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BACKGROUND: Functional magnetic resonance imaging (fMRI) holds promise as a noninvasive means of identifying neural responses that can be used to predict treatment response before beginning a drug trial. Imaging paradigms employing facial expressions as presented stimuli have been shown to activate the amygdala and anterior cingulate cortex (ACC). Here, we sought to determine whether pretreatment amygdala and rostral ACC (rACC) reactivity to facial expressions could predict treatment outcomes in patients with generalized anxiety disorder (GAD). METHODS: Fifteen subjects (12 female subjects) with GAD participated in an open-label venlafaxine treatment trial. Functional magnetic resonance imaging responses to facial expressions of emotion collected before subjects began treatment were compared with changes in anxiety following 8 weeks of venlafaxine administration. In addition, the magnitude of fMRI responses of subjects with GAD were compared with that of 15 control subjects (12 female subjects) who did not have GAD and did not receive venlafaxine treatment. RESULTS: The magnitude of treatment response was predicted by greater pretreatment reactivity to fearful faces in rACC and lesser reactivity in the amygdala. These individual differences in pretreatment rACC and amygdala reactivity within the GAD group were observed despite the fact that 1) the overall magnitude of pretreatment rACC and amygdala reactivity did not differ between subjects with GAD and control subjects and 2) there was no main effect of treatment on rACC-amygdala reactivity in the GAD group. CONCLUSIONS: These findings show that this pattern of rACC-amygdala responsivity could prove useful as a predictor of venlafaxine treatment response in patients with GAD.
We used fMRI to examine amygdala activation in response to fearful facial expressions, measured over multiple scanning sessions. 15 human subjects underwent three scanning sessions, at 0, 2 and 8 weeks. During each session, functional brain images centered about the amygdala were acquired continuously while participants were shown alternating blocks of fearful, neutral and happy facial expressions. Intraclass correlation coefficients calculated across the sessions indicated stability of response in left amygdala to fearful faces (as a change from baseline), but considerably less left amygdala stability in responses to neutral expressions and for fear versus neutral contrasts. The results demonstrate that the measurement of fMRI BOLD responses in amygdala to fearful facial expressions might be usefully employed as an index of amygdala reactivity over extended periods. While signal change to fearful facial expressions appears robust, the experimental design employed here has yielded variable responsivity within baseline or comparison conditions. Future studies might manipulate the experimental design to either amplify or attenuate this variability, according to the goals of the research.