There is some experimental evidence to support the existence of a connection between panic and respiration. However, only recent studies investigating the complexity of respiratory physiology have revealed consistent irregularities in respiratory pattern, suggesting that these abnormalities might be a vulnerability factor to panic attacks. The source of the high irregularity observed, together with unpleasant respiratory sensations in patients with panic disorder (PD), is still unclear and different underlying mechanisms might be hypothesized. It could be the result of compensatory responses to abnormal respiratory inputs or an intrinsic deranged activity in the brainstem network shaping the respiratory rhythm. Moreover, since basic physiological functions in the organism are strictly interrelated, with reciprocal modulations and abnormalities in cardiac and balance system function having been described in PD, the respiratory findings might arise from perturbations of these other basic systems or a more general dysfunction of the homeostatic brain. Phylogenetically ancient brain circuits process physiological perceptions/sensations linked to homeostatic functions, such as respiration, and the parabrachial nucleus might filter and integrate interoceptive information from the basic homeostatic functions. These physiological processes take place continuously and subconsciously and only occasionally do they pervade the conscious awareness as ‘primal emotions’. Panic attacks could be the expression of primal emotion arising from an abnormal modulation of the respiratory/homeostatic functions.

Panic disorder (PD) is a highly prevalent, debilitating disorder. The heritability of the disease has been estimated by twin studies to be between 30 and 60%. The vulnerability for PD overlaps with an increased risk of bipolar disorder in some families. Classical genetic methods such as linkage analysis and association studies have not yet identified genetic risk factors beyond doubt. However, two independent studies confirm linkage of a specific syndrome characterized by PD, bladder problems, severe headaches, mitral valve prolapse and thyroid dysfunction to genetic markers on chromosome 13q. Association studies, although showing divergent results, give some support to a causative role for the genes encoding for monoamine oxidase A (MAO-A), cholecystokinin (CCK) and catechol-O-methyltransferase (COMT). Finally, a somatic duplication of a 19-Mb region on chromosome 15 has been associated with PD, but this intriguing finding awaits confirmation.

There has been growing interest in the role of serotonin (5-hydroxytryptamine, 5-HT) in anxiety, including pathological states such as panic disorder. The technique of tryptophan depletion (TD), which causes an acute, temporary and reversible reduction in brain 5-HT levels, is a useful minimally invasive paradigm to aid the research of the role of 5-HT in various disorders. This review discusses the evidence supporting the hypothesis that 5-HT function is of importance in the neurobiology of panic disorder and considers in more detail how our understanding has been influenced by work using the technique of TD. Possible avenues for future research are also discussed.

Evidence for implication of cholecystokinin (CCK) in the neurobiology of panic disorder is reviewed through animal and human pharmacological studies. The results of these investigations raise two issues: (i) selectivity of action of CCK-2 agonists in anxiety disorders; and (ii) aberrations of the CCK system in anxiety disorders, both of which are discussed.

Cognitive behavioural therapy (CBT) has been proved to be very effective in the treatment of panic disorder. In this article we attempt to give a brief representation of more recent insights and techniques in the field of cognitive behavioural therapy in the treatment of panic disorder.