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Giampaolo Perna, Humanitas University, Italy, is a psychiatrist who has focussed his research on panic disorders. In a recent Faculty Review, he and his co-author, Daniela Caldirola, present a new hypothesis about the pathology of panic disorder. In this guest blog he elaborates on this and the evidence needed to prove this hypothesis.

F1000 Faculty Reviews are narrative reviews written by members of the F1000Prime Faculty providing an insight into certain scientific or clinical topics. These are commissioned and peer reviewed before publication to ensure that the final, published version is comprehensive and accessible.

As psychiatrists and clinical researchers, we started to treat panic attacks and panic disorder 25 years ago. Listening to the symptoms and needs of our patients, and thinking about their experiences have inspired us to conduct several experimental studies on this topic and to wonder what the source of panic attacks is. As a result, we have developed a personal view on the pathogenesis of panic. We hope that our hypothesis may foster debate and research on this controversial issue, with the final aim of helping affected people return to a wellbeing state in their lives.

How panic disorder affects people

Panic disorder is a chronic, debilitating anxiety disorder that exhibits a lifetime prevalence of 3–4% in the general population worldwide. Panic disorder is associated with psychiatric/medical comorbidity; it can result in significant impairment of daily functioning, work performance and quality of life – leading to relevant social costs.

One of the core features of panic disorder is recurrent, unexpected panic attacks. A panic attack is an abrupt surge of physical symptoms such as chest pain, palpitations, sensations of shortness of breath, feelings of choking, and dizziness/unsteadiness, which can be accompanied by intense discomfort and/or fear of dying/fear of losing control.

In addition, patients with panic disorder complain of several persistent physical symptoms between panic attacks, including respiratory difficulties, abnormalities in their heart rate, and dizziness. Patients may also exhibit anticipatory anxiety and/or maladaptive changes in behaviour related to panic attacks. Most individuals with panic disorder fear or avoid multiple situations in which panic attacks can occur, i.e., agoraphobia.

What we currently know about panic disorder

The pathophysiology of panic disorder is still not well understood. It is conceived as a mental disorder and is included in anxiety disorders in all the current psychiatric classifications. Panic attacks are considered “false alarms” related to abnormally sensitive defensive systems in the central nervous system.

Different opinions exist on the type of false alarm, including suffocation false alarm, inappropriate fear reactions, or catastrophic misinterpretation of harmless somatic sensations, but there is a consensus that these alarms are false because patients with panic disorder are physically healthy.

Our hypothesis on panic disorder

According to our hypothesis, panic disorder may not only be a mental disorder, but panic symptoms may arise from real, subtle alterations of physical functioning in these patients. Indeed, experimental studies have found that patients with panic disorder are physiologically different from people without panic disorder in several aspects, including the body as physiology in patients with panic disorder seems far from being perfect and stable.

It may result in a reduction of global physical flexibility and adaptability to changes. Consequently, panic alarms may be “real alarms” signaling that something is going wrong in the body and its physiological systems when the adaptability resources of an organism are insufficient to respond appropriately to ongoing internal/external changes during daily life. In other words, physical symptoms and discomfort experienced during panic attacks and in some feared environmental situations may not only be transient but real manifestations of an underlying decline in physical fitness, which becomes apparent under some circumstances.

Our hypothesis does not exclude that anxiety/fear mechanisms are involved in panic disorder, because anticipatory anxiety, fear conditioning processes, and phobic behaviours do exist in patients with panic disorder. Likewise, we do not state that panic disorder is a life-threatening medical disease, or that these patients have unrecognised medical diseases.

However, we think that the reduction of physical fitness could be the underlying cause of  panic disorder, while anxiety/fear are defensive mechanisms induced and sustained by repeated signals of subtly impaired body functioning. We propose considering panic in a broader perspective that provides a central role for the body, as clearly patients suggest.

Gathering evidence on our hypothesis

Much more research is required to demonstrate our hypothesis. Several lines of research may be followed to obtain more direct experimental evidence. For example, it should be tested if the improvement of cardiorespiratory function by physical treatments, e.g., physical exercise,  breathing training, actually reduces the occurrence of panic attacks in patients with panic disorders.

Longitudinal studies over the lifespan of patients with panic disorder and in individuals at risk of panic disorder should investigate the temporal relationships between abnormalities in body functioning and occurrence of panic attacks. These studies should take into account possible confounding factors, such as unhealthy behaviours and/or depression that can contribute to the reduction of physical fitness.

Finally, in individuals without panic disorder, it should be tested whether an association exists between decreased levels of cardiorespiratory/balance fitness and subthreshold panic symptoms or vulnerability to laboratory-induced panic attacks, and whether pharmacological manipulations aimed to decrease cardiorespiratory fitness lead to increased vulnerability to laboratory-induced panic attacks.