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Brain Imaging of Childhood Abuse Related Posttraumatic Stress Disorder

Disclosures. Grant SupportNIH: R01 MH56120, T32 MH067547, K24 MH076955(As co-investigator) R01 AG026255, R01 HL068630, R01 HL703824, R01 MH068791, P50 MH58922Veterans Administration: Merit Review, VET-HEAL AwardNational Alliance for Research on Schizophrenia and Depression (NARSAD)Indepen

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Brain Imaging of Childhood Abuse Related Posttraumatic Stress Disorder

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    1. Brain Imaging of Childhood Abuse Related Posttraumatic Stress Disorder J. Douglas Bremner, MD Emory University, Atlanta, Georgia www.dougbremner.com For copy of slides & disclosures

    2. Disclosures Grant Support NIH: R01 MH56120, T32 MH067547, K24 MH076955 (As co-investigator) R01 AG026255, R01 HL068630, R01 HL703824, R01 MH068791, P50 MH58922 Veterans Administration: Merit Review, VET-HEAL Award National Alliance for Research on Schizophrenia and Depression (NARSAD) Independent Investigator Award American Foundation for Suicide Prevention (AFSP) Georgia Research Alliance GlaxoSmithKline Investigator Initiated Medical Research Consulting Novartis GlaxoSmithKline Speakers Bureaus None Discussion of Off Label Medication Use Phenytoin

    3. Posttraumatic Stress Disorder Intrusive memories, nightmares, flashbacks, arousal, avoidance, startle, sleep disturbance, gaps in memory and concentration Associated with threat to life or other with fear/horror/helplessness (A) Affects 15% of traumatized individuals 16% of women with sexual abuse 8% lifetime PTSD prevalence (10% women) Abuse also associated with borderline personality disorder (BPD) and dissociative identity disorder (DID)

    4. Functional Neuroanatomy of Trauma Spectrum Disorders

    5. Stress Results in Decreased Hippocampal Neurogenesis

    6. Antidepressant Treatments Promote Hippocampal Neurogenesis

    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. Smaller Hippocampal Volume in Women with Childhood Abuse and Depression

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

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

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

    17. 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)

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

    19. Replications of Findings from Functional Imaging in PTSD

    20. Medial Prefrontal Cortical Dysfunction with Traumatic Memories in PTSD

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

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

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

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

    25. 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

    26. Fear Conditioning in PTSD Study Design Scan #?

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

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

    29. 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

    30. Increased Amygdala Activation in PTSD

    31. Glucocorticoids

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

    33. Increased Hippocampal Volume with Paxil in PTSD

    34. Brain Circuits in Trauma Spectrum Disorders: Brain Volumes

    35. Brain Circuits in Trauma Spectrum Disorders: Brain Function

    36. 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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