A neural systems approach to the study of the respiratory-type panic disorder

Abstract

Panic disorder (PD) patients are exquisitely and specifically sensitive to inhalations of 5-7 % carbon dioxide and infusions of 0.5 M sodium lactate. Another startling feature of clinical panic is the lack of increments of the ‘stress hormones’ corticotropin, cortisol and prolactin. PD is also more frequent in women and shows high comorbidity with childhood separation anxiety, late luteal period dysphoric disorder and depression. The hypothalamuspituitary- adrenal axis is nevertheless activated in fear-like panics marked by palpitations, tremor and sweating, that are devoid of suffocation symptoms. These and other data suggest the existence of both respiratory and non-respiratory types of panic attacks. Increasing evidence suggests, on the other hand, that panics are mediated at midbrain’s dorsal periaqueductal grey matter (DPAG). Therefore, here we summarized data showing that: (1) the DPAG harbors a suffocation alarm system which is activated by low intravenous doses of potassium cyanide (KCN); (2) KCN evokes defensive behaviors that are facilitated by hypercapnia, blocked by lesions of DPAG and attenuated by clinically effective treatments with panicolytics; (3) DPAG stimulations do not change the stress hormones when escape is prevented by stimulating the rats in a small compartment; (4) DPAG-evoked panics responses are facilitated in neonatally-isolated adult rats, a model of childhood separation anxiety; (5) DPAG-evoked panic-like behaviors are facilitated in diestrus phase of rat ovulatory cycle. It is proposed a neural model of panic attacks in which the PAG is the fulcrum of threatening signals from both forebrain and hindbrain. This model emphasizes the role of PAG as a suffocation alarm system.