The Addictive Dimensionality of Obesity

doi:10.1016/j.biopsych.2012.12.020

Biological Psychiatry

Volume 73, Issue 9, 1 May 2013, Pages 811-818

https://doi.org/10.1016/j.biopsych.2012.12.020 Get rights and content

Our brains are hardwired to respond and seek immediate rewards. Thus, it is not surprising that many people overeat, which in some can result in obesity, whereas others take drugs, which in some can result in addiction. Though food intake and body weight are under homeostatic regulation, when highly palatable food is available, the ability to resist the urge to eat hinges on self-control. There is no homeostatic regulator to check the intake of drugs (including alcohol); thus, regulation of drug consumption is mostly driven by self-control or unwanted effects (i.e., sedation for alcohol). Disruption in both the neurobiological processes that underlie sensitivity to reward and those that underlie inhibitory control can lead to compulsive food intake in some individuals and compulsive drug intake in others. There is increasing evidence that disruption of energy homeostasis can affect the reward circuitry and that overconsumption of rewarding food can lead to changes in the reward circuitry that result in compulsive food intake akin to the phenotype seen with addiction. Addiction research has produced new evidence that hints at significant commonalities between the neural substrates underlying the disease of addiction and at least some forms of obesity. This recognition has spurred a healthy debate to try and ascertain the extent to which these complex and dimensional disorders overlap and whether or not a deeper understanding of the crosstalk between the homeostatic and reward systems will usher in unique opportunities for prevention and treatment of both obesity and drug addiction.

Section snippets

Genetic Overlaps

Social and cultural factors contribute to the obesity epidemic. However, individual factors also help determine who will become obese in these environments. Though genetic studies have revealed point mutations that are overrepresented among obese individuals, obesity is largely thought to be under polygenic control. Indeed, the most recent whole genome-wide association study conducted in 249,796 individuals of European descent identified 32 loci associated with body mass index (BMI). However,

Molecular Overlaps: Focus on Dopamine

The decision to eat (or not) is not only influenced by the internal state of the caloric equation but also by nonhomeostatic factors, such as food palatability and environmental cues that trigger conditioned responses. The past decade has uncovered numerous molecular and functional interactions between the homeostatic and reward levels of food regulation. Specifically, several hormones and neuropeptides involved in energy homeostasis influence the DA reward pathway (9). Overall, homeostatic

Neurocircuitry and Behavioral Overlaps

The overwhelming urge to seek and consume the drug in addiction involves disruption not only of the reward circuitry but also of other circuits, including interoception, inhibitory control, mood and stress regulation, and memory (39). It can be argued that this neurocircuitry model of addiction also applies to certain types of obesity.

Summary and Implications

The human brain is a complex biological system that is organized in the layered architecture of interactive networks, sometimes called bowtie (111), whereby a narrowing funnel of many potential inputs converges onto a relatively small number of processes before fanning out again into a diversity of outputs. Eating behaviors present a great example of this architecture where the hypothalamus is a central knot of the metabolic bowtie (Figure 2A) and midbrain DA nuclei (VTA and substantia nigra)

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Cited by (284)

The relationship of food addiction with binge eating disorder and obesity: A network analysis study
2023, Appetite
Food addiction (FA) has been associated with binge eating disorder (BED) and obesity at varying levels of severity and treatment outcomes. Despite much debate and scientific interest in FA, the mechanisms that underlie its co-occurrence with both conditions are not yet well understood. In order to understand this relationship, this study explores FA in a clinical sample of individuals with BED and obesity using network analysis (NA). A total of 303 patients (151 with BED and 152 with obesity) completed a battery of tests that investigated eating psychopathology, eating behaviours, emotional dysregulation, depression and FA. Two different NAs were conducted to investigate the interaction between these variables and FA. The BED and obesity groups were comparable in age (38 ± 14 vs. 42 ± 13 years), body mass index (38.8 ± 8.5 vs 42.4 ± 7.8), sex and demographics. According to the expected influence values, binge eating severity and depression were identified as the central nodes in both networks. In the BED group, binge eating severity was the central node and showed strong connections to both FA and grazing. In contrast, in the obesity group, depression was the central node, but its connections were weak, with only marginal associations to FA. These results suggest that FA represents an important and distinct construct of the two populations. In patients with BED, FA is intimately connected to other loss-of-control-related eating behaviours, such as binge eating and grazing. Conversely, in those with obesity, depression explains the relationship of FA with pathological eating behaviours. The presence of FA seems to be a distinguishing characteristic in the psychopathology of patients suffering from obesity with and without BED, and this could have implications for the prevention, treatment and management of these disorders.
Association between food addiction with ultra-processed food consumption and eating patterns in a Brazilian sample
2023, Appetite
The study objectives were to determine whether consumption of ultra-processed foods (UPF) and eating patterns are associated with food addiction (FA) in a Brazilian sample. This is a cross-sectional study. The Brazilian Food and Nutrition Surveillance System tool assessed food consumption markers and dietary patterns. The modified Yale Food Addiction Scale 2.0 was used to determine FA. 5946 participants were included with a mean age of 24 ± 6 years, and 4371 (73.5%) were female. After statistical adjustments for confounders, individuals with FA had lower consumption of fresh fruits (PR: 0.88; 95%CI: [0.79; 0.97]), vegetables (PR: 0.87; 95%CI: [0.79; 0.97]), and beans (PR: 0.85; 95%CI: [0.77; 0.95]). They also had higher consumption of UPF: hamburgers/sausages (PR: 1.15; 95%CI: [1.04; 1.27]), instant noodles, packaged snacks, and/or salty cookies (PR: 1.27; 95%CI: [1.13; 1.42]), and sandwich cookies, sweets, and/or treats (PR: 1.26; 95%CI: [1.14; 1.40]). Positive associations between FA and having meals in front of the screen (PR: 1.48; 95%CI: [1.28; 1.71]) and having a late-night snack (PR: 1.24; 95%CI: [1.11; 1.39]) remained. The negative association between FA and skipping breakfast (PR: 0.76; 95%CI: [0.68; 0.85]) also remained. These eating patterns may contribute to FA, which could be potential targets for clinical intervention.
Toward neuromarkers for tailored smoking cessation treatments
2023, Addiction Neuroscience
Neurobiological models of addiction attribute vulnerability to compulsive drug use to dysregulated activity within the neural networks that underlie reward and executive functions. Empirical evidence suggests that (a) attributing high motivational salience to drug-related stimuli leads to compulsive drug seeking and (b) cognitive control deficits lead to compulsive drug taking. Noninvasive neuroimaging techniques enable brain activity monitoring during affective and cognitive processing and could pave the way to precision medicine for substance use disorders. Identifying robust neuromarkers of affective and cognitive dysregulation would allow clinicians to personalize treatments by targeting individual psychophysiological vulnerabilities. However, methodological choices have biased the field toward experimental paradigms that cannot optimally assess individual differences in the motivational salience of drug-related cues and in the ability to control drug-related decisions, hindering the identification of clinically relevant neuromarkers. Here we show that (a) accounting for neuroaffective reactivity to non-drug-related motivationally relevant stimuli when measuring the attribution of motivational salience to drug-related cues, and (b) assessing brain activity while participants make drug-related decisions with immediate consequences, yield replicable neuromarkers with potential clinical relevance. While we use tobacco use disorder as a model, we also show that the methodological issues highlighted here are relevant to other disorders characterized by maladaptive appetitive behaviors.
Operant Training for Highly Palatable Food Alters Translating Messenger RNA in Nucleus Accumbens D<inf>2</inf> Neurons and Reveals a Modulatory Role of Ncdn
2023, Biological Psychiatry
Highly palatable food triggers behavioral responses including strong motivation. These effects involve the reward system and dopamine neurons, which modulate neurons in the nucleus accumbens (NAc). The molecular mechanisms underlying the long-lasting effects of highly palatable food on feeding behavior are poorly understood.
We studied the effects of 2-week operant conditioning of mice with standard or isocaloric highly palatable food. We investigated the behavioral responses and dendritic spine modifications in the NAc. We compared the translating messenger RNA in NAc neurons identified by the type of dopamine receptors they express, depending on the kind of food and training. We tested the consequences of invalidation of an abundant downregulated gene, Ncdn.
Operant conditioning for highly palatable food increased motivation for food even in well-fed mice. In wild-type mice, free choice between regular and highly palatable food increased weight compared with access to regular food only. Highly palatable food increased spine density in the NAc. In animals trained for highly palatable food, translating messenger RNAs were modified in NAc neurons expressing dopamine D₂ receptors, mostly corresponding to striatal projection neurons, but not in neurons expressing D₁ receptors. Knockout of Ncdn, an abundant downregulated gene, opposed the conditioning-induced changes in satiety-sensitive feeding behavior and apparent motivation for highly palatable food, suggesting that downregulation may be a compensatory mechanism.
Our results emphasize the importance of messenger RNA alterations in D₂ striatal projection neurons in the NAc in the behavioral consequences of highly palatable food conditioning and suggest a modulatory contribution of Ncdn downregulation.
Habenula Volume and Functional Connectivity Changes Following Laparoscopic Sleeve Gastrectomy for Obesity Treatment
2023, Biological Psychiatry
Neuroimaging studies have revealed alterations in habenular (Hb) structure and functional connectivity (FC) in psychiatric conditions. The Hb plays a particularly critical role in regulating negative emotions, which trigger excessive food intake and obesity. However, obesity and weight loss intervention (i.e., laparoscopic sleeve gastrectomy [LSG])–associated changes in Hb structure and FC have not been studied.
We used voxel-based morphometry analysis to measure changes in gray matter volume (GMV) in the Hb in 56 patients with obesity at pre-LSG and 12 months post-LSG and in 78 normal-weight (NW) control participants. Then, we conducted Hb seed-based resting-state FC (RSFC) to examine obesity-related and LSG-induced alterations in RSFC. Finally, we used mediation analysis to characterize the interrelationships among Hb GMV, RSFC, and behaviors.
Compared with NW participants, Hb GMV was smaller in patients at pre-LSG and increased at 12 months post-LSG to levels equivalent to that of NW; in addition, increases in Hb GMV were correlated with reduced body mass index (BMI). Compared with NW participants, pre-LSG patients showed greater RSFCs of the Hb–insula, Hb–precentral gyrus, and Hb–rolandic operculum and weaker RSFCs of the Hb–thalamus, Hb–hypothalamus, and Hb–caudate; LSG normalized these RSFCs. Decreased RSFC of the Hb-insula was correlated with reduced BMI, Yale Food Addiction Scale rating, and emotional eating; reduced hunger levels were correlated with increased RSFCs of the Hb–thalamus and Hb–hypothalamus; and reduced BMI and Yale Food Addiction Scale ratings were correlated with increased RSFCs of the Hb–thalamus and Hb–hypothalamus, respectively. The bidirectional relationships between Hb GMV and RSFC of the Hb–insula contributed to reduced BMI.
These findings indicate that LSG increased Hb GMV and that its related improvement in RSFC of the Hb–insula may mediate long-term benefits of LSG for eating behaviors and weight loss.
More complex than you might think: Neural representations of food reward value in obesity
2022, Appetite
Obesity reached pandemic proportions and weight-loss treatments are mostly ineffective.
The level of brain activity in the reward circuitry is proposed to be proportionate to the reward value of food stimuli, and stronger in people with obesity. However, empirical evidence is inconsistent. This may be due to the double-sided nature of high caloric palatable foods: at once highly palatable and high in calories (unhealthy).
This study hypothesizes that, viewing high caloric palatable foods, a hedonic attentional focus compared to a health and a neutral attentional focus elicits more activity in reward-related brain regions, mostly in people with obesity. Moreover, caloric content and food palatability can be decoded from multivoxel patterns of activity most accurately in people with obesity and in the corresponding attentional focus.
During one fMRI-session, attentional focus (hedonic, health, neutral) was manipulated using a one-back task with individually tailored food stimuli in 32 healthy-weight people and 29 people with obesity. Univariate analyses (p < 0.05, FWE-corrected) showed that brain activity was not different for palatable vs. unpalatable foods, nor for high vs. low caloric foods. Instead, this was higher in the hedonic compared to the health and neutral attentional focus. Multivariate analyses (MVPA) (p < 0.05, FDR-corrected) showed that palatability and caloric content could be decoded above chance level, independently of either BMI or attentional focus.
Thus, brain activity to visual food stimuli is neither proportionate to the reward value (palatability and/or caloric content), nor significantly moderated by BMI. Instead, it depends on people's attentional focus, and may reflect motivational salience. Furthermore, food palatability and caloric content are represented as patterns of brain activity, independently of BMI and attentional focus. So, food reward value is reflected in patterns, not levels, of brain activity.

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ReviewThe Addictive Dimensionality of Obesity

Section snippets

Genetic Overlaps

Molecular Overlaps: Focus on Dopamine

Neurocircuitry and Behavioral Overlaps

Summary and Implications

Brain Res

Brain Res

Neuroscience

Physiol Behav

Trends Endocrinol Metab

Physiol Behav

Prog Neurobiol

Behav Brain Res

Neurosci Biobehav Rev

Neuroimage

Trends Cogn Sci

Neuroimage

Neuropharmacology

Life Sci

Neuroimage

Physiol Behav

Physiol Behav

Neuroimage

Neuroscience

Neuroimage

Neuroscience

Appetite

Neuropsychopharmacology

Neuroimage

Trends Neurosci

Biol Psychiatry

Neuroimage

Use of genome-wide expression data to mine the “Gray Zone“ of GWA studies leads to novel candidate obesity genes

PLoS Genet

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Nat Genet

Genetic variation and effects on human eating behavior

Annu Rev Nutr

Increased prevalence of the Taq I A1 allele of the dopamine receptor gene (DRD2) in obesity with comorbid substance use disorder: A preliminary report

Pharmacogenetics

Role of genetic variation in the cannabinoid type 1 receptor gene (CNR1) in the pathophysiology of human obesity

Pharmacogenomics

CNR1 gene polymorphisms in addictive disorders: A systematic review and a meta-analysis

Addict Biol

Dopamine for “wanting“ and opioids for “liking“: A comparison of obese adults with and without binge eating

Obesity (Silver Spring)

The role of the Asn40Asp polymorphism of the mu opioid receptor gene (OPRM1) on alcoholism etiology and treatment: A critical review

Alcohol Clin Exp Res

Obesity and addiction: Neurobiological overlaps

Obes Rev

Modulation of the mesolimbic dopamine system by leptin

Brain Res

GLP-1 neurons in the nucleus of the solitary tract project directly to the ventral tegmental area and nucleus accumbens to control for food intake

Endocrinology

Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite

J Clin Invest

Ghrelin administration into tegmental areas stimulates locomotor activity and increases extracellular concentration of dopamine in the nucleus accumbens

Addict Biol

Ventral tegmental area leptin receptor neurons specifically project to and regulate cocaine- and amphetamine-regulated transcript neurons of the extended central amygdala

J Neurosci

Insulin acts at different CNS sites to decrease acute sucrose intake and sucrose self-administration in rats

Am J Physiol Regul Integr Comp Physiol

Exposure to elevated levels of dietary fat attenuates psychostimulant reward and mesolimbic dopamine turnover in the rat

Behav Neurosci

Relationship between substance use and body mass index in young males

Am J Addict

Association between obesity and psychiatric disorders in the US adult population

Arch Gen Psychiatry

Reduced nicotine reward in obesity: Cross-comparison in human and mouse

Psychopharmacology (Berl)

Body mass index and marijuana use

J Addict Dis

Alcohol use disorders after bariatric surgery

Obes Surg

Issues for DSM-V: Should obesity be included as a brain disorder?

Am J Psychiatry

Dopamine signaling in the dorsal striatum is essential for motivated behaviors: Lessons from dopamine-deficient mice

Ann N Y Acad Sci

Review
The Addictive Dimensionality of Obesity