The Prefrontal Cortex and Stress

Travis DixonHealth Psychology

The role of the PFC in stress regulation could provide a deeper explanation of the warrior-worrier hypothesis.

The following information didn’t quite make the final cut of our new eBook: “Stress: A Student’s Guide to IB Health Psychology.” 

The prefrontal cortex (PFC) is important in stress because it’s connected with the amygdala through numerous neural networks. The PFC can increase or decrease amygdala activity depending on the thoughts generated by the PFC (i.e. how threatening we think a stressor is). This means that PFC activity can increase amygdala activity if we appraise a stressor as threatening, which will spark the HPA axis and create a stress response.

The PFC can increase or decrease activity in the amygdala, depending on how we appraise stressors.

The PFC provides another possible explanation for the Warrior/Worrier hypothesis – the idea that based on your genotype you have different stress reactions. fMRIs have shown Met/Mets (the worriers) and Val/Vals (the warriors) have differences in the connections between their PFCs and other brain areas, such as the hippocampus and the amygdala.[i]  This could explain their differences in stress reactions.

Read more:

The Warrior/Worrier Hypothesis

You might be a Met/Met homozygote (Met), a Val/Val homozygote (Val), or a Val/Met heterozygote (Val/Met). About 25% of people are Mets, 25% are Vals, and 50% are Val/Mets. The Mets have higher stress reactions and reduced expression of the COMT gene, resulting in lower levels of the COMT enzyme, resulting in increased levels of some neurotransmitters. For example, dopamine levels are 40% higher in Mets than Vals, especially in their prefrontal cortices. This could explain some differences between Vals and Mets in terms of stress.

While it seems the COMT gene might be related to stress because it affects PFC connections, adverse childhood experiences (ACEs) are another important factor to consider. Childhood trauma can reduce volume in important areas of the brain, like the PFC, amygdala and hippocampus and reduce connectivity between the PFC and amygdala.[ii] Therefore, it’s not just genetics that can have an effect. It’s also our environment.

Park et al. (2018) conducted a longitudinal study to see how stress might affect resting state functional connectivity (rs FC) between the amygdala and PFC. The researchers studied 79 kids aged between 4-7 years old and their parents completed a questionnaire to measure how much the kids were exposed to stressful life events. fMRI scans measured their amygdala-medial PFC rs FC. The results showed that greater exposure to stressful life events as a child (e.g. illness, a death in the family, divorce) was significantly correlated with weaker rs FC between the amygdala and mPFC.

These results are consistent with studies that show similar findings in teenagers – high levels of stress in childhood reduces the connectivity between the mPFC and the amygdala. This means the PFC is less able to use top-down processes to reduce activity in the amygdala. This is a risk factor for prolonged activation of the HPA axis and could explain why amygdala-mPFC rs FC is associated with stress-related mental illness later in life.

Heart rate variability is an indicator of your stress resilience. (You want to have high heart rate variability).

Amygdala-PFC rs FC has also been linked to cardiovascular disease (CVD) because of its relationship with heart rate variability (HRV). HRV is one way of measuring stress and physical health. It’s a calculation of the time variations between each heartbeat. It has been used as a predictor of mental and physical health problems, including CVD. High heart rate variability is a sign of better emotion regulation and overall health. Low HRV is associated with poorer mental and physical health and increased risk for CVD. Not surprisingly studies have found that stronger connectivity between the amygdala and the mPFC is associated with higher HRV.[iii]


(i) Tunbridge, E. M., Farrell, S. M., Harrison, P. J., & Mackay, C. E. (2013). Catechol-O-methyltransferase (COMT) influences the connectivity of the prefrontal cortex at rest. NeuroImage68, 49–54.

(ii) Martin H. TeicherCarl M. AndersonAnn Polcari. Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum. 
(iia) Oshri, A., Gray, J. C., Owens, M. M., Liu, S., Duprey, E. B., Sweet, L. H., & MacKillop, J. (2019). Adverse Childhood Experiences and Amygdalar Reduction: High-Resolution Segmentation Reveals Associations With Subnuclei and Psychiatric Outcomes. Child maltreatment24(4), 400–410.
(iii) Sakaki, M., Yoo, H. J., Nga, L., Lee, T. H., Thayer, J. F., & Mather, M. (2016). Heart rate variability is associated with amygdala functional connectivity with MPFC across younger and older adults. NeuroImage139, 44–52.