Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response.
OBJECTIVE
The anticipation of adverse outcomes, or worry, is a cardinal symptom of generalized anxiety disorder. Prior work with healthy subjects has shown that anticipating aversive events recruits a network of brain regions, including the amygdala and anterior cingulate cortex. This study tested whether patients with generalized anxiety disorder have alterations in anticipatory amygdala function and whether anticipatory activity in the anterior cingulate cortex predicts treatment response.


METHODS
Functional magnetic resonance imaging (fMRI) was employed with 14 generalized anxiety disorder patients and 12 healthy comparison subjects matched for age, sex, and education. The event-related fMRI paradigm was composed of one warning cue that preceded aversive pictures and a second cue that preceded neutral pictures. Following the fMRI session, patients received 8 weeks of treatment with extended-release venlafaxine.


RESULTS
Patients with generalized anxiety disorder showed greater anticipatory activity than healthy comparison subjects in the bilateral dorsal amygdala preceding both aversive and neutral pictures. Building on prior reports of pretreatment anterior cingulate cortex activity predicting treatment response, anticipatory activity in that area was associated with clinical outcome 8 weeks later following treatment with venlafaxine. Higher levels of pretreatment anterior cingulate cortex activity in anticipation of both aversive and neutral pictures were associated with greater reductions in anxiety and worry symptoms.


CONCLUSIONS
These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder.
Nitschke
Jack B
JB
Departments of Psychiatry and Psychology, University of Wisconsin, Madison, 53705-2280, USA. jnitschke@wisc.edu
Sarinopoulos
Issidoros
I
Oathes
Desmond J
DJ
Johnstone
Tom
T
Whalen
Paul J
PJ
Davidson
Richard J
RJ
Kalin
Ned H
NH
D000328:Adult; D000679:Amygdala / Q000502:physiology*; D001008:Anxiety Disorders / Q000175:diagnosis*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D006179:Gyrus Cinguli / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D055815:Young Adult