Anxiety

1. Anxiety

2. A hot topic Dialogue needed on mental health

3. What is it? What forms does it take? What causes it? When is it a problem? How do we diagnose it? How do we treat it? What brain regions would we expect to be involved? Anxiety

4. Why was the study done? -Inconsistencies in the literature. Hypotheses? -Abnormal fear response -Abnormal amygdala activity Etkin and Wager (2007) Functional Neuroimaging of Anxiety: A Meta- Analysis of Emotional Processing in PTSD, Social Anxiety Disorder, and Specific Phobia

5. Social anxiety, PTSD, and phobia Meta-analysis: -Inclusion criteria -What were the control studies? -They did ROI’s as well -Coactivation patterns (like functional connectivity?) Method

6. All three disorders showed some consistent hyperactivity. Hyperactivity was observed in the amygdala and insula in all three disorders. Amygdala/insula hyperactivity more common in SAD and phobia than PTSD Results

7. Only PTSD showed any consistent hypoactivity (in regions including ACC and prefrontal regions). In five studies, MPFC activity was negatively associated with PTSD symptom severity. -What might this mean? What confounds might explain the more complicated PTSD results? -More PET studies (authors address this) -More studies and patients (nearly twice as many)=more power (authors address this by pooling phobia and SAD data in coact. analysis) PTSD

8. Consistent cohypoactivation of medial frontal regions in PTSD Negative coactivation between ACC and amydala/insula in PTSD No coactiviation between frontal and limbic regions in SAD or phobias. Coactivation analysis

9. Common amygdalahyperactivation indicates hyperactive fear circuitry -Do we buy this? What does it really tell us? In PTSD, regions of both hypo-and hyperactivation in amygdala. Are we surprised? -Authors suggest a ventral, hyperactive fear acquisition region and a dorsal, hypoactive region resulting in “autonomic blunting”. Are we surprised by the insula hyperactivity? Why/why not? Discussion/Conclusions

10. Propose the rACC and VMPFC as emotional control centers based on previous research Propose PTSD to be more of an emotion regulation problem than a fear extinguishing problem based on hypoactivation in rACC and VMPFC Conclusions continued

11. Do we think that these three disorders involve a shared mechanism? Stress Inoculation? How might structural MRI help us understand these disorders better? Questions for discussion

12. Social Anxiety Disorder: Epidemiology, Biology, and Treatment Definition and prevalence How do we distinguish it? Two types: generalized and performance-type Any comments on the course/burden? Fink, Akimova, Spindelegger, Hahn, Lanzenberger, & kasper

13. Genetic factors: -linkage near norepinephrin transporter protein (elaboration?) -Adrenergic receptor gene polymorphism linked with low extraversion -Association of Corticitropin releasing hormone gene (which is key for instigating the stress response) and behavioral inhibition. Neurochemical factors: -Possible dysfunction of striataldopaminergic system -Increased amygdala activation has been associated with polymorphisms for the serotonin transporter and tryptophan hydroxylase-2 (also important for synthesis of serotonin). -Serotonin receptor distribution Biology

14. Tryptophan => serotonin =>melatonin Anyone heard of melatonin? Reminder

15. Figure 1. Serotonin-1A receptor distribution in the human brain. The distribution was measured with PET using the radioligand (carbonyl-11C) WAY-100635 and superimposed on magnetic resonance images. The picture shows coronal, sagittal and axial views of a male social anxiety patient (A) and a healthy male control subject (B). The colour bar indicates serotonin-1A receptor binding potential values. The serotonin-1A receptor binding is reduced across all brain regions in the patient

16. From Etkin and Wager. Hyperactivation in: -Parahippocampalgyrus -Fusiformgyrus-Attention to faces? -Globuspallidus -Inferior frontal gyrus -Superior Temporal Gyrus –ToM? -Amygdalae -Insula Anatomy/brain function

17. Recommendation for first line SSRI treatment. Possibly combine with psychotherapy, leading candidates being CBT and exposure therapy. SSRI’s are the most effective thusfar. SNRI’s are promising but not yet well-validated MAOI’s may have side effects Benzodiazapines and α2δ calcium-channel blockers can be a second line. Treatment

18. This article takes a largely biomedical perspective (i.e. treating the symptoms as a distinct disorder to be treated). What do you think of the efficacy/efficiency of this approach? Questions for discussion

19. Neural mechanisms of symptom improvements in generalized anxiety disorder following mindfulness training What is GAD? What is mindfulness? What theories were they testing? -Psychological and biological mechanisms? Hötzel and colleagues

20. Mindfulness=> increased affect labeling => decreased anxiety My criticism of this pathway hypothesis in a nutshell

21. Groups and treatments -Were groups well-matched? -Do we agree with the control treatment? It seemed to work, anyway. -What controls were lacking? (Greer) What stimuli did they use? -Why? Was this a good idea? (Liz) -What do they hypothesize about neutral faces? method

22. Baseline differences in amygdala activity to neutral faces only Decrease in PSS scores after treatment, but no difference between treatments. However, significantly greater decrease in BAI scores for mindfulness treatment. Amygdala response to neutral faces decreased after treatment, but no difference between treatments. results

23. MBSR patients showed greater increase in VLPFC activity than SME for neutral faces -Let’s talk about their post-hoc analyses… Negative correlation between change in VLPFC activity and change in BAI scores Similar results to angry faces, but what’s the deal with the pre-treatment comparison? results

24. Amygdala as seed region What did they find at baseline? -This is weird. Functional connectivity changed with mindfulness, but not with control. -rACC, rostral middle frontal cortex, right superior frontal cortex Amygdala connectivity to frontal regions was negatively correlated with BAI scores post-mindfulness intervention connectivity

25. There was increased connectivity after mindfulness, but the GAD patients were apparently not lacking in connectivity. How do we interpret this? “Catching up” to controls, or a completely different strategy? (Note that Etkin et al. 2009 did find differences in baseline connectivity) The discussion of connectivity between amygdala and DLPFC doesn’t add up… (p. 456) Discussion and conclusions

26. The authors propose that it is the ambiguousness of neutral faces that causes patients anxiety (“intolerance of uncertainty” model). What do you think? -Lack of salience=lack of distraction How would we account for the decrease in amygdalaacticity in both treatments, but the increase in connectivity only in meditation? Are different strategies being used? What do we make of the shift from a negative connectivity to positive connectivity after treatment? Questions for discussion

27. Why do so many people not seek treatment for anxiety? Are we satisfied with the current state of anxiety treatment/approaches to anxiety? What do you think could be improved? Etkin and Wager suggest that PTSD is more associated with emotional dysregulation than phobias or SAD. Yet Hötzel and colleagues cite an emotion dysregulation hypothesis for GAD. Why? General discussion

28. Who defines excessive worry? In what contexts might “anxiety disorders” not be considered disorders at all? What defines emotional dysregulation? PTSD research on campus: http://www.sciencedirect.com/science/article/pii/S1074742713002414 Philosophy of anxiety Questions for discussion