Respiration in Children at Risk for Panic Disorder

Pine et al¹ investigated the relationships between respiratory regulation and childhood anxiety disorders. They found that children with childhood anxiety disorders exhibited greater changes in somatic symptoms after CO₂ inhalation, and that those who developed panic symptoms had enhanced respiratory rate increases in response to CO₂ breathing, and elevated mean tidal volume levels and more variability in respiratory rate during room-air breathing. Similar findings have been reported in adults with panic disorder,² supporting the idea of common pathophysiological mechanisms. However, the question remains open as to whether respiratory dysregulation can be considered a biological trait marker of panic spectrum disorders. We³ have found behavioral hyperreactivity to CO₂ in healthy first-degree relatives of patients with panic disorder. In their study on a comparable study population, Coryell et al⁴ reported an abnormal physiologic regulation of respiration to occur. These studies provide initial evidence for respiration dysregulation as a trait marker for panic disorder. To further test this hypothesis, we are comparing dynamic respiration physiology in the healthy children of patients with panic disorder (C-PD) and in healthy children of subjects without psychiatric diagnoses (C-HS). Our study and preliminary results are summarized. We recruited 14 C-PD (mean ± SD age: 12.4 ± 3.1 years; 6 girls and 8 boys) and 20 C-HS (mean ± SD age: 12.3 ± 2.2 years; 12 girls and 8 boys). Parents and children were examined by structured diagnostic interviews for psychiatric disorders. Respiratory physiology was assessed by a stationary testing system (Quark b2; Cosmed, Rome, Italy) that allowed us to monitor respiratory functioning and pulmonary gas exchange on a breath-by-breath basis according to the latest recommendations of the American Thoracic Society and the European Respiratory Society. After obtaining written informed consent from both parents, each child was connected to the respiratory testing system by an open face mask and tested for 15 minutes between 4 PM and 6 PM according to a standardized procedure to minimize any confounding influences.⁵ Before starting respiratory testing, baseline anxiety was assessed by the State-Trait Anxiety Inventory for state anxiety, and visual analog scales for anxiety were administered immediately before, during, and at the end of the testing procedure. For data analyses, the first 3 minutes of registration were discarded and the artifacts removed while blinded to the diagnoses of the parents and children. The respiratory parameters comprised respiratory rate, tidal volume (TV), minute ventilation (MV), MV/end tidal O₂ (an index of oxygen chemosensitivity), MV/end tidal CO₂ (an index of CO₂ chemosensitivity), and TV/inspiratory time (inspiratory drive). For each respiratory parameter we calculated the mean, the average within-subject SDs, an indicator of the variabilty of the measure, and the approximate entropy,⁶ a complex indicator of the disorder of the measure. Nonparametric statistics were used. Children in the 2 groups did not differ in age, sex distribution, weight, height, State-Trait Anxiety Inventory scores, visual analog scale scores. Six C-PD (43%) and 3 C-HS (15%) had anxiety disorders. Respiratory rate (± SD) was higher in C-PD (20 ± 3.4) than in C-HS (16.8 ± 3.7) (z = 2.1, P<.04). Irregularities in respiratory measures were higher in the C-PD than in the C-HS group (Table 1). Differences in the irregularities remained significant even after excluding children with anxiety disorders from the analysis. The preliminary results of our study parallel the results of Pine et al¹ and support the idea that irregular or disordered breathing might be a trait marker of familial vulnerability to panic disorder. If confirmed, this finding could help identify children at risk for panic disorder. The aim is to develop a prevention program and to determine panic phenotypes for genetic studies.