Stress and Memory: 2

1. Stress and Memory: 2 Dr. Sarah N. Garfinkel Brighton and Sussex Medical School Applied Cognitive Psychology

2. Post Traumatic Stress Disorder (PTSD)

3. Vietnam veteran with PTSD related the following memory: . Iwas a body bagger (responsible for picking up dead bodies). We were going out in a chopper, picking up bodies. We had overlooked a marine who had been killed. By the time we went out to get him he had been dead for a week. I went to pick him up, and my arm went right through him. I was standing there, holding his heart, guts, and insides in my hand Bremner and Brett, 1997

4. PTSD: Symptom Clusters • Intrusion—memories of the trauma or “flashbacks” that occur unexpectedly; these may include nightmares or physical reactions such as a racing heart • Avoidance—avoiding people, places, thoughts, or activities that bring back memories of the trauma; this may involve feeling numb or emotionless, withdrawing from family and friends, or “self-medicating” by abusing alcohol or other drugs • Hyperarousal—feeling “on guard” or irritable, having sleep problems, having difficulty concentrating, feeling overly alert and being easily startled, having sudden outbursts of anger

5. PTSD prevalence • Statistics regarding this illness indicate that approximately 7%-8% of people in the United States will likely develop PTSD in their lifetime, with the lifetime prevalence in combat veterans and rape victims ranging from 10% to as high as 30%. • Institute of Psychiatry in London: “Studies of at-risk groups e.g. combat veterans, victims of natural disasters or criminal violence have yielded prevalence rates ranging form 3% to 58%”.

6. Outline • Memory for the original trauma • Stability over time? • Relationship between memory change and PTSD symptoms • Is a lack of memory for the trauma protective? • Treat or prevent PTSD by interventions that specifically target memory? • Altered neurocircuitry in PTSD • Predisposing factor vs. acquired sign? • Can this altered neurocircuitry contribute to the maintenance of fear memories?

7. Memory and PTSD • The person experienced, witnessed, or was confronted with an event or events that involved actual or threatened death or serious injury, or a threat to the physical integrity of self • The person’s response involved intense fear, helplessness or horror Assessed retrospectively: Memory for the trauma & memory for acute response to trauma

8. Memory for traumatic events • Stable and indelible vs. subject to alteration and distortion? “Indelible” conditioned fear responses (LeDoux, 1996; McGaugh 2003; Pitman 1989) Reconsolidation (Nader, Schafe, LeDoux 2000a; Schiller, Monfils, Raio, Johnson, LeDoux, Phelps 2010)

9. Severity of Trauma PTSD Interaction with vulnerability factors [genetics, childhood abuse, etc] Trauma PTSD Interaction with vulnerability factors [genetics, childhood abuse, etc] Perceived severityof Trauma

10. Memory amplification and PTSD: World Trade Center • 2641 disaster restoration workers during or after 9/11. • T1 & T2 [1 year later]. • [CAPS]: re-experiencing, avoidance/numbing & hyperarousal. • WTC Exposure Questionnaire: 11 exposure variables examined: • Memory change score: Number of exposure variables endorsed T2 – Number exposed T1

11. Traumatic endorsements between T1 and T2 Percentage of people Amplification of memory for two specific items (‘seeing bodies’ & ‘perceived life threat’) was associated with CAPS increase over time.

12. Tsunami Increased recall of threat intensity associated with increase in / lack of improvement in IES-R symptom score PTSD symptomatology Heir et al., 2009 Memory amplification

13. Nature of Traumatic Memory • Traumatic memory does not remain stable over time • Increase in propensity to endorse traumatic items predicts PTSD • Memory amplification: Unclear whether this is increasing or decreasing in accuracy

14. Does amnesia for the traumatic event play a protective role? • Traumatic events involving traumatic brain injury are associated with reduced prevalence of PTSD > Amnesia of the traumatic event may play a protective role (Mayou et al., 1993; Sbordone & Liter, 1995) • TBI and PTSD not mutually exclusive (Bryant & Harvey, 1998; Ohry et al., 1996). • >> These studies lack systematic investigation of memory for the event

15. Purpose: Direct assessment of the relationship between explicit memory of the traumatic event and subsequent development of PTSD in participants who had experienced TBI 120 subjects injured primarily in traffic accidents (90%). Initial evaluation took place within 24 hours after injury, during hospitalization. Also, follow up 7-10 days, 4 weeks and 6 months.

16. 55% 45% 23% met diagnostic criteria for PTSD at 6 months * 6% met diagnostic criteria for PTSD at 6 months

17. Question… If lack of memory for the traumatic event is “protective”, can: a) the memory be weakened and b) is a weakened memory protective against subsequent PTSD development?

18. Interfering with the trauma memory • Increased epinephrine is thought to mediate enhanced memory for emotional events Excess epinephrine Trauma PTSD symptoms Strong emotional memory and fear conditioning Young & Breslau, 2004 • Searing in of memory adrenergically mediated → Blocking (e.g. β – adrenergic blocker propranolol) interferes with memory formation.

19. CAPS Score Propranolol Placebo One-Month Propranolol Placebo Three-Month Pitman et al., (2002)

20. Skin Conductance Physiologic responses during personal script-driven imagery of the traumatic event that occurred 3 months earlier SC (sd) t=2.0, p=.03 Placebo Propranolol Findings not replicated (Stein et al., 2007). Administration time? 48 hours max vs. 1-6 used by Pitman

22. Interim Summary • Memory amplification over time is associated with PTSD symptoms • Blocking memory for the original trauma has a “protective” effect against getting PTSD • Amnesia following TBI • Drugs following trauma (impair memory consolidation)

23. Question… Does the trauma memory activate different parts of the brain in PTSD patients?

24. Symptom provocation studies Show traumatic reminders to patients with PTSD, and investigate whether different patterns of brain activity are observed.

25. Hyperactive Amygdala Amygdala is an area in the brain that underlies fear processing and expression Amygdala hyper-responsivity in PTSD has been reported during the presentation of personalized traumatic narratives (Shin et al., 2004) and cues (Driessen et al., 2004) combat sounds (Liberzon et al., 1999) combat photographs (Hendler et al., 2003) and trauma-related words (Protopopescu et al., 2005). Patients with PTSD from 9/11 viewing pictures from the attack (Silbersweig)

26. mPFC Involved in inhibitory control , underactive in PTSD patients (Lanius, Bluhm, Lanius, & Pain, 2005). PTSD pathophysiology, specifically as failures of midline prefrontal regions to inhibit subcortical limbic, especially amygdala, reactivity (e.g., Milad, Rauch, Pitman, & Quirk, 2006)

27. Question… Are brain alterations associated with PTSD 1)Pre-existing vulnerability factors or 2) acquired signs? TRAUMA Brain Differences PTSD Brain Differences PTSD

28. Hippocampus Area involved in learning and memory and particularly implicated in rich recollective autobiographical memories (Addis et al., 2004).

29. HippocampalVolume: Reduced in PTSD • Bremner et al., (1995) Vietnam veterans with (n = 26) and without PTSD (N = 22). PTSD subjects had 8% smaller right hippocampus volume & poorer performance on verbal memory measurements (Wechsler Memory Scale). • Bremner et al., (2003): 22 female adult survivors of childhood abuse with PTSD (N = 10) or without PTSD (N = 12). PTSD had 15% smaller hippocampal volume than abuse subjects without PTSD. No difference in memory measures. • Stein et al., (1997) assessed hippocamalvulume in 21 female adult survivors of severe childhood sexual abuse and 21 control subjects, and also administered cognitive tests (e.g. CVLT). Abuse subjects had 5% smaller left hippocampus size, but no differences or correlations were found on cognitive performance.

30. Exposure to severe stress can damage the hippocampus. • - Human studies show smaller hippocampal volume in individuals with PTSD. Nature Neuroscience5, 1242 - 1247 (2002) Published online: 15 October 2002; | doi:10.1038/nn958 Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma Mark W. Gilbertson1,2, Martha E. Shenton2, 3, 4, Aleksandra Ciszewski4, Kiyoto Kasai4, Natasha B. Lasko1, 2, 5, Scott P. Orr1, 2, 5 & Roger K. Pitman2, 5 Does this represent: 1) neurotoxic effect of trauma 2) a pre-existing condition that renders the brain more vulnerable to the development of pathological stress responses?

31. PTSD+ PTSD- Trauma-Exposed Trauma-UnExposed A Replication of previous research B Neurotoxicity Effect C Pre-existing Vulnerability

32. PTSD + PTSD - Exposed Un-Exposed

33. Combat Exposed Combat Un-Exposed PTSD Severity

34. Hippocampus: Conclusions • Smaller hippocampus in veterans with PTSD • Smaller hippocampus in PTSD represents a pre-existing, familial vulnerability factor rather than neurotoxic product of trauma and PTSD development

35. Triad of Structures: Amygdala Fear mPFC Hippocampus Memory Inhibition

36. Question… Does altered neurocircuitry in PTSD patients contribute to the maintenance of fear memories?

37. CS + E CS +

38. ?

41. Impaired safety memories • PTSD patients are not able to retain safety information (e.g. impaired extinction recall Milad et al., 2009). • > Can lead to the maintenance of fear memories • This is a consequence of getting PTSD, and not a predisposing factor (Milad et al., 2008)

42. Summary • Memory for the original trauma • Not stable over time • Increased memory change predicts PTSD • Lack of memory for the trauma is protective against subsequent PTSD • Preliminary evidence that PTSD can be treated via interventions that specifically target memory • Altered neurocircuitry in PTSD • Triad: Amygdala, mPFC and Hippocampus • Smaller hippocampus is a predisposing factor • Altered neurocircuitry can lead to the maintenance of fear memories

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