The role of the sympathetic nervous system, neuroinflammation and alterations of the brain in panic disorder

Panic disorder is characterized by recurrent unexpected panic attacks, with a panic attack being described as an abrupt surge of intense fear or discomfort that reaches a peak within minutes, during which time specific symptoms occur. Such symptoms include palpitations, sweating, shaking, sensations of shortness of breath, feelings of choking, chest pain or discomfort, nausea, dizziness, chills or heat sensations, paresthesias, derealization or depersonalization, fear of losing control, and fear of dying. Persistent concern or worrying of additional attacks or significant maladaptive change in behavior related to the attacks should follow at least one of the attacks [1]. Although the exact etiology of panic disorder is still unknown, the sympathetic nervous system and its influence on the immune system seem to play a central role in the development and progression of the disorder. Enhanced inflammation represented as an increase in pro-inflammatory cytokines has been reported in patients diagnosed with panic disorder [2]. Furthermore, increased systemic inflammation can lead to neuroinflammation, which can ultimately lead to alterations in brain structure and function [3], with recent findings supporting alterations in limbic and prefrontal cortical structures in panic disorder [4]. In this chapter, we will revise the influence of the sympathetic nervous system on inflammatory responses involving proinflammatory cytokines, and neuroinflammation which may ultimately lead to alterations in the structure and function of specific brain regions that are involved in the etiology of panic disorder.