Protect Yourself Against Stress and Mood Problems with the Oxytocin (OXTR) Gene

You’ve probably heard of oxytocin before. This important hormone neurotransmitter (neuropeptide) is pretty famous for its role in stress, social behavior and emotional bonding [R, R, R, R, R].

A lot of research has shown that people’s natural levels of oxytocin determine how friendly, empathetic, and trusting (“pro-social”) they are [R].

Boosting peoples’ oxytocin levels – such as by giving them nasal sprays that contain oxytocin – increases trust and promotes social cooperation in humans [R, R]. Similar results are seen when giving oxytocin to animals. For example, increasing oxytocin levels increases pro-social behavior and reduces social anxiety in both rats and mice [R, R].

Therefore, the level of oxytocin you have – and how sensitive you are to its effects – can play a major role in your behavior and mood on a daily basis. But how does it work?

In this post, we’re going to focus in on one of the main genetic mechanisms involved in determining how sensitive you are to social stress, and what this can tell you about your relative risk for developing chronic mood problems.

Oxytocin is a neurotransmitter that can have a powerful influence on your overall mood and long-term mental health.

The brain’s oxytocin system is complex, and there are many different mechanisms and pathways that are responsible for its diverse effects on mood, social behavior, interpersonal relationships, and even cognitive ability.

But when it comes to how you react to stress, one of the main mechanisms involves the effects of oxytocin on a specific brain structure: the amygdala.

The amygdala is well-known for its role in stimulating fear and anxiety in response to stressful or dangerous situations. However, its role is actually more complicated than just triggering or creating these emotional states: the amygdala is constantly “scanning” your environment for potential threats, and helping you to prepare for action accordingly. The more sensitive your amygdala is to signs of threat – and the more strongly it responds – the more stressed out and anxious you will feel [R, R].

So where does oxytocin fit into this? Well, oxytocin is one of the main neurotransmitters responsible for inhibiting the amygdala. In other words, having more oxytocin activity gives you better protection against stress, fear, and anxiety, since it counteracts the part of your brain that is triggering and amplifying your body’s stress responses in the first place [R, R, R, R, R].

This means that there are two main factors that determine how sensitive you are to these negative moods:

1. How sensitive your amygdala is. The larger and more active your amygdala is, the more easily it will trigger negative moods like stress and anxiety [R, R, R, R].
    
2. Your levels and sensitivity to oxytocin. If you have higher levels of oxytocin – or a greater number of oxytocin receptors in your brain – then you’ll be less susceptible to negative moods and emotions [R, R, R, R, R, R].

Oxytocin levels and amygdala activation are two of the most important factors that shape your mood.

The OXTR gene is important for your mood because it plays a role in both sides of the “stress reactivity” equation.

The gene itself codes for oxytocin receptors, which are the main mechanisms that allow oxytocin to shape and control how your brain processes information. In other words, the number of oxytocin receptors you have determine how sensitive your brain is to oxytocin’s effects (such as reducing stress and anxiety) [R, R].

Because oxytocin also suppresses amygdala activity, this gene also affects the sensitivity of your amygdala to potential threats. For example, if you have a copy of this gene that makes you less sensitive to oxytocin, your amygdala will be chronically over-active, which will cause it to grow larger and stronger. This, in turn, will further increase your sensitivity to common sources of stress and anxiety [R, R, R, R, R].

The OXTR gene affects multiple biological mechanisms that influence your overall sensitivity to stress and anxiety.

Below is your genotype for rs2254298, one of the most important and well-studied SNPs in the OXTR gene:

In general, the more common ‘GG’ genotype is the better one to have when it comes to being resilient against stress, anxiety, and other mood problems.

However, it does have a downside – while ‘GG’ carriers are happier and more social, they are at increased risk of experiencing loneliness [R].

On the other hand, the ‘A’ allele is associated with a tendency to experience less positive emotion overall [R]. This allele is also associated with greater sensitivity to stress, poorer stress management skills, and increased risk for a variety of mood-related disorders including depression, anxiety, and PTSD. Presumably, this is because people with the ‘A’ allele have oxytocin systems that are not working as efficiently [R, R, R].

For example, in a task where subjects were asked to evaluate a series of faces with different emotional expressions, people with the ‘A’ allele were more likely to interpret ambiguous or neutral faces as threatening [R].

Carriers of the ‘A’ allele also have larger amygdalas, as well as elevated neural activity in the amygdala when looking at facial expressions. This suggests that they are more easily “stressed out” by social cues in general [R, R, R].

This greater propensity for social stress and anxiety also translates into impaired decision-making behavior and executive function. For example, subjects with the ‘A’ allele are slower to categorize the emotions of different faces, suggesting that this added stress is probably affecting them cognitively as well [R, R, R, R].

So how significant are these effects in the bigger picture? Well, being more sensitive to stress has been linked to increased risk of developing chronic mood problems.

For example, if you take two groups of people who experienced early-life stress and sort them according to their genotype for this SNP, people with the ‘AA’ or ‘AG’ genotype will be significantly more likely to have a mood disorder than people with the more typical ‘GG’ genotype – even if their overall stress levels were similar [R, R, R]!

This illustrates how even individual genes can have a big impact on how we respond to stress, and can even affect the long-term consequences that this can have on our health.

The ‘A’ allele for rs2254298 is associated with an elevated risk of chronic mood problems, whereas the ‘GG’ genotype is associated with reduced risk.