Enhancement of serotonin uptake by cortisol: a possible link between stress and depression

Stress and depression are characterized by elevation of circulating cortisol, as well as by changes in physiological functions. In this study, we addressed the possibility that elevated cortisol is also associated with the origin and development of depression. We report here that cortisol at the nM-μM concentration range induces a substantial increase in serotonin uptake both in vitro, by human peripheral blood lymphocytes (PBLs) and cortical neuronal cells, and in vivo, by rabbit PBLs, owing to promotion of synthesis of the serotonin transporter. These findings offer a novel molecular mechanism for depression associated with stress. Accordingly, the elevated cortisol induced by stress increases serotonin uptake, under both rest and nerve stimulation, which is overtly expressed in symptoms of depression.     

Relation between catastrophizing and depression in chronic pain patients

The relation between catastrophizing, depression, and pain was examined in 125 chronic pain patients. The Coping Strategies Questionnaire (CSQ; Rosenstiel & Keefe, 1983) assessed patients' use of cognitive and behavioral strategies to cope with chronic pain. A significant association between catastrophizing and depression was found. In order to address questions of measurement redundancy, 6 clinical psychologists rated the degree to which items on the CSQ reflected depressive symptomatology. All items contained in the Catastrophizing subscale were rated by all psychologists as being reflective of symptoms of depression and were removed from the CSQ. When this subscale was excluded, none of the remaining CSQ subscales were significantly related to depression. The discussion addresses the interpretive difficulties that arise from hypothesizing mediating relations between variables that are conceptually and operationally confounded.     

Sex differences of salivary cortisol secretion in patients with major depression

Depression is associated with increased cortisol secretion and occurs more often in women than in men. Thus, it has been hypothesized that differences in cortisol secretion might, in part, be responsible for the greater risk of developing depression in women. However, only few studies have examined sex differences in baseline cortisol secretion in depressed patients and healthy controls. We examined sex effects on cortisol secretion in 52 medication-free patients with major depression (37 women, 15 men, mean ± SD age 35 ± 11 years, Hamilton Depression Scale mean score 27 ± 5) and 50 healthy age- and sex-matched control subjects. Salivary cortisol concentrations were measured at 8:00, 12:00, 16:00, and 22:00 h. Repeated measures analysis of covariance revealed a group × sex interaction (p = 0.05). Post hoc tests revealed higher cortisol concentrations in depressed compared to healthy men [F(1;29) = 7.5, p = 0.01]. No differences were found between depressed and non-depressed women. Our results do not support the hypothesis that differences in cortisol secretion between depressed and non-depressed subjects are more pronounced in women than in men. Study characteristics and methods as well as sex-specific confounding variables such as menstrual cycle, menopause and the use of oral contraceptives may account for inconclusive results across studies.     

Correlation between maternal stress and children's stress

Mothers (N = 168, M age = 37.0 yr., SD = 4.6) responded to a questionnaire of scales measuring sources of stress and symptoms of stress within themselves, and symptoms of stress in their 5-8-yr.-old children (61 girls, 98 boys; M age = 7.3 yr., SD = 1.0). Scores on all scales intercorrelated significantly, indicating a relationship between maternal stress and stress of the child. Both types of stress also correlated with the frequency of punishment of the child. Both maternal stress and frequency of punishment predicted stress symptoms in the children, maternal stress being a somewhat stronger predictor.     

A link between stress and depression: shifts in the balance between the kynurenine and serotonin pathways of tryptophan metabolism and the etiology and pathophysiology of depression

Alteration of tryptophan (TRP) metabolism elicited by proinflammatory cytokines has gained attention as a new concept to explain the etiological and pathophysiological mechanisms of major depression. The kynurenine (KYN) pathway, which is initiated by indoleamine 2,3-dioxygenase (IDO), is the main TRP metabolic pathway. It shares TRP with the serotonin (5-HT) pathway. Proinflammatory cytokines induce IDO under stress, promote the KYN pathway, deprive the 5-HT pathway of TRP, and reduce 5-HT synthesis. The resultant decrease in 5-HT production may relate to the monoamine hypothesis of major depression. Furthermore, metabolites of the KYN pathway have neurotoxic/neuroprotective activities; 3-hydroxykynurenine and quinolinic acid are neurotoxic, whereas kynurenic acid is neuroprotective. The hippocampal atrophy that appears in chronic depression may be associated with imbalances in neurotoxic/neuroprotective activities. Because proinflammatory cytokines also activate the hypothalamo-pituitary-adrenal (HPA) axis, these imbalances may inhibit the hippocampal negative feedback system. Thus, changes in the TRP metabolism may also relate to the HPA axis-hyperactivity hypothesis of major depression. In this article, we review the changes in TRP metabolism by proinflammatory cytokines under stress, which is assumed to be a risk factor for major depression, and the relationship between physiological risk factors for major depression and proinflammatory cytokines.     

Elevated content of cortisol in hair of patients with severe chronic pain: a novel biomarker for stress

Hair analysis has been used to reflect long-term systemic exposure to exogenous drugs and toxins. Several studies have demonstrated the feasibility of measuring endogenous steroid hormones, e.g. cortisol, in hair. Recently, a study in macaques showed a significant increase in hair cortisol levels induced by stress. We explored whether hair cortisol levels may be used as a biomarker for long-term stress in humans. Patients with severe chronic pain, aged 18 years or older, receiving opioid treatment for at least one year were recruited. Controls were non-obese (body mass index, BMI < 30 mg/kg(2)) adults. The Perceived Stress Scale (PSS) questionnaire was used to assess perceived stress over the last 4 weeks. A hair sample was obtained from the vertex posterior. Cortisol was measured using an enzyme-linked immunosorbent assay. We included fifteen patients (nine females and six males) and 39 non-obese control subjects (20 females, 19 males). PSS scores (median and range) were significantly higher in chronic pain patients (24: 12-28) than in controls (12: 3-31)(P < 0.001). Hair cortisol contents (median and range) were significantly greater in chronic pain patients (83.1: 33.0-205 g/mg) than in controls (46.1: 27.2-200 pg/mg) (P < 0.01). We conclude that hair cortisol contents are increased in patients with major chronic stress. Measurement of cortisol levels in hair constitutes a novel biomarker of prolonged stress.     

The relation of illness perceptions to stress,depression, and fatigue in patients with chronic lymphocytic leukaemia

Objective: Chronic lymphocytic leukaemia (CLL) is the most prevalent adult leukaemia and is incurable. The course and treatment of CLL is unique and characterised by repeated cycles of treatment, stable disease and relapse. Utilising a Self-Regulatory Model framework, we examined the relationship between patients’ illness perceptions and cancer-specific stress, depressive symptoms and fatigue. Our aim was to test illness perceptions as predictors of these outcomes when variance due to disease and treatment variables was controlled.

Design: Data were collected on 147 patients with relapsed/refractory CLL as they entered a phase II clinical trial of an investigational medication at a university affiliated, National Cancer Institute designated comprehensive cancer center.

Main outcome measures: Cancer-specific stress, depressive symptoms and fatigue interference.

Result:. Hierarchical multiple regression was used. Consequences and emotional representation were related to all outcomes (ps?p?p?Conclusion: Illness perceptions are related to cancer-specific stress, depressive symptoms and fatigue interference in relapsed/refractory CLL. Interventions targeted at restructuring maladaptive illness perceptions may have clinical benefit in this population.     

Correlation between maternal and infant cortisol varies by breastfeeding status

ObjectiveThe objective of this study was to examine associations of mother and infant salivary cortisol, measured three times over the course of a day, and assess whether these varied by breastfeeding status.MethodsWe conducted a cross-sectional study of 54 mothers and their infants aged 4–11 months. Mothers collected their own saliva and that of their infants upon awakening, 30 min after waking and at bedtime. Breastfeeding status was reported by mothers and cortisol level was measured in saliva in μg/dl using standard techniques. We used generalized linear models to evaluate relationships between maternal and infant cortisol levels, and assessed whether the relationship differed by breastfeeding status: formula only compared to partial and full breastfeeding, adjusting for infant sex, race, age, maternal education, and family income.ResultsThirty-four infants received formula only and 20 were either partially or fully breastfed. Breastfeeding was associated with higher household income, higher maternal education, and white race. Cortisol levels were higher among breastfed infants at all three time points. After adjustment, maternal cortisol levels were related with infant cortisol at bedtime only (regression estimate 0.06; 95% CI: 0.10, 1.1; p = 0.02). The adjusted association between bedtime maternal and infant cortisol was stronger among breastfeeding dyads than among formula-feeding dyads (regression estimate 1.0; 95% CI: 0.1, 2.0; p = 0.04 vs. 0.6; CI: −0.1, 1.3; p = 0.10). In addition, we assessed the influence of maternal education and household income in our adjusted model; income strengthened the observed association, whereas maternal education did not change the estimate.ConclusionsBreastfeeding mothers and infants had significant correlations for cortisol at bedtime, while formula-feeding dyads did not. These data suggest that several factors may contribute to cortisol synchrony observed in mother/infant dyads, including the transfer of cortisol in human milk, physical interaction such as skin-to-skin contact, and shared environment. In addition, our findings support household income as a possible contributor.     

自尊与心理性应激的关系初探

自尊水平影响着个体在应激情境中的内分泌反应,在以人个人主义文化下的研究发现,由于低自尊具有较低的内部控制力,因此在应激情境中的唾液皮质醇反应更强烈。但是在中国集体主义文化中,由于集体性自我的评价是自尊的一个重要组成部分,高自尊更加期望集体或社会的积极性评价,因此假设在心理性应激情境下（即个体的能力被否定的时候）,高自尊的应激反应会比低自尊更加强烈。本研究以健康大学生为被试,分别以Rosenberg自尊量表和特里尔社会应激测试（TSST）为实验手段,以自尊量表得分、主观应激报告（5点量表）和客观应激参数（心率和唾液皮质醇）为指标,在中国文化背景下探讨自尊与心理性应激的关系。结果发现,在TSST开始时（20分钟）自尊与心率呈正相关,自尊水平越高,心率越快;在TSST结束后（60分钟）自尊与唾液皮质醇水平呈正相关,自尊水平越高,唾液皮质醇水平越高。总体来说,相对于低自尊被试而言,高自尊被试在心理性应激情境中的反应更为强烈。     

Salivary cortisol concentrations, stress and quality of life in women with endometriosis and chronic pelvic pain

The objective of this study was to evaluate the perceived stress index, quality of life, and hypothalamus-pituitary-adrenal axis activity in women with endometriosis and chronic pelvic pain. For the study, 93 women with endometriosis and 82 healthy women volunteered. The visual analogue scale (VAS) (0=no pain; 10=severe pain) was used to determine pain intensity; the perceived stress questionnaire (PSQ) defined stress index, and the health-related quality-of-life (HRQOL)-SF-36 questionnaire was used to evaluate quality of life. Salivary cortisol was measured at 0800, 1600, and 2000 h and the awakening cortisol response was assessed to evaluate the hypothalamus-pituitary-adrenal axis activity. The results show that women with endometriosis and chronic pelvic pain of moderate intensity (4.1+/-0.58, mean+/-SEM) have higher levels of perceived stress (0.55+/-0.01 versus 0.42+/-0.01, p<0.05), a poorer quality of life expressed as lower scores for all items of the inventory and hypocortisolism. Lower levels of salivary cortisol were observed in all three samples collected, as well as in the awakening cortisol response, for women with endometriosis (0.19+/-0.09 microg/dl) when compared with controls (0.78+/-0.08 microg/dl, p<0.05 l), and it was independent of pain intensity and Mental health (MH) scores in SF-36. We concluded that women with endometriosis and chronic pelvic pain show low concentrations of salivary cortisol and a high level of perceived stress, associated with a poor quality of life. Whether the hypocortisolism was an adaptive response to the aversive symptoms of the disorder or a feature related to the etiology of endometriosis remains to be elucidated.     

Cognitive distortions as mediators between life stress and depression in adolescents

This research examined the possibility that cognitive distortions mediate between life stress and depression in an adolescent population. Measures of cognitive distortion, life stress, and depressive tendencies were administered to 103 ninth- to twelfth-grade high school students. It was predicted that measures of cognitive distortion would be better predictors of depressive tendencies than measures of life stress. It was also predicted that cognitive distortions would affect the perceived stressfulness of life events. In addition, it was predicted that three measures of cognitive distortion would be correlated and that the measure of immediate negative thinking would be a better predictor of depressive tendencies than the measures of dysfunctional attitudes and irrational beliefs. Findings from correlation and regression analyses were consistent with the predictions.     

Narrative exposure therapy for political imprisonment-related chronic posttraumatic stress disorder and depression

The psychological consequences of traumatic stress may last even into old age. In persons in their 60s and 70s who had been victims of political detention and torture four decades ago, we compared the outcome of narrative exposure therapy (NET) to that of psychoeducation (PED) only. From a group of 59 former political detainees, 18 who fulfilled the full PTSD criteria according to the Composite International Diagnostic Interview (CIDI) were offered and accepted participation in the treatment study. The participants were randomly assigned to either one session of PED (n=9) or five sessions of NET (n=9). Symptoms of PTSD (CIDI) and depression (Beck Depression Inventory, BDI) were assessed prior to treatment and after a 6-month follow-up. NET but not PED produced a significant reduction in post-traumatic symptoms and depression scores. Four out of 9 of those who completed NET, compared to 8/9 of those within the PED group, still had PTSD 6 months after the treatment had ended. These results indicate that NET may lead to the alleviation of post-traumatic and depression symptoms even when the conditions persist for excessive time periods.     

Endogenous cortisol level interacts with noradrenergic activation in the human amygdala

Animal studies show that high cortisol levels exert their effect on stressful task performance via modulation of the amygdala. Availability of noradrenaline in this brain region appears to be a critical prerequisite for this effect. This relationship between noradrenaline and cortisol is explained by an animal model where the amygdala constitutes a crucial region for this interaction. In humans this model has not been extensively tested so far. In a previously reported study human subjects (aged 20.93+/-2.38) were scanned using fMRI when watching sets of emotional and neutral pictures after taking the beta-adrenergic antagonist propranolol or placebo. Stimulus sets consisted of 92 pictures, divided in four emotional categories that ranged from neutral scenes of domestic objects (CAT1) to extremely negative scenes of mutilation or accidents (CAT4). Confrontation with arousing emotional pictures, accompanied by increased noradrenaline levels, evoked increased amygdala activation under placebo but not under betablocker condition. This new and additional analysis of this data set was carried out to determine the effect of differential endogenous cortisol levels on amygdala activation. Cortisol levels during scanning were determined using salivary samples and subjects were post hoc divided in a High (n=14) and Low cortisol group (n=14). When subjects were watching emotional stimuli, presumably associated with enhanced noradrenaline (NA) levels, amygdala activation was contrasted between the two cortisol groups. We hypothesized that emotional stimuli would elicit more amygdala activation in the High than in the Low cortisol group. Here we demonstrate indeed a significant interaction effect of the endogenous cortisol level with increasing activation in the amygdala under placebo but not under betablocker condition, thereby extending the rodent based model of a synergistic effect of the two stress hormones to the human.     

Cognitive functioning and cortisol profiles in first episode major depression

Major Depressive Disorder (MDD) is often associated with high levels of stress and disturbances in the Hypothalamic Pituitary Adrenal (HPA) system, yielding high levels of cortisol, in addition to cognitive dysfunction. Previous studies have shown a relationship between cortisol profile and cognitive functioning in recurrent MDD in general. More specifically, the association between hypercortisolism and cognitive functioning, such as memory and Executive Functioning (EF), and also more recently cortisol suppression has been explored. However, no studies have investigated these relationships in patients diagnosed with first episode MDD. The aim of the present study was to examine the relationship between cortisol levels before and after the Dexamethasone suppression test (DST) and cognitive function in first episode MDD patients. Twenty‐one patients meeting the DSM‐IV criteria for a first episode of MDD diagnosis were included in the study. The control group was matched for age, gender and education level. Cortisol was measured in saliva collected with Salivette sampling devices. Saliva samples were collected 4 times during a 24 hours period over two consecutive days: at awakening, after 45 minutes, after 7 hours and at 11 pm. Dexamethasone (1.0 mg) was given orally on Day 1 at 11 pm. The neuropsychological test battery consisted of standardized tests measuring executive functioning (EF) and memory functioning. Cortisol levels did not differ significantly between patients and controls on Day 1, except for the last sample before Dexamethasone administration, where the control group showed higher levels. Both groups showed suppression after Dexamethasone. On Day 2 there was a significant difference between groups at the third sample, showing a significantly lower level in the control group, suggesting that the controls have a more effective suppression profile than the patients. There were no significant correlations between cortisol levels before or after Dexamethasone and cognitive measures. The results indicate impairment on HPA‐axis functioning in first episode MDD patients, with less suppression functioning compared to healthy controls, but no relationship between cortisol profile and cognitive functioning in EF or Memory.     

Traumatic stress, dissociation, and limbic irritability in patients with unipolar depression being treated with SSRIs

Recent evidence suggests that stressful experiences may be related to deficits in inhibitory functions and temporo-limbic epileptic-like activity. The latter may produce psychosensory seizure-like symptoms that may also appear in nonepileptic conditions. This study assesses whether the increased presence of the seizure-like symptoms in 113 unipolar depressive patients treated with SSRIs is associated with significantly more severe symptoms of depression, traumatic stress, and dissociation in comparison with 86 healthy controls. Results indicate that seizure-like symptoms in depressive patients have significant association with depression, symptoms of dissociation, and traumatic stress. This association suggests that processess generating seizure-like symptoms may be related to symptoms of depression, traumatic stress, and dissociation.     

Differences in negative life events between patients with anxiety disorders,depression and hypochondriasis

This study investigated whether some categories of adverse life events are differentially associated with specific types of emotional disorders. A life self-report measure of major life events was completed by 42 subjects with diagnoses of anxiety disorders, 46 subjects with major depression, 26 subjects with hypochondriasis and 73 nonclinical subjects (controls). As predicted, the onset of anxiety disorders, depression, and hypochondriasis appears to be differentially related with life stress of ‘threat’, ‘loss’, and ‘health’, respectively, previously experienced by the clinical subjects. Also, there were significant differences between clinical and nonclinical subjects on both perceived life stress and number of life events reported. Findings suggest a differential implication of psychosocial stress categories in particular emotional disorders (i.e., anxiety, depressive and hypochondriacal disorders). These results expand previous findings that have demonstrated an association between negative life events and psychopathology.     

Illness perceptions are the main predictors of depression and anxiety symptoms in patients with chronic pain

Depression and anxiety symptoms in chronic pain are associated with adverse clinical outcomes, and appear highly related to patient’s illness perceptions as well as with marital adjustment. This study aimed to investigate the predictive value of pain variables, marital adjustment and illness perceptions on depression and anxiety in patients with chronic pain. Two hundred patients were recruited from a pain unit in a public hospital in the north of Portugal. Patients completed a questionnaire that assessed illness perceptions (IPQ-Brief), marital adjustment (revised dyadic adjustment scale), depression and anxiety symptoms (hospital anxiety depression scale) and pain variables (pain intensity and pain disability index). Depression and anxiety symptoms were associated with pain intensity, pain-related disability, marital adjustment and illness perceptions. Results from hierarchical regression showed that illness perceptions contributed significantly to depression and anxiety symptoms over and above the effects of pain intensity, pain-related disability and marital adjustment, after controlling for gender. In multivariate analyses, pain intensity, pain-related disability and marital adjustment were uniquely related to depression and anxiety symptoms, whereas specific illness perceptions were uniquely related to depression symptoms (identity, treatment control, emotional response and coherence) and to anxiety symptoms (identity, emotional response and concern). Perceptions of greater symptomatology (identity) and of emotional impact, and lesser perceptions of treatment control and understanding of chronic pain (illness comprehensibility) were significantly associated with increased depression symptoms. Perceptions of greater symptomatology (identity), emotional impact and greater concern were associated with anxiety symptoms. These findings indicate that the contribution of illness perceptions was greater than that made by traditional covariates, and may therefore be a useful basis for future psychological interventions.     

The cortisol awakening response: Associations with trait anxiety and stress reactivity

This study investigated the extent to which trait anxiety and state anxiety in response to stress are associated with the cortisol awakening response (CAR).Fifty-one healthy participants were recruited. State anxiety measures were taken in anticipation of and during a laboratory stressor. Salivary cortisol levels were measured immediately upon awakening (at 0, 15, 30, and 45 min) on two consecutive mornings. Cortisol awakening response was assessed by the area under the curve with respect to zero (AUC_G).The magnitude of the CAR was found to be negatively associated with both trait anxiety and anticipatory anxiety. Moreover, regression analysis showed that the effects of trait anxiety on the AUC_G were mediated by anticipatory anxiety.These results suggest that the CAR is influenced by trait anxiety. Moreover, the effect of trait anxiety on the CAR seems to operate by impacting on psychological stress reactivity (i.e., anticipatory anxiety).     

Overgeneral autobiographical memory and chronic interpersonal stress as predictors of the course of depression in adolescents

This study investigated whether overgeneral autobiographical memory (OGM) predicts the course of depression in adolescents. As part of a larger longitudinal study of risk for emotional disorders, 55 adolescents with a past history of major depressive disorder or minor depressive disorder completed the Autobiographical Memory Test. Fewer specific memories predicted the subsequent onset of a major depressive episode (MDE) over a 16-month follow-up period, even when covarying baseline depressive symptoms. This main effect was qualified by an interaction between specific memories and chronic interpersonal stress: Fewer specific memories predicted greater risk of MDE onset over follow-up at high (but not low) levels of chronic interpersonal stress. Thus, our findings suggest that OGM, in interaction with chronic interpersonal stress, predicts the course of depression among adolescents, and highlight the importance of measuring interpersonal stress in OGM research.     

Overgeneral autobiographical memory and chronic interpersonal stress as predictors of the course of depression in adolescents

This study investigated whether overgeneral autobiographical memory (OGM) predicts the course of depression in adolescents. As part of a larger longitudinal study of risk for emotional disorders, 55 adolescents with a past history of major depressive disorder or minor depressive disorder completed the Autobiographical Memory Test. Fewer specific memories predicted the subsequent onset of a major depressive episode (MDE) over a 16-month follow-up period, even when covarying baseline depressive symptoms. This main effect was qualified by an interaction between specific memories and chronic interpersonal stress: Fewer specific memories predicted greater risk of MDE onset over follow-up at high (but not low) levels of chronic interpersonal stress. Thus, our findings suggest that OGM, in interaction with chronic interpersonal stress, predicts the course of depression among adolescents, and highlight the importance of measuring interpersonal stress in OGM research.