The study, led by neuropsychiatrists Michael Lutter and Andrew Pieper from the University of Iowa, examined the effects of breeding two genetically altered mice. One of the mice lacked a gene called SAPAP3, which caused it to groom itself to the point that it had lesions in its skin, while the other mouse lacked a gene called MC4R, causing it to be obese. Deficiencies in MC4R are the most common single-gene cause of morbid obesity and over-eating in people. The gene is also suspected to play a part in compulsive behavior.
Based on previous studies, the team knew that obesity gene MC4R was related to compulsiveness in some sort of way. Their original intent was to see the effects breeding would have on compulsiveness.
“We knew in one mouse you could stimulate excessive grooming through this MC4R pathway, and in another mouse a different pathway (SAPAP3) caused compulsive grooming,” Lutter said. “So, we decided to breed the two mice together to see if it would have an effect on compulsive grooming.”
Their hypothesis was correct. The mice born to the two genetically altered mice had neither MC4R nor SAPAP3, and their grooming behavior was normal. This meant that the compulsiveness associated with a lack of SAPAP3 was balanced out by the lack of MC4R, which can cause compulsiveness when present — their brain cell communication patterns linked to compulsive behavior were normalized.
But going further than normalized grooming, the researchers also found that the mice didn’t grow to become obese. Although the mice had no MC4R, which could have caused them to become obese, the lack of SAPAP3 took away their compulsive behavior.
“We had this other, completely shocking finding — we completely rescued body weight and food intake in the double null mouse,” Lutter said. “So, not only were we affecting the brain regions involved in grooming and behavior, but we also affected the brain regions involved in food intake and body weight.”
Compulsive behavior has been associated with many forms of psychiatric disease, most notably obsessive-compulsive disorder (OCD), but also Tourette syndrome, and eating disorders.
When speaking about his specialty, MC4R, Lutter said, “I’m also interested in how these same molecules affect mood and anxiety and reward, because it’s known that there is a connection between anxiety and development of obesity.”
According to a 2006 National Institute of Mental Health-funded study, one out of four cases of obesity is associated with a mood or anxiety disorder. However, the causal relationship between the two remains undetermined. The study found that the increasing rates of obesity in the U.S. are in-line with the increasing rates of depression, bipolar disorder, panic disorder, and many other disorders. It also found that social and cultural factors seem to influence the presence of obesity, with the strongest connection among college-educated non-Hispanic whites ages 29 and younger.
However, Lutter believes that the connection between compulsive behavior and obesity lies in the evolutionary need to eat safe, clean food.
“Food safety has been an issue through the entire course of human evolution — refrigeration is a relatively recent invention,” he said. “Obsessive behavior, or fear of contamination, may be an evolutionary protection against eating rotten food.”
Sources: Lutter M, Pieper A, Xu P, et al. Double deletion of melanocortin 4 receptors and SAPAP3 corrects compulsive behavior and obesity in mice. PNAS. 2013.
Simon GE, Korff M, Saunders K, et al. Association Between Obesity and Psychiatric Disorders in the U.S. Adult Population. Archives of General Psychiatry. 2006