A randomized controlled trial of the effectiveness of a one-to-one peer support intervention on resilience, social support, and salivary cortisol in recently diagnosed women with breast cancer.

PURPOSE: Peer support has been suggested as a way to help women diagnosed with breast cancer to better cope with their situation, but studies on its effectiveness have conflicting results. This randomized controlled trial aimed to study the effectiveness of a one-to-one peer support intervention on psychological resilience, social support, and salivary cortisol among breast cancer patients. METHODS: The sample consisted of 121 newly diagnosed women at Onkologikoa Hospital. Patients who were prescribed chemotherapy were randomly assigned to Intervention Group 1 (IG1) or Control Group 1 (CG1). Similarly, those prescribed adjuvant radiotherapy were assigned to IG2 or CG2. Women in IG1 received 8 biweekly social support sessions from volunteer survivors who had successfully overcome breast cancer, while IG2 received 6 biweekly sessions. CG1 and CG2 only received standard care. Resilience, social support, and salivary cortisol were assessed at baseline (T1) and at the end of the intervention (T2). RESULTS: We found a non-significant, yet a small to moderate size increase in resilience from T1 to T2 in IG1 (p = 0.246; dDc = 0.47). Upon regression analysis, we observed that this increase was determined by changes in cortisol (ß = -0.658, p = 00.010), affective support (ß = -0.997, p = 00.014), and emotional support (ß = 0.935, p = 00.008). We also found a significant decrease in resilience levels in CG2 from T1 to T2 (p = 0.003; dDc = 0.88). CONCLUSION: The present study suggests that peer support can exert a protective psychological influence on women diagnosed with breast cancer, and further indicates an exciting avenue for future intervention development in the breast cancer care continuum. TRIAL REGISTRATION: ClinicalTrials.gov NCT05077371.

Resilience in Newly Diagnosed Breast Cancer Women: The Predictive Role of Diurnal Cortisol and Social Support.

BACKGROUND: Breast cancer is currently the most prevalent malignancy among women. Psychological resilience is an important factor that diminishes the stress-related emotional and psychosocial disturbances triggered when receiving the diagnosis. Furthermore, resilience appears to be associated with cortisol, the hormonal end-product of the hypothalamic-pituitary-adrenal axis; however, further studies are needed due to the mixed results reported. Thus, we aim to examine the predictive role of social support and cortisol in resilience among breast cancer patients. METHODS: A total of 132 women with primary breast cancer completed the Medical Outcomes Study-Social Support Survey (MOS-SSS) and the Resilience Scale (RS-14) and provided four salivary samples for the estimation of participants' total daily cortisol production, for which the formula of the area under the curve with respect to the ground (AUCg) was applied. Moderation analyses were performed to study the influence of social support and AUCg on psychological resilience levels. RESULTS: The regression analyses showed a direct significant effect for the emotional support subscale of MOS-SSS on resilience and the interaction between emotional support and AUCg was also found to be statistically significant. Specifically, the conditional effect of emotional support on resilience was found to be significant at middle (M = 3.08; p < .05) and low levels (M = .59; p < .001) of AUCg. CONCLUSIONS: Our results suggest that newly diagnosed breast cancer women with middle and low diurnal cortisol profiles may benefit more from emotional support based-interventions while women with high diurnal cortisol may need more individualized therapies.

Psychological resilience and cortisol levels in adults: A systematic review.

Resilience or the capacity to "bend but not break" refers to the ability to maintain or regain psychobiological equilibrium during or after exposure to stressful life events. Specifically, resilience has been proposed as a potential resource for staving off pathological states that often emerge after exposure to repeated stress and that are related to alterations in circulating cortisol. The aim of this systematic review of the literature was to gather evidence related to the relationship between psychological resilience and cortisol levels in adult humans. An extensive systematic search was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method in the PubMed and Web of Science databases. In total, 1256 articles were identified and, of these, 35 peer-reviewed articles were included in the systematic review. We categorized findings according to (1) the short and long-term secretion period covered by the cortisol matrices selected by studies and also according to (2) the differentiated diurnal, phasic (acute), and tonic (basal) components of the HPA output to which they refer and their relationships with resilience. Reported relationships between psychological resilience and distinct cortisol output parameters varied widely across studies, finding positive, negative, and null associations between the two variables. Notably, several of the studies that found no relationship between resilience and cortisol used a single morning saliva or plasma sample as their assessment of HPA axis activity. Despite limitations such as the great variability of the instruments and methods used by the studies to measure both resilience and cortisol, together with their high heterogeneity and small sample sizes, the evidence found in this systematic review points to the potential of resilience as a modifiable key factor to modulate the physiological response to stress. Therefore, further exploration of the interaction between the two variables is necessary for the eventual development of future interventions aimed at promoting resilience as an essential component of health prevention.

Anxiety and depression after breast cancer: The predictive role of monoamine levels.

PURPOSE: Despite the fact that the prevalence of anxiety and depression in breast cancer survivors is higher than in the general female population, the psychobiological substrate of this phenomenon has yet to be elucidated. We aimed to examine the predictive role of peripheral dopamine (DA), noradrenaline (NA), serotonin (5-HT) and kynurenine (KYN) in anxiety and depression among breast cancer survivors. METHOD: We evaluated 107 women using the Hospital Anxiety and Depression Scale, and monoamine levels were analyzed via high-performance liquid chromatography. RESULTS: High KYN levels predicted both disorders, while low NA and DA predicted anxiety and depressive symptoms, respectively. A negative conditional effect of 5-HT was found for anxiety and depression among younger women only, while being both middle-aged and younger influenced the negative conditional effect of DA on depression. CONCLUSION: Monoamine variations may render breast cancer survivors more vulnerable to anxiety and depression, with young women being especially vulnerable to the detrimental effect of low DA and 5-HT. Assessing subclinical psychobiological markers allows mental health nurses to identify vulnerable survivors prior to the onset of anxiety and depression, and to adjust nursing interventions accordingly.

Distress, proinflammatory cytokines and self-esteem as predictors of quality of life in breast cancer survivors.

OBJECTIVE: To examine the extent to which anxiety and depressive symptoms, self-esteem and proinflammatory cytokines interact to significantly predict quality of life in breast cancer survivors. METHODS: Cross-sectional data were collected from 134 breast cancer survivors. Hospital Anxiety and Depression Scale, Rosenberg Self-Esteem Scale and Quality of Life in Adult Cancer Survivors questionnaire, which includes the generic quality of life (QOL) and the quality of life related to cancer (QOLRC) subscales, were administered. Plasma IL-6 and TNF-α levels were measured using ELISA kits. Moderation analyses were performed to study the influence of psychobiological variables on quality of life. RESULTS: Anxiety and depressive symptoms, TNF-α predicted QOL scores, and both medium and high levels of TNF-α influenced the negative conditional effect of depressive symptoms on QOL. Anxiety symptoms and TNF-α was associated with QOLRC scores, and lower self-esteem predicted poorer QOLRC when women had high levels of TNF-α. CONCLUSIONS: These results highlight the booster effect of TNF-α for poorer quality of life in breast cancer survivors, both alone and in combination with depressive symptoms or low self-esteem. The study provides a framework for assessing subclinical markers, identifying vulnerable survivors and implementing psychological strategies to improve quality of life.

Active and Passive Coping Strategies: Comparing Psychological Distress, Cortisol, and Proinflammatory Cytokine Levels in Breast Cancer Survivors.

BACKGROUND: Breast cancer survivors can experience psychological distress, such as anxiety and depression, long after treatment has ended, and the development of such negative affective states has been related to the coping strategy used. OBJECTIVES: This pilot study aims to determine whether different coping strategies are associated with differences in psychological distress, cortisol, and tumor necrosis factor alpha (TNF-a) levels in breast cancer survivors. METHODS: 54 breast cancer survivors completed the Stress Coping Questionnaire and the Hospital Anxiety and Depression Scale and provided a blood sample for cortisol and proinflammatory cytokine measures. FINDINGS: Passive coping strategies were associated with higher psychological distress, cortisol, and TNF-a levels. The passive group had more avoidance and negative self-targeting and less positive reappraisal and focusing on a problem's solution.

Predictors of psychological distress in breast cancer survivors: A biopsychosocial approach.

OBJECTIVE: A cross-sectional study was conducted to examine the extent to which perceived social support, cortisol-awaking response (CAR) and tumour necrosis factor alpha (TNF-α) interact to statistically predict psychological distress in breast cancer survivors. METHOD: Moderation analyses were performed to study the influence of some psychobiological variables on psychological distress. The sample was comprised by 80 survivor women. RESULTS: TNF-α moderate the relation between social support and psychological distress, with both high and moderate levels being significant. In relation to age, a negative association between social support and psychological distress was found only in younger- and middle-age women, while lower levels of CAR were associated with psychological distress in older breast cancer survivors. CONCLUSION: This study provides a biopsychosocial approach about the predictors of psychological distress among breast cancer survivors. Social support interventions during and after treatment may help to improve women's longer-term health and quality of live during survivorship.

Reduced hippocampal IL-10 expression, altered monoaminergic activity and anxiety and depressive-like behavior in female mice subjected to chronic social instability stress.

Evidence indicates that release of pro-inflammatory cytokines induced by social stress contributes to affective disorders. Additionally, there are known sex differences in both the stress response and the stressors that can elicit this response. In this regard, the chronic social instability (CSI) rodent model of stress appears to be the best fit for the social nature of females. This study analyzed the effects of CSI on female mouse behavior, hippocampal cytokine expression, tryptophan metabolism and monoaminergic activity. The activity of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes were also measured. Results showed a decrease in sucrose consumption in stressed subjects, indicative of anhedonic behavior and an increase in climbing activity in the forced swimming test (FST) and in whisking behavior, which have been associated with anxiety. Decreased interleukin-10 (IL-10) expression was found in the hippocampus of the stressed mice, while no differences in pro-inflammatory cytokine expression and tryptophan (TRYP), kynurenine (KYN) or 3-hydroxy kynurenine (3-HK) levels were found. Increased hippocampal serotoninergic and noradrenergic activity was observed in stressed mice. The higher plasma corticosterone and lower hypothalamic glucocorticoid receptor (GR) expression levels showed an increase in HPA activity after CSI. No differences were found in the plasma estradiol levels or the central estrogen receptors (ERα and ERß) expression levels. These data indicate that the CSI stress-induced behavioral and physiological changes associated with anxiety and depressive disorders. Although additional studies are warranted, the results suggest an involvement of anti-inflammatory cytokines in the biobehavioral effects of social stress in female mice.

Melanoma tumors alter proinflammatory cytokine production and monoamine brain function, and induce depressive-like behavior in male mice.

Depression is a commonly observed disorder among cancer patients; however, the mechanisms underlying the relationship between these disorders are not well known. We used an animal model to study the effects of tumor development on depressive-like behavior manifestation, proinflammatory cytokine expression, and central monoaminergic activity. Male OF1 mice were inoculated with B16F10 melanoma tumor cells and subjected to a 21-day behavioral evaluation comprising the novel palatable food (NPF) test and tail suspension test (TST). The mRNA expression levels of proinflammatory cytokines, interleukin (IL)-1ß and IL-6, and tumor necrosis factor-alpha (TNF-α), were measured in the hypothalamus and hippocampus and the levels of IL-6 and TNF-α were measured in the blood plasma. We similarly determined the monoamine turnover in various brain areas. The tumors resulted in increasing the immobility in TST and the expression level of IL-6 in the hippocampus. These increases corresponded with a decrease in dopaminergic activity in the striatum and a decrease in serotonin turnover in the prefrontal cortex. Similarly, a high level of tumor development produced increases in the brain expression levels of IL-6 and TNF-α and plasma levels of IL-6. Our findings suggest that these alterations in inflammatory cytokines and monoaminergic system function might be responsible for the manifestation of depressive-like behaviors in tumor-bearing mice.

Coping with chronic social stress in mice: hypothalamic-pituitary-adrenal/ sympathetic-adrenal-medullary axis activity, behavioral changes and effects of antalarmin treatment: implications for the study of stress-related psychopathologies.

The aim of this study was to analyze the individual differences that lead to the development of psychopathological changes in response to chronic social stress. We also assessed the ability of an antagonist of the corticotrophin-releasing hormone (CRH) receptors to reverse the effects of stress. Male adult mice were exposed to repeated defeat experiences for 21 days using a sensorial contact model. After 18 days of defeat, two groups of subjects were established (active and passive), according to their behaviors during social confrontation. Antalarmin treatment was given for 4 and 6 days. The results corroborated previous data indicating that subjects who adopted a passive coping strategy had higher corticosterone levels after 21 days of defeat and decreased resting levels 3 days later. Moreover, they showed higher resting expression levels of hypothalamic CRH than their active counterparts. On day 24, the experimental animals were subjected to another social defeat to determine whether the stress response remained. The increase in corticosterone and hypothalamic CRH levels was similar for all of the stressed subjects, but the passive subjects also had a greater CRH response in the amygdala. Passive subjects had decreased levels of adrenal dopamine ß-hydroxylase, tyrosine hydroxylase and plasma adrenaline compared to the active subjects, and lower plasma noradrenaline levels than manipulated controls. The passive profile of physiological changes in both the hypothalamic-pituitary-adrenal and sympathetic-adrenal-medullary (SAM) axes has been associated with changes related to mood disorders, such as posttraumatic stress disorder and depression. The active coping profile is characterized by similar corticosterone resting levels to controls and increased SAM activity. Both profiles showed alterations in the novel palatable and forced swimming tests, with the passive profile being the most vulnerable to the effects of stress in this last test. Pharmacological treatment with antalarmin failed to reverse the effects of stress.

Effects of a putative antidepressant with a rapid onset of action in defeated mice with different coping strategies.

There is evidence suggesting that stressful social events may result in depressive-like disorders, but the development of these disorders depend on the way in which people cope with stress. Although antidepressants are useful their drawback is a delay in the therapeutic effects, moreover not all the patients show an adequate response to this treatment. The aim of this study was to analyse the effect of RS 67333, which is a 5-HT(4) receptor partial agonist and a putative antidepressant which exhibits a rapid onset of action and to determine whether this drug reverses the behavioural and physiological effects that are generated by chronic defeat in subjects who manifest a more vulnerable profile in their response to stress. Male mice were exposed to defeat for 21 consecutive days using a sensorial contact model. After 18 days of defeat, 2 groups of subjects were established, active and passive, in accordance with the behaviour that was manifested during social confrontation, and drug treatment was initiated for 5 days. Finally, the animals were subjected to a forced swimming test (FST). The results revealed higher corticosterone levels in passive mice after the last defeat. Additionally, 3 days after the last defeat, they showed lower corticosterone levels and higher splenic IL-6 and TNF-α levels and hypothalamic GR mRNA levels when compared to their active and manipulated control counterparts. Passive mice had higher 5-HT(1A) receptor mRNA levels than the manipulated controls and a lower MR/GR ratio than active mice. Similar to stress, the drug increased hypothalamic GR mRNA levels, but it did not affect other measured physiological variables or social behaviour, which suggested that the mechanism of this drug is not the most adequate for reversing stress-induced effects in this model. Nevertheless, the treatment increased swimming and decreased immobility in the FST, suggesting an antidepressant potential for this drug.

Behavioral coping strategies in response to social stress are associated with distinct neuroendocrine, monoaminergic and immune response profiles in mice.

Individual variation in behavioral coping strategies to stress implies that animals may have a distinct physiological adaptation to stress; these differences may underlie differences in vulnerability to stress-related diseases. This study was designed to test the hypothesis that different behavioral coping strategies (active vs. passive) are stable over time and that they would be associated with differences in hypothalamic-pituitary-adrenal (HPA) and sympathetic-adreno-medular (SAM) axes, and monoaminergic and immune activity. Male mice were subjected to social stress. Twelve days after the first social interaction, mice were subjected to a second identical social stress interaction. Behavior was videotaped and assessed during both sessions. One hour after the final social interaction, serum was collected for corticosterone and adrenaline concentrations and brains were collected for hypothalamic corticotrophin-releasing hormone (CRH) mRNA expression. Monoaminergic system activity was determined by mRNA expression of serotonin, dopamine and noradrenaline synthetic enzymes in the brain stem. Immune system activity was determined by mRNA expression of hypothalamic interleukin-1ß (IL-1ß) and splenic IL-1ß and interleukin-2 (IL-2). Mice engaging in a passive strategy had higher serum corticosterone and lower serum adrenaline concentrations than the active group. The passive group showed lower hypothalamic mRNA expression of IL-1ß and CRH and lower splenic mRNA expression of IL-2 and IL-1ß relative to mice in the active group. An active strategy was associated with higher expression of the dopaminergic synthetic enzyme, while a passive strategy was associated with decreased expression of the serotonergic synthetic enzyme. These findings indicate that individual coping strategies are stable over time and are related to differences in the physiological stress response and immune activity.

Individual differences in chronically defeated male mice: behavioral, endocrine, immune, and neurotrophic changes as markers of vulnerability to the effects of stress.

This study aimed to analyze different behavioral profiles in response to chronic social defeat using the sensorial contact model. We hypothesized that a passive profile, unlike an active one, would be associated with behavioral and physiological characteristics related to depression. Six-week-old OF1 male mice were subjected to defeat for 21 consecutive days. A combination of cluster and discriminant analyses of the behavior exhibited during confrontation on Day 21 established two behavioral profiles: active (n = 22) and passive (n = 34). Passive mice, with a high level of immobility and low non-social exploration, had higher plasma corticosterone concentrations than active mice after 21 days of defeat. Three days after the last defeat, passive mice had lower corticosterone levels than manipulated-control mice (n = 11). Higher levels of interleukin-6 and tumor necrosis factor-α (TNF-α) in the spleen and lower hippocampal brain-derived neurotrophic factor levels were observed in passive mice in comparison with those in active mice and the manipulated controls. The only differences observed in active mice in relation to the manipulated control were higher plasma corticosterone (Day 21) and TNF-α levels. The results show that different behavioral profiles in response to chronic defeat are associated with different physiological profiles, and that the passive profile presents physiological characteristics previously associated with depression.