The rising prevalence and dispersion of obesity in North America in the past decade is analogous to a communicable disease epidemic.1 Longitudinal and cross-sectional associations between major depressive disorder, schizophrenia, and obesity have been established.2,3 Existing evidence also indicates that there is an association between bipolar disorder and obesity.3-8 For example, of the first 500 participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) program, 377 were evaluated for height and weight. The average body mass index (BMI) for the sample was 27.7 ± 6.2 (normal BMI is 20 to 24.9). The results showed that 55% of the patients were either overweight (28%) with a BMI of 25 to 30 kg/m2 or obese (27%) with a BMI greater than 30 kg/m2, which is a much higher percentage than in the general population.8
Higher rates of excessive weight, obesity, and abdominal obesity are consistently reported in individuals with bipolar disorder in other epidemiological and clinical studies as well.4,6 Identified risk factors for obesity in the bipolar disorder population include female sex, economic status, level of education, amount of physical activity, and treatment with weight-gain–promoting agents.4,6 Additional determinants of body weight are total daily intake of simple carbohydrates, total energy intake, caffeine(Drug information on caffeine) consumption, comorbid binge-eating disorder, and number of previous depressive episodes.6,9
A look at the evidence
Compelling evidence also indicates that individuals with bipolar disorder are differentially affected by substance and alcohol(Drug information on alcohol) use disorders.10 When examined alone and together, substance use disorders and obesity were associated with a multi-episode course of bipolar disorder, suicidality, depression severity, decreased probability of symptomatic remission, and shorter time to episode recurrence compared with non–substance abusing and healthy-weight persons with bipolar disorder.10,11
Several investigations as well as media reports have pressed the point that moderate alcohol consumption may convey a protective effect for cardiovascular disease and diabetes.12 A possible mediator of this association is the reduced BMI associated with habitual moderate alcohol intake. In the aggregate, however, the possible somatic benefits of alcohol use in patients with bipolar disorder are significantly overshadowed by the liability and hazardous dysfunction associated with alcohol-related conditions.
Over the past decade, there has been an increasingly audible clarion call to conceptualize excessive eating (phenotypically expressed as obesity) as an addictive behavior.13 A defining characteristic of addiction is the overpowering motivational strength and decreased ability to control the desire to obtain a substance despite economic, social, and health-related consequences.14 In the case of excess weight and obesity, afflicted individuals continue to forage and ingest food despite the obvious social, interpersonal, and medical consequences. Neurobiological investigations increasingly support a heuristic model—namely that obesity and substance use disorders are subserved by overlapping and functionally abnormal reward motivation neural networks.
Substance abuse, obesity, and bipolar disorder
To the best of our knowledge, our group was the first to primarily evaluate the interrelationship between substance use disorders and overweight/obesity in a large population sample of persons with bipolar I disorder.15 The encompassing aims of the investigation were to provide further refinement to the pathophys-iological model subserving these co-occurring syndromes as well as to inform clinical practice.
The data for our analysis were extracted from the Canadian Community Health Survey–Mental Health and Well-Being; a component of the Canadian Community Health Survey, conducted by Statistics Canada. Respondents were residents of private dwellings; a multistage stratified cluster design was used to sample dwellings. Most interviews (86%) were conducted in person, the remainder by telephone. The responding sample totaled 36,984 persons aged 15 years or older, and the participation rate was high (77%).
BMI was computed after gathering information related to respondents’ height and weight. Alcohol dependence within the past year was determined using DSM-IV criteria, and illicit drug dependence within the past year was determined by self-report.16
In keeping with extant literature, individuals with bipolar I disorder had a significantly higher rate of substance dependence than did the general population. The age-adjusted rate of 
Overweight and obese participants with bipolar disorder had a significantly lower rate of substance dependence than did bipolar respondents with normal weight. The association between weight and substance dependence remained after a multivariate statistical analysis that controlled for the effect of sociodemographic factors, such as age and sex, as well as behavioral factors, including leisure-time physical activity and hypertension (Table).
In keeping with the a priori hypothesis, individuals with bipolar disorder with a history of substance dependence had lower rates of overweight and obesity than did non–substance-dependent bipolar respondents (Table). This association also remained after multivariate analysis.
Although not the primary emphasis of this study, we also determined that the inverse relationship between overweight/obesity and substance dependence applied to persons in the general population who did not screen positive for bipolar disorder.
Mechanisms behind the connection
When reviewed together, the results of our investigation indicated that 2 commonly encountered syndromes in bipolar disorder—overweight/obesity and substance dependence—are inversely associated. The translational value of these results has research and clinical implications. From the perspective of pathophysiological research, it could be conjectured that the interrelationship between both phenotypes in bipolar individuals reflects a common and competing abnormality in the brain reward system. For example, dopamine(Drug information on dopamine), a critical neurotransmitter in brain reward circuitry, is implicated in the pathophysiology of manic and depressive episodes, substance abuse, and obesity.
In keeping with this view, individuals who are obese or addicted to cocaine, alcohol, or opiates all exhibit similar down-regulation in striatal D2 receptor expression. An additional, or alternative, hypothesis is that opioidergic mechanisms may be salient because opioid receptor agonists stimulate appetite while opioid antagonists have the opposite effect. Other hypotheses would be that the relationship is an epiphenomenon of malnutrition and poor somatic health in substance-abusing individuals, or that the pharmacological treatments for bipolar disorder, which are often weight gain–promoting, are also salutary for substance use disorders.
Emerging models also indicate that ingestive neuropeptides (peptides that promote ingestion) may be salient to the association between food intake and alcohol-seeking behavior. The pleiotropic peptide leptin, for example, exerts effects on disparate somatic functions, including energy and temperature regulation, appetite, and reproductive hormonal function.17-18 It has been documented that circulating leptin levels, which increase as a function of BMI, exert an effect on cravings for alcohol.19,20
The results of our investigation need to be considered preliminary and in need of replication because of 4 methodological factors: first, a semistructured interview was used, rather than a clinical interview by a mental health practitioner; second, small sample size precluded adequate subgroup analysis; third, data collection was limited to the past year of substance use; and finally, the survey was based on self-report.
Summary
From a clinical perspective, all individuals with bipolar disorder who abuse alcohol or illicit substances need to be counseled on the benefits of adequate nutrition as part of a chronic disease-management model as it specifically relates to a comorbid substance use condition. Alternatively, one could conjecture that intensive weight management strategies in patients with bipolar disorder may alter their propensity for substance misuse, inviting the need for careful clinical surveillance. Preclinical models indicate that hunger intensifies cravings for illicit substance misuse, while caloric intake serves an opposing effect.13,21-22 These data also provide the impetus for practitioners to consider somatic and nutritional aspects in all individuals with bipolar disorder, notably persons with abnormal body weight.
