Elevated Salivary Cortisol Levels Research Articles

ODP387 Hemihypertrophy: A Rare Clinical Presentation of Cushing's disease

Abstract Background Hemihypertrophy is a rare clinical presentation of Cushing's disease. It has been described in three newborns with massive enlargement of adrenal glands in presence of other congenital abnormalities and in a 17-year-old female with pituitary adenoma with a genetic diagnosis of Beckwith Weidman syndrome. We describe a case of Cushing's disease with lower extremity hemihypertrophy in the absence of features suggestive of an underlying syndrome. 1,2 Clinical Case: A 12-year-old male with no significant past medical history presented with poor growth and rapid weight gain. In addition, he had hemihypertrophy of left lower extremity interfering with his physical activity. Physical exam showed Tanner Stage 1 for pubic hair and testicular volume of 4 ml bilaterally, with no signs of hirsutism, bruising or purplish striae. Initial work up showed normal thyroid hormone and growth factor levels. Midnight salivary cortisol levels were 238 ng/dl and 51 ng/dl respectively (range <100 ng/dl). One mg dexamethasone suppression test showed suppressed cortisol level of 1 mcg/dl. At the subsequent visit seven months later, he had gained 13.8 kg and grown 0.9 cm in height. Physical exam showed facial plethora and buffalo hump, which had not been present at the initial visit. Left and right leg circumference above the knee were 22 inches and 20 inches respectively. Repeat midnight cortisol levels on two separate occasions were 251 ng/dl and 441 ng/dl respectively. Repeat 1 mg dexamethasone suppression test showed suppressed cortisol levels of 1.2 mcg/dl. Because of clinical picture consistent with Cushing syndrome and elevated salivary cortisol levels, 24-hour urine cortisol levels were ordered that were 145 mcg and 276 mcg/24h respectively (range 1-45 mcg/24hours). ACTH was elevated at 65 pg/ml. CT scan of abdomen and pelvis was normal. Left leg ultrasound was normal. MRI of brain showed a 4 mm hypoenhancing lesion in the pituitary gland to the left of midline. A peripheral DDAVP stimulation test showed elevated ACTH and cortisol levels suggestive of pituitary origin. MRI of legs showed asymmetric fat deposition causing hemihypertrophy. Patient underwent transsphenoidal resection of pituitary adenoma with postoperative remission (postop cortisol nadir <1 mcg/dl). At follow up visit after surgery, patient had lost 0.2 kg, buffalo hump had disappeared, and left leg circumference had slightly improved. Genetic testing ispending. Conclusion This case demonstrates that hemihypertrophy can be a presenting symptom of Cushing's disease.

Abstract #1165446: Elevated Salivary Cortisol Levels Caused by Lip Balm Use

Endogenous Cushing syndrome is a disorder characterized by cortisol excess, with an incidence of 0.7-2.4 million of the population per year. 1 Approximately 10% of new cases each year affect the pediatric population. 2 The current recommendations for assessment of Cushing syndrome include either 24 hour urine free cortisol, dexamethasone suppression testing, or measurements of late night salivary cortisol levels. 3 Given its relative ease of collection and storage, as well as its high sensitivity and specificity, late-night salivary cortisol levels have become the most popular method for initial testing.

Human Stress Detection: Cortisol Levels in Stressed Speakers Predict Voice-Based Judgments of Stress.

Despite recent evidence of a positive relationship between cortisol levels and voice pitch in stressed speakers, the extent to which human listeners can reliably judge stress from the voice remains unknown. Here, we tested whether voice-based judgments of stress co-vary with the free cortisol levels and vocal parameters of speakers recorded in a real-life stressful situation (oral examination) and baseline (2 weeks prior). Hormone and acoustic analyses indicated elevated salivary cortisol levels and corresponding changes in voice pitch, vocal tract resonances (formants), and speed of speech during stress. In turn, listeners' stress ratings correlated significantly with speakers' cortisol levels. Higher pitched voices were consistently perceived as more stressed; however, the influence of formant frequencies, vocal perturbation and noise parameters on stress ratings varied across contexts, suggesting that listeners utilize different strategies when assessing calm versus stressed speech. These results indicate that nonverbal vocal cues can convey honest information about a speaker's underlying physiological level of stress that listeners can, to some extent, detect and utilize, while underscoring the necessity to control for individual differences in the biological stress response.

Virtual and real-life ostracism and its impact on a subsequent acute stressor

While ostracism constitutes a social stressor with negative effects on physical and mental health, social inclusion seems to increase resilience. This may be true not only for face-to-face settings, but also for computer-mediated interactions. Hence, this study examined the differences between ostracism and social inclusion in real-life or Virtual Reality (VR) regarding self-reported stress, neuroendocrine and cardiovascular reactivity in a subsequent real-life socio-evaluative task. 84 females were randomly assigned to a 3 (agency: face-to-face/human controlled VR-avatar/computer VR-agent) x 2 (inclusion status: inclusion/exclusion) between-subject design using a Cyberball paradigm. Subsequently, they were exposed to a real-life Trier Social Stress Test (TSST). Results indicate that the experience of ostracism constitutes a threat to fundamental social needs independent of agency. Excluded participants showed cardiovascular reactivity during TSST; also face-to-face and avatar excluded individuals had elevated salivary cortisol levels. Included participants reported more perceived social support during Cyberball and showed a blunted cortisol response to the TSST. These results suggest that face-to-face and avatar-related ostracism provokes responses in the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic nervous system (SNS). Furthermore, they reveal that social inclusion may act as a stress-protector as it alters HPA- and SNS-related stress responsiveness to subsequent stressors.

SAT-LB46 Depression as an Atypical Presentation of Cushing’s Disease

Introduction: Cushing’s disease is an abnormal secretion of ACTH from the pituitary that causes an increase in cortisol production from the adrenal glands. Resultant manifestations from this excess in cortisol include multiple metabolic as well as psychiatric disturbances which can lead to significant morbidity and mortality. Case: The patient is a 29 year old woman who presented with fatigue, decreased energy, poor memory and insomnia for 3 months. She noted irregular menses for 4 months. She was referred from her primary doctor for elevated salivary cortisol and DHEA levels. Evaluation revealed BP: 104/76, HR 78, RR 12, BMI 22.7. She was a thin woman without striae, moon face, buffalo hump or bruising. 24 hour urine free cortisol was 90.3 mcg/24hr. One mg dexamethasone suppression test resulted in an AM cortisol of 17.6 ug/dL and ACTH 25 pg/mL. An 8 mg dexamethasone suppression test showed a cortisol level of 1.2 ug/dL with an ACTH <5 pg/mL. The combined results were suggestive of Cushing’s disease. The patient went for MRI of the pituitary which showed a 4 mm hypoenhancing region on the right side of the gland suspicious for a microadenoma. The patient was followed closely and continued to report fatigue and insomnia. Inferior petrosal sinus sampling was performed. Venous blood sampling of ACTH from the periphery at 0 min, 5 min and 15 min were: <5 pg/mL, <5 pg/mL, and <5 pg/mL respectively. On the right at 0 min, 1 min, 5 min, 15 min ACTH levels were: 12 pg/mL, 14 pg/mL, 16 pg/mL, 14 pg/mL. On the left at 5 min and 15 min ACTH measured 8 pg/mL and 7 pg/mL. These findings confirmed the suspicion of a right-sided ACTH-secreting pituitary adenoma. She was referred to a neurosurgeon to evaluate for resection of the adenoma. Due to the ongoing symptoms, the neurosurgical removal of the lesion was expedited and scheduled within several weeks. While awaiting removal the patient sadly took her own life. Conclusion: Aside from the more commonly associated metabolic manifestations of elevated cortisol levels, psychiatric symptoms can be the initial complaint of patients with Cushing’s disease. Symptoms can include fatigue, depressive symptoms, insomnia, and sleep dysregulation. Currently the Endocrine Society Guideline for Cushing’s syndrome does not have any specific recommendations regarding depression screening. Psychiatric complications are a known manifestation of Cushing’s disease. Close follow up and urgent psychiatric referral with the onset of signs of depression or anxiety should be included as part of Cushing’s disease evaluation. Symptoms of mental health disturbances may be subtle and thus all patients with Cushing’s disease should be screened and monitored for underlying psychiatric illnesses. Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5152600/pdf/JMedLife-09-12.pdf

The Sheep Grimace Scale as an indicator of post-operative distress and pain in laboratory sheep.

The EU Directive 2010/63/EU changed the requirements regarding the use of laboratory animals and raised important issues related to assessing the severity of all procedures undertaken on laboratory animals. However, quantifiable parameters to assess severity are rare, and improved assessment strategies need to be developed. Hence, a Sheep Grimace Scale (SGS) was herein established by observing and interpreting sheep facial expressions as a consequence of pain and distress following unilateral tibia osteotomy. The animals were clinically investigated and scored five days before surgery and at 1, 3, 7, 10, 14 and 17 days afterwards. Additionally, cortisol levels in the saliva of the sheep were determined at the respective time points. For the SGS, video recording was performed, and pictures of the sheep were randomized and scored by blinded observers. Osteotomy in sheep resulted in an increased clinical severity score from days 1 to 17 post-surgery and elevated salivary cortisol levels one day post-surgery. An analysis of facial expressions revealed a significantly increased SGS on the day of surgery until day 3 post-surgery; this elevated level was sustained until day 17. Clinical severity and SGS scores correlated positively with a Pearson´s correlation coefficient of 0.47. Further investigations regarding the applicability of the SGS revealed a high inter-observer reliability with an intraclass correlation coefficient of 0.92 and an accuracy of 68.2%. In conclusion, the SGS represents a valuable approach for severity assessment that may help support and refine a widely used welfare assessment for sheep during experimental procedures, thereby meeting legislation requirements and minimizing the occurrence of unrecognized distress in animal experimentation.

Salivary Cortisol Profiles of Children with Hearing Loss.

It has long been speculated that effortful listening places children with hearing loss at risk for fatigue. School-age children with hearing loss experiencing cumulative stress and listening fatigue on a daily basis might undergo dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity resulting in elevated or flattened cortisol profiles. The purpose of this study was to examine whether school-age children with hearing loss show different diurnal salivary cortisol patterns than children with normal hearing. Participants included 32 children with mild to moderate hearing loss (14 males; 18 females) and 28 children with normal hearing (19 males; 9 females) ranging in age from 6 to 12 years. Saliva samples were obtained six times per day on two separate school days. Cortisol levels were measured by mass spectrometric detection after liquid-liquid extraction. Salivary cortisol levels between children with hearing loss and children with no hearing loss over the course of the day were examined with hierarchical linear modeling using mixed model statistical analysis. Between-group comparisons were also computed for the area under the curve, an analytical approach for calculating overall cortisol secretion throughout the day. Significant differences in the cortisol awakening response (CAR) were observed between children with hearing loss and children with normal hearing; however, no differences were observed between the two groups subsequent to the cortisol awakening response (60-min postawakening, 10:00 A.M., 2:00 P.M., and 8:00 P.M.). Compared with children with normal hearing, children with hearing loss displayed elevated cortisol levels at awakening and a reduced growth in cortisol secretion from awakening to 30-min postawakening. No significant differences in overall cortisol secretion throughout the day were found between groups (area under the curve). Finally, cortisol levels increased with increasing age for children with hearing loss but not for children with normal hearing. Results of this preliminary study indicate a possible dysregulation in HPA axis activity in children with hearing loss characterized by elevated salivary cortisol levels at awakening and a diminished increase in cortisol from awakening to 30-min postawakening. The pattern of elevated cortisol levels at awakening is consistent with some studies on adults with burnout, a condition characterized by fatigue, loss of energy, and poor coping skills. These findings support the idea that children with hearing loss may experience increased vigilance and need to mobilize energy promptly in preparation for the new day.

Altered circadian patterns of salivary cortisol in low-functioning children and adolescents with autism.

Reports of higher stress responsivity, altered sleep-wake cycle and a melatonin deficit in autism have stimulated interest in the cortisol circadian rhythm in individuals with autism. The study was conducted on 55 low-functioning children and adolescents with autism (11.3 ± 4.1 years-old) and 32 typically developing controls (11.7 ± 4.9 years-old) matched for age, sex and puberty. Behavioral assessment was performed using the Autism Diagnostic Observation Schedule (ADOS). Salivary samples for measurement of cortisol were collected during a 24-h period (at least 0800 h-Day 1, 1600 h, 0800 h-Day 2 for 46 individuals with autism and 27 controls, and 0800 h-Day 1, 1100 h, 1600 h, 2400 h, 0800 h-Day 2 for 13 individuals with autism and 20 controls). Overnight (2000 h-0800 h) urinary cortisol excretion was also measured. The autism group displayed significantly higher levels of salivary cortisol at all time-points, flatter daytime and nighttime slopes, higher 0800 h cortisol levels on Day 2 compared to Day 1, and greater variances of salivary and urinary cortisol. There was a significant relationship between salivary cortisol levels and impairments in social interaction and verbal language. Overnight urinary cortisol excretion was similar in the autism and control groups. Anticipation of the stressful collection procedure appears to contribute to the higher 0800 h-Day 2 versus 0800 h-Day 1 salivary cortisol levels in autism. This sensitization to stressors might be as, or even more, important clinically than exposure to novelty in autism. The similar group means for overnight urinary cortisol excretion indicate that basal HPA axis functioning is unaltered in low-functioning autism. The elevated salivary cortisol levels observed in autism over the 24-h period in a repeated stressful condition, flattened diurnal cortisol patterns and the apparent effect of anticipation are consistent with prior findings in high trait anxiety.

Effects of a psychosocial couple-based prevention program on adverse birth outcomes.

Although maternal stress and depression have been linked to adverse birth outcomes (ABOs), few studies have investigated preventive interventions targeting maternal mental health as a means of reducing ABOs. This randomized controlled study examines the impact of Family Foundations (FF)-a transition to parenthood program for couples focused on promoting coparenting quality, with previously documented impact on maternal stress and depression-on ABOs. We also examine whether intervention buffers birth outcomes from the negative effect of elevated salivary cortisol levels. We use intent-to-treat analyses to assess the main effects of the FF intervention on ABOs (prematurity, birth weight, pregnancy complications, Cesarean section, and days in hospital for mothers and infants) among 148 expectant mothers. We also test the interaction of cortisol with intervention condition status in predicting ABOs. FF participation was associated with reduced risk of C-section (OR .357, p < 0.05, 95 % CI 0.149, 0.862), but did not have main effects on other ABOs. FF significantly buffered (p < 0.05) the negative impact of maternal cortisol on birth weight, gestational age, and days in hospital for infants; that is, among women with relatively higher levels of prenatal cortisol, the intervention reduced ABOs. These results demonstrate that a psycho-educational program for couples reduces incidence of ABOs among higher risk women. Future work should test whether reduced maternal stress and depression mediate these intervention effects.

Salivary cortisol levels, but not salivary α‐amylase levels, are elevated in patients with rheumatoid arthritis irrespective of depression

Stress is recognized as an important factor in the etiology of rheumatoid arthritis (RA). Therefore, we explored multiple aspects of stress in RA patients. Salivary cortisol and α-amylase levels were measured as markers of the hypothalamic-pituitary-adrenal axis activity and sympatho-adrenomedullary system activity, respectively. Depression was assessed by the Beck Depression Inventory (BDI) and short-term analysis of the heart rate variability (HRV) was performed to evaluate the autonomic nervous system. The salivary cortisol levels of the RA patients were significantly higher than those of the normal controls (NC; 0.12±0.162μg/dL vs. 0.068±0.052μg/dL, P=0.006). There was no difference in salivary α-amylase levels between the RA and the NC. The BDI levels of the RA patients were significantly higher than the NC (13.7±8.9 vs. 6.4±6.9, P<0.001). Depression was more prevalent in RA patients than in the NC. The salivary cortisol levels were still significantly higher in the RA than the NC after controlling BDI by logistic regression analysis (P=0.002). There was no significant difference in the HRV of RA patients and the NC. The evaluation of relationship between stress measures and disease activity markers of RA revealed that only BDI was positively correlated with the visual analogue pain scale. Salivary cortisol levels and the BDI of RA patients were higher than those of the NC, and elevated salivary cortisol levels were independent of depression. However, the level of stress may not be correlated with disease activity in RA.

Neonatal Pain-Related Stress and NFKBIA Genotype Are Associated with Altered Cortisol Levels in Preterm Boys at School Age

Neonatal pain-related stress is associated with elevated salivary cortisol levels to age 18 months in children born very preterm, compared to full-term, suggesting early programming effects. Importantly, interactions between immune/inflammatory and neuroendocrine systems may underlie programming effects. We examined whether cortisol changes persist to school age, and if common genetic variants in the promoter region of the NFKBIA gene involved in regulation of immune and inflammatory responses, modify the association between early experience and later life stress as indexed by hair cortisol levels, which provide an integrated index of endogenous HPA axis activity. Cortisol was assayed in hair samples from 128 children (83 born preterm ≤32 weeks gestation and 45 born full-term) without major sensory, motor or cognitive impairments at age 7 years. We found that hair cortisol levels were lower in preterm compared to term-born children. Downregulation of the HPA axis in preterm children without major impairment, seen years after neonatal stress terminated, suggests persistent alteration of stress system programming. Importantly, the etiology was gender-specific such that in preterm boys but not girls, specifically those with the minor allele for NFKBIA rs2233409, lower hair cortisol was associated with greater neonatal pain (number of skin-breaking procedures from birth to term), independent of medical confounders. Moreover, the minor allele (CT or TT) of NFKBIA rs2233409 was associated with higher secretion of inflammatory cytokines, supporting the hypothesis that neonatal pain-related stress may act as a proinflammatory stimulus that induces long-term immune cell activation. These findings are the first evidence that a long-term association between early pain-related stress and cortisol may be mediated by a genetic variants that regulate the activity of NF-κB, suggesting possible involvement of stress/inflammatory mechanisms in HPA programming in boys born very preterm.

State anxiety and cortisol reactivity to skydiving in novice versus experienced skydivers

Previous studies have suggested that skydiving, a naturalistic stressor, is associated with increases in self-reported stress, anxiety and cortisol levels. However, it has not been established whether this stress reactivity is altered as a function of repeated exposure to skydiving. This is of interest due to previous observations that cortisol reactivity becomes habituated with repeated exposure to laboratory stressors, however, few studies have investigated such habituation to naturalistic stressors. State anxiety and cortisol reactivity to skydiving were measured in 11 first-time skydivers and 13 experienced skydivers (≥30 jumps, mean jumps=397.6), who were to complete a solo skydive. The novice skydivers reported significantly greater levels of state anxiety prior to the jump; however, there were no differences in pre-jump levels of salivary cortisol. Both groups exhibited significantly elevated salivary cortisol levels immediately post-jump, relative to i) pre-jump and ii) recovery. However, the two groups were indistinguishable with regard to their cortisol reactivity to the skydive. These findings support previous research demonstrating that skydiving elicits acute cortisol activation. Further, they suggest that i) cortisol reactivity does not habituate in experienced jumpers, and ii) that there is lack of concordance between self-reported levels of anxiety and biological stress reactivity in experienced skydivers.

Psychological stress is associated with altered levels of myeloid-derived suppressor cells in breast cancer patients

Our group has shown in a randomized clinical trial that psychological intervention to reduce stress in patients with stages II and III breast cancer led to enhanced immune function, fewer recurrences and improved overall survival. We hypothesized that patients with high levels of stress would have alterations in myeloid-derived suppressor cells (MDSC) compared to patients with lower stress. PBMC from 16 patients with high stress ( n = 8) or with low stress ( n = 8) after surgery as measured by the Impact of Event Scale (IES) questionnaire were evaluated for the presence of MDSC. Patients with higher IES scores had significantly elevated salivary cortisol levels ( P = 0.013; 13 μg/dl vs. 9.74 μg/dl). Levels of IL-1Rα were also significantly elevated in the higher IES group (45.09 pg/ml vs. 97.16 pg/ml; P = 0.010). IP 10, G-CSF, and IL-6 were all higher in the high stress group although not to a significant degree. Flow cytometric analysis for CD33+/HLA-DR-neg/CD15+/CD11b+ MDSC revealed increased MDSC in patients with lower IES scores ( P = 0.009). CD11b+/CD15+ cells constituted 9.4% of the CD33+/HLA DR-neg cell population in patients with high IES, vs. 27.3% in patients with low IES scores. Additional analyzes of the number of stressful events that affected the patients in addition to their cancer diagnosis revealed that this type of stress measure correlated with elevated levels of MDSC ( P = 0.064). These data indicate the existence of a complex relationship between stress and immune function in breast cancer patients.

Elevated salivary α-amylase and cortisol levels in unremitted and remitted depressed patients

Objective. Major depressive disorder (MDD) is often associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis via chronic stress. Psychosocial stress-induced activation of salivary α-amylase (sAA) represents sympathoadrenal medullary system (SAM) activity, and sAA has become an emerging biomarker for sympathetic nervous system activity. In contrast to salivary cortisol, sAA has been less extensively studied in depressed patients. The present study sought to address this problem by measuring sAA and salivary cortisol levels in patients with major depressive disorder. Methods. The authors recorded Spielberger State-Trait Anxiety Inventory (STAI) scores along with, levels of sAA and salivary cortisol in 28 patients with unremitted major depressive disorder, 43 remitted patients and 103 healthy volunteers. Results. STAI (State or Trait) measurements in unremitted patients with MDD were significantly increased compared with healthy controls and remitted patients. SAA and cortisol levels in unremitted patients were also significantly elevated compared to controls and remitted patients. Finally, sAA levels were significantly correlated with HRSD in unremitted patients with MDD. Conclusion. These preliminary results suggest that sAA may be a state-dependent marker of major depressive disorder in addition to salivary cortisol.

Behavioural, endocrine and immune responses to repeated social stress in pregnant gilts

Pregnant sows are exposed to various stressors in intensive pig husbandry that may have negative consequences on their health, reproductive performances and welfare. Social stress is one of these challenges, because gestating sows have to be housed in groups according to EU guidelines (2001/88/CE). The purpose of this study was to determine the consequences of repeated social stress in pregnant female pigs on their behavioural, endocrine and immunological responses and on pregnancy outcome. Pregnant gilts were submitted to a repeated social stress procedure induced by housing unfamiliar gilts in pairs changed twice a week between days 77 and 105 of gestation (S group, n = 18). Control gilts were housed in stable pairs during the same period (C group, n = 18). Agonistic behaviour was observed during the first 3 h after each grouping. Skin lesions were numbered 2 h after each grouping. Salivary cortisol was measured before and repeatedly during the 4 weeks of grouping. Gilts were immunized against keyhole limpet haemocyanin (KLH) on days 81 and 95 of gestation. Immunoglobulins G against KLH, proliferative responses to concanavalin A, lipopolysaccharide, pokeweed mitogen and KLH and peripheral blood leukocyte numbers were evaluated 1 week before the first grouping and 3 days after the last one. Agonistic interactions and skin lesions were observed in S gilts at each grouping, although there was a decline between the first and the last grouping (P < 0.05). The repeated social stress induced a sustained endocrine response as shown by elevated salivary cortisol levels from 1 to 48 h after grouping in S gilts compared to C gilts. The cellular as well as the humoral immunity and the leukocyte numbers were not influenced by social stress. Gestation length tended to be shorter in S gilts (P = 0.09), but litter size, piglet weight or mortality at birth were not affected. Variability of the response of S gilts to groupings was partly explained by their average success value determined according to the outcome (defeat or win) of all the groupings. In conclusion, our study demonstrates that the application of repeated social stress to pregnant gilts during the last third of their gestation repeatedly activates their hypothalamo–pituitary–adrenal axis but does not impair their immune function and pregnancy outcome.

EEG responses to mock facial expressions by infants of depressed mothers

EEG responses to mothers’ and strangers’ mock facial expressions (happy, surprised and sad) during a peek-a-boo game were recorded in 60, 3- to 6-month-old infants of depressed and non-depressed mothers. The infants of depressed mothers exhibited less positive and more negative affect and were less likely to look at the facial expressions displayed by both their mother and a stranger. The infants of depressed mothers showed greater relative right frontal EEG asymmetry than the infants of non-depressed mothers throughout the different expressions of the mothers and strangers and showed elevated salivary cortisol levels after the session. Both groups of infants showed significantly greater right frontal asymmetry during their mothers’ and stranger’s sad versus happy expression. In addition, infants showed greater right frontal EEG asymmetry during the stranger’s surprised versus happy expression.

EEG responses to mock facial expressions by infants of depressed mothers

EEG responses to mothers’ and strangers’ mock facial expressions (happy, surprised and sad) during a peek-a-boo game were recorded in 60, 3- to 6-month-old infants of depressed and non-depressed mothers. The infants of depressed mothers exhibited less positive and more negative affect and were less likely to look at the facial expressions displayed by both their mother and a stranger. The infants of depressed mothers showed greater relative right frontal EEG asymmetry than the infants of non-depressed mothers throughout the different expressions of the mothers and strangers and showed elevated salivary cortisol levels after the session. Both groups of infants showed significantly greater right frontal asymmetry during their mothers’ and stranger’s sad versus happy expression. In addition, infants showed greater right frontal EEG asymmetry during the stranger’s surprised versus happy expression.

Enhanced human memory consolidation with post-learning stress: interaction with the degree of arousal at encoding.

Abundant evidence indicates that endogenous stress hormones such as epinephrine and corticosterone modulate memory consolidation in animals. We recently provided the first demonstration that an endogenous stress hormone (epinephrine) can enhance human memory consolidation. However, these findings also suggested that post-learning stress hormone activation does not uniformly enhance memory for all recently acquired information; rather, that it interacts with the degree of arousal at initial encoding of material in modulating memory for the material. Here we tested this hypothesis by administering cold pressor stress (CPS) or a control procedure to subjects after they viewed slides of varying emotional content, and assessing memory for the slides 1 wk later. CPS, which significantly elevated salivary cortisol levels, enhanced memory for emotionally arousing slides compared with the controls, but did not affect memory for relatively neutral slides. These findings further support the view that post-learning stress hormone-related activity interacts with arousal at initial encoding to modulate memory consolidation.

Stress hormone levels of children of depressed mothers.

Research suggests that disruptions in early caretaking can have long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis, which mediates the stress response. Children of depressed mothers are at increased risk for developing internalizing problems in part because of disruptions in their caretaking environment. The present study investigated whether children of depressed mothers exhibit elevated salivary cortisol levels. Salivary cortisol samples were collected from 45 7- to 8-year-old children of mothers with a history of depression and 29 children of nondepressed mothers. Samples were collected soon after arrival to the laboratory and after a mild laboratory stressor and at home after wakeup and before bedtime. Children who had elevated levels of intemalizing symptoms and whose mothers had a history of depression showed elevated laboratory baseline cortisol levels. Children who were reported to have clinically significant internalizing symptoms were also more likely to show an elevated stress response to a mild laboratory stressor. When the longitudinal history of maternal depression was examined, matemal depression during the child's first 2 years of life was the best predictor of elevations in baseline cortisol at age 7 years. This study provides evidence that internalizing symptoms exist in conjunction with a more reactive hormonal stress system in children of depressed mothers. The results also provide preliminary evidence that exposure to maternal depression in the first 2 years of life may be related to children's cortisol levels later in life.

Acute hydrocortisone administration does not affect subjective responses to d-amphetamine in humans.

Stress and glucocorticoids facilitate and reinstate psychostimulant self-administration in rodents. However, the effects of stress and glucocorticoids on the subjective and behavioral effects of psychostimulants have not been well studied in humans. To examine the effects of acute hydrocortisone pretreatment on the subjective and behavioral effects of d-amphetamine. Hydrocortisone (100 mg) and d-amphetamine (20 mg) were administered orally to 16 healthy male and female volunteers in a four-session, placebo-controlled, within-subject, crossover design. To prevent stomach irritation, subjects received rantidine hydrochloride before each experimental session. Dependent measures included self-reported mood and subjective effects (Addiction Research Center inventory, the profile of mood states, and a series of visual analogue scales), vital signs, salivary cortisol, and psychomotor performance. Hydrocortisone elevated salivary cortisol levels, produced modest dysphoria, and reduced subjects' reports of wanting more drug. However, hydrocortisone pretreatment did not affect any of the physiological, behavioral, or subjective effects of d-amphetamine. In contrast to the effects of glucocorticoids in rodent studies, these results indicate that an acute increase in cortisol does not enhance the psychostimulant effects of d-amphetamine in humans.