Our work has been important in suggesting that GAD and GSP are indeed associated with different pathophysiologies. In recent work, we presented patients with GSP, patients with GAD, and no pathology individuals with angry, fearful, and neutral facial expression stimuli. Our data clearly suggested that the neural circuitry dysfunction in GSP and GAD differ. Specifically, we found that patients with GSP showed significantly increased activation to fearful relative to neutral expressions in several regions, including the amygdala. In contrast, patients with GAD showed significantly reduced activation to fearful relative to neutral faces compared to healthy individuals and patients with GSP but this was coupled with anomalously and significantly increased responses in a lateral region of prefrontal cortex. Importantly, a secondary analysis conducted with the subgroup of patients with comorbid GAD/GSP indicated that they presented with the pathologies associated with the GAD, but not the GSP. That is, these preliminary results strongly suggest the importance of a systematic examination and comparison of GSP, GAD, and comorbid GAD/GSP for a fuller disorder-specific understanding and development of new treatment targets.? ? In other recent work, we examined the neural responses to receipt of praise or criticism in GSP and GAD within a newly design novel statement paradigm. Participants were presented with positive, negative, and neutral statements (e.g., You are beautiful/ ugly/ human) that could be either about highly relevant and about themselves or less relevant about somebody else (e.g., He is beautiful). There were again two major results. First, there again was a clear double dissociation between the individuals with GSP and GAD with suggestions of a divergent subcortical response to social stimuli in the two populations. Second, the results indicated an important role for self-relevance and medial prefrontal cortex (MPFC), mediating self-relevance, in GSP. Thus, on this task patients with GSP showed significantly increased neural responses in MPFC and amygdala to negative comments about the self (criticism). However, the groups did not differ significantly in their neural responses to any of the other statement categories: neutral or positive comments about the self, or negative, neutral, or positive comments about others. ? ? In other recent work, we examined stimulus-reinforcement based decision making using a task that has previously been demonstrated to recruit the amygdala and vmPFC in healthy individuals. The data on this task also indicated a dissociation between GAD and GSP. Thus, only patients with GAD showed impairment on this task (relative to both patients with GSP and healthy individuals who did not significantly differ). Moreover, the patients with comorbid GAD/GSP also showed significant impairment on the task (relative to both patients with GSP and healthy individuals). However, the patients with comorbid GAD/GSP and those with GAD alone did not show significant differences in impairment. Thus, this work has underlined the importance of determining the separable pathophysiologies associated with the individual conditions.
| Blair, K S; Otero, M; Teng, C et al. (2017) Reduced optimism and a heightened neural response to everyday worries are specific to generalized anxiety disorder, and not seen in social anxiety. Psychol Med 47:1806-1815 |
