancestry, using the Admixture program, and MEQ from 1,453 individuals. We found an association between the degree of Amerindian (but not European of African) ancestry and morningness, equating to 0.16 units for each additional percent of Amerindian ancestry, after adjustment for age, sex, education, and residential zone. To our knowledge, this is the first published report identifying an association between genetic ancestry and MEQ, and above all, the first one based on ancestral contributions within individuals living in the same community. This previously unknown ancestral dimension of diurnal preference suggests a stratification between racial/ethnic groups in an as yet unknown number of genetic polymorphisms.

Timing and quality of sleep in a rural Brazilian family-based cohort, the Baependi Heart Study

Sleep is modulated by several factors, including sex, age, and chronotype. It has been hypothesised that contemporary urban populations are under pressure towards shorter sleep duration and poorer sleep quality. Baependi is a small town in Brazil that provides a window of opportunity to study the influence of sleep patterns in a highly admixed rural population with a conservative lifestyle. We evaluated sleep characteristics, excessive daytime sleepiness, and chronotype using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Morningness-Eveningness Questionnaire questionnaires, respectively. The sample consisted of 1,334 subjects from the Baependi Heart study (41.5% male; age: 46.5u2009±u200916.2 y, range: 18–89 years). Average self-reported sleep duration was 07:07u2009±u200901:31 (bedtime 22:32u2009±u200901:27, wake up time: 06:17u2009±u200901:25 hh:min), sleep quality score was 4.9u2009+u20093.2, chronotype was 63.6u2009±u200910.8 and daytime sleepiness was 7.4u2009±u20094.8. Despite a shift towards morningness in the population, chronotype remained associated with reported actual sleep timing. Age and sex modulated the ontogeny of sleep and chronotype, increasing age was associated with earlier sleep time and shorter sleep duration. Women slept longer and later, and reported poorer sleep quality than men (pu2009<u20090.0001). This study provides indirect evidence in support of the hypothesis that sleep timing was earlier prior to full urbanisation.

Shared Genetic Factors of Anxiety and Depression Symptoms in a Brazilian Family-Based Cohort, the Baependi Heart Study.

To investigate the phenotypic and genetic overlap between anxiety and depression symptoms in an admixed population from extended family pedigrees. Participants (n = 1,375) were recruited from a cohort of 93 families (mean age±SD 42±16.3, 57% female) in the rural town of Baependi, Brazil. The Hospital Anxiety and Depression Scale (HADS) was used to assess depression and anxiety symptoms. Heritability estimates were obtained by an adjusted variance component model. Bivariate analyses were performed to obtain the partition of the covariance of anxiety and depression into genetic and environmental components, and to calculate the genetic contribution modulating both sets of symptoms. Anxiety and depression scores were 7.49±4.01 and 5.70±3.82, respectively. Mean scores were affected by age and were significantly higher in women. Heritability for depression and anxiety, corrected for age and sex, were 0.30 and 0.32, respectively. Significant genetic correlations (ρg = 0.81) were found between anxiety and depression scores; thus, nearly 66% of the total genetic variance in one set of symptoms was shared with the other set. Our results provided strong evidence for a genetic overlap between anxiety and depression symptoms, which has relevance for our understanding of the biological basis of these constructs and could be exploited in genome-wide association studies.