Tamea Sisco
forms. Once thought to be primarily environmental, it is now considered to have both genetic and environmental components. In a Swedish adoption study, for example, the weight of the adult adoptees was strongly related to the body-mass index of the biological parents and to the body-mass index of the adoptive parents. The links to both genetic and environmental factors were dramatic. Other studies of adoptees and twins suggest that heredity is an important contributor to the development of obesity, whereas childhood environment has little or no influence. Moreover, the distribution of fat around the body has also been found to have heritable elements. The inheritance of subcutaneous fat distribution is genetically separable from body fat stored in other compartments (among the viscera in the abdomen, for example). It has been suggested that there is evidence for both single and multiple gene anomalies (Bouchard 1995).
Given the complex array of metabolic systems that contribute to overeating and obesity, it is not surprising that a number of neurochemical defects have been implicated. Indeed at least three such genes have been found: one associated with cholesterol production, one with fat transport and one related to insulin production (Bouchard 1995). The ob gene and its product the leptin protein have also been implicated in regulating long-term eating behavior (Zhang et al. 1994). Most recently another protein, glucagon-like peptide 1 (GLP-1) has been found to be involved in the regulation of short-term eating behavior (Turton et al. 1996). The relationship between leptin and GLP-1 is not known. The ob gene may be involved in the animal’s selection of fat, but perhaps not in the ingestion of carbohydrates, which appears to be regulated by the dopaminergic system. It may be that the ob gene is functionally linked to the opioid peptodergic systems involved in reward.
Whatever the relation between these systems, the complexity of compulsive eating disorders suggests that more than one defective gene is involved. Indeed, the relation between compulsive overeating and drug and alcohol addiction is well documented (Krahn 1991, Newman and Gold 1992). Neurochemical studies show that pleasure-seeking behavior is a common denominator of addiction to alcohol, drugs and carbohydrates (Blum et al. 1990). Alcohol, drugs and carbohydrates all cause the release of dopamine in the primary reward area of the brain, the nucleus accumbens. Although the precise localization and specificity of the pleasure-inducing properties of alcohol, drugs and food are still debated, there is general agreement that they work through the dopaminergic pathways of the brain. Other studies suggest the involvement of at least three other neurotransmitters serotonin, GABA and the opioid peptides.
Variants of the dopamine D2 receptor gene appear to be risk factors in obesity. The A1 allele was present in 45 percent of obese subjects as compared to 19 percent of nonobese subjects (Noble, Noble and Ritchie 1994). Furthermore, the A1 allele was not associated with a number of other metabolic and cardiovascular risks, including elevated levels of cholesterol and high blood pressure. In contrast, when the subject’s profile included factors such as parental obesity, a later onset of obesity and carbohydrate preference, the prevalence of the A1 allele rose to 85 percent. More recently another study found a significant association between genetic variants of the D2 receptor and obese subjects (Comings et al. 1993).
There is also an increased prevalence of the A1 allele in obese subjects who have severe alcohol and drug dependence (Blum et al. 1996a). When obesity, alcoholism and drug addiction were found in a patient, the incidence of the A1 allele rose to 82 percent. In contrast, the allele had an incidence of zero percent in nonobese patients who were also not substance abusers and did not have a family history of substance abuse. The presence of the dopamine D2 receptor gene variants increases the risk of obesity and related behaviors.
Pathological gambling-in which an individual becomes obsessed with the act of risking money or possessions for greater “payoffs”-occurs at a rate of less than two percent in the general population. Although it is the most socially acceptable of the behavioral addictions, pathological gambling has many affinities to alcohol and drug abuse. Clinicians have remarked on the similarity between the aroused euphoric state of the gambler and the “high” of the cocaine addict or substance abuser. Pathological gamblers express a distinct craving for the “feel” of gambling; they develop tolerance in that they need to take greater risks and make larger bets to reach a desired level of excitement, and they experience withdrawal-like symptoms (anxiety and irritability) when no “action” is available (Volberg and Steadman 1988). Indeed, there is a typical course of progression