Preliminary evidence for lymphocyte distribution differences at rest and after acute psychological stress in PTSD-symptomatic women☆
Introduction
Although it is widely recognized that exposure to “stress” alters lymphocyte distribution (Herbert and Cohen, 1993, Kiecolt-Glaser et al., 2002) surprisingly few studies have reported immune data from individuals with posttraumatic stress disorder (PTSD). Four controlled studies could be found: [Male combat veterans: Boscarino and Chang, 1999, Laudenslager et al., 1998; Adult female child abuse victims: Wilson et al., 1999; Mixed gender natural disaster victims: Ironson et al., 1997]. Only CD4+ and CD8+ cells were reported in all studies. Two studies (Laudenslager et al., 1998, Wilson et al., 1999) found no PTSD-related group differences, one study found PTSD-related reductions (Ironson et al., 1997), while another reported elevations (Boscarino and Chang, 1999) in CD4+ and CD8+ counts under resting conditions.
The lack of consistency in results across these studies may be due to differences in gender, stressor type, and timing of the assessment in relation to trauma onset. In addition, examination of lymphocyte redistribution following laboratory challenge suggests that sometimes group differences are evident only when subjects are acutely stressed. For example, blunted natural killer (NK) cell cytotoxicity and B-endorphin response, increased epinephrine and NK cell number and slow cortisol recovery were found in response to an acute psychological stressor in men reporting a high degree of “life stressors” as compared to men reporting a low degree of “life stressors” (Pike et al., 1997). In a study of male adults reporting very high or very low daily “hassles”, blunted NK cell number among the high stress group was reported in response to a brief psychological stressor (Benschop et al., 1994). Likewise, college students who scored high on a measure of trait “worry” had a blunted NK response to fear provocation compared to low worriers (Segerstrom et al., 1999).
These laboratory challenge studies found no group effects under resting conditions, but immune differences emerged across low and high stress groups under challenge. Extending a challenge procedure to individuals with PTSD symptoms may help to clarify the inconsistent immune findings of previous resting condition studies. Furthermore, the use of a challenge procedure among those with a history of high life stress with and without current PTSD symptoms may help determine whether lymphocyte distribution in PTSD is distinct from the pattern for high life stress alone.
Mothers of healthy children (controls) were compared to mothers of child cancer survivors with and without posttraumatic stress symptoms (PTSS). All cancer mothers can be characterized as having a high stress history due to frequent acute and prolonged stress associated with their child’s cancer diagnosis and treatment (Stuber et al., 1998). However, only a subset of cancer mothers show clinically significant posttraumatic stress symptoms (PTSS) (Stuber et al., 1996). Based on previous immune studies, we first predicted baseline (resting) group differences in lymphocyte distribution across PTSS versus non-symptomatic women. Due to the equivocal nature of CD4+ and CD8+ resting levels in previous studies of PTSD, we did not predict a direction for these resting group differences. Second, based on the life stress challenge studies, we hypothesized that all cancer mothers would show blunted immune responsivity (i.e., smaller change in NK, CD4+ and CD8+ cells following challenge) relative to control mothers. Finally, because interpersonal stressors appear to have a greater impact on lymphocyte distribution than non-social stressors (Herbert and Cohen, 1993), lymphocyte distribution was tested following a personalized challenge (individualized trauma imagery) and after a generic challenge (mental arithmetic). This allowed us to determine if group differences were limited to interpersonal (high impact) stressors or would emerge even under generic stress.
Section snippets
Subjects
Mothers of child cancer survivors were identified through tumor registry information collected on their children at the University of California, Los Angeles (UCLA) Medical Center. Cancer mothers were asked to participate only if their child was (a) alive; (b) off active cancer treatment; (c) considered a cancer “survivor” with no current relapse. Of 80 respondents to a recruitment letter that met eligibility criterion, 66 (82.5%) participated in a telephone interview (Phase I), which assessed
Subjects
The PDS assessment showed all cancer and control mothers reported having lived through or witnessed at least one traumatic event in the past and most reported multiple traumas. All subjects were asked to select the event that “bothers you the most” and answer all subsequent questions about PTSD symptoms with respect to that “worst” event. All cancer mothers reported their child’s cancer as the worst trauma experienced. Of 17 cancer mothers, 8 met all DSM-IV criterion (A–F) for PTSD and 2 met
Acknowledgments
The first author thanks Michael Irwin for his excellent feedback on an earlier draft, the mothers of child cancer survivors at UCLA for their generous participation; and finally, research assistants Irene Choi, Mark Power, Jennifer Bennett, Marleen Castaneda, and students too numerous to name for their diligent efforts in supporting this work.
References (26)
- et al.
Urinary cortisol and catecholamines in mothers of child cancer survivors with and without PTSD
Psychoneuroendocrinology
(2002) - et al.
Urinary dopamine and turn bias in traumatized women with and without PTSD symptoms
Behav. Brain Res.
(2003) - et al.
Elevated cytotoxicity in combat veterans with long-term post-traumatic stress disorder: preliminary observations
Brain Behav. Immun.
(1998) - et al.
Temporal stability of acute stressor-induced changes in cellular immunity
Int. J. Psychophysiol.
(1995) - et al.
Worry affects the immune response to phobic fear
Brain Behav. Immun.
(1999) - et al.
Is posttraumatic stress a viable model for understanding responses to childhood cancer?
Child Adolescent Psychiatric Clinics North America
(1998) - et al.
Posttrauma symptoms in childhood leukemia survivors and their parents
Psychosomatics
(1996) - et al.
Phenotype of blood lymphocytes in PTSD suggests chronic immune activation
Psychosomatics
(1999) - et al.
Internal consistencies of the original and revised Beck Depression Inventory
J. Clin. Psychol.
(1984) - et al.
Chronic stress affects immunologic but not cardiovascular responsiveness to acute psychological stress in humans
Am. J. Physiol.
(1994)
Higher abnormal leukocyte and lymphocyte counts 20 years after exposure to severe stress: Research and clinical implications
Psychosom. Med.
Autonomic, neuroendocrine, and immune responses to psychological stress: the reactivity hypothesis
Ann. N. Y. Acad. Sci.
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This research was made possible by support from: National Institute of Mental Health (#1K01-MH01939-01A2), American Cancer Society (#PF-4480), Norman Cousins program of Psychoneuroimmunology at UCLA (#34323), and General Clinical Research Center, UCLA Geffen School of Medicine (#5M01RR00865-25).