Objective: To present nationally representative findings on the prospective relationships between overweight and obesity and DSM-IV substance use, mood, and anxiety disorders.

Method: A nationally representative sample of 34,653 US adults was interviewed in Wave 1 (2001-2002) and Wave 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. The target population was the civilian population residing in households and group quarters, with gathered data adjusted to be representative of the civilian population of the United States on the basis of the 2000 Decennial Census. The main outcome measures were the incidence of DSM-IV substance use, mood, and anxiety disorders and changes in body mass index status during the 3-year follow-up period.

Results: Regression analyses that controlled for a wide array of covariates showed that overweight and obese women were at increased risk (P < .05) for incident major depressive disorder during the follow-up period (adjusted OR [AOR] = 1.3 [95% CI, 1.02-1.56] and AOR = 1.2 [95% CI, 1.02-1.51], respectively). Overweight men and obese men were at decreased risk (P < .05) of incident drug abuse and alcohol dependence (AOR = 0.7 [95% CI, 0.44-0.96] and AOR = 0.7 [95% CI, 0.52-0.97]), respectively. Obese women had a decreased risk (P < .05) of incident alcohol abuse and drug dependence (AOR = 0.6 [95% CI, 0.45-0.88] and AOR = 0.4 [95% CI, 0.21-0.91], respectively). Men with drug dependence and women with specific phobia had a decreased risk (P < .05) of becoming overweight or obese during the follow-up period (AOR = 0.4 [95% CI, 0.19-0.99] and AOR = 0.8 [95% CI, 0.66-0.95], respectively).

Conclusions: Increased risk of major depressive disorder among overweight and obese women could be attributed to stigma and greater body dissatisfaction among women in Western cultures. Overweight and obesity may serve as protective factors against developing incident substance use disorders, possibly due to shared neural functions in the brain underlying addictions to numerous substances. Results are discussed in terms of their clinical implications, including the need to update treatment guidelines for the management of overweight, obesity, and major depressive disorder.