A functional magnetic resonance imaging predictor of treatment response to venlafaxine in generalized anxiety disorder

Abstract

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.

Figure 1

fMRI statistical maps showing that pretreatment responsivity to fearful versus neutral faces is positively correlated in the left rACC (red) and negatively correlated in the left amygdala (blue) with subjects' drop in HAM-A scores after 8 weeks of treatment with venlafaxine. R=right, L=left. Images thresholded at p = .05, corrected.FvN=fear versus neutral contrast in the rACC(A) and amygdala(B). Y axis=drop in HAM-A scores after 8 weeks of treatment (i.e., pretreatment minus posttreatment score); X axis=fMRI percent signal change. Higher rACC reactivity and lower amygdala reactivity predict a greater drop in reported anxiety. Results are similar for the fear versus happy (FvH) contrast(C, D) but not the happy versus neutral (HvN) contrast (E, F) (data presented from the FvN contrast locus), showing that these effects are specific to fearful faces. Axes same as in (A) and (B). (G) rACC and amygdala responses to fearful versus neutral faces are negatively correlated showing that the subjects with higher rACC signal tend to be the subjects with lower amygdala signal. Both axes are fMRI percent signal change. fMRI, functional magnetic resonance imaging; HAM-A, Hamilton Anxiety Rating Scale; rACC, rostral anterior cingulate cortex.