Pathophysiology of Anxiety

The neurocircuitry of anxiety has been postulated to arise from the amygdala, the brain area that registers the emotional significance of environmental stimuli and stores emotional memories. The efferent pathways from the central nucleus of the amygdala travel to a multiplicity of critical brain structures, including the parabrachial nucleus (resulting in dyspnea and hyperventilation), the dorsomedial nucleus of the vagus nerve and nucleus ambiguous (activating the parasympathetic nervous system), and the lateral hypothalamus (resulting in SNS activation). Through reciprocal neuronal pathways connecting the amygdala to the medial prefrontal cortex, cognitive experience of the specific anxiety disorder differs, although fear symptoms may overlap. During panic attacks the fear is of imminent death; in social phobia, the fear is of embarassment; in postraumatic stress disorder, the traumatic memory is remembered or reexperienced; in obsessive-compulsive disorder, obsessional ideas recur and intrude; and in generalized anxiety disorder, anxiety is "free-floating" (i.e., not conditioned to specific situations or triggers).

Described in the past with terms such as cardiac neurosis, irritable heart syndrome, battle fatigue, and soldier's heart, panic disorder is the anxiety disorder most often associated with cardiovascular symptoms of chest pain, tachycardia, and dyspnea. Discrete panic attacks can be induced in the laboratory setting, especially in patients with panic disorder, by a variety of stimuli: sodium lactate, caffeine, isoproterenol, serotonin receptor agonist m-chlorophenylpiperazine (m-CPP), cholecystokinin tetrapeptide (CCK₄), inhalation of CO₂-enriched air, and voluntary acute hyperventilation of room air. The common element among these disparate inducers may be their ability to stimulate the respiratory rate with the induction of an accompanying subjective sense of breathlessness.

Although some researchers have proposed that patients with panic disorder have only a heightened sensitivity to and develop a learned intolerance of tachypnea, the higher concordance rate of panic disorder observed in monozygotic as compared with dizygotic twins and evidence of altered respiratory rhythym during sleep provide proof of a genetic diathesis and a biological abnormality, respectively, underlying the phenotype of panic disorder.

See also: Depression and Comorbid Medical Illness Depression and Cardiovascular Disease: Clinical Samples Pathophysiology Anxiety Disorders and Cardiovascular Disease Diminished Heart Rate Variability