Brain Imaging of Anxiety Disorders

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Functional Neuroanatomy of Traumatic Stress. . . . . . . . . . . . . . Amygdala. Hippocampus. Locus Coeruleus. Pituitary. Hypothalamus. OrbitofrontalCortex. Cerebral Cortex. . . Adrenal. . . . . . . CRF. ACTH. NE. extinction to fearthrough amygdalainhibition. long-term storage of traumatic memor

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Brain Imaging of Anxiety Disorders

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1. Brain Imaging of Anxiety Disorders J. Douglas Bremner, MD Emory University, Atlanta, Georgia www.dougbremner.com

2. Functional Neuroanatomy of Traumatic Stress

3. Functional Neuroanatomy of Trauma Spectrum Disorders

6. Replications of Findings from Functional Imaging in PTSD

7. PTSD Studies with Increased Amygdala Activation

8. Hippocampal Volume Reduction in Childhood Abuse-related PTSD

9. Hippocampal Volume Reduction in PTSD NORMAL PTSD

10. Effect Size Estimates for Hippocampal Volume in Adults with Chronic PTSD Versus Healthy Subjects

11. Effects of Paroxetine on Hippocampal-based Verbal Declarative Memory in PTSD

12. Increased Hippocampal Volume with Paxil in PTSD

13. Smaller Hippocampal and Amygdala Volume in Abused Women with BPD

14. Smaller Hippocampal Volume in Abused Women with Dissociative Identity Disorder

16. Women with Childhood Sexual Abuse-related PTSD Women with abuse and PTSD, women with abuse without PTSD, and women without abuse or PTSD-assess hippocampus with imaging & cortisol at rest and with stress Early childhood sexual abuse before the age of 13– defined as rape or molestation Abuse assessed with the Early Trauma Inventory All subjects free of psychotropic medication for four weeks before study

18. Failure of Hippocampal Activation in Women with PTSD Related to Childhood Sexual Abuse

19. Increased Cortisol Response To Trauma-Specific Stress in PTSD

20. Trauma and the Medial Prefrontal Cortex Medial prefrontal cortex involved in inhibition of fear responses in the amygdala (Quirk) Early stress associated with decreased dendritic branching in medial prefrontal cortex (Radley) Neurological damage associated with deficits in emotional responding (includes orbitofrontal cortex and anterior cingulate)

21. Medial Prefrontal Cortex in Stress & Emotion Orbitofrontal Cortex Gyrus rectus and medial orbitofrontal cortex Anterior Cingulate Subcallosal gyrus (area 25) mediates peripheral cortisol and sympathetic responses to stress Area 32 implicated in “normal emotion”, as well as attention/selection of action (Stroop) Anteromesal Prefrontal Cortex Superior & Middle Frontal Gyrus (9)

22. Decreased Anterior Cingulate Volume in Women with Abuse Related PTSD

23. Medial Prefrontal Cortical Dysfunction with Traumatic Memories in PTSD

24. Decreased Blood Flow during Memories of Abuse in Women with Childhood Sexual Abuse-related PTSD

25. Decreased Blood Flow During Recall of Emotionally Valenced Words in Abuse-related PTSD

26. Decreased Blood Flow with Emotional Stroop in Abused Women with and without PTSD

27. Neural Correlates of Memories of Abandonment in Borderline Personality Disorder with Early Trauma

28. Conditioned Fear in PTSD Pairing of light and shock leads to increased fear responding and increased startle to light alone (conditioned fear) Conditioned fear and startle response mediated by central nucleus of the amygdala Failure of extinction with lesions of medial prefrontal cortex (inhibits amygdala) Study design– habituation (blue square), fear acquisition (blue square + shock), extinction (blue square); control day– random shocks

29. Fear Conditioning in PTSD Study Design Scan #?

30. Increased Anxiety Symptoms with Fear Acquisition and Extinction in Abuse-related PTSD

31. Increased Blood Flow with Fear Acquisition versus Control in Abuse-related PTSD

32. Decreased Blood Flow in Medial Prefrontal Cortex/Anterior Cingulate with Extinction in PTSD

33. Increased Dissociation Correlates With Increased Amygdala Blood Flow During Fear Acquisition in PTSD patients

34. Increased Amygdala Activation in PTSD fMRI in conjunction with fear conditioning Neutral faces used as conditioned stimulus (CS); random interval between CS Unconditioned stimulus (shock) presented at end of CS presentation Second group received unpaired CS-UCS

35. Increased Amygdala Activation in PTSD

36. Brain Circuits in Trauma Spectrum Disorders: Brain Volumes

37. Brain Circuits in Trauma Spectrum Disorders: Brain Function

38. Conclusions Amygdala, hippocampus and prefrontal cortex mediate symptoms of PTSD and related trauma spectrum disorders (DID, BPD) Variations in interaction of stress with individual factors (genetics, etc) mediate differences in outcome Future research needed to assess similarities and differences in trauma spectrum disorders

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