Reduced levels of the endocannabinoid arachidonylethanolamide (AEA) in hair in patients with borderline personality disorder - a pilot study.

Endocannabinoids are involved in depressive and anxious symptoms and might play a role in stress-associated psychiatric disorders. While alterations in the endogenous cannabinoid system have been repeatedly found in patients with posttraumatic stress disorder (PTSD), this system has been mostly neglected in borderline personality disorder (BPD). However, there is first evidence for elevated serum levels of the endocannabinoids arachidonylethanolamide (AEA) and 2-arachidonyl-sn-glycerol (2-AG) in BPD patients compared to healthy controls and PTSD patients. In this study, hair endocannabinoids were analyzed, reflecting long-term endocannabinoid concentrations. We assessed AEA concentrations as well as 2-AG and the 2-AG main isomer 1-AG (1-AG/2-AG) in hair in women with BPD (n = 15) and age- and education-matched healthy women (n = 16). We found significantly reduced log AEA in BPD patients compared to healthy women (p = .03) but no differences in log 1-AG/2-AG concentrations. In addition, there was no association between 1-AG/2-AG and hair cortisol, but we found a non-significant correlation between hair concentrations of AEA and cortisol (p = .06). Our data indicate altered long-term release of endogenous cannabinoids in women with BPD depending on type of endocannabinoid. AEA has been suggested to modulate the basal activity of the endocannabinoid system and seems to attenuate depressive and anxious symptoms. Thus, chronically reduced AEA might contribute to psychiatric symptoms in BPD.

Association between major depression and cardiovascular risk: the role of antidepressant medication.

RATIONALE AND OBJECTIVES: Major depressive disorder (MDD) is associated with an increased risk for cardiovascular disease (CVD). Apart from biological and life style factors, the use of antidepressants and their potentially adverse effects might contribute to the increased CVD risk. Therefore, we compared cardiovascular risk profiles between relatively young depressed patients without CVD with and without antidepressant medication and healthy participants. METHODS: We investigated 44 depressed patients (with antidepressants N = 20 (13 women), mean age 43.2 years; without antidepressants N = 24 (15 women), mean age 40.0) and 41 healthy participants (matched for sex, age, education). As markers of CVD risk, blood pressure, body mass index (BMI), and plasma levels of fasting glucose, cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), and high sensitivity C-reactive protein (h-CRP) were measured. RESULTS: We found significant differences between groups for BMI (p < .01), systolic (p = .02) and diastolic blood pressure (p < .01), and glucose (p < .001). Post hoc analyses indicated differences between both patient groups compared to the healthy control group, but not between patients groups. Further controlling for BMI diminished the effect of diagnosis on blood pressure; however, this was not the case for glucose level. There were no between-group differences in cholesterol, LDL, HDL, and h-CRP. CONCLUSIONS: We found a clearly increased CVD risk in this group of rather young depressed patients. Importantly, there was no significant difference in CVD risk between patients with vs. without antidepressants. This suggests that major depression per se and not antidepressant medication is associated with increased CVD risk.

Increased hair testosterone but unaltered hair cortisol in female patients with borderline personality disorder.

A number of studies have reported on dysfunctions in steroid secretion, including altered cortisol and testosterone levels in borderline personality disorder (BDP) patients compared to healthy controls. The present study extends findings from blood and saliva studies to the cumulative measure of hair steroids. We investigated women with BPD (n=18) and age- and education-matched healthy women (n=17). We did not find differences between BPD patients and healthy women (p=0.40) concerning hair cortisol levels but increased hair testosterone levels among BPD patients compared to controls (p=0.03). These results remained when restricting the analyses to unmedicated patients. Our data indicate altered long-term testosterone but not cortisol levels in females with BPD. Future studies should address the possible impact of altered testosterone on medical illness processes including metabolic syndrome in this population.

Impact of Antenatal Glucocorticoid Therapy and Risk of Preterm Delivery on Intelligence in Term-Born Children.

CONTEXT: Women at risk of preterm delivery are routinely treated with synthetic glucocorticoids (sGCs). Although this therapy substantially reduces neonatal morbidity, concerns remain whether sGC excess may disrupt neurodevelopmental trajectories underlying cognitive functioning. OBJECTIVE: The present study is the first to disentangle direct effects of antenatal sGC treatment on possible long-term cognitive disadvantages from those of pregnancy complications and prematurity. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included a mixed-sex cohort of 222 term-born children (aged 6-11 years) consisting of three groups: children of mothers admitted to hospital for threatening preterm delivery who had been treated (n = 97) or untreated (n = 36) with sGCs, and controls without pregnancy complications (n = 89). INTERVENTION: Antenatal sGC treatment consisted of single courses with dexamethasone or betamethasone. MAIN OUTCOME MEASURE: Psychometric intelligence was assessed using a German adaption of Cattell's Culture Fair Test. RESULTS: Children born to mothers at risk for preterm delivery scored, on average, 6-7 IQ points below children of mothers without pregnancy complications, irrespective of antenatal sGC treatment. Compared to females, boys were found to be more susceptible to cognitive disadvantages associated with maternal risk for preterm delivery. CONCLUSIONS: Our data indicate that conditions related to a threatening preterm delivery rather than antenatal sGC treatment per se are associated with long-term decreases in the child's intelligence. Although these findings imply that a single course of sGC therapy does not aggravate long-term cognitive deficits, they highlight the need for interventions to reduce the detrimental consequences of distress induced by a threatening preterm delivery.

Hair cortisol and cortisol awakening response are associated with criteria of the metabolic syndrome in opposite directions.

Findings on the association between hypothalamic-pituitary-adrenal (HPA) axis activity and metabolic risk are equivocal. Different methods of measuring HPA activity might indicate adverse vs. beneficial effects of HPA activity on metabolic risk thus contributing to heterogenous findings. In this study, we aimed to determine whether (1) the salivary cortisol awakening response (CAR) as a marker of awakening-induced activation of the HPA axis and (2) hair cortisol as a marker of long-term cortisol secretion are associated with criteria of the metabolic syndrome. Therefore, we recruited 41 healthy individuals (26 women, mean age: 41.2 years) and 44 patients with major depression (28 women, 41.4 years) and assessed CAR and hair cortisol values as well as all criteria of the metabolic syndrome (abdominal obesity, blood pressure, plasma glucose, triglycerides and high-density cholesterol levels) according to the International Diabetes Federation. CAR and hair cortisol values were divided into tertiles. Across groups, participants with hair cortisol or hair cortisone in the highest tertile showed significantly more criteria of the metabolic syndrome compared to participants in the medium or low tertile (F2,64=3.37, p=.04). These results were corroborated by significant positive correlations between mean hair cortisol values with waist circumference (r=.29, p=.03), triglycerides (r=.34, p=.01) and systolic blood pressure (r=.29, p=.04) and between mean hair cortisone and triglycerides (r=.46, p<.01). In contrast, mean CAR values correlated negatively with diastolic (r=-.29, p=.03) and systolic blood pressure (r=-.32, p=.02). Our results indicate that higher hair cortisol and hair cortisone levels but lower CAR values are associated with an unfavorable metabolic and cardiovascular risk profile.

Elevated hair cortisol levels in chronically stressed dementia caregivers.

Hair cortisol concentrations (HCC) are assumed to reflect integrated long-term cortisol levels and have been proposed as a promising endocrine marker of chronic psychological stress. The current study examined HCC in relation to caregiving burden, a well-established naturalistic model of chronic stress in humans. HCC and relevant psychosocial data were examined in 20 caregivers of relatives with dementia and 20 non-caregiver controls matched for age and sex. Results revealed elevated HCC in dementia caregivers compared to non-caregiver controls (F(1,38)=4.4, p=.04, ηp2=.10). Further, within caregivers, a trend for a positive association of HCC with self-reported caregiving burden (r=.43, p=.058) and a positive association with depressiveness (r=.48, p=.045) were observed. No other associations between HCC and subjective measures were seen. These findings concur with the notion that HCC sensitively capture endocrine aberrations in stress-exposed groups.

Hair testosterone and visuospatial memory in middle-aged men and women with and without depressive symptoms.

BACKGROUND: Testosterone binds to androgen receptors, which can be found abundantly in the hippocampus. Associations between testosterone levels and visuospatial memory have been reported, albeit with inconsistent results. Previous studies have used point sampling of testosterone levels (blood, saliva) rather than long-term secretion measures. Hair analysis for steroids allows for retrospective ascertainment of cumulative steroid measures over several months. We examined hair testosterone and its association with verbal and visuospatial memory in middle-aged men and women with and without major depression. METHODS: We examined a total of 73 middle-aged individuals (35 depressed patients, and 38 age-, sex- and education-matched healthy subjects). We tested verbal (Auditory Verbal Learning Task) and visuospatial (Rey figure) memory and measured testosterone in the hair by liquid chromatography tandem mass spectrometry. RESULTS: Hair testosterone levels did not differ between patients and controls (mean 1.35pg/mg vs. 1.40pg/mg, SD 0.61 and 0.80, respectively). In men (n=24) but not women (n=49), hair testosterone was associated with visuospatial memory in a multiple regression analysis after controlling for age, education, body mass index, and depression (adjusted R(2)=0.56). CONCLUSIONS: With the new method of testosterone measurement in hair allowing for long-term cumulative ascertainment of testosterone secretion, we extend recent results of a male-specific role for testosterone in visuospatial memory.

Cortisol in hair, body mass index and stress-related measures.

Hair cortisol concentrations (HCC) are assumed to reflect integrated cortisol secretion over extended periods of time and may provide a sensitive marker for stress-associated endocrine changes. Here, we report data from two independent studies of 155 (study I) and 58 participants (study II) in which HCC associations with different stress-related measures and body mass index (BMI) were investigated. Consistent evidence for positive associations between HCC and BMI was seen across both studies (study I: r=.33, p<.001; study II: r=.42, p=.001). On the other hand, findings failed to reveal reliable HCC associations with psychosocial variables, showing only a positive relationship with self-reported social overload in study II (r=.29, p=.03) but not with other stress-related measures.

Elevated hair cortisol concentrations in endurance athletes.

Engaging in intensive aerobic exercise, specifically endurance sports, is associated with HPA axis activation indicated by elevated cortisol levels. Whether the repeated short-term elevations in cortisol levels result in higher long-term cortisol exposure of endurance athletes has been difficult to examine since traditional methods of cortisol assessments (saliva, blood, urine) reflect only relatively short time periods. Hair segment analysis provides a new method to assess cumulative cortisol secretion over prolonged time periods in a retrospective fashion. The aim of this study was to investigate cumulative cortisol secretion over several months reflecting intensive training and competitive races by examining hair cortisol levels of endurance athletes. Hair samples were obtained from 304 amateur endurance athletes (long-distance runners, triathletes, cyclists) and 70 controls. Cortisol concentrations were determined in the first to third 3-cm hair segments most proximal to the scalp. In addition, self-report measures of training volume were obtained. Endurance athletes exhibited higher cortisol levels in all three hair segments compared to controls (p<.001). Positive correlations between the cortisol concentration in the first hair segment and each indicator of training volume were found (all p<.01). These data suggest that repeated physical stress of intensive training and competitive races among endurance athletes is associated with elevated cortisol exposure over prolonged periods of time. These findings may have important implications with regard to somatic and mental health of athletes which should be investigated in future research.

Intraindividual stability of hair cortisol concentrations.

The analysis of cortisol in human hair constitutes a promising method for the retrospective assessment of cumulative cortisol secretion over extended periods of time. An implicit assumption underlying the use of this method is that in the absence of major life changes hair cortisol concentrations show a high level of intraindividual stability, i.e. single hair cortisol assessments exhibit considerable trait-specificity and are only to a smaller extent influenced by state-dependent factors. Here, we present data from two independent studies examining patterns of intraindividual stability in hair cortisol levels. In study I, 45 participants were examined at two sampling points carried out one year apart from each other. In study II, 64 individuals provided data at three sampling points which occurred at two-month intervals. In both studies, at each time point hair was sampled and relevant psychosocial and hair-related variables were assessed. Results of both studies consistently revealed strong test-retest associations for repeated hair cortisol measurements ('r's between 0.68 and 0.79, 'p's <0.0001). Findings of structural equation modelling applied to data of study II showed that single hair cortisol assessments comprise a strong trait component, explaining between 59 and 82% of variance, and are only to a lesser extent influenced by state-related factors. Only inconsistent evidence for covariation of changes in hair cortisol concentrations and simultaneous changes in perceived stress or other relevant variables was seen across the two studies. The current findings suggest a considerable degree of intraindividual stability in hair cortisol levels which highlights the utility of this method for obtaining trait estimates of long-term cortisol secretion in psychoneuroendocrinological research.

Introducing a novel method to assess cumulative steroid concentrations: increased hair cortisol concentrations over 6 months in medicated patients with depression.

Depression has been linked to increased cortisol concentrations using point measures taken from urine, blood, or saliva samples. However, with regard to hypercortisolism-induced consequences, long-term cumulative cortisol burden is of relevance. Our objective was to use hair analysis as a new method to assess cortisol exposure over 6 months in depressed patients and healthy controls. We examined 23 depressed patients (8 men and 15 women, mean age: 41.6 years ( ± standard deviation (SD), 13.1 years); mean duration of current depressive episode 9 months ( ± SD, 13 months)) and 64 healthy controls, matched for age and gender. Cortisol concentrations in two 3-cm hair segments from near to the scalp were analyzed, representing cortisol secretion during the 6 months prior to sampling. Compared with healthy individuals, depressed patients had higher hair cortisol concentrations in the first (mean ± SD: 26.7 ± 20.8 vs. 18.7 ± 11.5 pg/mg, p < 0.05) and second hair segment (mean ±  SD: 21.9 ± 23.7 vs. 13.4 ± 9.6 pg/mg, p < 0.05). In conclusion, hair cortisol analysis confirmed enhanced cortisol secretion in depressed patients over a prolonged time period. Because of the retrospective and cumulative nature of cortisol in hair, the assessment of hair cortisol concentration may help in addressing unanswered questions regarding hypothalamic-pituitary-adrenal axis overactivity and associated health consequences in psychiatric disorders.

Decreased hair cortisol concentrations in generalised anxiety disorder.

Previous research examining hypothalamic-pituitary-adrenal (HPA) axis activity in generalised anxiety disorder (GAD) has suggested a general hypercortisolism. These studies have mostly relied on salivary, plasma or urinary assessments, reflecting cortisol secretion over short time periods. The current study utilised the novel method of cortisol assessment in hair to obtain a retrospective index of cortisol secretion over a prolonged period of time. Hair cortisol levels were determined in 15 GAD patients and in 15 age- and gender-matched controls. In addition, participants collected six saliva samples (on awakening, +30 min, 12:00, 16:00, 20:00 h and at bedtime) on two consecutive weekdays for the assessment of the diurnal cortisol profile. Results revealed significantly lower (50-60%) cortisol levels in the first and second 3-cm hair segments of GAD patients compared to those of controls. No significant between-group differences were seen in diurnal cortisol profiles. The hair cortisol findings tentatively suggest that under naturalistic conditions GAD is associated with hypocortisolism. If corroborated by future research, this demonstrates the important qualities of cortisol measurement in hair as an ecologically valid, retrospective index of long-term cortisol secretion and as a marker for psychiatric disorders associated with hypo- or hypercortisolism.

Use of hair cortisol analysis to detect hypercortisolism during active drinking phases in alcohol-dependent individuals.

The assessment of cortisol levels in human hair has recently been suggested to provide a retrospective index of cumulative cortisol exposure over periods of up to 6 months. The current study examined the utility of hair cortisol analysis to retrospectively detect hypercortisolism during active drinking phases in alcoholics in acute withdrawal (n=23), the normalisation of cortisol output in abstinent alcoholics (n=25) and cortisol levels in age- and gender-matched controls (n=20). Scalp-near 3-cm hair segments were sampled and analysed for cortisol content. Results showed three to fourfold higher cortisol levels in hair samples of alcoholics in acute withdrawal than in those of abstinent alcoholics (p<.001) or controls (p<.001), with no differences between the latter two groups. The current hair cortisol findings closely mirror results of previous research using well-established measures of systemic cortisol secretion and thus provide further validation of this novel method.

Association of anhedonia with recurrent major adverse cardiac events and mortality 1 year after acute coronary syndrome.

CONTEXT: Depression consistently predicts recurrent events and mortality in patients with acute coronary syndrome (ACS), but it has 2 core diagnostic criteria with distinct biological correlates-depressed mood and anhedonia (loss of pleasure or interest). OBJECTIVE: To determine if depressed mood and/or anhedonia predict 1-year medical outcomes for patients with ACS. DESIGN: Observational cohort study of post-ACS patients hospitalized between May 2003 and June 2005. Within 1 week of admission, patients underwent a structured psychiatric interview assessing clinically impairing depressed mood, anhedonia, and major depressive episode (MDE). Also assessed were the Global Registry of Acute Coronary Events risk score, Charlson comorbidity index, left ventricular ejection fraction, antidepressant use, and depressive symptom severity using the Beck Depression Inventory. SETTING: Cardiac units of 3 university hospitals in New York and Connecticut. PARTICIPANTS: Consecutive sample of 453 patients with ACS (age, 25-93 years; 42% women). MAIN OUTCOMES MEASURES: All-cause mortality (ACM) and documented major adverse cardiac events (MACEs)-myocardial infarction, hospitalization for unstable angina, or urgent/emergency coronary revascularization)-actively surveyed for 1 year after admission. RESULTS: There were 67 events (16 deaths and 51 MACEs; 14.8%): 108 (24%) and 77 (17%) patients had anhedonia and depressed mood, respectively. Controlling for sex, age, and medical covariates, anhedonia (adjusted hazard ratio, 1.58; 95% confidence interval, 1.16-2.14; P < .01) was a significant predictor of combined MACE and ACM, but depressed mood was not. Anhedonia continued to significantly predict outcomes (P < .05) when additionally controlling for MDE diagnosis or depressive symptom severity. Findings were confirmed using depressed mood and anhedonia subscores from the Beck Depression Inventory in place of clinician interview ratings. CONCLUSIONS: Anhedonia identifies risk of MACE and ACM beyond that of established medical prognostic indicators, including MDE and depressive symptom severity. Correlates of anhedonia may add to the understanding of the link between depression and heart disease.

Children with high-functioning autism show a normal cortisol awakening response (CAR).

Individuals with high-functioning autism spectrum disorders (HFA) show difficulties in the ability to react to change. A recent study suggested that variations in the functioning of the hypothalamus-pituitary-adrenal axis, especially in one of its markers--the cortisol awakening response (CAR)--may be related to those difficulties in adolescents with Asperger's syndrome. The current study investigated the CAR in a younger sample with diagnoses from the whole autism spectrum: A group of children with HFA (N=15) was compared to a group of typically developing children (N=25). Findings suggest that the frequency of a CAR as well as the increase in cortisol levels from awakening to 30 min later were similar between groups, indicating that variations in the CAR in HFA may not be present early in life but only develop later in adolescence or may only occur in some diagnoses from the autism spectrum.

Visuospatial short-term memory explains deficits in tower task planning in high-functioning children with autism spectrum disorder.

Previous findings on planning abilities in individuals with high-functioning autism spectrum disorder (HFA) are inconsistent. Exploring possible reasons for these mixed findings, the current study investigated the involvement of memory in planning performance in 15 children with HFA and 17 typically developing controls. In addition to planning abilities (measured with the Tower of London), short-term memory and delayed recall for verbal as well as visuospatial material were assessed. Findings suggest that particularly reduced efficiency in visuospatial short-term memory is associated with Tower task planning deficits in children with HFA.

Hair as a retrospective calendar of cortisol production-Increased cortisol incorporation into hair in the third trimester of pregnancy.

Hair has long been used in toxicology, forensic science, doping control and other fields as a biological specimen for the detection of environmental agents, drugs, or toxins. Most recent evidence suggests that also hormones are incorporated and trapped inside the growing hair. This has led to the hypothesis that cortisol measurement of distinct hair segments could provide a retrospective calendar of cortisol production for the individual. In this first proof-of-concept study in humans, we analyzed cortisol in hair donated by mothers with a neonate child (n-Mothers; N=103), mothers with toddlers 3-9 months of age (t-Mothers; N=19), and control women (N=20). We cut hair strands from each women into at least three 3-cm segments, which, based on an average hair growth rate of 1cm per month, would represent hair grown over the past three, six, and nine months, respectively. Since in the third trimester of pregnancy there is a well-documented increased production of cortisol, we expected to see elevated levels of cortisol in the most proximal hair segment of women who had just given birth to a child (n-Mothers) compared with the control women. Likewise, we expected to see elevated levels in the second, third, or fourth segment of mothers of 3-month olds, 6-months olds, and 9-months olds, respectively. These hair segments, cut at 4-12 cm from the scalp, would represent hair grown throughout the third trimester of pregnancy. Results showed that there was a strong monotonic decline in cortisol concentration from the segment closest to the scalp to the most distal hair segment (p<0.0001). Cortisol levels decreased by 30-40% from one segment to the next for the most recent four hair segments. Segments from hair older than one year had similarly, low levels of cortisol. Comparisons of cortisol levels in hair between n-Mothers and control women yielded the expected results: cortisol levels in the first 3-cm hair segment (i.e., closest to the scalp) of n-Mothers were two-fold higher than in controls (p<0.0001), probably reflecting increased cortisol levels throughout the third trimester of pregnancy. No differences in cortisol content were apparent for the second or third 3-cm segments in n-Mothers (p>0.2). When hair from mothers with 6-9 months old toddlers was analyzed, the hair segment representing the third trimester period contained the same amount of cortisol as the hair grown more recently in mothers with 3-4 months old toddlers only. Age of the women, hair curvature, hair color, and frequency of hair washes per week were unrelated to cortisol levels. We conclude that cortisol measured in human hair can be a valid reflection of increased cortisol production for a period of up to six months. Due to a rapid decline of cortisol levels in human adult hair, a retrospective calendar of cortisol exposure may be limited to the past six months.

The cortisol awakening response (CAR): facts and future directions.

In humans, the secretion of cortisol from the adrenal glands follows a diurnal cycle with a profound increase after awakening. This increase after awakening, a phenomenon termed the cortisol awakening response (CAR), appears to be a distinct feature of the hypothalamus-pituitary-adrenal (HPA) axis, superimposing the circadian rhythmicity of cortisol secretion. Several studies point towards an important role of the hippocampus and, additionally, other brain structures (e. g. amygdala, prefrontal cortex, suprachiasmatic nucleus) in the regulation of the CAR. There is increasing knowledge that the CAR is influenced by a variety of factors such as gender, health status, and health behavior or stress perception. However, the exact function of the profound cortisol increase after awakening is still not clarified. We hypothesize that the anticipation of the upcoming day is of major relevance for the magnitude of the CAR. The present paper reviews the current knowledge on the neural regulation of the CAR and factors influencing this phenomenon and considerations are addressed concerning the exact function of the CAR.

Higher levels of central adiposity in healthy premenopausal women with family histories of premenopausal breast cancer.

Research strongly suggests that lower overall adiposity and higher central adiposity are independent risk factors for premenopausal breast cancer in the general population. We aimed to test the possibility that these factors may contribute to familial risk of premenopausal breast cancer. A convenience sample of healthy women, ages 25-49, was recruited to yield three study groups: (1) Women with first-degree family histories of premenopausal breast cancer, operationally defined as being diagnosed prior to age 50 (Group FH < 50, n = 39); (2) Women with first-degree family histories of postmenopausal breast cancer, operationally defined as being diagnosed at age 50 or after (Group FH > or = 50, n = 33); and (3) Women without a history of breast cancer in first-degree relatives (Group FH-, n = 132). Multinomial logistic regression analyses, including possible confounders, waist circumference, and BMI, revealed a lower BMI among FH < 50 compared to either FH- (OR = 0.72; 95% CI = 0.59-0.87), or FH > or = 50 women (OR = 0.75; 95% CI = 0.60-0.95), and higher waist circumferences in FH < 50 compared to either FH- (OR = 1.15; 95% CI = 1.06-1.25), or FH > or = 50 women (OR = 1.16; 95% CI = 1.05-1.28). No group differences were seen for waist skinfold measures. These results support the possibility that differences in patterns of adiposity may contribute to familial risk of premenopausal breast cancer, and suggest the importance of conducting large scale, population-based studies of the link between body size characteristics and familial breast cancer risk.