1

Underlying Neurobiology of Panic Disorder

Taha Saeed

School of Science, Honors College, Indiana University Perdue University

NSCI-B 201: Foundations of Neuroscience

Dr. Bethany Neal-Beliveau

December 2, 2022
 2

Panic disorder is an anxiety disorder in which a person has an increased likelihood of

having frequent and unexpected panic attacks. A panic attack is a sudden feeling of extreme fear

and anxiety in a situation where there is no clear sense of endangerment. Worrying about having

the next panic attack is when it develops into a panic disorder, causing the person to change their

behaviors and lifestyles to lower the risk of experiencing a panic attack. Symptoms of panic

attacks include having an increased heart rate, sweating, nausea, chest pain, and any other mental

or physical symptoms that prematurely activate the sympathetic nervous system. Although it is

not known what the root cause of developing panic disorder is, many studies support the idea

that it is genetically inherited and further affected by environmental and societal factors. Anyone

is susceptible to having a panic attack at least once in their life, however, the National Institute of

Mental Health estimates over 2.7% of the United States population (about 6 million American

adults) annually suffers from panic disorder. Treatment such as psychotherapy and antidepressant

medication can be taken to reduce the chances of having panic attacks but the fact that the

number of people still suffering is so high is very concerning. The following studies have been

conducted with the purpose of further understanding the neurobiology of panic disorder to

develop better treatment plans, with the eventual goal of helping to significantly lower that

percentage.

Perhaps the most important part of the studies was determining the regions of the brain in

which panic disorder patients have the most and least hyperactivity in. To do this, while the

subjects were performing block design tests, fMRI scans of their brains were taken (Wang,

2021). This study consisted of a group of subjects who suffered from panic disorder according to

DSM-5 and another group of subjects who acted as the healthy controls (Wang 2021). Each

subject was then shown either a positive/neutral description or a negative description of the
 3

upcoming picture (Wang, 2021). This process was repeated a total of 50 times for each subject,

with 25 of those descriptions being positive or neutral and the other 25 being negative, all of

which were shown at random (Wang, 2021). Subjects were also given a four-point valence rating

survey to express their level of anxiety during the viewing of the images, however, further fMRI

results yielded this to be irrelevant as there was an insignificant correlation that could have been

drawn between the two dependent variables (Wang, 2021).

The results of the fMRI scans of the subjects showed that the panic disorder group had

less activation in their right dorsal lateral prefrontal cortex (dlPFC) and right dorsal medial

prefrontal cortex (dmPFC) compared to the healthy control group while also exhibiting more

activation in the parietal cortex when reading a positive or neutral description that was followed

by a negative image (Wang, 2021). While this study focused on the regions of the brain that

would be affected because of implicit cognitive reappraisal in panic disorder patients, another

study sought to find the biological and clinical markers in panic disorder patients. The results of

this study found that there were structural changes in the amygdala, hippocampus, and cerebral

blood levels in the left and occipital cortex of the brain (Cosci, 2019). Additionally, it was found

that serotonin and norepinephrinergic systems were activated upon stimulation of perceiving a

panic attack, which caused irregular breathing, increased blood flow, and hypothalamic pituitary

adrenal axis dysregulation (Cosci, 2019).

Having located the regions of the brain and the neurotransmitter systems that are

activated and inactivated during panic attacks for panic disorder patients, it becomes easier to

narrow down what can be used as treatments to target these areas and systems. Research

conducted provided evidence for selective serotonin reuptake inhibitors and benzodiazepines as

the best pharmaceutical form of treatment for panic disorder patients (Ziffra, 2021). Further
 4

analysis provided evidence for alternatives to SSRIs, which include serotonin-norepinephrine

reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, and mirtazapine

(Ziffra, 2021). This study also provided evidence to hypothesize that not only antidepressants but

also anticonvulsants and antipsychotics could help treat panic disorder, but since these were not

tested, it is not possible completely draw that conclusion (Ziffra, 2021). Similarly to many other

mental health disorders, this study provided further evidence for psychotherapy being a powerful

tool to help suppress the frequency of panic attacks (Ziffra, 2021). Research that was done

concluded that cognitive-behavioral therapy allows for the best therapeutic treatment for panic

disorder (Ziffra, 2021).

From the latest studies conducted, there are now several directions where the future of

panic disorder research can be done to develop a more effective treatment. Biological clinical

markers which provided evidence for the DSM-5 definition of panic disorder included having

changes being made to the amygdala and hippocampus resulted in the activation of serotonin and

norepinephrinergic systems (Cosci, 2019). This study allowed for the determination of what

treatments could be used. Upon stimulation of implicit cognitive reappraisal, it was concluded

that particular prefrontal regions of the brain such as the dlPFC and dmPFC were activated less

in panic disorder patients compared to healthy controls while having more activation in their

right partial regions compared to healthy controls (Wang, 2021). This study enabled research on

the targeting of regions of the brain to be conducted and found that SSRIs and benzodiazepines

proved to be the most effective forms of treatment. Although there is still a lot unknown about

the human brain, new research and studies are being performed every day to understand the

causes and treatments for all mental disorders. Based on what is known now after these studies, it

can be inferred that the number of panic disorder patients, previously stated, is likely to decrease.
 5

References

Cosci, F., & Mansueto, G. (2019). Biological and Clinical Markers in Panic Disorder. Psychiatry

Investigation, 16(1), 27–36. https://doi.org/10.30773/pi.2018.07.26

NHS website. (2022, March 29). Panic disorder. nhs.uk.

https://www.nhs.uk/mental-health/conditions/panic-disorder/

Panic Disorder. (n.d.). National Institute of Mental Health (NIMH).

https://www.nimh.nih.gov/health/statistics/panic-disorder

Wang, H. Y., Xu, G. Q., Ni, M. F., Zhang, C. H., Li, X. L., Chang, Y., Sun, X. P., & Zhang, B.

W. (2021). Neural basis of implicit cognitive reappraisal in panic disorder: an event-

related fMRI study. Journal of Translational Medicine, 19(1).

https://doi.org/10.1186/s12967-021-02968-2

Ziffra M. Panic disorder: A review of treatment options. Ann Clin Psychiatry. 2021

May;33(2):124-133. doi: 10.127788/acp.0014. PMID: 33529291.