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

Abstract

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. We posited "that a physiologic misinterpretation by a suffocation monitor misfires an evolved suffocation alarm system. This produces sudden respiratory distress followed swiftly by a brief hyperventilation, panic, and the urge to flee. Carbon dioxide hypersensitivity is seen as due to the deranged suffocation alarm monitor. If other indicators of potential suffocation provoke panic, this theoretical extension is supported." In the original paper, we tested "the theory by examining Ondine's curse as the physiologic and pharmacologic converse of panic disorder, splitting panic in terms of symptomatology and challenge studies, reevaluating the role of hyperventilation, and reinterpreting the contagiousness of sighing and yawning, as well as mass hysteria." (Klein, 1993) Original SFA focused on relating the observed lactate and carbon dioxide hypersensitivity in panic disorder to a putative dysfunction in a hypothesized suffocation alarm. At the time, the underlying pathophysiology that might connect the apparent disparate "phenomena of panic during relaxation and sleep, late luteal phase dysphoric disorder, pregnancy, childbirth, pulmonary disease, separation anxiety, and treatment", was unknown.

Experiencing neonatal maternal separation increased the seizure threshold in adult male mice: Involvement of the opioid system

“…Under stressful conditions, the opioid system undergoes considerable changes that contribute to the regulation of several behaviors such as nociception, addiction, and seizure susceptibility [9][10][11]. In this regard, recent studies reported that experiencing adversity during childhood such as MS induced long-lasting alterations in the regulation of the endogenous opioid system in both humans and animals [12,13]. In this respect, previous research reported that MS stress reduced the pain threshold in animals and that this effect was correlated with hypofunction of the opioid system in the CNS [14][15][16].…”

Panico: nosografia di un'entità, clinica di un disturbo

“…Ad oggi non vi sono evidenze sufficienti per l'identificazione di un locus genetico altamente correlato alla sintomatologia del DP ed i substrati anatomofunzionali responsabili della patogenesi del disturbo rimangono ancora poco conosciuti (Perna et al, 2014;Santos et al, 2015). L'ipotesi di una disfunzione del sistema degli oppioidi endogeni o degli endocannabinoidi non ha ancora guadagnato larghi consensi (Bowers et al, 2012;Preter et al, 2014). Il fumo di sigaretta è un riconosciuto fattore di rischio per l'insorgenza del DP (Moreno et al, 2014;Bakhshaie et al, 2016).…”

Real-world Evaluation of a Novel Technology-enabled Capnometry-assisted Breathing Therapy for Panic Disorder

“…Growing evidence suggests that respiratory dysregulation is a central feature of PD. Klein and colleagues' 'suffocation false alarm' hypotheses regarding carbon dioxide hypersensitivity set the stage for the examination of the respiratory irregularities associated with panic disorder and related conditions 9,10 . In the case of panic disorder, chronic hyperventilation, lower end tidal CO 2 levels, respiratory rate and tidal volume irregularities, sighing, and breath-holding are characteristic features 11 .…”