The Influence of mTBI on Autonomic Dysregulation in Combat Veterans with PTSD

1. The Influence of mTBI on Autonomic Dysregulation in Combat Veterans with PTSD James L Spira, PhD, MPH, ABPP Brenda Wiederhold, PhD, MBA Kristy Center, MA Jenifer Murphy, MA Robert McLay, MD; PhD Dennis Wood, PhD Mark Wiederhold, MD, PhD

2. Prevalence (Terri Tanielian, RAND Report, April, 2008): • Since October 2001, approximately 1.64 million U.S. troops have deployed to support operations in Afghanistan and Iraq. • Approximately 18.5 percent of U.S. service members who have returned from Afghanistan and Iraq currently have post-traumatic stress disorder or depression (303,000); and 19.5 percent report experiencing a traumatic brain injury during deployment (320,000). • Roughly half of those who need treatment for these conditions seek it, but only slightly more than half who receive treatment get minimally adequate care. (25%) • Improving access to high-quality care (i.e., treatment supported by scientific evidence) can be cost-effective and improve recovery rates.

3. Prevalence Tanielian, 2008

4. Prevalence • The mental health of soldiers deteriorates with more combat and repeated tours: • 12% screen positive for mental health problems on first deployment, 19% on second deployment, and 27% on third or fourth deployment • Of veterans returning from Afghanistan, 5% of those with low combat experience, 11% of those with medium experience, and 27% of those with high experience screen positive for acute stress disorder. (Time Magazine, June 16, 2008)

5. Prevalence in Combat Veterans • The violent guerrilla tactics used by insurgents in Iraq will take a considerable toll on the mental health of troops, resulting in a lifetime of disability payments for many of those who return from war, U.S. Secretary of Veterans Affairs Anthony Principi (September 23, 2004).

6. Prevalence and Time Course • Kessler et al. (1995) found that one-third of the respondents with an index episode of PTSD failed to recover even after many years. • Breslau et al. (1998) found the median time to the remission of PTSD was 25 months. • PRIGERSON et al. (2001) found that although the risk of PTSD symptoms lasting longer than 2 years was significantly greater among men with combat trauma compared with men reporting other traumas as their most disturbing life event. Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB (1995) Posttraumatic StressDisorder in the National Comorbidity Survey. Arch Gen Psychiatry 52:1048-1060. Breslau N, Kessler RC, Chilcoat HD, Schultz LR, Davis GC, Andreski P (1998)Trauma and Posttraumatic Stress Disorder in the Community: The 1996 Detroit AreaSurvey of Trauma. Arch Gen Psychiatry 55:626-632 PRIGERSON, HG; MACIEJEWSKI, PK; ROSENHECK, RA (2001). Combat Trauma: Trauma with Highest Risk of Delayed Onset and Unresolved Posttraumatic Stress Disorder Symptoms, Unemployment, and Abuse Among Men. J Nervous and Mental Disease 189(2); 99-108

7. Types of PTSD • Acute Stress Disorder • Mix of hyperarousal and dissociative Sx 0-1mo • Acute PTSD • 1-3 mo • Chronic PTSD • 3 mo + • Delayed PTSD • Of a recent event, delayed onset • Of an earlier event, brought on by a recent event • Simple Acute vs Complex Chronic vs Complex Acute • Single event, mild predictors • Historical traumatic events, chronic sequelae • Complex Acute (co-morbid acute Dx: blast victims w/mTBI)

8. Consensus Panel on PTSD • Ballenger JC. Davidson JR. Lecrubier Y. Nutt DJ. Foa EB. Kessler RC. McFarlane AC. Shalev AY. • Title: Consensus statement on posttraumatic stress disorder from the International Consensus Group on Depression and Anxiety. [Review] [15 refs] • Source: Journal of Clinical Psychiatry. 61 Suppl 5:60-6, 2000. • EVIDENCE: The consensus statement is based on the 6 review articles that are published in this supplement and the scientific literature relevant to the issues reviewed in these articles. • CONCLUSION: Selective serotonin reuptake inhibitors are generally the most appropriate choice of first-line medication for PTSD, and effective therapy should be continued for 12 months or longer. The most appropriate psychotherapy is exposure therapy, and it should be continued for 6 months, with follow-up therapy as needed.

9. Experiential Therapies:Exposure • In the 1980’s, Terence Keane and colleagues found that exposure therapy was effective in treating the PTSD symptoms of Vietnam War veterans. • In the 90s, research by Edna Foa and her colleagues showed that exposure therapy was perhaps the most effective Tx for reducing PTSD symptoms of rape victims, including persistent fear. Improvements were seen immediately after exposure therapy, and sustained during a three-month follow-up. • Foa, E. B., Rothbaum, B. O., Riggs, D. S., & Murdock, T. B. (1991). The treatment of posttraumatic stress disorder in rape victims: A comparison between cognitive-behavioral procedures and counseling. Journal of Consulting and Clinical Psychology, 59, 715-723. • Foa, E. B., Meadows, E. A. (1997). Psychosocial treatments for posttraumatic stress disorder: A critical review. Annual Review of Psychology, 48, 449-480. • Keane, T. M. & Kaloupek, D. G. (1982). Imaginal flooding in the treatment of a posttraumatic stress disorder. Journal of Consulting and Clinical Psychology, 50, 138-140. • Keane, T. M., Fairbank, J. A., Caddell, J. M., & Zimering, R. T. (1989). Implosive (flooding) therapy reduced symptoms of PTSD in Vietnam combat veterans. Behavior Therapy, 20, 245-260

10. Types of Exposure Therapy 1) Flooding-type • Based on classical conditioning, • advocated by Foa, Rothbaum, and others • patients directly confront fears in order to activate and maintain high arousal • Theory states that once arousal subsides, memories will no longer be associated with high arousal • Generalized effects occur through lack of PTSD causing problems

11. Types of Exposure Therapy 2) Desensitization-type • Based upon arousal control • Advocated by Jacobson and others • Patients learn to minimize arousal (PMR) while progressively confronting an increased hierarchy of fears • Theory states that fear content will be reassociated with reduced arousal, eliminating symptoms and avoidant behavior. • Generalized effects occur through ability to have reduced arousal in the face of previous fear producing stimuli

12. Types of Exposure Therapy 3) Arousal Control • Based upon autonomic control and attentional retraining • CBT-based theory • Patients learn to control autonomic arousal and focus more fully in the moment while confronting as much arousal as they can manage, and exert control over • Theory states that gaining active control over fears will reduce irrational and automatic responses and improve coping strategies • Generalized effects occur through ability to control cognitive and physical reactions to whatever arousing stimuli occur, PTSD related or otherwise.

13. Arousal Control Autonomic Control Through biofeedback or other self-regulatory skill development Attentional retraining Attention is enhanced processing: Whatever you attend to, you enhance (worry, pain, noise, arousal / breath, warmth, work) Your brain/body support what you attend to: H-P-A axis (ANS activation; PAG relay; Limbic arousal; frontal interpretation – for SNS or PSNS) If you can address a problem, then do so, otherwise focus on neutral or positive sensations or activity Meditation helps reduce background “noise” and enhance foregrounded signal ZEN MEDITATION (signal emphasis) VIPASSANA MEDITATION (noise reduction)

14. Virtual Reality Facilitated Exposure Tx • We utilized a Virtual Iraq (developed by VRMC) with a variety of combat-related scenarios to control exposure variables • Therapists could control the degree of exposure with choice of scenario (to fit patient’s experience) and increasing level of stimuli within each scenario (sounds, violence, etc) • Patients wore headgear and earphones, and were able to move about their environments with the use of a joystick

15. Virtual Reality Facilitated Exposure Tx • Patients were first taught to control their autonomic arousal and attend more fully in the moment • Once achieved (after the first or second session, and with homework practice), they applied these skills in VR • Patients were continually physiologically monitored (HRV, SC, Respiration) • Arousal was observed, allowed to increase to specified parameters, and then patients were asked to decrease their arousal and focus in the moment without reactivity until arousal decreased sufficiently. • This was repeated continually until patients no longer became significantly aroused during sessions or outside of sessions

16. Study of PTSD with co-morbid mTBI • Theory 1: (Hogue et al) – mTBI does not have substantial psychological disability (or at least, it is difficult to assess) beyond that found in PTSD. Therefore, there should be no difference between PTSD patients with and without mTBI on autonomic dysregulation, assuming PCL-m is similar. • Theory 2: The dysregulation seen in TBI (and characterized by PCS) is significantly different than that seen in PTSD (cognitive and emotional disinhibition, sleep, fear reactions, etc). Therefore, PTSD pts with and without mTBI will show differences in autonomic dysregulation.

17. Study Design • Sample: 37 Navy and Marine combat veterans of OIF/OEF • 19 had significant blast exposure, with increasing levels of effect from feeling dazed and confused to memory loss • 37 patients were assessed for skin conductance at baseline • 9 patients were assessed for skin conductance at post-treatment follow-up

18. Study Design • Three conditions were assessed at Study Baseline and Follow-up: • 5” Rest (sit quietly as we make sure the equipment is working) • 5” Stress Recall (what are the most troubling thoughts and feelings you have associated with your combat experience?) • 5” Recuperation (put those thoughts out of your mind and rest as comfortably as you can)

19. Study Results - Baseline • Repeated measures ANOVA revealed that patients at baseline became aroused with stress recall, but were unable to reduce arousal during the recovery phase (p<.0001), with arousal in fact continuing to increase during the recovery phase (p<.007). • A Blast Exposure x Condition at time 1 indicated that the increase in SC scores during recovery was found for PTSD patients exposed to blast, but not for non-blast exposed PTSD patients (p<.05). • Further, regression analysis revealed that the more effects of blast (exposure, dazed and confused, memory loss) the greater the autonomic dysregulation (SC and HRV), and the less likely to be able to recover, compared to those with no blast exposure (p<.01).

20. For all patients at baseline: - There was less autonomic control over stress recall and recovery at time one than at time two

21. Study Results – Post-treatment • This difference between PTSD with and without mTBI was not found following the Arousal Control Virtual Reality Assisted Graded Exposure Therapy (VRGET), indicating that this type of treatment was successful in training patients with combat PTSD in autonomic control in the face of a stress recall, and facilitating the ability to reduce arousal following stress. • Further, cumulative blast score was directly correlated with SC recovery at time 1 (Spearman’s rho=.448; p<.05) indicating poor pre-treatment recovery of SC, yet this was not found at time 2 (r=.281, p<.542), indicating that blast no longer had an influence on SC recovery following VRGET treatment.

22. Study Results – Pre-Post Analysis • Repeated measures Condition (baseline, stress recall, and recovery) x Time (pre post intervention for all pt types) ANOVA (N=9) revealed: • 1) a significant difference for Condition (F=9.06; p<.017; Partial Eta Squared =.531 with observed power of .751), • 2) a significant difference for Time (F=5.97; p<.04; Partial Eta Squared = .427 with observed power of .574) • 3) a Condition x Time interaction (F=13.12; p<.007; Partial Eta Squared = .622 with an observed power of .887). • This shows that there was a statistical and clinical significant difference in response to stress recall and recovery over time for subjects with PTSD

23. Study Results – Pre-Post Analysis • Subsequent analysis showed that even though patients had no change in baseline SC over time, patients had significantly greater control over reactivity during stress recall and recuperation than they did at Baseline • Patients at time-2 had 57% greater recovery than they did at Baseline. • A simple regression demonstrated that cumulative blast score predicts baseline SC, stress recall SC, and recovery SC levels (p<.05 at time 1), but only predicts SC baseline at time 2, not stress or recovery. • Hence, while blast patients may continue to have higher baseline SC values, they have learned how to control their autonomic reactivity following treatment.

24. At Baseline: Blast exposed patients were not significantly different from non-blast exposed patients at Time 1 or at Time 2 (i.e. no blast x time interaction)

25. For Stress Recall: Blast exposed patients were significantly different from non-blast exposed patients at Time 1, but not at Time 2 (i.e. significant blast x time interaction)

26. For Recovery: Blast exposed patients were significantly different from non-blast exposed patients at Time 1, but not at Time 2 (i.e. significant blast x time interaction)

27. Results – PCL-M scores • PCL-M scores decreased significantly from pre to post treatment (p<.001) for all patients • There was no correlation between physiological arousal and any other PCL-M subscale or total score. • This may indicate that objective physiological arousal is not always associated with conscious cognitive arousal (especially in an active duty combatant population – ‘How are you feeling?’ -> “I’m fine, sir”).

28. Conclusions • These findings support Theory 2 • Even though PCL was similar for PTSD patients with and without mTBI, they differed in terms of autonomic reactivity to stress recall and ability to recuperate, demonstrating the dysregulation expected in TBI patients beyond that for PTSD alone.

29. Conclusions • PTSD patients with blast exposure had higher arousal during stress recall, and still higher arousal during recovery at pre-treatment assessment, indicating the importance of considering blast in treatment planning for patients with PTSD. • That this distinction disappeared after treatment further suggests that Arousal Control VRGET is an appropriate and effective treatment for patients with PTSD with or without mTBI.