Childhood adversity increases vulnerability for behavioral symptoms and immune dysregulation in women with breast cancer

Abstract

Women respond differentially to the stress-associated with breast cancer diagnosis and treatment, with some women experiencing more intense and/or sustained behavioral symptoms and immune dysregulation than others. Childhood adversity has been identified to produce long-term dysregulation of stress response systems, increasing reactivity to stressors encountered during adulthood. This study determined whether childhood adversity increased vulnerability for more intense and sustained behavioral symptoms (fatigue, perceived stress, and depressive symptoms), poorer quality of life, and greater immune dysregulation in women (N=40) with breast cancer. Evaluation was after breast surgery and through early survivorship. Hierarchical linear modeling was used to examine intra-individual and inter-individual differences with respect to initial status and to the pattern of change (i.e. trajectory) of outcomes. At initial assessment, women exposed to childhood emotional neglect/abuse had greater perceived stress, fatigue, depressive symptoms and poorer quality of life, as well as lower natural killer cell activity (NKCA). Although these outcomes improved over time, women with greater childhood emotional neglect/abuse exhibited worse outcomes through early survivorship. No effect was observed on the pattern of change for these outcomes. In contrast, childhood physical neglect predicted sustained trajectories of greater perceived stress, worse quality of life, and elevated plasma IL-6; with no effect observed at initial assessment. Thus, childhood adversity leaves an enduring imprint, increasing vulnerability for behavioral symptoms, poor quality of life, and elevations in IL-6 in women with breast cancer. Further, childhood adversity predisposes to lower NKCA at a critical time when this immune-effector mechanism is most effective at halting nascent tumor seeding.

Figure 1

Unconditional model estimates of the growth trajectories for (a) depressive symptoms, (b) perceives stress, (c) fatigue, (d) quality of life, (e) NKCA, and (f) plasma IL-6. Graphical representation of the unconditional effect of time on depressive mood (CESD scores), perceived stress (PSS scores), fatigue (MFSI scores), quality of life (QLI scores), natural killer cell activity (NKCA; lytic units 20%), and circulating level of IL-6. The initial evaluation (T1) occurred 7 ± 5 wks post surgery, and with respect to T1, subsequent evaluations were T2 = 5 ± 2 wks, T3 = 9 ± 2 wks, T4 = 15 ± 3 wks, T5 = 34 ± 3 wks.

Figure 2

Effect of emotional neglect/abuse on (a) depressive mood, (b) perceived stress, (c) fatigue, (d) quality of life, (e) NKCA. Graphical representation of the relationship between childhood emotional neglect/abuse (calculated as average upper/lower quartiles) and depressive mood (CESD scores), perceived stress (PSS scores), fatigue (MFSI scores), quality of life (QLI scores), and natural killer cell activity (NKCA; lytic units 20%). Graphs are estimated by the hierarchical linear models from the time of the initial assessment (T1) through an approximate 9-month period (T5). Women who reported greater levels of childhood neglect/abuse were estimated to have more depressive mood (b = 1.29, p =.002), greater perceived stress (b = 1.20, p <.001), more fatigue (b = .66, p =.04), poorer quality of life (b = −.69, p <.001), lower NKCA (b = −3.12, p =.01) at the initial assessment and through the 9-month study period. The initial evaluation (T1) occurred 7 ± 5 wks post surgery, and with respect to T1, subsequent evaluations were T2 = 5 ± 2 wks, T3 = 9 ± 2 wks, T4 = 15 ± 3 wks, T5 = 34 ± 3 wks.

Figure 3

Effect of physical neglect on (a) perceived stress and (b) quality of life, and (c) plasma IL-6. Graphical representation of the relationship between childhood physical neglect (calculated as average upper/lower quartiles) and perceived stress (PSS scores), quality of life (QLI scores), and circulating IL-6 level. Graphs are estimated by the hierarchical linear models from the time of the initial assessment (T1) through an approximate 9-month period (T5). At the initial assessment, there were no significant differences in perceived stress, quality of life, or plasma IL-6 between the women. However, those women who reported greater level of childhood physical neglect were estimated to have an increase in perceived stress (b = .23, p <.001; b quadratic = −.005, p =.004) over the first 16 weeks that remained elevated thereafter. Lower level of physical neglect was associated with faster improvement rate in quality of life (b= −.014, p =.06) and a greater decline in circulating IL-6 (b = .0009, p =.03). The initial evaluation (T1) occurred 7 ± 5 wks post surgery, and with respect to T1, subsequent evaluations were T2 = 5 ± 2 wks, T3 = 9 ± 2 wks, T4 = 15 ± 3 wks, T5 = 34 ± 3 wks.