DEPRESSION AND ANXIETY 27:643–651 (2010)
AMYGDALA ACTIVATION IN RESPONSE
TO FACIAL EXPRESSIONS IN PEDIATRIC
Jennifer C. Britton, Ph.D.,1,2?S. Evelyn Stewart, M.D.,3,4William D.S. Killgore, Ph.D.,2Isabelle M. Rosso, Ph.D.,2
Lauren M. Price, B.A.,2Andrea L. Gold, M.S.,2,5Daniel S. Pine, M.D.,1Sabine Wilhelm, Ph.D.,3
Michael A. Jenike, M.D.,3and Scott L. Rauch, M.D.2,3
Background: Exaggerated amygdala activation to threatening faces has been
detected in adults and children with anxiety disorders, compared to healthy
comparison (HC) subjects. However, the profile of amygdala activation in
response to facial expressions in obsessive–compulsive disorder (OCD) may be a
distinguishing feature; a prior study found that compared with healthy adults,
adults with OCD exhibited less amygdala activation to emotional and neutral
faces, relative to fixation [Cannistraro et al. (2004). Biological Psychiatry
56:916–920]. Methods: In the current event-related functional magnetic
resonance imaging (fMRI) study, a pediatric OCD sample (N512) and a HC
sample (N517) performed a gender discrimination task while viewing
emotional faces (happy, fearful, disgusted) and neutral faces. Results: Compared
to the HC group, the OCD group showed less amygdala/hippocampus activation in
all emotion and neutral conditions relative to fixation. Conclusions: Like
previous reports in adult OCD, pediatric OCD may have a distinct neural
profile from other anxiety disorders, with respect to amygdala activation in
response to emotional stimuli that are not disorder specific. Depression and
Anxiety 27:643–651, 2010.
r 2010 Wiley-Liss, Inc.
Key words: OCD; fMRI; neuroimaging; anxiety disorder; fear; disgust
Models of anxiety disorders, both in adults and
children, hypothesize amygdala hyperresponsivity to
threat-related stimuli.[1,2]Exaggerated amygdala acti-
vation has been observed during symptom provocation
using disorder-specific stimuli across a broad array of
anxiety disorder populations,[3–6]including obsessive–
compulsive disorder (OCD).[7,8]However, the exag-
gerated amygdala activation seen in anxiety disorders is
not limited to disorder-specific stimuli. Exaggerated
amygdala activation in response to emotional facial
expressions has been shown for a subset of adult and
childhood anxiety disorders.[9–16]
Not all anxiety disorders show exaggerated amygdala
activation to both disorder-specific and general emo-
tional stimuli. Activation profiles to these types of
Published online in Wiley InterScience (www.interscience.wiley.
Received for publication 19 February 2010; Revised 6 May 2010;
Accepted 10 May 2010
The authors disclose the following financial relationships within the past
3 years: Contract grant sponsors: David Judah Fund; The
Intramural Research Program of the National Institutes of Health
and the National Institute of Mental Health.
?Correspondence to: Jennifer C. Britton, National Institute of
Mental Health, 9000 Rockville Pike, Building 15K, Bethesda,
Maryland 20892. E-mail: email@example.com
1Mood and Anxiety Disorders Program, National Institute
of Mental Health, Bethesda, Maryland
2Brain Imaging Center,McLean
3Department of Psychiatry, Massachusetts General Hospital,
Massachusetts General Hospital, Boston, Massachusetts
5Department of Psychology, Yale University, New Haven,
rrrr 2010 Wiley-Liss, Inc.
stimuli may aid in differentiating among anxiety
disorders. Prior studies of adults with specific animal
snakes[3,5]and an absence of such exaggerated amyg-
exaggerated amygdala activation has been shown in
response to OCD-specific stimuli (e.g. disgusting
toilet water)in some
OCD,[7,8,18]less amygdala activation in response to
happy, neutral, and fearful faces has been found in
adult OCD subjects, compared to healthy subject.
This finding contrasts with other anxiety disorders
showing greater amygdala activation to such stimuli.
The current study extends these findings to children
by testing the hypothesis that less amygdala activation
in response to facial expressions also characterizes
studiesof adults with
METHODS AND MATERIALS
Individuals were recruited via local outpatient OCD clinics
and community advertisements as paid volunteers. All participants
were between 10 and 17 years old, English speaking, and had
normal or corrected-to-normal vision. Participants denied current
or past history of head injury, learning disability, medical illness,
or substance abuse/dependence. Before enrollment and after the
procedures were explained, written informed consent was obtained
from a parent/legal guardian and written informed assent was
obtained from the child/adolescent participant. All study procedures
were performed in accordance with the Human Research Commit-
tees at McLean Hospital and Partners Healthcare System.
The Kiddie Schedule for Affective Disorders and Schizophrenia
was administered to all participants.Individuals included in the
OCD group met DSM-IV criteria for this disorder.For feasi-
bility and ethical reasons, entry criteria for the OCD group
allowed for the presence of comorbid disorders as well as the use
of specified psychotropic medications (e.g. selective serotonin
reuptake inhibitors, tricyclic antidepressants, mood stabilizers).
Neuroleptic (e.g. traditional and atypical antipsychotics) and
antihypertensive medications were exclusionary. All individuals
included in the healthy comparison (HC) group were free from
any current Axis I psychiatric disorder and from psychotropic
medications. For all participants, symptom severity scores were
measured using Child Yale-Brown Obsessive Compulsive Scale
(CY-BOCS), Child Depression Inventory (CDI), Spielberger State-
Trait Inventory-Child Version (STAIC), the Yale Global Tic Severity
Scale[22–26]and a modified version of the Disgust Sensitivity Scale,
eliminating items not suitable for children and adolescents (i.e., 7, 14,
21, 24, and 27).
The final study sample included 12 individuals with OCD and
17 HC subjects, matched for age, gender, and handedness. This
final sample was obtained after data from individuals were excluded
for excessive head movement (3 OCD, 4 HC), technical problems
(4OCD, 1 HC), and poor behavioral responding during post-
scan tasks (1 OCD, 1 HC). Group characteristics are outlined in
Of note, each participant completed a set-shifting paradigmand
a visuospatial priming task[29,30]before this faces task was completed.
Results from those fMRI paradigms will be reported separately
GENDER DISCRIMINATION TASK
In an event-related fMRI design, participants viewed facial
expressions. Participants were instructed to indicate the gender of
the face by pressing one of two buttons. The left index finger button
was pressed if the face was identified as male and the right index
finger button was pressed if the face was identified as female (Fig. 1).
Facial expressions were selected from a stimulus set obtained from
Ruben Gur at the University of Pennsylvania.A total of sixty-four
identities each displaying happy, disgusted, fearful and neutral facial
expressions were presented. An equal number of male and female
individual identities were selected and the identities reflected the
minority population distribution within the regional area. These
color images were standardized using Photoshop CS2 and placed on a
black background. Face stimuli were presented for 1950ms, with a
50ms inter-stimulus interval of low-level fixation.
Four functional runs of this faces task were completed in the
scanner. Each run lasted 3min and 16s. All 64 individual identities
were presented within each run. The different expressions of each
identity were distributed evenly across the runs, so that each run had
an equal number of happy, disgusted, fearful, and neutral facial
TABLE 1. Group characteristics
Characteristic OCD Healthy comparison
Duration of illness (years)
12 (7 males)
17 (11 males)
Mean and standard deviation.
?Significant group difference Po.05. Child Yale Brown Obsessive
Compulsive Scale (CYBOCS), Child Depression Inventory (CDI),
Yale Global Tic Severity Scale (YGTSS), and modified Disgust
Sensitivity Scale-Revised (DS-R). R5Right, L5Left. The OCD
group endorsed the following current symptoms within previously
identified symptom dimensions: (1) aggression, sexual, religious,
somatic obsessions/checking compulsions (N57); (2) symmetry/
ordering/repeating (N57); (3) contamination/washing (N55);
and (4) hoarding (n52).[70,71]Of note, several individuals endorsed
symptoms of multiple subtypes; therefore, the totals exceed the
number of subjects in the OCD sample. In keeping with the expected
rates for pediatric OCD, the following comorbid illnesses were
present in the OCD group: generalized anxiety disorder (N52),
simple phobia (N52), agoraphobia (N51), major depression
(N52)/depression-NOS (N51), Tourette disorder (N51) and
attention-deficit hyperactivity disorder (N52). Primary medications
taken by OCD subjects included selective serotonin reuptake
inhibitors (N59) and tricyclic antidepressants (N53). In addition,
several individuals were taking secondary medications: mood stabi-
lizers (N53), stimulants (N54), desyrel (N51), memantine (N51),
atomoxetine (N51), zolpidem (N51) and lorazepam (N51).
644Britton et al.
Depression and Anxiety
The trial order was determined using an optimization tool for
event-related fMRI designs,which introduces ‘‘jitter’’ by inter-
spersing 1–5 consecutive fixation trials within each run to maximize
the ability to deconvolve the ‘‘blood oxygenation level dependent’’
(BOLD) signal according to trial type. In this task, 32 fixation trials
were included in each run. To avoid establishment of response
patterns, the identities were distributed such that the same gender
would not occur for more than three successive instances.
Stimuli were centered on a black background via standardized
software (E-Prime, Inc, 1.1) and displayed on a rear-projection
screen. Responses were collected via a Fiber Optic Response straight
button-box device (Current Designs, Philadelphia, PA) and recorded
Magnetic resonance images were collected with a Siemens Trio
3.0T syngo MR 2004A whole-body high-speed imaging device
equipped for echo planar imaging (EPI) (Siemens Medical Systems,
Iselin, NJ) and an 8-channel gradient head coil.
FUNCTIONAL MRI DATA ACQUISITION
An automated scout image was acquired and localized shimming
procedures were performed to optimize field homogeneity. A high-
resolution 3D MPRAGE sequence (TR/TE/flip angle52530ms/
3.39ms/71, 1.3?1.0mm in-plane resolution, and 1.33mm slice
thickness) was collected for spatial normalization. Before each
functional scan, 3–5s of acquisition were discarded to allow
longitudinal magnetization to reach equilibrium. Functional MRI
images were acquired using a gradient echo T2?-weighted sequence
(TR/TE/flip angle/FOV52s/30ms/901/200mm, orientation525
axial slices angled with the AC-PC line, slice thickness55mm with
no interslice skip, voxel size53.125?3.125?5mm, interleaved
excitation order and anterior-to-posterior phase encoding). Four
functional runs were completed, yielding 96 acquisition volumes
Immediately after scanning, all participants viewed a subset of
the faces on a computer outside the scanner. Via button press
responses, subjects rated the valence (?45very negative to
145very positive) and reported the emotion displayed on each face
using a forced choice task with happy, disgust, fear, and neutral as
data were analyzed using a 2 (group: OCD, HC)?4 (condition:
happy, disgust, fear and neutral) repeated measures analysis of
variance in SPSS 16.0. Statistical significance was determined using
an a-level of .05. Post hoc analyses using two-tailed t-tests and
multiple comparison correction were performed where indicated.
Preprocessing and image analysis was com-
pleted in SPM5.The parameters to motion-correct the functional
images to the mean image were calculated using six-parameter rigid
body spatial registration. Any EPI motion-related susceptibility was
removed via an unwarping procedure. For each individual, the
anatomical MPRAGE image was co-registered to the mean
functional image. Segmentation parameters were used to normalize
the functional images to the SPM5’s MNI T1 2?2?2 template.
Finally, the functional images were spatially smoothed with a 6mm
full-width-half-maximum Gaussian filter.
A general linear model was created for each individual. The
data were modeled using the onsets of happy, fearful, disgust,
and neutral as well as fixation trials, convolved with the canonical
hemodynamic response function. Each condition regressor contained
scan onset times for correct gender-discrimination trials only.
A separate error regressor, across all condition types, was included.
Time and dispersion derivatives were included in the model for
each condition. A high-pass filter with 128s cutoff was used to
eliminate low-frequency drift and AR1 correction was used to
remove any temporal autocorrelation. To isolate within-brain voxels,
the SPM masking threshold was reduced and an explicit mask
representing the combined gray and white matter volume was
included. A series of estimated betas, one for each regressor, was
generated to minimize the error term within the model. Contrasts
were generated by comparing the beta weights associated with BOLD
activations in response to each emotion and neutral face relative to
baseline (e.g. happy4fixation) and relative to neutral (e.g. happy4
neutral) across all runs.
A whole-brain, voxel-wise analysis was conducted using random-
effects analysis. Contrast images from each individual were entered
into a 2nd-level model. Two-sample t-tests were conducted to
determine significant group?condition interaction effects for each
emotion. Statistical significance was based on both a peak threshold
and as a means to correct for multiple comparisons at Po.05 level, a
spatial extent threshold. The spatial extent threshold within
anatomically defined ROIs was determined using Analysis for
Functional Neuroimage (AFNI)’s AlphaSim program based on a5.05,
1,000 Monte Carlo simulations and smoothness of 10mm.
At a Po.005 peak threshold, a 7-voxel cluster size in the amygdala
was needed. Regions implicated in the processing of emotion,
facial expressions and disgust (e.g. anterior cingulate, prefrontal
cortex, insula cortex)[35–38]were also examined using a Po.001
peak threshold and a 12-voxel cluster size. For completeness,
significant activations in additional regions using a Po.05 family-wise
error (FWE) corrected threshold were noted. Brain regions were
identified by visual inspection and cross-referenced with a Talairach
atlas.MNI coordinates are reported throughout the Results
T o further investigate the group differences and determine whether
the activation patterns were correlated with symptom severity or age,
one-sample t-tests and analysis of covariances models in each group were
examined in regions showing group difference using whole-brain analysis
with similar thresholds as described above.
Online (reaction time and accuracy) behavioral
Figure 1. Gender discrimination task. Fearful, disgusted, happy,
and neutral faces were displayed randomly. Subjects were
required to identify the gender of the face by button-press
645 Research Article: Pediatric OCD and Amygdala Response to Faces
Depression and Anxiety
The accuracy rates for determining gender of the
happy faces (OCD: 90.4%77.2, HC: 92.9%74.7),
disgusted faces (OCD: 89.7%76.8, HC: 91.5%76.2),
fearful faces (OCD: 89.5%76.4, HC: 91.8%75.8),
and neutral faces(OCD:
92.9%73.9) were not significantly different between
OCD and HC groups [P4.4]. No group or group-
condition effects were noted [P4.2].
The postscan ratings indicated that the faces were
appropriately valenced. The happy faces were rated more
positively (OCD: 1.371.5, HC: 1.970.8) than the
neutral faces (OCD: ?0.370.4, HC: 0.170.8). The
disgusted faces (OCD: ?1.770.8, HC: ?1.171.1) and
fearful faces (OCD: ?1.270.6, HC: ?0.771.0) were
rated more negatively than the neutral faces (condition
effect: F(3,81)569.8, Po.001). No condition?group
interaction was noted [P4.9]; however, the OCD group
rated the faces overall more negatively than did the HC
group [group effect: F(1, 27)55.1, Po.03].
The postscan ratings of emotion recognition indi-
cated that happy faces (OCD: 97.9%74.1, HC:
97.873.1) were rated with greater accuracy than
neutral faces (OCD: 90.1%79.0, HC: 92.679.7) and
83.8.6712.5). Fearful faces were recognized with the
lowest accuracy (OCD: 58.9%715.6, HC: 67.3713.2)
[condition effect: F(3, 81)571.9, Po.001]. The group
effect was not significant [P4.6].
expressions versus fixation, the OCD group showed
reduced activation at the amygdala/hippocampal border
compared to the HC group in all emotion and neutral
facial expression conditions (Table 2 and Fig. 2). No group
differences in amygdala activation to emotional faces
relative to neutral facial expressions were found (Table 3).
After accounting for CDI depression scores and age,
the group differences in amygdala response to faces
relative to fixation remained significant. Of note,
across both groups, age positively correlated with
amygdala [(20, 6, ?24), Z53.17, k518] and hippo-
campus [(?30, ?2, ?30), Z53.06, k524] activation in
response to happy versus fixation.
The amygdala activation did not correlate with
CY-BOCS, state anxiety scores or disgust sensitivity
scores in either group.
Group differences were detected
in cortical regions in response to emotional conditions
relative to neutral facial expressions (Table 3).
No significant group differences in cortical regions
in response to faces relative to fixation or in the insula
cortex activation in any contrast were found. No
additional regions were significant using a Po.05
FWE corrected threshold.
When comparing the activation to facial
TABLE 2. Activation patterns in response to facial expressions, relative to fixation in pediatric OCD subjects and healthy comparison subjects (HC)
?24, 2, ?26
?22, 2, ?24
?20, ?12, ?20
?22, 2, ?24
24, 2, ?26
28, 0, ?28
26, 4, ?28
28, 0, ?28
38, 18, ?6
42, 18, ?4
?38, 18, 2
?26, 0, ?28
?24, 0, ?28
?26, 0, ?28
28, 2, ?22
30, 0, ?28
Significant clusters at Po.05 corrected using a cluster level (47 voxels) for the amygdala and (412 voxels) for the insula. MNI coordinates provided. k5cluster values at Po.005 peak threshold
for amygdala and Po.001 peak threshold for insula.
646Britton et al.
Depression and Anxiety
Figure 2. Less amygdala/hippocampus activation in response to emotional and neutral faces in OCD compared to healthy controls.
The amygdala/hippocampus activation in response to emotional faces versus fixation [(?24, 2, ?26), Z53.22, k547; (24, 2, ?26),
Z53.48, k585] was lower in the OCD group compared to the healthy comparison group (not shown). Group differences (healthy
comparison4OCD) were detected in response to all emotions (fear: [(28, 0, ?28), Z53.61, k5131], disgust: [(?22, 2, ?24), Z53.25,
k524], happy: [(?20, ?12, ?20), Z53.27, k5112; (26, 4, ?28, Z53.28, k566]) and neutral [(?22, 2, ?24), Z53.39, k569; (28, 0,
?28), Z53.07, k519], relative to fixation. Significant group differences within the amygdala/hippocampus are displayed at Po.005.
These activations are corrected to Po.05 given the cluster level (47 voxels). The left amygdala is shown on the left side of the image.
TABLE 3. Activation patterns in response to emotional relative to neutral facial expression in pediatric OCD subjects
and healthy comparison subjects (HC)
All emotionFear DisgustHappy
XYZZk XYZZk XYZZk XYZZk
?16, 10, ?163.12 31
?32, 30, ?6 3.85 30
?2, 44, 24 3.3820
28, 6, ?22
?16, ?6, ?24
?22, 28, ?10
28, 6, ?243.1923
?32, 2, ?243.25 14
?42, 42, ?4 3.6424
?40, 40, ?6 4.4765
?42, 28, ?123.58 221
Significant clusters at Po.05 corrected using a cluster level (47 voxels) for the amygdala and (412 voxels) for the orbitofrontal cortex (OFC),
ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate (dACC), and insula. MNI coordinates provided. k5cluster values at Po.005
peak threshold for amygdala and Po.001 peak threshold for all other regions.
647 Research Article: Pediatric OCD and Amygdala Response to Faces
Depression and Anxiety
This study is the first to examine the neural response
to general emotional stimuli in a pediatric OCD
sample. In this study, less amygdala/hippocampus
activation to facial expressions relative to fixation was
found in a pediatric sample with OCD compared to
HC subjects, replicating previous work in adult
OCD.Due to the spatial resolution of fMRI, it is
difficult to pinpoint the exact location of the group
difference found at the border of the amygdala and
hippocampus; however, based on the previous litera-
ture in adult OCD as well as studies of emotional face
processing, this group difference likely emanates from
As in the previous study in adult OCD, the pediatric
OCD group exhibited less amygdala activation to
multiple facial expressions compared to the HC group.
The amygdala activation is less in response to positive
(i.e. happy), negative (i.e. fearful), and neutral facial
expressions. In addition, this study provides evidence
that the less amygdala activation in OCD patients
extends to other negative emotions, i.e. disgust. In the
literature, the amygdala has been shown to respond to
all of these different types of emotion[40–43]and given
the lack of specificity in a previous study,identifying
less amygdala activation to multiple emotions is not
surprising. Although OCD may be similar to other
anxiety disorders with respect to greater amygdala
activation during symptom provocation,the finding
of less amygdala activation to facial expressions, general
emotional stimuli, may distinguish OCD from other
Although speculative, the hyperactivity of the frontal
cortical regions found in OCD may dampen the
amygdala activation to disorder-irrelevant stimuli, such
as facial expressions. The increased cortical activity
may, in turn, suppress the subcortical and autonomic
systems.[10,44,45]Although no differences in frontal
cortical activation in response to emotional faces
relative to fixation were noted in this study, resting
state studies have consistently reported enhanced
activity in orbitofrontal–striatal regions in OCD.[46,47]
The tonic hyperactivity of the orbitofrontal regions in
OCD may have prevented the detection of phasic
changes in the amygdala and/or frontal cortical regions
to general emotional stimuli in this study. This finding
is consistent with the demonstrated blunted peripheral
autonomic response to general stressors not relevant to
OCD symptoms. Compared to HC subjects and other
anxiety disorder groups, patients with OCD had lower
levels of physiological responding to nondisorder-
related stressors (i.e. decreased physiological flexibi-
lity).On the other hand, disorder-specific stimuli or
increased disorder-related anxiety may elicit amygdala
OCD,[7,8]like other anxiety disorders. It is unclear
whether the different pattern of amygdala activation in
response to symptom provocation versus general
emotional stimuli applies to both adult and pediatric
OCD. Only one published study has examined
symptom provocation in pediatric OCD.In that
study, reduced activation
thalamic circuit as well as the insula was detected in
the pediatric OCD group relative to healthy controls;
however, no group differences were noted in the
amygdala. Future studies will need to determine the
pattern of amygdala activation to disorder-specific and
general emotional stimuli.
Less amygdala activation in pediatric OCD in
response to facial expressions could potentially be
explained by group differences in amygdala structure.
Previous literature has shown both decreased[50,51]and
increased amygdala volumes in OCD.To address
this potential issue regarding amygdala structure, two
separate structural analyses, including intracranial
volume as a covariate, were completed to investigate
any structural differences in the amygdala. A voxel-
based morphometry analysis assessed grey matter
density in a whole-brain analysis and an automated
segmentation method assessed anatomically defined
amygdala and hippocampus volumes.No group
differences in amygdala or hippocampus structure were
noted using either method.
observed that would help explain the group differences
in regional brain activation. The on-line performance
of gender discrimination was similar in OCD subjects
and comparison subjects and regressors coding accu-
rate trials were used in the analysis. However, the OCD
group did rate the faces more negatively after the fMRI
session. Lower amygdala activation in the face of
increased ratings of negative emotion is contrary to
what might be expected. Amygdala activation has been
shown to be modulated by arousaland is greater
with higher emotional intensity in anxious indivi-
duals.Therefore, one might have hypothesized
greater amygdala activation with greater negative
ratings rather than less activation.
The current finding in a pediatric sample extends
prior work in adult OCD, despite methodological
differences. In the adult study, individuals passively
viewed facial expressions in a block design.In the
current study in youth, individuals completed a
gender discrimination task in an event-related design.
Previous studies have used block designs to illustrate
exaggerated amygdala activation to facial expres-
sions.[9–12,56]The amygdala response to repeatedly
presenting faces in a blocked fashion is subject to
unfavorable habituation effects.[57,58]Habituation ef-
fects are reduced by using an event-related design.
With respect to the differences in task, it is well known
that amygdala activity is modulated by task demands.
In healthy subjects, cognitive tasks (e.g. rating and re-
appraising) tend to increase mPFC activation and con-
sequently reduce amygdala activation,[44,59]and threat
appraisal tasks tend to be associated with increased
amygdala activation.In most anxiety disorders, the
648 Britton et al.
Depression and Anxiety
exaggerated amygdala activation to facial expressions is
task independent. For example, exaggerated amygdala
activation has been noted in anxiety disorders using
passive viewing,[9,10,56]using emotion appraisal tasks
such as emotional labeling,and using incidental
processing tasks such as gender discrimination.[12,13]
Several limitations of this study should be noted.
First, the sample size of our pediatric OCD group is
modest, though comparable to that of other pediatric
functional neuroimaging studies. Despite the small
sample size, significant group differences in amygdala
activation were detected. Future studies examining
emotional activation patterns in pediatric populations
with increased numbers are needed. Second, our OCD
sample had higher depression symptoms compared
with the healthy controls. To address this in the current
study, when CDI depression scores were included as a
covariate of noninterest, the group differences in
amygdala/hippocampus remained significant. Addi-
tional analyses were also conducted by excluding
individuals with a comorbid diagnosis of MDD or
Depression NOS and the study results were not
altered. Finally, our pediatric OCD sample consisted
mostly of medicated individuals. Treatment effects on
amygdala activation have been previously reported in
adults with depression. Following antidepressant treat-
ment in depressed adults, exaggerated amygdala
activation to emotional faces was reduced[61,62]and
the coupling between frontal cortical regions and the
increased.Rather than changes in amygdala activa-
tion,antidepressant treatment effects reported in
adult OCD show reduced frontal hyperactivity.[65,66]It
is unclear what the effects of antidepressant medication
are in pediatric OCD. Although we cannot exclude the
possibility that medication may contribute to our
findings, the adult OCD subjects in a previous study
that demonstrated a comparable amygdala activation
pattern to emotional faces were medication-free.
Future studies should examine medication effects on
amygdala function in both adult and pediatric OCD.
Given that the neural pattern in response to
emotional faces observed in adults with OCD appears
to arise at an early age, the lower amygdala activation
to emotional faces in pediatric OCD found in this
study may precede symptom onset. Several findings
suggest that amygdala activation to facial expressions
may represent a risk factor for anxiety and depression;
however, the results are not straightforward due to
variations in the definition of risk and in task demands.
In concordant twin pairs at risk for anxiety and
depression determined by neuroticism, anxiety, and
less amygdala activation compared with the low-
risk adults when identifying gender on emotional
faces.Adolescents with behavioral inhibition, an
early-appearing personality temperament and anxiety-
disorder risk factor, have shown lower amygdala
activation in response to facial expressions during
passive viewing and greater amygdala activation during
emotion appraisal compared to behaviorally uninhibited
adolescents.In contrast, adolescent offspring of
parents with major depression show exaggerated amyg-
dala activation while passively viewing facial expres-
sions.Across all individuals, only amygdala activation
to happy faces relative to fixation was positively
correlated with age in the current study, which may
indicate that this group difference may be the final one
to develop. Longitudinal studies of individuals at-risk
for developing OCD and cross-sectional studies in
unaffected relatives should examine amygdala activation
in response to facial expressions to determine whether
this reduced amygdala activation may predict onset and/
or be an endophenotype of OCD.
In summary, the amygdala/hippocampus activation
to facial expressions, relative to fixation, was lower in a
pediatric OCD sample when compared to healthy age-
matched individuals. This finding replicates previous
work in adult OCD.Future studies are needed to
investigate whether this reduced amygdala activation
to facial expressions predicts symptom onset and is
present in unaffected relatives of OCD probands.
by the David Judah Fund (J. C. B., S. E. S.) and in part
by the Intramural Research Program of the National
Institutes of Health and the National Institute of
Mental Health (J. C. B., D. S. P.). We would like to
acknowledge the contributions of Jennifer Ragan, Anne
Chosak, Adriane Alpern, Elizabeth Flamm, Sarah
Glaser, Elizabeth Sadock for their assistance in con-
ducting assessments and the Brain Imaging Center
MRI technologists for their assistance with scanning.
A previous version of this work has been presented at
the American College of Neuropsychopharmacology
annual conference in December 2008.
This research was supported
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