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Key points
- Researchers have identified a novel brain pathway involved with panic-like responses.
- Neurons in the parabrachial nucleus influence the dorsal raphe nucleus, a key regulator of mood and stress.
- Blocking the peptide PACAP with drugs reduces panic-like symptoms.
- These results point to potential targets for faster, more effective treatments for panic disorder.
Panic disorder is a debilitating condition characterized by sudden and overwhelming bouts of intense fear, often accompanied by physical symptoms such as heart palpitations, hyperventilation, and dizziness. It affects approximately 2 to 3 percent of the population, making it a relatively common mental health condition. Unlike generalized anxiety, panic attacks can arise spontaneously and leave individuals feeling out of control.
Despite its prevalence, the neural mechanisms driving panic disorder remain poorly understood, limiting treatment options for those affected. Recent research has started to untangle the brain circuits involved in panic-like symptoms, offering promising insights into how panic-related behavior and physiology intertwine.
Mapping Panic in the Brain
A groundbreaking study by Kang et al., published in Nature Neuroscience (2024) sheds light on a previously unrecognized pathway in the brain that may underlie panic-like behaviors.
The research, conducted in mice, highlights a specific brain pathway involving neurons that produce a neuropeptide called PACAP. Neuropeptides are chemical messengers in the brain that help control stress and emotions. PACAP is a neuropeptide involved in stress regulation, and the authors studied neurons in a part of the brain called the parabrachial nucleus that produce PACAP and project to the dorsal raphe nucleus.
The parabrachial nucleus is a brain structure that takes sensory information from the body and sends it to other parts of the brain to signal threat and pain. The parabrachial nucleus plays a key role in helping the brain understand the body's internal state and external conditions, which helps the brain maintain balance (homeostasis) and respond to adverse conditions.
The dorsal raphe nucleus, located in the brainstem, acts as a control center for mood and stress. It is one of the main sources of serotonin in the brain, a neurotransmitter involved in emotional regulation, sleep, and arousal. By influencing serotonin release, the dorsal raphe nucleus plays a key role in controlling behaviors related to anxiety and panic.
The findings of Kang et al. provide compelling evidence for how brain circuits might control the physiological and behavioral symptoms associated with panic attacks—and offer potential targets for new treatments.
The Panic Circuit Uncovered
PACAP neurons in the parabrachial nucleus responded strongly to panic-inducing stimuli, such as exposure to high concentrations of carbon dioxide (CO2) and certain drugs. Activation of these neurons led to defensive behaviors and rapid physiological changes, such as increased breathing and heart rate.
Interestingly, these neurons were inhibited during fear conditioning or tests of anxiety-like behavior, suggesting that the pathway is specific to unconditioned panic responses rather than learned fear or generalized anxiety.
Reducing the activity of these neurons or blocking their function in the dorsal raphe with drugs effectively reduced panic-like symptoms.
From Bench to Bedside: Relevance for Mental Health Treatment
Current treatments, such as selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy, often take weeks to show effects or may fail to address the physiological symptoms of panic attacks. The discovery made by Kang et al. suggests that new treatments could focus on drugs that block PACAP activity in the dorsal raphe nucleus, potentially providing faster and more direct relief for panic symptoms.
Limitations and Challenges in Translation to Humans
While this study provides valuable insights into the neural mechanisms underlying panic-like behaviors, translating findings from mice to humans poses challenges. Animal models, while useful, may not fully capture the psychological and social complexities of human panic disorder. This means that results in mice do not always translate directly to people. Additionally, differences in brain structure and function between species raise questions about whether the PACAP pathway operates similarly in humans. Further studies involving human subjects will be needed to validate these findings and explore how they can be applied to clinical treatments.
Looking Forward
The findings by Kang et al. mark a significant step forward in decoding the neurobiology of panic disorder. By identifying a specialized circuit for panic-like symptoms, this research highlights new opportunities for intervention and offers hope for millions of individuals struggling with panic attacks. As neuroscience continues to uncover the brain's secrets, targeted treatments that address both psychological and physiological symptoms may soon become a reality.
References
Kang, S.J., Kim, JH., Kim, DI. et al. A pontomesencephalic PACAPergic pathway underlying panic-like behavioral and somatic symptoms in mice. Nat Neurosci 27, 90–101 (2024). https://doi.org/10.1038/s41593-023-01504-3
