Surreal image representing stress as a malleable force shaped by genetics and mindset.

Stress Mindset: How Your Genes Can Influence Your Reaction to Stress

Reese Marlowe in Mind & Education July 2025 • 4 min read.

"Unlocking the secrets of COMT and how your mindset can influence your body's response to stress."

Stress is a universal experience, but how we react to it varies widely. Some people crumble under pressure, while others thrive. Scientists are discovering that much of this variation comes down to our 'stress mindset'—the way we perceive stress and cognitive ,emotional, and physiological responses. Believing that stress is enhancing, versus debilitating, significantly alters how our bodies and minds respond.

A growing field of research is exploring how to shift stress mindsets to improve health, performance, and well-being. Studies have shown that simply watching short videos that highlight the enhancing effects of stress can lead to greater cognitive flexibility, heightened positive affect, and more adaptive hormonal responses.

However, individual responses to these mindset interventions can vary. Now, research is uncovering how our genes play a critical role. In particular, a gene called catechol-O-methyltransferase (COMT), which influences how our brains process stress hormones, appears to be a key moderator.

The COMT Gene: Your Body's Stress Moderator

Surreal image representing stress as a malleable force shaped by genetics and mindset.

The COMT gene provides instructions for making an enzyme that breaks down neurotransmitters like dopamine, epinephrine, and norepinephrine—all critical players in the stress response. Variations in the COMT gene, particularly a well-studied polymorphism called rs4680, can affect how efficiently this enzyme works. People with the 'Met' allele of this gene have a less active form of the enzyme, leading to higher levels of these neurotransmitters in the brain, especially in the prefrontal cortex, which is important for cognitive functions and stress appraisal.

Past research has linked COMT variations to differences in stress reactivity, emotional processing, and even placebo responses. Individuals with the Met/Met genotype sometimes show higher levels of anxiety and sensitivity to stress, but they may also be more responsive to interventions.

Stress Mindset: The belief that stress has enhancing versus debilitating properties.
COMT (Catechol-O-Methyltransferase): An enzyme that metabolizes catecholamines like dopamine, epinephrine, and norepinephrine.
rs4680 Polymorphism: A genetic variation in COMT that affects enzyme activity.
Met Allele: A version of the rs4680 polymorphism associated with lower COMT activity.

A new study has delved deeper into how COMT variations interact with stress mindset interventions. Researchers explored how the rs4680 polymorphism influences cognitive and emotional responses after participants watched videos designed to promote either a stress-is-enhancing (SIE) or stress-is-debilitating (SID) mindset. The study, published in PLOS One, reveals fascinating insights into how our genes and beliefs work together.

Harnessing Your Stress Response

These findings offer a promising path forward for tailoring stress management strategies to individual genetic profiles. By understanding how COMT and other genes influence our stress responses, we can develop more effective interventions that leverage the power of mindset to promote resilience and well-being.For those with the Met/Met genotype, embracing a stress-is-enhancing mindset may be particularly beneficial. By reframing stress as a challenge and opportunity for growth, these individuals can tap into their enhanced neurochemical responses and thrive under pressure. Future research will undoubtedly uncover more of the intricate interplay between our genes, mindsets, and stress responses.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1371/journal.pone.0195883, Alternate LINK

Title: Catechol-O-Methyltransferase Moderates Effect Of Stress Mindset On Affect And Cognition

Subject: Multidisciplinary

Journal: PLOS ONE

Publisher: Public Library of Science (PLoS)

Authors: Alia J. Crum, Modupe Akinola, Bradley P. Turnwald, Ted J. Kaptchuk, Kathryn T. Hall

Published: 2018-04-20

Everything You Need To Know

What is 'stress mindset,' and how does it influence our reaction to stress?

Stress mindset refers to the belief about whether stress is enhancing or debilitating. This belief significantly alters how our bodies and minds respond to stress. Believing that stress is enhancing can lead to greater cognitive flexibility, heightened positive affect, and more adaptive hormonal responses. However, individual responses can vary based on genetic factors like the COMT gene.

How does the COMT gene influence the stress response, and what is the significance of the rs4680 polymorphism?

The COMT (catechol-O-methyltransferase) gene provides instructions for making an enzyme that breaks down neurotransmitters like dopamine, epinephrine, and norepinephrine, which are critical in the stress response. The rs4680 polymorphism is a genetic variation within the COMT gene that affects how efficiently this enzyme works. Individuals with the 'Met' allele of this gene have a less active form of the enzyme, leading to higher levels of these neurotransmitters in the brain. This can affect stress reactivity, emotional processing, and even responses to interventions.

What is the 'Met' allele and how does it affect individuals with the Met/Met genotype?

The 'Met' allele is a version of the rs4680 polymorphism within the COMT gene, associated with lower COMT enzyme activity. Individuals with the Met/Met genotype have two copies of this allele, resulting in a less active enzyme and consequently, higher levels of neurotransmitters like dopamine in the brain. This genotype has been linked to potentially higher levels of anxiety and sensitivity to stress, but also greater responsiveness to mindset interventions. Future studies are needed to explore these potential differences and nuances.

How can understanding the interaction between the COMT gene and stress mindset interventions help in managing stress?

Understanding how variations in the COMT gene, specifically the rs4680 polymorphism, interact with stress mindset interventions allows for more tailored stress management strategies. By knowing an individual's genetic profile, interventions can be designed to leverage the power of mindset to promote resilience and well-being. For example, individuals with the Met/Met genotype may particularly benefit from embracing a stress-is-enhancing mindset, as they may experience enhanced neurochemical responses when reframing stress as a challenge and opportunity for growth. However, It's essential to note that individual responses can vary, and further research is needed to fully understand these interactions.

Can shifting to a stress-is-enhancing (SIE) mindset improve outcomes, and how do mindset interventions work?

Yes, research indicates that adopting a stress-is-enhancing (SIE) mindset can improve various outcomes. Mindset interventions, such as watching videos that highlight the positive effects of stress, can lead to greater cognitive flexibility, heightened positive affect, and more adaptive hormonal responses. For individuals with the Met/Met genotype of the COMT gene, embracing a stress-is-enhancing mindset may be particularly beneficial, potentially allowing them to tap into enhanced neurochemical responses and thrive under pressure. While the study focuses on the COMT gene and stress mindset, other genes and psychological factors also play a role in individual responses to stress, suggesting a more complex interplay.