ISSN 2051-8315
Psychopathology Review
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 Volume 3, Issue 1, 77-109, 2015
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A Cognitive-Neuropsychological Account of Treatment Action in Anxiety: Can We Augment Clinical Efficacy?

  Andrea Reinecke - Department of Psychiatry, University of Oxford, Oxford, UK
  Catherine Harmer - Department of Psychiatry, University of Oxford, Oxford, UK

Volume 3, Issue 1, 2015, Pages 77-109

Background: Anxiety disorders are common and disabling conditions. First-line pharmacological treatment with selective-serotonin-reuptake inhibitors (SSRI) and psychological treatment with cognitive-behaviour therapy (CBT) are effective intervention approaches, but not all patients respond, and relapse rates remain relatively high.
Aims: To identify cognitive and neurobiological mechanisms of action of pharmacological and psychological standard-ofcare treatments for anxiety disorders, to then logically derive potential add-on treatment ingredients that might serve to augment such effects.
Method: We summarise key published work that examined cognitive and neurobiological markers of anxiety disorders and the effects of SSRI and CBT on such parameters. We also discuss potential neuropsychological mechanisms of action of both treatments, and we suggest candidate add-on ingredients likely to improve such actions, based on their key effects.
Results: Anxiety disorders have been associated with hypervigilance for threat followed by an avoidance of deeper processing. Such effects appear to be underpinned by increased activation in brain areas involved in attention and monitoring, such as amygdala, insula, occipital cortex and dorsomedial prefrontal cortex, as well as alterations in areas implicated in emotion regulation, including lateral and ventral prefrontal cortex. Converging evidence suggests that both SSRI and CBT modulate cognitive bias and underlying functional abnormalities early during treatment, and that such changes moderate recovery from anxiety.
Conclusions: Pharmacological and psychological standard-of-care treatments for anxiety disorders seem to act by targeting cognitive bias early during treatment. A range of pharmacological and neurostimulation strategies known to impair fear memory reconsolidation or to improve fear extinction may have potential to improve the effects of psychological intervention. Such approaches might ultimately help to develop more effective, more economic treatment formats.

Table of Contents
Cognitive and Neurobiological Markers of Anxiety
 Cognitive Markers
 Neurobiological Markers
Sensitivity of Cognitive and Neurobiological Anxiety Markers to Standard Treatments
 The Effects of Pharmacological Treatments
 The Effects of Cognitive-Behaviour Therapy
Mechanisms of Action of Anxiety Treatments – a Cognitive-Neuropsychological Model
Implications: Treatment Combination Approaches
 Selective Serotonin Reuptake Inhibitors
 Yohimbine and Propranolol
 Physical Exercise
 Computerised Attentional Bias Modification
 Minimally Invasive Brain Stimulation
Future Directions

Correspondence to
Andrea Reinecke, Department of Psychiatry, Warneford Hospital, Oxford OX37JX, UK.

anxiety, threat processing, MRI, amygdala, cognitive-behaviour therapy, SSRI, glucocorticoids, cycloserine, propranolol, tDCS

Received 20 Nov 2013; Revised 19 Jan 2014; Accepted 18 Feb 2014; In Press 1 Oct 2015

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