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There are specific regions and pathways in the human brain that help us process fear. Alexey Kuzma/Stocksy
  • 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 study 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 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 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.

Their research appears in the journal Molecular Psychiatry.

Previous research carried out in rodents by Linköping University scientists found that downregulation of PRDM2 caused by alcohol dependence leads to increased stress responses and alcohol-seeking behavior.

Because of their earlier findings and the links between anxiety and alcohol use disorder, the research team hypothesized that reduced PRDM2 levels in the brain could be a mechanism that plays a role in both conditions.

Using rats to test their theory, the scientists conducted several fear conditioning experiments to investigate the role PRDM2 plays in fear memory processes.

After analyzing the data, the scientists found that PRDM2 plays a role in modifying the strength of fear-memory storage in the brain. It does this by regulating the pathway between the dorsomedial prefrontal cortex and basolateral amygdala (dmPFC-BLA). This pathway is believed to be involved in processing emotions, including fear and anxiety.

Specifically, the study authors discovered that the downregulation of PRDM2 in the dorsomedial prefrontal cortex heightens fear expression by altering how effectively the brain holds onto fear memories.

In addition, the researchers also identified that reduced PRDM2 levels impact specific genes that assist in the formation of contact points between neurons.

The findings suggest that this gene expression may increase nerve cell activity between the frontal lobes and amygdala in the brain, resulting in a heightened response to fear-associated cues.

Lead study author Estelle Barbier, an assistant professor in the Center for Social and Affective Neuroscience (CSAN) and the Department of Biomedical and Clinical Sciences (BKV) at Linköping University, told MNT:

“In our study, we identify a biological mechanism that increases the consolidation of fear-related memory, making them stronger and long lasting. We show that increased activity in the network between the frontal lobe and the amygdala increases learned reactions. We found that this is in part driven by a downregulation of the epigenetic enzyme PRDM2.”

Some people may be more prone to experiencing anxiety disorders or AUD, yet the reasons behind this aren’t fully understood. Still, several factors may contribute to the development of these conditions.

Dr. Edward Ratush, a board certified psychiatrist who specializes in addiction treatment and co-founder of SOHOMD, told MNT:

“A general answer is that both environmental and genetic factors play a role — 40% of first-degree relatives with a fear-based disorder may develop a fear-based disorder themselves. Having a relative with [a] fear-based disorder means you could have inherited a predisposition to such a symptom complex.”

“It is possible that some individuals naturally have low levels of PRDM2 in the [prefrontal cortex] (PFC). However, more work is needed to demonstrate it. To date, we do not have data concerning adverse life experiences, but we have found lower PRDM2 expression in the PFC of alcoholic brains. It is difficult to determine here whether this was a pre-existing condition or whether this was resulting from long-term alcohol exposure,” pointed out Prof. Barbier.

As scientists uncover more evidence on specific brain pathways and mechanisms that may contribute to AUD and fear-based mental health conditions, it may lead to new treatment options.

Dr. Ratush explained that currently, “there are many directions that are taken to treat fear-based disorders. Some focus on the fear circuits’ intensity with breathing exercises, meditation, and mindfulness.”

He said that “many psychotherapy modalities attempt to amplify the connectivity between emotional regions and cognitive analytical regions,” while more modern therapies had more specific targets.

“Newer technological strategies employ electrical stimulation — directly and indirectly — to enhance or interrupt a relevant circuit. And of course, medications focus on the [neuro] transmitters most associated with these circuits,” Dr. Ratush said.

Dr. Loftus explained that with EMDR and neurofeedback therapy, patients can be “guided through treatment to retrain the brain and neurological pathways that are involved with PTSD and fear-based anxiety symptoms.”

Still, Prof. Barbier noted:

“We currently do not have the technology to increase PRDM2. However, genes that are regulated by PRDM2 can also be good candidate[s] for pharmacotherapies to treat AUD and anxiety disorders.”

“Our findings suggest that PRDM2 may be a shared mechanism between AUD and anxiety disorders. Therefore, this may also lead to the discovery of candidate targets for treating the comorbid condition.”
— Estelle Barbier, lead author