S.02.03 Combinatorial pharmacogenomics provides clinical validity and utility for treating major depression

Abstract

There is a need to improve current treatments for anxiety through developing valid experimental human models of anxiety that allow us to more effectively evaluate novel pharmacological and psychological treatments (and mechanisms of action) in healthy volunteers, prior to evaluation in patient populations. Inhalation of air ‘enriched’ with 7.5% carbon dioxide (CO2) increases selfreport anxiety (worry, tension) and autonomic arousal (heart rate, blood pressure) and provides a novel experimental model of anxiety in healthy humans. Recent evidence from quantitative and qualitative methods suggests that 7.5% CO2 challenge can reliably model core symptoms of anxiety in healthy individuals, including dysfunction in neuropsychological mechanisms that characterise trait anxiety e.g. uncontrollable worry, poor attention control, hyper-vigilance and selective processing of environmental threat. Importantly, the comparable effects of CO2 challenge (in low anxious individuals) and trait anxiety on cognition and emotion processing appear to be independent of elevated state anxiety. Consequently CO2 inhalation may directly challenge neuropsychological mechanisms that characterise generalized trait anxiety rather than transient state anxiety. The model converges with other experimental human anxiety paradigms (e.g. social stress tests and worry induction), but importantly can readily translate into animal paradigms to identify cross-species neural mechanisms that mediate anxious responding. I will summarise evidence from on-going work that is using the CO2 model to evaluate a range of treatment interventions and modalities for anxiety. These include established and potential anxiolytic pharmacological drug treatments, psychological interventions (e.g. cognitive-behavioural attention training), and medical devices that can target prefrontal cortical mechanisms (e.g. trans-cranial direct current stimulation).