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Introduction
Generalized anxiety disorder (GAD) is a common psychiatric disorder that is characterized by excessive, uncontrollable worry and anticipatory anxiety. Recent epidemiological research estimates a lifetime prevalence of 4.1% (Grant et al. 2005) with significant impacts on healthcare systems (Hoffman et al. 2008). However, there have been relatively few studies of GAD compared with other psychiatric disorders (Dugas et al. 2010) and, in particular, very few functional imaging studies.
Recent functional magnetic resonance imaging (fMRI) studies have examined the response to emotional facial expressions in order to investigate the neural substrates of mood and anxiety disorders (Blair et al. 2008; Lee et al. 2008a; Matthews et al. 2008). A review of emotional processing in mood disorders reported that patients with major depressive disorder (MDD) generally show bias toward negative emotional stimuli and away from positive stimuli (Leppanen, 2006). Compared with controls, patients with MDD show an increased blood oxygen level dependent (BOLD) signal in the amygdala and ventral striatum to increasingly sad stimuli and a decreased BOLD signal in these areas to increasingly happy stimuli (Leppanen, 2006). However, another study specifically looking at fMRI face emotion processing results in patients with MDD found attenuation in frontolimbic and subcortical regions in response to negative (sad, angry) facial expressions (Lee et al. 2008a).
In studies of face processing in participants with GAD, the most consistent finding has been an increased ventrolateral prefrontal cortex (VLPFC) and/or anterior cingulate cortex (ACC) BOLD signal to negative face emotions (Monk et al. 2006, 2008; McClure et al. 2007; Blair et al. 2008). The prefrontal cortex and the ACC both have connections to the amygdala and have been implicated in emotional processing (Hariri et al. 2003; Ochsner et al. 2004). These findings could indicate either a change in function in these areas due to anxiety or a compensatory response based on change in another connected area.
BOLD signal in the VLPFC and ACC during face emotion processing has also been found to predict treatment response in GADs. A recent fMRI study of adolescent GAD patients before and after treatment found increased right VLPFC activation in response to angry facial expressions following treatment with either cognitive behavioural therapy or the selective serotonin reuptake...