when fear gets stuck: an epigenetic mechanism

Fear-based mental health conditions are common, impacting millions of people worldwide. Previous research has shown that specific regions and pathways in the brain may be responsible for processing fear. A new study from Linköping University in Sweden has revealed a biological mechanism that impacts fear pathways and how fear memories are stored in the brain. Their findings also shed light on the link between anxiety and alcohol use disorder.

According to statistics, approximately 284 million people worldwide experienced an anxiety disorder in 2017. Data also suggests that around 12 million adults experience post-traumatic stress disorder (PTSD) in the United States in any given year.

One of the primary causative factors among these mental health conditions is excessive fear. Fear is a natural emotion that helps ensure a human or animal responds appropriately to danger. Still, it can become excessive in some individuals and may lead to mental health conditions, including anxiety and PTSD.

In addition, a 2019 studyTrusted Source suggests that anxiety disorders can co-occur with alcohol use disorder (AUD). Despite the known facts about fear-based conditions, the mechanisms behind how the brain regulates fear are not well understood.

Dr. Mirela Loftus, medical director for Newport Healthcare, told Medical News Today:

“It has been known for some time that the fear pathway in the brain entails connections between the hippocampus, the place that helps us build memories; the amygdala, the place that helps process fear and traumatic memories; and the medial prefrontal cortex that acts like the command center and controls these areas.”

Recent research Trusted Source uncovered evidence on how these brain regions communicate fear — specifically, the pathways in the brain that transmit threat cues to the amygdala. The scientists who conducted the study also suggest these pathways are involved in creating unpleasant fearful memories.

Now, a new study Trusted Source from researchers at Linköping University, Sweden, may offer more clues as to how these fearful memories are processed and stored in the brain. The scientists found that reduced levels of an epigenetic enzyme called PRDM2 affect specific genes in the brain, resulting in increased nerve cell activity between the frontal lobes and the amygdala.

The researchers suggest this biological mechanism impacts how the brain strengthens and holds onto fear-related memories. Their discovery might also offer insight into the links between anxiety disorders and AUD.

Substantial evidence supports a role of prefrontal cortex-amygdala circuits in the regulation of fear and anxiety [12,13,14]. Functional imaging studies in humans show an increased functional connectivity between the dmPFC/anterior cingulate cortex (ACC) and the amygdala during threat processing in healthy individuals [47].

In individuals with generalized or social anxiety disorders, patients with the most severe symptoms also show the highest dmPFC/ACC-amygdala connectivity, suggesting that this circuit is not only involved in adaptive but also in maladaptive responses to stress [48]. Consistent with a role of the dmPFC/ACC-amygdala pathway in adaptative stress responses, animal research shows that fear expression critically relies on activation of the dmPFC-BLA pathway [11]. Cued conditioned fear strengthens the dmPFC excitatory synapses in the BLA [12], and optogenetic silencing of the dmPFC terminals in the BLA decreases both fear expression and active avoidance [1349].

Riccardo, B., Kanat, C., Michele, P. et al. An epigenetic mechanism for over-consolidation of fear memories. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01758-6

Their research appears in the journal Molecular PsychiatryTrusted Source originally published in Medical News Today https://www.medicalnewstoday.com/articles.

Image credit: “Dragon and Tiger” is a painting by Yokoyama Kazan which was uploaded to FineArtAmerica on January 27th, 2022.

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