There are three important strands to our work with patients with GSP and GAD: The first of these strands is determining the degree to which the pathology seen in GAD differs from that seen in GSP. In previous work, we were the first to demonstrate that patients with GSP and GAD differ in their responsiveness to emotional expression stimuli. Specifically, we showed that the heightened amygdala response to fearful expressions seen in GSP is not seen in patients with GAD. Indeed, they show indications of hypo-responsiveness. Over the past year, we have extended these results in two important ways: (a) only patients with GAD and not those with GSP show reduced optimistic bias. This appears to reflect dysfunction in the role of rostral medial frontal cortex in comparison processes;and (b) only patients with GSP and not those with GAD show dysfunction in the context of social referencing. Social referencing refers to the process by which an individual learns the value of objects and actions by witnessing another's reactions to them. The second strand concerns the specific nature of the functional impairment seen in GSP. In previous work, we have shown that GSP does not simply represent a heightened amygdala response to social threats. Instead, there appears additionally to be atypical self referential processing of social information. In short, our earlier work had indicated an important role for not only the amygdala but also medial prefrontal cortex (MPFC a region critical for self referential processing) in GSP. This year, we extended this work by showing that patients with GSP show heightened amygdala and medial prefrontal cortex responses when engaged in social referencing (watching another show an emotional reaction to an object) than comparison populations. In addition, patients with GSP show heightened amygdala responses to objects associated with another individuals emotional displays. Importantly, social referencing is thought to be important for the development and maintenance of phobias and the impairment may contribute to the persistence of this disorder. The third strand of work concerns the specific nature of the functional impairment seen in GAD. In particular, we have been examining whether some of the problems in emotional responding in GAD that we observed in our preliminary work with patients with this disorder might manifest in difficulties on decision making tasks. Following on from our previous results, we developed an optimistic bias task suitable for fMRI. Optimistic bias refers to the tendency of healthy individuals to consider that good things are more likely to occur to them, and bad things less likely to occur to them, than is statistically probable. Reduced optimistic bias is seen in depression and we showed that it is also seen in GAD but not GSP. Importantly, we identified the neuro-computational impairment that may underpin the impairment in GAD. Specifically, the role of rostral medial frontal cortex in the comparison of valenced event probabilities appears to be disrupted in GAD.

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U.S. National Institute of Mental Health
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Blair, K S; Vythilingam, M; Crowe, S L et al. (2013) Cognitive control of attention is differentially affected in trauma-exposed individuals with and without post-traumatic stress disorder. Psychol Med 43:85-95
Blair, Karina S; Otero, Marcela; Teng, Cindy et al. (2013) Dissociable roles of ventromedial prefrontal cortex (vmPFC) and rostral anterior cingulate cortex (rACC) in value representation and optimistic bias. Neuroimage 78:103-10
Blair, Karina S; Geraci, Marilla; Smith, Bruce W et al. (2012) Reduced dorsal anterior cingulate cortical activity during emotional regulation and top-down attentional control in generalized social phobia, generalized anxiety disorder, and comorbid generalized social phobia/generalized anxiety disorder. Biol Psychiatry 72:476-82
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DeVido, J; Jones, M; Geraci, M et al. (2009) Stimulus-reinforcement-based decision making and anxiety: impairment in generalized anxiety disorder (GAD) but not in generalized social phobia (GSP). Psychol Med 39:1153-61
Blair, Karina; Shaywitz, Jonathan; Smith, Bruce W et al. (2008) Response to emotional expressions in generalized social phobia and generalized anxiety disorder: evidence for separate disorders. Am J Psychiatry 165:1193-202