Prefrontal dysfunction during emotion regulation in generalized anxiety and panic disorders

Abstract

Background The mechanisms that contribute to emotion dysregulation in anxiety disorders are not well understood. Two common disorders, Generalized Anxiety Disorder (GAD) and Panic Disorder (PD), were examined to test the hypothesis that both disorders are characterized by hypo-activation in prefrontal cortex (PFC) during emotion regulation. A competing hypothesis that GAD in particular is characterized by PFC hyper-activation during emotion regulation (reflecting overactive top-down control) also was evaluated. Methods Twenty-two medication-free Healthy Control (HC), 23 GAD, and 18 PD participants underwent functional magnetic resonance imaging (fMRI) during a task that required them to reappraise (i.e., reduce) or maintain emotional responses to negative images. Results GAD participants reported the least reappraisal use in daily life, and reappraisal use was inversely associated with anxiety severity and functional impairment in these participants. During fMRI, HC demonstrated greater activation during both reappraisal and maintenance than either GAD or PD (who did not differ) in brain areas important for emotion regulation (e.g., dorsolateral and dorsomedial PFC). Furthermore, across all anxious participants, activation during reappraisal in dorsolateral and dorsomedial PFC was inversely associated with anxiety severity and functional impairment. Conclusions Emotion dysregulation in GAD and PD may be the consequence of PFC hypo-activation during emotion regulation, consistent with insufficient top-down control. The relationship between PFC hypo-activation and functional impairment suggests that the failure to engage PFC during emotion regulation may be part of the critical transition from dispositionally high anxiety to an anxiety disorder.

A systematic review of fMRI studies in generalized anxiety disorder: Evaluating its neural and cognitive basis

“…These findings are compatible with what Ball et al (Ball et al, 2013) have suggested about GAD dysfunction in emotional regulation process: the inability to sufficiently engage PFC in the service of emotion regulation could be a consequence of a chronic over-responsiveness of limbic circuitry that would, in turn, fatigue the topdown system, rendering it unable to effectively exert control when needed (Ball et al, 2013). Thus, the more chronic and severe the pathology, the less the PFC would be activated.…”

“…For the Reappraise condition, participants were asked to 'change the way that you think about the picture in order to decrease your negative emotions'. Suggested reappraisal strategies included generating a positive interpretation or taking a more detached perspective (Ball et al, 2013). As results, patients with GAD and PD demonstrated less dorsolateral and dorsomedial PFC activation than healthy controls during cognitive modulation of emotion (for both maintenance and reappraisal processes) and those with the least PFC activation reported the greatest anxiety severity and impairment.…”

“…In a recent study by Ball et al (Ball et al, 2013) 28 GAD patients, 18 panic disorder (PD) patients and 23 controls were asked to reappraise or maintain emotional responses to negative images selected from the International Affective Picture System (Lang et al, 2008). Reappraisal or 'changing how we think about a situation in order to decrease its emotional impact' (Gross, 2013) is one of the most studied forms of emotion regulation (Ball et al, 2013). Two processes were examined with the emotional regulation task: in each trial, individuals either maintained or reappraised their emotional responses to negative images.…”

Effects of childhood poverty and chronic stress on emotion regulatory brain function in adulthood

“…During reappraisal of negative stimuli, increased activity in the VLPFC, DLPFC, and mPFC regions is associated with diminished amygdala reactivity to negative stimuli as well as decreased perceived negative affect (21). Amygdala and PFC dysregulation has also been observed in populations with mood dysregulation, including depression (22), anxiety disorders (23,24) including posttraumatic stress disorder (25), impulsive aggression (26), and substance abuse (27). Aberrant amygdala reactivity and inefficient or blunted PFC regulatory function are considered a neurobiological mechanism involved in impaired emotion regulation in these psychiatric disorders.…”

Influence of 5-HTTLPR genotypes on structural and functional connectivity within amygdala-prefrontal cortex circuitry

“…Multi-modal neuroimaging studies provide considerable support for abnormalities in the structure, function, and functional connectivity of the PFC and amygdala in these disorders [5][6][7][8][9] . In addition, recent studies have also implicated abnormalities in the white matter connections between the PFC and amygdala in anxiety and depression, particularly in the ventral prefrontal white matter [10,11] .…”