Trait#94: Dopamine and impulsive eating (DRD2)
Monday, March 29, 2021. Author FitnessGenes
Monday, March 29, 2021. Author FitnessGenes
Dopamine (DA) is an important neurotransmitter (i.e. a chemical messenger molecule used to send signals between nerves) in the brain and central nervous system.
Brain networks that use dopamine play a role in:
It’s this last role in reward and motivation that has earned dopamine the (perhaps overly simplistic) moniker of the brain’s “pleasure chemical.” On this note, dopaminergic pathways in the brain play a role in cravings and reward related to intake of highly palatable food.
You can read more about dopamine in the Dopamine Metabolism (COMT) trait article.
Dopamine sends signals between nerves (neurons) by binding to and activating specialized receptors called dopamine receptors.
There are 5 major types of dopamine receptor, called D1- D5, which differ in their function and distribution in the brain.
D2 receptors are found in particularly high density in a deep structure called the striatum, which is part of the brain’s reward system. D2 receptors are also found in other parts of the brain, including the cerebral cortex (responsible for higher order functions such as planning, goal-directed behaviour), hippocampus (involved in emotion and memory), and hypothalamus (which plays a role in food intake and energy balance).
As well as activating nerves, D2 receptors are also found on presynaptic nerve endings, where they alter the production, packaging, and release of dopamine from synaptic vesicles.
Source: Brichta, L., Greengard, P., & Flajolet, M. (2013). Advances in the pharmacological treatment of Parkinson's disease: targeting neurotransmitter systems. Trends in neurosciences, 36(9), 543-554.
Several studies suggest that D2 receptors are involved in signalling the rewarding aspects of food and control of food intake. For example, neuroimaging studies have found that people with obesity had lower levels of D2 receptors in the striatum, which was thought to contribute to impulsive eating behaviours.
Over 10,000 years ago, when humans lived as hunter gatherers, the food supply would have been insecure. Consequently, we have evolved various mechanisms to maximise energy intake when food is available, allowing us to survive periods of scarcity.
In this respect, one of the major roles of dopaminergic brain networks is to integrate information about the nutritional value and sensory properties (e.g. sight, taste, smell) of foods, as well as our own internal state (e.g. when we last ate), and then optimise our behaviour to obtain and store energy.
On this note, different dopaminergic pathways in our brain regulate our motivation to eat foods that are high in energy (i.e. calories), such as those high in fat and sugar.
Dopamine pathways in the brain
We have four main pathways or ‘tracts’ in the brain that use dopamine:
- Mesocortical pathway (yellow in the diagram below)
This pathway projects from a region in the midbrain called the ventral tegmental area (VTA) and extends to the frontal cortex. It plays a role in cognition, learning, attention, inhibitory control, and other executive functions.
- Mesolimbic pathway (red)
This pathway extends from the VTA to a part of the brain called the striatum. The mesolimbic pathway plays a key role in reward and pleasure, and has been implicated in the process of addiction.
- Nigrostriatal pathway (blue)
This pathway extends from an area in the midbrain called the substantia nigra to the striatum. It plays a major role in the control of movement, as well as in reward.
- Tuberoinfundibular pathway (green)
The tuberoinfundibular pathway controls the secretion of prolactin – a hormone released by the pituitary gland that promotes milk production. The role of this pathway in eating behaviour is unclear.
Source: Yang, S., Boudier-Revéret, M., Choo, Y. J., & Chang, M. C. (2020). Association between Chronic Pain and Alterations in the Mesolimbic Dopaminergic System. Brain Sciences, 10(10), 701.
Dopamine pathways and eating behaviour
The individual dopamine pathways play slightly different roles in the control of eating behaviour.
- Mesolimbic pathway and food reward
Dopamine neurons in the mesolimbic pathway are involved in the signalling of food reward.
The term “reward” is tricky to define, has different components, and needs unpacking. In the simplest of terms, rewards are things we work to obtain through allocation of time, energy, and effort. This includes things such as food, water, sex, and drugs.
Our brain has a ‘reward system’ (which includes our dopaminergic pathways) that analyses information about these rewards, motivates us to obtain them, and generates feelings of pleasure when we do obtain them.
For instance, say you ate a slice of pizza. The taste, texture, and sensory experience of eating the pizza would give us feelings of pleasure. This pleasurable experience is known as the ‘liking’ aspect of reward.
Once we’ve eaten the pizza, we also learn to associate the pizza with pleasurable feelings. This is known as reward learning. More specifically, our reward system associates specific cues, such as the sight or smell of pizza, a particular social setting, or a specific emotion, with the pleasurable experience of eating pizza. The brain then attributes a ‘desire’ or ‘want’ to these various cues. To adopt the neuroscientific lingo, we say our brain attributes incentive salience to the pizza and its associated cues.
When we next see or smell pizza, feel a particular emotion, or enter a particular social setting, we then experience a desire to eat pizza, which is the “wanting” aspect of reward. This ‘wanting’ is thought to be mediated by activity in our mesolimbic dopamine pathway.
Source: Warlow, S. M., Baumgartner, H. M., Freeland, C. M., Naffziger, E. E., Olney, J. J., Berridge, K. C., & Robinson, M. J. (2020). Sensitization of incentive salience and the transition to addiction.
Mesolimbic dopaminergic neurons are particularly responsive to unexpected rewards. If someone suddenly handed you a free slice of pizza out of the blue, this would trigger greater dopamine activity than if you were sat at a restaurant expecting to eat pizza.
This is because dopamine is thought to signal reward prediction error – a discrepancy between expected and actual rewards. When a behaviour (e.g. going to fridge) results in a greater than expected reward (a leftover slice of pizza that we forgot about), we get a much bigger ‘dopamine hit’. This motivates us to repeat that same behaviour again.
A corollary of this, however, is that when we repeat this behaviour again (e.g. when we next go to the fridge), we expect the reward (i.e. we expect to find a slice of pizza). Therefore, if we do indeed find a slice of pizza, there is no reward prediction error, and we do not a receive a ‘dopamine hit’.
Consequently, we may seek out greater rewards (e.g. a tastier food): known as reward-seeking behaviour. We may also seek out new situations with new and unpredicted rewards, known as novelty-seeking behaviour.
Changes in dopaminergic activity in the mesolimbic (and other) pathways can affect how likely we are to engage in these reward and novelty-seeking behaviours.
- Mesocortical pathway and executive function
The mesocortical pathway, which connects to structures in our frontal lobe such as the prefrontal cortex, plays a key role in so-called executive functions. This term applies to a set of higher-order cognitive processes such as planning, learning, organisation, inhibitory control, attention and working memory.
So, how does this apply to eating behaviour? Dopaminergic activity in the mesocortical pathway is thought to underlie our inhibitory control of food intake. For example, if a slice of cake was placed in front of you, you may experience an instinctive desire or “wanting” to grab and eat it. Dopaminergic activity within the frontal cortex is thought to help us inhibit these impulsive (or “prepotent”) responses.
The mesocortical dopaminergic pathway is also involved in how we shift our attention to and away from food and food-related cues. Say, for example, you were working at your desk, and a colleague brought cookies to share. Dopaminergic activity in the mesocortical pathway would influence how strongly the cookies draw your attention, as well as how easily you can shift attention away from the cookies and back to the work task at hand.
Our ability to learn about the positive and negative repercussions of food intake may also be influenced by our mesocortical dopamine system.
- Nigrostriatal pathway and food reward
The nigrostriatal pathway also projects to the striatum and plays a role in food reward. In particular, the nigrostriatal pathway is thought to be important in reward learning – the way in which we learn which foods are pleasurable and attribute ‘wants’ that motivate us to eat these foods.
Your DRD2 gene encodes the dopamine D2 receptor.
A SNP (Single Nucleotide Polymorphism), known as the Taq1A polymorphism (rs1800497), gives rise to two different variants (“alleles”) of the DRD2 gene: the A1 allele and the A2 allele.
Studies have associated the A1 allele with a greater risk of impulsive eating, increased waist circumference, higher BMI, and obesity. As such, the A1 allele is considered the risk allele for unhealthy eating behaviour.
Your ‘Dopamine and impulsive eating trait’ result will tell you whether you carry the A1 risk allele.
As explained in the previous section, the Taq1A polymorphism gives rise to two different DRD2 gene variants: A1 and A2. Given that we inherit genes in pairs (one from our mother, one from our father), this generates three possible genotypes:
Neuroimaging studies suggest that people who carry the A1 risk allele (i.e. those with the A1/A1 and A1/A2 genotypes) have 30-40% fewer dopamine D2 receptors in part of the brain called the striatum.
The striatum is one of the reward centres of the brain and is a key region in the mesolimbic and nigrostriatal dopaminergic pathways. Reduced density of dopamine in D2 receptors in the striatum is therefore likely to affect the functioning of various dopaminergic brain circuits that regulate eating behaviour.
People who carry the A1 allele may be at greater risk of impulsive eating.
Impulsive eating refers to acting immediately on urges to eat, with little consideration of the future consequences of eating. For instance, instinctively eating a slice of cake at your desk, without thinking about how the subsequent sugar high may make you feel sick, put you off your lunch, or hamper your weight-loss goals, can be considered an example of impulsive eating behaviour.
On a related note, carriers of the A1 may also experience greater cravings for highly palatable food. For example, a study of Asian American college students found that those with the A1 allele reported significantly stronger cravings for carbohydrates and fast-food compared to those with the A2/A2 genotype.
The A1 allele and behavioural traits
The scientific literature suggests that rather than directly driving food intake, the A1 allele is associated with various heritable behavioural traits (or ‘endophenotypes’) that increase the risk of impulsive eating and other unhealthy eating behaviours.
These wider behavioural traits linked to the A1 allele include:
- High impulsivity
Impulsivity is defined as “a predisposition toward rapid unplanned reactions to internal or external stimuli without regard to the negative consequences of these reactions to the impulsive individuals or to others.”
Impulsivity can be thought of comprising two parts: impulsive action and impulsive choice. Impulsive action refers to the failure to inhibit inappropriate responses, whereas impulsive choice refers to decision-making processes that fail to consider future consequences.
Unsurprisingly, high impulsivity as a behavioural trait is linked to impulsive eating. For example, in an analysis of 51,368 subjects in the NutriNet-Sante Study, people with higher impulsivity scores consumed more calories, snacked more frequently, and had poorer quality diets with more high-sugar and high-salt foods and fewer fruit and vegetables.
Various neuropsychological tests can be used to assess impulsivity. One simple test is the ‘Go/No-Go Task’ where, for example, you click a button every time you see a blue dot on a screen (a Go trial), and refrain from clicking every time you see a red dot (a ‘No-Go’ trial). People with higher impulsivity tend to inappropriately click the button when seeing a red dot more often, because they have greater difficulty inhibiting a response.
On this note, individuals with the A1 allele have been shown to have higher impulsivity on Go/No-Go tasks and other neuropsychological tests. It is possible that the A1 allele contributes to impulsivity and impulsive eating by altering the function of the mesocortical dopaminergic pathways that regulate inhibitory control.
When it comes to impulsive eating, weaker inhibitory control would make it harder to resist the urge to eat highly palatable food.
- Tendency towards immediate gratification
Individuals with the A1 risk allele demonstrate steeper delay discounting. What this means is that they tend to prefer smaller, immediate rewards over larger, but delayed rewards. This behavioural trait is related to impulsivity.
For example, say I gave you the choice of receiving $30 today, or waiting 60 days and receiving $100. People with steeper delay discounting may be more likely to take the smaller, but more immediate, $30 option over the larger, but delayed, $100 option. This is because, despite the $100 being an objectively greater value, an individual’s ‘subjective value’ of the money reduces or gets ‘discounted’ over time. People with steeper delay discounting reduce their subjective valuation of a reward more quickly with time.
Another way of looking at steeper delay discounting is to say that such individuals are more sensitive or receptive to immediate rewards.
Source: Gray, J. C., & MacKillop, J. (2015). Impulsive delayed reward discounting as a genetically-influenced target for drug abuse prevention: a critical evaluation. Frontiers in Psychology, 6, 1104.
The graph above shows that people with low impulsivity would rather wait 50 days to receive $100 than accept anything under $68 today. By contrast, individuals with high impulsivity would happily accept anything above $18 today than wait 50 days for $100. This is because they are more sensitive to the immediate monetary reward.
So, how does this relate to eating behaviour?
People who are more sensitive to immediate rewards are more likely to place greater subjective value on easily accessible and highly palatable junk foods, leading to impulsive eating. On this note, a recent study found that steeper delay discounting was associated with higher BMI, with this relationship more pronounced in A1 risk allele carriers.
It’s also possible that people who discount future rewards more highly may be less receptive to the delayed rewards of healthy eating behaviours, e.g. healthier bodyweight, better physical fitness, improved mood.
Steeper delay discounting isn’t usually a conscious process, but is more likely due to the unconscious functioning of the brain’s reward systems, including mesolimbic dopaminergic pathways.
A1 allele carriers may have altered activity within these brain networks that leads them to attribute greater value, ‘wanting’ or ‘incentive salience’ to immediate food rewards. This may also explain the more intense food cravings seen in A1 allele carriers. In line with this, neuroimaging studies have found A1 carriers to have higher reactivity in brain reward centres to food and food-related cues.
Novelty-seeking is a behavioural trait typified by heightened reward in response to new stimuli and a desire to experience new sensations.
High novelty-seeking scores are shown to predict risky behaviour and have been linked to substance dependence, pathological gambling and, with regards to eating behaviour, overweight and obesity.
Carriers of the A1 allele have been shown to score more highly on measures of novelty-seeking, possibly due to changes in activity in dopaminergic pathways. This may, in turn, drive impulsive eating behaviours.
On this note, A1 allele carriers show greater dopaminergic activity in mesolimbic pathways when unexpectedly presented with a chocolate milkshake. This may reflect a tendency to have greater reward prediction error signals in response to unexpected food rewards.
- Impaired negative outcome learning
A1 allele carriers have been shown to learn to avoid actions with negative consequences less effectively than people with the A2/A2 genotype.
In one neuroimaging study, subjects played a computer game where they had to select symbols. Selecting some of these symbols resulted in positive feedback (e.g. a smiling face), whereas others were linked to negative feedback (e.g. an angry face). Over time, subjects should learn to avoid those symbols linked to negative feedback.
Researchers found that people with the A1 allele learned to avoid the negative symbols less effectively. Furthermore, neuroimaging showed that they had lower neural activity in regions of the mesocortical dopaminergic pathway in response to negative feedback.
Again, how does this relate to eating behaviour?
It is possible that carriers of the A1 risk allele may be less sensitive to and less able to learn from the negative consequences of impulsive eating behaviour.
For example, if you ate an entire box of chocolates, you may feel sick afterwards. However, if your brain is wired up to send a weaker negative feedback signal after feeling sick, you are less likely to avoid eating an entire box of chocolates again in the future.
A few studies have found that people carrying the A1 risk allele have less success with weight loss diets.
For example, in a study of obese post-menopausal women following a caloric restriction diet, those with the A1 allele lost significantly less weight than those with the A2/A2 genotype.
Another study of severely obese individuals found that subjects with the A1 allele lost less weight over a 12-week formula diet and regained more weight during the 40-week maintenance phase.
It is likely that these difficulties with weight-loss relate to impulsive eating behaviours that make it difficult to restrict food intake when presented with multiple opportunities to eat. In support of this, one study found that A1 carriers allocated to a vegan diet were less successful in reducing fat intake.
Your trait looks at the Taq1A (rs1800497) SNP of your dopamine D2 receptor (DRD2) gene. Based on whether or you carry the A1 risk allele linked to impulsive eating, you will be classified into one of two major bands:
As evidence suggests that being overweight or obese can also dysregulate dopaminergic functioning and alter eating behaviour, your insights and actions will also vary depending on whether your lifestyle survey data suggest you are overweight/obese.
To find out your result, please log in to truefeed.
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