M. A. Van Duinen

Respiratory patterns in panic disorder reviewed: a focus on biological challenge tests

Objective:  To provide a systematic review of studies investigating respiration in PD and comments on relative inconsistencies.

Desynchrony of fear in phobic exposure

Intuitively, phobic exposure would seem to be a very stressful experience. However, it is not clear whether the characteristic feature of a classic stress response, activation of the hypothalamic-pituitary-adrenal (HPA) axis, is present in phobic fear. Some instances of phobic fear have been found to be accompanied by robust increases in cortisol, whereas in other instances a dissociation between subjective-behavioural arousal and the HPA-axis has been found. The latter is referred to as desynchrony of fear. The aim of the current study was to test the hypothesis that phobic fear is similar to normal fear and, as such, is accompanied by a robust increase in cortisol values. In all, 16 spider phobic subjects and 16 healthy controls participated in the study. During and following a standardised stepwise exposure paradigm, saliva samples were collected for cortisol determination. In contrast to the controls, the spider phobics reacted with a strong fear reaction to the spiders. However, cortisol levels remained unaffected. The phobic response did not resemble the classic ‘fight or flight’ response. Some suggest that the HPA-axis response has become extinguished in modern man. Yet, it is possible that phobic fear is not a derivative of an ancient fear but rather a separate entity that relies on other neuroendocrinological systems.

Acute administration of roflumilast enhances immediate recall of verbal word memory in healthy young adults

ABSTRACT The need for new and effective treatments for dementia remains indisputably high. Phosphodiesterase inhibitors (PDE‐Is) have proven efficacy as cognitive enhancers based on their positive effects in numerous preclinical studies. Especially the PDE4 subfamily is of interest due to its expression in the hippocampus, the key structure for memory formation. The current study investigates the memory enhancing effects of the clinically approved PDE4‐I roflumilast in a test battery including the Verbal Learning Task (VLT) combined with electroencephalography (EEG) recording. This acute study was conducted according to a double‐blind, randomized, placebo‐controlled, 4‐way crossover design. Three capsulated dosages of roflumilast HCl (Daxas) and a placebo were administered in four study periods. Administration occurred 1 h before testing to reach maximal plasma concentrations. Memory performance was assessed using a 30 word Verbal Learning Task. The number of words recalled both immediately and after 45 min and 24 h were included as outcome measures. EEG was recorded during the cognitive tasks on the first day. Different event‐related potentials (ERPs) were considered with special emphasis on P600, as this peak has been related to word learning. Memory performance was significantly improved after acute administration of 100 &mgr;g roflumilast. Specifically, immediate recall performance on the VLT increased 2–3 words, accompanied by an enhanced P600 peak during word presentation at the third learning trial. No side effects typical for PDE4‐Is were reported for the lowest and effective dose of 100 &mgr;g roflumilast. The current proof‐of‐concept study shows for the first time the potential of low‐dose roflumilast administration as a memory enhancer in humans. HighlightsEffects of the PDE4 inhibitor roflumilast on verbal word memory were tested in healthy subjects.Memory performance was measured with the Verbal Learning Task.Immediate recall performance was improved at a non‐emetic dose of 100 &mgr;g.Effect was accompanied by an enhanced P600 peak during word presentation.Acute roflumilast administration improves immediate recall in healthy young human subjects.

Challenging Anxiety: A Focus on the Specificity of Respiratory Symptoms

Physiological symptoms are characteristic features of anxiety states. Presumably, specific psychophysiological profiles differentiate between anxiety disorders, which would offer potential for diagnostic purposes. Abundant evidence points to a causal relationship between panic disorder and instability of respiratory regulation. However, the specificity of most measures that indicate aberrant functioning of the respiratory system in PD can be questioned. Possibly, the traditional measures of respiratory functioning are too restricted. The underlying respiratory vulnerability in PD seems to constitute a subtle, unstable trait, which calls for more sensitive and sophisticated measures of respiratory variability and chaos. To increase the probability of finding parameters with diagnostic specificity, the application of disorder specific challenge paradigms is recommended.