Brain reward responses to food stimuli among female monozygotic twins discordant for BMI

Obese individuals are characterized by altered brain reward responses to food. Despite the latest discovery of obesity-associated genes, the contribution of environmental and genetic factors to brain reward responsiveness to food remains largely unclear. Sixteen female monozygotic twin pairs with a mean BMI discordance of 3.96 ± 2.1 kg/m(2) were selected from the Netherlands Twin Register to undergo functional MRI scanning while watching high- and low-calorie food and non-food pictures and during the anticipation and receipt of chocolate milk. In addition, appetite ratings, eating behavior and food intake were assessed using visual analog scales, validated questionnaires and an ad libitum lunch. In the overall group, visual and taste stimuli elicited significant activation in regions of interest (ROIs) implicated in reward, i.e. amygdala, insula, striatum and orbitofrontal cortex. However, when comparing leaner and heavier co-twins no statistically significant differences in ROI-activations were observed after family wise error correction. Heavier versus leaner co-twins reported higher feelings of hunger (P = 0.02), cravings for sweet food (P = 0.04), body dissatisfaction (P < 0.05) and a trend towards more emotional eating (P = 0.1), whereas caloric intake was not significantly different between groups (P = 0.3). Our results suggest that inherited rather than environmental factors are largely responsible for the obesity-related altered brain responsiveness to food. Future studies should elucidate the genetic variants underlying the susceptibility to reward dysfunction and obesity. CLINICAL TRIAL REGISTRATION NUMBER: NCT02025595

Bivariate genetic modelling of the response to an oral glucose tolerance challenge: A gene x environment interaction approach

AIMS/HYPOTHESIS: Twin and family studies have shown the importance of genetic factors influencing fasting and 2 h glucose and insulin levels. However, the genetics of the physiological response to a glucose load has not been thoroughly investigated. METHODS: We studied 580 monozygotic and 1,937 dizygotic British female twins from the Twins UK Registry. The effects of genetic and environmental factors on fasting and 2 h glucose and insulin levels were estimated using univariate genetic modelling. Bivariate model fitting was used to investigate the glucose and insulin responses to a glucose load, i.e. an OGTT. RESULTS: The genetic effect on fasting and 2 h glucose and insulin levels ranged between 40% and 56% after adjustment for age and BMI. Exposure to a glucose load resulted in the emergence of novel genetic effects on 2 h glucose independent of the fasting level, accounting for about 55% of its heritability. For 2 h insulin, the effect of the same genes that already influenced fasting insulin was amplified by about 30%. CONCLUSIONS/INTERPRETATION: Exposure to a glucose challenge uncovers new genetic variance for glucose and amplifies the effects of genes that already influence the fasting insulin level. Finding the genes acting on 2 h glucose independently of fasting glucose may offer new aetiological insight into the risk of cardiovascular events and death from all causes

Toward Understanding Massive Star Formation

Although fundamental for astrophysics, the processes that produce massive stars are not well understood. Large distances, high extinction, and short timescales of critical evolutionary phases make observations of these processes challenging. Lacking good observational guidance, theoretical models have remained controversial. This review offers a basic description of the collapse of a massive molecular core and a critical discussion of the three competing concepts of massive star formation: - monolithic collapse in isolated cores - competitive accretion in a protocluster environment - stellar collisions and mergers in very dense systems We also review the observed outflows, multiplicity, and clustering properties of massive stars, the upper initial mass function and the upper mass limit. We conclude that high-mass star formation is not merely a scaled-up version of low-mass star formation with higher accretion rates, but partly a mechanism of its own, primarily owing to the role of stellar mass and radiation pressure in controlling the dynamics.Comment: 139 pages, 18 figures, 5 tables, glossar

Endophenotypes in a Dynamically Connected Brain

We examined the longitudinal genetic architecture of three parameters of functional brain connectivity. One parameter described overall connectivity (synchronization likelihood, SL). The two others were derived from graph theory and described local (clustering coefficient, CC) and global (average path length, L) aspects of connectivity. We measured resting state EEG in 1,438 subjects from four age groups of about 16, 18, 25 and 50 years. Developmental curves for SL and L indicate that connectivity is more random at adolescence and old age, and more structured in middle-aged adulthood. Individual variation in SL and L were moderately to highly heritable at each age (SL: 40–82%; L: 29–63%). Genetic factors underlying these phenotypes overlapped. CC was also heritable (25–49%) but showed no systematic overlap with SL and L. SL, CC, and L in the alpha band showed high phenotypic and genetic stability from 16 to 25 years. Heritability for parameters in the beta band was lower, and less stable across ages, but genetic stability was high. We conclude that the connectivity parameters SL, CC, and L in the alpha band show the hallmarks of a good endophenotype for behavior and developmental disorders

A Neptune-sized transiting planet closely orbiting a 5–10-million-year-old star

Theories of the formation and early evolution of planetary systems postulate that planets are born in circumstellar disks, and undergo radial migration during and after dissipation of the dust and gas disk from which they formed^1, 2. The precise ages of meteorites indicate that planetesimals—the building blocks of planets—are produced within the first million years of a star’s life^3. Fully formed planets are frequently detected on short orbital periods around mature stars. Some theories suggest that the in situ formation of planets close to their host stars is unlikely and that the existence of such planets is therefore evidence of large-scale migration^4, 5. Other theories posit that planet assembly at small orbital separations may be common^6, 7, 8. Here we report a newly born, transiting planet orbiting its star with a period of 5.4 days. The planet is 50 per cent larger than Neptune, and its mass is less than 3.6 times that of Jupiter (at 99.7 per cent confidence), with a true mass likely to be similar to that of Neptune. The star is 5–10 million years old and has a tenuous dust disk extending outward from about twice the Earth–Sun separation, in addition to the fully formed planet located at less than one-twentieth of the Earth–Sun separation

The Netherlands study of depression in older persons (NESDO); a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>To study late-life depression and its unfavourable course and co morbidities in The Netherlands.</p> <p>Methods</p> <p>We designed the Netherlands Study of Depression in Older Persons (NESDO), a multi-site naturalistic prospective cohort study which makes it possible to examine the determinants, the course and the consequences of depressive disorders in older persons over a period of six years, and to compare these with those of depression earlier in adulthood.</p> <p>Results</p> <p>From 2007 until 2010, the NESDO consortium has recruited 510 depressed and non depressed older persons (≥ 60 years) at 5 locations throughout the Netherlands. Depressed persons were recruited from both mental health care institutes and general practices in order to include persons with late-life depression in various developmental and severity stages. Non-depressed persons were recruited from general practices. The baseline assessment included written questionnaires, interviews, a medical examination, cognitive tests and collection of blood and saliva samples. Information was gathered about mental health outcomes and demographic, psychosocial, biological, cognitive and genetic determinants. The baseline NESDO sample consists of 378 depressed (according to DSM-IV criteria) and 132 non-depressed persons aged 60 through 93 years. 95% had a major depression and 26.5% had dysthymia. Mean age of onset of the depressive disorder was around 49 year. For 33.1% of the depressed persons it was their first episode. 41.0% of the depressed persons had a co morbid anxiety disorder. Follow up assessments are currently going on with 6 monthly written questionnaires and face-to-face interviews after 2 and 6 years.</p> <p>Conclusions</p> <p>The NESDO sample offers the opportunity to study the neurobiological, psychosocial and physical determinants of depression and its long-term course in older persons. Since largely similar measures were used as in the Netherlands Study of Depression and Anxiety (NESDA; age range 18-65 years), data can be pooled thus creating a large longitudinal database of clinically depressed persons with adequate power and a large set of neurobiological, psychosocial and physical variables from both younger and older depressed persons.</p

The heritability of beta cell function parameters in a mixed meal test design

Aims/hypothesis: We estimated the heritability of individual differences in beta cell function after a mixed meal test designed to assess a wide range of classical and model-derived beta cell function parameters. Methods: A total of 183 healthy participants (77 men), recruited from the Netherlands Twin Register, took part in a 4 h protocol, which included a mixed meal test. Participants were Dutch twin pairs and their siblings, aged 20 to 49 years. All members within a family were of the same sex. Insulin sensitivity, insulinogenic index, insulin response and postprandial glycaemia were assessed, as well as model-derived parameters of beta cell function, in particular beta cell glucose sensitivity and insulin secretion rates. Genetic modelling provided the heritability of all traits. Multivariate genetic analyses were performed to test for overlap in the genetic factors influencing beta cell function, waist circumference and insulin sensitivity. Results: Significant heritabilities were found for insulinogenic index (63%), beta cell glucose sensitivity (50%), insulin secretion during the first 2 h postprandial (42-47%) and postprandial glycaemia (43-52%). Genetic factors influencing beta cell glucose sensitivity and insulin secretion during the first 30 postprandial min showed only negligible overlap with the genetic factors that influence waist circumference and insulin sensitivity. Conclusions/interpretation: The highest heritability for postprandial beta cell function was found for the insulinogenic index, but the most specific indices of heritability of beta cell function appeared to be beta cell glucose sensitivity and the insulin secretion rate during the first 30 min after a mixed meal. © The Author(s) 2011

Interoception across Modalities: On the Relationship between Cardiac Awareness and the Sensitivity for Gastric Functions

The individual sensitivity for ones internal bodily signals (“interoceptive awareness”) has been shown to be of relevance for a broad range of cognitive and affective functions. Interoceptive awareness has been primarily assessed via measuring the sensitivity for ones cardiac signals (“cardiac awareness”) which can be non-invasively measured by heartbeat perception tasks. It is an open question whether cardiac awareness is related to the sensitivity for other bodily, visceral functions. This study investigated the relationship between cardiac awareness and the sensitivity for gastric functions in healthy female persons by using non-invasive methods. Heartbeat perception as a measure for cardiac awareness was assessed by a heartbeat tracking task and gastric sensitivity was assessed by a water load test. Gastric myoelectrical activity was measured by electrogastrography (EGG) and subjective feelings of fullness, valence, arousal and nausea were assessed. The results show that cardiac awareness was inversely correlated with ingested water volume and with normogastric activity after water load. However, persons with good and poor cardiac awareness did not differ in their subjective ratings of fullness, nausea and affective feelings after drinking. This suggests that good heartbeat perceivers ingested less water because they subjectively felt more intense signals of fullness during this lower amount of water intake compared to poor heartbeat perceivers who ingested more water until feeling the same signs of fullness. These findings demonstrate that cardiac awareness is related to greater sensitivity for gastric functions, suggesting that there is a general sensitivity for interoceptive processes across the gastric and cardiac modality