The Genetics of Bliss

The phrase “nature vs. nurture” calls to mind the idea that the traits that make us who we are, such as our strength, weight, and personality, result from a complex combination of genetic factors and life experiences.  This combination is so, well, complicated that scientists still haven’t entirely figured out where genetics ends and environmental contributions take over in the way our traits develop. After all, our genetics and life experiences are constantly influencing one another throughout our lifetime.  

Because nature and nurture are so intertwined, and because complex traits are governed by many genes, it is a rare that researchers find a single gene that can directly impact a complex trait such as personality.  Yet, this is exactly what happened when researchers reported the “bliss gene,” which encodes an enzyme that degrades the body’s natural cannabinoid neurotransmitter (Minkov, Bond, 2015). The mainstream press reported this finding as the discovery of the genetic marker for happiness (New York Times, Vice). They made it sound like scientists had made a breakthrough discovery that would affect us all. But, unfortunately, the media seriously oversold and oversimplified these scientific findings. This week, we will look closer at claims about the bliss gene and discuss whether it is truly the key to happiness.  

The basics of bliss

So why is this so-called bliss gene?  This gene encodes an enzyme called Fatty Acid Amide Hydrolase (FAAH for short), which degrades our body’s natural cannabinoid molecule, anandamide (an-AN-duh-mide; whose name is rooted in the Sanskrit word for “bliss.”)  Human beings can express two versions, or alleles, of the FAAH gene: FAAH-A, which is rare, and the FAAH-C, which is more common. For the sake of simplicity, we’ll refer to these two alleles as A and C from here on out.  Because humans have two copies of each of our genes, we also have two copies of the FAAH gene, which means we can carry one of three possible combinations of the alleles: AA, AC, or CC. C (the more common allele) creates a version of FAAH that is better at degrading anandamide than the version created by A, so individuals carrying CC naturally have less anandamide in their bodies. Individuals carrying AA have high levels and individuals carrying AC have medium levels.   

OK, so let’s think for a minute. We all know of cannabis, the plant that our nervous system’s cannabinoid signaling system is named after.  When we think of cannabis, we think of calm, happy, and hungry people. Based on this, wouldn’t we predict that people carrying the C allele, the stronger allele that degrades our natural cannabinoid faster, would therefore be anxious, depressed, and eating less?  And wouldn’t we also predict that individuals carrying the A allele, who have more natural cannabinoid in their systems, would be, well…high all the time?

As always with biology, nothing is ever that simple; if we take a group of people with the AA genotype, they might be happier as a whole compared to a group of CC people, but that doesn’t necessarily mean that each individual in that group is jumping for joy.  

Why we think that the bliss gene can predict whether someone will be happy

In their research, the scientists that popularized the bliss gene typically surveyed populations of people from countries all over the world. They asked these people to report how happy they felt and then they compared these ratings to whether those surveyed had the A or C allele.  In general, people from countries with a higher prevalence of A (overall higher levels of anandamide in the population) tended to say that they were happier than people from countries where C was more common (overall lower levels of anandamide in the population). Based on this research alone, we might be tempted to conclude that we can predict how happy a person is likely to be based on whether they have zero, one, or two copies of the A allele.

But there’s more! Humans carrying two copies of the A allele (the happy folks) can tolerate more pain and cold, and they also get used to scary situations faster. These traits can certainly be assets, and some researchers have suggested that this makes carriers of the A allele resistant to developing another complex condition caused by both genes and environmental factors: PTSD.  

However, this is where the fun with the FAAH-A allele stops: Other scientists have found that people carrying AA alleles and who have experienced repetitive childhood trauma are more likely to develop depression, anxiety, alcoholism and substance abuse issues, and are less responsive to specific psychiatric drugs when they are suffering from mental illness.

The fact that the FAAH-A allele is associated with good attributes in one context and negative ones in another is a perfect example of how the interplay between the environment and our genes can directly influence who we are.

The Link between Environment and Genetics

Life experiences such as early childhood trauma can contribute to diseases such as depression, anxiety, or alcoholism because they influence a process called epigenetics.  Epigenetics happens when something in a person’s environment causes the machinery in their cells to turn on or turn off specific genes.  As you might guess, the bliss gene works with other genes to regulate anandamide levels, their ability to do so is likely affected by environmental challenges like early childhood trauma.

Cause for hope and a chance of bliss

Although the bliss gene may not directly cause bliss, it may help us figure out how to treat psychiatric disorders.  To simplify psychiatric care, doctors, sadly, do not personalize treatments for every patient to the fullest extent. Rather, psychiatrists group patients with the same psychiatric disorders together and use predetermined strategies to treat everyone.  

But this might change with the discovery that the bliss gene and other genes affect mood. Today, it’s easy for us to sequence our genes and determine if we carry the AA, AC, or CC combination of FAAH alleles.  With this power, researchers intend to determine which alleles  psychiatric disorders have and try to predict how much anandamide they have in their bodies so they can create targeted strategies to better treat them.  This personalized approach will revolutionize psychiatric care because it will allow doctors to predict how their patients will respond to certain drugs based on their DNA. For example, if a patient is found to be AA, doctors can start a patient out on drugs that they know work in people carrying the AA alleles.  Ultimately this will give patients fewer discouraging setbacks as they find out their medications don’t work.

While the A allele can help us understand how to treat psychiatric conditions, knowledge about the C allele (which is associated with lower anandamide levels) could help us develop more effective treatments for pain. Since anandamide blocks pain, scientists are looking for ways to boost anandamide levels by inhibiting FAAH, the enzyme that breaks it down.   In fact, according to animal studies, if you have the CC allele and your body hasn’t been exposed to high levels of anandamide all of your life, using a drug to boost its own natural cannabinoid might actually reduce your pain, depression, and anxiety.  Developing drugs like this is incredibly attractive, especially because it can reduce doctors’ and patients’ reliance on opioids.  Ultimately, the more we learn about the FAAH gene and its role in our emotional state, the more we may be able better understand ourselves and control its activity in our never-ending pursuit of bliss.  But since we can’t be too sure of how genes affect someone’s disposition, there’s no telling how long the path will be to pure bliss.

References

1. Minkov, M., Bond, M.H. (2015). A Genetic Component to National Differences in Happiness, Journal of Happiness Studies, DOI 10.1007/s10902-015-9712-y
2. Vice https://motherboard.vice.com/en_us/article/8q8kb4/this-gene-mutation-causes-some-people-to-feel-naturally-high
3. Times https://www.nytimes.com/2015/03/08/opinion/sunday/the-feel-good-gene.html
4. Spagnolo, P., Ramchandani, V., Schwandt, M., Kwako, L., George, D., Mayo, L., … Heilig, M. (2016). FAAH Gene Variation Moderates Stress Response and Symptom Severity in Patients with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence. Alcoholism, clinical and experimental research (Vol. 40). http://doi.org/10.1111/acer.13210
5. Jack C. Sipe, Kyle Chiang, Alexandra L. Gerber, Ernest Beutler, and Benjamin F. Cravatt.  A missense mutation in human fatty acid amide hydrolase associated with problem drug use.  PNAS June 11, 2002. 99 (12) 8394-8399; https://doi.org/10.1073/pnas.082235799
6. Judit Lazary, Nora Eszlari, Gabriella Juhasz, Gyorgy Bagdy.  Genetically reduced FAAH activity may be a risk for the development of anxiety and depression in persons with repetitive childhood trauma.  European Neuropsychopharmacology. Volume 26, Issue 6, June 2016, Pages 1020-1028
7. Zuzanna E Zajkowska, Amir Englund, and Patricia A Zunszain. Towards a personalized treatment in depression: endocannabinoids, inflammation and stress response.  PHARMACOGENOMICS VOL. 15, NO. 5 REVIEW. 2014.

Kate Proudfoot received her Ph.D. in cell and molecular biology from the University of Chicago. Kate is also an organizer for Expanding Your Horizons Chicago, a one-day symposium aimed at engaging middle school girls in science.