Current perspectives on brain circuits involved in food addiction-like behaviors.

There is an emerging view that the increased availability of energy-dense foods in our society is contributing to excessive food consumption which could lead to food addiction-like behavior. Particularly, compulsive eating patterns are predominant in people suffering from eating disorders (binge-eating disorder, bulimia and anorexia nervosa) and obesity. Phenotypically, the behavioral pattern exhibits a close resemblance to individuals suffering from other forms of addiction (drug, sex, gambling). Growing body of evidence in neuroscience research is showing that excessive consumption of energy-dense foods alters the brain circuits implicated in reward, decision-making, control, habit formation, and emotions that are central to drug addiction. Here, we review the current understanding of the circuits of food addiction-like behaviors and highlight the future possibility of exploring those circuits to combat obesity and eating disorders.

Neurobiological and neuropharmacological aspects of food addiction.

This review aims to draw attention to current studies on syndromes related to food eating behavior, including food addiction, and to highlight the neurobiological and neuropharmacological aspects of food addiction toward the development of new therapies. Food addiction and eating disorders are influenced by several neurobiological factors. Changes in feeding behavior, food addiction, and its pharmacological therapy are related to complex neurobiological processes in the brain. Thus, it is not surprising that there is inconsistency among various individual studies. In this review, we assessed literature including both experimental and clinical studies regarding food addiction as a feeding disorder. We selected articles from animal studies, randomized clinical trials, meta-analyses, narrative, and systemic reviews given that, crucial quantitative data with a measure of neurobiological, neuropharmacological aspects and current therapies of food addiction as an outcome. Thus, the main goal to outline here is to investigate and discuss the association between the brain reward system and feeding behavior in the frame of food addiction in the light of current literature.

Converging vulnerability factors for compulsive food and drug use.

Highly palatable foods and substance of abuse have intersecting neurobiological, metabolic and behavioral effects relevant for understanding vulnerability to conditions related to food (e.g., obesity, binge eating disorder) and drug (e.g., substance use disorder) misuse. Here, we review data from animal models, clinical populations and epidemiological evidence in behavioral, genetic, pathophysiologic and therapeutic domains. Results suggest that consumption of highly palatable food and drugs of abuse both impact and conversely are regulated by metabolic hormones and metabolic status. Palatable foods high in fat and/or sugar can elicit adaptation in brain reward and withdrawal circuitry akin to substances of abuse. Intake of or withdrawal from palatable food can impact behavioral sensitivity to drugs of abuse and vice versa. A robust literature suggests common substrates and roles for negative reinforcement, negative affect, negative urgency, and impulse control deficits, with both highly palatable foods and substances of abuse. Candidate genetic risk loci shared by obesity and alcohol use disorders have been identified in molecules classically associated with both metabolic and motivational functions. Finally, certain drugs may have overlapping therapeutic potential to treat obesity, diabetes, binge-related eating disorders and substance use disorders. Taken together, data are consistent with the hypotheses that compulsive food and substance use share overlapping, interacting substrates at neurobiological and metabolic levels and that motivated behavior associated with feeding or substance use might constitute vulnerability factors for one another. This article is part of the special issue on 'Vulnerabilities to Substance Abuse'.

Alterations in reward network functional connectivity are associated with increased food addiction in obese individuals.

Functional neuroimaging studies in obesity have identified alterations in the connectivity within the reward network leading to decreased homeostatic control of ingestive behavior. However, the neural mechanisms underlying sex differences in the prevalence of food addiction in obesity is unknown. The aim of the study was to identify functional connectivity alterations associated with: (1) Food addiction, (2) Sex- differences in food addiction, (3) Ingestive behaviors. 150 participants (females: N = 103, males: N = 47; food addiction: N = 40, no food addiction: N = 110) with high BMI ≥ 25 kg/m2 underwent functional resting state MRIs. Participants were administered the Yale Food Addiction Scale (YFAS), to determine diagnostic criteria for food addiction (YFAS Symptom Count ≥ 3 with clinically significant impairment or distress), and completed ingestive behavior questionnaires. Connectivity differences were analyzed using a general linear model in the CONN Toolbox and images were segmented using the Schaefer 400, Harvard-Oxford Subcortical, and Ascending Arousal Network atlases. Significant connectivities and clinical variables were correlated. Statistical significance was corrected for multiple comparisons at q < .05. (1) Individuals with food addiction had greater connectivity between brainstem regions and the orbital frontal gyrus compared to individuals with no food addiction. (2) Females with food addiction had greater connectivity in the salience and emotional regulation networks and lowered connectivity between the default mode network and central executive network compared to males with food addiction. (3) Increased connectivity between regions of the reward network was positively associated with scores on the General Food Cravings Questionnaire-Trait, indicative of greater food cravings in individuals with food addiction. Individuals with food addiction showed greater connectivity between regions of the reward network suggesting dysregulation of the dopaminergic pathway. Additionally, greater connectivity in the locus coeruleus could indicate that the maladaptive food behaviors displayed by individuals with food addiction serve as a coping mechanism in response to pathological anxiety and stress. Sex differences in functional connectivity suggest that females with food addiction engage more in emotional overeating and less cognitive control and homeostatic processing compared to males. These mechanistic pathways may have clinical implications for understanding the sex-dependent variability in response to diet interventions.

Brain-gut-microbiome interactions in obesity and food addiction.

Normal eating behaviour is coordinated by the tightly regulated balance between intestinal and extra-intestinal homeostatic and hedonic mechanisms. By contrast, food addiction is a complex, maladaptive eating behaviour that reflects alterations in brain-gut-microbiome (BGM) interactions and a shift of this balance towards hedonic mechanisms. Each component of the BGM axis has been implicated in the development of food addiction, with both brain to gut and gut to brain signalling playing a role. Early-life influences can prime the infant gut microbiome and brain for food addiction, which might be further reinforced by increased antibiotic usage and dietary patterns throughout adulthood. The ubiquitous availability and marketing of inexpensive, highly palatable and calorie-dense food can further shift this balance towards hedonic eating through both central (disruptions in dopaminergic signalling) and intestinal (vagal afferent function, metabolic endotoxaemia, systemic immune activation, changes to gut microbiome and metabolome) mechanisms. In this Review, we propose a systems biology model of BGM interactions, which incorporates published reports on food addiction, and provides novel insights into treatment targets aimed at each level of the BGM axis.

A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to food addiction.

Food addiction is linked to obesity and eating disorders and is characterized by a loss of behavioral control and compulsive food intake. Here, using a food addiction mouse model, we report that the lack of cannabinoid type-1 receptor in dorsal telencephalic glutamatergic neurons prevents the development of food addiction-like behavior, which is associated with enhanced synaptic excitatory transmission in the medial prefrontal cortex (mPFC) and in the nucleus accumbens (NAc). In contrast, chemogenetic inhibition of neuronal activity in the mPFC-NAc pathway induces compulsive food seeking. Transcriptomic analysis and genetic manipulation identified that increased dopamine D2 receptor expression in the mPFC-NAc pathway promotes the addiction-like phenotype. Our study unravels a new neurobiological mechanism underlying resilience and vulnerability to the development of food addiction, which could pave the way towards novel and efficient interventions for this disorder.

Overeating and food addiction in Major Depressive Disorder: Links to peripheral dopamine.

The concept of food addiction refers to addiction-like behaviours that develop in association with the intake of highly palatable foods. Previous research indicates that a high proportion of individuals with Major Depressive Disorder (MDD) meet the criteria for food addiction, and are also at an increased risk of weight gain and chronic disease. In the central nervous system, dopamine is a neurotransmitter associated with reward salience and food intake, whereas peripheral dopamine is involved in sympathetic stress regulation, digestion and gastrointestinal motility. However, little research has examined relationships between peripheral dopamine, depressive symptoms and problematic eating behaviours in MDD. Biometrics, psychopathology and plasma dopamine levels were compared between participants with MDD (n = 80) and controls (n = 60). Participants were sub-categorised into those meeting or not meeting Yale Food Addiction Scale (YFAS) criteria. Psychometric measures of mood and appetite were used to assess MDD symptoms, problematic eating behaviours and food-addiction related symptoms. Twenty-three (23; 29%) MDD participants met the Yale criteria for food addiction. Depressed individuals meeting YFAS criteria had significantly greater psychopathology scores for both mood and eating compared to depressed individuals not meeting YFAS criteria and controls. A significant interaction between food addiction status and sex was also observed for plasma dopamine levels. Plasma dopamine levels correlated positively with disordered eating behaviours in females, and negatively in males. The results provide evidence that depressogenic excess eating and weight gain are associated with peripheral dopamine levels. Longitudinal research is warranted investigating endocrine dysregulation and excess eating in MDD, which may inform interventions and reduce chronic disease risk in affected individuals.

Chronic calorie-dense diet drives differences in motivated food seeking between obesity-prone and resistant mice.

Obesity results from overconsumption of energy, partly because of the inability to refrain from highly palatable rewarding foods. Even though palatable food is available to everyone, only a fraction of the population develops obesity. We previously showed that following chronic exposure to highly palatable food animals that gained the most weight also showed addictive-like motivation to seek for palatable food. An important question remains-is this extreme, addictive-like, motivation to consume palatable food the cause or the consequence of diet-induced obesity? Here, we show that obesity-prone (OP) mice exhibit higher motivation for palatable food consumption compared with obesity-resistant mice even before developing obesity, but that the full manifestation of this high motivation to eat is expressed only after chronic exposure to high-fat-high-sugar (HFHS) diet. HFHS diet also impairs performance in the operant food-seeking task selectively in OP mice, an impairment that persists even after 2 weeks of abstinence from HFHS food. Overall, our data suggest that while some aspects of food motivation are high in OP mice already before developing obesity, the chronic exposure to HFHS food accentuates it and drives the development of obesity.

Insula to ventral striatal projections mediate compulsive eating produced by intermittent access to palatable food.

Compulsive eating characterizes many binge-related eating disorders, yet its neurobiological basis is poorly understood. The insular cortex subserves visceral-emotional functions, including taste processing, and is implicated in drug craving and relapse. Here, via optoinhibition, we implicate projections from the anterior insular cortex to the nucleus accumbens as modulating highly compulsive-like food self-administration behaviors that result from intermittent access to a palatable, high-sucrose diet. We identified compulsive-like eating behavior in female rats through progressive ratio schedule self-administration and punishment-resistant responding, food reward tolerance and escalation of intake through 24-h energy intake and fixed-ratio operant self-administration sessions, and withdrawal-like irritability through the bottle brush test. We also identified an endocrine profile of heightened GLP-1 and PP but lower ghrelin that differentiated rats with the most compulsive-like eating behavior. Measures of compulsive eating severity also directly correlated to leptin, body weight and adiposity. Collectively, this novel model of compulsive-like eating symptoms demonstrates adaptations in insula-ventral striatal circuitry and metabolic regulatory hormones that warrant further study.

Is weight status associated with peripheral levels of oxytocin? A pilot study in healthy women.

The neuropeptide oxytocin is best known for its role during parturition and the milk-let down reflex. Recent evidence identifies a role for oxytocin in eating behaviour. After oxytocin administration, caloric intake is reduced with stronger inhibitory effects in individuals with obesity. Whether the experience of visual food cues affects secretion or circulating levels of oxytocin is unknown. This pilot study had three aims: 1) to measure fasting appetite hormones with a focus on plasma oxytocin concentrations; 2) determine whether healthy vs. hyperpalatable visual food cues differentially altered plasma oxytocin; and 3) assess whether appetite hormone responses to healthy vs. hyperpalatable food images depended on weight or food addiction status. Eighteen healthy women of varying weight status, with/without self-reported food addiction were recruited. Study participants completed a set of standardised questionnaires, including Yale Food Addiction Scale, and attended a one-off experimental session. Blood was collected before and after viewing two sets of food images (healthy and hyperpalatable foods). Participants were randomly allocated in a crossover design to view either healthy images or hyperpalatable foods first. A positive correlation between BMI and plasma oxytocin was found (r2 = 0.32, p = 0.021) at baseline. Oxytocin levels were higher, and cholecystokinin levels lower, in food addicted (n = 6) vs. non-food addicted females (p = 0.015 and p<0.001, respectively). There were no significant changes (p>0.05) in plasma oxytocin levels in response to either healthy or hyperpalatable food images. Given that endogenous oxytocin administration tends to suppress eating behaviour; these data indicate that oxytocin receptor desensitization or oxytocin resistance may be important factors in the pathogenesis of obesity and food addiction. However, further studies in larger samples are needed to determine if peripheral oxytocin is responsive to visual food cues.

Food cue reactivity in food addiction: A functional magnetic resonance imaging study.

BACKGROUND: While neuroimaging studies have revealed that reward dysfunction may similarly contribute to obesity and addiction, no prior studies have examined neural responses in individuals who meet the "clinical" food addiction phenotype. METHODS: Women (n = 44) with overweight and obesity, nearly half of whom (n = 20) met criteria for moderate-to-severe Yale Food Addiction Scale 2.0 (YFAS 2.0) food addiction, participated in a functional magnetic resonance imaging cue reactivity task. Participants viewed images of highly processed foods, minimally processed foods, and household objects while thinking about how much they wanted each item. Differences in neural responses by YFAS 2.0 food addiction to highly processed and minimally processed food cues were investigated. RESULTS: There was a significant interaction between participant group and neural response in the right superior frontal gyrus to highly versus minimally processed food cues (r = 0.57). Individuals with YFAS 2.0 food addiction exhibited modest, elevated responses in the superior frontal gyrus for highly processed food images and more robust, decreased activations for minimally processed food cues, whereas participants in the control group showed the opposite responses in this region. Across all participants, the household items elicited greater activation than the food cues in regions associated with interoceptive awareness and visuospatial attention (e.g., insula, inferior frontal gyrus, inferior parietal lobe). CONCLUSIONS: Women with overweight or obesity and YFAS 2.0 food addiction, compared to those with only overweight or obesity, exhibited differential responses to highly and minimally processed food cues in a region previously associated with cue-induced craving in persons with a substance-use disorder. Overall, the present work provides further support for the utility of the food addiction phenotype within overweight and obesity.

Food Addiction Symptoms and Amygdala Response in Fasted and Fed States.

Few studies have investigated the underlying neural substrates of food addiction (FA) in humans using a recognised assessment tool. In addition, no studies have investigated subregions of the amygdala (basolateral (BLA) and central amygdala), which have been linked to reward-seeking behaviours, susceptibility to weight gain, and promoting appetitive behaviours, in the context of FA. This pilot study aimed to explore the association between FA symptoms and activation in the BLA and central amygdala via functional magnetic resonance imaging (fMRI), in response to visual food cues in fasted and fed states. Females (n = 12) aged 18-35 years completed two fMRI scans (fasted and fed) while viewing high-calorie food images and low-calorie food images. Food addiction symptoms were assessed using the Yale Food Addiction Scale. Associations between FA symptoms and activation of the BLA and central amygdala were tested using bilateral masks and small-volume correction procedures in multiple regression models, controlling for BMI. Participants were 24.1 ± 2.6 years, with mean BMI of 27.4 ± 5.0 kg/m2 and FA symptom score of 4.1 ± 2.2. A significant positive association was identified between FA symptoms and higher activation of the left BLA to high-calorie versus low-calorie foods in the fasted session, but not the fed session. There were no significant associations with the central amygdala in either session. This exploratory study provides pilot data to inform future studies investigating the neural mechanisms underlying FA.

Neuroanatomical correlates of food addiction symptoms and body mass index in the general population.

The food addiction model suggests neurobiological similarities between substance-related and addictive disorders and obesity. While structural brain differences have been consistently reported in these conditions, little is known about the neuroanatomical correlates of food addiction. We therefore aimed to determine whether symptoms of food addiction related to body mass index (BMI), personality, and brain structure in a large population-based sample. Participants of the LIFE-Adult study (n = 625; 20-59 years old, 45% women) answered the Yale Food Addiction Scale (YFAS) and further personality measures, underwent anthropometric assessments and high-resolution 3T-neuroimaging. A higher YFAS symptom score correlated with higher BMI, eating behavior traits, neuroticism, and stress. Higher BMI predicted significantly lower thickness of (pre)frontal, temporal and occipital cortex and increased volume of left nucleus accumbens. In a whole-brain analysis, YFAS symptom score was not associated with significant differences in cortical thickness or subcortical gray matter volumes. A hypothesis-driven Bayes factor analysis suggested a small, additional contribution of YFAS symptom score to lower right lateral orbitofrontal cortex thickness over the effect of BMI. Our study indicates that symptoms of food addiction do not account for the major part of the structural brain differences associated with BMI in the general population. Yet, symptoms of food addiction might explain additional variance in orbitofrontal cortex, a hub area of the reward network. Longitudinal studies implementing both anatomical and functional MRI could further disentangle the neural mechanisms of addictive eating behaviors.

Subjective experiences of highly processed food consumption in individuals with food addiction.

Highly processed foods (e.g., pizza, chocolate) have been more associated with indicators of food addiction than have minimally processed foods (e.g., fruits, vegetables), although findings have been primarily self-reported. The present study utilized behavioral methods from the addiction literature to assess whether (a) foods differ in their associations with subjective experience indicators of abuse liability and (b) individual differences in subjective experiences and eating behavior emerge using the Yale Food Addiction Scale 2.0 (YFAS 2.0). Women (n = 44) with overweight or obesity, 38.6% with YFAS 2.0 food addiction, rated facets of subjective experience (e.g., craving) during a taste test task and ad libitum consumption period. A hierarchical linear model assessed whether foods were differentially associated with each subjective experience (Level 1) and individual differences by food addiction (Level 2). Associations between subjective experiences and eating behavior were also examined. Highly processed, relative to minimally processed, foods were more associated with indicators of abuse liability, although individuals with food addiction reported decreased enjoyment for and intentions to consume highly processed foods. Subjective experiences were associated with greater consumption of highly processed foods for participants with food addiction. The present work provides further support for the rewarding nature of highly processed foods, evidenced by closer associations with subjective experiences reported for drugs of abuse compared to minimally processed foods. In addition, highly processed food intake was related to elevated subjective experience reports for these foods for those with food addiction, paralleling findings in individuals with a substance-use disorder for the relevant drug. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

When food becomes an obsession: Overweight is related to food-related obsessive-compulsive behavior.

In this study, it was examined whether overweight is associated with food-related obsessions and compulsions. Participants with a healthy weight (n = 27) and participants who were overweight (n = 33) filled out the Yale-Brown-Cornell Eating Disorder Scale, the Eating Obsessive-Compulsive Scale, and the Emotional and Behavioral Reactions to Intrusions Questionnaire to assess frequency, distress, control, and reactance associated with food-related preoccupations and compulsions. Overweight participants showed increased food-related preoccupations, compulsive eating, and heightened emotional and behavioral reactance compared to participants with a healthy weight. Increased food-related obsessive-compulsiveness was also associated with unhealthy eating patterns.

The effects of individual circadian rhythm differences on insomnia, impulsivity, and food addiction.

PURPOSE: Individuals can generally be divided into morning, neither and evening types according to behavioral, psychological, and biological variables including appetite levels, usual meal times, sleep times, and melatonin secretion. These factors together identify a person as being part of a certain chronotype, i.e., as feeling more efficient either in the morning (morning type) or later in the day (evening type). Food addiction is defined as addictive behavior toward palatable foods and is thought to be one of the underlying risk factors for obesity. Our aim in this study was to investigate the relationship between circadian rhythm differences and food addiction via insomnia and impulsivity in university students. METHOD: Participants were 1323 university students, filled out a package of psychological tools, including the Morningness-Eveningness Questionnaire, Insomnia Severity Index, Barratt Impulsiveness Scale Short Form, and Yale Food Addiction Scale. Logistic regression analysis was used to investigate direct relation of food addiction with insomnia, impulsivity and obesity, and mediation regression analysis was used to investigate the indirect effect of circadian rhythm differences on food addiction. RESULTS: Our findings indicated that evening types were more prone to insomnia and impulsivity, and also insomnia and impulsivity significantly contributed to the variance of food addiction. Although there was no significant linear relationship between circadian rhythm differences and food addiction, evening-type circadian preferences were indirectly associated with higher food addiction scores mediated by insomnia and impulsivity. CONCLUSION: The most remarkable result of our work was that circadian rhythm differences seem to indirectly effect on food addiction through elevated insomnia and impulsivity. LEVEL OF EVIDENCE: Level V, descriptive cross-sectional survey.

Food addiction distinguishes an overweight phenotype that can be reversed by low calorie diet.

Similarities in neural activation patterns in obese and substance-dependent subjects led to the food addiction concept, but studies exploiting this issue for obesity stratification are missing. We assessed brain activation in response to food cues using 18 F-2-fluoro-2-deoxy-glucose-PET in 36 overweight women, stratified by low or high food addiction groups according to the Yale Food Addiction Scale (YFAS). Assessments were repeated after a 3-month diet. We found greater activation in thalamus, hypothalamus, midbrain, putamen, and occipital cortex (reward), but not in prefrontal and orbitofrontal cortices (control/reward receipt) in the high-YFAS versus low-YFAS group. In high-YFAS subjects, orbitofrontal responsiveness was inversely related to YFAS severity and hunger rating, and positive associations were observed between regional brain activation and lipid intake. A 3-month diet abolished group differences in brain activation. Our data suggest that food addiction distinguishes an overweight phenotype that can be reversed by diet, opening to personalized strategies in obesity treatment.

Food addiction and impaired executive functions in women with obesity.

BACKGROUND: Individuals with obesity (OB) often report suffering from addiction-like symptoms. As in addictions, deficits in executive function domains, such as decision-making and sustained attention, are found in OB. No study to date has examined the associations between food addiction, OB, and neuropsychological performance. METHOD: Thirty-three adult women with OB and 36 healthy weight controls completed the Yale Food Addiction Scale Version 2.0, a validated instrument used to assess food-related addictive behaviours. Additionally, participants completed computerized versions of the Iowa Gambling Task (IGT) and Conners' Continuous Performance Test, second edition (CPT-II) to examine decision-making and attentional control, respectively. RESULTS: Food addiction criteria were met in 24.2% of the participants with OB and in 2.8% of the control group. In the OB group, food addiction severity levels were negatively correlated with overall scores on the IGT. Participants with OB meeting criteria for food addiction committed more omissions and perseveration errors on the CPT-II compared with those without food addiction. CONCLUSIONS: Our results point to an association between food addiction severity levels and impairments in decision-making and attentional capacity in individuals with OB. Given the heterogeneity found in OB, it stands to reason that this subset of patients with food addiction could potentially benefit from interventions targeting neuropsychological deficits.

Early Childhood Obesity Risk Factors: Socioeconomic Adversity, Family Dysfunction, Offspring Distress, and Junk Food Self-Medication.

PURPOSE OF REVIEW: To explore the sequence and interaction of infancy and early childhood risk factors, particularly relating to disturbances in the social environment, and how the consequences of such exposures can promote weight gain and obesity. RECENT FINDINGS: This review will argue that socioeconomic adversity is a key upstream catalyst that sets the stage for critical midstream risk factors such as family strain and dysfunction, offspring insecurity, stress, emotional turmoil, low self-esteem, and poor mental health. These midstream risk factors, particularly stress and emotional turmoil, create a more or less perfect foil for calorie-dense junk food self-medication and subtle addiction, to alleviate uncomfortable psychological and emotional states. Disturbances in the social environment during infancy and early childhood appear to play a critical role in weight gain and obesity, through such mechanisms as insecurity, stress, and emotional turmoil, eventually leading to junk food self-medication and subtle addiction.