Editing Panic attack (section)

==Pathophysiology==
[[File:The Amygdala - Psych 1010.jpg|thumb|The amygdala - the fear response system in our brain thought to be involved in the origin of panic attacks]]
When panic attacks occur, people experience the sudden onset of fear and anxiety in the setting of no actual perceived threat (ex. your mind believes there is something threatening your wellbeing, but there is nothing actual life-threatening occurring). This fear-based response leads to a release of a hormone called [[adrenaline]] (also known as epinephrine), which brings about the [[fight-or-flight response]]. The human nervous state consists of the sympathetic nervous system, which is responsible for the fight-or-flight (active) response, and the parasympathetic nervous system, which is responsible for the rest-and-digest (passive) response.<ref name=":6">{{Citation |last1=Alshak |first1=Mark N. |title=Neuroanatomy, Sympathetic Nervous System |date=2024 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK542195/ |access-date=2024-11-04 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31194352 |last2=Das |first2=Joe M.}}</ref> The sympathetic nervous system prepares our body for strenuous physical activity (i.e. fight or flight) by affecting different bodily functions such as increasing heart rate, increasing breathing, sweating and many others, leading to the physical symptoms that accompany a panic attack.<ref name=":6" /> The exact mechanism behind panic attacks remains unclear; there are several different ideas for why some people experience panic attacks while others don't. The current theories include the fear network model, theory of acid-base disturbances in the brain, and irregular activity of the amygdala (i.e. the part of the brain responsible for controlling emotions, such as fear, and identifying threats).<ref name=":7">{{cite journal |last1=Maren |first1=Stephen |date=November 2009 |title=An Acid-Sensing Channel Sows Fear and Panic |journal=Cell |volume=139 |issue=5 |pages=867–869 |doi=10.1016/j.cell.2009.11.008 |pmid=19945375 |s2cid=18322284 |hdl-access=free |hdl=2027.42/83231}}</ref><ref name=":11">{{Cite journal |last1=Vollmer |first1=L L |last2=Strawn |first2=J R |last3=Sah |first3=R |date=2015-05-26 |title=Acid–base dysregulation and chemosensory mechanisms in panic disorder: a translational update |journal=Translational Psychiatry |language=en |volume=5 |issue=5 |pages=e572 |doi=10.1038/tp.2015.67 |issn=2158-3188 |pmc=4471296 |pmid=26080089}}</ref><ref name=":12">{{Cite journal |last1=Kim |first1=Jieun E |last2=Dager |first2=Stephen R |last3=Lyoo |first3=In Kyoon |date=December 2012 |title=The role of the amygdala in the pathophysiology of panic disorder: evidence from neuroimaging studies |journal=Biology of Mood & Anxiety Disorders |language=en |volume=2 |issue=1 |page=20 |doi=10.1186/2045-5380-2-20 |doi-access=free |issn=2045-5380 |pmc=3598964 |pmid=23168129}}</ref><ref name=":9">{{Cite journal |last=Lai |first=Chien-Han |date=2019-01-25 |title=Fear Network Model in Panic Disorder: The Past and the Future |journal=Psychiatry Investigation |language=en |volume=16 |issue=1 |pages=16–26 |doi=10.30773/pi.2018.05.04.2 |issn=1738-3684 |pmc=6354036 |pmid=30176707}}</ref>

=== Fear network model ===
The fear network model hypothesizes that parts of our brain responsible for controlling the fear response that is created by the area of the brain where the amygdala is located (called the limbic system) is unable to control the fear sufficiently, leading to panic attacks.<ref name=":9" /> It is thought that dysfunction of the area responsible for controlling fear could be due to stress experienced in childhood, along with a genetic component as well.<ref name=":9" /> In summary, the fear network model states that the network in our brains responsible for responding to fear and then controlling that fear is not working properly, creating the inability for our brains to control fear that is occurring without any sort of external threat, leading to panic attacks.<ref name=":9" />

=== Acid-base disturbances theory ===
This theory suggests that there is a part of the amygdala that is able to identify when the pH in our brain decreases, i.e. becomes more acidic.<ref name=":7" /> This part of the amygdala is called the acid-sensing ion channel.<ref name=":7" /> Since panic attacks typically occur without an obvious external trigger (meaning there is usually nothing life-threatening happening to cause a panic attack), studies have shown that panic attacks may be caused by internal triggers.<ref name=":11" /> One such internal trigger is the amygdala sensing acidosis, which can be caused by inhaling CO2 (carbon dioxide).<ref name=":7" /><ref name=":11" /> In fact, one study has shown that people with a history of panic attacks had disturbances in their pH level minutes before having a panic attack.<ref name=":11" />

Another theory, called the false suffocation alarm theory, is associated with the idea of acid-base imbalances in the amygdala.<ref name=":7" /><ref name=":11" /> In this theory, inhalation of CO2 causes accumulation of acid in the blood and difficulty breathing, leading our brain to believe that we are suffocating, causing fear and panic.<ref name=":7" /> Studies have shown that inhaling CO2 can cause fear in people who do not have any prior history of panic attacks.<ref name=":7" /> This information has allowed scientists to suggest that panic attacks could be caused by our brain's inability to stop alarm signals that make us feel like we're suffocating.<ref name=":7" />

=== Amygdala dysfunction theory ===
The amygdala in the human brain has several distinct sections that are responsible for our fear response. This theory suggests that problems in any of these brain areas or the connections between them could lead to excessive fear responses, like panic attacks. Studies have shown that in both animal and human subjects with a history of panic attacks, the amygdala is hyperactive with decreased volume when compared to the control. Another role the amygdala may play in panic attacks is decreased inhibition of amygdalar activity (i.e. the amygdala is not being shut down like it normally should), leading to increased levels of anxiety. A link between childhood traumatic experiences, as well as genetic abnormalities, has been found in those with a dysfunctional amygdala.<ref name=":12" />

===Neurotransmitter imbalances===
Many [[neurotransmitter]]s are affected when the body is under the increased [[stress (biology)|stress]] and [[anxiety]] that accompany a panic attack. Some include [[serotonin]], [[GABA]] (gamma-aminobutyric acid), [[dopamine]], [[norepinephrine]], and [[glutamate]].<ref name="By2013" />

An increase of serotonin in certain pathways of the brain seems to be correlated with reduced anxiety. More evidence that suggests serotonin plays a role in anxiety is that people who take [[Selective serotonin reuptake inhibitor|selective serotonin reuptake inhibitors]] (SSRIs) tend to feel a reduction of anxiety when their brain has more serotonin available to use.<ref name="By2013">{{cite journal |last1=Bystritsky |first1=Alexander |last2=Khalsa |first2=Sahib S. |last3=Cameron |first3=Michael E. |last4=Schiffman |first4=Jason |date=2013 |title=Current Diagnosis and Treatment of Anxiety Disorders |journal=Pharmacy and Therapeutics |volume=38 |issue=1 |pages=30–57 |pmc=3628173 |pmid=23599668}}</ref>

The main inhibitory neurotransmitter in the [[central nervous system]] (CNS) is GABA. This neurotransmitter acts by inhibiting, or blocking nerve signals, which is very helpful in anxiety. In fact, medications that increase GABA activity in the brain, such as [[benzodiazepine]]s and [[barbiturate]]s, help with reducing anxiety almost immediately.<ref name="By2013" />

Dopamine's role in anxiety is not well understood. Some [[antipsychotic medication]]s that block dopamine production have been proven to treat anxiety. However, this may be attributed to dopamine's tendency to increase feelings of [[self-efficacy]] and confidence, which indirectly reduces anxiety. On the other hand, other medications that increase dopamine levels have also been found to improve anxiety.<ref name="By2013" />

Many physical symptoms of anxiety, such as rapid heart rate and hand tremors, are regulated by norepinephrine. Drugs that counteract norepinephrine's effect may be effective in reducing the physical symptoms of a panic attack.<ref name="By2013" /> On the other hand, some medications that raise overall norepinephrine levels, such as [[Tricyclic antidepressant|tricyclic antidepressants]] and [[Serotonin–norepinephrine reuptake inhibitor|serotonin–norepinephrine reuptake inhibitors]] (SNRIs), can be effective for treating panic attacks over the long term by reducing the sudden increases in norepinephrine that happen during a panic attack.<ref>{{cite journal |last1=Montoya |first1=Alonso |last2=Bruins |first2=Robert |last3=Katzman |first3=Martin A |last4=Blier |first4=Pierre |date=1 March 2016 |title=The noradrenergic paradox: implications in the management of depression and anxiety |journal=Neuropsychiatric Disease and Treatment |volume=12 |pages=541–557 |doi=10.2147/NDT.S91311 |pmc=4780187 |pmid=27042068 |doi-access=free}}</ref>

Because glutamate is the primary excitatory neurotransmitter involved in the central nervous system (CNS), it can be found in almost every neural pathway in the body. Glutamate is likely involved in conditioning, which is the process by which certain fears are formed, and extinction, which is the elimination of those fears.<ref name="By2013" />

=== Cardiac mechanism ===
People who have been diagnosed with panic disorder have approximately double the risk of heart disease.<ref name="pmid24923348">{{cite journal |last1=Soares-Filho |first1=Gastao L. F. |last2=Arias-Carrion |first2=Oscar |last3=Santulli |first3=Gaetano |last4=Silva |first4=Adriana C. |last5=Machado |first5=Sergio |last6=Nardi |first6=Alexandre M. Valenca and Antonio E. |last7=Nardi |first7=AE |date=31 July 2014 |title=Chest Pain, Panic Disorder and Coronary Artery Disease: A Systematic Review |journal=CNS & Neurological Disorders Drug Targets |volume=13 |issue=6 |pages=992–1001 |doi=10.2174/1871527313666140612141500 |pmid=24923348}}</ref>  Panic attacks can cause chest pain by affecting blood flow in arteries of the heart. During a panic attack, the body's stress response is triggered which can cause the small vessels of the heart to tighten, leading to chest pain. The body's nervous system and rapid breathing during a panic attack can cause spasming of the arteries of the heart (also known as [[vasospasm]]). This can reduce blood flow to the heart, causing damage to heart tissue and chest pain, despite normal heart scans.<ref name=":1">{{Cite journal |last1=Huffman |first1=Jeff C. |last2=Pollack |first2=Mark H. |last3=Stern |first3=Theodore A. |date=2002-04-01 |title=Panic Disorder and Chest Pain: Mechanisms, Morbidity, and Management |url=https://www.psychiatrist.com/pcc/panic-disorder-chest-pain-mechanisms-morbidity-management |journal=The Primary Care Companion for CNS Disorders |volume=4 |issue=2 |pages=54–62 |doi=10.4088/PCC.v04n0203 |issn=2155-7780 |pmc=181226 |pmid=15014745}}</ref>

In individuals with a history of [[coronary artery disease]], panic attacks and stress can make chest pain worse by increasing the heart's need for oxygen. This occurs because increased heart rate, blood pressure, and stress responses (i.e. the sympathetic nervous system) puts more strain on the heart.<ref name=":1" /><ref>{{Cite journal |last1=Soares-Filho |first1=Gastão Luiz |last2=Mesquita |first2=Claudio |last3=Mesquita |first3=Evandro |last4=Arias-Carrión |first4=Oscar |last5=Machado |first5=Sergio |last6=González |first6=Manuel |last7=Valença |first7=Alexandre |last8=Nardi |first8=Antonio |date=2012 |title=Panic attack triggering myocardial ischemia documented by myocardial perfusion imaging study. A case report |journal=International Archives of Medicine |language=en |volume=5 |issue=1 |pages=24 |doi=10.1186/1755-7682-5-24 |doi-access=free |issn=1755-7682 |pmc=3502479 |pmid=22999016}}</ref><ref>{{Cite web |title=Elevated troponin linked to mental stress ischemia in heart disease patients |url=https://www.sciencedaily.com/releases/2016/04/160403195916.htm |access-date=2024-04-16 |website=ScienceDaily |language=en}}</ref>