Respiratory manifestations of panic disorder: causes, consequences and therapeutic implications

Abstract

Multiple respiratory abnormalities can be found in anxiety disorders, especially in panic disorder (PD). Individuals with PD experience unexpected panic attacks, characterized by anxiety and fear, resulting in a number of autonomic and respiratory symptoms. Respiratory stimulation is a common event during panic attacks. The respiratory abnormality most often reported in PD patients is increased CO 2 sensitivity, which has given rise to the hypothesis of fundamental abnormalities in the physiological mechanisms that control breathing in PD. There is evidence that PD patients with dominant respiratory symptoms are more sensitive to respiratory tests than are those who do not manifest such symptoms, and that the former group constitutes a distinct subtype. Patients with PD tend to hyperventilate and to panic in response to respiratory stimulants such as CO 2 , 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. This theory might explain why medication and cognitive-behavioral therapy are both clearly effective. Our aim was to review the relationship between respiration and PD, addressing the respiratory subtype of PD and the hyperventilation syndrome, with a focus on respiratory challenge tests, as well as on the current mechanistic concepts and the pharmacological implications of this relationship.Keywords: Panic disorder; Anxiety; Respiration; Hyperventilation; Carbon dioxide. ResumoMúltiplas anormalidades respiratórias podem ser encontradas em pacientes com transtornos de ansiedade, particularmente no transtorno de pânico (TP). Indivíduos com TP experimentam ataques de pânico inesperados, caracterizados por ansiedade, medo e diversos sintomas autonômicos e respiratórios. A estimulação respiratória é um fenômeno comum durante os ataques de pânico. A anormalidade respiratória mais citada em pacientes com TP é a sensibilidade aumentada para o CO 2 , que originou a hipótese de uma disfunção fundamental nos mecanismos fisiológicos de controle da respiração no TP. Há evidências de que pacientes com TP com sintomas respiratórios predominantes são mais sensíveis a testes respiratórios do que aqueles sem a manifestação de tais sintomas, representando um subtipo distinto. Pacientes com TP tendem a hiperventilar e a reagir com pânico como resposta a estimulantes respiratórios como o CO 2 , gerando uma ativação de um circuito de medo hipersensível. Apesar de a fisiologia respiratória desses pacientes permanecer normal, algumas evidências recentes apontam a presença de disfunções subclínicas na respiração e em outras funções relacionadas à homeostase corporal. O circuito do medo, composto pelo hipocampo, córtex pré-frontal medial, amígd...

Cardiorespiratory Optimal Point: A Submaximal Exercise Variable to Assess Panic Disorder Patients

“…Several studies have investigated respiratory symptoms in PD patients [2], [31], [32], [33] and found that, during PA, respiratory complaints are common, such as dyspnea and tachypnea. Some specific respiratory tests aimed at inducing PA have been used, demonstrating that respiratory maneuvers, such as hyperventilation [34], carbon dioxide inhalation [35] and voluntary apnea [36], may increase anxiety in PD patients and thereby trigger a PA.…”

“…They could be a real diagnostic challenge since it is quite often difficult to distinguish between a real clinical abnormal respiratory or circulatory condition from one commonly seen during panic attacks (PA) [2], [3]. Despite a very high lifetime prevalence of about 28% [4] for PA in adult subjects, It is worthwhile to note there are very limited amount of data about exercise and panic and, more specifically, about what role, if any, could cardiopulmonary exercise testing play in the clinical assessment of these patients.…”

“…Some evidence suggests that these patients may have subclinical respiratory and other abnormalities [3] related to body homeostasis during rest [2], as, for example, hyperventilation syndrome [6], with increased sensitivity to carbon dioxide (CO 2 ) [7], [8]. This increased CO 2 sensitivity led to the most well accepted current hypothesis to explain the occurrence of PA, the theory of false suffocation alarm, that is related to abnormal control mechanisms of respiration in these patients [9].…”

Respiratory manifestations of panic disorder in animals and humans: A unique opportunity to understand how supramedullary structures regulate breathing

“…Owing to its projections to the periaqueductal gray (PAG), the CeA can initiate behavioral responses observed during a panic attack such as immobility, trotting, galloping, defecation, and micturition (Sardinha et al, 2009;Schimitel et al, 2012). Furthermore, Fig.…”

Chronic serotonin–norepinephrine reuptake transporter inhibition modifies basal respiratory output in adult mouse in vitro and in vivo

“…Respiratory disturbances have emerged as a common feature in individuals suffering from panic disorder and often present as hyperventilation, increased sensations of breathlessness, and/or alterations in the response to carbon dioxide (Nardi et al 2009; Sardinha et al 2009). It has generally been accepted that these symptoms are the consequence of a faulty or maladaptive control center within the brainstem (Klein, 1993), and as such neurotransmitter systems within this region have become a potential target for a number of available therapeutics.…”