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

Facial emotion recognition, face scan paths, and face perception in children with neurofibromatosis type 1.

“…When required to identify the emotions depicted in video vignettes, adults with NF1 displayed significantly poorer recognition of anger compared to healthy controls. Contrary to expectations, correlational analyses in the NF1 group failed to reveal a significant relationship between emotion recognition performance and total gray matter volume in the amygdala, a region strongly associated with negative emotion processing in neurotypical individuals and other clinical populations (e.g., Adams, Gordon, Baird, Ambady, & Kleck, 2003; Phan, Fitzgerald, Nathan, & Tancer, 2006; Whalen et al, 2001). Nevertheless, a nonsignificant trend was observed whereby larger gray matter volume in the left fusiform gyrus was associated with poorer overall emotion recognition in those with NF1.…”

Amygdala and Ventrolateral Prefrontal Cortex Activation to Masked Angry Faces in Children and Adolescents With Generalized Anxiety Disorder

“…Youth with GAD exhibited greater right ventrolateral prefrontal cortex activation than healthy peers, with no between-group differences in the amygdala. Ventrolateral prefrontal cortex activation was greater in youth having GAD with mild anxiety relative to those with severe anxiety, consistent with studies 15,[25][26][27] implicating the ventrolateral prefrontal cortex in emotion regulation through effects on the amygdala. However, as with most prior reports, this study 4 involved events containing prolonged presentation of threats.…”

“…Such studies consistently find that adults with various anxiety disorders exhibit altered activation in the amygdala and the prefrontal cortex, [14][15][16][17][18][19] with positive correlations between amygdala activation and anxiety severity. 15 These studies typically present threats under prolonged viewing conditions in which the nature of the threat can be readily discerned. Prior research implicates the amygdala and associated circuitry in processing rapidly presented threats.…”

Neural Response to Self- and Other Referential Praise and Criticism in Generalized Social Phobia

“…Previous work has reported increased amygdala response in patients with GSP to facial expressions 4,5,11. In the current study, we found similarly increased amygdala BOLD response in the patients with GSP relative to the HCs to self-referential criticism, another class of social stimuli.…”

“…Previous work implicates emotion-relevant hyperresponsiveness in GSP for one class of social stimuli, facial expressions 4-6,8,9,11,36. Specifically, research shows that GSP involves greater responding than in healthy subjects to a variety of facial expressions, including negative (harsh, angry, fearful, or disgusted),4-6,8,9,11 positive,8 and neutral5,10 expressions.…”

“…However, imaging studies find more generalized perturbation in facial expression processing. Thus, functional magnetic resonance imaging (fMRI) studies have indicated that GSP involves increased activity in several regions, including the amygdala and anterior cingulate, to various facial expressions, including harsh,11 angry,4,5,8,9 fearful,4,5 disgusted,6 happy,8 and neutral5,10 expressions. That is, GSP appears to involve increased responsiveness to social stimuli in emotion-relevant brain regions regardless of valence.…”

The misclassification of facial expressions in generalised social phobia

“…Neuroimaging studies have consistently reported that facial expressions particularly of negative emotions, i.e. anger, disgust and fear result in enhanced amygdala responses in people with social phobia compared with healthy controls (Blair et al, 2008;Phan, 2006;Stein, Goldin, Sareen, Zorrilla, & Brown, 2002;Straube, Kolassa, Glauer, Mentzel, & Miltner, 2004). As in our study these studies also report no differences in the accuracy of the identification of emotions (Phan, 2006).…”

“…anger, disgust and fear result in enhanced amygdala responses in people with social phobia compared with healthy controls (Blair et al, 2008;Phan, 2006;Stein, Goldin, Sareen, Zorrilla, & Brown, 2002;Straube, Kolassa, Glauer, Mentzel, & Miltner, 2004). As in our study these studies also report no differences in the accuracy of the identification of emotions (Phan, 2006). This would suggest that despite there being no differences in the explicit evaluation of expressions the viewing of facial expressions in individuals with social phobia results in different effects in the brain compared with healthy controls particularly in areas associated with the evaluation of threat.…”

Contributions to the development and validation of fMRI-based biomarkers for drug discovery in social anxiety disorder

“…The interaction between paroxetine and placebo groups measured at basal and studyend, the effects were of activation, at variance with the attenuation reported in the early anxiolytic literature in healthy volunteers (Paulus et al 2005;Arce et al 2008;Simmons et al 2009). However, other discrepant results like ours have been reported, showing SSRI to increase amygdala activation (Tendolkar et al 2011), placebo to reduce it (Furmark et al 2008) or SAD patients displaying lower amygdala activation than healthy volunteers -163- (Britton et al 2010;Phan et al 2006). The heterogeneity of these results suggest that the results of this paradigm may depend on setup-specific conditions (Freitas-Ferrari et al 2010) or different phenotype-driven neural expressions of SAD (Furmark et al 2008).…”

“…Some studies have shown a heightened amygdala response to emotional (mainly harsh) faces in SAD patients (M. B. Phan et al 2006;Evans et al 2008;), but we are not aware of similar findings in a non-clinical population such ours. The psychophysiological interaction observed guided the exploratory analysis towards considering a bivariate model of the relationship between symptom severity and activation of not one, but two emotional processing areas (fusiform gyrus and amygdala).…”

“…But these findings have not always been consistent across studies (M. B. Phan et al 2006). Functional connectivity studies will reveal further details of these modulatory relationships.…”

“…Therefore our analysis would have suboptimal sensitivity. In this context, using happy faces as the control condition could be more appropriate (Phan et al 2006). The purpose of the example above is to show the important need of having robust a priori knowledge of the phenomenon under study when building the experimental design or model.…”

“…These tasks have captured attention as candidates for the development of symptom-measuring biomarkers: In multiple studies, SAD patients have shown increased amygdala activation (with respect to controls) while doing emotional face processing tasks (M. B. Veit et al 2002;Straube et al 2005;Phan et al 2006;Etkin & Wager 2007;Brühl et al 2014). However, results also indicate that the amygdala activation related to emotional processing may not be stable across time (Campbell et al 2007), especially in SAD patients (Sladky et al 2012).…”

Residual effects of cannabis use on attentional bias towards fearful faces

“…Reutter et al (2017) found enhanced N2pc correlated with increased social anxiety. Assuming the N2pc reflects theta oscillations in the visual cortex, which is mediated by theta oscillations in the amygdala, it is no surprise that fMRI research has found hyperactivation of the amygdala when viewing negative facial expressions in patients with generalized social phobia (Phan et al, 2006). In this current study, only cannabis users had enhanced N2pc amplitudes towards fearful faces, suggesting that unlike P1, cannabis users had increased attentional bias which resembles the finding in anxiety disorders (Bar-Haim et al 2007).…”

The Pathology of Social Phobia Is Independent of Developmental Changes in Face Processing

“…Two studies have reported enhanced amygdala responding to neutral expressions in adult SP, emphasizing the importance of contrasting response to emotional and neutral face-event types (3, 8). However, a further four studies (4, 6, 9, 11), like the current study, did not, suggesting that SP is not associated with heightened responsiveness to face stimuli generally. In contrast, hyper-responsiveness to angry expressions has been found with more consistency (4, 6, 7, 9, 13), though see (11).…”

“…However, a further four studies (4, 6, 9, 11), like the current study, did not, suggesting that SP is not associated with heightened responsiveness to face stimuli generally. In contrast, hyper-responsiveness to angry expressions has been found with more consistency (4, 6, 7, 9, 13), though see (11). Finally, only two previous studies of SP (4, 11) used fearful faces, the stimulus class most consistently shown to engage the amygdala of healthy adolescents and adults (28), and these generated inconsistent findings.…”

“…However, prior work is inconsistent regarding amygdala responding to happy faces in healthy individuals (28). Moreover, while two studies found increased amygdala responses to happy expressions in adult SP (6, 13), three others reported normal responding (3, 4, 9). As such, we chose to include angry and fearful but not happy expressions.…”

“…This increased responsiveness appears emotion-specific, in that it occurs consistently for emotional, and particularly negative-valence, expressions (e.g., 4, 6, 7, 9, 11, 13), but typically not for neutral or positive expressions (e.g., 4, 6, 9, 11) though see (3, 8). Given that perturbed emotion-specific processing has been demonstrated relatively consistently across laboratories in adult SP, we would expect to observe similar emotion-specific findings in adolescent SP if the pathology of the disorder does not vary independently.…”

Predicting Treatment Response in Social Anxiety Disorder From Functional Magnetic Resonance Imaging

“…However, the locations of activations that predicted response were not the regions most consistently reported in studies comparing brain responses in patients with SAD and typical control groups, such as the amygdala and other limbic areas. 24,45 In the present study, even when using a specific region of interest, no association with treatment response was found in the amygdala despite its robust activation to all experimental conditions. This may be consistent with a prior study reporting no abnormality in the amygdala response to angry faces in SAD.…”

Long-Term Behavioral Programming Induced by Peripuberty Stress in Rats Is Accompanied by GABAergic-Related Alterations in the Amygdala

“…Chronic immobilization stress was previously found to induce dendritic hypertrophy in excitatory neurons in the BLA in rats [81] and atrophy in amygdaloid interneurons accompanied by significantly reduced levels of GAD67 mRNA and protein in mice [82]. Although more studies are needed to verify this view, a bias towards amygdala excitation in the excitation/inhibition balance would be in agreement with evidence in clinical populations that typically display alterations in emotionality and social behaviors, such as autism and anxiety disorders patients [83]–[85]. Interestingly, mice deficient in GAD65 show increased anxiety-like behaviors [86].…”

Common and Distinct Amygdala-Function Perturbations in Depressed vs Anxious Adolescents

“…Owing to strong longitudinal and family-based aggregation among MDD and anxiety disorders manifest in adolescents and adults,3–10,14 one might expect brain imaging findings in adult MDD and anxiety16–21,24 to parallel the findings observed in this study in adolescents. Nevertheless, few imaging studies contrast anxious and depressed adults with any paradigm; none use paradigms similar to the one used herein, which shows that different conclusions emerge concerning between-group comparisons as a function of relatively subtle task-related features.…”

“…Existing data support competing hypotheses. On the one hand, data in adults,16–21,24 together with the strong cross-sectional, longitudinal, and familial relationships among adolescent and adult anxiety and MDD,3–10,14 raise the expectation of overlapping amygdala perturbations, consistent with a “shared diathesis” perspective 11,12. On the basis of these data, one might expect similarly biased amygdala engagement in anxious and depressed adolescents relative to healthy peers.…”

“…However, noncomorbid cases of anxiety and depression2,10,14 raise questions about neural differences. In adults, biased amygdala engagement occurs in major depressive disorder (MDD)15–18 and anxiety disorders 19–24. For both conditions, increased amygdala activation has been reliably seen, suggesting shared neural-circuitry dysfunction.…”