Reduced Cingulate Gyrus Volume Associated with Enhanced Cortisol Awakening Response in Young Healthy Adults Reporting Childhood Trauma

Background

Preclinical studies have demonstrated the relationship between stress-induced increased cortisol levels and atrophy of specific brain regions, however, this association has been less revealed in clinical samples. The aim of the present study was to investigate the changes and associations of the hypothalamic-pituitary-adrenal (HPA) axis activity and gray matter volumes in young healthy adults with self-reported childhood trauma exposures.

Methods

Twenty four healthy adults with childhood trauma and 24 age- and gender-matched individuals without childhood trauma were recruited. Each participant collected salivary samples in the morning at four time points: immediately upon awakening, 30, 45, and 60 min after awakening for the assessment of cortisol awakening response (CAR). The 3D T1-weighted magnetic resonance imaging data were obtained on a Philips 3.0 Tesla scanner. Voxel-based morphometry analyses were conducted to compare the gray matter volume between two groups. Correlations of gray matter volume changes with severity of childhood trauma and CAR data were further analyzed.

Results

Adults with self-reported childhood trauma showed an enhanced CAR and decreased gray matter volume in the right middle cingulate gyrus. Moreover, a significant association was observed between salivary cortisol secretions after awaking and the right middle cingulate gyrus volume reduction in subjects with childhood trauma.

Conclusions

The present research outcomes suggest that childhood trauma is associated with hyperactivity of the HPA axis and decreased gray matter volume in the right middle cingulate gyrus, which may represent the vulnerability for developing psychosis after childhood trauma experiences. In addition, this study demonstrates that gray matter loss in the cingulate gyrus is related to increased cortisol levels.     

The Relationship between Cortisol Activity during Cognitive Task and Posttraumatic Stress Symptom Clusters

Background

The latest development in the dimensional structure of posttraumatic stress disorder (PTSD) is a novel 6-factor model, which builds on the newly released DSM-5. One notable gap in the literature is that little is known about how distinct symptom clusters of PTSD are related to hypothalamic–pituitary–adrenal (HPA) axis activity when people perform a relatively less stressful cognitive task. The purpose of this study was to investigate the relationship between cortisol activity when individuals perform cognitive tasks in the laboratory and a contemporary phenotypic model of posttraumatic stress symptomatology in earthquake survivors.

Methods

Salivary cortisol while performing cognitive tasks was collected and analyzed in 89 adult earthquake survivors. The PTSD Checklist for the DSM-5 (PCL-5) was used to assess the severity of total PTSD as well as six distinct symptom clusters. Regression analyses were conducted to examine the associations between the six distinct PTSD symptom clusters and cortisol profiles.

Results

The results showed that the score of the negative affect symptom cluster, but not anhedonia or other clusters, was positively associated with cortisol levels before and during the cognitive tasks.

Conclusion

The results showed that higher cortisol levels before and during cognitive tasks might be specifically linked to a distinct symptom cluster of PTSD—negative affect symptomatology. This suggests that a distinction should be made between negative affect and anhedonia symptom clusters, as the 6-factor model proposed.     

Differences in Salivary Alpha-Amylase and Cortisol Responsiveness following Exposure to Electrical Stimulation versus the Trier Social Stress Tests

Background

Cortisol is an essential hormone in the regulation of the stress response along the HPA axis, and salivary cortisol has been used as a measure of free circulating cortisol levels. Recently, salivary alpha-amylase (sAA) has also emerged as a novel biomarker for psychosocial stress responsiveness within the sympathetic adrenomedullary (SAM) system.

Principal Findings

We measured sAA and salivary cortisol in healthy volunteers after exposure to the Trier Social Stress Test (TSST) and electric stimulation stress. One hundred forty-nine healthy volunteers participated in this study. All subjects were exposed to both the TSST and electric stimulation stress on separate days. We measured sAA and salivary cortisol levels three times immediately before, immediately after, and 20 min after the stress challenge. The State (STAI-S) and Trait (STAI-T) versions of the Spielberger Anxiety Inventory test and the Profile of Mood State (POMS) tests were administered to participants before the electrical stimulation and TSST protocols. We also measured HF, LF and LF/HF Heart Rate Variability ratio immediately after electrical stimulation and TSST exposure. Following TSST exposure or electrical stimulation, sAA levels displayed a rapid increase and recovery, returning to baseline levels 20 min after the stress challenge. Salivary cortisol responses showed a delayed increase, which remained significantly elevated from baseline levels 20 min after the stress challenge. Analyses revealed no differences between men and women with regard to their sAA response to the challenges (TSST or electric stimulations), while we found significantly higher salivary cortisol responses to the TSST in females. We also found that younger subjects tended to display higher sAA activity. Salivary cortisol levels were significantly correlated with the strength of the applied electrical stimulation.

Conclusions

These preliminary results suggest that the HPA axis (but not the SAM system) may show differential response patterns to distinct kinds of stressors.     

Childhood Physical and Sexual Abuse History and Leukocyte Telomere Length among Women in Middle Adulthood

Objective

Abuse victimization in childhood is associated with a variety of age-related cardiometabolic diseases, but the mechanisms remain unknown. Telomeres, which form the protective caps at the ends of chromosomes, have been proposed as measures of biological age, and a growing body of research suggests that telomere attrition may help to explain relationships between stress and cardiometabolic degradation. We examined the association between childhood abuse victimization and leukocyte telomere length among 1,135 participants in the Nurses’ Health Study II (NHSII).

Methods

The NHSII ascertained physical and sexual child abuse histories in 2001. Telomere length was measured in genomic DNA extracted from peripheral blood leukocytes collected between 1996 and 1999. The ratio of telomere repeat copy number to a single gene copy number (T/S) was determined by a modified version of the quantitative real-time PCR telomere assay. Telomere length was log-transformed and corrected for assay variation across batch. We regressed telomere length on childhood abuse exposure variables and covariates using linear regression.

Results

We observed a reduction in telomere length associated with moderate physical abuse versus no physical abuse, but there was no evidence of a dose-response relationship for increased severity of physical abuse. No associations were noted for sexual abuse.

Conclusions

We found no evidence of an association between severity of childhood physical or sexual abuse and leukocyte telomere length in the NHSII.     

Prenatal and Postpartum Evening Salivary Cortisol Levels in Association with Peripartum Depressive Symptoms

Background

The biology of peripartum depression remains unclear, with altered stress and the Hypothalamus-Pituitary-Adrenal axis response having been implicated in its pathophysiology.

Methods

The current study was undertaken as a part of the BASIC project (Biology, Affect, Stress, Imaging, Cognition), a population-based longitudinal study of psychological wellbeing during pregnancy and the postpartum period in Uppsala County, Sweden, in order to assess the association between evening salivary cortisol levels and depressive symptoms in the peripartum period. Three hundred and sixty-five pregnant women from the BASIC cohort were recruited at pregnancy week 18 and instructed to complete a Swedish validated version of the Edinburgh Postnatal Depression Scale at the 36th week of pregnancy as well as the sixth week after delivery. At both times, they were also asked to provide evening salivary samples for cortisol analysis. A comprehensive review of the relevant literature is also provided.

Results

Women with postpartum EPDS score ≥ 10 had higher salivary evening cortisol at six weeks postpartum compared to healthy controls (median cortisol 1.19 vs 0.89 nmol/L). A logistic regression model showed a positive association between cortisol levels and depressive symptoms postpartum (OR = 4.1; 95% CI 1.7–9.7). This association remained significant even after controlling for history of depression, use of tobacco, partner support, breastfeeding, stressful life events, and sleep problems, as possible confounders (aOR = 4.5; 95% CI 1.5–14.1). Additionally, women with postpartum depressive symptoms had higher postpartum cortisol levels compared to both women with depressive symptoms antenatally and controls (p = 0.019 and p = 0.004, respectively).

Conclusions

Women with depressive symptoms postpartum had higher postpartum cortisol levels, indicating an altered response of the HPA-axis in postpartum depression.     

Influence of the 5-HT3A Receptor Gene Polymorphism and Childhood Sexual Trauma on Central Serotonin Activity

Background

Gene-environment interactions are important for understanding alterations in human brain function. The loudness dependence of auditory evoked potential (LDAEP) is known to reflect central serotonergic activity. Single nucleotide polymorphisms (SNPs) in the 5-HT3A serotonin receptor gene are associated with psychiatric disorders. This study aimed to investigate the effect between 5-HT3A receptor gene polymorphisms and childhood sexual trauma on the LDAEP as an electrophysiological marker in healthy subjects.

Methods

A total of 206 healthy subjects were recruited and evaluated using the childhood trauma questionnaire (CTQ) and hospital anxiety and depression scale (HADS). Peak-to-peak N1/P2 was measured at five stimulus intensities, and the LDAEP was calculated as the linear-regression slope. In addition, the rs1062613 SNPs of 5-HT3A (CC, CT, and TT) were analyzed in healthy subjects.

Results

There was a significant interaction between scores on the CTQ-sexual abuse subscale and 5-HT3A genotype on the LDAEP. Subjects with the CC polymorphism had a significantly higher LDEAP than T carriers in the sexually abused group. In addition, CC genotype subjects in the sexually abused group showed a significantly higher LDAEP compared with CC genotype subjects in the non-sexually abused group.

Conclusions

Our findings suggest that people with the CC polymorphism of the 5-HT3A gene have a greater risk of developing mental health problems if they have experienced childhood sexual abuse, possibly due to low central serotonin activity. Conversely, the T polymorphism may be protective against any central serotonergic changes following childhood sexual trauma.     

Social Stress Increases Cortisol and Hampers Attention in Adolescents with Excess Weight

Objective

To experimentally examine if adolescents with excess weight are more sensitive to social stress and hence more sensitive to harmful effects of stress in cognition.

Design and Methods

We conducted an experimental study in 84 adolescents aged 12 to 18 years old classified in two groups based on age adjusted Body Mass Index percentile: Normal weight (n=42) and Excess weight (n=42). Both groups were exposed to social stress as induced by the virtual reality version of the Trier Social Stress Task --participants were requested to give a public speech about positive and negative aspects of their personalities in front of a virtual audience. The outcome measures were salivary cortisol levels and performance in cognitive tests before and after the social stressor. Cognitive tests included the CANTAB Rapid Visual Processing Test (measuring attention response latency and discriminability) and the Iowa Gambling Task (measuring decision-making).

Results

Adolescents with excess weight compared to healthy weight controls displayed increased cortisol response and less improvement of attentional performance after the social stressor. Decision-making performance decreased after the social stressor in both groups.

Conclusion

Adolescents who are overweight or obese have increased sensitivity to social stress, which detrimentally impacts attentional skills.     

Childhood Adversities and Adult Headache in Poland and Germany

Objective

Various childhood adversities have been found to be associated with chronic pain in adulthood. However, associations were moderate in most studies, i.e. odds ratios (OR) were between one and two.

Method

An internet survey was performed in 508 Polish and 500 German subjects. A total of 19 childhood adversities were selected and their associations with headaches explored. Age, gender and country were included as potential confounders, as well as their two-way interaction with the risk factors.

Results

Two strong risk factors were identified. (1) A combined score for physical and emotional neglect showed an odds ratio (OR) of 2.78 (p < .002) to the frequency of headache in adulthood as a main effect. (2) Father having had chronic pain showed an OR of 4.36 (p < .001) with headache in adulthood for women, but not for men (OR = 0.86, p < .556). The majority of the examined childhood adversities were not associated with adult headache, neither when tested individually nor as a sum score.

Conclusion

This study confirms results from previous ones that childhood adversities may play a role in the development of adult headache, but it is a rather minor one. Contrary to other studies, neglect turned out to be one of the strongest predictors.     

Cross-Country Differences in Basal and Stress-Induced Cortisol Secretion in Older Adults

Objective

Several studies have emphasized the association between socioeconomic status (SES) and inadequate response of the biological stress system. However, other factors related to SES are rarely considered, such as cultural values, social norms, organization, language and communication skills, which raises the need to investigate cross-country differences in stress response. Although some studies have shown differences in cortisol levels between immigrants and natives, there is no cross-country evidence regarding cortisol levels in country-native elders. This is particularly important given the high prevalence of stress-related disorders across nations during aging. The current study examined basal diurnal and reactive cortisol levels in healthy older adults living in two different countries.

Methods

Salivary cortisol of 260 older adults from Canada and Brazil were nalyzed. Diurnal cortisol was measured in saliva samples collected at home throughout two working days at awakening, 30 min after waking, 1400 h, 1600 h and before bedtime. Cortisol reactivity was assessed in response to the Trier Social Stress Test (TSST) in both populations.

Results

Our results showed that even under similar health status, psychological and cognitive characteristics, Brazilian elders exhibited higher basal and stress-induced cortisol secretion compared to the Canadian participants.

Conclusion

These findings suggest that country context may modulate cortisol secretion and could impact the population health.     

Avoidant Personality Disorder versus Social Phobia: The Significance of Childhood Neglect

Objectives

Avoidant personality disorder (AvPD) and social phobia (SP) are common disorders both in the community and in clinical settings. Whether the two disorders represent different severity levels of social anxiety disorder is currently in dispute. The relationship between AvPD and SP is probably more complex than previously assumed. Several environmental, temperamental, and constitutional factors may play a role in the etiology of AvPD and SP. Better knowledge about childhood experiences may shed light on similarities and differences between the two disorders. The aim of this study was to compare self-reported childhood experiences in AvPD and SP patients.

Design

This is a cross-sectional multi-site study of 91 adult patients with AvPD and/ or SP. We compared patients with AvPD with and without SP (AvPD group) to patients with SP without AvPD (SP group).

Methods

The patients were examined using structured diagnostic interviews and self-report measures, including Child Trauma Questionnaire, Parental Bonding Instrument, and Adult Temperament Questionnaire.

Results

Both AvPD and SP were associated with negative childhood experiences. AvPD patients reported more severe childhood neglect than patients with SP, most pronounced for physical neglect. The difference between the disorders in neglect remained significant after controlling for temperamental factors and concurrent abuse.

Conclusions

The study indicates that childhood neglect is a risk factor for AvPD and may be one contributing factor to phenomenological differences between AvPD and SP.     

Cortisol Awakening Response Is Linked to Disease Course and Progression in Multiple Sclerosis

Objectives

Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has frequently been reported in multiple sclerosis (MS). So far, HPA axis function in MS has predominantly been studied under pharmacological stimulation which is associated with a series of methodological caveats. Knowledge of circadian cortisol patterns and cortisol awakening response (CAR) is still limited.

Methods

A total of 77 MS patients (55 relapsing-remitting MS (RRMS)/22 secondary-progressive MS (SPMS)) as well as 34 healthy control (HC) subjects were enrolled. Diurnal cortisol release was assessed by repeated salivary cortisol sampling. Neurological disability was rated by the Kurtzke’s Expanded Disability Status Scale (EDSS). Depressive symptoms and perceived stress were assessed by self-report measures.

Results

RRMS but not SPMS patients differed in circadian cortisol release from HC subjects. Differences in cortisol release were restricted to CAR. Treated and treatment naïve RRMS patients did not differ in CAR. In a RRMS follow-up cohort (nine months follow-up), RRMS patients with EDSS progression (≥0.5) expressed a significantly greater CAR compared to HC subjects. RRMS patients with a stable EDSS did not differ from HC subjects. Neither depressive symptoms nor perceived stress ratings were associated with CAR in RRMS patients. In a step-wise regression analysis, EDSS at baseline and CAR were predictive of EDSS at follow-up (R² = 67%) for RRMS patients.

Conclusions

Circadian cortisol release, in particular CAR, shows a course specific pattern with most pronounced release in RRMS. There is also some evidence for greater CAR in RRMS patients with EDSS progression. As a consequence, CAR might be of predictive value in terms of neurological disability in RRMS patients. The possible role of neuroendocrine-immune interactions in MS pathogenesis is further discussed.     

Intimate Partner Violence Is Associated with Stress-Related Sleep Disturbance and Poor Sleep Quality during Early Pregnancy

Objectives

To examine the associations of Intimate partner violence (IPV) with stress-related sleep disturbance (measured using the Ford Insomnia Response to Stress Test [FIRST]) and poor sleep quality (measured using the Pittsburgh Sleep Quality Index [PSQI]) during early pregnancy.

Methods

This cross-sectional study included 634 pregnant Peruvian women. In-person interviews were conducted in early pregnancy to collect information regarding IPV history, and sleep traits. Adjusted odds ratios (aOR) and 95% confidence intervals (95%CIs) were calculated using logistic regression procedures.

Results

Lifetime IPV was associated with a 1.54-fold increased odds of stress-related sleep disturbance (95% CI: 1.08–2.17) and a 1.93-fold increased odds of poor sleep quality (95% CI: 1.33–2.81). Compared with women experiencing no IPV during lifetime, the aOR (95% CI) for stress-related sleep disturbance associated with each type of IPV were: physical abuse only 1.24 (95% CI: 0.84–1.83), sexual abuse only 3.44 (95%CI: 1.07–11.05), and physical and sexual abuse 2.51 (95% CI: 1.27–4.96). The corresponding aORs (95% CI) for poor sleep quality were: 1.72 (95% CI: 1.13–2.61), 2.82 (95% CI: 0.99–8.03), and 2.50 (95% CI: 1.30–4.81), respectively. Women reporting any IPV in the year prior to pregnancy had increased odds of stress-related sleep disturbance (aOR = 2.07; 95% CI: 1.17–3.67) and poor sleep quality (aOR = 2.27; 95% CI: 1.30–3.97) during pregnancy.

Conclusion

Lifetime and prevalent IPV exposures are associated with stress-related sleep disturbance and poor sleep quality during pregnancy. Our findings suggest that sleep disturbances may be important mechanisms that underlie the lasting adverse effects of IPV on maternal and perinatal health.     

Cortisol Patterns Are Associated with T Cell Activation in HIV

Objective

The level of T cell activation in untreated HIV disease is strongly and independently associated with risk of immunologic and clinical progression. The factors that influence the level of activation, however, are not fully defined. Since endogenous glucocorticoids are important in regulating inflammation, we sought to determine whether less optimal diurnal cortisol patterns are associated with greater T cell activation.

Methods

We studied 128 HIV-infected adults who were not on treatment and had a CD4⁺ T cell count above 250 cells/µl. We assessed T cell activation by CD38 expression using flow cytometry, and diurnal cortisol was assessed with salivary measurements.

Results

Lower waking cortisol levels correlated with greater T cell immune activation, measured by CD38 mean fluorescent intensity, on CD4⁺ T cells (r = −0.26, p = 0.006). Participants with lower waking cortisol also showed a trend toward greater activation on CD8⁺ T cells (r = −0.17, p = 0.08). A greater diurnal decline in cortisol, usually considered a healthy pattern, correlated with less CD4⁺ (r = 0.24, p = 0.018) and CD8⁺ (r = 0.24, p = 0.017) activation.

Conclusions

These data suggest that the hypothalamic-pituitary-adrenal (HPA) axis contributes to the regulation of T cell activation in HIV. This may represent an important pathway through which psychological states and the HPA axis influence progression of HIV.     

Impact of Childhood Abuse on the Risk of Non-Suicidal Self-Injury in Mainland Chinese Adolescents

Background

Childhood abuse has been associated with significant increases in non-suicidal self-injury (NSSI) behaviors in adolescents; however, only general definitions of this risk indicator have been examined. This study identified relationships between specific forms of childhood abuse and NSSI in mainland Chinese adolescents.

Method

A total of 14,221 cases were retained from an epidemiological study involving adolescents from junior and senior middle schools. Information relating to the perpetrator, perceived harm, timing of exposure to different types of childhood abuse, and NSSI were obtained. Logistic regression was used to analyze relationships between each form of childhood abuse and NSSI.

Results

Approximately 51.0% of the students reported at least one abusive childhood experience. Nearly one in four students (24.9%) reported that they had engaged in NSSI in the past 12 months. Each type of childhood abuse, occurring at any time within the first 16 years of life, especially in situations of continuous exposure, was significantly associated with NSSI. A significant graded relationship was found between number of abusive childhood experiences and NSSI. Students maltreated by parents or others were at high risk of engaging in NSSI, the risk was greater in students maltreated by both; students who had been exposed to childhood abuse with no perceived harm still demonstrated an elevated risk for NSSI. The pattern of associations did not vary by gender.

Conclusions

These findings suggest that experiencing any of various forms of childhood abuse should be considered a risk factor for NSSI during adolescence. Further research should focus upon psychosocial, neural, and genetic factors that might moderate or mediate the onset of NSSI in adolescents who have experienced childhood abuse.     

Testing the Validity and Reliability of the Shame Questionnaire among Sexually Abused Girls in Zambia

Purpose

The aim of the current study is to test the validity and reliability of the Shame Questionnaire among traumatized girls in Lusaka, Zambia.

Methods

The Shame Questionnaire was validated through both classical test and item response theory methods. Internal reliability, criterion validity and construct validity were examined among a sample of 325 female children living in Zambia. Sub-analyses were conducted to examine differences in construct validity among girls who reported sexual abuse and girls who did not.

Results

All girls in the sample were sexually abused, but only 61.5% endorsed or reported that sexual abuse had occurred. Internal consistency was very good among the sample with alpha = .87. Criterion validity was demonstrated through a significant difference of mean Shame Questionnaire scores between girls who experienced 0–1 trauma events and more than one traumatic event, with higher mean Shame Questionnaire scores among girls who had more than one traumatic event (p = .004 for 0–1 compared to 2 and 3 events and p = .016 for 0–1 compared to 4+ events). Girls who reported a history of witnessing or experiencing physical abuse had a significantly higher mean Shame Questionnaire score than girls who did not report a history of witnessing or experiencing physical abuse (p<.0001). There was no significant difference in mean Shame Questionnaire score between girls who reported a sexual abuse history and girls who did not. Exploratory factor analysis indicated a two-factor model of the Shame Questionnaire, with an experience of shame dimension and an active outcomes of shame dimension. Item response theory analysis indicated adequate overall item fit. Results also indicate potential differences in construct validity between girls who did and did not endorse sexual abuse.

Conclusions

This study suggests the general utility of the Shame Questionnaire among Zambian girls and demonstrates the need for more psychometric studies in low and middle income countries.     

Childhood Maltreatment and BMI Trajectories to Mid-Adult Life: Follow-Up to Age 50y in a British Birth Cohort

Background

Childhood maltreatment including abuse and neglect has been associated with adult obesity, but evidence on life-course development of obesity or BMI gain is unclear. We aim to establish whether childhood maltreatments are related to obesity or BMI at different life-stages 7y-50y and to identify possible explanations for associations.

Methods

Childhood physical, psychological and sexual abuse, neglect and BMI at seven ages were recorded in the 1958 birth cohort (n~15,000). Associations of child maltreatments with BMI at separate ages were tested using linear regression or logistic regression for obesity, and with rate of child-to-adult BMI gain using multilevel models. We adjusted for potential covariates.

Results

Abuse was reported in ~12% of the population. Abuse was not associated with elevated childhood BMI, but adult associations were observed: i.e. the abused had faster child-adult BMI gain than the non-abused; associations were independent of adult covariates. For physical abuse in both genders there was a positive linear association of ~0.006/y zBMI gain with age after adjustment for all covariates. Similarly, there was a linear association of physical abuse with obesity risk: e.g. among females from a low OR_adjusted of 0.34 (0.16,0.71) at 7y to 1.67 (1.25,2.24) at 50y. In females faster zBMI gains with age of ~0.0034/y were observed for sexual abuse and increases in obesity risk were faster: from a low OR_adjusted of 0.23 (0.06,0.84) at 7y to 1.34 (0.86,2.10) at 50y. Psychological abuse and neglect associations were less consistent.

Conclusions

Childhood maltreatment associations with BMI or obesity varied across life: physical and, in females, sexual abuse were associated with faster lifetime BMI gains, which may have detrimental long-term health consequences.     

Influence of Sex on Suicidal Phenotypes in Affective Disorder Patients with Traumatic Childhood Experiences

Objectives

In the current study, we aimed to investigate the impact of childhood trauma on suicidal behaviour phenotypes in a group of patients with diagnosed affective disorder (unipolar or bipolar affective disorder).

Patients and Methods

Patients with and without a history of childhood abuse, measured by Childhood Trauma Questionnaire (CTQ), were assessed to explore risks for suicidal behaviour (including suicide attempt, self-harm and non-suicidal self-injury). The tested sample consisted of 258 patients (111 males and 147 females, in-patients and out-patients at the Department of Psychiatry and Psychotherapy, Medical University of Vienna and University Hospital Tulln, Lower Austria). Psychiatric diagnoses were derived from the SCAN (Schedules for Clinical Assessment in Neuropsychiatry) interview. In addition, patients were administered the Lifetime Parasuicidal Count (LPC), Suicidal Behaviour Questionnaire (SBQ-R), and Viennese Suicide Risk Assessment Scale (VISURIAS) questionnaires.

Results

In contrast to male suicide attempters, female suicide attempters showed both significantly higher total CTQ scores (p<0.001), and higher CTQ subscores (emotional, physical and sexual abuse, as well as emotional and physical neglect) in comparison to the non-suicidal control group. Besides, females with a history of self-harming behaviour (including suicidal intention) and Non-Suicidal-Self Injury (NSSI) had significantly higher CTQ total scores (p<0.001) than the control group.

Conclusion

These findings suggest gender differences in suicidal behaviour after being exposed to childhood trauma.     

The Early Endocrine Stress Response in Experimental Subarachnoid Hemorrhage

Introduction

In patients with severe illness, such as aneurysmal subarachnoid hemorrhage (SAH), a physiologic stress response is triggered. This includes activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. The aim of this study was to investigate the very early responses of these systems.

Methods

A porcine animal model of aneurysmal SAH was used. In this model, blood is injected slowly to the basal cisterns above the anterior skull base until the cerebral perfusion pressure is 0 mm Hg. Sampling was done from blood and urine at -10, +15, +75 and +135 minutes from time of induction of SAH. Analyses of adrenocorticotropic hormone (ACTH), cortisol, aldosterone, catecholamines and chromogranin-A were performed.

Results

Plasma ACTH, serum cortisol and plasma aldosterone increased in the samples following induction of SAH, and started to decline after 75 minutes. Urine cortisol also increased after SAH. Urine catecholamines and their metabolites were found to increase after SAH. Many samples were however below detection level, not allowing for statistical analysis. Plasma chromogranin-A peaked at 15 minutes after SAH, and thereafter decreased.

Conclusions

The endocrine stress response after aneurysmal SAH was found to start within 15 minutes in the HPA axis with early peak values of ACTH, cortisol and aldosterone. The fact that the concentrations of the HPA axis hormones decreased 135 minutes after SAH may suggest that a similar pattern exists in SAH patients, thus making it difficult to catch these early peak values. There were also indications of early activation of the sympathetic nervous system, but the small number of valid samples made interpretation difficult.     

Relative Metabolic Stability,but Disrupted Circadian Cortisol Secretion during the Fasting Month of Ramadan

Background

Chronic feeding and sleep schedule disturbances are stressors that exert damaging effects on the organism. Practicing Muslims in Saudi Arabia go through strict Ramadan fasting from dawn till sunset for one month yearly. Modern era Ramadan practices in Saudi Arabia are associated with disturbed feeding and sleep patterns, namely abstaining from food and water and increasing daytime sleep, and staying awake and receiving food and water till dawn.

Hypothesis

Strict Ramadan practices in Saudi Arabia may influence metabolism, sleep and circadian cortisol secretion.

Protocol

Young, male Ramadan practitioners were evaluated before and two weeks into the Ramadan. Blood samples were collected at 9.00 am and 9.00 pm for measurements of metabolic parameters and cortisol. Saliva was collected serially during the day for cortisol determinations.

Results

Ramadan practitioners had relative metabolic stability or changes expected by the pattern of feeding. However, the cortisol circadian rhythm was abolished and circulating insulin levels and HOMA index were increased during this period.

Discussion

The flattening of the cortisol rhythm is typical of conditions associated with chronic stress or endogenous hypercortisolism and associated with insulin resistance.

Conclusions

Modern Ramadan practices in Saudi Arabia are associated with evening hypercortisolism and increased insulin resistance. These changes might contribute to the high prevalence of chronic stress-related conditions, such as central obesity, hypertension, metabolic syndrome and diabetes mellitus type 2, and their cardiovascular sequelae observed in the Kingdom.     

Usefulness of Time-Point Serum Cortisol and ACTH Measurements for the Adjustment of Glucocorticoid Replacement in Adrenal Insufficiency

Background

Adjustment of daily hydrocortisone dose on clinical criteria lacks sensitivity for fine tuning. Long term hydrocortisone (HC) over-replacement may lead to increased morbidity and mortality in patients with adrenal insufficiency (AI). Biochemical criteria may help detecting over- or under-replacement but have been poorly evaluated.

Methods

Multicenter, institutional, pharmacokinetic study on ACTH and cortisol plasma profiles during HC replacement in 27 AI patients compared to 29 matched controls. All AI patients were administered HC thrice daily at doses of 6, 10 and 14 mg/m²/d. Blood samples were drawn hourly from 0800h to 1900h. The main outcome measures were: i) plasma peak cortisol and cortisol area under the curve (AUC) in AI patients compared to controls, ii) correlations between cortisol AUC vs single-point cortisol or ACTH decrease from baseline (ΔACTH) and iii) the predictive value of the two latters for obtaining AI patients’ cortisol AUC in the control range.

Results

Cortisol peaks were observed 1h after each HC intake and a dose response was demonstrated for cortisol peak and cortisol AUC. The comparison of AI patients’ cortisol AUC to controls showed that 81.5% AI patients receiving 6mg/m²/d were adequately replaced, whereas most patients receiving higher doses were over-replaced. The correlation coefficient between 1000h/1400h cortisol concentrations and 0800-1900h cortisol AUC were 0.93/0.88 respectively, whereas the 0800-1200h ΔACTH fairly correlated with 0800-1900h cortisol AUC (R = 0.57). ROC curve analysis indicated that the 1000h and 1400h cortisol concentrations best predicted over-replacement.

Conclusions

Patients receiving a 6mg/m² hydrocortisone daily dose exhibited the most physiological daytime cortisol profile. Single point plasma cortisol correlated with daytime cortisol AUC in AI patients. Although hydrocortisone dose should be currently determined on clinical grounds, our data suggest that single point plasma cortisol may be an adjunct for further hydrocortisone dose adjustment in AI patients.