Attenuated responses to emotional expressions in women with generalized anxiety disorder M. E. Palm*, R. Elliott, S. McKie, J. F. W. Deakin and I. M. Anderson The University of Manchester, Neuroscience & Psychiatry Unit, Stopford Building, Manchester, UK Background. Generalized anxiety disorder (GAD) is under-researched despite its high prevalence and large impact on the healthcare system. There is a paucity of functional magnetic resonance imaging (fMRI) studies that explore the neural correlates of emotional processing in GAD. The present study investigated the blood oxygen level dependent (BOLD) response to processing positive and negative facial emotions in patients with GAD. Method. A total of 15 female GAD patients and 16 female controls undertook an implicit face emotion task during fMRI scanning. They also performed a face emotion recognition task outside the scanner. Results. The only behavioural difference observed in GAD patients was less accurate detection of sad facial expressions compared with control participants. However, GAD patients showed an attenuated BOLD signal in the prefrontal cortex to fearful, sad, angry and happy facial expressions and an attenuated signal in the anterior cingulate cortex to happy and fearful facial expressions. No differences were found in amygdala response. Conclusions. In contrast with previous research, this study found BOLD signal attenuation in the ventrolateral and medial prefrontal cortex and the anterior cingulate cortex during face emotion processing, consistent with a hypothesis of hypo-responsivity to external emotional stimuli in GAD. These decreases were in areas that have been implicated in emotion and cognition and may reflect an altered balance between internally and externally directed attentional processes. Received 9 October 2009 ; Revised 4 July 2010 ; Accepted 8 July 2010 ; First published online 18 August 2010 Key words : Anxiety, emotion, fMRI, GAD. 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 preva- lence 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 com- pared 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 emotion- al facial expressions in order to investigate the neural substrates of mood and anxiety disorders (Blair et al. 2008 ; Lee et al. 2008 a ; 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 stim- uli and away from positive stimuli (Leppanen, 2006). Compared with controls, patients with MDD show an increased blood oxygen level dependent (BOLD) sig- nal in the amygdala and ventral striatum to increas- ingly 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 sub- cortical regions in response to negative (sad, angry) facial expressions (Lee et al. 2008 a). In studies of face processing in participants with GAD, the most consistent finding has been an in- creased 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 * Address for correspondence : Dr M. E. Palm, Nowgen, A Centre for Genetics in Healthcare, NIHR Biomedical Research Centre, The University of Manchester, The Nowgen Centre, 29 Grafton Street, Manchester M13 9WU, UK. (Email : marisha.palm@manchester.ac.uk) Psychological Medicine (2011), 41, 1009–1018. f Cambridge University Press 2010 doi:10.1017/S0033291710001455 ORIGINAL ARTICLE