Cognitive functioning and emotion processing in breast cancer survivors and controls: An ERP pilot study

Diagnosis and treatment of breast cancer is a very emotionally aversive and stressful life event, which can lead to impaired cognitive functioning and mental health. Breast cancer survivors responding with repressive emotion regulation strategies often show less adaptive coping and adverse outcomes. We investigated cognitive functioning and neural correlates of emotion processing using ERPs. Self‐report measures of depression, anxiety, and fatigue, as well as hair cortisol as an index of chronic stress, were assessed. Twenty breast cancer survivors (BCS) and 31 carefully matched healthy controls participated in the study. After neuropsychological testing and subjective assessments, participants viewed 30 neutral, 30 unpleasant, and 30 pleasant pictures, and ERPs were recorded. Recognition memory was tested 1 week later. BCS reported stronger complaints about cognitive impairments and more symptoms of depression, anxiety, and fatigue. Moreover, they showed elevated hair cortisol levels. Except for verbal memory, cognitive functioning was predominantly in the normative range. Recognition memory performance was decreased in cancer survivors, especially for emotional contents. In ERPs, survivors showed smaller late positive potential amplitudes for unpleasant pictures relative to controls in a later time window, which may indicate less elaborative processing of this material. Taken together, we found cognitive impairments in BCS in verbal memory, impaired emotional picture memory accuracy, and reduced neural activity when breast cancer survivors were confronted with unpleasant materials. Further studies and larger sample sizes, however, are needed to evaluate the relationship between altered emotion processing and reduced memory in BCS in order to develop new treatment strategies.     

Hair cortisol as a measure of the stress response to social adversity in young children

Hair cortisol has the potential to provide insight into young children's long-term stress response to social adversity. This study investigated associations between children's exposure to adversity from pregnancy to 2 years of age and their hair cortisol at 2 years, using a longitudinal cohort of children enriched for adversity risk, whose mothers were recruited during pregnancy through the “right@home” trial. Exposures were 18 maternal socioeconomic and psychosocial indicators of adversity, examined as concurrent, cumulative, and longitudinal exposure from pregnancy to 2 years. Hair samples were analyzed from 319/603 (53%) children participating at 2 years. Multivariable regression analyses for concurrent exposure showed three indicators of adversity were associated with higher hair cortisol (housing tenure of public rental, paying board or living rent free; not living in a safe place; higher maternal stress symptoms), one with lower hair cortisol (housing problems), and 14 indicators with no evidence of association. There was no evidence of association for the cumulative adversity count. Longitudinal exposure showed “intermittent” and “persistent” high maternal stress symptoms were associated with higher hair cortisol. The small number of associations identified suggests that hair cortisol is limited as a measure of stress response to social adversity in children at 2 years.     

Hair cortisol levels as a retrospective marker of hypothalamic-pituitary axis activity throughout pregnancy: comparison to salivary cortisol

Maternal stress during pregnancy is associated with negative maternal/child outcomes. One potential biomarker of the maternal stress response is cortisol, a product of activity of the hypothalamic-pituitary-adrenal axis. This study evaluated cortisol levels in hair throughout pregnancy as a marker of total cortisol release. Cortisol levels in hair have been shown to be easily quantifiable and may be representative of total cortisol release more than single saliva or serum measures. Hair cortisol provides a simple way to monitor total cortisol release over an extended period of time. Hair cortisol levels were determined from each trimester (15, 26 and 36 weeks gestation) and 3 months postpartum. Hair cortisol levels were compared to diurnal salivary cortisol collected over 3 days (3 times/day) at 14, 18, 23, 29, and 34 weeks gestational age and 6 weeks postpartum from 21 pregnant women. Both salivary and hair cortisol levels rose during pregnancy as expected. Hair cortisol and diurnal salivary cortisol area under the curve with respect to ground (AUCg) were also correlated throughout pregnancy. Levels of cortisol in hair are a valid and useful tool to measure long-term cortisol activity. Hair cortisol avoids methodological problems associated with collection other cortisol measures such as plasma, urine, or saliva and is a reliable metric of HPA activity throughout pregnancy reflecting total cortisol release over an extended period.     

Salivary cortisol levels and the cortisol response to dexamethasone before and after EMDR: a case report

Trauma survivors with posttraumatic stress disorder (PTSD) have been shown to have lower basal cortisol levels in the urine, plasma, and saliva than in trauma survivors without PTSD, nontraumatized mentally ill, or healthy subjects. We report on a case study in which we measured pre- and post-Eye Movement Desensitization and Reprocessing (EMDR) treatment salivary cortisol levels and salivary cortisol response to 0.50 mg of dexamethasone in a 41-year-old female with chronic PTSD symptoms. Our goal was to determine whether symptom improvement following trauma-focused treatment (EMDR) is associated with changes in basal salivary cortisol or in the cortisol response to dexamethasone administration. Our findings show moderate symptom improvement, an increase in basal cortisol levels, and a more attenuated cortisol hypersuppression in response to the dexamethasone suppression test following EMDR treatment. These results suggest the potential utility of including neuroendocrine measures in the assessment of treatment outcome in PTSD.     

Innovations in biological assessments of chronic stress through hair and nail cortisol: Conceptual,developmental, and methodological issues

Much of the existing research on biological mechanisms underlying the stress experience has focused largely on moment-to-moment stress, rather than on chronic stress, an arguably more powerful predictor of long-term outcomes. Recent methodological innovations have paved the way for new lines of research on chronic stress, with promising implications for developmental researchers and for those who study health and adversity. In particular, there are increasing studies that have focused on chronic stress assessments by relying on cortisol derived from hair and nails as a biomarker for chronic stress. In this paper, we provide an overview of their use, describe how hair and nail cortisol ought to be conceptualized differently across the lifespan, how developmental factors may impact its interpretation, and the circumstances under which its use may be more methodologically sensible. The purpose of this review is to provoke further discussion and encourage careful research designs that utilize hair and nail cortisol for understanding the effects of chronic stress exposure from the early developmental period, across adverse contexts, and in association with psychological and physical health outcomes.     

Prenatal maternal hair cortisol concentrations are related to maternal prenatal emotion dysregulation but not neurodevelopmental or birth outcomes

Hair cortisol concentrations measured during pregnancy have emerged as a novel biomarker for prenatal stress exposure. However, associations between prenatal stress and distress, broadly defined, and hair cortisol concentrations during pregnancy are inconsistent. We examined relations among hair cortisol concentrations during the third trimester with (a) emotion dysregulation and (b) detailed measures of maternal prenatal stress. We also examined the predictive validity of maternal hair cortisol during pregnancy for adverse newborn health outcomes. Cortisol concentrations were derived from 6 cm of hair during the third trimester of pregnancy. Mothers reported on their emotion dysregulation and stress at this time. A standardized newborn neurobehavioral exam was conducted shortly after birth and newborn birth weight and gestational age were assessed from medical records. All hypotheses were preregistered on the Open Science Framework (osf.io/279ng). High levels of emotion dysregulation, but not stress, were predictive of high hair cortisol concentrations. Maternal prenatal BMI mediated the relation between maternal prenatal emotion dysregulation and hair cortisol concentrations. There was no association between hair cortisol and infant birth outcomes. This research supports the notion that transdiagnostic markers of psychopathology are important correlates of hair cortisol concentrations during pregnancy.     

Prenatal treatment with glucocorticoids sensitizes the hpa axis response to stress among full-term infants

The objective of this study was to determine the consequences for HPA axis functioning among healthy full-term newborns of prenatal treatment with the synthetic glucocorticoid (GC), betamethasone, which is the routine treatment for threatened preterm delivery. Ninety full-term infants were recruited into two study groups (30 betamethasone treated; 60 comparison group matched for GA at birth and sex). The cortisol and behavioral response to the painful stress of a heel-stick blood draw was assessed 24 hr after birth. Full-term infants exposed to prenatal betamethasone displayed a larger cortisol response to the heel-stick procedure, despite no differences in baseline levels. Further, within the recommended window of betamethasone administration (24-34 gestational weeks), infants exposed to betamethasone earlier in gestation displayed the largest cortisol response to the heel-stick. These data add to accumulating evidence that prenatal exposure to elevated GCs programs the development of the HPA axis.     

Chronic stress in dogs subjected to social and spatial restriction. II. Hormonal and immunological responses.

Two groups of beagles, accustomed to spacious group housing, were subjected to social and spatial restriction and studied for manifestations of chronic stress with a time interval of 7 weeks between the groups. The change from outside group housing (the control period) to individual housing in small indoor kennels resulted in sustained decreases in urinary adrenaline/creatinine and noradrenaline/creatinine ratios for the total group. Urinary dopamine/creatinine and noradrenaline/adrenaline ratios were statistically unaffected. Socially and spatially restricted dogs that had experienced pleasant weather during the control period showed (a) increased salivary and urinary cortisol concentrations, (b) a diminished responsiveness of the pituitary-adrenal axis to a sudden sound blast or exogenous CRH, (c) intact plasma ACTH and cortisol suppressions after dexamethasone administration, and (d) increased concanavalin A induced lymphocyte proliferations. When social and spatial restriction was preceded by a control period during which the weather was bad, these physiological responses were either augmented (lymphocyte proliferation), or offset (salivary and urinary cortisol), or directed oppositely (CRH-induced ACTH and cortisol responses). Together with the previously presented behavioral observations, these data suggest that bad weather conditions during spacious outdoor group housing induced early stress that attenuated the negative appraisal of the subsequent period of social and spatial restriction. In comparison to male dogs, bitches showed increased HPA responses to a sound blast or exogenous CRH. Their increased attenuations of the ACTH and cortisol responses to CRH after 5 weeks of restricted housing indicates that bitches are not only more susceptible to acute stress, but also to chronic housing stress. It is concluded that the quality of circumstances preceding a period of affected well-being determines the magnitude and even the direction of the behavioral and physiological stress responses. Basal salivary and urinary cortisol measurements are useful for the assessment of chronic stress, and of poor welfare in dogs. The use of urinary catecholamine, peripheral leucocyte, and lymphocyte proliferation measures requires further investigation.     

Salivary dehydroepiandrosterone secretion in response to acute psychosocial stress and its correlations with biological and psychological changes

We investigated dehydroepiandrosterone (DHEA) secretion in response to acute psychosocial stress and the relations of DHEA secretion to cortisol secretion, cardiovascular activity, and negative mood changes. Thirty-three male students (mean age 22.6 years) were subjected to the psychosocial stress test "Trier Social Stress Test" (TSST), in which the participants were asked to deliver a speech and perform a mental arithmetic task in front of two audiences. Collections of saliva, measurements of blood pressure and heart rate, and assessments of negative mood by visual analog scales were conducted before, during, and after TSST. Acute psychosocial stress significantly increased salivary DHEA level by an average of 60% immediately after TSST. The peak of DHEA concentration preceded that of cortisol concentration by about 10 min. DHEA response was moderately correlated to cortisol response (r=.34, r(s)=.49) but not to cardiovascular response. Lower DHEA level and elevated cortisol/DHEA ratio during TSST were significantly and moderately correlated with increased negative mood during and after TSST. These results indicated that an acute increase in DHEA concentration under stressful situations might be partly mediated by the activity of hypothalamus-pituitary-adrenal axis and could have some significance in the improvement of negative mood.     

5·12汶川地震前后灾区焦虑抑郁障碍病人症状对比研究

目的探索5.12汶川地震对幸存者焦虑和抑郁情绪的影响。方法通过对德阳市人民医院神经内科2007年5月12日～2009年5月12日的1298名就诊者,进行汉密尔顿焦虑量表和汉密尔顿抑郁量表评估病人的结果比较,以发现地震对幸存者的焦虑、抑郁情绪的影响。结果地震后单纯焦虑障碍发病率明显增加(P0.05),女性焦虑障碍和抑郁障碍的程度明显高于男性,并且地震对幸存者的认知障碍产生了比较大的影响。结论5.12汶川地震对灾区群众的情绪产生了较大影响。     

Tobacco usage interacts with postdisaster psychopathology on circadian salivary cortisol.

Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) have been associated with increased rates of tobacco usage as well as with dysregulations of the hypothalamus-pituitary-adrenal (HPA) axis. At the same time tobacco also affects the HPA axis. This paper examines the relationships between PTSD, posttraumatic MDD, smoking and levels of circadian cortisol 2-3 years postdisaster. Subjects were survivors of the Enschede fireworks disaster. The sample consisted of 38 healthy survivors, 40 subjects with PTSD, and 17 subjects with posttraumatic MDD. The Composite International Diagnostic Interview was used to determine mental disorders in accordance with DSM-IV criteria. Salivary cortisol samples were collected at home immediately upon awakening, 30 min after awakening, at noon, and at 10 p.m. Quantity of smoking was measured through self-report. The results of the study show that salivary cortisol concentrations were higher in smoking subjects. Survivors with MDD following the disaster had a flatter diurnal cortisol curve than subjects with PTSD or healthy survivors. In survivors with PTSD and healthy individuals the usual dynamic pattern of increase in cortisol past awakening was present, while we did not observe this in posttraumatic MDD. These survivors with MDD tended to use more tobacco per day, and the cortisol group differences could only be revealed when we adjusted for quantity of smoking. Smoking, which may be an important palliative coping style in dealing with posttraumatic arousal symptoms, seems to mediate the relationship between traumatic stress and the HPA-axis.     

Aberrations in lymphocyte subpopulations and function during psychological stress

Eight trainees in psychiatry taking their final oral fellowship examinations were compared with 16 controls to determine the effect of stress on their immune system. Two measures of stress were utilized to distinguish the highly stressed subjects from those minimally stressed. T cell subpopulations, B cell numbers, mitogen reactivity, natural killer cell activity, plaque forming cell responsiveness, antigen specific T suppressor cell activity, and hormone levels were studied 2 weeks before and 2 weeks after the exam. The results demonstrated transiently elevated numbers of T and B lymphocytes but impaired plaque forming cell and mitogen responsiveness in the highly stressed group prior to their exam which normalized later. The results support the concept that stress may significantly alter the immune response in man.     

实验性应激对STZ昆明小鼠血糖水平影响的对照研究

目的 :了解慢性实验性应激对 STZ昆明小鼠血糖水平的影响和作用特点。方法 :取 STZ鼠 4 0只 ,正常昆明小鼠 2 0只 ,按血糖、性别配对后分为四组。实验性应激方法为限制、旋转和拥挤 ,为时六周 ,实验后每两周复查一次血糖。结果 :慢性应激可使雄性 STZ昆明小鼠血糖明显升高。药物、应激与性别单一因素对血糖的作用均不明显 ,药物与应激的交互作用对第 4、 6周血糖作用明显 ,药物、应激与性别三者的交互作用对第 6周血糖作用明显。结论 :慢性实验性应激刺激能使 STZ鼠血糖显著升高 ;雄鼠对应激的血糖反应性比雌鼠敏感。     

Physiological indicators of salinity stress in the grey mullet,Mugil cephalus,Linnaeus, 1758 juveniles

Grey mullet (Mugil cephalus) juveniles were subjected to salinity stress in order to determine physiological response and recovery. Variations in the most important blood physiological indicators of stress (i.e., cortisol and glucose) were analyzed after application of stress. According to the results, the concentration of cortisol increased significantly 30 min after delivery of fish to water with 15 and 25 ppt salinities. The elevated levels of cortisol returned to basal levels 60 min after application of stress (P?>?0.05). Plasma cortisol and glucose did not show significant changes after delivery of fish to water with 35 ppt salinity (P?>?0.05). The elevation of plasma glucose occurred 30 and 60 min after delivery of fish to water with 15 and 25 ppt salinities (P?>?0.05). Our study demonstrated that low salinities are stressful for grey mullet juveniles.     

Plasma catecholamines: Exaggerated elevation is associated with stress susceptibility

The ability to survive acute stress differs markedly between individual rats. In order to determine whether ability to survive stress is correlated with aberrations of the sympathoad-renomedullary response, we measured plasma and tissue catecholamines (CA's) and blood glucose before, during, and for 5 hr after footshock stress. Splenic weights and liver glycogen were measured at sacrifice. Rats that survived the post-stress period (survivors) were compared to rats that did not survive (lethalities). Our results revealed a malignant rise of plasma CA's in lethalities beginning at stress onset and continuing until death. Plasma CA's in lethalities during stress were over 200% of those in survivors, whereas tissue CA's were reduced in both groups. Paradoxically, responses to circulating and neuronal CA's appeared to be diminsished in lethalities. Lethalities, but not survivors, became profoundly hypoglycemic after stress, in spite of their elevated plasma CA's. Likewise, evidence of significant splenic contraction was absent in lethalities. Thus, elevated plasma CA concentrations and reduced target organ responsiveness are associated with stress-induced lethality.     

Adrenal and behavioral responses of swine restricted to varying degrees of mobility

Adrenal and behavioral responses in swine restricted to varying degrees of mobility were examined to determine what component may impose chronic stress. The components of restriction considered were the inability to turn around and/or move freely. For 5 to 6 weeks 32 pigs were restrained such that pigs A) could move freely; B) could not turn around or move freely; C) could not turn around but could move back and forth the same distance as pigs in A; or D) could turn around but not move freely. After 4 weeks no significant differences due to degree of restraint were found in the profile of serum cortisol concentrations, neutrophil:lymphocyte ratio and ambulatory abilities; however overall cortisol concentrations were higher in pigs that could turn around but not move freely. Increases in serum cortisol due to ACTH injection were higher in pigs that could turn around but not move freely. No alterations in the manner in which gilts stood up and layed down could be observed. Collectively these data suggest that swine adapt when mobility is restricted to not turning around and not moving freely but cannot when animals can turn around but not move freely.     

The α7 nicotinic acetylcholine receptor and the acute stress response: maternal genotype determines offspring phenotype

α7 Nicotinic acetylcholine receptors (α7nAchRs) modulate immune activation by suppressing production of pro-inflammatory cytokines in peripheral immune cells. α7nAchRs also modulate inhibitory output in the hippocampus, which provides input to key circuits of the HPA axis. Therefore, the α7 nicotinic acetylcholine receptor gene (CHRNA7) may be associated with cortisol stress response. Polymorphisms in the CHRNA7 promoter decrease its expression and may dampen the cholinergic response, leading to an increase in inflammation. Increased inflammation may change the intrauterine environment, altering neuroendocrine development in the offspring. Maternal CHRNA7 genotype could affect an offspring's HPA regulation via reprogramming in utero. Patients with allergic disorders have a differential cortisol response to stress. This study utilized samples collected from a cohort of 198 adolescents in a previous study of atopic disorders, who demonstrated a disturbance in HPA response associated with atopy. Salivary cortisol samples collected from the adolescents after a series of laboratory procedures and DNA samples collected from the adolescents and their parents were used for further analysis. DNA samples were genotyped for allelic variation in the CHRNA7 promoter. Genetic association analyses with the cortisol levels were performed in the adolescents. Maternal genotype influences were investigated for the CHRNA7 gene. We also included maternal and child atopy diagnosis as covariates in determining cortisol levels and tested for association of CHRNA7 to atopy. Polymorphisms in the CHRNA7 promoter were associated with lower cortisol levels after a small laboratory stress. Our findings also show that although the child's CHRNA7 genotype affects stress response, the maternal genotype has a stronger influence on cortisol release after stress in male offspring. These effects were independent of atopy status.     

Intercorrelations between serum, salivary, and hair cortisol and child-reported estimates of stress in elementary school girls

To evaluate the impact of stress on children's well-being, it is important to have valid and reliable stress assessment methods. Nevertheless, selection of an appropriate method for a particular research question may not be straightforward, as there is currently no consensus on a reference method to measure stress in children. This article examined to what extent childhood stress can be estimated accurately by stressor questionnaires (i.e., Coddington life events scale) and biological markers (serum, salivary, and hair cortisol) using the Triads (a triangulation) method in 272 elementary school girls. Salivary cortisol was shown to most accurately indicate true childhood stress for short periods in the past (i.e., last 3 months), whereas hair cortisol may be preferred above salivary measurements for periods more distant and thus for chronic stress assessment. However, applicability should be confirmed in larger and more heterogeneous populations.     

Genetic characteristics of hepatitis B virus genotypes as a factor for interferon-induced HBeAg clearance

The factors determining the responsiveness of different hepatitis B virus (HBV) genotypes to interferon treatment are not fully understood. We investigated the relationship between HBV genetic characteristics and the outcome of short (16 weeks) or prolonged (32 weeks) treatment with standard interferon-alpha in a prospectively followed cohort of 103 patients across Europe with HBeAg positive chronic hepatitis B. INNO-LiPA assays and HBV DNA sequencing were used to determine HBV genotypes, mutations in the core promoter and precore/core regions. After 16-weeks interferon-alpha treatment, the rate of HBeAg clearance was higher in genotype A versus all other genotypes (P = 0.014), or genotype D alone (P = 0.05). The HBV genome analysis revealed that: (i) after 16-weeks treatment, an HBV subpopulation with core promoter mutations emerged or increased (P < 0.001) only in genotype A; (ii) the core gene of genotype A has the lowest number of amino acid variations in comparison with genotypes B, C, or D. Logistic regression analysis identified genotype A as a positive predictor of short (16 weeks) treatment response (P = 0.001; odds ratio 6.19, 95 confidence interval 1.94-19.8), having a greater impact than baseline HBV DNA or alanine aminotransferase (ALT) levels. In contrast, the response to prolonged interferon-alpha treatment was not different between HBV genotypes. These results suggest that HBV genotype A responds earlier to interferon treatment than other genotypes, which is associated with its molecular characteristics. The optimal duration of interferon-based therapies in chronic hepatitis B may vary between different HBV genotypes.