UNIVERSITY OF ILLINOIS AT CHICAGO
Department of Psychiatry
Fifth Annual Research Forum – Extravaganza 2014
POSTER TITLE
Amygdala Subregion Reactivity to Social Signals of Threat in Generalized Social
Anxiety Disorder is Normalized “Early” in Cognitive Behavioral Therapy
DISEASE/KEY
WORDS:
fMRI; brain imaging, social anxiety, psychotherapy, emotion processing
AUTHORS:
Heide Klumpp, Daniel A. Fitzgerald, Sheila D’Sa, Amy Kennedy, Julia Roberts, Scott
Langenecker, Stewart A. Shankman, K. Luan Phan
MENTEE
CATEGORY:
Junior Faculty
BACKGROUND:
Generalized social anxiety disorder (‘gSAD’) is a widespread, debilitating illness
characterized by a threat processing bias that contributes to exaggerated fears of
potential scrutiny. The pathophysiology of threat bias involves heightened neural
sensitivity to threat-relevant signals as evidenced by amygdala hyper-reactivity to
social signals of threat in gSAD. Cognitive Behavioral Therapy (CBT) is first-line
psychotherapy for gSAD. It attempts to reduce symptoms by means of cognitive
strategies (e.g., negating dysfunctional beliefs) at the beginning of therapy and
subsequently focuses on facing fears via exposure techniques. In addition to
decreases in symptomatology, CBT is associated with reductions in threat bias yet
findings of reductions in amygdala response to threat faces after CBT have been
mixed. Inconsistencies may relate to amygdala subregions, which play distinct roles
in threat processing. Subregions include the basolateral amygdala (BLA), which
among other functions is critical to automatic threat assessment. The superficial
amygdala (SFA) is involved in processing socially relevant stimuli, and the central
medial amygdala (CMA) is implicated in the expression of fear behaviors to
imminent/unavoidable threat. Little is known about BLA, SFA, and CMA activation
during threat processing in the context of CBT.
As part of an on-going study, 10 patients undergoing 12 weeks of individual CBT
participated in functional magnetic resonance imaging (fMRI) at 3 time points: Week
0 (pre-CBT), Week 6 (end of cognitive focus/start of fear exposures), and Week 12
(post-CBT). For comparison, 8 healthy controls (HC) also underwent fMRI at Weeks
0, 6, and 12. During fMRI all subjects completed an Emotional Face Matching Task
designed to isolate brain (e.g., amygdala) response to signals of threat. Faces
comprised angry, fearful, and happy faces which were contrasted against simple
geometric shapes. Using bilateral BLA, SFA, CMA anatomical-based regions of
interest (ROI), we extracted from each subject parameter estimates of activation
averaged across all voxels to Fear (> Shapes), Angry (> Shapes), and Happy (>
Shapes). In SPSS, extractions for each ROI for each face type were submitted to a 2
METHODS:
RESEARCH MENTOR:
K. Luan Phan
UNIVERSITY OF ILLINOIS AT CHICAGO
Department of Psychiatry
(Group) x 2 (Laterality) x 3 (Time) Analysis of Variance with time as a repeated
measure. Significant main effects for group or group-related interactions were
followed-up by two-tailed t-tests (independent, paired). The clinician-administered
Liebowitz Social Anxiety Scale (“LSAS”) was used to examine symptom severity.
RESULTS:
CONCLUSIONS:
Significant Group effects emerged for fearful faces but not for angry or happy faces.
In BLA, there was a significant main effect for Time that was moderated by a Group x
Time interaction. The gSAD group exhibited exaggerated bilateral amygdala
reactivity to fearful faces compared to HC at Week 0 but not at Weeks 6 or 12.
Within the gSAD group, BLA reactivity to fearful faces was significantly decreased by
Week 6 with no further change noted at Week 12. In HC, no significant changes in
BLA response over the course of time were observed. In SFA, a significant main
effect for Time was moderated by a Group x Time interaction. There was also a main
effect for Laterality with activation greater for right than left SFA across subjects. No
Group x Time x Laterality interaction was observed. Follow-up analysis revealed a
non-significant trend towards greater SFA reactivity in gSAD relative to HC at Week 0.
No group differences emerged at Week 6, however, at Week 12 the gSAD group
showed a significant reduction in SFA response relative to HC. Within the gSAD
group, there was a significant decrease in SFA reactivity to fearful faces at Week 6
with no further decrease at Week 12. Again, in HC there were no significant changes
in SFA response over time. For CMA, no group-related findings were revealed.
Regarding symptom severity, LSAS was significantly reduced at Weeks 6 and 12 in
gSAD. No correlations between LSAS and significant findings were observed.
Preliminary findings indicate pre-CBT exaggerated bilateral BLA and SFA reactivity to
fearful faces in gSAD relative to HC. By the mid-point of 12 weeks of treatment,
activation in these amygdala subregions in gSAD was analogous to BLA and SFA
response in HC. Notably, the HC group did not show changes in response in these
regions over time indicating reliable activation to fearful faces in controls. In CBT for
gSAD Week 6 largely marks the end of the cognitive phase of CBT and start of
systematic exposures to fears. The BLA and SFA are in general input regions for
sensory information and results suggest cognitive therapy may reduce neural
sensitivity to threat-relevant signals potentially by engaging prefrontal regions. Thus,
future analyses will include psychophysiological interactions analyses to examine
amygdala-prefrontal interactions. Also, further study is needed to rule out nonspecific effects such as time spent in psychotherapy. Lastly, a lack of power may
have reduced our ability to detect group effects for angry faces or correlations
between significant results and symptom severity. Nevertheless, data suggests BLA
and SFA reactivity is modulated by CBT relatively early in the course of treatment.