Preliminary evidence for lymphocyte distribution differences at rest and after acute psychological stress in PTSD-symptomatic women

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Abstract

This study investigated circulating natural killer (NK), CD4+ and CD8+ cells in response to acute psychological challenge among mothers of child cancer survivors with and without posttraumatic stress symptoms (PTSS). Control mothers of healthy children (n = 9) were compared to 17 cancer mothers with (PTSS: n = 9) and without PTSS (No PTSS: n = 7) under conditions of rest, after a generic stressor (MAT: mental arithmetic task) and a personalized stressor (script-driven trauma imagery), and after recovery from each stressor. Results indicate the PTSS group had higher percentage CD4+ and lower CD8+ levels than non-symptomatic women and blunted NK reactivity to generic challenge. Multiple regression analyses indicated PTSS effects were independent of self-reported distress. Contrary to expectations, cancer mothers without PTSS were not significantly different from controls on tonic or phasic immune outcomes. Also unlike predictions, reactivity to challenge was greatest to the non-social MAT stressor compared to the personalized challenge for all groups. Conclusions are constrained by study limitations (e.g., small sample size and potential phase order effects). Nonetheless, results are consistent with an emerging literature on PTSS-associated immune differences and further suggest these effects may be distinct from that associated with subjective distress more generally.

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.

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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).

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