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Psychiatric Times. Vol. 21 No. 1
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Gender Differences in Panic Disorder

By Gregory A. Leskin, Ph.D., and Javaid I. Sheikh, M.D., M.B.A.
| January 1, 2004
Dr. Leskin is a clinical psychologist at the Veterans Affairs Palo Alto Health Care System and the National Center for Post-Traumatic Stress Disorder. Dr. Sheikh is professor of psychiatry at Stanford University School of Medicine.

Suffocation False Alarm

The suffocation false alarm theory (Klein, 1993) explores the possible function of sex hormones and panic in an integrated suffocation monitoring system. A triggered suffocation alarm may initially elicit acute distressing breathlessness and provoke escape efforts. Also, chronic hyperventilation lowers PCO2 and bicarbonate levels, thus lowering blood carbon dioxide levels from the suffocation alarm threshold. Klein (1993) viewed chronic hyperventilation as an adaptive strategy. Several experimental studies have induced initial hypercapnic states in panic-prone individuals through CO2 inhalation and lactate infusion to demonstrate how respiration potentially mediates bodily symptoms in panic.

In one study, the physiological response to CO2 in female patients with panic disorder differed significantly across multiple indicators, including at-rest breathing rate and end-tidal CO2 (Papp et al., 1997). Female patients showed the greatest CO2 sensitivity, illustrated by their highest respiratory rate. These findings suggest that female patients with panic disorder may have a hypersensitive suffocation alarm and may efficiently compensate for hypoxia and hypercapnia.

In order to explain these types of respiration-related gender differences, suffocation false alarm theory illustrates the potential relationship between increased panic during conditions such as premenstrual syndrome and late luteal phase dysphoric disorder (Klein, 1993). Specifically, this theory postulates that progesterone(Drug information on progesterone) and estrogen stimulate chronic hyperventilation during the luteal phase of the reproductive cycle. Progesterone withdrawal in the premenstrual phase may yield a sharp increase in PCO2 levels.

Similarly, as the estrogen levels fall during ovulation, hyperventilation occurs in response to the higher carbon dioxide levels in expiratory respiration (Klein, 1993). Thus, some females with a low suffocation threshold may be vulnerable to panic, particularly at times during the luteal phase of their menstrual cycle.

Other Theories

Separation anxiety disorder has been shown to be a precursor of panic disorder (Gittelman and Klein, 1984; Lipsitz et al., 1994). Separation-distress theory (Panksepp, 1998) posits that similar physiological mechanisms that mediate separation-distress (i.e., emotional pain, protest, despair, detachment) and audio-vocal responses (crying) may also direct motivations toward social affiliation. Indeed, closely aligned and overlapping neurochemical circuits may underlie separation anxiety and panic. That is, absence of primary attachment figures or contact comfort can lead to an emotionally distressful somatic response such as uttering anguished sounds accompanied by tears. Moreover, according to this theory, these distressing vocalizations may be internalized and experienced as panic.

Porges (1998) suggested that the ventral and dorsal vagal complex, two components of the mammalian autonomic nervous system, control and coordinate affective communication and emotional responses. For example, the ventral vagal complex controls vocalization, tears, ventilation via bronchi and facial muscles. According to polyvagal theory, an emotional response to separation activates withdrawal of vagal tone and increases heart rate and respiration. Withdrawal of vagal tone (i.e., parasympathetic activity) has also been put forth as an explanation for the somatic symptoms of panic attack (George et al., 1989).

Both polyvagal theory and separation-distress describe how gender differences may affect the activation or inhibition of emotional responses to social engagement. For example, Panksepp's (1998) separation-distress theory also suggested that testosterone may lower males' emotional sensitivity to pain and reduce distressing vocalizations, thereby explaining some of the gender differences in the prevalence of panic.

Conclusion

Several studies indicate a higher female-to-male ratio in panic disorder. Various theoretical explanations for these differences point to possible physiological differences, including the possible influence of sex hormones on respiration.

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References
1. Eaton WW, Kessler RC, Wittchen HU, Magee WJ (1994), Panic and panic disorder in the United States. Am J Psychiatry 151(3):413-420.
2. George DT, Nutt DJ, Walker WV et al. (1989), Lactate and hyperventilation substantially attenuate vagal tone in normal volunteers. A possible mechanism of panic provocation? Arch Gen Psychiatry 46(2):153-156.
3. Gittelman R, Klein DF (1984), Relationship between separation anxiety and panic and agoraphobic disorders. Psychopathology 17(suppl 1):56-65.
4. Harrison WM, Sandberg D, Gorman JM et al. (1989), Provocation of panic with carbon dioxide inhalation in patients with premenstrual dysphoria. Psychiatry Res 27(2):183-192.
5. Joyce PR, Bushnell JA, Oakley-Browne MA et al. (1989), The epidemiology of panic symptomatology and agoraphobic avoidance. Compr Psychiatry 30(4):303-312.
6. Katerndahl DA, Realini JP (1993), Lifetime prevalence of panic states. Am J Psychiatry 150(2):246-249.
7. Kessler RC, McGonagle KA, Zhao S et al. (1994), Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 51(1):8-19.
8. Klein DF (1993), False suffocation alarms, spontaneous panics, and related conditions. An integrative hypothesis. Arch Gen Psychiatry 50(4):306-317 [see comments].
9. Lipsitz JD, Martin LY, Mannuzza S et al. (1994), Childhood separation anxiety disorder in patients with adult anxiety disorders. Am J Psychiatry 151(6):927-929.
10. Maier W, Buller R (1988), One-year follow-up of panic disorder. Outcome and prognostic factors. Eur Arch Psychiatry Neurol Sci 238(2):105-109.
11. Panksepp J (1998), Affective Neuroscience: The Foundations of Human and Animal Emotions. New York: Oxford University Press.
12. Papp LA, Martinez JM, Klein DF et al. (1997), Respiratory psychophysiology of panicdisorder: three respiratory challenges in 98 subjects. Am J Psychiatry 154(11):1557-1565[see comment].
13. Porges SW (1998), Love: an emergent property of the mammalian autonomic nervous system. Psychoneuroendocrinology 23(8):837-861.
14. Reed V, Wittchen HU (1998), DSM-IV panic attacks and panic disorder in a community sample of adolescents and young adults: how specific are panic attacks? J Psychiatr Res 32(6):335-345.
15. Sandberg D, Endicott J, Harrison W et al. (1993), Sodium lactate infusion in late luteal phase dysphoric disorder. Psychiatry Res 46(1):79-88.
16. Seeman MV (1997), Psychopathology in women and men: focus on female hormones. Am J Psychiatry 154(12):1641-1647 [see comment].
17. Sheikh JI, Leskin GA, Klein DF (2002), Gender differences in panic disorder: findings from the National Comorbidity Survey. Am J Psychiatry 159(1):55-58 [see comment].
18. Stein MB, Schmidt PJ, Rubinow DR, Uhde TW (1989), Panic disorder and the menstrual cycle: panic disorder patients, health control subjects, and patients with premenstrual syndrome. Am J Psychiatry 146(10):1299-1303.
19. Yonkers KA, Zlotnick C, Allsworth J et al. (1998), Is the course of panic disorder the same in women and men? Am J Psychiatry 155(5):596-602.


 
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