Higher Basal Cortisol Levels Research Articles

IL-6 Enhances the Negative Impact of Cortisol on Cognition among Community-Dwelling Older People without Dementia

There is growing evidence that high basal cortisol levels and systemic inflammation independently contribute to cognitive decline among older people without dementia. The present cross-sectional study examined (a) the potential synergistic effect of cortisol levels and systemic inflammation on executive function and (b) whether this effect is more prominent among older people with mild cognitive impairment (MCI). A sub-sample of 99 patients with MCI and 84 older people without cognitive impairment (CNI) (aged 73.8 ± 7.0 years) were recruited from a large population-based cohort in Crete, Greece, and underwent comprehensive neuropsychiatric and neuropsychological evaluation and a single morning measurement of cortisol and IL-6 plasma levels. Using moderated regression models, we found that the relation between cortisol and executive function in the total sample was moderated by IL-6 levels (b = -0.994, p = 0.044) and diagnostic group separately (b = -0.632, p < 0.001). Moreover, the interaction between cortisol and IL-6 levels was significant only among persons with MCI (b = -0.562, p < 0.001). The synergistic effect of stress hormones and systemic inflammation on cognitive status appears to be stronger among older people who already display signs of cognitive decline. Targeting hypercortisolemia and inflammation may be a promising strategy toward improving the course of cognitive decline.

Is There Any Correlation between Baseline Serum Cortisol Levels and Disease Severity in PCR-Positive COVID-19 Patients with and without Diabetes Mellitus?

Background: COVID-19 has caused a pandemic and is associated with significant mortality. The pathophysiology of COVID-19, affecting many organs and systems, is still being investigated. The hypothalamus, pituitary gland, and possibly adrenal glands are the targets of SARS-CoV-2 because of its angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) receptors expression. Hypocortisolemia can be seen in the postinfection period. COVID-19 infection tends to be severe in diabetic patients due to immune dysfunction. In this study, our aim was to investigate the relationship between basal cortisol levels and the course of COVID-19 infection in diabetic and non-diabetic patients. Methods: Our retrospective study included 311 PCR-positive COVID-19 patients over the age of 18 who were hospitalized in Ankara City Hospital Infectious Diseases Department or Intensive Care Unit (ICU) between 15 March 2020 and 15 May 2020. Serum basal cortisol, fasting plasma glucose (FPG), HbA1c values, and diabetes history were recorded within the first 24 h of hospitalization. The presence of pulmonary involvement was noted from the patients’ imaging records. Pregnant and breastfeeding women, patients with chronic liver disease or chronic kidney disease, and patients who were already using steroids or had started COVID-19 infection treatment within the 72 h before blood collection were excluded from the study. Results: Of the 311 patients, 100 had Type 2 Diabetes Mellitus (T2D), while 211 did not. The age, serum basal cortisol, and glucose levels of the patients with T2D (64.51 ± 12.29, 19.5 ± 13.12, and 143.5 (77–345)) were higher than those of the patients without T2D (46.67 ± 16.38, 15.26 ± 8.75, and 96 (65–202)), and the differences were statistically significant (p = 0.004, p = 0.004, and p < 0.001, respectively). The basal cortisol values of the ICU patients (27.89 (13.91–75)) were significantly higher than those of the ward patients (13.68 (1.48–51.93)) and patients who were transferred to the ICU from the ward due to worsening conditions (19.28 (7.74–55.21)) (p < 0.001 and p = 0.007, respectively). The factors affecting ICU admission were determined to be age, T2D history, basal cortisol, and elevation in FPG using univariate logistic regression analysis. In the multiple logistic regression analysis, age, basal cortisol level, and infiltrative involvement in thorax CT were determined to be the risk factors affecting intensive care admission. Conclusion: High basal cortisol levels in patients with T2D may predict the severity of COVID-19 infection or mortality. Although high basal cortisol levels are among the risk factors affecting ICU admission, patients with COVID-19 should also be evaluated in terms of clinical and laboratory findings and relative adrenal insufficiency.

Hypothalamic-pituitary-adrenal axis attenuation and obesity risk in sexually abused females

BackgroundChildhood sexual abuse (CSA) confers elevated risks for obesity in females. Mechanisms that explain this link remain unclear. This study tracked serum basal cortisol levels with body mass index (BMI) from childhood into adulthood to test whether hypothalamic-pituitary-adrenal (HPA) axis attenuation accounts for elevated obesity risks for sexually abused females. MethodsData drew from six timepoints of a longitudinal study of the impact of CSA on development. Participants were females aged 6–16 years at time of study enrollment with substantiated CSA and demographically matched non-abused peers. Analyses included only participants who did not have obesity at study enrollment. Main outcomes were BMI growth trajectories across ages 6–27 (n = 150; 66 abused, 84 comparisons) and early adulthood obesity status (ages 20–27; n = 133; 62 abused, 71 comparison). HPA axis functioning indicators were intercept and linear slope parameters extracted from multilevel growth trajectories of serum basal cortisol levels across development. Racial-ethnic minority status, parity, steroid medication use, depression history and disordered eating history were covaried. ResultsWhile controlling for covariates, multilevel modeling indicated that high initial serum basal cortisol levels in childhood and attenuated cortisol growth rate over time (i.e., HPA axis attenuation) were associated with accelerated BMI accumulation (p < .01). Attenuated cortisol growth rate mediated the effect of CSA on accelerated BMI accumulation and on elevated adulthood obesity rates (p < .05). ConclusionThis work establishes a mechanistic association between HPA axis attenuation and obesity, suggesting that trauma treatments for abuse survivors should include interventions that reduce health consequences associated with dysregulated stress physiology.

Vasopressin V1B Receptor Antagonists as Potential Antidepressants.

Accumulating evidence shows that certain populations of depressed patients have impaired hypothalamus-pituitary-adrenal (HPA) axis function. Arginine-vasopressin (AVP) is one of the primary factors in HPA axis regulation under stress situations, and AVP and its receptor subtype (V1B receptor) play a pivotal role in HPA axis abnormalities observed in depression. Based on this hypothesis, several non-peptide V1B receptor antagonists have been synthesized, and the efficacies of some V1B receptor antagonists have been investigated in both animals and humans. V1B receptor antagonists exert antidepressant-like effects in several animal models at doses that attenuate the hyperactivity of the HPA axis, and some of their detailed mechanisms have been delineated. These results obtained in animal models were, at least partly, reproduced in clinical trials. At least 2 V1B receptor antagonists (TS-121 and ABT-436) showed tendencies to reduce the depression scores of patients with major depressive disorder at doses that attenuate HPA axis hyperactivity or block the pituitary V1B receptor. Importantly, TS-121 showed a clearer efficacy for patients with higher basal cortisol levels than for those with lower basal cortisol levels, which was consistent with the hypothesis that V1B receptor antagonists may be more effective for patients with HPA axis hyperactivity. Therefore, V1B receptor antagonists are promising approaches for the treatment of depression involving HPA axis impairment such as depression.

Critical illness?related corticosteroid insufficiency in children: A single center, prospective, cohort study

Background: Although guidelines for diagnosis and management of critical illness?related corticosteroid insufficiency (CIRCI) in adults are developed, there is a paucity of data on CIRCI in children. Objective: To study the incidence, risk factors, mechanism, and associations of CIRCI in children using adrenocorticotropic hormone (ACTH) stimulation test. Materials and Methods: Single?center prospective cohort study was conducted in eight bedded pediatric intensive care unit of teaching hospital over a period of 1 year. Serum total cortisol concentration was measured in 110 critically ill children before and after stimulation with 250 ?g ACTH. CIRCI was defined by post?ACTH increment in serum cortisol ?9 ?g/dl. Children with and without CIRCI were compared. Results: Incidence of CIRCI was 38.2%. Children with CIRCI had higher median age (34 vs. 18 months), higher pediatric risk of mortality score (17.79±2.60 vs. 16.37±3.68), and significantly higher basal cortisol levels (27.37±11.64 vs. 22.02±7.26) (p=0.004) than those without CIRCI. There was a significantly higher (p=0.000) requirement of catecholamines (2.71±0.457 vs. 2.00±0.792) and higher additional fluid boluses (15.79±4.7 vs. 10.65±4.60) in children with CIRCI. However, duration of catecholamine use was not significantly different between two groups. The presence of CIRCI was not found to be an independent risk factor for mortality. For each additional use of catecholamine, the risk of CIRCI increased to 5.6 times; and for each extra fluid bolus, the risk increased to 1.2 times. Conclusion: CIRCI occurs in a wide spectrum of diseases in critically ill children associated with increased need for catecholamine and fluids. CIRCI is likely to be multifactorial in etiology and associated with high basal cortisol levels.

Effects of basal and acute cortisol on cognitive flexibility in an emotional task switching paradigm in men

The stress hormone cortisol is assumed to influence cognitive functions. While cortisol-induced alterations of declarative memory in particular are well-investigated, considerably less is known about its influence on executive functions. Moreover, most research has been focused on slow effects, and rapid non-genomic effects have not been studied. The present study sought to investigate the impact of acute cortisol administration as well as basal cortisol levels on cognitive flexibility, a core executive function, within the non-genomic time frame. Thirty-eight healthy male participants were randomly assigned to intravenously receive either cortisol or a placebo before performing a task switching paradigm with happy and angry faces as stimuli. Cortisol levels were measured at six points during the experiment. Additionally, before the experiment, basal cortisol measures for the cortisol awakening response were collected on three consecutive weekdays immediately following awakening and 30, 45, and 60min after. First and foremost, results showed a pronounced impact of acute and basal cortisol on reaction time switch costs, particularly for angry faces. In the placebo group, low basal cortisol was associated with minimal switch costs, whereas high basal cortisol was related to maximal switch costs. In contrast, after cortisol injection, basal cortisol levels showed no impact. These results show that cognitive flexibility-enhancing effects of acute cortisol administration are only seen in men with high basal cortisol levels. This result supports the context dependency of cortisol administration and shows the relevance of taking basal cortisol levels into account.

Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress.

Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress.

Differences in inhibitory avoidance, cortisol and brain gene expression in TL and AB zebrafish.

Recently, we established an inhibitory avoidance paradigm in Tupfel Long-Fin (TL) zebrafish. Here, we compared task performance of TL fish and fish from the AB strain; another widely used strain and shown to differ genetically and behaviourally from TL fish. Whole-body cortisol and telencephalic gene expression related to stress, anxiety and fear were measured before and 2 h post-task. Inhibitory avoidance was assessed in a 3-day paradigm: fish learn to avoid swimming from a white to a black compartment where a 3V-shock is given: day 1 (first shock), day 2 (second shock) and day 3 (no shock, sampling). Tupfel Long-Fin fish rapidly learned to avoid the black compartment and showed an increase in avoidance-related spatial behaviour in the white compartment across days. In contrast, AB fish showed no inhibitory avoidance learning. AB fish had higher basal cortisol levels and expression levels of stress-axis related genes than TL fish. Tupfel Long-Fin fish showed post-task learning-related changes in cortisol and gene expression levels, but these responses were not seen in AB fish. We conclude that AB fish show higher cortisol levels and no inhibitory avoidance than TL fish. The differential learning responses of these Danio strains may unmask genetically defined risks for stress-related disorders.

Benzocaine and clove oil as anesthetics for pejerrey (Odontesthes bonariensis) fingerlings

Pejerrey (Odontesthes bonariensis) is a native species from Rio Grande do Sul, Uruguay and Argentina where it is of great economic importance for artisanal fishing. One difficulty in laboratory research with pejerrey is related to its sensitivity, as it presents higher basal cortisol levels than other freshwater species. For this reason, the aim of this work was to evaluate the efficiency of benzocaine and clove oil as anesthetics for pejerrey fingerlings. Two experiments were done where fingerlings (57±7.8mm and 1.1±0.44g) were exposed to benzocaine with concentrations between 40mgL-1 and 120mgL-1 and to clove oil with concentrations between 12mgL-1 and 75mgL-1. Survival, anesthesia induction time and recovery time for each pharmaceutics were evaluated. Both benzocaine and clove oil pharmaceutics showed efficiency as anesthetics for pejerrey fingerlings, with negative correlation between the dose of anesthetics and the anesthesia induction time. For benzocaine, the concentrations between 80mgL-1 and 100mgL-1 showed better results, as for clove oil the optimal concentrations were between 25mgL-1 and 50mgL-1. On the other hand, the anesthesia recovery time did not present significant variation on the different concentrations of the tested products. The tested products are highly metabolizable by pejerrey.

Problematic drinking and physiological responses among female college students

Problematic drinking is a widespread problem among college students, and can contribute to alcohol dependence during later adulthood, particularly among females. The current study assessed vulnerability for alcohol-related consequences by comparing self-reported drinking with coping styles and physiological and behavioral stress responses during a challenging task. Cardiovascular measurements and saliva samples were taken from 88 female students at the beginning of the experiment and after the task. Hypothalamic–pituitary–adrenal (HPA) activity was measured by assessing cortisol and dehydroepiandrosterone (DHEA) salivary levels. The behavioral task consisted of a set of three anagrams of increasing difficulty, the last of which had no possible solution, to test the distress tolerance of the participants. Results showed that the majority of participants (70%) reported drinking in the six months prior to data collection, most of whom reported at least one incident of binge drinking. Excessive alcohol use was related to an impaired physiological response to stress during the impossible task. College students who drank to cope with stress had significantly higher basal levels of cortisol and DHEA, an indication of HPA axis over-regulation, while their stress response remained remarkably flat. Self-reported consequences of drinking were related to motives for drinking and lower DHEA levels. Regression analysis indicated that higher cortisol levels mediated the relationship between motives for drinking and problematic drinking.

Hypothalamic–pituitary–adrenal axis tonus is associated with hippocampal microstructural asymmetry

It is well-established that prolonged high levels of cortisol have adverse effects on hippocampal neurons and glial cells. Morphometric studies linking hippocampus volume to basal HPA-axis activity, however, have yielded less consistent results. Asymmetry may also be considered, since there is growing evidence for hemispheric lateralization in brain systems regulating arousal and emotion. Here we tested the hypotheses that individual variations in basal morning and afternoon/evening cortisol levels would be associated with the degree of hemispheric asymmetry in hippocampal microstructure. Fifty healthy adults aged 19 to 86 years were included in the analyses. Diffusion-weighted imaging was acquired from all subjects. Hippocampal mean diffusivity (MD) and volume was extracted. Cortisol measures were based on 5 morning and 3 afternoon/evening saliva samples. Higher left relative to right hippocampus MD was associated with higher basal cortisol levels. Associations were anatomically specific and not attributable to hippocampal volume asymmetry. No correlation between hippocampal volume and MD was observed, suggesting that MD and volume index distinct biological properties of the hippocampus. Observed associations raise a number of possibilities, among them an asymmetric role of the hippocampus on HPA-axis regulation, or conversely, that individual variations in secreted cortisol, perhaps associated with stress, may have lateralized effects on hippocampal microstructure. Our results point to an important relationship between the limbic system and neuroendocrine function in terms of left-right asymmetries, raising additional questions about how the limbic system is related to neuroendocrine functions.

Adrenal function in adult long-term survivors of nephroblastoma and neuroblastoma

BackgroundAdrenal insufficiency, or relative insufficiency, might partly explain increased mortality rates in nephroblastoma and neuroblastoma survivors after unilateral adrenalectomy. ObjectiveTo assess adrenal function and its metabolic effects in survivors after adrenalectomy. MethodsIn this cross-sectional study, 67 adult long-term survivors of nephroblastoma, 36 survivors of neuroblastoma and 49 control subjects participated. Adrenal function was assessed by a 1μg short Synacthen-test. Levels of cortisol, adrenocorticotrophic hormone (ACTH), low (LDL-C) and high-density lipoprotein-cholesterol (HDL-C), triglycerides, apolipoprotein-B, glucose and insulin were assessed in blood samples taken at baseline. In addition, cortisol levels were assessed after 30 (t=30) and 60min. Homoeostatic Model Assessment (HOMA) was calculated. ResultsAdrenal insufficiency was not present in survivors. Interestingly, baseline serum cortisol levels were higher in survivors after unilateral adrenalectomy (mean 503nmol/l) (N=46) than in survivors with both adrenals intact (mean 393nmol/l, P=0.002) (N=52), and than in controls (mean 399nmol/l, P=0.013) (N=49). After correcting for age, sex and use of oral oestrogens, unilateral adrenalectomy was independently associated with elevated baseline cortisol and ACTH levels. Baseline cortisol levels were positively associated with triglycerides (P<0.001), LDL-C (P=0.004), apolipoprotein-B (P<0.001) and HOMA (P=0.008). ConclusionsNo adrenal insufficiency was observed in survivors of nephroblastoma and neuroblastoma. Survivors treated with unilateral adrenalectomy had relatively high basal cortisol and ACTH levels, indicating a higher central setpoint of the hypothalamic-pituitary-adrenal axis. This higher setpoint was associated with lipid concentrations and insulin resistance and can therefore influence the cardiovascular risk profile in long-term survivors of nephroblastoma and neuroblastoma.

Short and long-term effects of smoking on cortisol in older adults

We investigated concurrent as well as long-term effects of smoking on cortisol. The population consisted of 2508 elderly adults. Current smokers, as opposed to former smokers, had higher basal cortisol levels and higher morning increases of cortisol. Overall, pack-years was related to morning cortisol rise, but this was accounted for by current smokers. Time since quitting was positively associated with a greater decline in daytime cortisol indicating that the effects of smoking remit. This suggests that smoking has short-term, rather than long-term, consequences on cortisol secretion patterns.

Evaluation of pituitary function after traumatic brain injury in childhood

Post-traumatic hypopituitarism is well described amongst adult traumatic brain injury (TBI) survivors. We aimed to determine the prevalence and clinical significance of pituitary dysfunction after head injury in childhood. Retrospective exploratory study. 33 survivors of accidental head injury (27 boys). Mean (range) age at study was 13·4 years (5·4-21·7 years) and median (range) interval since injury 4·3 years (1·4-7·8 years). Functional outcome at study: 15 good recovery, 16 moderate disability, two severe disability. Early morning urine osmolality and basal hormone evaluation were followed by the gonadotrophin releasing hormone (GnRH) and insulin tolerance (n = 25) or glucagon tests (if previous seizures, n = 8). Subjects were not primed. Head injury details were extracted from patient records. No subject had short stature (mean height SD score +0·50, range -1·57 to +3·00). Suboptimal GH responses (<5 μg/l) occurred in six peri-pubertal boys (one with slow growth on follow-up) and one postpubertal adolescent (peak GH 3·2 μg/l). Median peak cortisol responses to insulin tolerance or glucagon tests were 538 and 562 nm. Nine of twenty-five and two of eight subjects had suboptimal responses, respectively, two with high basal cortisol levels. None required routine glucocorticoid replacement. In three, steroid cover was recommended for moderate/severe illness or injury. One boy was prolactin deficient. Other basal endocrine results and GnRH-stimulated LH and FSH were appropriate for age, sex and pubertal stage. Abnormal endocrine findings were unrelated to the severity or other characteristics of TBI or functional outcome. No clinically significant endocrinopathy was identified amongst survivors of accidental childhood TBI, although minor pituitary hormone abnormalities were observed.

Assessment of Adrenal Functions in Patients with Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and extrarenal manifestations may be observed in many organ systems. Hypothalamus-pituitary-adrenal axis was not evaluated extensively in patients with ADPKD. We aimed to evaluate this axis in these patients. Twenty two patients with ADPKD and 27 healthy subjects were enrolled. Basal dehydroepiandrosterone sulfate (DHEAS) levels and cortisol and DHEA responses to low dose short adrenocorticotropin stimulation test were assessed. Correlation analyses of these parameters with glomerular filtration rates (GFR), renal volumes and pain characteristics in patients with ADPKD were performed. Patients with ADPKD had higher basal cortisol levels (12.1 ± 3.4 vs. 9.6 ± 4.3 μg/dL, p=0.033), and higher basal cortisol/DHEAS ratios (0.073 ± 0.05 vs. 0.045 ± 0.02, p=0.015) compared to controls. None of the subjects had inadequate response to adrenocorticotropin stimulation. Patients with ADPKD had lower delta cortisol (absolute increase between peak and basal) levels (10.3 ± 2.8 vs. 12.6 ± 4.2 μg/dL, p=0.026) compared to controls. Subgroup analysis showed that significant differences existed only between female patients and female controls. There was no significant correlation between cortisol levels and renal volumes or GFR. A significant correlation was found only between delta cortisol and pain frequency in female patients. Patients with ADPKD had higher basal cortisol levels, higher basal cortisol/DHEAS ratios and lower delta cortisol levels compared to controls, indicating promptly stimulated zona fasciculata function. Further studies are needed to confirm these results and to investigate possible underlying mechanisms.

Several Candidates in Running as Anxiety-Disorder Biomarker

Several Candidates in Running as Anxiety-Disorder Biomarker

Cytokine Inhibition after Glucocorticoid Exposure in Healthy Men with Low versus High Basal Cortisol Levels

Objective: The balance between glucocorticoid (GC) release and GC sensitivity in target cells is believed to be important to maintain homeostasis in the neuroendocrine control of inflammation. We investigated the impact of in vivo exposure to adrenocorticotropic hormone (ACTH) and dexamethasone (DEX) on GC sensitivity measured in vitro in healthy individuals with high versus low baseline cortisol levels. Methods:136 healthy male volunteers were screened twice and sorted according to their 24-hour urinary free cortisol (UFC) excretion. The 10 individuals with the highest UFC (290 ± 87 nmol/24 h) and the 10 with the lowest UFC (168 ± 34 nmol/24 h) were further tested. Measurements were performed at baseline, after a low dose (0.5 μg/1.73 m²) of ACTH challenge and after 2 weeks’ exposure to DEX (0.1 mg twice daily). GC sensitivity was assessed in vitro as the ability of DEX to inhibit lipopolysaccharide-stimulated production of the cytokines interleukin 1-β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in a whole-blood assay. Results:After exposure to DEX in vivo, inhibition of IL-6 and TNF-α decreased. Also, after DEX in vivo, low-cortisol men showed lower inhibition of IL-1β and IL-6, both compared to the high-cortisol group and their own baseline levels. Conclusion: A downregulation of GC sensitivity in leukocytes after exposure to an exogenous GC seems to occur most strongly in men with low cortisol levels.

Serotonin transporter gene variation, infant abuse, and responsiveness to stress in rhesus macaque mothers and infants

A functional polymorphism in the promoter region of the serotonin transporter (5-HTTLPR) gene has been associated with variation in anxiety and hypothalamus–pituitary–adrenal (HPA) axis function in humans and rhesus macaques. Individuals carrying the short allele are at a higher risk for developmental psychopathology, and this risk is magnified in short allele carriers who have experienced early life stress. This study investigated the relationship between 5-HTTLPR allelic variation, infant abuse, and behavioral and hormonal responses to stress in rhesus macaques. Subjects were 10 abusive mothers and their infants, and 10 nonabusive mother–infant pairs. Mothers and infants were genotyped for the rh5-HTTLPR, and studied in the first 6 months of infant life. For mothers and infants, we measured social group behavior, behavioral responses to handling procedures, and plasma concentrations of ACTH and cortisol under basal conditions and in response to stress tests. The proportion of individuals carrying the short rh5-HTTLPR allele was significantly higher among abusive mothers than controls. Among mothers and infants, the short allele was associated with higher basal cortisol levels and greater hormonal stress responses in the infants. In addition, infants who carried the short rh5-HTTLPR allele had higher anxiety scores than infants homozygous for the long allele. The rh5-HTTLPR genotype also interacted with early adverse experience to impact HPA axis function in the infants. These results are consistent with those of previous studies which demonstrate associations between serotonergic activity and anxiety and stress reactivity, and add additional evidence suggesting that genetic variation in serotonergic function may contribute to the occurrence of abusive parenting in rhesus macaques and modulate emotional behavior and HPA axis function.

Salivary cortisol levels and infant temperament shape developmental trajectories in boys at risk for behavioral maladjustment

Behavioral problems in young children can take on a variety of forms, which are linked to distinct antecedents and co-occurring markers. Internalizing difficulties in young children, for example, have been linked to individual differences in infant temperament and cortisol levels. In addition, there is growing evidence that these biobehavioral mechanisms are also shaped by gender. Four-year-old children participated in a study examining the relations between salivary cortisol and behavioral maladjustment as a function of gender and temperament. Both longitudinal (maternal report of infant temperament at 9 months) and concurrent (morning salivary cortisol at age 4) data were used to predict two forms of maladjustment: 'Withdrawal' (maternal report of internalizing behavior and laboratory observation of social reticence) and 'Acting Out' (maternal report of externalizing behavior and laboratory observation of solitary active play). High basal cortisol levels were strongly associated with Withdrawal in male participants. However, the relation was significant only in boys who exhibited high levels of negative temperament in infancy. There were no comparable findings with 'Acting Out' beyond a main effect of gender reflecting greater difficulty in boys. The data suggested that there are unique biobehavioral mechanisms shaping specific patterns of maladjustment in childhood.

Cortisol and Children’s Adjustment: The Moderating Role of Sympathetic Nervous System Activity

We examined relations among cortisol, markers of sympathetic nervous system (SNS) activity (including salivary alpha-amylase and skin conductance level), and children's adjustment. We also tested the Bauer et al. (Journal of Developmental and Behavioral Pediatrics, 23(2), 102-113, 2002) hypothesis that interactions between the SNS and cortisol would be associated with internalizing and externalizing problems. Saliva samples were obtained from 8- to 9-year-olds before and after a laboratory assessment battery, and were assayed for cortisol and alpha-amylase (sAA). Basal skin conductance level (SCL) was measured during resting conditions. Parents reported on child adjustment. Interactions between basal SNS and cortisol levels explained moderate amounts of unique variance in children's externalizing and internalizing problems. More specifically, higher basal cortisol levels were positively associated with higher internalizing and externalizing problems among children with higher SNS activity, as compared to children with lower SNS activity. Findings underscore the utility of including information about the coordination between hypothalamic-pituitary-adrenal (HPA) and SNS activity in biosocial models of atypical child development.