The high prevalence rates of anxiety disorders emphasize the need to understand the underlying mechanisms. Panic disorder (PD) is an anxiety disorder that is particularly debilitating, as the panic attacks are unexpected and peak quickly (American Psychiatric Association, 2013). The diagnostic criteria require at least four of the following symptoms: palpitations, sweating, trembling, shortness of breath or smothering, feelings of choking, chest pain, nausea, dizziness, chills or heat sensations, paresthesia, derealisation or depersonalization, fear of losing control and fear of dying (American Psychiatric Association, 2013). This paper will examine the epigenetics perspective and catastrophic misinterpretations model to help explain the symptoms of PD, as well as consider its limitations. The epigenetics perspective and catastrophic misinterpretations model are reciprocal in explaining the symptoms of PD.
The epigenetics perspective is useful for understanding PD symptoms. Epigenetics are changes in gene expression (instead of DNA) due to interactions with the environment (Nieto, Patriquin, Nielsen & Kosten, 2016). Corticotropin releasing hormone receptor 1 (CRHR1) plays a critical role in the hypothalamic-pituitary-adrenal (HPA) axis during stressful situations; CRHR1 triggers a chain reaction in the HPA axis, which releases cortisol and triggers the stress response (Schartner et al., 2017). Schartner et al. (2017) found that CRHR1 methylation (adding methyl group to DNA which changes gene expression) in PD patients was significantly decreased as compared to controls. Findings suggest CRHR1 hypomethylation causes increased CRHR1 expression, indicating a link between the stress response and PD (Shartner et al., 2017).
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Shimada-Sugimoto et al. (2017) conducted an epigenome-wide association study (EWAS) to consider whether different levels of DNA methylation is associated with PD. The results revealed that DNA methylation levels in 40 CpG sites were significantly different between PD and control subjects (Shimada-Sugimoto et al., 2017). Furthermore, Lurato et al. (2017) conducted a replication of the previous EWAS, stratified by gender. Although no association was found for male participants, methylation differences were found in female participants and the HECA gene was hypermethylated for female PD patients (Lurato et al., 2017). Also, DNA methylation of monoamine oxidase A (MAOA) and glucocorticoid receptor genes are significantly altered in PD patients (Domschke et al., 2017; Nieto et al., 2016). The studies show DNA methylation in PD patients is evidently altered, increasing the stress response.
Catastrophic misinterpretations model explains symptoms of PD. This model proposes that physiological sensations (e.g. palpitations) cause distress due to biased appraisals (Bailey & Wells, 2015). PD patients perceive relatively harmless symptoms as serious and life-threatening, resulting in panic attacks and avoidance behaviour (Bailey & Wells, 2015). Ohst & Tuschen-Caffier (2018) conducted a meta-analysis of studies comparing the strength of catastrophic misinterpretations of bodily sensations and external events among PD patients, patients with other anxiety disorders and healthy controls. The findings revealed that PD patients have significantly more catastrophic misinterpretations of bodily sensations than other groups (Ohst & Tuschen-Caffier, 2018). Regarding external events, PD patients had similar effects with patients with other anxiety disorders; the similar effects may be due to systematic influences (Ohst & Tuschen-Caffier, 2018). Furthermore, Bailey & Wells (2015) found that catastrophic misinterpretations in anxiety-provoking situations are dependent on metacognitive beliefs (beliefs about thinking). Bailey & Wells (2015) claim that negative metacognitive beliefs (e.g. “I need to stop worrying”) are more harmful than positive metacognitive beliefs (e.g. “worrying is useful”), as it escalates feeling of distress. This finding supports the catastrophic misinterpretations model and demonstrates the impact maladaptive cognitions has on PD.
The epigenetics perspective and catastrophic misinterpretations model are reciprocally related to the symptoms of PD. Individuals with PD have a hyperactive HPA axis and experience epigenetic changes during stressful events, causing physiological sensations. As a result, PD patients develop catastrophic misinterpretations of these bodily sensations, which worsens the symptoms and causes panic attacks. Furthermore, epigenetic changes in the DNA methylation and hyperactivity of the HPA axis causes heightened “fight or flight” bodily sensations, such as palpitations, sweating, trembling and shortness of breath, as seen in PD patients. Other bodily sensations of PD patients are likely due to related epigenetic changes. Also, catastrophic misinterpretations model explains the following symptoms of PD: derealisation, depersonalization, fear of losing control and dying. PD patients misattribute their physiological sensations as abnormal and develop maladaptive cognitions which exacerbate their symptoms. Both perspectives are integral for a comprehensive understanding of the symptoms.
Although the epigenetic perspective and catastrophic misinterpretation model provides insight to PD, there are several limitations. The epigenetic studies were fewer in number (only two EWAS), had small sample sizes and lacked replication studies. The meta-analysis study of catastrophic misinterpretations had relatively few studies that meet all criteria (Ohst & Tuschen-Caffier, 2018). Also, the meta-analysis had systematic influence: the measurement of anxiety was not exhaustive and there was inconsistency in instruments (Ohst & Tuschen-Caffier, 2018).
Overall, the epigenetic perspective and catastrophic interpretation model helps explain the symptoms of PD. Epigenetically driven changes in the HPA axis and DNA methylation increases physiological sensations that are seen in PD patients. These symptoms are then misinterpreted as life-threatening and cause distress in PD patients. Future studies are required to extend the knowledge on PD and replication studies are recommended.
References
- American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: Author.
- Bailey, R., & Wells, A. (2015). Metacognitive beliefs moderate the relationship between catastrophic misinterpretation and health anxiety. Journal of Anxiety Disorders, 34, 8–14. http://dx.doi.org/10.1016/j.janxdis.2015.05.005
- Domschke, K., Ziegler, C., Richter, J., Mahr, M., Gajewska, A., Lang, T., Pauli, P., Rief, W., Kircher, T., Arolt, V., Hamm, A. O., Deckert, J. (2017). From candidate gene to (epi)genome-wide analysis of therapy response in adult anxiety disorders. European Neuropsychopharmacology, 27(4), 534-535. doi: 10.1016/S0924-977X(17)31015-5
- Lurato, S., Carillo-Roa, T., Arloth, J., Czamara, D., Diener-Hölzl, L., Lange, J., Müller-Myhsok, B., Binder, E. B., Erhardt, A. (2017). DNA methylation signatures in panic disorder. Translational Psychiatry, 7, 1-10. doi: 10.1038/s41398-017-0026-1
- Nieto, S. J., Patriquin, M. A., Nielsen, D. A., & Kosten, T. A. (2016). Don’t worry; be informed about the epigenetics of anxiety. Pharmacology, Biochemistry and Behavior, 146–147, 60– 72. doi: 10.1016/j.pbb.2016.05.006
- Ohst, B. & Tuschen-Caffier, B. (2018). Catastrophic misinterpretation of bodily sensations and external events in panic disorder, and other anxiety disorders, and healthy subjects: A systematic review and meta-analysis. PLoS ONE, 13(3), 1-11. doi: 10.1371/journal.pone.0194493
- Schartner, C., Ziegler, C., Schiele, M. A., Kollert, L., Weber, H., Zwanzger, P., Arolt, V., Pauli, P., Dechkert, J., Reif, A., Domschke, K. (2017). CRHR1 promoter hypomethylation: An epigenetic readout of panic disorder? European Neuropsychopharmacology, 27(4), 360- 371. http://dx.doi.org/10.1016/j.euroneuro.2017.01.005
- Shimada-Sugimoto, M., Otowa, T., Miyagawa, T., Umekage, T., Kawamura, Y., Bundo, M., Kazuya, L., Tochigi, M., Kasai, K., Tanii, H., Okazaki, Y., Tokunaga, K., Sasaki, T. (2017). Epigenome-wide association study of DNA methylation in panic disorder. Clinical Epigenetics, 9(6), 1-11. doi: 10.1186/s13148-016-0307-1
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