Stress, Reward, and Cognition in the Obese Brain

C H A P T E R

16 Stress, Reward, and Cognition in the Obese Brain Antonio Verdejo-Garcia1, Cristina Martin-Perez2, Naomi Kakoschke1 1

Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, VIC, Australia; 2Mind, Brain and Behavior Centre, Universidad de Granada, Granada, Spain

O U T L I N E Introduction: Stress, Appetite, and Control 187 Stress, Craving, and Motivational/Affective Biases in Obesity 189 Stress and Cognition in Obesity

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INTRODUCTION: STRESS, APPETITE, AND CONTROL Stress, the pattern of physiological and psychological responses to events that disturb people’s stability, increases appetite and reduces cognitive control. Appetite can temporarily decrease during stressful situations, but it increases soon afterward, leading to specific consumption of high-energy foods.1,2 This occurs through a negative reinforcement mechanism, that is, more rewarding food (i.e., highly palatable food, or “comfort food”) is needed to alleviate the stressful event.3 The biological mechanism involves well-described interactions between glucocorticoids, appetite-related hormones (e.g., ghrelin, leptin, insulin), and the brain’s dopaminergic reward system.4e6 As a result, stress can facilitate reward-related

Stress: Physiology, Biochemistry, and Pathology https://doi.org/10.1016/B978-0-12-813146-6.00016-3

Stress and Brain Function and Structure in Obesity

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Conclusions

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References

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appetitive biases and responses. The hypothalamus also conveys information to brain regions of the limbic system, such as the amygdala and the hippocampus, implicated in the formation of food reward memories and emotional learning.7 In addition, stress can impair higherorder cognitive processes, such as sustained attention, inhibitory control, working memory, and cognitive flexibility, via neuroadaptations in the prefrontal cortex and its connections with the striatum and the limbic system.8e10 Failure in these processes, which are usually grouped under the label “cognitive control,” result in more impulsive, habit-based, and less goal-driven, eating behavior. This eating behavior can be reflected, for instance, in more snacking or greater consumption of food that is immediately rewarding (e.g., confectionary food, food high in sugar, fat, and salt) versus

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well-paced meals and healthier options that are better in the long-term (e.g., health-based selected meals, fresh products such as veggies or fish). As a result, both acute stressful events and chronic life stressors can reduce selfcontrol over reward-related eating.11 Therefore, stress-related sensitization of reward-related appetitive mechanisms and emotional learnings via negative reinforcement and deterioration of cognitive control abilities can turn into a perfect storm of unhealthy eating (Fig. 16.1). KEY POINTS • Stress can increase appetite and impair cognitive control over reward-driven or “comfort” eating. • Overweight and obese individuals experience high levels of personal and social stress, and are more sensitive to the impact of these stressors. • Therefore, understanding the impact of stress on motivation and cognition is crucial to explain the drivers of overweight and obesity.

• In this chapter, we summarize the neurobiological basis of the interaction between stress, appetite and cognitive control systems, and analyze the evidence on the impact of stress on food-related motivation and learning, higher-order cognition and eating behavior, as well as their implications for obesity. People who are overweight or obese are exposed to higher levels of stress. They experience more person-centered stress, as evinced by elevated levels of anxiety and depression.12 They also suffer more interpersonal and social stress, as indicated by increased prejudice and discrimination.13,14 A third and more specific source of stress is the “vicious cycle” of dietary restraint and weight regain, which puts a lot of strain during dieting and triggers shame, selfblame, and guilt following weight regain.15,16 In addition to experiencing more stress, people with obesity are also more sensitive to this stress, that is, they show greater cortisol response than healthy-weight controls to the same stressor17,18

FIGURE 16.1 Diagrammatic schema illustrating the impact of stress on homeostatic regulation, reward and affective systems, as well as the prefrontal “self-control” system. These impacts foster reward-driven food intake (e.g., highly palatable foods) and “comfort food”erelated emotional learnings, and “shuts down” prefrontal control over reward and emotional eating responses.

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and exhibit cognitive control deficits compared with healthy-weight controls with similar sociodemographic characteristics.19 The directionality of the links between overweight and obesity, stress, and cognition is still a matter of debate, but emerging longitudinal research suggests that early stress predates weight gain, which in turn produces cognitive and brain deficits.20,21 Nonetheless, it is likely that this sequence unfolds in the context of pre-existing biological vulnerabilities, as the gene variants associated with obesity are also linked to susceptibility to negative affectivity and impulsive (i.e., low cognitive control) personality.22,23 Regardless of directionality, people who are overweight or obese are more likely to show stress-related alterations in motivation and emotion (e.g., negative affectivity, reward-driven biases), as well as cognitive deficits and brain structural and functional abnormalities. In the next sections, we review the evidence on each of these topics, that is, stress and motivation/emotion, cognition, and the brain, and conclude with a discussion and tentative model of the impacts of stress and cognition, as well as their clinical implications.

STRESS, CRAVING, AND MOTIVATIONAL/AFFECTIVE BIASES IN OBESITY An emerging area of research suggests that food cravings are relevant to understanding the impact of stress on obesity. Food craving refers to an internal state characterized by an intense desire or irresistible urge to consume a specific type of food.24e26 Researchers have proposed both theoretical and empirical links between stress and a change in eating patterns, including craving highly palatable foods (i.e., foods high in fat and/or sugar), which is associated with increased body weight.2,27 For example, Lemmens et al.28 investigated the effect of acute psychological stress induced by a laboratorybased stress paradigm (i.e., an unsolvable mathematical problem) on food cravings. They found that in the absence of hunger, overweight participants reported higher food cravings for highly

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palatable foods (e.g., desserts, snacks) when under stress (vs. rest), while no difference was found between the stress and rest conditions in the normal-weight participants. The results suggest that excess weight individuals may be triggered by rewarding food cues following exposure to stress.28 Another study by Rosenberg et al.29 used a classic paradigm to induce stress, namely, the Trier Social Stress Task (TSST), which consists of a nonanticipated public speech, typically followed by a complex math subtraction task.30 They found that participants with obesity showed higher sweet food craving compared with healthy-weight controls postTSST, and sweet food craving was positively associated with perceived psychological stress. However, the majority of research on stress and food cravings has focused on chronic stress. An early cross-sectional study examined whether self-reported person-centered stress (i.e., anxiety, depression, general psychological distress) impacted food cravings among women with overweight and obesity.31 They found that increased psychological distress was related to higher food cravings, particularly for sweet foods and fast foods.31 Food cravings have also been investigated in the context of self-reported interpersonal stressors in a number of domains, including work, marriage, and relationships, family, and social life. Specifically, Tryon et al.32 found that self-reported chronic stress based on scores in a questionnaire (The Wheaton Chronic Stress Inventory) was positively associated with food cravings among normal-weight women. Similarly, another study demonstrated that among women who were overweight, chronic stress was related to increased sweet food craving, which, in turn, was positively associated with leptin levels, waist circumference, and percent body fat.33 A recent cross-sectional study using a large sample of adults found that chronic psychosocial stress (assessed with an interview) was positively associated with food craving and BMI.34 Furthermore, Chao et al.34 found that food craving partially mediated the association between chronic stress and body mass index, which is consistent with the idea that food craving is an important contributor to the relationship between stress and obesity.

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A recent longitudinal study reported findings from the subsample of these communityrecruited participants who were followed up 6-months later.35 The prospective data showed that chronic stress was not a significant predictor of change in food craving over time; however, low levels of both chronic stress and food cravings were reported in this sample of generally healthy-weight individuals. Nevertheless, the literature indicates that acute and chronic stress are associated with food craving, typically for highly palatable foods, suggesting the need for further experimental and longitudinal research investigating the effect of stress on food craving. An emerging area of research has examined the impact of stress on motivational and affective biases toward food cues. To date, the literature on acute stress and motivational biases has focused on attentional bias for food cues, namely, selective automatic processing, including increased interference by, and orientation toward, food cues relative to other cues.36 Attentional bias is typically measured via response latencies on a Stroop task or a Visual Dot-Probe Task, which provides an objective marker of motivation.37 Most laboratory research has examined the effect of acute stress on attentional bias for food cues. For example, Newman et al.38 used an experimental stress paradigm to induce acute stress through the anticipation of a brief presentation. They found that “external eaters” (i.e., people who tend to eat in response to external food cues) in the stressful condition showed a stronger attentional bias for snack food cues compared with the stress-free condition (Newman et al., 2008). Research has also shown that perceived stress is positively associated with an attentional bias for unhealthy food cues, and that stress-induced negative affect enhances reactivity to food cues as indicated by an increased attentional bias for such cues.39 There is a noted dearth of research examining the impact of stress on motivational and affective biases toward food-related cues, and the studies to date have focused on establishing the role of attentional bias in stress-induced eating in normal-weight samples. Notwithstanding, the two studies exploring the role of stress on motivational responses to food cues consistently

showed that acute stress is associated with automatic orienting of attention toward unhealthy food cues.

STRESS AND COGNITION IN OBESITY Experimental studies can examine the impact of acute stress on cognitive function. Using the TSST procedure, our group examined the impact of acute stress on cognitive performance in tests of sustained attention, inhibitory control, and decision-making among overweight and obese adolescents and well-matched healthy-weight peers. We showed that adolescents who were overweight and obese had higher cortisol response and poorer sustained attention performance than the healthy-weight group after the TSST stressor.18 Sustained attention is crucial to maintain goals “on line” and plan behavior accordingly and thus deficits in the process can result in habit-based “slips” (e.g., snacking) and/or impulsive responses (e.g., unhealthy food intake, binge eating). We also found that stress produced deterioration of decisionmaking performance (i.e., the ability to select choices associated with long-term vs. shortterm reward), but there were no differences between overweight/obese and normal weight adolescents, that is, stress impacted long-term based decision-making regardless of weight status. Nevertheless, other stressedecisionmaking studies have shown that “emotional eating,” an eating behavior phenotype that is overrepresented among overweight and obese individuals is a moderator of this relationship. Specifically, individuals with elevated “emotional eating” are more sensitive to the negative impact of stress on decision-making and more likely to overeat after an acute stress manipulation.40,41 Using a similar acute stress manipulation design and cognitive outcomes, a study in middle-aged adults also found that participants who were overweight and obese had higher cortisol response and poorer performance in declarative memory tasks, albeit not in cognitive control tasks, compared with healthy-weight controls after the TSST stressor.17

STRESS AND BRAIN FUNCTION AND STRUCTURE IN OBESITY

Altogether, current evidence suggests that acute stressors generate a greater stress response and a more negative impact on cognition among overweight/obese versus healthy-weight individuals. However, more research is needed to delineate the cognitive processes that are specifically impacted. In addition, the “emotional eating” phenotype seems to be particularly relevant to define individual variations in the cognitive response to stress, with people high in emotional eating being more likely to suffer the negative impact of stress on cognitive control and decision-making. Insights from the acute stress literature are also useful to understand the findings from research on more stable stress-related traits and the impact of chronic stress on cognition. Using trait impulsivity measures, our group and others have shown that adolescents and adults who are overweight and obese have specific elevations of negative urgency, that is, the tendency to make impulsive acts and decisions while experiencing strong negative emotions.42,43 These findings fit with longitudinal evidence showing a sequential relationship between adolescent internalizing problems (i.e., depression and anxiety), heightened impulsivity, and weight gain and subsequent deficits in attention and memory.20 Depression symptoms are also associated with cognitive control deficits (poorer inhibitory control) and longitudinal weight gain.44 Although very few studies have examined the impact of chronic stress markers on cognition, existing evidence strongly suggests that accumulated stress, indicated by proxy measures, can specifically impact cognitive control abilities. For example, one study showed that levels of Creactive protein, which is a marker of stressrelated low-grade inflammation, were negatively associated with performance in a cognitive flexibility task.45 Adopting a different model of chronic stress, the perception of childhood maternal care among adolescents, one study has also shown that low maternal care (i.e., high chronic stress) is associated with higher energy intake in a food choice test.46 These findings are aligned with the neurobiological evidence that have established that chronic stress can produce substantial neuroadaptations in cortical

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and limbic structures via inflammatory processes and epigenetic changes in neurotrophic factors such as BDNF.9

STRESS AND BRAIN FUNCTION AND STRUCTURE IN OBESITY Stress has a negative impact on the function of the systems that control appetite, as well as the neuroanatomical structure of the brain and some of the regions specifically implicated in emotion regulation and higher-order cognition. The cross-talk between the hypothalamus and striatum, limbic, and prefrontal regions is illustrated by the intrinsic functional connectivity between these regions during a resting state (Fig. 16.2). Functional magnetic resonance imaging (fMRI) studies are well poised to interrogate the brain substrates of acute stresserelated effects on appetite systems, as they can measure brain activation and connections during stressful events. Existing fMRI studies have consistently shown that overweight and obese individuals, compared with healthy-weight controls, have greater activation in the brain’s reward system (i.e., striatum and orbitofrontal cortex regions) during acute stress.47,48 Specifically, participants who were overweight or obese exhibited heightened activation in the hypothalamus, the striatum, and the insula while listening to script-guided imagery based on their own personal stressful experiences, and these activations were positively correlated with insulin and glucose levels. By examining the impact of stress on the brain substrate of “real-time” caloric beverage intake, a fMRI study has also shown significant activation of the amygdala.49 Altogether, these studies confirm that acute stress hyperactivates the brain regions that code reward and affective value. In a recent study, our group has shown that these regions are also importantly involved in the “real-time” selection of high-energy versus low-energy beverages.50 Moreover, we have shown that abnormal connectivity between the hypothalamus and regions of the brain’s reward and emotional systems is associated with highenergy food choices and weight gain.50,51

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FIGURE 16.2 (A) Resting-state functional connectivity between the hypothalamus and the striatum, limbic, and medial prefrontal regions. (B) A stress manipulation (exposure to the Trier Social Stress Task) interrupts the connectivity between the hypothalamus (energy needs) and the striatum and orbitofrontal cortex (reward valuation) among people who are overweight and obese. The “communication breakdown” might underpin reward-driven, nonhomeostatic food choices.

Therefore, fMRI studies indicate that stressrelated sensitization of the reward (striatum, orbitofrontal cortex) and the limbic systems (amygdala) can predispose overweight and obese individuals to consume more highenergy food. On the other hand, using a different type of stressor, that is, an interpersonal challenge, our group has shown that the negative impact of stress on the “obese brain” can be broader and more intricate. We used a wellvalidated social game called the Ultimatum Game, in which participants receive monetary offers from another person, “the proposer,” who is in fact a fictitious character (the fictitious nature is unbeknown to participants). Half of the offers are fair (approximately 50/50 split), but the other half is unfair (the proposer suggests to keep >70% of the money), which tends to generate a strong negative affective reaction in the participant, reflected in activation of brain’s emotional regions such as the amygdala, the insula, and the anterior cingulate cortex.52 We reasoned that overweight and obese participants

would be more sensitive to unfair offers, and hence we could detect brain activation differences with healthy-weight controls. Indeed we found that participants who were overweight or obese showed abnormally decreased activation than controls in the anterior cingulate and the insula, as well as midbrain regions associated with reward prediction.53 Although the psychological interpretation of these brain findings is uncertain, we speculated that the high levels of interpersonal stress suffered by overweight and obese individuals had made them “give up” on fairness (akin to a sense of hopelessness), as reflected in their blunted brain’s emotional response. Fewer studies have examined the impact of chronic stress on brain function or structure, but importantly, their results are consistent with those from acute stress studies. By grouping participants into high and low chronic stress groups according to their scores in a self-report questionnaire (The Wheaton Chronic Stress Inventory), a study has shown that chronic stress

REFERENCES

is associated with hyperactivation of regions of the brain’s reward and emotional systems in response to high-energy food images.54 Specifically, participants with high chronic stress, compared with low-stress controls, showed higher activation in the striatum, the orbitofrontal cortex, the amygdala, and the anterior cingulate cortex, as well as higher connectivity between the striatum and the amygdala (i.e., reward and emotional regions). Interestingly, they also showed lower activation in brain regions implicated in cognitive control, such as the dorsolateral and ventrolateral prefrontal cortices. In another study, in which chronic stress was operationalized as low perceived maternal care during childhood, higher levels of chronic stress were also associated with less activation in superior frontal, parietal, and temporal cortex regions implicated in cognitive control.46 Studies examining the impact of chronic stress on brain structure have primarily focused on gross markers of brain atrophy. For example, a recent study has shown that excessive adiposity and higher levels of C-reactive protein are significantly associated with ventricular enlargement.55 Importantly, using brain perfusion measures, it has also been established that fat accumulation is associated with reduced myocardial perfusion after a pharmacologically induced (dobutamine) stress challenge.56 Longitudinal research has also shown that increases in adiposity are significantly associated with progressive atrophy in the hippocampus, which is one of the key regions for stress regulation.21 These findings indicate that, although chronic stress is a risk factor for obesity, excessive adiposity can also aggravate the impact of acute and chronic stressors on brain structure and function.

CONCLUSIONS Stress has a significant impact on consumption of highly palatable foods, via its impact on motivational, affective, learning, and higher-order cognitive processes, underpinned by the crosstalk between the hypothalamus and other

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homeostatic regulation regions and the brain’s reward and emotional systems. People who are overweight and obese experience high levels of stress and are particularly sensitive to the effects of stress on appetite and cognition. This “double vulnerability” is important to understanding the problems that overweight and obese individuals experience when trying to control food intake and manage weight. In the long-term, both stress and adiposity have neuroadaptive effects on key regions for cognitive control and emotion regulation, including the prefrontal cortex and the hippocampus. Therefore, the cognitive, affective, and brain structural and functional characteristics of overweight and obese individuals need to be factored in during treatment. Although the causal and temporal pathway of the interactions between stress, cognitive and affective phenotypes, and brain alterations is not yet fully understood, current evidence supports the view that early stress can generate trait- and state-related cognitive-affective vulnerabilities, which result in unhealthy eating, weight gain, and body fat accumulation, and ultimately brain deterioration. Therefore, preventative strategies directed to reduce or regulate stress among children and adolescents can also be beneficial to consolidate healthy eating habits and prevent obesity.

References 1. Adam TC, Epel ES. Stress, eating and the reward system. Physiol Behav. 2007;91(4):449e458. 2. Sinha R, Jastreboff AM. Stress as a common risk factor for obesity and addiction. Biol Psychiatr. 2013;73(9): 827e835. 3. Yau YH, Potenza MN. Stress and eating behaviors. Minerva Endocrinol. 2013;38(3):255e267. 4. Burghardt PR, Love TM, Stohler CS, et al. Leptin regulates dopamine responses to sustained stress in humans. J Neurosci. 2012;32(44):15369e15376. 5. Maniam J, Morris MJ. The link between stress and feeding behaviour. Neuropharmacology. 2012;63(1): 97e110. 6. Sominsky L, Spencer SJ. Eating behavior and stress: a pathway to obesity. Front Psychol. 2014;5:434. 7. Dallman MF. Stress-induced obesity and the emotional nervous system. Trends Endocrinol Metab. 2010;21(3): 159e165.

194

16. STRESS, REWARD, AND COGNITION IN THE OBESE BRAIN

8. Girotti M, Adler SM, Bulin SE, Fucich EA, Paredes D, Morilak DA. Prefrontal cortex executive processes affected by stress in health and disease. Prog Neuro Psychopharmacol Biol Psychiatry. 2017;85:161e179. 9. McEwen BS, Eiland L, Hunter RG, Miller MM. Stress and anxiety:Structural plasticity and epigenetic regulation as a consequence of stress. Neuropharmacology. 2012;62(1):3e12. 10. Pruessner JC, Dedovic K, Pruessner M, et al. Stress regulation in the central nervous system: evidence from structural and functional neuroimaging studies in human populationsd2008 Curt Richter Award Winner. Psychoneuroendocrinology. 2010;35(1):179e191. 11. Roberts CJ, Campbell IC, Troop N. Increases in weight during chronic stress are partially associated with a switch in food choice towards increased carbohydrate and saturated fat intake. Eur Eat Disord Rev. 2014;22(1): 77e82. 12. Hemmingsson E. A new model of the role of psychological and emotional distress in promoting obesity: conceptual review with implications for treatment and prevention. Obes Rev. 2014;15(9):769e779. 13. Agerstro¨m J, Rooth DO. The role of automatic obesity stereotypes in real hiring discrimination. J Appl Psychol. 2011;96(4):790e805. 14. Strauss RS, Pollack HA. Social marginalization of overweight children. Arch Pediatr Adolesc Med. 2003;157(8): 746e752. 15. Dulloo AG, Jacquet J, Montani JP, Schutz Y. How dieting makes the lean fatter: from a perspective of body composition autoregulation through adipostats and proteinstats awaiting discovery. Obes Rev. 2015;16(S1): 25e35. 16. Morris MJ, Beilharz JE, Maniam J, Reichelt AC, Westbrook RF. Why is obesity such a problem in the 21st century? The intersection of palatable food, cues and reward pathways, stress, and cognition. Neurosci Biobehav Rev. 2015;58:36e45. 17. Lasikiewicz N, Hendrickx H, Talbot D, Dye L. Stress, cortisol and central obesity in middle aged adults. Obes Facts. 2013;6:44. 18. Verdejo-Garcia A, Moreno-Padilla M, Garcia-Rios MC, et al. Social stress increases cortisol and hampers attention in adolescents with excess weight. PLoS One. 2015a; 10(4):e0123565. 19. Yang Y, Shields GS, Guo C, Liu Y. Executive function performance in obesity and overweight individuals: a meta-analysis and review. Neurosci Biobehav Rev. 2017; 84:225e244. 20. Brook JS, Zhang C, Saar NS, Brook DW. Psychosocial predictors, higher body mass index, and aspects of neurocognitive dysfunction. Percept Mot Skills. 2009;108(1): 181e195. 21. Cherbuin N, Sargent-Cox K, Fraser M, Sachdev P, Anstey KJ. Being overweight is associated with hippocampal atrophy: the PATH through Life Study. Int J Obes. 2015;39(10):1509e1514.

22. Rivera M, Rovira P, Cervilla J, et al. The VAL66MET BDNF genetic polymorphism does not modify the association between major depression and body mass index (BMI). Eur Neuropsychopharmacol. 2017;27:S447. 23. Sevgi M, Rigoux L, Ku¨hn AB, et al. An obesitypredisposing variant of the FTO gene regulates D2Rdependent reward learning. J Neurosci. 2015;35(36): 12584e12592. 24. Waters A, Hill A, Waller G. Bulimics’ responses to food cravings: is binge-eating a product of hunger or emotional state? Behav Res Ther. 2001;39(8):877e886. 25. Weingarten HP, Elston D. The phenomenology of food cravings. Appetite. 1990;15(3):231e246. 26. White MA, Whisenhunt BL, Williamson DA, Greenway FL, Netemeyer RG. Development and validation of the food-craving inventory. Obesity. 2002; 10(2):107e114. 27. Potenza MN, Grilo CM. How relevant is food craving to obesity and its treatment? Front Psychiatr. 2014;5:164. 28. Lemmens SG, Rutters F, Born JM, WesterterpPlantenga MS. Stress augments food ‘wanting’and energy intake in visceral overweight subjects in the absence of hunger. Physiol Behav. 2011;103(2):157e163. 29. Rosenberg N, Bloch M, Avi IB, et al. Cortisol response and desire to binge following psychological stress: comparison between obese subjects with and without binge eating disorder. Psychiatr Res. 2013;208(2):156e161. 30. Kirschbaum C, Pirke KM, Hellhammer DH. The ‘trier social stress test’ea tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology. 1993;28(1e2):76e81. 31. Lim SS, Norman RJ, Clifton PM, Noakes M. Hyperandrogenemia, psychological distress, and food cravings in young women. Physiol Behav. 2009;98(3):276e280. 32. Tryon MS, DeCant R, Laugero KD. Having your cake and eating it too: a habit of comfort food may link chronic social stress exposure and acute stressinduced cortisol hyporesponsiveness. Physiol Behav. 2013b;114:32e37. 33. Macedo DM, Diez-Garcia RW. Sweet craving and ghrelin and leptin levels in women during stress. Appetite. 2014;80:264e270. 34. Chao A, Grilo CM, White MA, Sinha R. Food cravings mediate the relationship between chronic stress and body mass index. J Health Psychol. 2015;20(6):721e729. 35. Chao AM, Jastreboff AM, White MA, Grilo CM, Sinha R. Stress, cortisol, and other appetite-related hormones: prospective prediction of 6-month changes in food cravings and weight. Obesity. 2017;25(4):713e720. 36. Jansen A, Houben K, Roefs A. A cognitive profile of obesity and its translation into new interventions. Front Psychol. 2015;6:1807. 37. Werthmann J, Jansen A, Roefs A. Worry or craving? A selective review of evidence for food-related attention biases in obese individuals, eating-disorder patients, restrained eaters and healthy samples. Proc Nutr Soc. 2015;74(2):99e114.

REFERENCES

38. Newman E, O’Connor DB, Conner M. Attentional biases for food stimuli in external eaters: possible mechanism for stress-induced eating? Appetite. 2008;51(2): 339e342. 39. Hepworth R, Mogg K, Brignell C, Bradley BP. Negative mood increases selective attention to food cues and subjective appetite. Appetite. 2010;54(1):134e142. 40. Davis C, Levitan RD, Muglia P, Bewell C, Kennedy JL. Decision-making deficits and overeating: a risk model for obesity. Obesity. 2004;12(6):929e935. 41. van Strien T, Ouwens MA, Engel C, de Weerth C. Hunger, inhibitory control and distress-induced emotional eating. Appetite. 2014;79:124e133. 42. Delgado-Rico E, Rı´o-Valle JS, Gonza´lez-Jime´nez E, Campoy C, Verdejo-Garcı´a A. BMI predicts emotiondriven impulsivity and cognitive inflexibility in adolescents with excess weight. Obesity. 2012;20(8): 1604e1610. 43. Mobbs O, Cre´pin C, Thie´ry C, Golay A, Van der Linden M. Obesity and the four facets of impulsivity. Patient Educ Couns. 2010;79(3):372e377. 44. Stinson EJ, Krakoff J, Gluck ME. Depressive symptoms and poorer performance on the stroop task are associated with weight gain. Physiol Behav. 2018;186:25e30. 45. Lasselin J, Magne E, Beau C, et al. Low-grade inflammation is a major contributor of impaired attentional set shifting in obese subjects. Brain Behav Immun. 2016;58: 63e68. 46. Machado TD, Dalle Molle R, Reis RS, et al. Interaction between perceived maternal care, anxiety symptoms, and the neurobehavioral response to palatable foods in adolescents. Stress. 2016;19(3):287e294. 47. Jastreboff AM, Potenza MN, Lacadie C, Hong KA, Sherwin RS, Sinha R. Body mass index, metabolic factors, and striatal activation during stressful and neutral-relaxing states: an FMRI study. Neuropsychopharmacology. 2011;36(3):627e637.

195

48. Jastreboff AM, Sinha R, Lacadie C, Small DM, Sherwin RS, Potenza MN. Neural correlates of stressand food cueeinduced food craving in obesity: association with insulin levels. Diabetes Care. 2013;36(2):394e402. 49. Rudenga KJ, Sinha R, Small DM. Acute stress potentiates brain response to milkshake as a function of body weight and chronic stress. Int J Obes. 2013;37(2):309e316. 50. Harding IH, Andrews ZB, Mata F, et al. Brain substrates of unhealthy versus healthy food choices: influence of homeostatic status and body mass index. Int J Obes. 2018;42(3):448e454. 51. Contreras-Rodrı´guez O, Vilar-Lo´pez R, Andrews ZB, Navas JF, Soriano-Mas C, Verdejo-Garcı´a A. Altered cross-talk between the hypothalamus and nonhomeostatic regions linked to obesity and difficulty to lose weight. Sci Rep. 2017;7(1):9951. 52. Sanfey AG, Rilling JK, Aronson JA, Nystrom LE, Cohen JD. The neural basis of economic decisionmaking in the ultimatum game. Science. 2003; 300(5626):1755e1758. 53. Verdejo-Garcı´a A, Verdejo-Roma´n J, Rio-Valle JS, Lacomba JA, Lagos FM, Soriano-Mas C. Dysfunctional involvement of emotion and reward brain regions on social decision making in excess weight adolescents. Hum Brain Mapp. 2015b;36(1):226e237. 54. Tryon MS, Carter CS, DeCant R, Laugero KD. Chronic stress exposure may affect the brain’s response to high calorie food cues and predispose to obesogenic eating habits. Physiol Behav. 2013a;120:233e242. 55. Lai YH, Liu CC, Kuo JY, et al. Independent effects of body fat and inflammatory markers on ventricular geometry, midwall function, and atrial remodeling. Clin Cardiol. 2014;37(3):172e177. 56. Hall ME, Brinkley TE, Chughtai H, et al. Adiposity is associated with gender-specific reductions in left ventricular myocardial perfusion during dobutamine stress. PLoS One. 2016;11(1):e0146519.