Stress and Genetics

In the past few days, I’ve been delighted to discover a recent study by one of my old favorite researchers—someone I’ve quoted often in the past—Dr. Eric Nestler. I became fascinated all the way back in 2004 by research he did about the concept of cellular memory and how it provides an explanation for why some people get sick while others with the same risk factors do not. His team found that addictions and other severe stressors cause stable changes in the chromatin and gene expression that alter how DNA is expressed and influence neuronal development and behavioral outcomes.

Since then, Dr. Nestler has evidently not been idle. He published the paper I’m going to discuss today two years ago, alongside Dr. Scott Russo, and this one deals with another subject of great interest to me (and hopefully, to you), the science of resistance to stress. If you’d like to read it yourself, the official title is: Neurobiological basis of stress resilience.

When the paper talks about stress resilience, it is referring to the capacity of humans to endure stress without manifesting the disordered behaviors that are often associated with it. This is a timely issue, since we are currently in the middle of an unprecedented epidemic of anxiety and depression. We were arguably already in an epidemic before COVID hit, and things are far worse now. Dr. Nestler notes one study from the University of Michigan which found that approximately 35% of students and nearly 45% of women on campus have a DSM-diagnosable disorder of anxiety or depression. That’s a significantly higher diagnostic bar than merely having anxiety or depression that negatively affects them to some extent, which makes the numbers all the more striking.

As someone who focuses on therapies for preventative health and wellbeing, I’m especially excited by the idea of conscious processes that can physically alter gene expression and brain health in order to prevent or perhaps even heal the adverse effects of severe stress. And even though much of Nestler’s work is focused on the potential for targeted drugs to treat these effects, he also emphasizes numerous times throughout the paper that resilience is an active process. In fact, he even gives a list of ten positive factors of human resilience. When I first saw this list, I said to my son, “We could have written this,” because it’s striking how well it aligns with what we talk about here on the blog, and with the findings of some of my other favorite sources like the Harvard Grant study. Here are the factors:

1. Positive attitude, realistic optimism.
2. Cognitive flexibility through cognitive reappraisal.
3. Embrace a personal moral compass.
4. Find a resilient role model.
5. Face your fears.
6. Develop active coping skills.
7. Establish and nurture a supportive social network.
8. Attend to physical well-being.
9. Train regularly and rigorously in multiple areas.
10. Recognize, utilize, and foster signature strengths.

What a wonderful list! I’m particularly intrigued by that second item: cognitive flexibility through cognitive reappraisal, because the implication here is something that I’ve been saying for years: most erroneous memories are erroneous in their framing, and if you are able to take active steps to adjust that subconscious framing, it can greatly improve you psychological, and even your physical health.

Dr. Frankl’s paper actually gives direct evidence of what I’ve been calling the devolution of memory, where stressful fight-or-flight triggers become mistakenly associated with all sorts of things that are of no material threat to us, with the result of putting us into a chronically stressful state. Here’s what the paper has to say:

“The PFC [prefrontal cortex] and hippocampus are thought to encode information about traumatic stress and provide cognitive control over emotional behavior. Under chronic stress, traumatic memories can become inflexibly encoded and generalized to non-threatening stimuli. When couple with a loss of top-down cognitive control of PFC, this can manifest as severe avoidance-like behavior and difficulties with emotional regulation.”

In other words, we are seeing compelling evidence that stress and memories that we interpret as traumatic—whether or not anything objectively traumatic actually happened—become overgeneralized and too easily activated. Not only that, but the result causes molecule-level changes to our cells, which alter the way they react to stimulus and potentially make us more vulnerable to illness and disease.

But the good news (and it’s very good news), is that we are not confined to drugs as a solution, as it seems evident now that some of the most powerful ways we have of counteracting this align extremely well with traditional wisdom of living a healthy lifestyle. Things like being part of a community, having a personal moral code, having a positive mental outlook, and facing your fears. The responsibility of living well, it seems, is one of the best things for our health and happiness.

Have a blessed, wonderful day!

Dr. Alex Loyd