Relation of neural response to palatable food tastes and images to future weight gain: Using bootstrap sampling to examine replicability of neuroimaging findings.

Because understanding neural vulnerability factors that predict future weight gain may guide the design of more effective obesity prevention programs and treatments, we tested whether neural response to palatable food tastes and images predicted future weight gain. We recruited 135 initially healthy weight adolescents, to reduce the possibility that a history of overeating affected neural responsivity, had them complete fMRI paradigms examining neural response to tastes of milkshakes that varied in fat and sugar content and images of palatable foods, and assessed BMI annually over a 3-year follow-up. We used a novel bootstrapping analytic approach to investigate the replicability of the fMRI findings. Whole-brain analyses indicated that lower response in the pre-supplemental motor area to high-fat/low-sugar milkshake taste predicted future BMI gain in the full sample and in 5 out of the 10 bootstrap samples. Elevated response in the precentral gyrus/Rolandic operculum to images of appetizing foods predicted future BMI gain in the full sample and in 4 out of the 10 bootstrap samples. Other peaks that emerged in the full sample did not replicate in most of the bootstrap samples, suggesting they were not reliable. Region of interest analyses did not replicate the predictive effects of peaks reported in past papers that used similar paradigms, including the evidence that TaqIA polymorphism moderated the relation of striatal response to palatable food tastes to future weight gain. Results suggest that lower responsivity of a region implicated in motor processing in response to palatable taste was associated with greater BMI gain over time, and further that bootstrap sampling may be useful for estimating the replicability of findings that emerge from whole brain analyses or regions of interest analyses with the full sample.

An experimental therapeutics test of whether adding dissonance-induction activities improves the effectiveness of a selective obesity and eating disorder prevention program.

OBJECTIVE: Compare the Healthy Weight obesity and eating disorder prevention program, which promotes participant-driven gradual lifestyle changes to bring energy intake and expenditure into balance, to a new intervention, Project Health, which adds activities to create cognitive dissonance about unhealthy eating, a sedentary lifestyle, and excess body fat, and an obesity education video-control condition. METHOD: College students at risk for both outcomes because of weight concerns (N=364, 72% female) were randomized to condition, completing pretest, posttest, and 6, 12 and 24-month follow-up assessments. RESULTS: Project Health participants showed significantly smaller increases in measured body mass index (BMI) through 2-year follow-up than both Healthy Weight participants and controls (both d=-0.18), and significantly lower onset of overweight/obesity over 2-year follow-up than Healthy Weight participants and controls (13 vs 21% and 22%). Healthy Weight and Project Health participants showed significantly greater eating disorder symptom reductions than controls through 2-year follow-up. Healthy Weight and Project Health participants showed marginally lower eating disorder onset over follow-up than controls (3 and 3% vs 8% respectively). CONCLUSIONS: The reduced increases in BMI and future overweight/obesity onset for Project Health relative to both an active matched intervention and a minimal intervention control condition are noteworthy, especially given the short 6-h intervention duration. The reduction in eating disorder symptoms for Healthy Weight and Project Health relative to controls was also encouraging. Results suggest that adding dissonance-induction activities increased weight loss effects. Yet, effects for both were generally small and the eating disorder onset prevention effects were only marginal, potentially because intervention groups included both sexes, which reduced eating disorder incidence and sensitivity.

Brain substrates of unhealthy versus healthy food choices: influence of homeostatic status and body mass index.

BACKGROUND/OBJECTIVES: Unhealthy dietary choices are a major contributor to harmful weight gain and obesity. This study interrogated the brain substrates of unhealthy versus healthy food choices in vivo, and evaluated the influence of hunger state and body mass index (BMI) on brain activation and connectivity. SUBJECTS/METHODS: Thirty adults (BMI: 18-38 kg m-2) performed a food-choice task involving preference-based selection between beverage pairs consisting of high-calorie (unhealthy) or low-calorie (healthy) options, concurrent with functional magnetic resonance imaging (fMRI). Selected food stimuli were delivered to participants using an MRI-compatible gustometer. fMRI scans were performed both after 10-h fasting and when sated. Brain activation and hypothalamic functional connectivity were assessed when selecting between unhealthy-healthy beverage pairings, relative to unhealthy-unhealthy and healthy-healthy options. Results were considered significant at cluster-based family-wise error corrected P<0.05. RESULTS: Selecting between unhealthy and healthy foods elicited significant activation in the hypothalamus, the medial and dorsolateral prefrontal cortices, the anterior insula and the posterior cingulate. Hunger was associated with higher activation within the ventromedial and dorsolateral prefrontal cortices, as well as lower connectivity between the hypothalamus and both the ventromedial prefrontal cortex and dorsal striatum. Critically, people with higher BMI showed lower activation of the hypothalamus-regardless of hunger state-and higher activation of the ventromedial prefrontal cortex when hungry. CONCLUSIONS: People who are overweight and obese have weaker activation of brain regions involved in energy regulation and greater activation of reward valuation regions while making choices between unhealthy and healthy foods. These results provide evidence for a shift towards hedonic-based, and away from energy-based, food selection in obesity.

Cognitive regulation of food craving: effects of three cognitive reappraisal strategies on neural response to palatable foods.

OBJECTIVE: Obese versus lean individuals show greater reward region and reduced inhibitory region responsivity to food images, which predict future weight gain. Thinking of the costs of eating palatable foods and craving suppression have been found to modulate this neural responsivity, but these cognitive reappraisal studies have primarily involved lean participants. Herein we evaluated the efficacy of a broader range of reappraisal strategies in modulating neural responsivity to palatable food images among individuals who ranged from lean to obese and tested whether body mass index (BMI) moderates the effects of these strategies. MATERIALS AND METHODS: Functional magnetic resonance imaging assessed the effects of three cognitive reappraisal strategies in response to palatable food images versus an imagined intake comparison condition in a sample of adolescents (N=21; M age=15.2). RESULTS: Thinking of the long-term costs of eating the food, thinking of the long-term benefits of not eating the food and attempting to suppress cravings for the food increased activation in inhibitory regions (for example, superior frontal gyrus, ventrolateral prefrontal cortex) and reduced activation in attention-related regions (for example, precuneus and posterior cingulate cortex). The reappraisal strategy focusing on the long-term benefits of not eating the food more effectively increased inhibitory region activity and reduced attention region activity compared with the other two cognitive reappraisal strategies. BMI did not moderate the effects. DISCUSSION: These novel results imply that cognitive reappraisal strategies, in particular those focusing on the benefits of not eating the food, could potentially increase the ability to inhibit appetitive motivation and reduce unhealthy food intake in overweight individuals.

Relation of regional gray and white matter volumes to current BMI and future increases in BMI: a prospective MRI study.

OBJECTIVE: This study tested whether global and regional brain volumes correlated with body mass index (BMI) and increases in BMI over 1-year follow-up. METHODS: A total of 83 young females (M age=18.4, s.d.=2.8; BMI range=17.3-38.9) were scanned using magnetic resonance imaging. Voxel-based morphometry was used to assess global brain volume and regional gray matter (GM) and white matter (WM) volumes in regions implicated in taste, reward and inhibitory control. RESULTS: Obese participants had less total GM volume than lean and overweight participants. Obese participants had lower total WM volume than overweight participants. BMI correlated with higher WM volumes in the middle temporal gyrus, fusiform gyrus, parahippocampal gyrus, Rolandic operculum and dorsal striatum. Trend-level reduced GM volumes in the superior frontal gyrus and middle frontal gyrus were related to increases in BMI over 1-year follow-up. CONCLUSION: Findings suggest that BMI is related to global and regional differences in brain matter volume in female adolescents. Most importantly, findings suggest that low GM volume in regions implicated in inhibitory control are related to future weight gain. Results taken in conjunction with prior findings suggest that abnormalities in regional GM volumes, but not WM volumes, increase the risk for future weight gain and abnormalities in regional WM volumes, but not GM volumes, are secondary to weight gain.

Negative affect amplifies the relation between appetitive-food-related neural responses and weight gain over three-year follow-up among adolescents.

Obesity is a major public health concern that is associated with disruption in food reward-related brain function. This study examined if negative affect and stressful events enhance the relation between the food reward-related neural response and future weight gain. Initially healthy weight adolescents (N = 135) completed fMRI paradigms in which they tasted milkshakes and viewed palatable food images, and reported on negative affect and stressful events at baseline; BMI was measured annually over 3-year follow-up. Whole-brain analyses revealed that among participants with higher negative affect, weight gain over 3-year follow-up was predicted by elevated response to appetitive versus unappetitive food images in the left hippocampus, and elevated response in the vermis and the bilateral precuneus to tastes of milkshake versus tasteless solution. Among participants who experienced more stressful events, elevated right middle occipital gyrus response to milkshakes predicted future weight gain. Profiling analyses suggested that participants with higher negative affect or more stressful events who later gained weight reported engaging in more restrained eating and eating disorder-related behaviors. Results suggest that negative affect or stressful events may amplify the relation of neural response to food and the risk for future weight gain.

Pathways and mechanisms linking dietary components to cardiometabolic disease: thinking beyond calories.

Calories from any food have the potential to increase risk for obesity and cardiometabolic disease because all calories can directly contribute to positive energy balance and fat gain. However, various dietary components or patterns may promote obesity and cardiometabolic disease by additional mechanisms that are not mediated solely by caloric content. Researchers explored this topic at the 2017 CrossFit Foundation Academic Conference 'Diet and Cardiometabolic Health - Beyond Calories', and this paper summarizes the presentations and follow-up discussions. Regarding the health effects of dietary fat, sugar and non-nutritive sweeteners, it is concluded that food-specific saturated fatty acids and sugar-sweetened beverages promote cardiometabolic diseases by mechanisms that are additional to their contribution of calories to positive energy balance and that aspartame does not promote weight gain. The challenges involved in conducting and interpreting clinical nutritional research, which preclude more extensive conclusions, are detailed. Emerging research is presented exploring the possibility that responses to certain dietary components/patterns are influenced by the metabolic status, developmental period or genotype of the individual; by the responsiveness of brain regions associated with reward to food cues; or by the microbiome. More research regarding these potential 'beyond calories' mechanisms may lead to new strategies for attenuating the obesity crisis.

Obesity and addiction: can a complication of surgery help us understand the connection?

Obesity is a multifactorial, chronic disease that has proven difficult to treat. An increased understanding of aetiological mechanisms is critical to the development of more effective obesity prevention and treatment strategies. A growing body of empirical evidence has demonstrated parallels between obesity, overeating and substance abuse, including shared behavioural, psychological and neurophysiological factors implicated in the excessive intake of both food and substances of abuse. Several different lines of research have recently emerged that hold the potential to shed light on the connection between obesity, food reward and addiction, with studies examining changes in alcohol use/misuse after weight loss surgery providing a particularly interesting perspective on these interrelationships. However, these lines of investigation have proceeded in relative isolation, and relevant research findings have yet to be integrated in a synthesized, comprehensive manner. To provide an opportunity to achieve such a synthesis, a scientific symposium was convened at the Radcliffe Institute in Cambridge, Massachusetts. Invited participants were researchers working in diverse domains related to the intersection between obesity and addiction. Extensive discussion was generated suggesting novel research directions. In this article, we summarize and synthesize the symposium participants' ongoing research in this area, incorporating additional relevant research holding potential clues regarding the connections between obesity, weight loss surgery and addiction.

Neuroimaging and neuromodulation approaches to study eating behavior and prevent and treat eating disorders and obesity.

Functional, molecular and genetic neuroimaging has highlighted the existence of brain anomalies and neural vulnerability factors related to obesity and eating disorders such as binge eating or anorexia nervosa. In particular, decreased basal metabolism in the prefrontal cortex and striatum as well as dopaminergic alterations have been described in obese subjects, in parallel with increased activation of reward brain areas in response to palatable food cues. Elevated reward region responsivity may trigger food craving and predict future weight gain. This opens the way to prevention studies using functional and molecular neuroimaging to perform early diagnostics and to phenotype subjects at risk by exploring different neurobehavioral dimensions of the food choices and motivation processes. In the first part of this review, advantages and limitations of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), pharmacogenetic fMRI and functional near-infrared spectroscopy (fNIRS) will be discussed in the context of recent work dealing with eating behavior, with a particular focus on obesity. In the second part of the review, non-invasive strategies to modulate food-related brain processes and functions will be presented. At the leading edge of non-invasive brain-based technologies is real-time fMRI (rtfMRI) neurofeedback, which is a powerful tool to better understand the complexity of human brain-behavior relationships. rtfMRI, alone or when combined with other techniques and tools such as EEG and cognitive therapy, could be used to alter neural plasticity and learned behavior to optimize and/or restore healthy cognition and eating behavior. Other promising non-invasive neuromodulation approaches being explored are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Converging evidence points at the value of these non-invasive neuromodulation strategies to study basic mechanisms underlying eating behavior and to treat its disorders. Both of these approaches will be compared in light of recent work in this field, while addressing technical and practical questions. The third part of this review will be dedicated to invasive neuromodulation strategies, such as vagus nerve stimulation (VNS) and deep brain stimulation (DBS). In combination with neuroimaging approaches, these techniques are promising experimental tools to unravel the intricate relationships between homeostatic and hedonic brain circuits. Their potential as additional therapeutic tools to combat pharmacorefractory morbid obesity or acute eating disorders will be discussed, in terms of technical challenges, applicability and ethics. In a general discussion, we will put the brain at the core of fundamental research, prevention and therapy in the context of obesity and eating disorders. First, we will discuss the possibility to identify new biological markers of brain functions. Second, we will highlight the potential of neuroimaging and neuromodulation in individualized medicine. Third, we will introduce the ethical questions that are concomitant to the emergence of new neuromodulation therapies.

How do risk factors work together? Mediators, moderators, and independent, overlapping, and proxy risk factors.

OBJECTIVE: The authors developed a methodological basis for investigating how risk factors work together. Better methods are needed for understanding the etiology of disorders, such as psychiatric syndromes, that presumably are the result of complex causal chains. METHOD: Approaches from psychology, epidemiology, clinical trials, and basic sciences were synthesized. RESULTS: The authors define conceptually and operationally five different clinically important ways in which two risk factors may work together to influence an outcome: as proxy, overlapping, and independent risk factors and as mediators and moderators. CONCLUSIONS: Classifying putative risk factors into these qualitatively different types can help identify high-risk individuals in need of preventive interventions and can help inform the content of such interventions. These methods may also help bridge the gaps between theory, the basic and clinical sciences, and clinical and policy applications and thus aid the search for early diagnoses and for highly effective preventive and treatment interventions.

Subtyping bulimic women along dietary restraint and negative affect dimensions.

Etiologic models of bulimia center on dieting and negative affect, yet no research has subtyped bulimic individuals according to whether they fit dietary versus negative affect profiles. This study subtyped 265 bulimic women along dieting and depressive dimensions and tested whether subtypes showed differences in eating pathology, clinical correlates, and treatment response. Cluster analysis revealed a pure dietary subtype (62%) and a mixed dietary-depressive subtype (38%). Whereas dietary and dietary-depressive bulimic women showed similar levels of bulimic behaviors, the latter reported more eating and weight obsessions; social maladjustment; higher rates of mood, anxiety, eating, impulse control, and personality disorders; and poorer treatment response. Results suggest dieting is a central feature of bulimia, but depressive affect occurs in only a subset of cases. However, the combination of dieting and depressive affect seems to signal a more severe variant of bulimia.

Psychiatric comorbidity in women with binge eating disorder: prevalence rates from a non-treatment-seeking sample.

This study provides estimates of comorbid psychiatric disorders in women with binge eating disorder (BED). Sixty-one BED and 60 control participants, who were recruited from the community, completed the Structured Clinical Interview for DSM-III-R Axis I and Axis II disorders and self-report measures of eating and general psychiatric symptomatology. Regarding psychiatric diagnoses, women with BED had higher lifetime prevalence rates for major depression, any Axis I disorder, and any Axis II disorder relative to controls. BED women also evidenced greater eating and psychiatric symptomatology than did controls. Results suggest that the prevalence of comorbid psychiatric disorders in BED may be lower than previously indicated by clinical studies.

The relation between adolescent alcohol use and peer alcohol use: a longitudinal random coefficients model.

Longitudinal latent growth models were used to examine the relation between changes in adolescent alcohol use and changes in peer alcohol use over a 3-year period in a community-based sample of 363 Hispanic and Caucasian adolescents. Both adolescent alcohol use and peer alcohol use were characterized by positive linear growth over time. Not only were changes in adolescent alcohol use closely related to changes in peer alcohol use, but the initial status on peer alcohol use was predictive of later increases in adolescent alcohol use and the initial status on adolescent alcohol use was predictive of later increases in peer alcohol use. These results are inconsistent with models positing solely unidirectional effects between adolescent alcohol use and peer alcohol use.

Support for the continuity hypothesis of bulimic pathology.

There has been debate as to whether bulimia represents the endpoint of an eating disorder continuum (the continuity hypothesis) or is categorically different from subthreshold bulimia or an absence of eating disorders (the discontinuity hypothesis). The present study tested whether differences among bulimic, subthreshold bulimic, and control women on weight-concern and psychopathology variables better accord with the continuity or discontinuity hypothesis. These 3 groups were compared on body mass, thin-ideal internalization, body dissatisfaction, dietary restraint, depressive symptoms, anxiety symptoms, and temperamental emotionality. Discriminant function analysis and follow-up pairwise contrasts indicated that the continuity hypothesis was supported for measures of both weight concern and psychopathology. Research and treatment implications of the continuity perspective are discussed.

Naturalistic weight-reduction efforts prospectively predict growth in relative weight and onset of obesity among female adolescents.

This study examined the prospective relations of naturalistic weight-reduction efforts to growth in relative weight and onset of obesity with data from a community study of female adolescents (N = 692). Initial self-labeled dieting, appetite suppressant/laxative use, incidental exercise, vomiting for weight-control purposes, and binge eating predicted elevated growth in relative weight over the 4-year period. Dietary restraint, self-labeled dieting, exercise for weight-control purposes, and appetite suppressant/laxative use predicted an increased risk for obesity onset. Data imply that the weight-reduction efforts reported by adolescents are more likely to result in weight gain than in weight loss and suggest the need to educate youth on more effective weight-control strategies.

A prospective test of the dual-pathway model of bulimic pathology: mediating effects of dieting and negative affect.

Because there have been few longitudinal investigations of integrative etiological theories of bulimia nervosa, this study prospectively tested the dual-pathway model using random regression growth curve models and data from a 3-wave community sample of adolescent girls (N = 231). Initial pressure to be thin and thin-ideal internalization predicted subsequent growth in body dissatisfaction, initial body dissatisfaction predicted growth in dieting and negative affect, and initial dieting and negative affect predicted growth in bulimic symptoms. There was prospective evidence for most of the hypothesized mediational effects. Results are consistent with the assertion that pressure to be thin, thin-ideal internalization, body dissatisfaction, dieting, and negative affect are risk factors for bulimic pathology and provide support for the dual-pathway model.

Prospective differential prediction of adolescent alcohol use and problem use: examining the mechanisms of effect.

This prospective study tested the assertion that psychopathology would predict both adolescent alcohol use and problem use, whereas socialization factors would predict only use, and explored mechanisms by which predictors led to problem use in a community sample of families (N = 216). Externalizing symptoms, parental alcoholism, peer influences, and parental support were indirectly related to negative consequences through their effects on use level. Externalizing symptoms, internalizing symptoms, peer influences, and parental approval of use directly predicted consequences, controlling for the indirect effects through use level. Internalizing pathology potentiated the relation between consumption and consequences, whereas parental support and control mitigated this relation. Collectively, findings provided mixed support for the assertion that psychopathology would predict both use and problem use, whereas socialization factors would predict only use.

Relation of media exposure to eating disorder symptomatology: an examination of mediating mechanisms.

Although investigators have postulated that the thin ideal for women espoused in the media is related to the high rates of eating disorders among females, little research has examined the relation between media exposure and eating pathology. This study assessed the relation of media exposure to eating disorder symptoms and tested whether gender-role endorsement, ideal-body stereotype internalization, and body satisfaction mediated this effect. In data from 238 female undergraduates, structural equation modeling revealed a direct effect of media exposure on eating disorder symptoms. Furthermore, mediational linkages were found for gender-role endorsement, ideal body stereotype internalization, and body satisfaction. The results support the assertion that internalization of sociocultural pressures mediate the adverse effects of the thin ideal.

Age of onset for binge eating and purging during late adolescence: a 4-year survival analysis.

This prospective study examined age of onset for binge eating and purging among girls during late adolescence and tested whether dieting and negative affectivity predicted these outcomes. Of initially asymptomatic adolescents, 5% reported onset of objective binge eating, 4% reported onset of subjective binge eating, and 4% reported onset of purging. Peak risk for onset of binge eating occurred at age 16, whereas peak risk for onset of purging occurred at age 18. Adolescents more often reported onset of a single symptom rather than multiple symptoms, and symptoms were episodic. Dieting and negative affectivity predicted onset of binge eating and purging. Findings suggest that late adolescence is a high-risk period for onset of bulimic behaviors and identify modifiable risk factors for these outcomes.

Body-image and eating disturbances predict onset of depression among female adolescents: a longitudinal study.

This study examined data from a 4-year school-based longitudinal study (n = 1,124), to test whether the increase in major depression that occurs among girls during adolescence may be partially explained by the body-image and eating disturbances that emerge after puberty. Elevated body dissatisfaction, dietary restraint, and bulimic symptoms at study entry predicted onset of subsequent depression among initially nondepressed youth in bivariate analyses controlling for initial depressive symptoms. Although the unique effect for body dissatisfaction was not significant in the multivariate model, this set of risk factors was able to fairly accurately foretell which girls would go on to develop major depression. Results were consistent with the assertion that the body-image- and eating-related risk factors that emerge after puberty might contribute to the elevated rates of depression for adolescent girls.