Background: Sighs, breaths wit larger tidal volumes than surrounding breaths, have been reported as being more frequent in patients with anxiety disorders.Methods: Sixteen patients wit panic disorder, 15 with generalized anxiety disorder, and 19 normal control subjects were asked to sit quietly for 30 min. Respiratory volumes and timing were recorded wit inductive plethysmography and expired pCO(2), from nasal prongs.Results: Panic disorder patients sighed more and had tonically lower end-tidal pCO(2) than control subjects, whereas generalized anxiety disorder patients were intermediate. sighs defined as >2.0 times the subject mean discriminated groups best. Sigh frequency was more predictive of individual pCO(2) levels than was minute volume. Ensemble averaging of respiratory variables for sequences of breaths surrounding sighs showed no evidence that sighs were triggered by increased pCO(2) or reduced tidal volume in any group. sigh breaths were larger in panic disorder patients than in control subjects. After sighs, pCO(2) and tidal volume did not return to baseline levels as quickly in panic disorder patients as in control subjects.Conclusions: Hypocapnia in panic disorder patient sin related to sigh frequency. In none of the groups was sighing a homeostatic response. panic disorder patients show less peripheral chemoreflex gain than control subjects, which would maintain low pCO(2) levels after sighing. Biol Psychiatry 2001;49:606-614 (C) 2001 Society of Biological Psychiatry.

Objective Because breath holding causes arterial pCO2 to increase, we used it to test the hypothesis that in panic disorder (PD) a biological suffocation monitor is pathologically sensitive. Method Nineteen patients with PD, 17 with generalized anxiety disorder (GAD), and 22 normal controls took deep breaths on signal and held them until a release signal was given 30 seconds later. This was repeated 12 times separated by 60-second normal breathing periods. Results PD patients reported having had in the past more symptoms of shortness of breath when anxious, and more frequent frightening suffocation experiences than the other groups. However, increases in self-rated anxiety between periods of normal breathing and periods of breath holding were similar in all three groups. Skin conductance, blood pressure, and T-wave amplitude reactions to breath holdings were also similar, but heart rate acceleration upon taking a deep breath was greater in GAD patients. Before and after individual breath holdings, end-tidal pCO2 was lower in PD patients than in normal controls; GAD patients were intermediate. Inspiratory flow rate did not differ between groups. Conclusions Our physiological results provide no direct support for an overly sensitive suffocation alarm system in PD. Lower pCO2 may be due to anxiety causing hyperventilation in patients prone to panic.

The ability to relax was assessed in 14 patients with panic disorder (PD) and 15 non-anxious control subjects for 10 min. Before and after relaxation, subjects performed a standardized activating task of talking continuously for 4 min. The fractional decline in reported anxiety, tension, and alertness between the first talking period and the relaxation minimum did not differ between groups, although absolute levels of anxiety and tension were higher for PD patients. The fractional decline in skin conductance between the first talking period and the last minute of relaxation was less for PD patients than control subjects, while their increase in skin temperature was greater. Skin conductance showed a linear decline over the logarithm of relaxation time, the slope of which was less steep for PD patients. Goodness of fit of skin conductance over log time was also significantly poorer for PD patients. Heart rate levels or slopes did not differ between groups. Autonomic differences between PD and control subjects were largely due to six patients who reported having panic attacks during the test and higher pretest anxiety levels. In conclusion, indicators of relaxation were inconsistent. Skin conductance suggested autonomic instability during quiet sitting in patients who panic or who are prone to panic.

The complete absence of handling of male rats during neonatal development (from birth to postnatal day 21) correlates with an impairment of latent inhibition [J. Feldon, I. Weiner, From an animal model of an attentional deficit towards new insights into the pathophysiology of schizophrenia, J. Psychiatr. Res. 26 (1992) 345–366.]. Such nonhandling of rats reportedly also correlates with a decreased expression of reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd) reactivity in the hippocampus in adult rats (6 months of age) when compared with rats of the same age that were handled during the same neonatal period [R.R. Vaid, B.K. Yee, U. Shalev, J.N. Rawlins, I. Weiner, J. Feldon, S. Totterdell, Neonatal nonhandling and in utero prenatal stress reduce the density of NADPH-diaphorase-reactive neurons in the fascia dentata and Ammon's horn of rats, J. Neurosci. 17 (1997) 5599–5609.]. The present study investigated whether such a decrease in NADPHd activity would be detectable at earlier ages. Therefore, the present study assessed the density of nitric oxide (NO) producing neurons in the fascia dentata and Ammon's horn in 28-, 54-, and 118-day-old nonhandled and handled male rats using NADPHd histochemistry and immunohistochemical localization of neuronal isoform of nitric oxide synthase (nNOS), a NADPHd. This showed that in these three age groups, the numbers of NADPHd positive neurons per unit area throughout the hippocampus of rats that received no handling during neonatal development did not differ significantly from those of rats that received regular daily handling. In addition, we found in the rats of 118 days of age that the areal density of nNOS immunopositive neurons in the hippocampus also did not differ significantly between nonhandled and handled rats. Nevertheless, in a parallel study, rats from the same experimental group receiving identical treatments showed the expected impairment of latent inhibition at 4 months of age [R. Weizman, J. Lehmann, S. Leschiner, I. Allmann, T. Stoehr, C. Heidbreder, A. Domeney, J. Feldon, M. Gavish, Long-lasting effect of early handling on the peripheral-type benzodiazepine receptor, Pharmacol. Biochem. Behav. in press.]. These results suggest that nonhandling of rats during the early neonatal period, that does result in impairment in latent inhibition, does not affect the numbers of NO producing neurons in the hippocampus in rats of young ages, including the age of observed impairment of latent inhibition.