Cortico-Limbic Responses to Masked Affective Faces Across Ptsd, Panic Disorder, and Specific Phobia

Abstract

Background Exaggerated amygdala and reduced ventromedial prefrontal cortex (vmPFC) responsiveness during emotional processing have been reported in studies examining individual anxiety disorders. Studies are needed, however, that directly compare activation of amygdalo-cortical circuitry across multiple anxiety disorders within the same study. Here we compared cortico-limbic neurocircuitry across three different anxiety disorders using a well-validated emotional probe task. Methods Sixty-five adult volunteers, including 22 healthy controls (HC) and participants meeting DSM-IV criteria for either post-traumatic stress disorder (14 PTSD), panic disorder (14 PD), specific animal phobia (15 SP) underwent functional magnetic resonance imaging (fMRI) at 3T while passively viewing backward-masked images of faces expressing fear, happy, and neutral emotions. Results A group comprising all three anxiety disorders showed greater activation within the left amygdala and reduced activation within the vmPFC compared to the HC group during the masked fear versus neutral condition. Pairwise group comparisons showed that amygdala activation only reached significance for the PTSD versus HCs, while decreased vmPFC was only evident for SP and PD groups versus the HC group. Furthermore, activation did not differ among the anxiety groups when contrasted directly with one another. A similar pattern was observed for masked happy versus neutral faces. Conclusions Exclusive of specific diagnostic category, anxiety disorders were generally associated with increased activation of the amygdala and reduced activation within vmPFC. Categorical distinctions were generally weak or not observed and suggest that functional differences may reflect the magnitude of responses within a common neurocircuitry across disorders rather than activation of distinct systems.

The impact of cue learning, trait anxiety and genetic variation in the serotonin 1A receptor on contextual fear

“…In agreement with the earlier findings (Baas, 2013), in the initially unaware subjects trait anxiety was correlated with startle responding to the threat context after they were made aware of the CS-US contingency through instructions. This finding is in line with observed hypoactivity in brain areas associated with down-regulation of fear (the ventro-medial prefrontal cortex) in neuroimaging studies in patients with anxiety disorders like panic disorder and post-traumatic stress disorder (PTSD, Killgore et al, 2014;Rougemont-Bücking et al, 2011). The inhibition of contextual fear after learning about more specific predictors of threat (safety signal; depends on adaptive regulation in a relatively ambiguous situation that is likely to involve the same regions (Rougemont-Bücking et al, 2011).…”

Precision psychiatry: a neural circuit taxonomy for depression and anxiety

“…Amygdala hyperactivation during non-conscious threat processing has been reported in current depressive disorder, 39 generalised anxiety disorder, 40 generalised social phobia– anxiety disorder, 40–42 specific phobia, 43 and panic disorder. 40,43 ACC hypoactivation during threat processing has been observed in generalised anxiety disorder 33,44 and generalised social anxiety, 44 and task context-dependent ACC hyperactivation in anxiety disorder. 33 …”

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“…The role of the amygdala in the etiology and maintenance of PTSD and other fear-and anxiety-based disorders has been very well characterized in translational neuroscience (Etkin and Wager, 2007). Specifically, amygdala activation in response to threatening stimuli is increased in PTSD, GAD, social anxiety disorder, specific phobia, and PD (Fonzo et al, 2015;Killgore et al, 2014;Monk et al, 2008). This heightened amygdala response to stress is associated with increased IL-6 production (Inagaki et al, 2012;Muscatell et al, 2015).…”