We have completed maintenance on DiscoverMagazine.com and action may be required on your account. Learn More

The Strange World of "Reward Deficiency Syndrome" (Part 2)

Neuroskeptic iconNeuroskeptic
By Neuroskeptic
Jul 5, 2015 9:07 PMNov 19, 2019 9:54 PM


Sign up for our email newsletter for the latest science news

In Part 1 of this post, I discussed a new scientific journal in the field of addiction medicine, called the

Journal of Reward Deficiency Syndrome (JRDS).

What drew my attention to this journal was the unusual fact that the founding editor, Dr Kenneth Blum, also founded the company that publishes it - as well as being an author on almost all of the articles in the first issue, and the developer of the eponymous concept of "reward deficiency syndrome" (RDS). In this post I'll look into the science of RDS.

On PubMed, a search for "reward deficiency syndrome" returns 65 hits, with the first one in 1995. Blum is an author on 44 of these papers (68%). On the other hand, Blum has published over 200 PubMed papers so, while RDS is largely Blum's work, Blum's work is not limited to RDS. One of his early papers looked at the rather excellent topic of "Effects of vodka and bourbon on sleeping time in mice." RDS is Blum's neurobiological model of addictions - including drug abuse, alcoholism, compulsive gambling, and so on. By this theory, a substantial minority of people ("over 30% of the US population"in fact) suffer from an innate defect in the brain's reward circuitry, the neural pathways that respond to pleasant stimuli. People with this 'reward deficiency syndrome' (RDS) struggle to experience pleasure from everyday things. This, in turn, drives sufferers to seek out additional sources of pleasure, such as drugs, to satisfy their lack of reward. Thus addictions arise. The major cause of the RDS is said to be a deficit in dopamine neurotransmission, and in particular, reduced expression of the dopamine D2 receptor (D2R). According to Blum, a particular genetic variant of the D2R gene, the A1 allele of the Taq1A polymorphism, is the cause of many, perhaps even most, cases of addiction. In 1990, Blum and colleagues published a paper in the prestigious Journal of the American Medical Association, called Allelic Association of Human Dopamine D2 Receptor Gene in Alcoholism. Using molecular genetic techniques that were very advanced for the time, these researchers reported that Taq1A is associated with alcoholism. The A1 allele was found in 69% of a sample of 35 alcoholics, as compared to only 20% of 35 healthy controls without the disorder. This extremely strong association suggested that the D2R A1 allele was a major cause of alcoholism. The 1990 JAMA paper has since been cited over 1,000 times, and there's no doubt that it was a pioneering piece of work. Twenty five years later, Blum still promotes the idea that Taq1A is strongly associated with alcoholism as well as other addictions. For instance, in an article published earlier this year in JRDS, Blum et al. write that

[The Blum et al. (1990) JAMA paper] was fraught with controversy from the scientific community, but now almost a quarter of a century later it has been globally confirmed, and it [i.e. A1] is considered a major gene involved in all addictive behaviors.

Although the authors of this article go on to note that there have been some negative studies too, the overall message is that Blum et al. (1990) has been "confirmed". Similarly, in a 2012 article for a popular audience, he wrote that

Given that about 30% of us are born with genetically induced low dopamine brain function [i.e. A1] how can we overcome this survival variant of human nature and prevent excessive craving behavior?... a Bayesian mathematical formulation was used to predict the lifetime risk for any RDS behavior if you carry the A1 version of the DRD2 gene at birth. Total risk for any behavior was predicted to be as high as 74%.

However, the claim of a strong association between TaqA1 and alcoholism has not stood the test of time very well. According to a 2007 meta-analysis of 40 studies of this polymorphism in alcoholism (from Marcus Munafo), the evidence suggests that the association is much weaker than originally reported. The meta-analytic odds ratio was 1.21, compared to the original 1990 report that set the odds ratio at 8.73. (An odds ratio of 1.00 means no effect.) 8.73 is a dramatic odds ratio, while 1.21 is a modest one. Here's the forest plot from the 2007 meta-analysis, showing that more recent studies (at the bottom) tended to find smaller effects (closer to the line of odds ratio 1).

Another 2013 meta-analysis of alcoholism and DRD2 Taq1A likewise found a small association. The A1 allele has also been studied in the context of other disorders. For instance, one recent meta-analysis found a link to Tourette's, but another review of 29 studies found no evidence of a link to smoking, despite early claims of a strong association. It's very common that the first report of a genetic association turns out to be the strongest one, and that subsequent studies either find a weaker effect or none at all. In fact this problem is so common that it's got its own name, the 'decline effect'. Psychiatric genetics is especially prone to this. Today, 'candidate gene' studies focusing on a single polymorphism, of which Blum et al. (1990) is a classic example, are now somewhat discredited for this reason. So the fact that the early claims about Taq1A have only been replicated to a modest degree is unremarkable, and it doesn't mean that RDS is no longer valid as a conceptual model. The broad idea that addictions are a kind of self-medication for defective reward circuitry remains an interesting one. What is remarkable however is that Blum appears to have commercialized the idea that Taq1A A1 is a marker for addictions, and the idea that certain nutritional therapies can boost dopamine and thus treat "RDS". Stay tuned for Part 3 in which I'll look into these commercial aspects.

Part 3 is now up. Here's a link to Part 1.

1 free article left
Want More? Get unlimited access for as low as $1.99/month

Already a subscriber?

Register or Log In

1 free articleSubscribe
Discover Magazine Logo
Want more?

Keep reading for as low as $1.99!


Already a subscriber?

Register or Log In

More From Discover
Recommendations From Our Store
Shop Now
Stay Curious
Our List

Sign up for our weekly science updates.

To The Magazine

Save up to 40% off the cover price when you subscribe to Discover magazine.

Copyright © 2024 Kalmbach Media Co.