ArticleLiterature Review

Ovarian Hormones and Reward Processes in Palatable Food Intake and Binge Eating

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Abstract

Ovarian hormones are associated with risk for binge eating in women. Recent animal and human studies suggest that food-related reward processing may be one set of neurobiological factors that contribute to these relationships, but additional studies are needed to confirm and extend findings.

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... In humans, the fluctuation of endogenous estrogens in females has been associated with binge eating behavior or the intake of highly palatable foods (Ma et al., 2020). This is supported by literature in rodents such that food reward for sucrose pellets varies across the estrous cycle (Richard et al., 2017). ...
... This is supported by literature in rodents such that food reward for sucrose pellets varies across the estrous cycle (Richard et al., 2017). In both human and animal models, the presence of high estrogen levels is associated with a reduction in palatable food intake (Ma et al., 2020;Richard et al., 2017), although it has been reported that high levels of estrogen increase palatable food intake. For example, in female rats, E2 treatment is associated with a greater intake of a palatable diet (chocolate cake mix) (Boswell et al., 2006), yet others do not report such an association using a similarly palatable chocolate/fat diet (Butera et al., 2010). ...
Article
Women are vulnerable to developing mental disorders that are associated with circulating estrogens. Estrogens, especially 17β-estradiol (E2), have a wide array of effects on the brain, affecting many behavioral endpoints associated with mental illness. By using a total estrogen receptor (ER) α knockout (KO), an ERα knock in/knock out (KIKO) that lacks a functional DNA-binding domain, and wild type (WT) controls treated with either oil or E2, we evaluated ERα signaling, dependent and independent of the estrogen response element (ERE), on avoidance behavior, social interactions and memory, and palatable ingestive behavior using the open field test, the elevated plus maze, the light dark box, the 3-chamber test, and palatable feeding. We found that ERα does not mediate control of anxiety-like behaviors but rather yielded differences in locomotor activity. In evaluating social preference and social recognition memory, we observed that E2 may modulate these measures in KIKO females but not KO females, suggesting that ERE-independent signaling is likely involved in sociability. Lastly, observations of palatable (high-fat) food intake suggested an increase in palatable eating behavior in oil-treated KIKO females. Oil-treated KO females had a longer latency to food intake, indicative of an anhedonic phenotype compared to oil-treated WT and KIKO females. We have observed that social-related behaviors are potentially influenced by ERE-independent ERα signaling and hedonic food intake requires signaling of ERα.
... It has been observed in girls that high levels of leptin in the blood are related to high stress [117]. Several investigations in women have investigated the existence of differential responses to appetizing food throughout the cycle, concluding that in phases with a high concentration of estrogen, motivation for reward is lower, so emotional hunger is reduced; on the contrary, in the luteal phase where the predominant levels are those of progesterone, the desire for appetizing food increases exponentially [118]. Women more susceptible to binge eating have compromised interoceptive awareness of physiological states [119], resulting in dietary limitation that, as a consequence, could negatively affect the dopaminergic system [118]. ...
... Several investigations in women have investigated the existence of differential responses to appetizing food throughout the cycle, concluding that in phases with a high concentration of estrogen, motivation for reward is lower, so emotional hunger is reduced; on the contrary, in the luteal phase where the predominant levels are those of progesterone, the desire for appetizing food increases exponentially [118]. Women more susceptible to binge eating have compromised interoceptive awareness of physiological states [119], resulting in dietary limitation that, as a consequence, could negatively affect the dopaminergic system [118]. ...
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Major depressive disorder (MDD) is an incapacitating condition characterized by loss of interest, anhedonia and low mood, which affects almost 4% of people worldwide. With rising prevalence, it is considered a public health issue that affects economic productivity and heavily increases health costs alone or as a comorbidity for other pandemic non-communicable diseases (such as obesity, cardiovascular disease, diabetes, inflammatory bowel diseases, etc.). What is even more noteworthy is the double number of women suffering from MDD compared to men. In fact, this sex-related ratio has been contemplated since men and women have different sexual hormone oscillations, where women meet significant changes depending on the age range and moment of life (menstruation, premenstruation, pregnancy, postpartum, menopause…), which seem to be associated with susceptibility to depressive symptoms. For instance, a decreased estrogen level promotes decreased activation of serotonin transporters. Nevertheless, sexual hormones are not the only triggers that alter neurotransmission of monoamines and other neuropeptides. Actually, different dietary habits and/or nutritional requirements for specific moments of life severely affect MDD pathophysiology in women. In this context, the present review aims to descriptively collect information regarding the role of malnutrition in MDD onset and course, focusing on female patient and especially macro- and micronutrient deficiencies (amino acids, ω3 polyunsaturated fatty acids (ω3 PUFAs), folate, vitamin B12, vitamin D, minerals…), besides providing evidence for future nutritional intervention programs with a sex-gender perspective that hopefully improves mental health and quality of life in women.
... Like ghrelin, estrogen influences the rewarding properties of food. Clinical data show that food cravings for high-fat, palatable foods, as well as binge-eating episodes,increase in the luteal phase of the menstrual cycle when estrogen levels are low and similar results have been seen in rodents (see (93)for review). Moreover, eating disorders like binge-eating, anorexia and bulimia nervosa are primarily diagnosed in females, and have been associated with dysregulation of reward circuitry (94). ...
Article
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Ghrelin is considered one of the most potent orexigenic peptide hormones and one that promotes homeostatic and hedonic food intake. Research on ghrelin, however, has been conducted predominantly in males and particularly in male rodents. In female mammals the control of energy metabolism is complex and it involves the interaction between ovarian hormones like estrogen and progesterone, and metabolic hormones. In females, the role that ghrelin plays in promoting feeding and how this is impacted by ovarian hormones is not well understood. Basal ghrelin levels are higher in females than in males, and ghrelin sensitivity changes across the estrus cycle. Yet, responses to ghrelin are lower in female and seem dependent on circulating levels of ovarian hormones. In this review we discuss the role that ghrelin plays in regulating homeostatic and hedonic food intake in females, and how the effects of ghrelin interact with those of ovarian hormones to regulate feeding and energy balance.
... Indeed, components of negative emotionality, emotion regulation, and emotion-based rash action are associated with early pubertal maturation (e.g., Mendle et al., 2007;Ullsperger & Nikolas, 2017) and binge eating risk (Culbert et al., 2015;Lavender et al., 2015). Furthermore, differences in the timing of pubertal hormone exposure result in permanent changes in the brain and behavior (Graber, 2013;Zehr et al., 2007), including within biological systems implicated in binge eating (e.g., monoaminergic and mesocorticolimbic systems; Becker, 2009;Ma et al., 2020). Moving forward, it will be important to explore whether emotion-based mechanisms and/or organizational effects of ovarian hormones drive early pubertal timing effects on binge eating. ...
Article
Introduction Early pubertal timing increases risk for disordered eating (DE) in females, but the extent to which associations persist after puberty and are relevant to all types of DE symptoms is unclear. Factors that link pubertal timing and DE also remain unknown, although leading theories posit that adiposity and body-focused psychosocial factors play a key role. Thus, this study examined pubertal timing effects on several types of DE symptoms in young adult women and evaluated whether body mass index (BMI), pressures for thinness, thin-ideal internalization, and/or history of weight-based teasing account for such associations. Methods This study included a racially and ethnically diverse sample of 342 female college students (Mage = 20.44, SD = 3.46). Women retrospectively reported their age at onset of menses, which served as the pubertal timing indicator, and completed self-report questionnaires on DE symptoms, perceived pressures for thinness, thin-ideal internalization, and history of weight-based teasing. BMI was calculated from height/weight measurements. Results Earlier pubertal timing was associated with body dissatisfaction and binge eating, but not other DE symptoms (dieting, excessive exercise, muscle building) in young adult women. BMI accounted for pubertal timing effects on body dissatisfaction, whereas none of the examined factors explained pubertal timing effects on binge eating. Conclusions Earlier pubertal timing may exert long-term effects on only some DE symptoms in women, and the etiologic factors underlying pubertal timing effects on DE outcomes may differ across symptom types.
... Similarly to N/OFQ-NOP system, considerable evidence suggested sex differences in other orexigenic signaling mechanisms implicated in binge eating, such those depending on the relaxin-family peptide-3 [244,245] and orexin-1 receptors [246][247][248]. This is not surprising considering that sexual dimorphism has been described in binge eating behavior both in humans [249][250][251] and animals [252][253][254][255][256]. In light of the complex role of N/OFQ in feeding regulation, and based on the current knowledge, it is difficult to provide an unambiguous interpretation of the effect of NOP on binge eating. ...
Article
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Nociceptin/orphanin FQ (N/OFQ) is a 17-residue neuropeptide that binds the nociceptin opioid-like receptor (NOP). N/OFQ exhibits nucleotidic and aminoacidics sequence homology with the precursors of other opioid neuropeptides but it does not activate either MOP, KOP or DOP receptors. Furthermore, opioid neuropeptides do not activate the NOP receptor. Generally, activation of N/OFQ system exerts anti-opioids effects, for instance toward opioid-induced reward and analgesia. The NOP receptor is widely expressed throughout the brain, whereas N/OFQ localization is confined to brain nuclei that are involved in stress response such as amygdala, BNST and hypothalamus. Decades of studies have delineated the biological role of this system demonstrating its involvement in significant physiological processes such as pain, learning and memory, anxiety, depression, feeding, drug and alcohol dependence. This review discusses the role of this peptidergic system in the modulation of stress and stress-associated psychiatric disorders in particular drug addiction, mood, anxiety and food-related associated-disorders. Emerging preclinical evidence suggests that both NOP agonists and antagonists may represent a effective therapeutic approaches for substances use disorder. Moreover, the current literature suggests that NOP antagonists can be useful to treat depression and feeding-related diseases, such as obesity and binge eating behavior, whereas the activation of NOP receptor by agonists could be a promising tool for anxiety.
... Studies in women with bulimia nervosa report an increased frequency of binge episodes during the mid-luteal phase (Edler et al., 2007;Lester et al., 2003). Corresponding to this, cyclic changes in ovarian hormones have also been associated with eating behaviors, such as food intake, in adult women (Ma et al., 2020). For example, during the ovulatory phase of the menstrual cycle, food intake is at its lowest (Asarian and Geary, 2013;Buffenstein et al., 1995;Czaja and Goy, 1975;Dalvit-McPhillips, 1983), whereas during the mid-luteal or premenstrual phases, food intake reaches its peak (Asarian and Geary, 2006;Hirschberg, 2012;Leeners et al., 2017). ...
Article
Disordered eating is often associated with marked psychological and emotional distress, and severe adverse impact on quality of life. Several factors can influence eating behavior and drive food consumption in excess of energy requirements for homeostasis. It is well established that stress and negative affect contribute to the aetiology of eating disorders and weight gain, and there is substantial evidence suggesting sex differences in sub-clinical and clinical types of overeating. This review will examine how negative affect and stress shape eating behaviors, and how the relationship between the physiological, endocrine, and neural responses to stress and eating behaviors differs between men and women. We will examine several drivers of overeating and explore possible mechanisms underlying sex differences in eating behavior.
... Yet, the effects of lower concentrations of testosterone on LOC-eating persist into adulthood (Culbert, Shope, Sisk, & Klump, 2020). Importantly, GH are hypothesized to increase LOC-eating by modulating "wanting for" and neurobiological sensitivity to the rewarding and pleasurable aspects of palatable foods (Culbert et al., 2021;Ma et al., 2020), particularly among females. Empirical tests of this theory in youth are needed. ...
Article
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Objective Among youth with overweight, food cravings (FC) are associated with loss‐of‐control (LOC)‐eating, but the impact of sex‐associated biological characteristics on this relationship is unknown. We examined whether sex and gonadal hormone concentrations moderated the relationships between FC and LOC‐eating severity among healthy boys and girls across the weight strata in natural and laboratory environments. Method Using ecological momentary assessment (EMA), FC, and LOC‐eating severity were reported 3–5 times a day for 2 weeks. In the laboratory, participants reported FC, consumed lunch from a buffet test meal designed to simulate LOC‐eating, and rated LOC‐eating severity during the meal. Results Eighty‐seven youth (13.0 ± 2.7 years, 58.6% female, 32.2% with overweight/obesity) participated. EMA measured general and momentary FC were positively associated with LOC‐eating severity (ps < .01), with no differences by sex (ps = .21–.93). Estradiol and progesterone significantly moderated the relationships between FC and LOC‐eating such that general FC and LOC‐eating severity were only positively associated among girls with greater (vs. lower) estradiol (p = .01), and momentary FC and LOC‐eating severity were only positively associated among girls with greater (vs. lower) progesterone (p = .01). Boys' testosterone did not significantly moderate the associations between FC and LOC‐eating severity (ps = .36–.97). At the test meal, pre‐meal FC were positively related to LOC‐eating severity (p < .01), without sex or hormonal moderation (ps = .20–.64). Discussion FC were related to LOC‐eating severity in boys and girls. In the natural environment, gonadal hormones moderated this relationship in girls, but not boys. The mechanisms through which gonadal hormones might affect the relationship between FC and LOC‐eating warrant investigation.
... Endogenous estrogens, on the other hand, are demonstrated to have anorexigenic effects through their action on central estrogen receptors (34,36). In both humans and rhesus macaques, EI is lowest in the periovulatory phase when estradiol is the highest (35). ...
Article
Objective This study aimed to perform a preliminary investigation of the impact of combined hormonal contraceptive (CHC) use on weight loss during an 18‐month behavioral weight‐loss trial. Methods Adults (n = 170; 18‐55 years; BMI 27‐42 kg/m²) received a weight‐loss intervention that included a reduced‐calorie diet, a progressive exercise prescription, and group‐based behavioral support. Premenopausal women (n = 110) were classified as CHC users (CHC, n = 17) or non‐CHC users (non‐CHC, n = 93). Changes in weight were examined within groups using a linear mixed model, adjusted for age and randomized group assignment. Results At 6 M, weight was reduced from baseline in both CHC (mean, −6.7 kg; 95% CI: −9.8 to −3.7 kg) and non‐CHC (−9.1 kg; −9.1 to −6.4 kg). Between 6 and 18 M, CHC regained weight (4.9 kg; 0.9 to 8.9 kg), while weight remained relatively unchanged in non‐CHC (−0.1 kg; −1.8 to 1.6 kg). At 18 M, weight was relatively unchanged from baseline in CHC (−1.8 kg; −7.3 to 3.6 kg) and was reduced from baseline in non‐CHC (−7.9 kg; −10.2 to −5.5 kg). Conclusions In this secondary data analysis, CHC use was associated with weight regain after initial weight loss. Prospective studies are needed to further understand the extent to which CHC use influences weight loss and maintenance.
Article
Background : As eating behavior changes in relation to the menstrual cycle and weight changes with menopausal transition, ovarian hormones appear to be involved in regulating eating behavior. However, observations are contradictory and are difficult to compare, due to methodological problems related to nutritional epidemiology. To better understand the relationship between ovarian steroid hormones and eating behavior, our study evaluates women's responses to visual food cues at different points in the menstrual cycle with their specific serum estrogen/progesterone levels and women's responses in the case of strong estrogen changes in the context of fertility treatments. Methods : We collected data from 129 women, 44 of whom received in vitro fertilization (IVF) at the Department of Reproductive Endocrinology, University Hospital Zurich. A total of 85 women with natural cycles were recruited at the University Hospital Zurich (n=37) and at the Hannover Medical School (n=48). Our observational study used 4 different measurement time points across the natural cycle and 2 measurement time points in women with supraphysiological estradiol levels during fertility treatments. Using a second cycle, we then tested our results for replication. At these predefined time points, women were shown pictures of 11 categories of food, with 4 items for each category and blood samples for measurement of hormone levels were taken. Food preferences registered at the time of the investigation were indicated on a visual analogue scale (0-100). Results : We did not find any statistically significant association between women's serum hormone levels and the rating of visually presented food, either during the menstrual cycle or during fertility treatments after controlling for multiple testing (all p>0.005). Ratings for fruits, vegetables, and carbohydrates showed a significant linear decline throughout the first menstrual cycle (p<0.01), which did not replicate in the second cycle (p>0.05). In contrast, the ratings for sweets showed a significant linear decline in both cycles (both p<0.01), with a mean rating of 54.2 and 48.8 in the menstrual phase of the first and second cycle, respectively, to a mean rating of 47.7 and 43.4 in the premenstrual phase of the first and second cycle, respectively. During fertility treatments, no food rating showed a significant change (all p>0.05). Mood such as negative and positive affects did not influence ratings for visual food cues neither throughout the menstrual cycles nor during fertility treatment. Conclusions : Serum levels of estradiol and progesterone do not correlate with food ratings in women, even when estradiol levels are above the physiological level of a natural menstrual cycle. Since, except for sweets, significant changes in food ratings in a first cycle did not replicate in a second menstrual cycle, significant findings from the literature based on animal or human studies focusing on a single-cycle have to be interpreted with caution.
Article
Background: Increased circulating levels of the steroid hormone 17β-estradiol (E2) are associated with higher levels of binge drinking in women. In female mice, estrogen receptors in the ventral tegmental area, a dopaminergic region of the brain involved in the motivation to consume ethanol, regulate binge-like ethanol intake. We recently developed a brain-penetrant selective estrogen receptor degrader (SERD), YL3-122, that could be used to test the behavioral role of brain estrogen receptors and hypothesized that treating female mice with this compound could reduce binge-like ethanol drinking. Methods: Female C57BL/6J mice were treated systemically with YL3-122 and a related SERD with low brain penetrance, XR5-27, and tested for binge-like ethanol consumption in the drinking in the dark (DID) test. Mice were also tested for sucrose and water consumption and blood ethanol clearance after treatment with the SERDs. Finally, the effect of ethanol exposure on Esr1 gene expression was measured in the ventral tegmental area (VTA), prefrontal cortex (PFC), and ventral hippocampus (vHPC) of male and female mice by quantitative real-time PCR after 4 DID sessions. Results: YL3-122 reduced ethanol consumption when mice were in diestrus and not estrus. YL3-122 also decreased sucrose consumption, but did not alter water intake or blood ethanol clearance. XR5-27 did not affect any of these measures. Binge-like ethanol drinking resulted in increased Esr1 transcript in the VTA of both sexes, male vHPC, and female PFC. Conclusions: These results indicate that SERD treatment can decrease binge-like ethanol drinking in female mice and in theory could be a novel strategy to reduce binge drinking in women, with the caveat that effectiveness may depend on menstrual cycle phase. In addition, Esr1 transcript is increased by binge ethanol exposure in both sexes but in a brain region-specific manner.
Article
Objective: Palatable food (PF) intake is significantly greater in females than males and increases during adolescence. Previous data suggest that puberty and ovarian hormones may contribute to these sex and developmental differences, but few studies have examined this possibility. The aim of the current study was to address these gaps by examining trajectories of PF and chow intake during pre-puberty, puberty, and adulthood in intact female rats (Study 1) as well as in those receiving pre-pubertal ovariectomies (P-OVX) (Study 2). Method: We examined our study aims using archival data from 66 intact Sprague-Dawley female rats (Study 1) and 77 P-OVX and 79 intact Sprague-Dawley female rats (Study 2). PF and chow intake were measured using a free-choice, intermittent exposure paradigm in which rats were exposed to both food types starting in pre-puberty and continuing into adulthood. Results: Mixed linear models revealed a specific effect of puberty on PF intake in both studies. PF intake increased substantially during puberty in all rats, but increases were particularly pronounced in P-OVX rats in Study 2. By contrast, chow intake increased significantly during pre-puberty (rather than puberty) in both studies, and these increases were relatively unaffected by P-OVX. Discussion: Findings confirm a specific effect of puberty and ovarian hormone removal on PF intake in female rats. Differential trajectories of PF versus chow intake highlight potential reward-based processes in pubertal and ovarian hormone effects on PF intake in females.
Article
Eating disorders (ED) are complex mental illnesses and are not a result of personal choice. Full recovery from an ED is possible. The severity and inherent lethality of an ED is undisputed, and the role of the registered dietitian nutritionist (RDN) is essential. Clinical symptomology presents at varying developmental milestones and is perpetuated through a sociocultural evaluation of beauty and drive for ascetic idealism. ED are globally prevalent in 4.4% of the population aged 5 to 17 years, yet affect individuals across the entire lifespan, including all cultures and genders. The Behavioral Health Nutrition Dietetic Practice Group, along with the Academy of Nutrition and Dietetics Quality Management Committee, revised the Standards of Practice (SOP) and Standards of Professional Performance (SOPP) for RDNs in Eating Disorders. Including the RDN in ED treatment is vital for all levels of care. The RDN must be perceptive to negative symptoms indicative of psychological triggers when exploring food belief systems, patterns of disinhibition, and nutrition misinformation with clients. Through a conscious awareness of medical, psychological, and behavioral strategies, the implementation of the SOP and SOPP supports a dynamic and holistic view of ED treatment by the RDN. The SOP and SOPP are complementary resources for RDNs and are intended to be used as self-evaluation tools for assuring competent practice in ED and for determining potential education, training, supervision, and mentorship needs for advancement to a higher practice level in a variety of settings.
Article
Background Individuals with eating disorders (EDs) have increased rates of major depressive disorder (MDD) and anxiety disorders. Yet, few studies have investigated rates of EDs and their symptoms in individuals presenting with MDD/anxiety disorders. Identifying potential disordered eating in people with MDD/anxiety disorders is important because even subclinical disordered eating is associated with reduced quality of life, and undiagnosed eating pathology may hinder treatment progress for both MDD/anxiety disorders and comorbid EDs. Method We compared rates of EDs (anorexia nervosa, bulimia nervosa, binge‐eating disorder, and other specified feeding and eating disorders) and their symptoms in 130 women with, and 405 women without, lifetime MDD or an anxiety disorder (generalized anxiety disorder, obsessive–compulsive disorder, social phobia, specific phobia, panic disorder, agoraphobia, or post‐traumatic stress disorder) recruited from the population‐based Michigan State University Twin Registry. Lifetime ED and MDD/anxiety diagnoses, and lifetime clinically significant disordered eating behaviors (e.g., binge eating, excessive exercise) were assessed using the Structured Clinical Interview for DSM‐IV (SCID). Results Among participants with lifetime MDD or any anxiety disorder, 13% met criteria for a lifetime ED and 39% reported engaging in at least one lifetime clinically significant disordered eating behavior (e.g., binge eating) on the SCID. In contrast, only 3% of participants without a history of MDD/an anxiety disorder met criteria for a lifetime ED, and only 11% reported lifetime clinically significant disordered eating behavior. Discussion Our findings suggest that women with MDD and anxiety disorders have elevated rates of EDs, and it is therefore imperative to screen for disordered eating in these populations.
Article
Recent research on the health impacts of added sugar has prompted the comparison of the effects of its two major components, glucose and fructose. Fructose was identified as a risk factor for obesity and metabolic syndrome. However, due to the differences in metabolic responses and responsivity of reward circuitry to palatable food, it is unknown if glucose and fructose induce similar appetite-related responses in humans with varying weights. This study compared the behavioral responses to food in young females of a healthy weight (n = 31) and with excess weight (n = 28). We hypothesized: (1) the inhibitory effect of glucose (versus fructose) on food-related responses would be greater in subjects of a healthy weight than in those with overweight/obesity; (2) subjects with overweight/obesity would exhibit a stronger preference for food than subjects with a healthy weight. After an overnight fast, the subjects ingested a glucose or equicaloric fructose beverage on two separate days, respectively. Then, they completed liking and wanting ratings and two decision-making tasks, followed by ad libitum food intake. The results revealed that fructose reduced both liking and wanting for food in subjects with overweight/obesity, and also decreased caloric intake in all subjects. Relative to the healthy weight group, subjects with overweight/obesity preferred the immediate reward. Moreover, only in the healthy weight group, liking and wanting scores for food were positively associated with actual food consumption. Overall, fructose (versus glucose) showed an acute inhibitory effect on appetite-related responses in subjects with excess weight.
Article
Background: Low emotion differentiation (the tendency to experience vague affective states rather than discrete emotions) is associated with psychopathology marked by emotion regulation deficits and impulsive/maladaptive behavior. However, research examining associations between emotion differentiation and dysregulated eating is nascent and has yet to incorporate measures of clinically significant binge eating. Different measures of emotion differentiation have also been used, impeding cross-study comparisons. We therefore examined associations between several emotion differentiation measures and binge eating-related phenotypes across a spectrum of severity. Methods: Women (N = 482) from the Michigan State University Twin Registry completed the Positive and Negative Affect Schedule (PANAS) daily for 45 consecutive days. Three measures of negative/positive emotion differentiation (NED/PED) were created using the intraclass correlation coefficient (ICC), average interitem correlation, and average daily variance between negative/positive emotion ratings on the PANAS. Associations between NED/PED measures and emotional eating (EE) and a history of binge eating episodes (BEs) were then examined, controlling for affect intensity and BMI. Results: Lower PED was associated with greater odds of BEs across the ICC and average interitem correlation measures, and more EE on the daily variance measure. Findings involving NED were less consistent; lower NED was associated with greater EE and greater odds of BEs using the daily variance measure only. Conclusion: Low PED is associated with clinically significant binge eating, and some aspects of NED may also be relevant for binge eating-related phenotypes. Further research examining the constructs captured by different emotion differentiation measures and their relevance to binge eating is needed.
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This review takes a historical perspective on concepts in the psychology of motivation and emotion, and surveys recent developments, debates and applications. Old debates over emotion have recently risen again. For example, are emotions necessarily subjective feelings? Do animals have emotions? I review evidence that emotions exist as core psychological processes, which have objectively detectable features, and which can occur either with subjective feelings or without them. Evidence is offered also that studies of emotion in animals can give new insights into human emotions. Beyond emotion, motivation concepts have changed over decades too, and debates still continue. Motivation was once thought in terms of aversive drives, and reward was thought of in terms of drive reduction. Motivation-as-drive concepts were largely replaced by motivation-as-incentive concepts, yet aversive drive concepts still occasionally surface in reward neuroscience today. Among incentive concepts, incentive salience is a core motivation process, mediated by brain mesocorticolimbic systems (dopamine-related systems) and sometimes called ‘wanting’ (in quotation marks), to distinguish it from cognitive forms of desire (wanting without quotation marks). Incentive salience as ‘wanting’ is separable also from pleasure ‘liking’ for the same reward, which has important implications for several human clinical disorders. Ordinarily, incentive salience adds motivational urgency to cognitive desires, but ‘wanting’ and cognitive desires can dissociate in some conditions. Excessive incentive salience can cause addictions, in which excessive ‘wanting’ can diverge from cognitive desires. Conversely, lack of incentive salience may cause motivational forms of anhedonia in depression or schizophrenia, whereas a negatively-valenced form of ‘fearful salience’ may contribute to paranoia. Finally, negative ‘fear’ and ‘disgust’ have both partial overlap but also important neural differences.
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Objective In recent decades there has been growing interest in the use of neuroimaging techniques to explore the structural and functional brain changes that take place in those with eating disorders. However, to date, the majority of research has focused on patients with anorexia nervosa. This systematic review addresses a gap in the literature by providing an examination of the published literature on the neurobiology of individuals who binge eat; specifically, individuals with bulimia nervosa (BN) and binge eating disorder (BED). Methods A systematic review was conducted in accordance with PRISMA guidelines using PubMed, PsycInfo, Medline and Web of Science, and additional hand searches through reference lists. 1,003 papers were identified in the database search. Published studies were included if they were an original research paper written in English; studied humans only; used samples of participants with a diagnosed eating disorder characterised by recurrent binge eating; included a healthy control sample; and reported group comparisons between clinical groups and healthy control groups. Results Thirty-two papers were included in the systematic review. Significant heterogeneity in the methods used in the included papers coupled with small sample sizes impeded the interpretation of results. Twenty-one papers utilised functional Magnetic Resonance Imaging (fMRI); seven papers utilized Magnetic Resonance Imaging (MRI) with one of these using both MRI and Positron Emission Technology (PET); three studies used Single-Photon Emission Computed Tomography (SPECT) and one study used PET only. A small number of consistent findings emerged in individuals in the acute phase of illness with BN or BED including: volume reduction and increases across a range of areas; hypoactivity in the frontostriatal circuits; and aberrant responses in the insula, amygdala, middle frontal gyrus and occipital cortex to a range of different stimuli or tasks; a link between illness severity in BN and neural changes; diminished attentional capacity and early learning; and in SPECT studies, increased rCBF in relation to disorder-related stimuli. Conclusions Studies included in this review are heterogenous, preventing many robust conclusions from being drawn. The precise neurobiology of BN and BED remains unclear and ongoing, large-scale investigations are required. One clear finding is that illness severity, exclusively defined as the frequency of binge eating or bulimic episodes, is related to greater neural changes. The results of this review indicate additional research is required, particularly extending findings of reduced cortical volumes and diminished activity in regions associated with self-regulation (frontostriatal circuits) and further exploring responses to disorder-related stimuli in people with BN and BED.
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The feeding process is required for basic life, influenced by environment cues and tightly regulated according to demands of the internal milieu by regulatory brain circuits. Although eating behaviour cannot be considered "addictive" under normal circumstances, people can become "addicted" to this behaviour, similarly to how some people are addicted to drugs. The symptoms, cravings and causes of "eating addiction" are remarkably similar to those experienced by drug addicts, and both drug-seeking behaviour as eating addiction share the same neural pathways. However, while the drug addiction process has been highly characterised, eating addiction is a nascent field. In fact, there is still a great controversy over the concept of "food addiction". This review aims to summarize the most relevant animal models of "eating addictive behaviour", emphasising binge eating disorder, that could help us to understand the neurobiological mechanisms hidden under this behaviour, and to improve the psychotherapy and pharmacological treatment in patients suffering from these pathologies.
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Context Homeostatic energy balance is controlled via the hypothalamus, whereas regions controlling reward and cognitive decision-making are critical for hedonic eating. Eating varies across the menstrual cycle peaking at the midluteal phase. Objective To test responses of females with regular cycles during midfollicular and midluteal phase and of users of monophasic oral contraception pills (OCPs) to visual food cues. Design Participants performed a functional magnetic resonance imaging while exposed to visual food cues in four time points: fasting and fed conditions in midfollicular and midluteal phases. Patients Twenty females with regular cycles and 12 on monophasic OCP, aged 18 to 35 years. Main Outcome Measures Activity in homeostatic (hypothalamus), reward (amygdala, putamen and insula), frontal (anterior cingulate cortex, dorsolateral prefrontal cortex), and visual regions (calcarine and lateral occipital cortex). Setting Tertiary hospital. Results In females with regular cycles, brain regions associated with homeostasis but also the reward system, executive frontal areas, and afferent visual areas were activated to a greater degree during the luteal compared with the follicular phase. Within the visual areas, a dual effect of hormonal and prandial state was seen. In females on monophasic OCPs, characterized by a permanently elevated progesterone concentration, activity reminiscent of the luteal phase was found. Androgen, cortisol, testosterone, and insulin levels were significantly correlated with reward and visual region activation. Conclusions Hormonal mechanisms affect the responses of women's homeostatic, emotional, and attentional brain regions to food cues. The relation of these findings to eating behavior throughout the cycle needs further investigation.
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Changes in ovarian hormones predict changes in emotional eating across the menstrual cycle. However, prior studies have not examined whether the nature of associations varies across dysregulated eating severity. The current study determined whether the strength and/or nature of hormone/dysregulated eating associations differ based on the presence of clinically diagnosed binge episodes (BEs). Participants included 28 women with BEs and 417 women without BEs who provided salivary hormone samples, ratings of emotional eating, and BE frequency for 45 days. Results revealed stronger associations between dysregulated eating and ovarian hormones in women with BEs as compared to women without BEs. The nature of associations also differed, as progesterone moderated the effects of lower estradiol levels on dysregulated eating in women with BEs only. Although hormone/dysregulated eating associations are present across the spectrum of pathology, the nature of associations may vary in ways that have implications for etiological models and treatment.
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There are significant gender differences in course, symptomology, and treatment of substance use disorders. In general data from clinical and preclinical studies of substance use disorders suggest that women are more vulnerable than men to the deleterious consequences of drug use at every phase of the addiction process. In addition data from epidemiologic studies suggest that the gender gap in the prevalence of substance use is narrowing particularly among adolescence. Therefore, understanding the role of estrogen and progesterone in mediating responses to drugs of abuse is of critical importance to women's health. In this review we will discuss findings from clinical and preclinical studies of 1) reproductive cycle phase; 2) endogenous ovarian hormones; and 3) hormone replacement on responses to stimulants, nicotine, alcohol, opioids, and marijuana. In addition, we discuss data from recent studies that have advanced our understanding of the neurobiologic mechanisms that interact with estrogen and progesterone to mediate drug-seeking behavior.
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The rate of affective disorder is substantially higher in women than in men, and considerable evidence points to the actions of ovarian hormones in mediating this disparity. In this Opinion, we discuss the hypothesis that cyclic changes in ovarian hormone levels produce cyclic alterations in connectivity between the intrinsic networks of the brain. These alterations produce specific temporal windows within the menstrual cycle when internetwork connectivity is increased, associated with increased stress reactivity and better memory for unpleasant, arousing events, leading to increased negative mood and susceptibility to affective disorder. Our windows of vulnerability model offers insights for both treatment of affective disorder and research on sex differences in the brain.
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Central and peripheral signals regulating energy homeostasis interact tightly with neuronal pathways to modulate the hedonic component of food intake. Dysregulation of these interactions could explain the development of binge eating disorder (BED) and/or obesity and the increasing incidence of food addiction. In this review, we have highlighted the crucial role of peripheral hormones, such as leptin and ghrelin, among others, in these nonhomeostatic pathways. We have also emphasised the relevance of central cannabinoid pathway and lateral hypothalamus, with orexin and melanin-concentrating hormone neurons, as the critical hub controlling motivation and reward. Throughout the manuscript, we have focused on mechanisms learned from animal models of BED/food addiction in order to understand how these peripheral signals can modulate the motivation to eat. Understanding these mechanisms could help us to develop new treatment options for BED and/or obesity.
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This review is intended to summarize the literature on the modulation of the human reward system by estradiol. It will integrate previous neuroimaging findings in current rodent models, which suggest a dopamine-agonistic effect of physiological estradiol that may increase reward sensitivity in females. In human research, most neuroimaging studies have addressed menstrual cycle-related differences in reward-related brain activation and behaviors by comparing phases of high versus low estradiol availability. Few studies have also used pharmacological intervention to induce different hormonal states for comparisons of high and low estradiol, while others have also assessed the correlations between brain activation and state-related estradiol to infer causality. Since most human samples were small (n < 30) and the majority of studies used region-of-interest approaches or reported neuroimaging results that were incorrected for multiple comparisons, it is currently undetermined whether estradiol promotes human reward sensitivity to a similar extent as it does in rodents.
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Modern psychology has long focused on the body as the basis of the self. Recently, predictive processing accounts of interoception (perception of the body 'from within') have become influential in accounting for experiences of body ownership and emotion. Here, we describe embodied selfhood in terms of 'instrumental interoceptive inference' that emphasises allostatic regulation and physiological integrity. We apply this approach to the distinctive phenomenology of embodied selfhood, accounting for its non-object-like character and subjective stability over time. Our perspective has implications for the development of selfhood and illuminates longstanding debates about relations between life and mind, implying, contrary to Descartes, that experiences of embodied selfhood arise because of, and not in spite of, our nature as 'beast machines'.
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Objective Emotional eating has been linked to ovarian hormone functioning, but no studies to‐date have considered the role of brain function. This knowledge gap may stem from methodological challenges: Data are heterogeneous, violating assumptions of homogeneity made by between‐subjects analyses. The primary aim of this paper is to describe an innovative within‐subjects analysis that models heterogeneity and has potential for filling knowledge gaps in eating disorder research. We illustrate its utility in an application to pilot neuroimaging, hormone, and emotional eating data across the menstrual cycle. Method Group iterative multiple model estimation (GIMME) is a person‐specific network approach for estimating sample‐, subgroup‐, and individual‐level connections between brain regions. To illustrate its potential for eating disorder research, we apply it to pilot data from 10 female twins (N = 5 pairs) discordant for emotional eating and/or anxiety, who provided two resting state fMRI scans and hormone assays. We then demonstrate how the multimodal data can be linked in multilevel models. Results GIMME generated person‐specific neural networks that contained connections common across the sample, shared between co‐twins, and unique to individuals. Illustrative analyses revealed positive relations between hormones and default mode connectivity strength for control twins, but no relations for their co‐twins who engage in emotional eating or who had anxiety. Discussion This paper showcases the value of person‐specific neuroimaging network analysis and its multimodal associations in the study of heterogeneous biopsychosocial phenomena, such as eating behavior.
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The aims of the current study were to update the inclusion list of relevant neuroimaging studies, meta‐analyse the neuroimaging data and thus synthesize a brain map showing locations with differential activations between men and women. Published studies to 2017 were retrieved and included into the analysis if they evaluated patients' brain responses to food or eating stimuli with functional magnetic resonance imaging or positron emission tomography and reported activation differences between the sexes in the form of brain coordinates based on whole‐brain analysis. Eight studies that comprised a total of 231 participants fulfilled the inclusion criteria. Men had larger neural responses to food stimuli than women in the anterior and middle cingulate, which are related to emotion regulation. Meanwhile, women had larger neural responses to food stimuli than men in the parahippocampus, the thalamus and the precuneus, which are collectively relevant in the context of promotion of eating. The differential brain responses to food or eating stimuli between men and women may shed light on the neurobiology to help explain the sex differences in eating behaviour.
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Substance use disorders (SUDs) remain problematic as many individuals are untreated or do not benefit from the currently available interventions. Thus, there is an urgent need to develop novel pharmacological interventions to treat SUDs. Evidence suggests that the female sex hormone, progesterone, attenuates the craving for and the euphoric effects of drugs of abuse. Research to date has demonstrated that progesterone may modulate responses to drugs of abuse and may have utility as a novel treatment for SUDs. A literature search was conducted to identify and examine studies that administered exogenous progesterone. Sixteen publications were identified, exploring the utility of exogenous progesterone or its metabolite, allopregnanolone, among a range of substances, including amphetamines (one study), benzodiazepines (one study), cocaine (nine studies), and tobacco/nicotine (five studies). Results indicated that exogenous progesterone and, its metabolite allopregnanolone, demonstrated preliminary efficacy as a treatment for substance use in both men and women. Notably, progesterone appears to target negative affect and augment cognitive functioning, especially among female substance users. Additional research is needed to explore the potential use of exogenous progesterone and allopregnanolone in the treatment of SUDs, including that associated with alcohol and opioids, but considering the current promising findings, exogenous progesterone and allopregnanolone may have utility as novel pharmacological treatments for SUDs.
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Until recently, steroid hormones were believed to act only on cells containing intracellular receptors. However, recent evidence suggests that steroids have specific and rapid effects at the cellular membrane. Using whole-cell patch-clamp techniques, 17 beta-estradiol was found to reduce Ba2+ entry reversibly via Ca2+ channels in acutely dissociated and cultured neostriatal neurons. The effects were sex-specific, i.e., the reduction of Ba2+ currents was greater in neurons taken from female rats. 17 beta-Estradiol primarily targeted L-type currents, and their inhibition was detected reliably within seconds of administration. The maximum reduction by 17 beta-estradiol occurred at picomolar concentrations. 17 beta-Estradiol conjugated to bovine serum albumin also reduced Ba2+ currents, suggesting that the effect occurs at the membrane surface. Dialysis with GTP gamma S prevented reversal of the modulation, suggesting that 17 beta-estradiol acts via G-protein activation. 17 alpha-Estradiol also reduced Ba2+ currents but was significantly less effective than 17 beta-estradiol. Estriol and 4-hydroxyestradiol were found to reduce Ba2+ currents with similar efficacy to 17 beta-estradiol, whereas estrone and 2-methoxyestriol were less effective. Tamoxifen also reduced Ba2+ currents but did not occlude the effect of 17 beta-estradiol. These results suggest that at physiological concentrations, 17 beta-estradiol can have immediate actions on neostriatal neurons via nongenomic signaling pathways.
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The existence of sex differences was studied in a rat model of operant self-administration of a chocolate-flavored beverage (CFB), which possesses strong reinforcing properties and is avidly consumed by rats. Whether these differences occurred concomitantly to changes in extracellular dopamine in the dialysate obtained from the nucleus accumbens, was assessed by intracerebral microdialysis. Male, ovariectomized and intact female rats showed similar self-administration profiles, with minor differences in both acquisition and maintenance phases. Intact females self-administered larger amounts of CFB, when expressed per body weight, than males and ovariectomized females, in spite of similar values of lever-responding, latency to the first lever-response and consumption efficiency (a measure of rat's licking effectiveness) in males, ovariectomized and intact females and no difference in breakpoint value and number of lever-responses emerged when males, ovariectomized and intact females were exposed to a progressive ratio schedule of reinforcement. Intracerebral microdialysis revealed a slight but significant increase in dopamine activity in the shell of the nucleus accumbens of male rats when compared to intact female rats during CFB self-administration. The above differences may be caused by the hormonal (mainly estradiol) fluctuations that occur during the estrus cycle in intact females. Accordingly, in intact females CFB self-administration and dopamine activity were found to fluctuate across the estrus cycle, with lower parameters of CFB self-administration and lower dopamine activity in the Proestrus and Estrus phases vs. the Metestrus and Diestrus phases of the cycle.
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Within the adult female, estrogen signaling is well-described as an integral component of the physiologically significant hypothalamic-pituitary-gonadal axis. In rodents, the timing of ovulation is intrinsically entwined with the display of sexual receptivity. For decades, the importance of estradiol activating intracellular estrogen receptors within the hypothalamus and midbrain/spinal cord lordosis circuits has been appreciated. These signaling pathways primarily account for the ability of the female to reproduce. Yet, often overlooked is that the desire to reproduce is also tightly regulated by estrogen receptor signaling. This lack of emphasis can be attributed to an absence of nuclear estrogen receptors in brain regions associated with reward, such as the nucleus accumbens, which are associated with motivated behaviors. This review outlines how membrane-localized estrogen receptors affect metabotropic glutamate receptor signaling within the rodent nucleus accumbens. In addition, we discuss how, as estrogens drive increased motivation for reproduction, they also produce the untoward side effect of heightening female vulnerability to drug addiction.
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Central regulation of food intake is a key mechanism contributing to energy homeostasis. Many neural circuits that are thought to orchestrate feeding behavior overlap with the brain's reward circuitry both anatomically and functionally. Manipulation of numerous neural pathways can simultaneously influence food intake and reward. Two key systems underlying these processes-those controlling homeostatic and hedonic feeding-are often treated as independent. Homeostatic feeding is necessary for basic metabolic processes and survival, while hedonic feeding is driven by sensory perception or pleasure. Despite this distinction, their functional and anatomical overlap implies considerable interaction that is often overlooked. Here, we argue that the neurocircuits controlling homeostatic feeding and hedonic feeding are not completely dissociable given the current data and urge researchers to assess behaviors extending beyond food intake in investigations of the neural control of feeding. Rossi and Stuber discuss the entangled neurocircuitry that governs feeding and reward. Using insights from recently developed molecular and genetic tools, the authors argue that homeostatic feeding and hedonic feeding are highly interrelated and urge investigators to measure more than food intake when probing neuronal control of feeding.
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Background: Functional magnetic resonance imaging (fMRI) has provided insight on how neural abnormalities are related to the symptomatology of the eating disorders (EDs): anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). More specifically, an increasingly growing number of brain imaging studies has shed light on how functionally connected brain networks contribute not only to disturbed eating behavior, but also to transdiagnostic alterations in body/interoceptive perception, reward processing and executive functioning. Methods: This narrative review aims to summarize recent advances in fMRI studies of patients with EDs by highlighting studies investigating network alterations that are shared across EDs. Results and conclusion: Findings on reward processing in both AN and BN patients point to the presence of altered sensitivity to salient food stimuli in striatal regions and to the possibility of hypothalamic inputs being overridden by top-down emotional-cognitive control regions. Additionally, innovative new lines of research suggest that increased activations in fronto-striatal circuits are strongly associated with the maintenance of restrictive eating habits in AN patients. Although significantly fewer studies have been carried out in patients with BN and BED, aberrant neural responses to both food cues and anticipated food receipt appear to occur in these populations. These altered responses, coupled with diminished recruitment of prefrontal cognitive control circuitry, are believed to contribute to the binge eating of palatable foods. Results from functional network connectivity studies are diverse, but findings tend to converge on indicating disrupted resting-state connectivity in executive networks, the default-mode network and the salience network across EDs.
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Binge-eating disorder (BED) is the most prevalent eating disorder with estimates of 2-5% of the general adult population. Nonetheless, its pathophysiology is poorly understood. Furthermore, there exist few therapeutic options for its effective treatment. Here we review the current state of binge-eating neurobiology and pharmacology, drawing from clinical therapeutic, neuroimaging, cognitive, human genetic and animal model studies. These studies, which are still in their infancy, indicate that while there are many gaps in our knowledge, several key neural substrates appear to underpin binge-eating may be conserved between human and animals. This observation suggests that behavioral intermediate phenotypes or endophenotypes relevant to BED may be modeled in animals, facilitating the identification and testing of novel pharmacological targets. The development of novel, safe and effective pharmacological therapies for the treatment of BED will enhance the ability of clinicians to provide optimal care for people with BED.
Article
Background: Obesity is caused by an imbalance between energy intake, i.e. eating and energy expenditure (EE). Severe obesity is more prevalent in women than men worldwide, and obesity pathophysiology and the resultant obesity-related disease risks differ in women and men. The underlying mechanisms are largely unknown. Pre-clinical and clinical research indicate that ovarian hormones may play a major role. Objective and rationale: We systematically reviewed the clinical and pre-clinical literature on the effects of ovarian hormones on the physiology of adipose tissue (AT) and the regulation of AT mass by energy intake and EE. Search methods: Articles in English indexed in PubMed through January 2016 were searched using keywords related to: (i) reproductive hormones, (ii) weight regulation and (iii) central nervous system. We sought to identify emerging research foci with clinical translational potential rather than to provide a comprehensive review. Outcomes: We find that estrogens play a leading role in the causes and consequences of female obesity. With respect to adiposity, estrogens synergize with AT genes to increase gluteofemoral subcutaneous AT mass and decrease central AT mass in reproductive-age women, which leads to protective cardiometabolic effects. Loss of estrogens after menopause, independent of aging, increases total AT mass and decreases lean body mass, so that there is little net effect on body weight. Menopause also partially reverses women's protective AT distribution. These effects can be counteracted by estrogen treatment. With respect to eating, increasing estrogen levels progressively decrease eating during the follicular and peri-ovulatory phases of the menstrual cycle. Progestin levels are associated with eating during the luteal phase, but there does not appear to be a causal relationship. Progestins may increase binge eating and eating stimulated by negative emotional states during the luteal phase. Pre-clinical research indicates that one mechanism for the pre-ovulatory decrease in eating is a central action of estrogens to increase the satiating potency of the gastrointestinal hormone cholecystokinin. Another mechanism involves a decrease in the preference for sweet foods during the follicular phase. Genetic defects in brain α-melanocycte-stimulating hormone-melanocortin receptor (melanocortin 4 receptor, MC4R) signaling lead to a syndrome of overeating and obesity that is particularly pronounced in women and in female animals. The syndrome appears around puberty in mice with genetic deletions of MC4R, suggesting a role of ovarian hormones. Emerging functional brain-imaging data indicates that fluctuations in ovarian hormones affect eating by influencing striatal dopaminergic processing of flavor hedonics and lateral prefrontal cortex processing of cognitive inhibitory controls of eating. There is a dearth of research on the neuroendocrine control of eating after menopause. There is also comparatively little research on the effects of ovarian hormones on EE, although changes in ovarian hormone levels during the menstrual cycle do affect resting EE. Wider implications: The markedly greater obesity burden in women makes understanding the diverse effects of ovarian hormones on eating, EE and body adiposity urgent research challenges. A variety of research modalities can be used to investigate these effects in women, and most of the mechanisms reviewed are accessible in animal models. Therefore, human and translational research on the roles of ovarian hormones in women's obesity and its causes should be intensified to gain further mechanistic insights that may ultimately be translated into novel anti-obesity therapies and thereby improve women's health.
Article
Eating disorders are highly sexually differentiated disorders that exhibit a female predominance in risk. Most theories focus on psychosocial explanations to the exclusion of biological/genetic influences. The purpose of this descriptive review is to evaluate evidence from animal and human studies in support of gonadal hormone effects on sex differences in binge eating. Although research is in its nascent stages, findings suggest that increased prenatal testosterone exposure in males appears to protect against binge eating. Although pubertal testosterone may exert additional protective effects, the prenatal period is likely critical for the decreased risk observed in males. By contrast, studies indicate that in females it is the lack of prenatal testosterone coupled with the organizational effects of pubertal ovarian hormones that may lead to increased binge eating. Finally, twin data suggest that changes in genetic risk may underlie these hormone influences on sex differences across development. Expected final online publication date for the Annual Review of Clinical Psychology Volume 13 is May 7, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Article
We investigated the combined effects of menstrual cycle phase and acute stress on reward-related processing, employing a monetary incentive delay task in combination with EEG. Females participated during late follicular and late luteal phases, performing in both control and stress conditions. We found evidence for both independent and interaction effects of phase and stress on reward-related brain activity. Phase modulated the sensitivity to feedback valence, with a stronger signaling of negative performance outcomes in the late follicular versus late luteal phase. In contrast, in the control condition, the late luteal versus late follicular phase was associated with a heightened sensitivity to reward condition, with enhanced performance monitoring in potential-reward versus no-reward trials. Stress decreased attentional preparation during reward anticipation, but increased the influence of reward condition on the processing of positive performance outcomes. We found no evidence for an increased sensitivity to stress during the late luteal versus late follicular phase.
Article
Because binge eating and emotional eating vary through the menstrual cycle in human females, we investigated cyclic changes in binge-like eating in female rats and their control by estrogens. Binge-like eating was elicited by three cycles of 4 days of food restriction and 4 days of free feeding followed by a single frustrative nonreward-stress episode (15 min visual and olfactory exposure to a familiar palatable food) immediately before presentation of the palatable food. Intact rats showed binge-like eating during the diestrous and proestrous phases of the ovarian cycle, but not during the estrous (periovulatory) phase. Ovariectomized (OVX) rats not treated with estradiol (E2) displayed binge-like eating, whereas E2-treated OVX rats did not. The procedure did not increase signs of anxiety in an open-field test. OVX rats not treated with E2 that were subjected to food restriction and sacrificed immediately after frustrative nonreward had increased numbers of cells expressing phosphorylated extracellular signal-regulated kinases (ERK) in the central nucleus of the amygdala (CeA), paraventricular nucleus of hypothalamus (PVN), and dorsal and ventral bed nuclei of the stria terminalis (BNST) compared with nonrestricted or E2-treated rats. These data suggest that this female rat model is appropriate for mechanistic studies of some aspects of menstrual-cycle effects on emotional and binge eating in human females, that anxiety is not a sufficient cause of binge-like eating, and that the PVN, CeA, and BNST may contribute to information processing underlying binge-like eating.
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Food intake is reduced by estrogenic hormones, levels of which vary throughout life and fluctuate throughout the ovarian cycle in females. However, estrogens have also been shown to increase reward derived from drugs of abuse, where motivational properties of drugs and progression to addiction are potentiated by estrogens. Whether reward derived from food, and specifically motivational properties of food, are altered by estrogens remains unknown. Here we investigated the effect of the estrous cycle on food reward behavior and show estrous cycle dictated variability in food motivation, measured by progressive ratio operant conditioning, in female rats. Reward behavior was lowest on days associated with high estrogen signaling. We therefore also examined the actions of subcutaneously administered β-estradiol on food reward and found that β-estradiol reduced food reward behavior. The ventral tegmental area (VTA) is a crucial node of the neurocircuitry underlying motivated behavior and estrogen receptors are expressed in this nucleus. Thus, we examined whether the effects of estrogens on reward were exerted directly at the level of the VTA. Intra-VTA microinjection of β-estradiol led to a significant reduction in food-motivated behavior. Interestingly, this effect was not accompanied by a reduction in chow intake or body weight, nor did it alter locomotor activity. Importantly, removal of the ovaries produced a potent and lasting elevation in food reward and food-seeking behavior, suggesting that ovarian sex steroids are critical for maintenance of normal food reward behavior. These data reveal a novel role for estrogens in the control of food reward behavior.
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In this paper, we integrate recent theoretical and empirical developments in predictive coding and active inference accounts of interoception (including the Embodied Predictive Interoception Coding model) with working hypotheses from the theory of constructed emotion to propose a biologically plausible unified theory of the mind that places metabolism and energy regulation (i.e. allostasis), as well as the sensory consequences of that regulation (i.e. interoception), at its core. We then consider the implications of this approach for understanding depression. We speculate that depression is a disorder of allostasis, whose myriad symptoms result from a ‘locked in’ brain that is relatively insensitive to its sensory context. We conclude with a brief discussion of the ways our approach might reveal new insights for the treatment of depression. This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’.
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Adolescents are the highest consumers of sugar sweetened drinks. Excessive consumption of such drinks is a likely contributor to the development of obesity and may be associated with enduring changes in the systems involved in reward and motivation. We examined the impact of daily sucrose consumption in young male and female rats (N = 12 per group) across the adolescent period on the motivation to perform instrumental responses to gain food rewards as adults. Rats were or were not exposed to a sucrose solution for 2 h each day for 28 days across adolescence [postnatal days (P) 28–56]. They were then trained as adults (P70 onward) to lever press for a palatable 15% cherry flavored sucrose reward and tested on a progressive ratio (PR) schedule to assess motivation to respond for reinforcement. Female rats exposed to sucrose had higher breakpoints on the PR schedule than controls, whereas male rats exposed to sucrose had lower breakpoints than controls. These results show that consumption of sucrose during adolescence produced sex-specific behavioral changes in responding for sucrose as adults.
Article
Although rewards are physical stimuli and objects, their value for survival and reproduction is subjective. The phasic, neurophysiological and voltammetric dopamine reward prediction error response signals subjective reward value. The signal incorporates crucial reward aspects such as amount, probability, type, risk, delay and effort. Differences of dopamine release dynamics with temporal delay and effort in rodents may derive from methodological issues and require further study. Recent designs using concepts and behavioral tools from experimental economics allow to formally characterize the subjective value signal as economic utility and thus to establish a neuronal value function. With these properties, the dopamine response constitutes a utility prediction error signal.
Article
Biobehavioral features associated with binge-eating disorder (BED) have been investigated; however, few systematic reviews to date have described neuroimaging findings from studies of BED. Emerging functional and structural studies support BED as having unique and overlapping neural features as compared with other disorders. Neuroimaging studies provide evidence linking heightened responses to palatable food cues with prefrontal areas, particularly the orbitofrontal cortex (OFC), with specific relationships to hunger and reward-sensitivity measures. While few studies to date have investigated non-food-cue responses; these suggest a generalized hypofunctioning in frontostriatal areas during reward and inhibitory control processes. Early studies applying neuroimaging to treatment efforts suggest that targeting neural function underlying motivational processes may prove important in the treatment of BED.
Article
The ability to learn from errors or the positive outcomes of one's actions has been connected to a differential functionality of the mesolimbic dopamine system. Variations in dopaminergic transmission and D2-receptor (DRD2) density in the striatum may thereby incline the individual to be either more reward- or punishment-sensitive. The steroid hormones estradiol (E2) and progesterone (PROG) are known to modulate dopaminergic tone. While E2 may enhance dopaminergic release and reduces DRD2, PROG may oppose these effects and attenuates dopaminergic responses. In women, marked changes in the concentration of these hormones occur across the menstrual cycle. Hence, the aim of this study was to assess whether reinforcement learning is modulated by menstrual cycle phase. Fifteen female subjects underwent fMRI while performing a probabilistic feedback learning task twice during their menstrual cycle - once in a phase dominated by E2 (late follicular phase), and a second time in the presence of high PROG (mid luteal phase).The goal of the learning task was to select the more frequently rewarded symbols from 3 symbol pairs, which was enforced by probabilistic feedback. A behavioral post-test examined learning performance and the tendency towards reward or punishment sensitivity (i.e., preference to choose the most often rewarded symbol 'A' or to avoid the least often rewarded symbol 'B', respectively). We found that individual reward sensitivity was enhanced in the follicular relative to the luteal phase, while the ability to learn from negative feedback was compromised. In contrast, during the luteal phase this behavior was reversed and women showed an enhanced punishment learning bias. On the neural level, activation of the dorsal anterior cingulate cortex and adjacent rostral cingulate zone (dACC/RCZ) was decreased when subjects received negative feedback in the follicular relative to the luteal phase. Additionally, in the luteal phase an enhanced ability to learn from negative feedback was accompanied by a stronger signal in the dACC/RCZ in response to negative feedback. These findings provide initial evidence for intra-individual differences in reward and punishment sensitivity due to naturally occurring hormonal changes across the menstrual cycle.
Article
The motivation to seek out and consume rewards has evolutionarily been driven by the urge to fulfill physiological needs. However in a modern society dominated more by plenty than scarcity, we tend to think of motivation as fueled by the search for pleasure. Here, we argue that two separate but interconnected sub-cortical and unconscious processes direct motivation: " wanting " and " liking. " These two psychological and neuronal processes and their related brain structures typically work together, but can become dissociated, particularly in cases of addiction. In drug addiction, for example, repeated consumption of addictive drugs sensitizes the mesolimbic dopamine system, the primary component of the " wanting " system, resulting in excessive " wanting " for drugs and their cues. This sensitizing process is long-lasting and occurs independently of the " liking " system, which typically remains unchanged or may develop a blunted pleasure response to the drug. The result is excessive drug-taking despite minimal pleasure and intense cue-triggered craving that may promote relapse long after detoxification. Here, we describe the roles of " liking " and " wanting " in general motivation and review recent evidence for a dissociation of " liking " and " wanting " in drug addiction, known as the incentive sensitization theory (Robinson and Berridge 1993). We also make the case that sensitization of the " wanting " system and the resulting disso-ciation of " liking " and " wanting " occurs in both gambling disorder and food addiction.
Article
This paper presents a biopsychological theory of drug addiction, the 'Incentive-Sensitization Theory'. The theory addresses three fundamental questions. The first is: why do addicts crave drugs? That is, what is the psychological and neurobiological basis of drug craving? The second is: why does drug craving persist even after long periods of abstinence? The third is whether 'wanting' drugs (drug craving) is attributable to 'liking' drugs (to the subjective pleasurable effects of drugs)? The theory posits the following. (1) Addictive drugs share the ability to enhance mesotelencephalic dopamine neurotransmission. (2) One psychological function of this neural system is to attribute 'incentive salience' to the perception and mental representation of events associated with activation of the system. Incentive salience is a psychological process that transforms the perception of stimuli, imbuing them with salience, making them attractive, 'wanted', incentive stimuli. (3) In some individuals the repeated use of addictive drugs produces incremental neuroadaptations in this neural system, rendering it increasingly and perhaps permanently, hypersensitive ('sensitized') to drugs and drug-associated stimuli. The sensitization of dopamine systems is gated by associative learning, which causes excessive incentive salience to be attributed to the act of drug taking and to stimuli associated with drug taking. It is specifically the sensitization of incentive salience, therefore, that transforms ordinary 'wanting' into excessive drug craving. (4) It is further proposed that sensitization of the neural systems responsible for incentive salience ('for wanting') can occur independently of changes in neural systems that mediate the subjective pleasurable effects of drugs (drug 'liking') and of neural systems that mediate withdrawal. Thus, sensitization of incentive salience can produce addictive behavior (compulsive drug seeking and drug taking) even if the expectation of drug pleasure or the aversive properties of withdrawal are diminished and even in the face of strong disincentives, including the loss of reputation, job, home and family. We review evidence for this view of addiction and discuss its implications for understanding the psychology and neurobiology of addiction.
Article
Mood disorders are twice as frequent in women than in men. Risk mechanisms for major depression include adverse responses to acute changes in sex-steroid hormone levels, eg postpartum in women. Such adverse responses may involve an altered processing of rewards. Here we examine how women's vulnerability for mood disorders is linked to sex-steroid dynamics by investigating the effects of a pharmacologically induced fluctuation in ovarian sex-steroids on the brain response to monetary rewards. In a double-blinded placebo controlled study, healthy women were randomized to receive either placebo or the Gonadotropin Releasing Hormone agonist (GnRHa) Goserelin, which causes a net decrease in sex-steroid levels. Fifty-eight women performed a gambling task while undergoing functional MRI at baseline, during the mid-follicular phase, and again following the intervention. The gambling task enabled us to map regional brain activity related to the magnitude of risk during choice and to monetary reward. The GnRHa intervention caused a net reduction in ovarian sex-steroids (estradiol and testosterone) and increased depression symptoms. Compared to placebo, GnRHa reduced amygdala's reactivity to high monetary rewards. There was a positive association between the individual changes in testosterone and changes in bilateral insula response to monetary rewards. Our data provide evidence for the involvement of sex steroid hormones in reward processing. A blunted amygdala response to rewarding stimuli following a rapid decline in sex-steroid hormones may reflect a reduced engagement in positive experiences. Abnormal reward processing may constitute a neurobiological mechanism by which sex-steroid fluctuations provoke mood disorders in susceptible women.Neuropsychopharmacology accepted article preview online, 06 August 2015. doi:10.1038/npp.2015.236.
Chapter
Sex and reproductive condition often have very dramatic effects on the behaviors, affecting body weight and composition in a wide variety of species, although most of the experimental work has been performed with rats. Gonadal steroids also affect behavioral and physiological regulation of body weight. A great deal of descriptive research and simple endocrinological approaches have given a good idea of how regulatory behaviors and body weight fluctuate with variations in reproductive status and which hormones are responsible for these fluctuations. A variety of factors, including diet palatability, environmental temperature, relative levels of various metabolic hormones, and the opportunity to exercise in running wheels, affect body weight level in rats. Several kinds of neurological damage may also raise or lower body weight set-point. Animals expend calories in a wide variety of ways, but the two principal sources of energy loss (and the two most affected by behavior) are exercise and heat loss to the environment. In female rats, estradiol is the principal ovarian steroid influencing behavioral regulation of energy balance, as well as progesterone also affects weight regulation in female rats. An estrogen-like compound could be used to lower body weight and combat obesity in human being. An ideal weight-control drug would be one that acts on neural weight-regulating systems to lower body weight set-point without being estrogenic or anti-estrogenic in other hormone-sensitive systems. Food intake is linked to sex hormone secretion to ensure that eating and energy stores will increase during pregnancy, and the fluctuations during estrous cycles are simply a by-product of this association.
The gonadal hormone estradiol modulates mesolimbic dopamine systems in the female rat. This modulatory effect is thought to be responsible for the observed effects of estradiol on motivated behaviors. Dopamine acting in the nucleus accumbens is thought to be important for the attribution of incentive motivational properties to cues that predict reward delivery, while dopamine in the striatum is associated with the expression of repetitive or stereotyped behaviors. Elevated concentrations of estradiol are associated with increased motivation for sex or cues associated with access to a mate, while simultaneously attenuating motivation for food. This shift in motivational salience is important for adaptive choice behavior in the natural environment. Additionally, estradiol's adaptive effects on motivation can be maladaptive when increasing motivation for non-natural reinforcers, such as drugs of abuse. Here we discuss the effect of estradiol on mesotelencephalic dopamine transmission and subsequent effects on motivated behaviors.
Article
Accumulating evidence from human and rodent studies suggests that females are more sensitive to the motivating and rewarding properties of drugs of abuse. Numerous reports implicate estradiol in enhancing drug-related responses in females, yet the neurobiological mechanisms underlying this effect of estradiol are unknown. Because dendritic spine plasticity in the nucleus accumbens (NAc) is linked to the addictive effects of drugs, we examined the influence of estradiol on dendritic spines in this region. Previously our laboratory demonstrated that in female medium spiny neurons, estradiol activates metabotropic glutamate receptor subtype five (mGluR5), a G protein-coupled receptor already implicated in the etiology of drug addiction. Thus, we sought to determine whether mGluR5 is a part of the mechanism by which estradiol affects dendritic spine density in the NAc. To test this hypothesis, ovariectomized female rats were treated with the mGluR5 antagonist, MPEP, or vehicle prior to estradiol (or oil) treatment and 24 h later dendritic spine density was evaluated by DiI labeling and confocal microscopy. We found that estradiol decreased dendritic spine density in the NAc core and that pretreatment with MPEP blocked this effect. In contrast, MPEP had no effect on dendritic spine density in the NAc shell or CA1 region of the hippocampus, two regions in which estradiol increased the density of dendritic spines. As dendritic spine plasticity in the NAc core has behavioral consequences for drug addiction, these data provide a clue as to how estradiol acts in females to enhance behavioral responses to drugs of abuse.
Article
Post-traumatic stress disorder (PTSD) is twice as common in women as in men, a major public health problem whose neurobiological basis is unknown. In pre-clinical studies using fear conditioning and extinction paradigms, women and female animals with low estrogen levels exhibit impaired extinction retrieval, but the mechanisms that underlie these hormone-based discrepancies have not been identified. There is much evidence that estrogen can modulate dopaminergic transmission, and here we tested the hypothesis that dopamine-estrogen interactions drive extinction processes in females. Intact male and female rats were trained on cued fear conditioning, and received an i.p. injection of a D1 agonist or vehicle prior to extinction learning. As previously reported, females that underwent extinction during low estrogen estrous phases (estrus/metaestrus/diestrus - EMD) froze more during extinction retrieval than those that had been in the high-estrogen phase (proestrus; PRO). However, D1 stimulation reversed this relationship, impairing extinction retrieval in PRO, and enhancing it in EMD. We also combined retrograde tracing and fluorescent immunohistochemistry to measure c-fos expression in infralimbic (IL) projections to the basolateral area of the amygdala (BLA), a neural pathway known to be critical to extinction retrieval. Again we observed diverging, estrous-dependent effects - SKF treatment induced a positive correlation between freezing and IL-BLA circuit activation in EMD animals, and a negative correlation in PRO animals. These results show for the first time that hormone-dependent extinction deficits can be overcome with non-hormone-based interventions, and suggest a circuit-specific mechanism by which these behavioral effects occur.Neuropsychopharmacology accepted article preview online, 17 December 2013. doi:10.1038/npp.2013.338.
Article
Although the intake of high-fat and high-sugar food activates mesolimbic reward, gustatory, and oral somatosensory brain regions, contributing to overeating, few studies have examined the relative role of fat and sugar in the activation of these brain regions, which would inform policy, prevention, and treatment interventions designed to reduce obesity. We evaluated the effect of a high-fat or high-sugar equicaloric chocolate milkshake and increasing fat or sugar milkshake content on the activation of these regions. Functional magnetic resonance imaging was used to assess the neural response to the intake of high-fat/high-sugar, high-fat/low-sugar, low-fat/high-sugar, and low-fat/low-sugar chocolate milkshakes and a tasteless solution in 106 lean adolescents (mean ± SD age = 15.00 ± 0.88 y). Analyses contrasted the activation to the various milkshakes. High-fat compared with high-sugar equicaloric milkshakes caused greater activation in the bilateral caudate, postcentral gyrus, hippocampus, and inferior frontal gyrus. High-sugar compared with high-fat equicaloric milkshakes caused greater activation in the bilateral insula extending into the putamen, the Rolandic operculum, and thalamus, which produced large activation regions. Increasing sugar in low-fat milkshakes caused greater activation in the bilateral insula and Rolandic operculum; increasing fat content did not elicit greater activation in any region. Fat caused greater activation of the caudate and oral somatosensory regions than did sugar, sugar caused greater activation in the putamen and gustatory regions than did fat, increasing sugar caused greater activity in gustatory regions, and increasing fat did not affect the activation. Results imply that sugar more effectively recruits reward and gustatory regions, suggesting that policy, prevention, and treatment interventions should prioritize reductions in sugar intake. This trial was registered at clinicaltrials.gov as DK092468.