Failure of Anterior Cingulate Activation and Connectivity With the Amygdala During Implicit Regulation of Emotional Processing in Generalized Anxiety Disorder

• Published in: The American journal of psychiatry Vol. 167; no. 5; pp. 545 - 554
• Main Authors: Etkin, Amit, Prater, Katherine E., Hoeft, Fumiko, Menon, Vinod, Schatzberg, Alan F.
• Format: Journal Article
• Language: English
• Published: Arlington, VA American Psychiatric Association 01.05.2010
• Subjects: Adaptation, Psychological - physiology; Adult; Adult and adolescent clinical studies; Amygdala - physiopathology; Anxiety; Anxiety Disorders - physiopathology; Anxiety disorders. Neuroses; Biological and medical sciences; Case-Control Studies; Conflict (Psychology); Emotions - physiology; Female; Gyrus Cinguli - physiopathology; Humans; Magnetic Resonance Imaging; Male; Medical sciences; Miscellaneous; Neural Pathways - physiopathology; Neurosciences; Psychiatric Status Rating Scales; Psychology. Psychoanalysis. Psychiatry; Psychopathology; Psychopathology. Psychiatry; Studies; Affect affectivity; Amygdala; Central nervous system; Anxiety disorder; Cognition; Basal ganglion; Activation; Emotion emotionality; Encephalon; Cingulate cortex; Generalized anxiety disorder; Information processing; Amygdaloid nucleus; Failure
• ISSN: 0002-953X; 1535-7228; 1535-7228
• DOI: 10.1176/appi.ajp.2009.09070931

ObjectiveClinical data suggest that abnormalities in the regulation of emotional processing contribute to the pathophysiology of generalized anxiety disorder, yet these abnormalities remain poorly understood at the neurobiological level. The authors recently reported that in healthy volunteers the pregenual anterior cingulate regulates emotional conflict on a trial-by-trial basis by dampening activity in the amygdala. The authors also showed that this process is specific to the regulation of emotional, compared to nonemotional, conflict. Here the authors examined whether this form of noninstructed emotion regulation is perturbed in generalized anxiety disorder. MethodSeventeen patients with generalized anxiety disorder and 24 healthy comparison subjects underwent functional MRI while performing an emotional conflict task that involved categorizing facial affect while ignoring overlaid affect label words. Behavioral and neural measures were used to compare trial-by-trial changes in conflict regulation. ResultsComparison subjects effectively regulated emotional conflict from trial to trial, even though they were unaware of having done so. By contrast, patients with generalized anxiety disorder were completely unable to regulate emotional conflict and failed to engage the pregenual anterior cingulate in ways that would dampen amygdalar activity. Moreover, performance and brain activation were correlated with symptoms and could be used to accurately classify the two groups. ConclusionsThese data demonstrate that patients with generalized anxiety disorder show significant deficits in the noninstructed and spontaneous regulation of emotional processing. Conceptualization of anxiety as importantly involving abnormalities in emotion regulation, particularly a type occurring outside of awareness, may open up avenues for novel treatments, such as by targeting the medial prefrontal cortex.