A mechanistic model for individualised treatment of anxiety disorders based on predictive neural biomarkers. Issue 5 (24th April 2020)

• Record Type: Journal Article
• Authors: Brehl, Anne-Kathrin; Kohn, Nils; Schene, Aart Herman; Fernández, Guillen
• Is Part Of: Psychological medicine. Volume 50:Issue 5(2020)
• Page Start: 727
• Page End: 736
• Publication Date: 2020-04-24
• Subjects: Anxiety, -- PTSD, -- social phobia, -- panic disorder, -- generalized anxiety disorder, -- noradrenaline, -- locus coeruleus, -- PFC, -- amygdala, -- exposure therapy; Psychiatry -- Periodicals; Medicine and psychology -- Periodicals; Clinical psychology -- Periodicals; 616.89
• DOI: 10.1017/S0033291720000410
• Languages: English
• ISSNs: 0033-2917

Abstract

Abstract: Increased amygdala responsiveness is the hallmark of fear and a characteristic across patients with anxiety disorders. The amygdala is embedded in a complex regulatory circuit. Multiple different mechanisms may elevate amygdala responsiveness and lead to the occurrence of an anxiety disorder. While top-down control by the prefrontal cortex (PFC) downregulates amygdala responses, the locus coeruleus (LC) drives up amygdala activation via noradrenergic projections. This indicates that the same fearful phenotype may result from different neural mechanisms. We propose a mechanistic model that defines three different neural biomarkers causing amygdala hyper-responsiveness in patients with anxiety disorders: (a) inherent amygdala hypersensitivity, (b) low prefrontal control and (c) high LC drive. First-line treatment for anxiety disorders is exposure-based cognitive behavioural therapy, which strengthens PFC recruitment during emotion regulation and thus targets low-prefrontal control. A treatment response rate around 50% (Loerinc et al., 2015, Clinical Psychological Reviews, 42, 72–82) might indicate heterogeneity of underlying neurobiological mechanisms among patients, presumably leading to high variation in treatment benefit. Transforming insights from cognitive neuroscience into applicable clinical heuristics to categorise patients based on their underlying biomarker may support individualised treatment selection in psychiatry. We review literature on the three anxiety-related mechanisms and present a mechanistic model that may serve as a rational for pathology-based diagnostic and biomarker-guided treatment selection in psychiatry.