Commonalities and differences in the neural substrates of threat predictability in panic disorder and specific phobia

Abstract

Different degrees of threat predictability are thought to induce either phasic fear or sustained anxiety. Maladaptive, sustained anxious apprehension is thought to result in overgeneralization of anxiety and thereby to contribute to the development of anxiety disorders. Therefore, differences in threat predictability have been associated with pathological states of anxiety with specific phobia (SP) representing phasic fear as heightened response to predictable threat, while panic disorder (PD) is characterized by sustained anxiety (unpredictable threat) and, as a consequence, overgeneralization of fear. The present study aimed to delineate commonalities and differences in the neural substrates of the impact of threat predictability on affective processing in these two anxiety disorders.Twenty PD patients, 20 SP patients and 20 non-anxious control subjects were investigated with an adapted NPU-design (no, predictable, unpredictable threat) using whole-head magnetoencephalography (MEG).Group independent neural activity in the right dlPFC increased with decreasing threat predictability. PD patients showed a sustained hyperactivation of the vmPFC under threat and safety conditions. The magnitude of hyperactivation was inversely correlated with PDs subjective arousal and anxiety sensitivity. Both PD and SP patients revealed decreased parietal processing of affective stimuli. Findings indicate overgeneralization between threat and safety conditions and increased need for emotion regulation via the vmPFC in PD, but not SP patients. Both anxiety disorders showed decreased activation in parietal networks possibly indicating attentional avoidance of affective stimuli. Present results complement findings from fear conditioning studies and underline overgeneralization of fear, particularly in PD.

Exercise decreases defensive responses to unpredictable, but not predictable, threat

“…Fear and anxiety have been distinguished at the neural level in both humans (Herrmann, Beier, et al, 2016; Herrmann, Boehme, et al, 2016; Klahn et al, 2016, 2017) and animals (for reviews: Davis et al, 2010; Walker, Toufexis, & Davis, 2003). Additionally, a plethora of psychopharmacological (Bradford, Shapiro, & Curtin, 2013; Grillon, Baas, Pine, et al, 2006; Grillon et al, 2015; Grillon, Chavis, Covington, & Pine, 2009; Hogle, Kaye, & Curtin, 2010; Moberg & Curtin, 2009) and clinical (Bradford, Curtin, & Piper, 2015; Chamberlain et al, 2013; Gorka et al, 2013; Gorka et al, 2016; Gorka, Lieberman, Shankman, & Phan, 2017; Gorka, Liu, Sarapas, & Shankman, 2015; Grillon et al, 2008; Grillon, Pine, Lissek, et al, 2009; Grillon, Morgan, Davis, & Southwick, 1998; Hogle et al, 2010; Klahn et al, 2016, 2017; Moberg & Curtin, 2009; Schroijen et al, 2016) studies have advanced knowledge of mental health and treatment by comparing these two states. Indeed, fear and anxiety distinctly characterize psychiatric disorders (American Psychiatric Association, 2013) and constitute separate negative valence system constructs in the National Institutes of Health Research Domain Criteria (NIH RDoC).…”

“…Fear and anxiety have been explored experimentally using the Neutral-Predictable-Unpredictable (NPU) threat test (Bradford et al, 2013; Chamberlain et al, 2013; Gorka, Nelson, Sarapas, et al, 2013; Gorka, Nelson & Shankman, 2013; Gorka et al, 2015; Gorka et al, 2017; Gorka, Lieberman, Phan, & Shankman, 2016; Grillon et al, 1998; Grillon, Baas, Pine, et al, 2006; Grillon, Pine, Baas, et al, 2006; Grillon, Chavis, Covington, et al, 2009; Grillon, Pine, Lissek, et al, 2009 Grillon et al, 2008, 2011, 2015; Grillon, Cordova, Morgan, Charney, & Davis, 2004; Herrmann, Beier, et al, 2016; Herrmann, Boehme, et al, 2016; Hogle et al, 2010; Kaye, Bradford, & Curtin, 2016; Klahn et al, 2016, 2017; Klinkenberg et al, 2016; Moberg & Curtin, 2009; Nelson, Hodges, Hajcak, & Shankman, 2015; Schroijen et al, 2016). The NPU threat test consists of a neutral condition (N), and two threat conditions that involve administration of predictable (P) and unpredictable (U) shocks (Schmitz & Grillon, 2012).…”

“…With regard to internalizing disorders, the NPU threat test offers a valuable means to explore clinically relevant mechanisms (Ballard et al, 2014; Gorka, Nelson & Shankman, 2013; Gorka et al, 2015, 2017; Grillon et al, 1998, 2008; Grillon, Pine, Lissek, et al, 2009; Klahn et al, 2016, 2017). For example, individuals with posttraumatic stress (Grillon, Pine, Lissek, et al, 2009) and panic disorders (Gorka et al, 2013; Grillon et al, 2008; Nelson et al, 2013) display elevated anxiety-potentiated, but not fear-potentiated, startle.…”

“…Fear is a phasic response to a predictable threat, and anxiety is a sustained state of apprehension evoked by an unpredictable threat (Davis et al, 2010). Fear and anxiety have been distinguished at the neural level in both humans (Herrmann, Beier, et al, 2016;Herrmann, Boehme, et al, 2016;Klahn et al, 2016Klahn et al, , 2017 and animals (for reviews: Davis et al, 2010;Walker, Toufexis, & Davis, 2003).…”

“…Additionally, a plethora of psychopharmacological (Bradford, Shapiro, & Curtin, 2013;Grillon et al, 2015; TA B L E 1 Sample characteristics. Sex, age, heart rate, and fitness level (VO2-peak) of participants (means and SDs) Grillon et al, 2008;Grillon, Pine, Lissek, et al, 2009; Morgan, Davis, & Southwick, 1998;Hogle et al, 2010;Klahn et al, 2016Klahn et al, , 2017Moberg & Curtin, 2009;Schroijen et al, 2016) (Bradford et al, 2013;Chamberlain et al, 2013;Gorka, Nelson, Sarapas, et al, 2013;Gorka et al, 2015;Gorka et al, 2017;Grillon, Chavis, Covington, et al, 2009;Grillon, Pine, Lissek, et al, 2009Grillon et al, 2008, 2011Grillon, Cordova, Morgan, Charney, & Davis, 2004;Herrmann, Beier, et al, 2016;Herrmann, Boehme, et al, 2016;Hogle et al, 2010;Kaye, Bradford, & Curtin, 2016;Klahn et al, 2016Klahn et al, , 2017Klinkenberg et al, 2016;Moberg & Curtin, 2009;Nelson, Hodges, Hajcak, & Shankman, 2015;Schroijen et al, 2016). The NPU threat test consists of a neutral condition (N), and two threat conditions that involve administration of predictable (P) and unpredictable (U) shocks (Schmitz & Grillon, 2012).…”