The role of prefrontal-subcortical circuitry in negative bias in anxiety: Translational, developmental and treatment perspectives

Abstract

Anxiety disorders are the most common cause of mental ill health in the developed world, but our understanding of symptoms and treatments is not presently grounded in knowledge of the underlying neurobiological mechanisms. In this review, we discuss accumulating work that points to a role for prefrontal-subcortical brain circuitry in driving a core psychological symptom of anxiety disorders - negative affective bias. Specifically, we point to converging work across humans and animal models, suggesting a reciprocal relationship between dorsal and ventral prefrontal-amygdala circuits in promoting and inhibiting negative bias, respectively. We discuss how the developmental trajectory of these circuits may lead to the onset of anxiety during adolescence and, moreover, how effective pharmacological and psychological treatments may serve to shift the balance of activity within this circuitry to ameliorate negative bias symptoms. Together, these findings may bring us closer to a mechanistic, neurobiological understanding of anxiety disorders and their treatment.

Keywords: Anxiety; circuit; negative bias; prefrontal cortex.

Figure 1.

Schematic summarising findings and proposed simplified model of negative affective bias in anxiety. Bi-directional excitatory connections between dorsal regions of the mPFC/ACC and the amygdala promote negative bias, while inhibitory connections between ventral regions coupled with the amygdala inhibit negative bias. The ventral inhibitory circuit may only fully develop in adulthood, meaning that adolescence is a period of high vulnerability to negative bias. Successful treatments (SSRIs and CBT) may be effective via promotion of the ventral circuit and inhibition of the dorsal circuit. ACC: anterior cingulate cortex; mPFC: medial prefrontal cortex; CBT: cognitive-behavioural therapy; SSRI: selective serotonin reuptake inhibitor.