Dissociation-a common feature of posttraumatic stress disorder (PTSD)-involves disruptions in the usually integrated functions of consciousness, memory, identity, and perception of the self and the environment.
Dissociation-a common feature of posttraumatic stress disorder (PTSD)1,2-involves disruptions in the usually integrated functions of consciousness, memory, identity, and perception of the self and the environment.3 Acute dissociative responses to psychological trauma have been found to predict the development of chronic PTSD.4-9 Moreover, a chronic pattern of dissociation in response to reminders of the original trauma and minor stressors has been found to develop in persons who experience acute dissociative responses to psychological trauma.9
Bremner and associates10 hypothesized that there may be 2 subtypes of acute trauma response that represent unique pathways to chronic stress-related psychopathology: one is primarily dissociative and the other is predominantly intrusive and hyperaroused. Using data from our own neuroimaging studies,11-16 we will show that these 2 subtypes of response can persist in persons with chronic PTSD17 and that they are associated with distinct patterns of neural activation upon exposure to reminders of traumatic events.
The term “dissociation” has denoted a wide variety of phenomena in the literature encompassing both states and traits. Here the focus is on dissociative symptomatic responses to trauma-related stimuli in PTSD-particularly states of depersonalization and derealization. We have operationalized this definition with 4 questions from the Responses to Script-Driven Imagery Scale, which is a validated measure of evoked symptoms that we developed to advance psychobiological and treatment outcome research in PTSD.18
• Did what you were experiencing seem unreal to you, like you were in a dream or watching a movie or play?
• Did you feel like you were a spectator watching what was happening to you, like an observer or outsider?
• Did you feel disconnected from your body?
• Did you feel like you were in a fog?
For most clinicians, these are familiar descriptions of some of their PTSD patients’ responses to trauma-related stimuli and situations, and such states are witnessed firsthand in their offices.
Functional brain imaging studies
Over the past 15 years, the application of functional neuroimaging research on PTSD has resulted in an explosion of new data that have begun to reveal the brain circuits that are involved in the pathophysiology of this disorder. Studies that use positron emission tomography (PET) and blood oxygenation level–dependent functional MRI (BOLD fMRI) have examined neural responses to a variety of stimuli, including fearful, happy, and neutral faces; trauma-related images and sounds; and “script-driven imagery” of traumatic experiences. A recent review and meta-analysis found that persons with PTSD tend to exhibit greater brain activation in the amygdala and insula than persons without PTSD; these structures are involved in fear conditioning and the perception of bodily states (among other functions), respectively.19 Moreover, the dorsal anterior cingulate cortex (ACC), rostral ACC and ventromedial prefrontal cortex, which are involved in the experience and regulation of emotion, have repeatedly been observed to be less activated in patients with PTSD than in controls who have a history of trauma but not PTSD.19
Our research has shown that in patients with PTSD, psychobiological responses to recalling traumatic experiences can differ significantly, and a sizable proportion do not fit the conventionally studied “reexperiencing/hyperaroused” response.20,21 For example, in our initial brain imaging studies, approximately 70% of patients relived their traumatic experience and showed an increase in heart rate while recalling the traumatic memory,11,13 while the other 30% had a dissociative response with no concomitant increase in heart rate.14,15
We have investigated the neuronal circuitry that underlies reexperiencing/hyperaroused and dissociative responses in PTSD using BOLD fMRI and script-driven imagery. In this paradigm, patients construct a narrative of their traumatic experience that is later read to them while they are in the scanner. They are instructed to recall the traumatic memory as vividly as possible during “trauma scripts” and immediately afterward while the MRI scanner measures oxygen use in different brain areas.
Our first study involved 9 patients with sexual abuse– or motor vehicle accident–related PTSD and 9 controls who had a history of sexual abuse or motor vehicle accidents but in whom PTSD never developed. Figure 1 demonstrates that compared with controls, patients who relived their traumatic experience and had a hyperaroused response to the traumatic script exhibited significantly less activation in the rostral ACC and medial prefrontal cortex as well as in the thalamus and occipital cortices.11 Lower levels of ACC activation and medial prefrontal activation are consistent with previous PET studies of sexual abuse and combat-related PTSD.10,17,22 These brain activation patterns differ strikingly from those observed in a second study of 7 patients who dissociated in response to the traumatic script and of 10 trauma-exposed controls.12 Figure 2 shows that these dissociative patients had higher levels of brain activation in the rostral ACC and dorsal ACC, medial prefrontal cortex, and areas in the superior and middle temporal cortices.
The most remarkable findings in these 2 studies are the opposite patterns of brain activation. The more typical reexperiencing/hyperaroused group exhibited abnormally low activation in the medial anterior brain regions that are implicated in arousal modulation and emotion regulation more generally (ACC and medial prefrontal cortex), while the dissociative group exhibited abnormally high activation in these regions.
These findings are entirely consistent with the phenomenology and clinical presentations of patients with PTSD who need help to overcome pathological overengagement or underengagement with traumatic memories and the associated emotions and bodily experiences. Low activation in these regions is consistent with failed inhibition of limbic reactivity associated with hyperaroused overengagement. High activation is consistent with hyperinhibition of those same limbic regions in states of pathological underengagement with trauma-related emotions.
More specifically, the findings are compatible with the corticolimbic model of depersonalization. That model postulates that depersonalization involves a corticolimbic disconnection in which left medial prefrontal activation with reciprocal amygdala inhibition results in hypoemotionality and decreased arousal, while right dorsolateral prefrontal cortex activation with reciprocal ACC inhibition leads to an emptiness of mental content.23 In this model, after a threshold of anxiety is reached, the medial prefrontal cortex inhibits emotional processing in limbic structures (eg, the amygdala) that, in turn, leads to a dampening of sympathetic output and reduced emotional experience.
In support of this model, there is significant evidence for medial prefrontal involvement in both the monitoring and the modulation of emotions.24,25 Furthermore, several studies suggest that the prefrontal cortex has inhibitory influences on the emotional limbic system, including PET studies that showed a negative correlation between blood flow in the left prefrontal cortex and the amygdala.26,27
The activations we found in the superior and middle temporal cortices during dissociative states in PTSD are consistent with the temporal lobe hypothesis of dissociation. The epilepsy literature has described dissociative symptoms with seizures of various foci, including both right and left hemispheres.28,29 Penfield and Rasmussen30 have also reported depersonalizationlike symptoms in response to stimulation of the superior and middle temporal cortices during neurosurgery.
Moreover, Teicher and colleagues31 have explored the relationship between early abuse and limbic system dysfunction as measured by the Limbic System Checklist-33.31 This checklist includes symptoms that are often experienced by persons with temporal lobe epilepsy and may explain why some patients with PTSD who have more extreme dissociative pathology exhibit pseudopsychotic symptoms that can mimic a psychotic disorder and result in misdiagnosis.32 Limbic System Checklist-33 scores have been found to correlate strongly with Dissociative Experiences Scale scores.31,33 Thus, altered activation of the superior and middle temporal cortex may contribute to the dissociative experiences that patients have while recalling their traumas.
Importantly, individual differences in responses to trauma reminders can be conceptualized categorically, as qualitatively different response subtypes, as well as dimensionally, as involving different symptom severities and associated neural activation patterns within each response subtype. In addition, even patients who have PTSD without major dissociative pathology may have dissociative responses when traumatic memories are triggered. Thus, in a subsequent study, we used fMRI to examine correlations between severities of reexperiencing and dissociative responses to trauma scripts and activity in regions associated with awareness and regulation of arousal and emotions.16 The study included 27 patients with PTSD that had resulted primarily from traumatic motor vehicle accidents; these patients had differing degrees of dissociative pathology but relatively mild dissociative symptoms overall. Subjective experiences of state reexperiencing and dissociative symptom responses to trauma scripts in the fMRI were assessed with the Response to Script-Driven Imagery Scale.18
As hypothesized, state reexperiencing severity was positively correlated with right anterior insula activation and was negatively correlated with activation of rostral ACC, while dissociative response severity was negatively correlated with right anterior insula activation and positively correlated with activation of medial prefrontal cortex and dorsal ACC. In addition, dissociation severity correlated positively with left medial prefrontal cortex and right superior temporal cortex activation and correlated negatively with left superior temporal cortex activation.
The dissociation findings are consistent with those in our study using the categorical approach to compare severely dissociative patients who have PTSD with trauma-exposed controls. They are particularly noteworthy because the present participants had relatively low trait dissociation levels on average, which was similar to our previous participants with PTSD who displayed predominantly hyperaroused reexperiencing responses11-levels of dissociation that characterize many patients with PTSD who are encountered in clinical practice-and much lower trait and state dissociation than the “dissociative” script responders in our other prior study. Finally, these findings provide support for a model of such dissociative reactivity as a form of emotion dysregulation that involves extreme underengagement mediated by midline prefrontal inhibition of limbic activity. Figure 3 summarizes these findings while visually presenting a broader emotion dysregulation account of reactivity to trauma-related stimuli in PTSD.
In summary, these results suggest that patients with PTSD can have significantly different responses to traumatic script-driven imagery. Our studies may shed light on key biological dimensions of the disorder. As noted, about 70% of patients in our studies relived their traumatic experience and showed an increase in heart rate while recalling the traumatic memory,11 while the other 30% showed a dissociative response with no concomitant increase in heart rate. Interestingly, attempts to correctly classify PTSD cases through the use of discriminant functions based on psychophysiological responses to reminders, including expected increased heart rate, have historically resulted in false-negative classifications in the range of 30% or more.34
The fMRI findings that we have reported here add to the emerging evidence of experiential and neurobiological differences between dissociative versus nondissociative responses to traumatic reminders. These results also provide further support for a dissociative subtype of PTSD that may stem from more severe childhood experiences of abuse and neglect.1,35
However, all patients who are seen in clinical practice may not fit neatly into “reexperiencing/hyperaroused” versus “dissociative” subtypes of PTSD. Some exhibit both types of responses at different times and in different contexts (eg, those involving actual and perceived inability to physically escape). Indeed, our own (unpublished) data collected during a treatment study of more than 50 patients with PTSD showed that within a single experimental session that involved 2 script-driven trauma imagery exposures, one-third reported dissociative responses to one script and reexperiencing/hyperaroused responses to the other. Nevertheless, patients with a history of chronic early life trauma tend to exhibit significantly more dissociative symptoms than patients who have experienced adult traumatic events.1,2
Exposure-based treatments for PTSD (eg, prolonged exposure and eye movement desensitization and reprocess) consist of repeated exposure to trauma-related stimuli and have the strongest empirical support.36 Critically, the in-session exposures are designed to overcome avoidance of such stimuli by providing a safe context in which patients can fully engage with trauma-related and “corrective” (safety) information. In this way, exposure treatment is designed to overcome and reduce avoidance symptoms, which, in turn, should reduce reexperiencing and hyperarousal symptoms and, ultimately, eliminate the disorder itself.37
However, as Foa and colleagues38 suggested, caution must be taken with patients who exhibit significant dissociative and numbing symptoms because these can prevent emotional engagement with trauma-related information and thereby reduce treatment effectiveness.39,40 It is therefore crucial to assess dissociative pathology and to provide interventions that reduce dissociative symptomatic responses to trauma-related stimuli before commencing exposure-based treatments.36 Failure to do so can exacerbate PTSD and related symptoms, including dissociation, and can increase the patient’s overall distress and functional impairment.
Cloitre and colleagues41 recently developed an integrative and empirically supported “phase-based” intervention for long-term, child abuse–related PTSD often associated with significant dissociative symptomatology. Their approach delivers a stage-oriented model that uses skills training in emotion regulation before engaging in exposure-based therapy. Their treatment manual42 has session-by-session guidelines; suggestions for tailoring interventions to individuals; and handouts, worksheets, and other tools for managing symptoms, building emotion regulation skills, and processing traumatic memories and associated feelings. Moreover, Ogden and colleagues43 have published a comprehensive book on key principles and practical clinical skills for addressing somatic, emotional, and cognitive components of self-regulation and stabilization in patients with PTSD and related disorders that result from early life trauma.
In addition, the International Society for the Study of Trauma and Dissociation (www.isst-d.org) offers in-person and distance-learning training for clinicians who work with clients with severe dissociative symptoms. Vermilyea44 has also published an excellent self-help book for patients with PTSD and dissociative symptoms that retails for around $20.
Future treatment outcome research should focus on complex childhood abuse–related PTSD with considerable dissociative symptomatology to shed light on which interventions are most effective and how they can be optimally timed in a phase-oriented treatment model. However, as all clinicians know, when it comes to helping the unique individuals who come to one’s office or clinic, there are limits to the applicability of findings from controlled clinical trials because of their selection biases and other limits to external validity.45 Mindful of this reality, we close this section with cogent observations from Judith Herman’s recently published editorial, “Craft and Science in the Treatment of Traumatized People.”46 A pioneer in the study and treatment of survivors of severe child abuse, Herman is also author of the classic Trauma and Recovery,47 which remains an authoritative text on “phase-oriented” treatment of psychological trauma, particularly for patients with significant dissociative pathology.
"When we prescribe, we have to figure out which antidepressant is right for each particular patient. Even in the simplest cases, we don’t currently know how to predict a successful fit. Most practitioners become familiar with a few medications and learn the nuances of prescribing within that repertoire. It turns out that some lucky patients will respond well to just about any of the medications, whereas about 10% or more won’t respond to anything currently available. For the rest, we resort to trial and error. It would be nice if we had some systematic basis for determining which medication will be best for which patient, but we don’t. So we use our clinical instincts, for lack of a better guide. . . .
The same may be true of the many psychotherapies for psychological trauma. We see some patients, particularly adults in good health with good social supports who suffer a single-incident trauma, who will probably do reasonably well with any of a wide range of treatment or self-help options. We see some patients at the extreme end of the complex trauma/dissociative disorder spectrum who may be beyond the reach of any treatment currently known. In between are all the rest-patients who may respond well to one form of treatment but not another-and as yet we don’t know very well how to predict the best match. We recognize that treatment of trauma is a complex biological, psychological, and social project that unfolds in stages over time and may involve many different treatment modalities to reach a stage of optimal recovery."46
There is compelling evidence not only from clinical practice but also from biological research that patients with PTSD can show both reexperiencing/hyperaroused and dissociative responses to recalling traumatic experiences and for corresponding subtypes of PTSD. These different responses and subtypes can be viewed as extremes of dysregulation that involve overengagement and underengagement with trauma-related emotional and somatosensory information. Each response type appears to have distinct CNS correlates, and the severities of each response type have been correlated in predicted ways with neural activity in brain regions that are responsible for emotional awareness and emotion regulation. Finally, these findings have important implications for treatment, including the need to assess patients with PTSD for dissociative symptomatology and to treat dissociative symptoms before using exposure-based approaches.
1. van der Kolk BA, Pelcovitz D, Roth S, et al. Dissociation, somatization, and affect dysregulation: the complexity of adaptation of trauma. Am J Psychiatry. 1996;153(7 suppl):83-93. Review.
2. Stovall-McClough KC, Cloitre M. Unresolved attachment, PTSD, and dissociation in women with childhood abuse histories. J Consult Clin Psychol. 2006;74:219-228.
3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders Revised, Fourth Edition. Washington, DC: American Psychiatric Association; 2000:519-533.
4. Bryant RA. Acute stress reactions: can biological responses predict posttraumatic stress disorder? CNS Spectr. 2003;8:668-674.
5. Bremner JD, Southwick S, Brett E, et al. Dissociation and posttraumatic stress disorder in Vietnam combat veterans. Am J Psychiatry. 1992;149:328-332.
6. Marmar CR, Weiss DS, Schlenger WE, et al. Peritraumatic dissociation and posttraumatic stress in male Vietnam theater veterans. Am J Psychiatry. 1994;151:902-907.
7. Koopman C, Classen C, Spiegel D. Predictors of posttraumatic stress symptoms among survivors of the Oakland/Berkeley, California, firestorm. Am J Psychiatry. 1994;151:888-894.
8. Shalev AY, Peri T, Canetti L, Schreiber S. Predictors of PTSD in injured trauma survivors: a prospective study. Am J Psychiatry. 1996;153:219-225.
9. Bremner JD, Innis RB, Ng CK, et al. Positron emission tomography measurement of cerebral metabolic correlates of yohimbine administration in combat-related posttraumatic stress disorder. Arch Gen Psychiatry. 1997;54:246-254.
10. Bremner JD, Staib LH, Kaloupek D, et al. Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: a positron emission tomography study. Biol Psychiatry. 1999;45:806-816.
11. Lanius RA, Williamson PC, Densmore M, et al. Neural correlates of traumatic memories in posttraumatic stress disorder: a functional MRI investigation. Am J Psychiatry. 2001;158:1920-1922.
12. Lanius RA, Williamson PC, Boksman K, et al. Brain activation during script-driven imagery induced dissociative responses in PTSD: a functional MRI investigation. Biol Psychiatry. 2002;52:305-311.
13. Lanius RA, Williamson PC, Densmore M, et al. The nature of traumatic memories: a 4-T fMRI functional connectivity analysis. Am J Psychiatry. 2004;161:36-44.
14. Lanius RA, Williamson PC, Bluhm RL, et al. Functional connectivity of dissociative responses in posttraumatic stress disorder: a functional magnetic resonance imaging investigation. Biol Psychiatry. 2005;57:873-884.
15. Lanius RA, Bluhm R, Lanius U, Pain C. A review of neuroimaging studies in PTSD: heterogeneity of response to symptom provocation. J Psychiatr Res. 2006;40:709-729.
16. Hopper JW, Frewen PA, van der Kolk BA, Lanius RA. Neural correlates of reexperiencing, avoidance, and dissociation in PTSD: symptom dimensions and emotion dysregulation in responses to script-driven trauma imagery. J Trauma Stress. 2007;20:713-725.
17. Bremner JD, Narayan M, Staib LH, et al. Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder. Am J Psychiatry. 1999;156:1787-1795.
18. Hopper JW, Frewen PA, Sack M, et al. The responses to script-driven imagery scale (RSDI): assessment of state posttraumatic symptoms for psychobiological and treatment research. J Psychopathol Behav Assess. 2007;29:249-268.
19. Etkin A, Wager TD. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am J Psychiatry. 2007;164:1476-1488.
20. Keane TM. Guest editorial. Posttraumatic stress disorder. Future directions in science and practice. J Rehabil Res Dev. 2008;45:vii-x.
21. Orr SP, Roth WT. Psychophysiological assessment: clinical applications for PTSD. J Affect Disord. 2000;61:225-240.
22. Shin LM, McNally RJ, Kosslyn SM, et al. Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: a PET investigation. Am J Psychiatry. 1999;156:575-584.
23. Sierra M, Berrios GE. Depersonalization: neurobiological perspectives. Biol Psychiatry. 1998;44:898-908.
24. Reiman EM, Lane RD, Ahern GL, et al. Neuroanatomical correlates of externally and internally generated human emotion. Am J Psychiatry. 1997;154:918-925.
25. Damasio AR. Descartes’ Error: Emotion, Reason, and the Human Brain. New York: G.P. Putnam’s Sons; 1994.
26. Drevets WC, Videen TO, Price JL, et al. A functional anatomical study of unipolar depression. J Neurosci. 1992;12:3628-3641.
27. Davidson RJ, Sutton SK. Affective neuroscience: the emergence of a discipline. Curr Opin Neurobiol. 1995;5:217-224.
28. Kenna JC, Sedman G. Depersonalization in temporal lobe epilepsy and the organic psychoses. Br J Psychiatry. 1965;111:293-299.
29. Devinsky O, Putnam F, Grafman J, et al. Dissociative states and epilepsy. Neurology. 1989;39:835-840.
30. Penfield W, Rasmussen T. The Cerebral Cortex of Man: A Clinical Study of Localization of Function. New York: Macmillan; 1950:157-181.
31. Teicher MH, Glod CA, Surrey J, Swett C Jr. Early childhood abuse and limbic system ratings in adult psychiatric outpatients. J Neuropsychiatry Clin Neurosci. 1993;5:301-306.
32. Kluft RP. First-rank symptoms as a diagnostic clue to multiple personality disorder. Am J Psychiatry. 1987;144:293-298.
33. Teicher MH, Ito Y, Glod CA, et al. Preliminary evidence for abnormal cortical development in physically and sexually abused children using EEG coherence and MRI. In: Yehuda R, McFarlane AC, eds. Psychobiology of Posttraumatic Stress Disorder. Vol 821. New York: New York Academy of Sciences; 1997:160-175.
34. Prins A, Kaloupek DG, Keane TM. Psychophysiological evidence for autonomic arousal and startle in traumatized adult populations. In: Friedman MJ, Charney DS, Deutch AY, eds. Neurobiological and Clinical Consequences of Stress: From Normal Adaptation to PTSD. Philadelphia: Lippincott-Raven; 1995:291-314.
35. Ginzburg K, Koopman C, Butler LD, et al. Evidence for a dissociative subtype of post-traumatic stress disorder among help-seeking childhood sexual abuse survivors. J Trauma Dissociation. 2006;7:7-27.
36. Foa EB, Keane TM, Friedman MJ. Effective Treatments for PTSD: Practice Guidelines from the International Society for Traumatic Stress Studies. 2nd ed. New York: Guildford Press; 2008.
37. Foa EB, Kozak MJ. Emotional processing of fear: exposure to corrective information. Psychol Bull. 1986;99:20-35.
38. Foa EB, Cahill SP, Boscarino JA, et al. Social, psychological, and psychiatric interventions following terrorist attacks: recommendations for practice and research. Neuropsychopharmacology. 2005;30:1806-1817.
39. Jaycox LH, Foa EB, Morral AR. Influence of emotional engagement and habituation on exposure therapy for PTSD. J Consult Clin Psychol. 1998;66:185-192.
40. Jaycox LH, Zoellner L, Foa EB. Cognitive-behavior therapy for PTSD in rape survivors. J Clin Psychol. 2002;58:891-906.
41. Cloitre M, Koenen KC, Cohen LR, Han H. Skills training in affective and interpersonal regulation followed by exposure: a phase-based treatment for PTSD related to childhood abuse. J Consult Clin Psychol. 2002;70:1067-1074.
42. Cloitre M, Cohen LR, Koenen KC. Treating Survivors of Childhood Abuse: Psychotherapy for the Interrupted Life. New York: Guilford Press; 2006.
43. Ogden P, Mintun K, Pain C. Trauma and the Body: A Sensorimotor Approach to Psychotherapy. New York: W.W. Norton; 2006.
44. Vermilyea EG. Growing Beyond Survival: A Self-Help Toolkit for Managing Traumatic Stress. Baltimore: Sidran Press; 2007.
45. Spinazzola J, Blaustein M, van der Kolk BA. Posttraumatic stress disorder treatment outcome research: the study of unrepresentative samples? J Trauma Stress. 2005;18:425-436.
46. Herman J. Craft and science in the treatment of traumatized people. J Trauma Dissoc. 2008;9:293-300.
47. Herman JL. Trauma and Recovery. 2nd ed. New York: Basic Books; 1997.