Cumulative lifetime stress exposure and leukocyte telomere length attrition: The unique role of stressor duration and exposure timing

BACKGROUND:Stress exposure occurring across the lifespan increases risk for disease, potentially involving telomere length shortening. Stress exposure during childhood and adulthood has been cross-sectionally linked with shorter telomere length. However, few longitudinal studies have examined telomere length attrition over time, and none have investigated how stressor duration (acute life events vs. chronic difficulties), timing (childhood vs. adulthood), and perceived severity may be uniquely related to telomere length shortening. METHODS:To address these issues, we administered a standardized instrument for assessing cumulative lifetime stress exposure (Stress and Adversity Inventory; STRAIN) to 175 mothers of children with Autism Spectrum Disorder or neurotypical children and measured their leukocyte telomere length (LTL) at baseline and 2 years later. RESULTS:Greater count of lifetime stressors was associated with shorter LTL at baseline and greater LTL attrition over time. When separating lifetime stressors into acute life events and chronic difficulties, only greater count of chronic difficulties significantly predicted shorter baseline LTL and greater LTL attrition. Similarly, when examining timing of stressor exposure, only greater count of chronic childhood difficulties (age < 18) significantly predicted shorter baseline LTL and greater LTL attrition over the 2-year period in mid-life. Importantly, these results were robust while controlling for stressors occurring during the interim 2-year period. Post-hoc analyses suggested that chronic difficulties occurring during earlier childhood (0-12 years) were associated with greater LTL attrition. Cumulative stressor severity predicted LTL attrition in a parallel manner, but was less consistently associated with baseline LTL. CONCLUSIONS:These data are the first to examine the effects of different aspects of cumulative lifetime stress exposure on LTL attrition over time, suggesting that accumulated chronic difficulties during childhood may play a unique role in shaping telomere shortening in midlife

Stimulant use for self-management of pain among safety-net patients with chronic non-cancer pain.

BackgroundChronic pain affects one-fifth of US adults. Reductions in opioid prescribing have been associated with increased non-prescription opioid use and, chronologically, increased stimulant (methamphetamine and cocaine) use. While non-prescription opioid use is commonly attributed to pain self-management, the role of stimulants in managing pain is unclear.MethodsWe analyzed baseline data from a longitudinal study of patients with chronic non-cancer pain in an urban safety-net healthcare system who had been prescribed an opioid for ≥3 of the last 12 months, and had a history of non-prescription opioid, cocaine, or amphetamine use (N = 300). We estimated the prevalence and identified correlates of stimulant use to treat pain among a subgroup of patients who reported past-year stimulant use (N = 105). Data sources included computer-assisted questionnaire (demographics, substance use, pain), clinical exam and procedures (pain, pain tolerance), and chart abstraction (opioid prescriptions). We conducted bivariate analyses to assess associations between demographics, pain characteristics, non-opioid therapies, substance use, opioid prescriptions, and self-reported symptoms, with reporting using stimulants to treat pain. Demographic variables and those with significant bivariate associations were included in a multivariable logistic regression model.ResultsFifty-two percent of participants with past-year stimulant use reported using stimulants in the past year to treat pain. Participants who used stimulants for pain reported slightly higher average pain in the past 3 months (median of 8 (IQR: 6-8) vs 7 (7-9) out of 10, p = 0.049). In the multivariable analysis, female gender (AOR= 3.20, 95% CI: 1.06-9.63, p = 0.039) and higher score on the Douleur Neuropathique 4 neuropathic pain questionnaire (AOR = 1.34, 95% CI: 1.05-1.70, p = 0.017) were associated with past-year stimulant use to treat pain.ConclusionStimulants may be used for pain self-management, particularly for neuropathic pain and among women. Our findings suggest an underexplored motivation for stimulant use in an era of reduced access to prescribed opioids

Cell aging and resilience: associations between daily emotion regulation and increased telomerase activity

Rationale : Chronic stress has been related to lower telomerase, an enzyme that helps preserve the integrity of DNA and slow immunological aging. However, it is unknown whether daily psychological processes reflecting healthy emotion regulation protect against stress-related immune-aging. Methods : We examined basal telomerase activity in a sample of 72 healthy premenopausal women across a range of stress levels, including 35 mothers caring for a child with autism and 37 low-stress control mothers of healthy children. Participants completed a nightly diary over the course of a week, reporting their exposure to positive and negative events. Then they rated the extent to which they employed various emotion-regulation strategies in response to these events. Within-subject weekly means for all measures were calculated. In addition, composite scores for positive affect in response to positive daily events and negative affect in response to daily stressors were calculated, and weekly means obtained. Depressive symptoms were assessed using the Inventory of Depressive Symptoms. On day 4 of the study week, a fasting blood draw was performed to measure peripheral blood mononuclear cells (PBMC) telomerase activity. Results : Higher telomerase activity was significantly associated with the use of more resilient emotion regulation strategies, including more positive emotional responses to positive daily events (r=0.27, p=0.02) and increased savoring of positive daily events (r=0.24, p=0.04). In general, negative emotional responses and rumination in response to daily stressors were not related to telomerase with two exceptions: lower telomerase was associated with greater emotional suppression (r= − 0.34, p<0.01) and higher levels of depressive symptoms (r= − 0.24, p=0.05). There were no overall differences in telomerase activity between caregivers versus controls. Conclusion : These are the first findings to link daily emotion-regulation processes to telomerase activity. Daily emotion regulation strategies characterized by greater engagement with the positive and lower emotional suppression are associated with increases in telomerase, which may contribute to resilient immune cell aging. Emotion regulation, particularly in relation to the use of strategies that maintains a positive outlook in the face of stressful life exposures, may protect against cell aging