Panic, suffocation false alarms, separation anxiety and endogenous opioids

Abstract

This review paper presents an amplification of the suffocation false alarm theory (SFA) of spontaneous panic [Klein DF (1993). False suffocation alarms, spontaneous panics, and related conditions. An integrative hypothesis. Arch Gen Psychiatry; 50:306-17.]. SFA postulates the existence of an evolved physiologic suffocation alarm system that monitors information about potential suffocation. Panic attacks maladaptively occur when the alarm is erroneously triggered. That panic is distinct from Cannon's emergency fear response and Selye's General Alarm Syndrome is shown by the prominence of intense air hunger during these attacks. Further, panic sufferers have chronic sighing abnormalities outside of the acute attack. Another basic physiologic distinction between fear and panic is the counter-intuitive lack of hypothalamic-pituitary-adrenal (HPA) activation in panic. Understanding panic as provoked by indicators of potential suffocation, such as fluctuations in pCO(2) and brain lactate, as well as environmental circumstances fits the observed respiratory abnormalities. However, that sudden loss, bereavement and childhood separation anxiety are also antecedents of "spontaneous" panic requires an integrative explanation. Because of the opioid system's central regulatory role in both disordered breathing and separation distress, we detail the role of opioidergic dysfunction in decreasing the suffocation alarm threshold. We present results from our laboratory where the naloxone-lactate challenge in normals produces supportive evidence for the endorphinergic defect hypothesis in the form of a distress episode of specific tidal volume hyperventilation paralleling challenge-produced and clinical panic.

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision

“…Neurobiological dysfunctions that have been found in anxiety and OCD patients include dysfunctions of serotonin, noradrenaline, dopamine, gamma-aminobutyric acid, cholecystokinin, glutamate, or endogenous opioid receptors or the hypothalamic-pituitary-adrenal (HPA) axis. The reader is referred to comprehensive reviews of the field (Charney and Bremner 1999;Connor and Davidson 1998;Gorman et al 2000;Jetty et al 2001;Hen 2006, 2008;Li et al 2001;Nutt et al 1998;Ressler and Mayberg 2007;Schneier et al 2000;Stein 2000; Also, a maladaptive physiological suffocation alarm system was postulated (Klein 1993;Preter and Klein 2008).…”

Lifelong Opioidergic Vulnerability Through Early Life Separation: A Recent Extension of the False Suffocation Alarm Theory of Panic Disorder

“…This can be experimentally reproduced in adult panic sufferers, but also in children with separation anxiety disorder (Pine et al 2000;Preter and Klein, 2008).…”

“…This was also noted by others, e.g., Faravelli and Pallanti (1989), Kaunonen et al (2000), Milrod et al 2004. We noted that "[p]atients highly comorbid for multiple anxiety disorders are particularly likely to recall childhood SAD (Lipsitz et al, 1994)", and that " [c]laims that separation anxiety equivalently antecedes other anxious states (Van der Molen et al, 1989) may be due to diagnostically ambiguous limited symptom attacks and the unreliability of the questionnaire method". We concluded that "in the only controlled, long-term, direct, blind, clinical interview follow-up of separation-anxious, school-phobic children, the only significant finding was an increased PD rate" (Preter and Klein, 2008) .…”

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We briefly reference previous material on Klein's suffocation false alarm theory (SFA) of panic disorder (Klein, 1993) and its amplification in 2008 (Preter andKlein, 2008). We then discuss a recent finding showing a fundamental difference in opioidergic reactivity to a naloxone challenge in psychiatrically and medically healthy adults, based on the presence or absence of childhood separation/parental loss.

In 1993, Klein published the original SFA theory of panic disorder (Klein, 1993), attempting to integrate the multiplicity of apparently unrelated clinical and laboratory observations.

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“…This suggested a potential missing link: " Klein and Fink (1962) posited a developmental pathophysiological link between [clinical levels of] separation anxiety and PD and subsequent agoraphobia, since 50% of hospitalized agoraphobics reported severe early separation anxiety that often prevented school attendance. Further, panic, in this group, was frequently precipitated by bereavement, or separation [...] (Preter and Klein, 2008). This was also noted by others, e.g., Faravelli and Pallanti (1989), Kaunonen et al (2000), Milrod et al 2004. We noted that "[p]atients highly comorbid for multiple anxiety disorders are particularly likely to recall childhood SAD (Lipsitz et al, 1994)", and that " [c]laims that separation anxiety equivalently antecedes other anxious states (Van der Molen et al, 1989) may be due to diagnostically ambiguous limited symptom attacks and the unreliability of the questionnaire method".…”