What causes panic disorder? Crucial new research

by | Jan 25, 2024

There were no crossing lights or a gate arm. The panic disorder locomotive slammed into me in 1973. And at 19-years-old, the course of my life was forever changed. So what fuels this runaway train? Scientists thought they were close, until this came along…

’…we’ve found a specific brain circuit outside of the amygdala that is linked to panic attacks and could inspire new panic disorder treatments that differ from current available panic disorder medications that typically target the brain’s serotonin system.’

Those who have studied up on their panic disorder know the drill.

Our senses send messages to the amygdala for interpretation. If it senses a threat, and isn’t overruled by the cerebral cortex, it sounds an alarm and all panic hell breaks loose.

But wouldn’t you know it, crucial new research says, “Not exactly.”

This is huge news. Are you ready?

Salk scientists uncover key brain pathway mediating panic disorder symptoms

Effective medical interventions don’t appear out of thin air. Without research and deep understanding, it just doesn’t happen.

If you get that, the headline had to have grabbed your attention.

Researchers at the Salk Institute for Biological Studies, La Jolla, California, have found a brain circuit of specialized neurons that mediate panic-like symptoms in mice.

”Come on, Bill, mice?” Keep in mind, there are extraordinary anatomical, genetic, and physiological similarities between humans and rodents.

Now, imagine the far-reaching impact of creating a map of the regions, neurons, and connections in the brain that mediate panic attacks. That’s exactly what the Salk research team has begun to do.

Their findings were published in the journal Nature Neuroscience on January 4, 2024.

The circuit

The brain circuit discovered by the team consists of neurons whose primary task is to send and receive a neuropeptide – a small protein that sends messages throughout the brain – called pituitary adenylate cyclase-activating polypeptide (PACAP).

And catch this – the team determined that PACAP, along with the neurons that produce its receptor, are possible druggable targets for new panic disorder treatments.

Why is that important? A druggable target is a biological target that’s known or predicted to bind with high affinity to a drug. Furthermore, by definition, the binding of the drug to a druggable target must alter the function of the target with a therapeutic benefit to the patient.

Can you see how monumental this discovery is?

According to senior author and associate professor Sung Han…

We’ve been exploring different areas of the brain to understand where panic attacks start. Previously, we thought the amygdala, known as the brain’s fear center, was mainly responsible – but even people who have damage to their amygdala can still experience panic attacks, so we knew we needed to look elsewhere.

Now, we’ve found a specific brain circuit outside of the amygdala that is linked to panic attacks and could inspire new panic disorder treatments that differ from current available panic disorder medications that typically target the brain’s serotonin system.

To me, well-considered unique approaches, in this case working outside of the serotonin system, bring great hope.

Brain mapping

what causes panic disorder

Brainstem

As they began putting their panic disorder brain map together, it makes sense that the team prioritized the brain’s alarm center – the lateral parabrachial nucleus (PBL). It’s located in the pons, which is part of the brainstem.

As you may know, the brainstem, just 2.5% of the brain’s weight, is the home of our most basic life-supporting functions: regulation of cardiac and respiratory function, helps control heart and breathing rate, regulates our central nervous system, manages the sleep cycle, and more.

And that’s likely why the PBL was implicated by the team in generating panic and bringing about emotional and physical changes.

But that’s not all. The team discovered that the PBL also produces the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP), Significance? It’s known as the master regulator of stress responses.

Sure seems like the team was in the right neighborhood; however, the links between the players were unclear. And that’s why they turned to a mouse model to continue their mapping.

From co-first author and senior research associate Sukjae Kang…

Emotional and stress-related behaviors have been associated with PACAP-expressing neurons in the past. By mimicking panic attacks in the mice, we were able to watch those neurons’ activity and discover a unique connection between the PACAP brain circuit and panic disorder.

On to the rodents…

The discovery

what causes panic disorder

Raphe nuclei as part of the serotonin pathway

In their work with mice, the team found that during a panic attack, PACAP-expressing neurons became activated. Once activated, they released PACAP neuropeptide messengers to another part of the brainstem called the dorsal raphe nucleus, where neurons expressing PACAP receptors reside.

The released PACAP messengers activate those receptor neurons, thereby producing panic-associated behavioral and physical symptoms in the mice.

The team believe that discovering the connection between panic disorder and the PACAP brain circuit was an important step forward in their effort to map panic disorder in the brain,

The team also found that by inhibiting PACAP signaling, they could disrupt the flow of PACAP neuropeptides and reduce panic symptoms – a promising finding for the future development of panic disorder-specific interventions

The difference between panic and anxiety

Let’s wrap things up with what seems to be a puzzling observation. According to Dr. Han, despite panic disorder being categorized as an anxiety disorder, there are many ways that panic and anxiety are different.

For instance, panic induces physical symptoms, such as shortness of breath, pounding heart rate, sweating, and nausea. Anxiety doesn’t directly induce those symptoms. And panic attacks are uncontrollable and often spontaneous, while other anxiety disorders, like post-traumatic stress disorder (PTSD), are more memory-based and have predictable triggers.

According to Han, the differences are why it’s critical to construct this panic disorder brain map, so researchers can create interventions specially tailored to panic disorder.

Han summarizes…

We found that the activity of PACAP-producing neurons in the brain’s parabrachial nucleus is inhibited during anxiety conditions and traumatic memory events – the mouse’s amygdala actually directly inhibits those neurons.

Because anxiety seems to be operating conversely to the panic brain circuit, it would be interesting to look at the interaction between anxiety and panic, since we need to explain now how people with anxiety disorder have a higher tendency to experience panic attack.

The team are excited and motivated – the work will continue..

Comforting and hopeful

Bob Seger nailed it in his song “Against the Wind”: “Wish I didn’t know now what I didn’t know then.” But those were the cards I was dealt in 1973.

I mean, so go brain disease and the evolution of knowledge.

Over the years, we’ve reviewed a lot of research here on Chipur. In my opinion, this study is as powerful as it gets. Sure, it’ll take time to bear fruit, but just knowing we’re in right neck of the woods, and the work continues, is comforting and hopeful.


Check out the Salk news release, which includes a link to the study.

Brainsten image: Blausen.com staff (2014). “Medical gallery of Blausen Medical 2014”. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436Creative Commons Attribution 3.0

Raphe nuclei image: Brain_bulbar_region.svg. No changes made. This file is licensed under the Creative Commons Attribution 2.5 Generic license.

Plenty more Chipur emotional and mental health info and inspiration articles. Peruse the titles.

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