A meta-analysis of the relationship between brain dopamine receptors and obesity: a matter of changes in behavior rather than food addiction?

Abstract

Addiction to a wide range of substances of abuse has been suggested to reflect a ‘Reward Deficiency Syndrome'. That is, drugs are said to stimulate the reward mechanisms so intensely that, to compensate, the population of dopamine D2 receptors (DD2R) declines. The result is that an increased intake is necessary to experience the same degree of reward. Without an additional intake, cravings and withdrawal symptoms result. A suggestion is that food addiction, in a similar manner to drugs of abuse, decrease DD2R. The role of DD2R in obesity was therefore examined by examining the association between body mass index (BMI) and the Taq1A polymorphism, as the A1 allele is associated with a 30–40% lower number of DD2R, and is a risk factor for drug addiction. If a lower density of DD2R is indicative of physical addiction, it was argued that if food addiction occurs, those with the A1 allele should have a higher BMI. A systematic review found 33 studies that compared the BMI of those who did and did not have the A1 allele. A meta-analysis of the studies compared those with (A1/A1 and A1/A2) or without (A2/A2) the A1 allele; no difference in BMI was found (standardized mean difference 0.004 (s.e. 0.021), variance 0.000, Z=0.196, P<0.845). It was concluded that there was no support for a reward deficiency theory of food addiction. In contrast, there are several reports that those with the A1 allele are less able to benefit from an intervention that aimed to reduce weight, possibly a reflection of increased impulsivity.

DRD2: Bridging the Genome and Ingestive Behavior

“…There are associations with waist circumference (p=0.01 for men and p=0.07 for women in GIANT 3 ), fasting glycemia (p=0.02 in MAGIC 4 ), insulin sensitivity (p=0.01 in MAGIC) and risk for type 2 diabetes (p=0.08) in DIAGRAM 5 ). Of note, a meta-analysis of 33 studies with mostly small samples (under 100) reported no relationship between BMI and A1 allele status [64]. This finding is not surprising since this SNP explains only a small percent of the variance in BMI of the population, making larger samples, and more accurate measures of adiposity necessary to observe reliable associations.…”

Psychological and Neurobiological Correlates of Food Addiction

“…Substance addictions also show evidence of reward deficiency syndrome (Blum et al, 2000), a neural adaptation in response to continued exposure to a substance (or behavior, eg, gambling), that occurs when repeated engagement stimulates reward mechanisms so powerfully that the population of dopamine D2 receptors (D2R) declines (Benton & Young, 2016; Blum et al, 2000, 2014; Gyollai et al, 2014). Due to this decrease in D2R, increased intake is necessary in order to elicit the same degree of reward that was previously achieved through a lower dose (Blum et al, 2000).…”

“…Due to this decrease in D2R, increased intake is necessary in order to elicit the same degree of reward that was previously achieved through a lower dose (Blum et al, 2000). A further indication of the reward deficiency syndrome is the presence of intense cravings and withdrawal symptoms (Benton & Young, 2016). Similar reductions in D2Rs are hypothesized to occur in FA.…”

“…Benton and Young (2016) performed a meta-analysis to determine the relationship between BMI and the presence of Taq1A polymorphism, an A1 allele found to be associated with a lower number of D2R in both healthy and alcoholic subjects (Jonsson et al, 1999; Noble, Blum, Ritchie, Montgomery, & Sheridan, 1991; Pohjalainen et al, 1998). They found no significant effects of the A1 allele on BMI, and therefore concluded that there was no support for the reward deficiency theory of FA (Benton & Young, 2016).…”

Interaction between the obesity-risk gene FTO and the dopamine D2 receptor gene ANKK1/TaqIA on insulin sensitivity

“…With regard to food intake, carriers of the ANKK1 risk allele have reduced responses to palatable and energy-dense food in brain regions involved in reward processing [38]. While the polymorphism is not a major determinant of body weight per se [39], carriers of the risk allele have difficulty losing or maintaining body weight [39,40]. Specifically, an attenuated response to food in the striatum of risk-allele carriers was a predictor of further weight gain [41].…”