Towards a translational experimental model of anxiety for pharmacological and psychological treatment development.

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Anxiety symptoms are common in the general population, and patients with anxiety disorders have severe and persistent symptoms that cause significant personal distress, impair everyday function and reduce quality of life. Generalized Anxiety Disorder (GAD) is a severe and long-lasting condition which includes excessive and persistent anxiety and worry, difficulty concentrating and hyper-vigilance. Current treatments for anxiety have limitations. Drug treatments are not effective in all patients, and some produce unwanted side-effects. Research has identified several chemical processes in the brain that might be involved in the development of anxiety, and could be targeted by new, more effective drug treatments. However, existing methods of developing new drug treatments are expensive and rely on extensive development work in small animals, (for example, examining the effects of drugs on patterns of behaviour in animals that 'look like' the anxiety symptoms that we see in human patients). These 'animal models' of anxiety are not effective in predicting which drugs will become successful treatments and which will not, and for every new treatment successfully developed, many more will fail. Thus there is a clinical and economic need to develop better, more efficient ways of evaluating potential new drug treatments in 'human models of anxiety' that are better able to identify those drugs which may be helpful in clinical practice. When healthy humans inhale air enriched with 7.5% carbon dioxide (CO2) they report feeling anxious and nervous, experience increased heart rate and blood pressure and become hypervigilant for threatening information in the environment. This 'CO2 model' mimics (in healthy volunteers) the clinical symptoms that we see in patients with GAD and provides a new test that we can use to evaluate the potential effectiveness of new drug treatments for anxiety. The proposed research will examine i) the potential effectiveness of a range of new promising drug treatments on CO2-induced anxiety in healthy individuals, and ii) whether established drug treatments can limit the negative effects of CO2-inhalation in patients with anxiety disorders. The CO2 model can also be used to evaluate new psychological treatments for anxiety. Cognitive-Behaviour Therapy (CBT) is an effective psychological treatment for anxiety that modifies problematic patterns of thinking and behaviour that underlie anxiety. However CBT is not effective in all patients thus research has moved towards developing improved versions of CBT (so called 'third-wave interventions') that include forms of mental training that help individuals to better control and reduce their worrying thoughts and cope with distressing thoughts when they arise. Though 'third-wave' interventions are effective for depression, their effectiveness for anxiety disorders is unclear, furthermore the 'active ingredient(s)' in these training packages are not well defined. The CO2 model provides an excellent experimental tool that will allow us to examine the extent to which different aspects of 'third-wave treatments' (i.e. attention control vs. coping), reduce elevated feelings of anxiety, physiological arousal and hypervigilance in healthy individuals when they inhale CO2. Finally, access to existing psychological treatments for anxiety is limited, therefore efforts have moved towards developing novel 'computerized' treatment packages that can be delivered on-line and that aim to correct problems with attention control and hypervigilance. So called 'attentional bias modification' computerized training packages have some effectiveness in reducing anxiety, but the extent to which they produce prolonged benefits when stressful situations are encountered is not known. We will examine the effects of an 'attentional bias modification' treatment on CO2-induced anxiety, autonomic arousal and hypervigilance in healthy individuals.