Materiały źródłowe

• #1 Panic disorder in adults: Epidemiology, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/panic-disorder-in-adults-epidemiology-pathogenesis-clinical-manifestations-course-assessment-and-diagnosis

  Panic attacks and panic disorder are common problems in both primary and psychiatric specialty care. […] In panic disorder, patients experience recurrent untriggered panic attacks with one month or more of worry about future attacks, or a maladaptive change in behavior related to the attacks. […] This topic will address the epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis of panic disorder.

• #1 The role of the amygdala in the pathophysiology of panic disorder: evidence from neuroimaging studies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3598964/

  Although the neurobiological mechanisms underlying panic disorder (PD) are not yet clearly understood, increasing amount of evidence from animal and human studies suggests that the amygdala, which plays a pivotal role in neural network of fear and anxiety, has an important role in the pathogenesis of PD. […] The amygdala has been suggested to have a critical role in PD, while there have been a few studies that indicate otherwise. […] It has been suggested that the amygdala has a critical role in the development of panic attacks and the pathogenesis of PD. […] The amygdala is known to have 13 nuclei, which can be categorized into lateral, basal and central subregions. […] Theoretically, disruption in any of these brain areas and connections along these areas, or any imbalance in the network can cause maladaptive and exaggerated fear responses such as panic attacks, increased basal anxiety or arousal, and excessive worrying.

• #1 The role of the amygdala in the pathophysiology of panic disorder: evidence from neuroimaging studies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3598964/

  Structural, chemical, and functional alterations in these amygdalar areas have been reported in neuroimaging studies in patients with PD. […] The effect size for group differences was greater in the right amygdala than the left amygdala across all four studies that have reported the amygdalar volume reduction. […] Reasons for the potentially greater deficits in the right amygdala than in the left amygdala in patients with PD may be understood in a large body of literature on hemispheric organization for processing emotions such as fear. […] Some of the evidence indicates that amygdalar deficits, particularly the deficit in the right amygdala, may predispose to PD. […] The amygdala has been reported to have a crucial role in the pathophysiology of PD. […] Enhanced conditionality and resistance to extinction are known as risk factors in progression from panic attack to PD. […] As an important element of the anxiety neurocircuitry, altered amygdalar function and structure may facilitate the progression to PD.

• #1 Panic Disorder: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/287913-overview

  The neuroanatomic model suggests that panic attacks are mediated by a „fear network” in the brain that involves the amygdala, hypothalamus, and brainstem centers. […] According to a 2024 study, a specific brain circuit outside the amygdala has been linked to panic attacks. The lateral parabrachial nucleus (PBL) in the pons, known as the brain’s alarm center, is likely implicated in generating panic and causing emotional and physical changes. Researchers discovered that this brain area produces a neuropeptide called pituitary adenylate cyclase-activating polypeptide (PACAP), which is known as a master regulator of the stress response. […] The cognitive theory suggests that patients with panic disorder have a heightened sensitivity to internal autonomic cues (eg, tachycardia). […] Furthermore, stress and environmental factors may play a role in the disorder.

• #1 Panic Disorder: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/287913-overview

  The apparent neurochemical dysfunction behind panic disorder may involve autonomic imbalance, decreased gamma-aminobutyric acid (GABA)ergic tone, allelic polymorphism of the catechol-O-methyltransferase (COMT) gene, increased adenosine receptor function, increased cortisol, diminished benzodiazepine receptor function, and disturbances in serotonin, serotonin transporter (5-HTTLPR) and promoter (SLC6A4) genes, norepinephrine, dopamine, cholecystokinin, and interleukin 1beta. […] Some authors theorize that panic disorder may represent a state of chronic hyperventilation and carbon dioxide receptor hypersensitivity. […] The serotonergic model suggests an exaggerated or inefficient postsynaptic receptor response to synaptic serotonin, potentially in the signal transduction cascade. Some studies report subsensitivity of serotonin 1A (5HT1A) receptors.

• #1 Pharmacologic Management of Acute and Chronic Panic Disorder

  https://www.uspharmacist.com/article/pharmacologic-management-of-acute-and-chronic-panic-disorder

  The noradrenergic theory states that patients experiencing PD have presynaptic NE autoreceptors that are hypersensitive to stimulation by NE. Research surrounding the noradrenergic model has revealed that administration of drugs that stimulate noradrenergic activity, thus releasing NE and increasing glutamate levels that result in feelings of anxiety, precipitate panic attack in those with PD and not in normal volunteers. […] Currently, two research models are being conducted around the role of 5-HT in panic disorders. First, the 5-HT excess model suggests that PD patients have an increased level of 5-HT or that they are hypersensitive to 5-HT. In contrast, the 5-HT deficit model proposes that there are regions in the brain where 5-HT reduces panic behavior and that a deficit of 5-HT would, therefore, facilitate a panic response. Consequently, clinical studies have shown that drugs used to increase 5-HT levels by blocking the reuptake are effective in the treatment of PD.

• #1 Pharmacologic Management of Acute and Chronic Panic Disorder

  https://www.uspharmacist.com/article/pharmacologic-management-of-acute-and-chronic-panic-disorder

  Panic disorder (PD) has an estimated prevalence of approximately 5% in the United States. Though the etiology and pathophysiology of PD are not completely understood, there are several proposed mechanisms thought to contribute to its development. PD can manifest as a sudden onset of fear followed by somatic symptoms such as chest pain, tachycardia, and dizziness. […] The etiology of PD is not fully understood; however, it is thought that genetics, neurobiology, stress, and life events play significant roles in its development. Several studies have shown that the risk of PD is eight times higher in those with first-degree relatives with PD compared to those with no family history. […] Though the exact pathophysiology of PD is currently unknown, it is thought that abnormal functioning of gamma-aminobutyric acid (GABA), norepinephrine (NE), serotonin (5-HT), and corticotropin-releasing factor (CRF) neurotransmitter systems play a role. GABA is an inhibitory central nervous system (CNS) neurotransmitter that reduces neuronal excitability when it binds to the GABAA receptor. The GABA receptor model postulates that PD is a result of a lack of central inhibition and decreased GABA concentrations, leading to uncontrolled anxiety during panic attacks.

• #1 Neurochemical and genetic factors in panic disorder: a systematic review | Translational Psychiatry

  https://www.nature.com/articles/s41398-024-02966-0

  GABAergic neurons inhibitory influence on dorsomedial and posterior hypothalamus nuclei is identified, potentially reducing the excitability of neurons involved in panic-like responses. The dorsomedial hypothalamus (DMH) is highlighted as a specific hypothalamic nucleus relevant to the genesis and maintenance of panic disorder. […] Altered brain lactate and glutamate concentrations, along with identified genetic polymorphisms linked to PD, further contribute to the intricate neurochemical landscape associated with the disorder. […] A prominent biological theory shedding light on the etiology of PD proposes that panic symptoms result from an imbalance in one or more neurotransmitters, including serotonin, norepinephrine, dopamine, and gamma-aminobutyric acid (GABA). […] Neurochemical theories suggest dysregulated functioning of neurotransmitters, such as a deficiency in the serotonergic system or excess serotonin.

• #1 ▶ Panic And The Brain: Understanding The Neuroscience Behind Panic Attacks

  https://mindease.io/wellness-blog/panic-attack-neuroscience

  Dysregulation of the HPA axis can lead to excessive cortisol production, potentially precipitating panic attacks. Scientific research points to a link between an overactive HPA axis and panic disorder. A review conducted by Abelson, et al. (2007) found that individuals with panic disorder exhibited a hyperactive HPA axis, which could contribute to their panic symptoms. […] Understanding the role of the HPA axis in panic attacks underscores the importance of addressing chronic stress and promoting strategies to regulate this vital stress response system.

• #1 Panic Disorder and Burnout in the Workplace: Review of the Evidence and Recommendations for Future Research | IntechOpen

  https://www.intechopen.com/chapters/84130

  The activation of the HPA axis has also been linked to anticipatory anxiety, which in turn can increase the probability of a panic attack. […] Panic attacks are often described by psychologists as attacks taking place to notify the person that there is something wrong in their lives. Lack of control in one’s life could be a reason a panic attack can occur. […] Work environments with low sense of psychological safety can resemble a cage, meaning that they limit the employees’ ability for control and autonomy; this results in a sense of helplessness, which can lead to high stress levels and potentially panic attacks.

• #1 SciELO Brazil – Respiratory manifestations of panic disorder: causes, consequences and therapeutic implications Respiratory manifestations of panic disorder: causes, consequences and therapeutic implications

  https://www.scielo.br/j/jbpneu/a/n9MHhWBxVcc5QK3jpBTgQpP/

  Multiple respiratory abnormalities can be found in anxiety disorders, especially in panic disorder (PD). […] The respiratory abnormality most often reported in PD patients is increased CO2 sensitivity, which has given rise to the hypothesis of fundamental abnormalities in the physiological mechanisms that control breathing in PD. […] Patients with PD tend to hyperventilate and to panic in response to respiratory stimulants such as CO2, triggering the activation of a hypersensitive fear network. […] Although respiratory physiology seems to remain normal in these subjects, recent evidence supports the idea that they present subclinical abnormalities in respiration and in other functions related to body homeostasis. […] The fear network, composed of the hippocampus, the medial prefrontal cortex, the amygdala and its brain stem projections, might be oversensitive in PD patients.

• #1 SciELO Brazil – The role of hyperventilation: hypocapnia in the pathomechanism of panic disorder The role of hyperventilation: hypocapnia in the pathomechanism of panic disorder

  https://www.scielo.br/j/rbp/a/LYGwM34pwzsgpYnjbSw5xbS/

  OBJECTIVE: The authors present a profile of panic disorder based on and generalized from the effects of acute and chronic hyperventilation that are characteristic of the respiratory panic disorder subtype. The review presented attempts to integrate three premises: hyperventilation is a physiological response to hypercapnia; hyperventilation can induce panic attacks; chronic hyperventilation is a protective mechanism against panic attacks. […] The panic attacks experienced by individuals with panic disorder develop on the basis of metabolic acidosis, which is a compensatory response to chronic hyperventilation. The attacks are triggered by a sudden increase in (pCO2) when the latent (metabolic) acidosis manifests as hypercapnic acidosis. The acidotic condition induces catecholamine release.

• #1 SciELO Brazil – The role of hyperventilation: hypocapnia in the pathomechanism of panic disorder The role of hyperventilation: hypocapnia in the pathomechanism of panic disorder

  https://www.scielo.br/j/rbp/a/LYGwM34pwzsgpYnjbSw5xbS/

  Catecholamines can provoke panic when hyperventilation causes the hypercapnia to switch to hypocapnic alkalosis (overcompensation) and catecholamine sensitivity begins to increase. […] Therapeutic approaches should address long-term regulation of the respiratory pattern and elimination of metabolic acidosis. […] Chronic hyperventilation predisposes an individual to PD, since compensatory mechanisms (such as alterations in renal function and tissue buffer capacity) lead to chronic metabolic acidosis, which remains latent until it is activated by chronic hypocapnia. The acidosis manifests when hyperventilation decreases or hypercapnia develops (metabolic + respiratory acidosis). Acidosis induces catecholamine release, and the activity of locus coeruleus increases. […] The pathogenesis of panic attacks can include defensive mechanisms resembling 'freezing behavior’, since prolonged hypercapnia induces strong catecholamine release. However, the sympathetic response arises when tissue catecholamine sensitivity increases due to subsequent hyperventilation.

• #1 SciELO Brazil – Respiratory manifestations of panic disorder: causes, consequences and therapeutic implications Respiratory manifestations of panic disorder: causes, consequences and therapeutic implications

  https://www.scielo.br/j/jbpneu/a/n9MHhWBxVcc5QK3jpBTgQpP/

  Klein proposed that panic attack results from the dysregulation of a phylogenetically evolved alarm system directed at monitoring signals of suffocation. […] The influence of genetics on CO2-induced panic has also been studied. […] Many authors have found that healthy relatives of panic disorder patients are significantly more likely to react to CO2 challenge than are healthy subjects without a familial history of panic disorder. […] Panic attacks are thought to originate from an abnormally sensitive fear network, centered in the central nucleus of the amygdala (CNA). […] Panic originates from within an abnormally sensitive fear network, which includes the prefrontal cortex, insula, thalamus and amygdalae, as well as amygdalar projections to the brain stem and hypothalamus. […] There is a substantial amount of data demonstrating that respiratory stimulation is a common event in panic disorder patients during a panic attack.

• #1 Panic attack – Wikipedia

  https://en.wikipedia.org/wiki/Panic_attack

  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. 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. 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. […] 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. This part of the amygdala is called the acid-sensing ion channel. 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. One such internal trigger is the amygdala sensing acidosis, which can be caused by inhaling CO2 (carbon dioxide). 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.

• #1 Random Panic Attacks: Here’s What Happens to Your Body

  https://www.webmd.com/anxiety-panic/panic-attack-happening

  Your body’s fight or flight response is behind these intense physical symptoms. Normally when you encounter a threat — whether it’s a grizzly bear or a swerving car — your nervous system springs into action. The hormone adrenaline floods into your bloodstream, putting your body on high alert. Your heartbeat quickens, which sends more blood to your muscles. Your breathing becomes fast and shallow, so you can take in more oxygen. Your blood sugar spikes. Your senses get sharper. […] With random panic attacks, your body goes on alert for no reason. Researchers don’t know exactly what triggers them. But the physical effects are real: During a panic attack, the adrenaline levels in the body can spike by 2 1/2 times or more. […] Scientists are still studying how panic attacks affect the brain. It’s possible that the parts of the brain that are tied to fear become more active during an episode. One recent study found that people with panic disorder had lots of activity in a part of their brains tied to the fight or flight response. […] Other studies have found possible links between panic disorder and the chemicals in your brain. The condition may also be linked to an imbalance in serotonin levels, which can affect your moods.

• #1 Neurochemical and genetic factors in panic disorder: a systematic review | Translational Psychiatry

  https://www.nature.com/articles/s41398-024-02966-0

  This systematic review addresses the complex nature of Panic Disorder (PD), characterized by recurrent episodes of acute fear, with a focus on updating and consolidating knowledge regarding neurochemical, genetic, and epigenetic factors associated with PD. […] The review reveals patterns of altered expression in various biological systems, including neurotransmission, the Hypothalamic-Pituitary-Adrenal (HPA) axis, neuroplasticity, and genetic and epigenetic factors leading to neuroanatomical modifications. Noteworthy findings include lower receptor binding of GABAA and serotonin neurotransmitters in the amygdala. […] The involvement of orexin (ORX) neurons in the dorsomedial/perifornical region in triggering panic reactions is highlighted, with systemic ORX-1 receptor antagonists blocking panic responses. Elevated Interleukin 6 and leptin levels in PD patients suggest potential connections between stress-induced inflammatory changes and PD.

• #1 Panic Disorders – Harvard Health

  https://www.health.harvard.edu/a_to_z/panic-disorders-a-to-z

  Panic disorder is a type of anxiety disorder. A person with panic disorder has panic attacks. These are repeated, unexpected episodes of intense fear and anxiety accompanied by physical symptoms that are similar to the body’s normal response to danger. […] Although researchers do not completely understand why some people develop panic disorder, they believe that the illness involves a disturbance in brain pathways that regulate emotion. Also, it is possible that people with panic disorder may have inherited a „fight or flight” response that is either more sensitive than normal or responds more intensely than usual. […] Studies of close relatives of people with panic disorder show that this disease has a genetic (inherited) basis. These relatives are four to eight times more likely to develop the illness than people with no family history of the problem.

• #1

  https://www.omim.org/entry/167870

  Schumacher et al. (2011) provided a review of the genetics of panic disorder. They noted that there is high (80%) comorbidity with other psychiatric disorders, including agoraphobia, mood disorders, substance abuse, and other anxiety disorders. Associated personality traits include anxiety sensitivity, behavioral inhibition, neuroticism, and harm avoidance. Women are more susceptible to development of the disorder, which has an average age of onset at 23.6 years. […] Like many other complex behavioral traits, panic disorder is likely caused by an interaction of multiple loci, rather than a single locus. […] There is considerable evidence for a familial component to anxiety disorders in general and panic attacks in particular. […] Noyes et al. (1978) reported that the risk for 'anxiety neurosis’ among first-degree relatives of patients with the disorder was 18% compared to 3% for controls. Pauls et al. (1980) analyzed 19 kindreds with panic disorder and concluded that the segregation suggested autosomal dominant inheritance.

• #1 Neurochemical and genetic factors in panic disorder: a systematic review | Translational Psychiatry

  https://www.nature.com/articles/s41398-024-02966-0

  Additionally, abnormal chemoreceptor reactivity may be implicated in the etiology of PD, with inhibitory and excitatory neurotransmitters like glutamate, gamma-amino butyric acid, cholecystokinin, adenosine, dopamine, and norepinephrine potentially playing a role in panic regulation. […] Genetic studies form a significant aspect of biological theories, proposing an inherited genetic predisposition in individuals with PD. […] The respiratory subtype of PD has demonstrated a higher familial prevalence in comparison to the non-respiratory subtype in several studies. […] Although twin studies have provided valuable insights, suggesting a link between genetic factors and the pathogenesis of PD with moderate heritability contributions, criticisms include the failure to identify a mode of inheritance aligning with Mendelian patterns. […] The review underscores the potential impact of neurochemical, genetic, and epigenetic factors on the development and expression of PD. […] The review emphasizes the significance of understanding genetic variations and epigenetic modifications in unraveling the complex etiology of PD.

• #1 Gene found responsible for susceptibility to panic disorder | ScienceDaily

  https://www.sciencedaily.com/releases/2013/11/131128133921.htm

  A study published points, for the first time, to the gene trkC as a factor in susceptibility to a panic disorder. […] The researchers define the specific mechanism for the formation of fear memories which will help in the development of new pharmacological and cognitive treatments. […] It was known that this disease had a neurobiological and genetic basis and for some time the search had been on to discover which genes were involved in its development, with certain genes being implicated without their physiopathological contribution being understood. […] Now, for the first time, researchers from the Centre for Genomic Regulation (CRG) have revealed that the gene NTRK3, responsible for encoding a protein essential for the formation of the brain, the survival of neurons and establishing connections between them, is a factor in genetic susceptibility to panic disorder.

• #1 Panic disorder | Symptoms, Causes & Treatment | Britannica

  https://www.britannica.com/science/panic-disorder

  panic disorder, anxiety disorder characterized by repeated panic attacks that leads to persistent worry and avoidance behavior in an attempt to prevent situations that could precipitate an attack. Panic attacks are characterized by the unexpected, sudden onset of intense apprehension, fear, or terror and occur without apparent cause. […] The underlying cause of panic disorder appears to arise from a combination of genetic and environmental factors. One of the most significant genetic variations that has been identified in association with panic disorder is mutation of a gene designated HTR2A (5-hydroxytryptamine receptor 2A). This gene encodes a receptor protein in the brain that binds serotonin, a neurotransmitter that plays an important role in regulating mood. People who possess this genetic variant may be susceptible to irrational fears or thoughts that have the potential to induce a panic attack. Environmental and genetic factors also form the basis of the suffocation false alarm theory. This theory postulates that signals about potential suffocation arise from physiological and psychological centres involved in sensing factors associated with suffocation, such as increasing carbon dioxide and lactate levels in the brain. People affected by panic disorder appear to have an increased sensitivity to these alarm signals, which produce a heightened sense of anxiety. This increased sensitivity results in the misinterpretation of nonthreatening situations as terrifying events. […] Altered activity of neurotransmitters such as serotonin can give rise to depression. Thus, there exists a close association between panic disorder and depression, and a large percentage of persons suffering from panic disorder go on to experience major depression within the next few years.

• #1 Serotonin Function in Panic Disorder: Important, But Why? | Neuropsychopharmacology

  https://www.nature.com/articles/1300880

  In sum, the results of genetic association studies suggest that some gene variants of the 5-HT system, such as MAO-A uVNTR, 5-HT2A 102TC, and probably 5-HT1A -1019CG and 5-HTTLPR, may contribute to the susceptibility to PD. […] However, the 5-HT-ergic genetic influence seems to be differently related to PD phenotypes and may be gender-dependent. […] A better understanding of 5-HT function will lead toward an elucidation of the origins of panic attacks and the improved clinical management of PD.

• #1 Panic Disorders – Harvard Health

  https://www.health.harvard.edu/a_to_z/panic-disorders-a-to-z

  Some people with panic disorder first develop symptoms after a stressful life event, such as divorce, job loss or a death in the family. Scientists still do not understand exactly how panic attacks are triggered, but there is growing evidence that stress early in life makes a person more likely to develop panic symptoms. […] People who have panic disorder have a relatively high risk for developing other types of psychiatric problems. In fact, at the time of diagnosis, more than 90% of people with panic disorder also have major depression, another anxiety disorder, a personality disorder or some form of substance abuse.

• #1 Panic Disorder and Panic Attacks

  https://www.webmd.com/anxiety-panic/mental-health-panic-disorder

  Most often, panic attacks come „out of the blue.” One may even begin while you’re sleeping. Using drugs or alcohol to try to deal with panic disorder can make the symptoms worse. Attacks may come after the use of mind-altering drugs. And some medications can cause panic attacks, including some antidepressants. […] Panic disorder may start after: A serious illness or accident, The death of a close friend, Separation from family, The birth of a baby. […] People with this disorder often also have major depression, although there is no evidence that one condition causes the other. If you’re 40 or older and have panic disorder, you may have depression or another hidden medical condition. Talk to your doctor to find out what’s going on.

• #1 Panic Attacks & Panic Disorder: Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/4451-panic-attack-panic-disorder

  Experts dont know exactly why some people experience panic attacks or develop panic disorder. Your brain and nervous system play key roles in how you perceive and handle fear and anxiety. Researchers think that dysfunction of your amygdala the part of your brain that processes fear and other emotions may be at the root of these conditions. They also think chemical imbalances in gamma-aminobutyric acid (GABA), cortisol and serotonin may play a large role. […] Your risk of having panic disorder increases if you have: A family history: Anxiety disorders, including panic disorder, often run in families. You have a 40% increased risk of developing panic disorder if one of your first-degree relatives (biological siblings, children or parents) has the condition. Mental health conditions: People who have anxiety disorders, depression or other mental health conditions are more prone to panic attacks. Adverse childhood experiences (ACEs): ACEs are negative experiences that happen between the ages of 1 and 17. These experiences are usually traumatic events. ACEs can contribute to the development of panic attacks and panic disorder.

• #1 Panic disorder – Wikipedia

  https://en.wikipedia.org/wiki/Panic_disorder

  Panic disorder is a mental and behavioral disorder, specifically an anxiety disorder characterized by reoccurring unexpected panic attacks. Panic attacks are sudden periods of intense fear that may include palpitations, sweating, shaking, shortness of breath, numbness, or a feeling that something terrible is going to happen. The exact cause of panic disorder is not fully understood, however there are a number of factors linked to the disorder such as a stressful or traumatic life event, having close family members with the disorder and an imbalance of neurotransmitters. Diagnosis involves ruling out other potential causes of anxiety including other mental disorders, medical conditions such as heart disease or hyperthyroidism, and drug use. […] Studies investigating the relationship between interoception and panic disorder have shown that people with panic disorder feel heartbeat sensations more intensely when stimulated by pharmacological agents, suggesting that they experience heightened interoceptive awareness compared to subjects without Parkinson’s disease.

• #1 Overcoming Panic Disorder

  https://give.brighamandwomens.org/overcoming-panic-disorder/

  Anxiety and panic are interrelated, and both contribute to panic disorder, says Gabe Gruner, LICSW, a psychotherapist at the Psychiatry Outpatient Clinic at Brigham and Womens Hospital. […] The low-level of arousal that comes from anxiety about future panic attacks can trigger an actual panic attack. […] About one third of people with panic disorder will show symptoms of agoraphobia, the fear of public or enclosed places where escape might be difficult. […] The underlying mechanism that drives panic disorder is called anxiety sensitivity, a phenomenon where an individual becomes afraid of their bodily sensations, explains Gruner. […] When people have high anxiety sensitivity, they can mistake natural bodily sensations as harmful physical health symptoms, and this can lead to more anxiety and trigger panic attacks.

• #1 Overcoming Panic Disorder

  https://give.brighamandwomens.org/overcoming-panic-disorder/

  The process of learning to fear bodily sensations is called interoceptive conditioning. […] The following three factors contribute to interoceptive conditioning, higher anxiety sensitivity and development of panic disorder. […] Gruner says that panic disorder often starts with an unexpected panic attack that surprises the person. […] Many individuals with panic disorder realize they have the disorder after a trip to the emergency room (ER), as panic attack symptoms can easily be mistaken for a heart attack or stroke. […] Many people who are concerned about panic disorder visit their primary care provider (PCP). […] Gruner advises individuals to be wary if their PCP prescribes benzodiazepines. […] Ideally, a PCP would recommend a therapist or psychiatrist. […] Panic disorder is one of the most treatable anxiety disorders.

• #1 Reasons for Panic Attacks – 6 Causes, Expert Tools & How to Cope

  https://www.livi.co.uk/your-health/6-causes-of-panic-attacks-and-expert-tools-for-how-to-cope/

  Another way of putting it is that your fight or flight system has become hypersensitive. […] The physiological reactions that occur during a panic attack come from the body’s fight or flight response. […] This stress response begins in the brain where the amygdala, the area to do with emotional processing, sends a signal to the hypothalamus, the area that communicates with the rest of the body. […] The hypothalamus activates the sympathetic nervous system, which signals to the adrenal glands to produce more adrenaline. […] As a result, your heart beats faster, breathing is quicker and more blood and oxygen go to your muscles, preparing your body to fight or run away. […] It becomes a problem if this response is repeatedly triggered when there is no actual danger, as it does during a panic attack, because your brain can’t distinguish between a real or perceived threat.

• #1 Mental Health Info – CPH IMH

  https://www3.ha.org.hk/cph/imh/en/mental-health-info/2/3/6/panic-disorder

  Recent medical research found that imbalance of serotonin in brain causes anxiety response happens without real threat and out of control. The patients misunderstand the anxiety symptoms to be something life threatening. For example, the patients misunderstand the increased heart rate as a sign of heart attack, increased breathing as a sign of impending suffocation or going mad. This misunderstanding triggers a vicious cycle, escalating the anxiety symptoms. In severe cases, excessive breathing leads to an abnormally low blood carbon dioxide level and symptoms like numbness and tingling sensation in lips and limbs, dizziness and headache. […] After proper treatment, 70-80% patients with panic disorder can recover. Without treatment, panic disorder can get worse and linger for long time. Both medication and psychological treatment can relieve symptoms and lower the risk of relapse. The patients personality and resilience to stress affect the treatment outcome and risk of relapse.

• #1 Serotonin Function in Panic Disorder: Important, But Why? | Neuropsychopharmacology

  https://www.nature.com/articles/1300880

  The investigation of 5-HT-ergic treatment effects on the sensitivity to panicogenic agents is another pertinent way to clarify the protective role of 5-HT in PD. […] The brain-imaging studies point to a reduced density of 5-HTT as well as 5-HT1A receptors in PD. […] It is conceivable that these changes reflect a deficit in 5-HT neurotransmission or a compensatory process in the 5-HT system that attempts to increase the availability of synaptic 5-HT. […] The critical question which remains to be answered is whether there is a deficit in 5-HT synthesis and/or in 5-HT neurotransmission in patients with PD. […] The imaging data also serve to elucidate the place of the 5-HT system in the neuronal circuitry of PD. […] The results of previous studies argued against a major role for the 5-HT2C receptor Cys23Ser polymorphism in PD.

• #1 Panic disorder – Wikipedia

  https://en.wikipedia.org/wiki/Panic_disorder

  Past research concluded that there is irregular norepinephrine activity in people who have panic attacks. Current research also supports this perspective as it has been found that those with panic disorder also have a brain circuit that performs improperly. This circuit consists of the amygdala, central gray matter, ventromedial nucleus of the hypothalamus, and the locus ceruleus. […] Researchers studying some individuals with panic disorder propose they may have a chemical imbalance within the limbic system and one of its regulatory chemicals GABA-A. The reduced production of GABA-A sends false information to the amygdala which regulates the body’s „fight or flight” response mechanism and, in return, produces the physiological symptoms that lead to the disorder. […] The neuroanatomy of panic disorder largely overlaps with that of most anxiety disorders. Neuropsychological, neurosurgical, and neuroimaging studies implicate the insula, amygdala, hippocampus, anterior cingulate cortex (ACC), lateral prefrontal cortex, and periaqueductal grey. During acute panic attacks, viewing emotionally charged words, and rest, most studies find elevated blood flow or metabolism. However, the observation of amygdala hyperactivity is not entirely consistent, especially in studies that evoke panic attacks chemically.

• #1 Panic disorder – Wikipedia

  https://en.wikipedia.org/wiki/Panic_disorder

  The frontal cortex is implicated in panic disorder by multiple lines of evidence. Damage to the dorsal ACC has been reported to lead to panic disorder. Elevated ventral ACC and dorsolateral prefrontal cortex during symptom provocation and viewing emotional stimuli have also been reported, although findings are not consistent. […] Recently, researchers have begun to identify mediators and moderators of aspects of panic disorder. One such mediator is the partial pressure of carbon dioxide, which mediates the relationship between panic disorder patients receiving breathing training and anxiety sensitivity; thus, breathing training affects the partial pressure of carbon dioxide in a patient’s arterial blood, which in turn lowers anxiety sensitivity. Another mediator is hypochondriacal concerns, which mediate the relationship between anxiety sensitivity and panic symptomatology; thus, anxiety sensitivity affects hypochondriacal concerns which, in turn, affect panic symptomatology.

• #1 Panic Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430973/

  Many neurotransmitters and peptides within the central nervous system appear to play a major role in the physical manifestations. Results of brain imaging studies have shown characteristic changes, including increased flow and receptor activity, in specific geographic regions, including the limbic and frontal regions. The amygdala is proposed as the main area of dysfunction. […] There are two main theories that attempt to explain why patients are more likely to experience panic attacks. The first hypothesizes that susceptible patients lack the appropriate neurochemical mechanisms, which would normally inhibit serotonin, and this increased serotonin causes alterations in the fear network model of the autonomic nervous system. The second theorizes that a deficiency in endogenous opioids results in separation anxiety and increased awareness of suffocation.

• #1 The science behind panic attacks — and what you can do to manage them |

  https://ideas.ted.com/the-science-behind-panic-attacks-and-what-can-you-do-to-manage-them/

  Panic attacks begin with something that causes your heart to race it could even be caused by something as innocuous as a jolt of caffeine. […] But once an attack is triggered, the cascade of physiological responses in the body is fairly universal. […] Your amygdala a pair of almond-sized nerve bundles buried in the deep brain that plays a key role in processing emotions sends a distress signal to your hypothalamus a tiny command center that sits atop the brainstem and coordinates involuntary bodily functions such as breathing, blood pressure and heartbeat. […] Panic attacks typically peak and subside within 10 or 15 minutes, and there are a handful of solid techniques that can help you ride them out. […] Ultimately, panic attacks are just fear of fear, says clinical psychiatrist Cindy Aaronson PhD.

• #1 Panic Attacks & Panic Disorder: Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/4451-panic-attack-panic-disorder

  Theres often no specific trigger for panic attacks. But people who have a phobia can experience phobia-related triggers that lead to a panic attack. […] Psychotherapy, medications or a combination of both are very effective in treating panic attacks and panic disorder. How long youll need treatment depends on the severity of the condition and how well you respond to treatment. […] Specific types of psychotherapy that can help with panic attacks and panic disorder include: Cognitive behavioral therapy (CBT): In this type of therapy, you discuss your thoughts and emotions with a mental health professional, such as a licensed counselor or psychologist. This specialist helps identify panic attack triggers so you can change your thinking, behaviors and reactions. […] Medications that can help treat panic attacks and panic disorder include: Antidepressants: Certain antidepressant medications can make panic attacks less frequent or less severe.

• #1 Serotonin Function in Panic Disorder: Important, But Why? | Neuropsychopharmacology

  https://www.nature.com/articles/1300880

  Clinical studies consistently show the efficacy of medications which increase the synaptic availability of 5-HT, such as monoamine oxidase (MAO) inhibitors and selective 5-HT re-uptake inhibitors (SSRIs), in the treatment of PD. […] Despite the initial worsening of anxiety with SSRI treatment, numerous observations of the antipanic effect of 5-HT provide support for the 5-HT-deficit hypothesis. […] Altogether, these clinical data are in favor of the 5-HT-deficit hypothesis in PD. […] The 5-HT-ergic mechanisms of anxiety and panic have been studied experimentally using dFEN and m-chlorophenylpiperazine (m-CPP) as challenge agents. […] Taken together, the duality of 5-HT system in the mediation of different types of anxiety, as well as the complex reciprocal relationship within the panic circuitry, may explain the difficulty in uncoupling the anxiogenic and panicogenic effects of 5-HT-ergic agents.

• #1 Mental Health Info – CPH IMH

  https://www3.ha.org.hk/cph/imh/en/mental-health-info/2/3/6/panic-disorder

  Imbalance of serotonin in brain disturbs the normal functioning of the anxiety response. Therefore, to manage the symptoms of panic disorder, doctors use a type of medication which regulates the transmission of serotonin in brain. With proper dosage, most patients will start to improve in 4 to 6 weeks. […] Cognitive behavioral therapy is the major kind of psychological treatment for panic disorder. Psychological treatment for panic disorder covers two main areas. First, it increases patients knowledge on panic disorder, including the cause of illness and symptoms. This knowledge relieves patients misunderstanding which includes the unjustified negative feeling, worry and false assumptions about the illness. […] Secondly, patients are taught how to handle bodily discomfort and other anxiety symptoms, such as muscle relaxation and regulation of breathing. When a patient is anxious, his breathing becomes rapid and shallow, and disturb the balance of oxygen and carbon dioxide in body. The patient is advised to breathe slowly and adopt diaphragmatic breathing so that breathing becomes deeper and slower and the balance of oxygen and carbon dioxide resumes.

• #1 The science behind panic attacks — and what you can do to manage them |

  https://ideas.ted.com/the-science-behind-panic-attacks-and-what-can-you-do-to-manage-them/

  Therapy can help too. Aaronsons group found that cognitive behavioral therapy, which is designed to gradually help you modify your behavioral responses to life events, can strengthen the neural connections between the frontal cortex and the amygdala. […] Ultimately, panic attacks are just fear of fear, says Aaronson.

• #1 Pharmacologic Management of Acute and Chronic Panic Disorder

  https://www.uspharmacist.com/article/pharmacologic-management-of-acute-and-chronic-panic-disorder

  To date, the exact pathogenesis of PD and guidelines for the treatment of this disorder have not been concretely established. Multiple lines of inquiry and research are being conducted on the mechanism of panic attacks, and as more information is revealed, the targeted treatment of PD will continue to improve.

• #1 Gene found responsible for susceptibility to panic disorder | ScienceDaily

  https://www.sciencedaily.com/releases/2013/11/131128133921.htm

  This study by the CRG researchers reveals that the way in which the memories resulting from a panic attack are stored is what ultimately ends up producing the disorder, which usually appears between 20 and 30 years of age. […] Although it has a genetic basis, it is also influenced by other environmental factors, such as accumulated stress. […] „The problem is that drugs have many side effects and psychotherapy is not really aimed at specific moments in the process of forming and forgetting fear memories. […] In our work we have defined a specific creation mechanism for these fear memories that could help in the development of new drugs and, also, in identifying the key moments for applying cognitive therapy,” indicates D’Amico.

• #2 Panic Disorder: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/287913-overview

  Panic disorder is characterized by the spontaneous and unexpected occurrence of panic attacks, the frequency of which can vary from several attacks per day to only a few attacks per year. Panic attacks are defined as a period of intense fear in which 4 or more of 13 defined symptoms develop abruptly and peak rapidly less than 10 minutes from symptom onset. […] Although such attacks can occur in other anxiety disorders, these attacks often occur without a discernible predictable precipitant in panic disorder. […] To meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) criteria for panic disorder, panic attacks must be associated with longer than 1 month of subsequent persistent worry about: (1) having another attack or consequences of the attack, or (2) significant maladaptive behavioral changes related to the attack. To make the diagnosis of panic disorder, panic attacks cannot directly or physiologically result from substance use (intoxication or withdrawal), medical conditions, or another psychiatric disorder.

• #2 The role of the amygdala in the pathophysiology of panic disorder: evidence from neuroimaging studies | Biology of Mood & Anxiety Disorders | Full Text

  https://biolmoodanxietydisord.biomedcentral.com/articles/10.1186/2045-5380-2-20

  Although the neurobiological mechanisms underlying panic disorder (PD) are not yet clearly understood, increasing amount of evidence from animal and human studies suggests that the amygdala, which plays a pivotal role in neural network of fear and anxiety, has an important role in the pathogenesis of PD. […] It has been suggested that the amygdala has a critical role in the development of panic attacks and the pathogenesis of PD. […] The amygdala has been reported to have a crucial role in the pathophysiology of PD. […] Increased amygdalar activity with volumetric deficits was noted in patients with PD, although not always consistent. […] This altered function and structure of the amygdala may be partly due to dysregulated brain metabolism. […] Enhanced conditionality and resistance to extinction are known as risk factors in progression from panic attack to PD. […] Altered amygdalar function and structure may facilitate the progression to PD.

• #2 Serotonin Function in Panic Disorder: Important, But Why? | Neuropsychopharmacology

  https://www.nature.com/articles/1300880

  The essential role of serotonin (5-hydroxytryptamine (5-HT)) system in the neurobiology and pharmacotherapy of panic disorder (PD) continues to be a topic of intensive interdisciplinary research. […] The challenge and treatment studies generally confirm the specific inhibitory influence of 5-HT on panicogenesis. […] The findings of genetic association studies suggest that certain 5-HT-related genes may contribute to the susceptibility to PD; however, these data are rather limited and inconsistent. […] It appears that, even if not the primary etiological factor in PD, the 5-HT function conveys important vulnerability, as well as adaptive factors. […] The specific involvement of 5-HT in the pathogenesis and neurobiology of PD has been extensively tested in a broad scope of investigations including clinical and experimental studies, brain imaging, and genetics.

• #2 SciELO Brazil – Respiratory manifestations of panic disorder: causes, consequences and therapeutic implications Respiratory manifestations of panic disorder: causes, consequences and therapeutic implications

  https://www.scielo.br/j/jbpneu/a/n9MHhWBxVcc5QK3jpBTgQpP/

  Multiple respiratory abnormalities can be found in anxiety disorders, especially in panic disorder (PD). […] The respiratory abnormality most often reported in PD patients is increased CO2 sensitivity, which has given rise to the hypothesis of fundamental abnormalities in the physiological mechanisms that control breathing in PD. […] Patients with PD tend to hyperventilate and to panic in response to respiratory stimulants such as CO2, triggering the activation of a hypersensitive fear network. […] Although respiratory physiology seems to remain normal in these subjects, recent evidence supports the idea that they present subclinical abnormalities in respiration and in other functions related to body homeostasis. […] The fear network, composed of the hippocampus, the medial prefrontal cortex, the amygdala and its brain stem projections, might be oversensitive in PD patients.

• #2 Panic attack – Wikipedia

  https://en.wikipedia.org/wiki/Panic_attack

  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. 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. 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. […] 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. This part of the amygdala is called the acid-sensing ion channel. 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. One such internal trigger is the amygdala sensing acidosis, which can be caused by inhaling CO2 (carbon dioxide). 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.

• #2 Panic attack – Wikipedia

  https://en.wikipedia.org/wiki/Panic_attack

  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. 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).

• #2

  https://www.omim.org/entry/167870

  In a study of 32 monozygotic (MZ) and 53 dizygotic (DZ) adult same-sex twin pairs, Torgersen (1983) found that the frequency of anxiety disorders was twice as high in the MZ as in the DZ pairs. Panic disorder and agoraphobia with panic attacks were more than 5 times more frequent in the MZ twins. […] In a review, Schumacher et al. (2011) noted that the estimated heritability of panic disorder is 48%, and that most cases show complex genetic inheritance. […] Johnson et al. (2010) showed that orexin (HCRT; 602358) may be involved in panic disorder and anxiety, both of which are disorders associated with increased arousal, hypervigilance, and stimulation of the autonomic nervous system. A rat model of panic disorder showed increased activation of Hcrt-positive cells in the dorsomedial-perifornical hypothalamus after sodium lactate administration that correlated with anxious behavior compared to nonpanic rats. This response was attenuated with siRNA against the Hcrt gene, as well as by antagonists to the Hcrt receptor (HCRTR1; 602392) injected directly into the stria terminalis. These attenuating effects mimicked treatment with benzodiazepines, which result in increased GABAergic activity. Finally, cerebrospinal fluid levels of orexin were increased among 53 individuals with panic anxiety compared to controls, suggesting that the orexin system may be involved in the pathophysiology of panic anxiety.

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