When Food Is an Addiction

Introduction

Over 1/3 of adults in the United States are considered obese, defined as body mass index (BMI) ≥30, and an additional 1/3 are considered overweight, defined as BMI ≥25. Obesity is one of the leading public health problems in the United States, contributing to significant morbidity, mortality, and public health cost. Obesity-related illnesses, including cardiovascular disease, stroke, and certain types of cancer are some of the leading causes of preventable deaths. Medical costs of managing obesity and obesity-related illnesses accounts for nearly over 20% of healthcare spending, over $190 billion in 2005, which, if unchecked, could exceed $66 billion by 2030.

Certainly, environmental factors have important implications in obesity. High calorie, palatable foods, which are staples of the so-called “Western” diet, and increasingly sedentary lifestyles have contributed to the obesity epidemic. Traditionally, primary care physicians will recommend diet and exercise for obese patients; however, nonadherence is high, and even when some patients adhere to strict diet and exercise regimens, they are unable to lose weight, possibly due to genetic and epigenetic factors. Similarly, not all individuals who eat high calorie diets and/or engage in sedentary lifestyles become obese, providing further evidence that endogenous factors may be relevant to the pathophysiology of obesity. Given the enormous public health burden associated with obesity, substantial efforts and resources have been directed toward further understanding mechanisms and pathophysiology of obesity in order to develop a more sophisticated understanding of the illness as well as more effective management and treatment strategies.

Increasingly, because investigation into “peripheral” causes (e.g., lipid dysregulation, insulin sensitivity) has failed to make an impression on the problem of obesity as a whole, conceptualization of obesity and treatment developments has shifted to more central causes. While neuroendocrine influences on appetite and satiety are well characterized, neuroscientists are increasingly investigating brain systems involving reward, motivation, and hedonic experiences as they relate to hedonic eating. Through much preclinical and clinical research based on dopaminergic function, two parallel models of obesity have emerged, the reward deficit model and the reward surfeit model. In the former model, striatal dopamine is increased in response to food, suggesting a positive-reinforcement schedule of reward, whereas the latter model suggests that affected individuals have a genetically determined baseline blunted DA release, resulting in cravings and search for rewarding stimuli (including food).

An abundance of evidence exists for both of these models, and a discussion of the competing hypotheses is beyond the scope of this chapter. However, this dichotomy raises an important point. Obesity is a syndrome, principally defined by an epidemiologically based cutoff on weight, a continuous metric. However, in 1972, John Feighner, Eli Robbins, and Sam Guze of the Department of Psychiatry at Washington University in St. Louis School of Medicine, inspired by the practice in other disciplines in medicine, implored clinicians and researchers to define psychiatric illness by longitudinal history, family history, pathophysiology, and delimitation from other illness in addition to the clinical picture. This tradition has continued in every iteration of the Diagnostic and Statistical Manual for Psychiatric Disorders (DSM) since DSM III was published in 1980. Thus, that obesity, which in a strict sense is a cross-sectional clinical description, should have multiple, valid and replicable evidence bases for pathophysiology is a foregone conclusion, and thus one must focus on both “top down” (i.e., phenotypically driven) as well as bottom-up (neuroscience informed) components when classifying obesity in terms of its psychiatric components.

In this chapter, we will largely focus on the reward-deficit model, which as described by Blum et al., is a well-validated model of drug and alcohol addiction (called the “Reward Deficiency Syndrome) and extend this idea that in some individuals, obesity may be the manifestation of food addiction. We will discuss historical concepts, advances in fundamental neuroscience, clinical descriptions, relationship to substance use disorders, other behavioral addictions, and eating disorders, and ultimately treatment.

Preclinical Evidence

Behavioral Pharmacology

The idea that certain, highly palatable foods containing sugar and/or fat could have addictive properties was inspired by the behavioral (i.e., DSM) criteria for substance use disorders, specifically tolerance, withdrawal, and loss of control. In a series of classic experiments in Bartley Hoebel's laboratory at Princeton University, rodents were given 12-h access to both lab chow and glucose/sucrose solutions and then subsequently deprived of food for 12 hours. This cycle was repeated for 3 weeks, which induces a state of spontaneous binge eating when exposed to food. Compared to control rodents offered ad libitum access to a sucrose solution and/or lab chow, the rats in the 12-h access/restriction group show binge usage (increased intake during the first hour of food exposure), spontaneous binge periods during the time when food is offered, increased lever presses for sugar, and opioid-like withdrawal symptoms either following either sugar/chow removal or naloxone administration. Additionally, rats on a maintenance/restricted intake paradigm demonstrate locomotor cross-sensitization to amphetamine and increased alcohol intake. A critical observation from these experiments is that simply having unlimited access to food or sugar does not produce an addiction-like phenotype; the restricted access paradigm appears absolutely necessary for the behavioral change to occur.

Interestingly, when rats binge on sugar alone, they do not gain weight, yet when rats are offered sugar and fat, they tend to binge and gain weight. Rats that binge on fat alone do not show evidence of opioid-like withdrawal when naloxone is administered, yet binge-prone rats will tolerate high levels of shock when it is paired with a high sugar/high fat food available for consumption. Additionally, Bocarsley et al. found that rats with access to solutions containing high fructose corn syrup, one of the commonest additives in food today, experienced increased abdominal adiposity, weight gain, and hypertriglyceridemia. Collectively, these preclinical findings indicate that individual macronutrients may selectively modulate addictive-like behaviors through both convergent and divergent mechanisms. As humans typically consume food consisting of a multifarious array of nutrients, we can envisage a model in which high sugar, high fat foods consumed in the so-called “western diet” interact with underlying genetic and environmental factors, resulting in the food addiction-obesity syndrome.

Neurotransmitter Systems: Dopamine

Many decades of research have implicated the neurotransmitter dopamine (DA) as central to drug addiction in terms of binge intoxication (acute surge in striatal dopamine release in the nucleus accumbens [NAc] with substance use), withdrawal negative affect (depletion of dopamine following cessation), and preoccupation/anticipation (dopamine release in the presence of anticipating use or experiencing use-associated salience). Emerging evidence suggests that parallel changes in dopamine release, receptor density, and receptor gene expression characteristic of drug addiction may underlie the behavioral manifestations of rats who display addictive behaviors regarding food. Food intake results in striatal dopamine release, and in rats exposed to food ad libitum after satiety is achieved, the novelty of the food, even highly palatable food, wears off and dopamine release is blunted. However, in rats who binge on highly palatable food, dopamine release in the nucleus accumbens (NAc) surges as occurs in the binge-intoxication of drugs of abuse. Additionally, obese rats have been found to have a downregulation of D2 receptors, a consistent phenomenon found in addiction, and D2R knockout rats demonstrate compulsive like food seeking behavior when exposed to highly palatable foods.

Neurotransmitter Systems: Opioids

The endogenous opioid system also appears to have important implications for overconsumption of highly palatable foods and food addiction. In murine models, binge-like consumption of highly palatable foods is associated with increased expression of the mu-opioid receptor (MOR) in the cingulate cortex, hippocampus, locus coeruleus, and shell of the nucleus accumbens, key areas involved in emotion, memory, and stress response that have similarly been implicated in addiction. As such, a variety of MOR agonists have been shown to increase intake of highly palatable foods, particularly in binge-eating animals, and MOR antagonists such as naltrexone have been shown to decrease binge consumption of highly palatable foods. As mentioned previously, administration of MOR antagonist naloxone produces symptoms similar to opioid withdrawal in rats with a history of sugar binging.

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