Elsevier

Biological Psychiatry

Volume 63, Issue 9, 1 May 2008, Pages 858-863
Biological Psychiatry

Original Article
A Functional Magnetic Resonance Imaging Predictor of Treatment Response to Venlafaxine in Generalized Anxiety Disorder

https://doi.org/10.1016/j.biopsych.2007.08.019Get rights and content

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.

Section snippets

Participants

Thirty subjects (24 female subjects) shown to be right-handed (26) were studied. Fifteen of these subjects (12 female subjects) answered a local newspaper advertisement seeking individuals with GAD for a venlafaxine treatment study (mean age 27 ± 7 [SD] years; range 19–52). The 15 control subjects who were also recruited via newspaper advertisement (mean age 33 ± 11 [SD] years; range 20–51) did not differ significantly in age [t(28) = 1.79, p > .05] or in years of education [t(28) = .58, p >

fMRI Predictor of Treatment Response in Subjects with GAD: Reported Anxiety

Table 1 presents pretreatment and posttreatment HAM-A scores for all subjects. Individual differences in decrease in HAM-A scores were then correlated with pretreatment amygdala and rACC responsivity of subjects with GAD to fearful faces. Figure 1A depicts a significant positive correlation between drop in HAM-A scores (y axis) and pretreatment rACC (x = −12, y = 32, z = 22) responsivity (x axis) to fearful faces when compared with neutral faces (r = .61, p = .016). Figure 1B shows a

Discussion

Pretreatment fMRI responsivity during presentation of biologically relevant stimuli associated with threat (i.e., fearful faces) predicted treatment response to venlafaxine in subjects with GAD. Specifically, greater rACC and lesser amygdala responsivity to fearful faces predicted greater decreases in anxiety after 8 weeks of treatment. This effect was specific to fearful faces, as no such effect was observed to either happy or neutral faces when directly contrasted (Figure 1E and F).

Given the

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