Evening preference correlates with regional brain volumes in the anterior occipital lobe.

Chronotype or diurnal preference is a questionnaire-based measure influenced both by circadian period and by the sleep homeostat. In order to further characterize the biological determinants of these measures, we used a hypothesis-free approach to investigate the association between the score of the morningness-eveningness questionnaire (MEQ) and the Munich chronotype questionnaire (MCTQ), as continuous variables, and volumetric measures of brain regions acquired by magnetic resonance imaging (MRI). Data were collected from the Baependi Heart Study cohort, based in a rural town in South-Eastern Brazil. MEQ and anatomical 1.5-T MRI scan data were available from 410 individuals, and MCTQ scores were available from a subset of 198 of them. The average MEQ (62.2 ± 10.6) and MCTQ (average MSFsc 201 ± 85 min) scores were suggestive of a previously reported strong general tendency toward morningness in this community. Setting the significance threshold at P > .002 to account for multiple comparisons, we observed a significant association between lower MEQ score (eveningness) and greater volume of the left anterior occipital sulcus (ß = -0.163, p = .001) of the occipital lobe. No significant associations were observed for MCTQ. This may reflect the smaller dataset for MCTQ, and/or the fact that MEQ, which asks questions about preferred timings, is more trait-like than the MCTQ, which asks questions about actual timings. The association between MEQ and a brain region dedicated to visual information processing is suggestive of the increasingly recognized fluidity in the interaction between visual and nonvisual photoreception and the circadian system, and the possibility that chronotype includes an element of masking.

Heritability of semantic verbal fluency task using time-interval analysis.

Individual variability in word generation is a product of genetic and environmental influences. The genetic effects on semantic verbal fluency were estimated in 1,735 participants from the Brazilian Baependi Heart Study. The numbers of exemplars produced in 60 s were broken down into time quartiles because of the involvement of different cognitive processes-predominantly automatic at the beginning, controlled/executive at the end. Heritability in the unadjusted model for the 60-s measure was 0.32. The best-fit model contained age, sex, years of schooling, and time of day as covariates, giving a heritability of 0.21. Schooling had the highest moderating effect. The highest heritability (0.17) was observed in the first quartile, decreasing to 0.09, 0.12, and 0.0003 in the following ones. Heritability for average production starting point (intercept) was 0.18, indicating genetic influences for automatic cognitive processes. Production decay (slope), indicative of controlled processes, was not significant. The genetic influence on different quartiles of the semantic verbal fluency test could potentially be exploited in clinical practice and genome-wide association studies.

Metabolic syndrome alters relationships between cardiometabolic variables, cognition and white matter hyperintensity load.

Cardiometabolic risk factors influence white matter hyperintensity (WMH) development: in metabolic syndrome (MetS), higher WMH load is often reported but the relationships between specific cardiometabolic variables, WMH load and cognitive performance are uncertain. We investigated these in a Brazilian sample (aged 50-85) with (N = 61) and without (N = 103) MetS. Stepwise regression models identified effects of cardiometabolic and demographic variables on WMH load (from FLAIR MRI) and verbal recall performance. WMH volume was greater in MetS, but verbal recall performance was not impaired. Age showed the strongest relationship with WMH load. Across all participants, systolic blood pressure (SBP) and fasting blood glucose were also contributors, and WMH volume was negatively associated with verbal recall performance. In non-MetS, higher HbA1c, SBP, and number of MetS components were linked to poorer recall performance while higher triglyceride levels appeared to be protective. In MetS only, these relationships were absent but education exerted a strongly protective effect on recall performance. Thus, results support MetS as a construct: the clustering of cardiometabolic variables in MetS alters their individual relationships with cognition; instead, MetS is characterised by a greater reliance on cognitive reserve mechanisms. In non-MetS, strategies to control HbA1c and SBP should be prioritised as these have the largest impact on cognition.

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: 46.5 ± 16.2 y, range: 18-89 years). Average self-reported sleep duration was 07:07 ± 01:31 (bedtime 22:32 ± 01:27, wake up time: 06:17 ± 01:25 hh:min), sleep quality score was 4.9 + 3.2, chronotype was 63.6 ± 10.8 and daytime sleepiness was 7.4 ± 4.8. 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 (p < 0.0001). This study provides indirect evidence in support of the hypothesis that sleep timing was earlier prior to full urbanisation.

Plasma leptin concentrations are highly correlated to emotional states throughout the day.

Previous work has shown that leptin appears to regulate the plasma levels of hormones such as adrenocorticotropic hormone (ACTH) and cortisol in humans and that it has antidepressant effects in animals. It is unknown whether fluctuations in circulating leptin levels are correlated to changes in human emotions. This study was conducted to determine whether minute-to-minute fluctuations in the plasma concentrations of human leptin were associated with psychological variables. Leptin was sampled every 7 min throughout the day in 10 healthy subjects (five men and five women) studied in a clinical research center, and visual analog scales were applied every hour. We found highly significant correlations between fluctuations in plasma leptin concentrations and three psychological variables: sadness, carbohydrate craving and social withdrawal. We showed that during the course of the day increases in leptin levels are associated with decreased search for starchy foods, decreased feelings of sadness and increased social withdrawal. Our findings support the hypothesis that during the course of the day as leptin levels increase individuals subjectively feel happier (less sad) and have less inclination to interact socially. Conversely, when leptin levels decrease, we show increases in sadness and social cooperation, which might facilitate the search for food. We suggest that increased human leptin levels may promote positive feelings and that decreased leptin levels might modulate inner states that motivate and facilitate the search for nutrients.

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 2,202 kcal, with a macronutrient composition of 53% carbohydrates, 31% fats and 17% proteins. The mean energy intake of the eating episodes followed by vomiting was 1,331 kcal 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.

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.

Synchronicity of frequently sampled thyrotropin (TSH) and leptin concentrations in healthy adults and leptin-deficient subjects: evidence for possible partial TSH regulation by leptin in humans.

Leptin signals the status of energy reserves to the brain. Leptin stimulates biosynthesis of TRH in vitro and influences the activity of the hypothalamic-pituitary-thyroid axis in vivo in rodents. Because blood levels of both leptin and TSH display diurnal variation with a distinct nocturnal rise, we sought to determine whether a relationship exists between fluctuations in circulating leptin and TSH. We measured serum leptin and TSH levels every 7 min for 24 h in five healthy men and found that both leptin and TSH levels are highly organized and pulsatile. A similar pattern of leptin and TSH rhythms was observed, with TSH and leptin levels reaching a nadir in late morning and a peak in the early morning hours. Importantly, cosinor analysis on the absolute leptin and TSH levels revealed a statistically significant fit for a 24-h period and the two hormones showed similar probabilities of rhythm and superimposable peak values. Furthermore, this study shows a strong positive Pearson correlation between the 24-h patterns of variability of leptin and TSH in healthy subjects. Finally, the ultradian fluctuations in leptin levels showed pattern synchrony with those of TSH as determined by cross-correlation analysis, by cross-approximate enthropy and Bayessian analysis applied independently. To further explore whether these associations could reflect an underlying regulation of TSH secretion by leptin, we also studied frequently sampled leptin and TSH levels in four brothers, members of a family with leptin deficiency (one normal homozygote, two heterozygotes, and one leptin-deficient homozygote). Leptin levels of the homozygous leptin-deficient subject are detectable but bioinactive, and the rhythm of his TSH is disorganized. 24-h pattern of leptin and TSH variability in the heterozygous subjects, although significantly correlated, showed a weaker correlation compared with the strong correlation in the normal subjects. These data are consistent with the possibility that leptin may regulate TSH pulsatility and circadian rhythmicity, but interventional studies are needed to definitively prove whether leptin regulates the minute-to-minute oscillations and ultradian rhythm of TSH levels.

Individual reactivity and physiology of the stress response.

The biological response to stress involves the activation of two main neuroendocrine components, the hypothalamic-pituitary-adrenal axis and the sympathoadrenal medullary systems. Looking at the responses to stressors in a laboratory setting, e.g., cortisol production after exercising on a treadmill, is a valid and controlled way to study how people react to psychological and physical stressors. A common finding in such studies is that individuals respond bimodally to stress. More recently, researchers have been interested in the possible reasons why healthy individuals exhibit differential reactivity to stressors. The literature on the neuroendocrine responses to stress, with a particular focus on investigations of individual reactivity to psychological and physical stressors, is reviewed.

Case series: increased vulnerability to obsessive-compulsive symptoms with repeated episodes of Sydenham chorea.

The association between obsessive-compulsive symptoms (OCS) and Sydenham chorea (SC) supports the hypothesis of a common neuroimmunological dysfunction in basal ganglia associated with group A beta-hemolytic streptococcal infection underlying both conditions. Four children with 2 distinct SC episodes were evaluated to assess the course of OCS. All patients developed OCS during their second episodes (3 met criteria for obsessive-compulsive disorder [OCD]), but not in their first episodes (2 developed OCS and met criteria for OCD). These data suggest that the recurrence of SC episodes may result in a cumulative effect, thus increasing the risk of appearance and intensification of OCS.

Sex differences in circulating human leptin pulse amplitude: clinical implications.

Leptin, a product of fat cells, provides a signal of nutritional status to the central nervous system. Leptin concentrations have ultradian and diurnal fluctuations. We conducted this study to assess sex differences in the levels of organization of frequently sampled leptin concentrations in healthy, normal weight women and men. Leptin levels were sampled every 7 min for 24 h in 14 healthy, normal weight individuals (6 women and 8 men). The 14 leptin time series containing a total of 2898 leptin measurements were assessed by 1) algorithms that characterize statistically significant pulsatility, 2) Spectral (Fourier) analysis, 3) analysis of time intervals and variability, and 4) approximate entropy. We found that frequently sampled plasma leptin concentrations have a 24-h profile that is numerically more than twice as high in women as in men, and leptin pulse amplitude is likewise more than twice as high in women. However, healthy men and women have nearly identical concentration-independent and frequency-related 24-h and ultradian patterns. Leptin concentrations have nonrandom fluctuations over 24 h, independent of their absolute value and underlying 24-h periodicity, that are similar in men and women. Ultradian periodicities detected by Fourier time series have similar values in men and women. The strongest distinction between the sexes in the level of organization of leptin concentration is not at the level of pulse organization or oscillation frequency, but, rather, in the mass or amount of leptin released (or removed) per unit time, indicating that women might be more resistant to the effects of leptin than men. Because leptin is clinically relevant to the regulation of body weight, future studies should examine whether the relative leptin resistance exhibited by women might contribute to their increased susceptibility to disorders whose pathophysiology involves dysregulation of food intake and body weight.

Obsessive-compulsive and related symptoms in children and adolescents with rheumatic fever with and without chorea: a prospective 6-month study.

OBJECTIVE: The incidence and course of neuropsychiatric symptoms were determined in pediatric patients with rheumatic fever. METHOD: The Leyton Obsessional Inventory and National Institute of Mental Health Global Obsessive-Compulsive Scale were used to evaluate children and adolescents who had rheumatic fever with Sydenham's chorea (N=30) or without chorea (N=20). They were assessed three times over 6 months from the onset of rheumatic fever. Psychiatric diagnoses were also determined. RESULTS: Obsessive-compulsive symptoms abruptly appeared and peaked during the 2 months after the onset of rheumatic fever in 21 patients with chorea (70.0%) and were absent in all patients without chorea. Obsessive-compulsive disorder (OCD) was diagnosed in five patients with chorea (16.7%). CONCLUSIONS: The association between Sydenham's chorea and OCD supports suggestions that similar mechanisms involving the basal ganglia underlie both disorders. Obsessive-compulsive symptoms occurred at the beginning of rheumatic fever, so early psychopathological assessments are essential.

Synchronicity of frequently sampled, 24-h concentrations of circulating leptin, luteinizing hormone, and estradiol in healthy women.

Leptin, an adipocyte hormone, is a trophic factor for the reproductive system; however, it is still unknown whether there is a dynamic relation between fluctuations in circulating leptin and hypothalamic-pituitary-ovarian (HPO) axis hormones. To test the hypothesis that fluctuations in plasma leptin concentrations are related to the levels of luteinizing hormone (LH) and estradiol, we sampled plasma from six healthy women every 7 min for 24 h during days 8-11 of the menstrual cycle. Cross-correlation analysis throughout the 24-h cycle revealed a relation between release patterns of leptin and LH, with a lag of 42-84 min but no significant cross-correlation between LH and estradiol. The ultradian fluctuations in leptin levels showed pattern synchrony with those of both LH and estradiol as determined by cross-approximate entropy (cross-ApEn). At night, as leptin levels rose to their peak, the pulsatility profiles of LH changed significantly and became synchronous with those of leptin. LH pulses were fewer, of longer duration, higher amplitude, and larger area than during the day. Moreover, the synchronicity of LH and leptin occurred late at night, at which time estradiol and leptin also exhibited significantly stronger pattern coupling than during the day. We propose that leptin may regulate the minute-to-minute oscillations in the levels of LH and estradiol, and that the nocturnal rise in leptin may determine the change in nocturnal LH profile in the mid-to-late follicular phase that precedes ovulation. This may explain the disruption of hypothalamic-pituitary-ovarian function that is characteristic of states of low leptin release, such as anorexia nervosa and cachexia.

Plasma leptin levels are increased in survivors of acute sepsis: associated loss of diurnal rhythm, in cortisol and leptin secretion.

Recent animal and human studies have suggested that leptin secretion is closely linked to the functions of the hypothalamic-pituitary-adrenal (HPA) axis and the immune system, both of which are crucial in influencing the course and outcome of critical illness. Therefore, we measured basal plasma leptin levels and examined the circadian secretion of leptin, in parallel with the hormones of the HPA axis and a key cytokine, interleukin-6, in critically ill patients with acute sepsis. Sixteen critically ill patients from the University of Leipzig Intensive Care Unit were recruited for this study. All of these patients fulfilled the standard diagnostic criteria for sepsis. Plasma leptin levels were measured in all patients and controls at 09:00. In addition, in a subgroup of eight critically ill patients and all of the nine controls plasma leptin, cortisol, ACTH and interleukin-6 concentrations were measured every 4 hours for 24 hours. Mean plasma leptin levels were three-fold higher (18.9 +/- 4.5 ng/ml) in critically ill patients than controls (3.8 +/- 1.0 ng/ml, p < 0.05). Similarly, ACTH levels were lower (7.8 +/- 3.4 pmol/l) in patients than in controls (17.1 +/- 1.5 pmol/l, p < .001), while plasma cortisol levels were increased (947.6 +/- 144 nmol/l) in patients compared to controls (361.1 +/- 29, p < 0.001). Morning plasma interleukin-6 levels were markedly elevated in all patients with sepsis (1238.0 +/- 543.1 pg/ml) versus controls (6.4 +/- 1.7, p < 0.001). The controls exhibited a nyctohemeral fluctuation in plasma leptin levels with peak levels at 23:00; in contrast, septic patients, had no nocturnal rise of leptin. In healthy controls, plasma leptin and cortisol had reciprocal circadian rhythms with high nocturnal leptin levels and low nocturnal cortisol concentrations; in critically ill patients, this relation was abolished. Mean leptin levels were three-fold higher in patients who survived the septic episode (25.5 +/- 6.2, n = 10) than in non-survivors (8.0 +/- 3.7, n = 6, p < 0.01). We conclude that in addition to its function as an anti-obesity factor, leptin may play a role in a severe stress state such as acute sepsis.

Human leptin levels are pulsatile and inversely related to pituitary-adrenal function.

Leptin communicates nutritional status to regulatory centers in the brain. Because peripheral leptin influences the activity of the highly pulsatile adrenal and gonadal axes, we sought to determine whether leptin levels in the blood are pulsatile. We measured circulating leptin levels every 7 minutes for 24 hours, in six healthy men, and found that total circulating leptin levels exhibited a pattern indicative of pulsatile release, with 32.0 +/- 1.5 pulses every 24 hours and a pulse duration of 32.8 +/- 1.6 minutes. We also show an inverse relation between rapid fluctuations in plasma levels of leptin and those of adrenocorticotropic hormone (ACTH) and cortisol that could not be accounted for on the basis of glucocorticoid suppression of leptin. As leptin levels are pulsatile, we propose that a key function of the CNS is regulated by a peripheral pulsatile signal. In a separate pilot study we compared leptin pulsatility in 414 plasma samples collected every 7 minutes for 24 hours from one obese woman and one normal-weight woman. We found that high leptin levels in the obese subject were due solely to increased leptin pulse height; all concentration-independent pulsatility parameters were almost identical in the two women. Leptin pulsatility therefore can be preserved in the obese.

Clinical characteristics and course of anorexia nervosa in Latin America, a Brazilian sample.

The authors present the clinical description of a sample of anorexic patients from an eating disorder program from a non-English developing country. The patients were diagnosed according to DSM-III-R criteria and treated with a multidisciplinary approach. Similarities to and differences from other Western patient studies are discussed.

Childhood sexual abuse and bulimia nervosa: a comparison of American, Austrian, and Brazilian women.

OBJECTIVE: This study was designed to assess the prevalence of childhood sexual abuse among women with bulimia nervosa in three countries: the United States, Austria, and Brazil. In addition, it assessed whether bulimic subjects might have experienced more severe sexual abuse than women in the general population and whether bulimic subjects who report abuse might display greater psychopathology than those who do not report abuse. METHOD: Thirty-three university students in Innsbruck, Austria, 33 university students in Boston, and 25 women in São Paulo, Brazil, all meeting DSM-III-R criteria for bulimia nervosa, were recruited by advertisement. Detailed histories of sexual abuse, obtained at the conclusion of a comprehensive evaluation interview, were prepared, translated into English, and rated by an investigator who was blind to the nationality of the subject. Subjects were compared on frequency of eating binges, history of major depression, body mass index, and satisfaction with body image. RESULTS: Narrowly defined childhood sexual abuse was reported by 24%-36% of women in the three countries, although only 15%-32% of women reported abuse before the onset of bulimia nervosa. There were no significant differences between countries in rates of abuse. Overall, these rates appear no greater than those reported in comparable studies of women in the general population. The data also did not support the hypothesis that bulimic subjects had endured more severe sexual abuse than other women, nor was there a significant association between history of childhood sexual abuse and severity of bulimic symptoms. CONCLUSIONS: These findings add to the weight of evidence suggesting that childhood sexual abuse is not a risk factor for bulimia nervosa.