Acute treatment with the PDE4 inhibitor roflumilast improves verbal word memory in healthy old individuals: a double-blind placebo-controlled study.

There is ample evidence that phosphodiesterase 4 (PDE4) inhibition can improve memory performance in animal studies. In the present study, we examined the acute effects of the PDE4 inhibitor roflumilast on memory performance in healthy individuals (60-80 years of age). We tested the effects of acute roflumilast administration (100, 250, 1000 μg) in a double-blind, placebo-controlled, 4-way crossover design.

Acute administration of roflumilast enhances sensory gating in healthy young humans in a randomized trial.

Introduction: Sensory gating is a process involved in early information processing which prevents overstimulation of higher cortical areas by filtering sensory information. Research has shown that the process of sensory gating is disrupted in patients suffering from clinical disorders including attention deficit hyper activity disorder, schizophrenia, and Alzheimer's disease. Phosphodiesterase (PDE) inhibitors have received an increased interest as a tool to improve cognitive performance in both animals and man, including sensory gating.

Phosphodiesterase Inhibition and Regulation of Dopaminergic Frontal and Striatal Functioning: Clinical Implications.

Background: The fronto-striatal circuits are the common neurobiological basis for neuropsychiatric disorders, including schizophrenia, Parkinson's disease, Huntington's disease, attention deficit hyperactivity disorder, obsessive-compulsive disorder, and Tourette's syndrome. Fronto-striatal circuits consist of motor circuits, associative circuits, and limbic circuits. All circuits share 2 common features.

The PDE4 inhibitor roflumilast improves memory in rodents at non-emetic doses.

Enhancement of central availability of the second messenger cAMP is a promising approach to improve cognitive function. Pharmacological inhibition of phosphodiesterase type 4 (PDE4), a group of cAMP hydrolyzing enzymes in the brain, has been shown to improve cognitive performances in rodents and monkeys. However, inhibition of PDE4 is generally associated with severe emetic side-effects.

Treatment of Cognitive Impairment in Schizophrenia: Potential Value of Phosphodiesterase Inhibitors in Prefrontal Dysfunction.

No pharmacological treatment is available to date that shows satisfactory effects on cognitive symptoms in patients diagnosed with schizophrenia. Phosphodiesterase inhibitors (PDE-Is) improve neurotransmitter signaling by interfering in intracellular second messenger cascades. By preventing the breakdown of cAMP and/or cGMP, central neurotransmitter activity is maintained.

The use of EEG parameters as predictors of drug effects on cognition.

It has been shown to be difficult to predict whether cognition-enhancing effects of drugs in animal studies have the same effect in humans. Various issues in translating findings from animal to human studies can be identified. Here we discuss whether EEG could be considered as a possible tool to translate the effects of cognition enhancers across species.

Medically unexplained dyspnoea and panic.

Medically unexplained dyspnoea in the pulmonary setting is often accompanied by considerable levels of anxiety, suggestive of psychopathology, in particular panic disorder (PD). This pilot study investigates the value of the Multidimensional Dyspnea Profile as a tool to facilitate identification of a specific dyspnoea profile suggestive of comorbid PD. The verbal descriptors, feeling depressed, air hunger and concentrating on breathing, significantly differentiated between the two groups of patients with pulmonary disease with and without PD.

Increased plasma corticosterone levels after periaqueductal gray stimulation-induced escape reaction or panic attacks in rats.

The hypothalamo-pituitary-adrenal (HPA) axis is involved in stress, depression and anxiety. Controversy exists on HPA axis activation during panic attacks (PAs). We examined whether the HPA axis is involved in the escape or panic-like response in an animal model of PAs induced by electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats.

Genetic moderation of CO2-induced fear by 5-HTTLPR genotype.

Inhalation of an increased concentration of carbon dioxide (CO(2)) has been shown to induce a state of negative affect in healthy subjects that is closely related to the clinical phenomenon of panic. It has been suggested that the vulnerability to CO(2) is moderated by differences in serotonin (5-HT) activity, caused by a functional polymorphism in the promoter region of the 5-HT transporter (5-HTTLPR) gene. Our aim was to examine the relationship between bi- and tri-allelic 5-HTTLPR genotype and the affective response to different dosages of inhaled CO(2) in healthy volunteers.

Cigarette smoking and 35% CO(2) induced panic in panic disorder patients.

Background: A disproportionately large number of persons with panic disorder (PD) smoke cigarettes compared to people in the general population and individuals with other anxiety disorders. Clinical and epidemiological data suggest that cigarette smoking increases the risk for the development and maintenance of PD. The carbon dioxide (CO(2)) challenge is well established as experimental model for panic.

Objective and subjective measures in recovery from a 35% carbon dioxide challenge.

Objectives: Because hyperventilation, dyspnea, and a feeling of choking are often core features of a panic attack, respiration has been one of the most widely studied physiological parameters in panic disorder (PD) patients. A respiratory subgroup of PD, with distinct etiological pathways, has also been suggested. Investigation of the recovery phase following a respiratory challenge may be a reliable way to establish respiratory impairment in PD patients.

Carbon dioxide-induced emotion and respiratory symptoms in healthy volunteers.

A number of evidences have established that panic and respiration are closely related. Clinical studies indicated that respiratory sensations constitute a discrete cluster of panic symptoms and play a major role in the pathophysiology of panic. The aim of the present study was to explore the phenomenology of an experimental model of panic in healthy volunteers based on the hypothesis that: (1) we can isolate discrete clusters of panic symptoms, (2) respiratory symptoms represent a distinct cluster of panic symptoms, and (3) respiratory symptoms are the best predictor of the subjective feeling of panic, as defined in the DSM IV criteria.

Validation of the electronic Visual Analogue Scale of Anxiety.

Currently, the use of electronic scales is increasing rapidly, which is not surprising considering its accuracy, the ease of use and the increased compliance. The value of Visual Analogue Scales as a mean to objectify subjective variables has long been recognised. The current study aimed to validate the electronic Visual Analogue Scale of Anxiety (eVAAS).

Effects of experimental panic on neuroimmunological functioning.

Objective: Psychoimmunological research in panic disorder (PD) so far focussed on single time point evaluation in resting conditions. No robust evidence for changes in the immune system was found using this method. However, PD is characterized by the occurrence of unexpected panic attacks (PAs).

CO2 challenge induced HPA axis activation in panic.

The hypothalamic-pituitary-adrenal axis (HPA axis) plays a critical role in stress management. Involvement of this physiological axis in the underlying mechanisms of panic disorder (PD) has been suggested. Studies using 35% CO(2) inhalation to provoke panic found no evidence for robust increases in cortisol levels in PD.

CO2 challenge results in hypothalamic-pituitary-adrenal activation in healthy volunteers.

The 35% CO(2) challenge is known to induce symptoms of a panic attack both in panic disorder (PD) patients and healthy volunteers. Although the challenge applies more to PD patients, studies in healthy volunteers provide the opportunity to isolate the physical symptoms from the disorder and to focus on the direct effect from the challenge on stress responsive systems. One of the main stress responsive systems is the hypothalamic-pituitary-adrenal (HPA) axis.

Salivary cortisol in panic: are males more vulnerable?

Objectives: The underlying mechanisms of panic attacks (PA's) are still unclear. Theories focusing on these mechanisms differ in their description of the relationship between panic and fear. The main controversy concerns whether a PA resembles the classical flight response, or whether it is qualitatively different from fear.

Hypothalamic-pituitary-adrenal axis function following a 35% CO2 inhalation in healthy volunteers.

Rationale: The hypothalamic-pituitary-adrenal axis (HPA axis) is a central component of the brain's neuroendocrine response to stress. The extent of increase in cortisol secretion, provides an index of the HPA axis activity, and in this way, objectively reflects perceived stress. In healthy subjects, the 35% CO(2) inhalation does hardly induce stress, as expressed in anxiety.

Mood, prolactin and cortisol responses following intravenous L-tryptophan challenge: evidence for serotonergic vulnerability in first-degree relatives of bipolar patients.

Central serotonergic vulnerability indicated by altered mood and neuroendocrine responses to an intravenous (i.v.) tryptophan (Trp) challenge was assessed in healthy adult unaffected first-degree relatives of bipolar disorder (BD) patients (n = 30) (family history; FH).