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PTSD Looking Back & Looking Ahead: Progress and Challenges

PTSD Looking Back & Looking Ahead: Progress and Challenges. Matthew J. Friedman, MD, Ph.D. Executive Director National Center for PTSD. Validity of PTSD is Well-Established. PTSD has proven to be a very useful and valid diagnosis after 25 years of clinical use

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PTSD Looking Back & Looking Ahead: Progress and Challenges

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  1. PTSDLooking Back & Looking Ahead: Progress and Challenges Matthew J. Friedman, MD, Ph.D. Executive Director National Center for PTSD

  2. Validity of PTSD is Well-Established • PTSD has proven to be a very useful and valid diagnosis after 25 years of clinical use • Although there have been minor revisions to the diagnostic criteria the core concept has withstood the test of time

  3. The PTSD Concept • Inability to cope with overwhelming stress may be followed by a distinctive pattern of symptoms • It does not presume that this is the only possible psychiatric outcome

  4. Research Supports the PTSD Concept • PTSD and PTSD symptoms rank among the most common new onset post-traumatic clinical problems • Before DSM-III, there was no way to identify people so affected

  5. The PTSD Hypothesis Made it Possible to: • Predict how affected people react to traumatic reminders • Differentiate them from non-affected people or those with depression or other anxiety disorders • Develop unique therapeutic approaches (e.g. CBT & medication) that could not have been envisioned without the PTSD model

  6. PTSD is a Disorder of Reactivity • Its alterations are best revealed by responses to psychological or pharmacological probes • In contrast, depression is a shift in basal state, alterations are best revealed by measurement of tonic activity

  7. PTSD has a Wealth of Animal Models Unequaled in Psychiatry • Traumatic stress can be operationalized as uncontrollable or unpredictable stress • Laboratory-induced physiological and neurohormonal alterations resemble those seen in PTSD • Brain systems affected by uncontrollable stress and fear conditioning resemble those affected in PTSD

  8. PTSD has Provided a New and Powerful Tool for Translational Research • Translation of important clinical observations into rigorous experimental protocols • Translation of laboratory findings into testable clinical approaches

  9. Is PTSD the Only Post-Traumatic Outcome? No Prospective studies show that people may develop new-onset depression, other anxiety disorders, alcoholism or behavioral alterations without PTSD But that is not what we are here to discuss today

  10. Prevalence of PTSD in the General Population • Large national probability sample of US adults (Ns > 5000) • National Comorbidity Survey (1995) • National Comorbidity Survey-Replication (2005) • Benchmark for prevalence of mental disorders in US • Lifetime PTSD prevalence 6.8% (NCS-R) • 10% women (NCS) • 5% men (NCS)

  11. Combat Exposure in the NCS • Any combat veteran’s lifetime PTSD prevalence = 39% • Male combat > all other male trauma • Lifetime PTSD prevalence • Delayed onset • Unresolved symptoms • Functional impairment (unemployment, being fired, divorce or separation, spousal abuse)

  12. Changes in the PTSD Diagnostic Criteria • Symptom clusters: • Symptoms expanded from DSM-III to III-R and IV • Added duration and distress/impairment • Revised stressor criterion

  13. Biological Profile • The diagnosis has distinguished people with a unique set of biological abnormalities. • These include: • psychophysiological reactivity • neurohormonal profiles • EKG abnormalities • structural and functional brain imaging alternations

  14. The Stress System The stress system coordinates the generalized stress response which takes place when a stressor of any kind exceeds a threshold The main components are: • HPA system • LC/NE system • Immunological system

  15. Are there structural brain abnormalities associated with PTSD?

  16. Left Right abused children abused children Hippocampal Volume in PTSD(% DIFFERENCE BETWEEN PTS AND Controls) combat abuse + MDD childhood abuse childhood abuse combat combat ?? trauma MVA Vythilingam 2001 (unpublished)

  17. Are there functional brain abnormalities associated with PTSD?

  18. MEDIAL PFC & Ant Cingulate Bremner 99Lanius ’00(scripts) Bremner 99Shin ’01(emotional stroop) Shin 97 Semple ’00 Shin 99 HIPPOCAMPUS Bremner 99 OFC Semple 93 Shin 99 Rauch 96 Rauch 96 (combat scripts) Shin 99 (CSA scripts) Liberzon 99(combat sounds) Bremner 99 (CSA scripts) Shin 97 (CSA scripts) Bremner 99 (combat slides Rauch ‘00 (masked faces) & sounds) Semple ’00 (auditory CPT) Bremner 2001 (unpub, fear conditioning) AMYGDALA

  19. Increased Blood Flow with Fear Acquisition versus Control in Abuse-Related PTSD Orbitofrontal Cortex Superior Temporal Gyrus Left Amygdala Yellow areas represent areas of relatively greater increase in blood flow with paired vs. unpaired US-CS in PTSD women alone, z>3.09; p<0.001

  20. Decreased Blood Flow During Recall Of Emotionally Valenced Words In Abuse-Related PTSD Retrieval of Word pairs like “blood-stench” Left hippocampus Medial prefrontal & Orbitofrontal Cortex Fusiform, inferior temporal gyrus

  21. Psychological and Biological Mechanisms We know that: • a number of psychological mechanisms such as negative cognitions, threat appraisal, coping behaviors, information/memory processing and cognitive strategies predict PTSD; • animal models of fear conditioning and neurobiological models concerning the human stress response provide a useful context for understanding acute distress and PTSD; and • exposure to stress during crucial developmental periods may produce stable abnormalities in stress response systems.

  22. PTSD Treatment Options Psychosocial Exposure Therapy Cognitive Therapy Anxiety Management Desensitization Hypnotherapy Pharmacological TCAs MAOIs SSRIs Mood Stabilizers Anti-anxiety Agents

  23. Sertraline Flexible-Dose PTSD Study Weeks 0 1 2 3 4 6 8 10 12 0 Adjusted Mean Change in CAPS-2Total Score -10 -20 -30 * -40 Placebo (N=90) Sertraline (N=93) * p < .001 at week 12 Mean dose for completers = 151.3 mg Brady K et al. JAMA. 2000;283:1837-1844.

  24. Paroxetine Fixed-Dose PTSD Study 0 Paroxetine 20 mg Paroxetine 40 mg -5 Placebo -10 -15 Adjusted Mean Change in CAPS-2 Total Score -20 -25 * -30 * * -35 * * -40 * -45 4 8 12 Week LOCF dataset * p < 0.001 vs placebo Marshall RD, Beebe KL, Oldham M, et al. Am J Psychiatry 2001;158:1982-1988.

  25. Wait-list control SIT PE Prolonged Exposure (PE) Therapy, Stress Inoculation Training (SIT) and Their Combination for Female Assault Victims with PTSD (9 Sessions) 35 30 25 20 PTSD Symptoms (PSS-I) PE/SIT 15 10 5 0 Week 0 Week 5 3 Months 6 Months PSS-I = Post Traumatic Stress Disorder Symptom Scale—Interview; Foa et al, 1999b

  26. Controversy #1 PTSD is not a Legitimate Diagnosis • Battle still wages after 25 years • Being fought in the media as well as scientific journals • Institute of Medicine hearings in U.S. • PTSD’s dubious parentage • Emerged from converging social (feminist, veteran) movements rather than traditional scientific and clinical sources

  27. Controversy #1 (continued) Legitimacy of PTSD diagnosis • Criticism & negative reception has spurred an outpouring of rigorous research • Clinical phenomenology, cognition, brain imaging, personal dynamics • Factor analysis of PTSD symptom clusters has generally validated construct • People with PTSD exhibit significant differences from non-affected individuals

  28. Controversy #2 PTSD Needlessly Pathologizes Normal Reactions to Abusive Violence This argument fails to acknowledge that some people cope successfully with traumatic events and manifest normal distress while others exhibit clinically significant symptoms The purpose of any diagnosis is to inform treatment decisions - not to “pathologize”

  29. Controversy #3PTSD is a Euro-American Culture-Bound Syndrome • PTSD has been documented throughout the world1,2 • Comparable PTSD prevalence in Nairobi embassy and Oklahoma City bombings3 • Men: 26% Nairobi, 20% Oklahoma City • Women: 35% Nairobi, 34% Oklahoma City • Although there may be culture-specific idioms of distress, PTSD appears to encompass a pattern of universal post-traumatic distress 1de Jong et al., 2001; 2 Green et al., 2004; 3 North et al., 2005

  30. Controversy #4PTSD primarily serves a litigious rather than a clinical purpose • Stressor  Causality  Liability • Geometric rise in PTSD-related civil litigation and disability claims • Great concern about amount of money at stake • Big difference between challenging validity of PTSD as a clinical diagnosis and questioning the quality of forensic or disability evaluations

  31. Controversy #5Traumatic Memories are not Valid • When external verification possible - most memories are accurate • Recovered Memory Controversy spurred much useful research • Accurate memories may be lost and later recovered • Some traumatic memories are not accurate • The veracity of any specific recovered memory must be judged on a case-by-case basis

  32. Controversy #6Verbal Reports are Unreliable • Excellent structured interviews and assessment tools have been developed • Reliability of retrospective self-report data among 260 Vietnam theater veterans was recently confirmed by archival records and other external sources (Dohrenwend et al., 2006)

  33. Looking Ahead #1Is PTSD a “Stress-Related Fear Circuitry Disorder?” • Joint APA/WHO initiative being considered for DSM-V/ICD-11 • Based on common neurocircuitry, cognitive alterations and neurohormonal changes • Would cluster PTSD with panic disorder, simple phobia and social phobia

  34. Is PTSD a Fear Circuitry Disorder? Neurocircuitry: Disruption of restraining influence of medial prefrontal cortex (especially ACC) Chain reaction brought about from activation of amygdala by fear stimuli1 1Vermetten & Bremner, 2002; Charney 2004)

  35. Is PTSD a Fear Circuitry Disorder? • Cognitive / Behavioral: PTSD as a model from Pavlovian Conditioning (Kolb, 1989), and Activated Fear Networks (Lang, 1977; Foa & Kozak, 1986).

  36. Potential Non-Verbal Diagnostic Implications of Stress Related Fear Circuitry Model • Stimulus-driven paradigms: Auditory / Visual / Narratives: CV / Electrodermal / Electromyographic/ Brain Imaging (Orr et al., 2004 / Kaufman et al., 2004) CSFP (Geracioti et al 2006) • Pharmacological probes: Super suppression on DST: (Yehuda et al., 1997) Yohimbine (Southwick 1993; Bremner 1997)

  37. Looking Ahead #1 (continued)Is PTSD a “Stress-Related Fear Circuitry Disorder?” • Other emotions besides fear also often present • Sadness, grief, anger, shame & disgust • May not be a nosological problem since the goal is to cluster diagnoses according to a common denominator • Would be a conceptual problem since clinical problems often extend beyond fear-based appraisals and reactions • Shame, anger, substance abuse, aggression, horror, helplessness without personal fear (e.g. medical personnel, graves registration, etc.)

  38. Looking Ahead #2 (continued)Should PTSD be Considered a Dimensional Rather Than a Categorical Disorder? • Subsyndromal/partial PTSD • Chronic non-traumatic stress syndromes • Chronic stress-related medical disorders

  39. Subsyndromal/Partial PTSD Affective Disorders: DSM I, II, III (III-R) and IV DSM-I DSM-II DSM-III/ DSM-IV III-R BAD/Manic-Depression X X X X MDD/Psychotic Depression X X X X Dysthmia/Depressive Neurosis X X X X Cycolthymia/Affective Personality X X X X Involuntary Meloncholia X (Other) Mood Disorder NOS X X Atypical Bipolar/NOS X X Atypical Depressive/NOS X X Adj Disorder - Depressed X X Adj Disorder - Mixed Anx/Dep X X

  40. PSSD - Post-Severe Stress Disorder “Severe” vs. “Traumatic” Stress Are there enduring psychiatric syndromes caused by acute or chronic non-traumatic but severe stress? Divorce, failure, bankruptcy, illness, bereavement Does PSSD differ from PTSD?

  41. Chronic Stress Syndrome • PSSD has medical consequences • PTSD also has medical consequences Both affect HPA, cardiovascular, immunological, and other systems • Should “medical” illnesses precipitated by stress be included with PSSD/PTSD as “stress disorders?” • Chronic Fatigue Syndrome • Fibromyalgia • Peripheral Vascular Disease • Endocrinopathies • etc

  42. Looking Ahead #3New Directions for Psychosocial Treatment • Despite success of CBT (PE, CT, CPT and EMDR) there is evidence for the efficacy of treatments that do not focus on traumatic material • SIT - focuses on symptom management rather than trauma processing • Present centered therapies have also been effective • SIT and PCT do better in recruitment and retention

  43. Looking Ahead #3 (continued)New Directions for Psychosocial Treatment • Need predictors of treatment outcome • Case matching - some may be better candidates for trauma processing and others for present-centered approaches or medication

  44. Looking Ahead #3 (continued)New Directions for Psychosocial Treatment • EMDR - How does it work? • Is it CBT in disguise? • Does it work through a unique mechanism? • Using brain imaging techniques might be a way to approach this issue

  45. Looking Ahead #3 (continued)New Directions for Psychosocial Treatment • Third Wave Influenced by Eastern & “mindfulness” approaches that emphasize acceptance • Little evidence of efficacy so far • Comorbidity • Substance abuse (Seeking Safety) • Traumatic brain injury • Technology • Web based, virtual reality, telehealth

  46. Looking Ahead #4New Directions for Biological Research • Need to expand focus beyond serotonin and norepinephrine • CRF, NPY, GABA, glutamate, dopamine, etc. • Is PTSD a final common pathway (like fever or edema) that can be caused by different patterns of psychobiological alterations? • Genetic research on resilience and vulnerability

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