Deep Brain Stimulation for Obesity

Obesity has become a worldwide epidemic, with prevalence increasing substantially in both developing and developed countries. The Centers for Disease Control and Prevention estimates that, in the United States, 16.9% of children 2 to 19 years of age and 34.9% of adults older than 19 years of age are obese, with 5.7% of the population considered morbidly obese. ^, Morbid obesity is linked with premature death, impaired quality of life, and multiple comorbidities, including type 2 diabetes, cardiovascular disease, musculoskeletal disease, and certain cancers. Annual obesity-related health care costs are estimated at nearly $190 billion in the United States alone.

Body mass index (BMI) is commonly used to assess fat composition of the body. It does not measure body fat directly, but studies have shown that it correlates to direct measures of body fat such as underwater weighing and dual-energy x-ray absorptiometry. ^, BMI is calculated by dividing weight in kilograms by the square of height in meters. A healthy weight is considered to be associated with a BMI from 18.5 to 24.5, while overweight is defined as a BMI of 25 to 29.9. Obesity is defined as a BMI greater than or equal to 30, and morbid obesity is regarded as a BMI greater than or equal to 40 or greater than 35 with comorbidities.

Obesity is most commonly approached as a problem of energy imbalance; however, more recent analyses have suggested that obesity should also be interpreted within the scope of psychiatric diseases. From an energy standpoint, obesity or weight gain is thought to result from a net positive energy balance, where energy intake (food consumption) exceeds energy expenditure (a combination of resting metabolic rate [RMR], physical activity, and the thermic effect of food). Theories for the burgeoning obesity epidemic are myriad, but the problem is multifactorial and is generally regarded as resulting from the perfect storm of more easily available food, higher-calorie foods, and more sedentary lifestyles than witnessed in previous centuries.

In addition to such environmental factors, genetic factors have been increasingly shown to play a role in obesity. The metabolic theory implies an imbalance of circulatory peptide hormones such as ghrelin, obestatin, nesfatin-1, leptin, and insulin interacting with genetic factors leading to obesity. Ghrelin, insulin, and leptin have been shown to act directly on the central nervous system to modulate both metabolism and food intake behaviors. The “incentive salience theory” of food reward recognizes a hedonic component as well as a reward-seeking, motivational component mediated by activation of the mesolimbic dopamine circuitry. Dysregulation of the mesolimbic dopamine system has been implicated in binge eating. ^, In support of the “incentive salience theory,” binge eating was included as a mental disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

Whatever the cause, the population has been searching for an effective solution. The US market is overcrowded with weight-loss supplements, appetite suppressants, exercise plans, and dietary plans. Physicians have also been armed with weight-loss medications that act on both sides of the energy equation. The failure of medications to control obesity has been the impetus for surgical treatments such as gastric bypass, gastric banding (gastroplasty), and intragastric balloon placement. Although bariatric surgery has successfully facilitated weight loss in many patients refractory to other measures, there is a significant risk for morbidity and mortality associated with these procedures. Despite initial weight loss, some patients regain a significant amount of weight, even with technically successful surgery.

Deep brain stimulation (DBS) has become a well-established treatment option for movement disorders such as Parkinson disease, essential tremor, and dystonia. Because of its effectiveness in the treatment of these diseases, the low rates of complications, and the reversibility of the treatment modality, DBS is being investigated as a treatment option for medically refractory psychiatric conditions such as Tourette syndrome, obsessive-compulsive disorder, and depression. The growing recognition of the brain as the source of metabolism and appetite control has led to a resurgence of interest in treating obesity with a brain surgery strategy such as DBS. To understand the rationale behind different potential brain targets for DBS in the treatment of obesity, we provide a review of the neuroanatomy linked with body weight and discuss the various studies supporting DBS as a treatment option.