Amygdala activation in response to facial expressions in pediatric obsessive-compulsive disorder. [Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't]

Department of Psychology, Yale University, New Haven, Connecticut
Depression and Anxiety (Impact Factor: 4.41). 07/2010; 27(7):643 - 651. DOI: 10.1002/da.20718
Source: PubMed


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 (N=12) and a HC sample (N=17) 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, 2010. © 2010 Wiley-Liss, Inc.

Download full-text


Available from: William D. S. Killgore,
41 Reads
  • Source
    • "However, amygdala over-responsiveness was not always observed in Anxiety Disorders (Marsh et al., 2008, Whalen et al., 2008) and per se may not be the most appropriate endpoint for pharmacologic studies. For example, a lower or equal, and not higher, amygdala response to negative emotional stimuli was observed in subjects with Anxiety Disorders (Phan et al., 2006; Marsh et al., 2008); and a higher, and not lower, activation to emotionally neutral stimuli were reported (Britton et al., 2010; Cooney et al., 2006), while no effects of amygdala response was found using agomelatine , a novel effective anxiolytic/antidepressant treatment (Lees et al., 2010). These observations suggested the engagement of regulatory processes generated in other components of the fear, stress and anxiety circuit, e.g., the prefrontal cortex (PFC) and anterior cingulate cortex (ACC), areas associated with cognitive appraisal and top– down emotion regulation (Etkin et al., 2006; Goldin et al., 2009; Blair et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies suggest that pharmacologic effects of anxiolytic agents can be mapped as functional changes in the fear, stress and anxiety brain circuit. In this work we investigated the effects of a standard treatment, paroxetine (20mg/day), in subjects with Social Anxiety Disorder (SAD) versus placebo using different fMRI paradigms. The fMRI sessions, performed before and after the treatment, consisted of a public exposition of recorded performance task (PERPT), an emotional face processing task (EFPT) and a 6-min resting state followed by an off-scanner public speaking test. Paroxetine significantly improved the clinical conditions of SAD patients (n=17) vs. placebo (n=16) as measured with Clinical Global Inventory - Improvement (CGI-I) while no change was seen when using Liebowitz Social Anxiety Scale, as expected given the small size of the study population. Paroxetine reduced the activation of insula, thalamus and subgenual/anterior cingulate cortex (ACC) in PERPT. Resting-state fMRI assessment using Independent Component Analysis indicated that paroxetine reduced functional connectivity in insula, thalamus and ACC when compared with placebo. Both paradigms showed significant correlation with CGI-I in rostral prefrontal cortex. Conversely, paroxetine compared to placebo produced activation of right amygdala and bilateral insula and no effects in ACC when tested with EFPT. No treatment effects on distress scores were observed in the off-scanner Public Speaking Test. Overall this study supports the use of fMRI as sensitive approach to explore the neurobiological substrate of the effects of pharmacologic treatments and, in particular, of resting state fMRI given its simplicity and task independence.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 10/2013; 24(1). DOI:10.1016/j.euroneuro.2013.09.004 · 4.37 Impact Factor
  • Source
    • "An abnormal amygdala response to emotional stimuli was reported in OCD patients, albeit with inconsistent results, showing both hyper-(Cardoner et al., 2011) and hypo-responsiveness (Britton et al., 2010). Consistent with a previous study showing less amygdala activation in OCD patients in response to multiple emotional stimuli (Britton et al., 2010), subjects in the present study exhibited decreased FC in the AMY to both incentive cues. OCD patients also showed increased FC between the NA and posterior insula during gain anticipation, but the FC between these regions was decreased during resting-state. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Compulsive behaviors in obsessive-compulsive disorder (OCD) may be related to deficits in reward processing mediated by corticostriatal circuitry, a brain network implicated in the pathophysiology of OCD. Performing compulsive actions can be perceived as a reward to OCD patients because it temporarily reduces the anxiety provoked by obsessions. Although most OCD literature provides evidence of altered regional activity in these corticostriatal circuits, very little is known about the connectivity between individual regions of the corticostriatal-limbic circuits, including the cognitive and affective neural circuitry associated with OCD. Thus, this study investigated the differences in functional connectivity (FC) patterns in this network during resting-state and incentive processing. Nineteen patients with OCD and 18 well-matched healthy controls were scanned during resting-state and a monetary incentive delay task (task state). FC was assessed using both voxel-wise and region-of-interest (ROI)-wise analyses. Voxel-wise FC analysis with the nucleus accumbens seed revealed that patients with OCD exhibited increased FC between the nucleus accumbens and the lateral orbitofrontal cortex during resting-state. Additionally, these patients showed decreased FC between the nucleus accumbens and limbic areas such as the amygdala during incentive processing. Exploratory ROI-wise FC analysis revealed that OCD patients demonstrated enhanced FC between the nucleus accumbens and the lateral orbitofrontal cortex and increased total connectivity of the lateral orbitofrontal cortex during resting-state. Additionally, patients showed alterations in FC between resting and task state. This study provides evidence that patients with OCD have altered FC in the corticostriatal-limbic network, particularly in striatal-amygdala and striatal-orbitofrontal circuitry, during incentive processing and resting-state. These findings also emphasize that functional connections in the network are modulated by affective/motivational states and further suggest that OCD patients may have abnormalities of such modulation in this network.
    Clinical neuroimaging 06/2013; 3:27-38. DOI:10.1016/j.nicl.2013.06.013 · 2.53 Impact Factor
  • Source
    • "Two studies of children/adolescents that included a wide age range (9–17 years old, Ns=31 and 17) showed significantly greater amygdala responses to fearful than to neutral faces (Guyer et al., 2008; Monk et al., 2003). Similarly, the healthy controls (mean age 13 years old, N=17) in a study of pediatric obsessive–compulsive disorder showed significant right amygdala activity for fearful versus neutral faces and significant bilateral amygdala responses to the combined contrast of fearful, happy, and disgusted faces versus neutral faces (Britton et al., 2010). On the other hand, studies that have included or focused on younger children have not consistently shown greater amygdala responses to fearful or emotional than to neutral faces. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The amygdala is a key region in emotion processing. In particular, fMRI studies have demonstrated that the amygdala is active during the viewing of emotional faces. Previous research has consistently found greater amygdala responses to fearful than to neutral faces in adults, convergent with a focus in the animal literature on the amygdala's role in fear processing. Studies have shown that the amygdala also responds differentially to other facial emotion types in adults. Yet the literature regarding when this differential amygdala responsivity develops is limited and mixed. Thus, the goal of the present study was to examine amygdala responses to emotional and neutral faces in a relatively large sample of healthy school-age children (N = 52). Although the amygdala was active in response to emotional and neutral faces, the results did not support the hypothesis that the amygdala responds differentially to emotional faces in 7- to 12-year-old children. Nonetheless, amygdala activity was correlated with the severity of subclinical depression symptoms and with emotional regulation skills. Additionally, sex differences were observed in frontal, temporal, and visual regions, as well as effects of pubertal development in visual regions. These findings suggest important differences in amygdala reactivity in childhood.
    Cognitive Affective & Behavioral Neuroscience 05/2013; DOI:10.3758/s13415-013-0167-5 · 3.29 Impact Factor
Show more