Association between Amygdala Hyperactivity to Harsh Faces and Severity of Social Anxiety in Generalized Social Phobia

The interaction between gaze and facial expression in the amygdala and extended amygdala is modulated by anxiety

“…Since social anxiety and sex differences have also been shown to predict the amygdala response to angry faces (McClure et al, 2004 ; Phan et al, 2006 ) we examined the influence of these factors on amygdala activity. Neither were found to independently predict the amygdala response, and all reported correlations remained significant after partialing out the effects of social anxiety (FNE) and sex differences (See Supplementary Material ).…”

“…As expected, state and trait anxiety scores were correlated ( r = 0.50, P < 0.01). Given that recent evidence has shown social anxiety influences the neural response to fearful and angry faces (Phan et al, 2006 ; Evans et al, 2007 ) we also sought to account for the influence of this dimension. Participants therefore completed the Brief Fear of Negative Evaluation (FNE) revised scale, a measure of sensitivity to negative evaluation by others and avoidance of social-evaluative situations (Carleton et al, 2006 ).…”

Defining biotypes for depression and anxiety based on large-scale circuit dysfunction: a theoretical review of the evidence and future directions for clinical translation

“…Amygdala over-reactivity elicited by implicit or non-conscious processing of threat-related stimuli has been reported in current depressive disorder [77–81] (for review, [82] ), generalized anxiety disorder [83] , generalized social phobia/anxiety disorder [83–85] , specific phobia [86] , and panic disorder [83,86] . Excessive amygdala activity elicited by masked threat faces has also been associated with a dimension of trait anxiety and with neuroticism in otherwise healthy people [87] consistent with a trait-like phenotype of hyper-reactivity to sources of threat (Table 1).…”

Developmental psychopathology: Attention Deficit Hyperactivity Disorder (ADHD)

“…But even though an unavoidable confrontation with individual anxiety-laden situations is assumed to have effect on ADHD symptomatology, no causal direction between ADHD and anxiety can be stated [ 60 ]. An overall increased level of arousal as well as the tendency to hyper-focus can facilitate the development of an anxiety disorder [ 61 , 62 ]. Different studies about the comorbidity of ADHD and anxiety disorders underline these findings.…”

Childhood trauma history differentiates amygdala response to sad faces within MDD

“…However, a number of factors other than childhood trauma are also linked to amygdala response including sex, (Killgore and Yurgelun-Todd, 2001; Schneider et al, 2000) severity of illness, (Drevets, 2003) anxiety, (Phan et al, 2006; Etkin and Wager, 2007) adult onset trauma (Shin et al, 2005) and basal glucocorticoid activity (Drevets et al, 2002). …”

Cognitive Neural Mechanism of Social Anxiety Disorder: A Meta-Analysis Based on fMRI Studies

“…A total of 1297 publications were retrieved from initial search, among which 37 studies met the inclusion criteria (654 participants in the SAD groups and 594 participants in the control groups). There were 15 studies that adopted emotional faces as task stimuli [ 6 , 10 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ], 8 that presented specific situations as task stimuli [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ], and the other 14 employed other types of tasks [ 7 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. In total, the coordinates where SAD groups performed significantly better or significantly worse than control groups were 335 and 115 respectively (see specific characteristics in Table 1 ).…”

Aberrant Amygdala-Frontal Cortex Connectivity During Perception of Fearful Faces and at Rest in Generalized Social Anxiety Disorder

“…Task Activations. The EFMT is designed to detect between group differences in amygdala activity, [10,14] and thus, we restrict our report of activations to between group results. gSAD patients showed greater right amygdala activity than HCs in the fearful versus happy faces contrast (P < .05, cluster extent > 200 voxels).…”

“…Evidence of a link between amygdala hyperactivity and symptom severity suggests it is a core deficit in the pathophysiology of gSAD [10] . Although less commonly implicated [11] , abnormalities within the prefrontal cortex (PFC) are hypothesized to underlie gSAD patients’ failure to effectively modulate amygdala reactivity, consequently leading to enhanced anxiety, social threat perception, and/or reticence to engage in social interactions [12] .…”

“…Although less commonly implicated [11] , abnormalities within the prefrontal cortex (PFC) are hypothesized to underlie gSAD patients’ failure to effectively modulate amygdala reactivity, consequently leading to enhanced anxiety, social threat perception, and/or reticence to engage in social interactions [12] . Consistent with this hypothesis, gSAD patients show atypical reactivity to the detection of social signals of threat in areas such as the anterior cingulate cortex (ACC) [10; 13] , and dorsal and ventral medial PFC (mPFC) [14] . Given their strong reciprocal structural connections with the amygdala [15] , discrete areas of the PFC are well-positioned to play a significant role in the regulation of fear and emotional responding.…”

“…[9] Evidence of a link between amygdala hyperactivity and symptom severity suggests it is a core deficit in the pathophysiology of gSAD. [10] Although less commonly implicated, [11] abnormalities within the prefrontal cortex (PFC) are hypothesized to underlie gSAD patients' failure to effectively modulate amygdala reactivity, consequently leading to enhanced anxiety, social threat perception, and/or reticence to engage in social interactions. [12] Consistent with this hypothesis, gSAD patients show atypical reactivity to the detection of social signals of threat in areas such as the anterior cingulate cortex (ACC), [10,13] and dorsal and ventral medial PFC (mPFC).…”

Trajectory of heart period to socioaffective threat in shy children

“…Although it has been argued that fear and anger are avoidance‐ and approach‐related emotions, respectively, they are both conceptualized as threat‐related emotions and previous research has shown links between shyness and threat‐related biases in children (e.g., LoBue & Pérez‐Edgar, ; Muris, Merckelbach, & Damsma, ; Pérez‐Edgar et al, ). Neuroimaging studies provide further support of both anger and fear being conceptualized as threat‐related emotions, with each being associated with heightened amygdala activity, a key brain region implicated in social and threat‐processing and perception (e.g., Etkin & Wager, ; Klumpp, Angstadt, Nathan, & Phan, ; Phan, Fitzgerald, Nathan, & Tancer, ).…”

Social vision: Sustained perceptual enhancement of affective facial cues in social anxiety

“…The possible reorganization of the sensory visual cortex correspondent to alterations in motivational thresholds associated with excessive social apprehension is supported by animal and human work revealing that the functional neuroarchitecture of the adult visual cortex is subject to changes related to behavioral contingencies (Karmarkar & Dan, 2006; Li et al, 2004) and re-entrant modulation from higher visual areas including temporal cortex and deep structures such as the amygdala (Damasio, 1998; Leppänen & Nelson, 2009; Sabatinelli et al, 2005; 2009)—areas consistently shown during functional neuroimaging to be hyper-reactive to facial stimuli in social phobia patients (Birbaumer et al, 1998; Evans et al, 2008; Phan et al, 2006; Schneider et al, 1999; Stein et al, 2002; Straube et al, 2004, Veit et al, 2002). Although speculative, the heightened attention to emotional faces may be the result of visual system plasticity secondary to chronic expectations of interpersonal failure typical of social anxiety (Andrews et al, 1994; Foa et al, 1996; Poulton & Andrews, 1996; Rapee & Heimberg, 1997).…”

“…Although heightened sensitivity specific to angry expressions would seem most consistent with the nosology of social anxiety, vigilance to other expressions has frequently been revealed in both ERP (Kolassa et al, 2007; 2009; Wieser et al, 2010) and hemodynamic imaging (Amir et al, 2005, Birbaumer et al, 1998; Phan et al, 2006; Stein et al, 2002) studies—even to happy faces (Yoon et al, 2007; Straube et al, 2005) and aversive non-social scenes (Shah et al, 2009). Much of the evidence for exaggerated reactivity to “harsh” facial expressions has been demonstrated as the mean response to heterogeneous aversive displays (angry, fearful, disgusted) (e.g., Moser et al, 2008; Phan et al, 2006; Stein et al, 2002).…”

“…Much of the evidence for exaggerated reactivity to “harsh” facial expressions has been demonstrated as the mean response to heterogeneous aversive displays (angry, fearful, disgusted) (e.g., Moser et al, 2008; Phan et al, 2006; Stein et al, 2002). In post hoc tests of the BOLD response to individual aversive contents, Phan and colleagues revealed that the overall effect was attributable to reliable, similar magnitude amygdala activity to angry, fearful and disgusted faces.…”

“…Concerning neurophysiological underpinnings, hemodynamic imaging studies have revealed that relative to controls socially anxious individuals and patients show exaggerated activation of limbic circuitry, particularly amygdala (Birbaumer et al, 1998; Evans et al, 2008; Phan et al, 2006; Schneider et al, 1999; Stein et al, 2002; Straube et al, 2004, 2005; Veit et al, 2002), in response to emotional facial expressions, again presented for a wide range of durations (i.e., 100 ms – 2500 ms). Less frequently an a priori area of interest, concurrent hyper-reactivity has also been observed in the extrastriate visual cortex (Evans et al, 2008; Goldin et al, 2009; Pujol et al, 2009; Straube et al, 2004; 2005).…”

Behavioral inhibition: A neurobiological perspective

“…On the whole, these studies failed to find a consistent association between BIS/trait anxiety scores and autonomic responses to stimuli or tasks designed to activate the BIS [26,30,[35][36][37][38][39]48,51]. In addition to the evidence of dissociation between BI and trait anxiety on the one hand and the amygdala on the other, there is evidence of neural dissociation between BI and trait anxiety.…”

“…No or inconsistent correlations between CW-BIS, SP(SR)Q, and STAI-T and hypothesized neural substrates of the BIS (ie, amygdala) as indexed by SCL and SR is therefore a relatively consistent finding (see also [38,39]) and may expose a lack of sensitivity/specificity in these self-report measures of BIS temperament. The suggestion that STAI-T is more sensitive to affective tone and physiologic output of the BIS than the CW-BIS scale [30] is not consistent with the data of Cornwell et al [37], which showed that STAI-T did not correlate with SCL or SR at baseline or during speech performance.…”

“…Several recent studies investigated the biological correlates of the BIS and trait anxiety as measured by a variety of self-report scales [26,30,[35][36][37][38][39]48,51]. On the whole, these studies failed to find a consistent association between BIS/trait anxiety scores and autonomic responses to stimuli or tasks designed to activate the BIS [26,30,[35][36][37][38][39]48,51].…”

“…Operationally, this has entailed the use of self-report "BIS" scales possibly lacking in specificity and sensitivity, as well as the use of experimental paradigms and fear-inducing stimuli that appear to be too nonspecific. For example, factors such as social versus nonsocial anxiety [30,37,38], temperament-valence interactions [36], or attentional demands [51] appear to be exerting significant confounding effects. There also has been, with few exceptions [50••,53••], a failure to consider cortical or subcortical substrates of BI and trait anxiety other than the amygdala.…”

“…Of possible interest in this regard, Cornwell et al [37] found that subjective state anxiety (measured by STAI-State) correlated with FNE, SSPS, and STAI-T (but not SR) during speech, suggesting that neither "general" trait nor "general" state anxiety mediates the correlation between trait social anxiety and SR found by these authors. Phan et al [38] also recently reported on a functional MRI (fMRI) study that found significant amygdala hyperactivation to aversive (anger/disgust/fear) facial expressions in 10 subjects with generalized social phobia (GSP), whereas 10 healthy controls subjects showed slight deactivation. The results confirmed several previous studies but also revealed a significant correlation between the blood oxygen level-dependent signal change and symptom severity in the GSP group as measured by the Liebowitz Social Anxiety Scale.…”

“…Taken together, these studies suggest a link between social anxiety as distinct from general trait anxiety and physiologic responsiveness. In addition, the failure to find an association between general trait anxiety and SR in a speech task [37], as well as the observation of amygdala deactivation to aversive stimuli in normal controls [38], is yet more evidence of a dissociation between these kinds of anxiogenic stimuli, which theoretically should activate the BIS and this brain structure. Questions about the validity of self-report measures of BIS temperament are echoed by Cogswell et al [24], who caution against the unqualified use of self-report scales, emphasizing both the need to improve their validity and investigate their behavioral correlates in order to properly examine their theoretical bases.…”

Influence of the fusiform gyrus on amygdala response to emotional faces in the non-clinical range of social anxiety

“…Increased amygdala responsiveness to emotional face processing has been a typical finding in fMRI studies of social anxiety patients (Stein et al 2002; Veit et al 2002; Straube et al 2004, 2005; Phan et al 2006; Yoon et al 2007). Nevertheless, it was not always obvious whether fusiform gyrus showed an abnormal activation, as few authors have specifically investigated fusiform gyrus activation in SAD.…”

“…Consistent with our findings, an fMRI study reported that children with this disorder tended to show reduced right fusiform gyrus activation, particularly in response to ‘forward’ faces compared to ‘angled’ faces, with no increase in amygdala activation (Garrett et al 2004). Specifically in social phobia, several studies did not find abnormal fusiform gyrus response to faces (Phan et al 2006; Campbell et al 2007; Stein et al 2007 b ), whereas Straube et al (2004) observed greater fusiform gyrus activation relative to control subjects for implicit, and not explicit, processing of angry faces. In another study, fusiform gyrus response to faces was larger in social phobic patients with high anxiety scores (Straube et al 2005).…”

“…Functional imaging studies of emotional face perception have shown increased amygdala activation in anxiety-prone subjects (Rauch et al 2000; Hariri et al 2002; Stein et al 2007 b ) and patients with social anxiety disorders (Stein et al 2002; Veit et al 2002; Straube et al 2004, 2005; Phan et al 2006; Yoon et al 2007). However, this increase in activation may depend on precise task conditions (Straube et al 2004), may be relatively modest in effect size (Cooney et al 2006; Yoon et al 2007) and may not be sustained throughout assessment (Campbell et al 2007).…”