Faculty Bibliography

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.

OBJECTIVES/OBJECTIVE:We have previously reported that cognitive deficits are cross-sectionally associated with elevated cortisol in depressed patients. Here, we longitudinally examined if changes in cortisol secretion during treatment are associated with improvement of cognition. METHODS:Cognitive function and salivary cortisol levels were longitudinally examined in 52 patients with major depression before and after 3 weeks of standardized selective serotonin reuptake inhibitor (SSRI) and an add-on treatment modulating the mineralocorticoid receptor and compared to a healthy control group (n=50) matched for age, gender and years of education. RESULTS:Across add-on treatment groups, SSRI treatment reduced salivary cortisol in patients to levels of healthy controls (time×group interaction p=.05). In patients, reduction of cortisol significantly correlated with improvement in depressive symptoms (r=.52, p<.01), speed of information processing (r=.50, p<.01), and cognitive set-shifting (r=.34, p=.03). Improved depressive symptoms were only associated with improved attention and working memory. CONCLUSIONS:Improvement of some cognitive domains during SSRI treatment was associated with decreasing cortisol secretion and was only to a lesser extent associated with improved depressive symptoms.

BACKGROUND:Statins are among the most commonly prescribed medications worldwide. Although their benefits for cardiovascular disease are well established, the effects of statins on depressive symptoms are unknown. METHOD/METHODS:We examined the association between baseline statin use (2000-2002) and subsequent depressive symptoms in a prospective cohort study of 965 outpatients with coronary disease from 12 outpatient clinics in the San Francisco Bay Area. Depressive symptoms were assessed annually for 6 years using the Patient Health Questionnaire (PHQ) (primary outcome measure). We evaluated the cross-sectional association between statin use and risk of depressive symptoms at baseline and the longitudinal association between baseline statin use and risk of depressive symptoms during follow-up. RESULTS:Of the 965 participants, 629 (65%) used statins. At baseline, statin users had lower mean ± SE PHQ depression scores than nonusers (4.8 ± 0.2 vs 5.9 ± 0.3, P < .01). Statin users were less likely than nonusers to have depression (PHQ score ≥ 10) at baseline (17% vs 24%; P = .02) and during follow-up (28% vs 40%; P < .01). Among the 776 patients without depressive symptoms at baseline (PHQ < 10), statin use was associated with a 48% decreased odds of developing depression during follow-up (odds ratio [OR], 0.52; 95% CI, 0.38-0.73; P < .01). After we adjusted for potentially confounding variables, statin use remained associated with a 38% decreased odds of subsequent depression (adjusted OR, 0.62; 95% CI, 0.41-0.95; P = .02). CONCLUSIONS:We found that statin use was associated with a decreased risk of subsequent depressive symptoms in patients with coronary heart disease. Whether use of statins prevents depressive symptoms deserves further study.

OBJECTIVE:To investigate the association between childhood trauma and multiple sclerosis (MS) by comparing histories of child abuse and neglect between patients with MS and adults from the general population in a cross-sectional case-control study. Previous research has demonstrated a connection between MS and a variety of emotional stressors, but childhood trauma, which is known to have long-lasting negative consequences for physical health decades into adulthood, has not been studied. METHODS:The self-reported Childhood Trauma Questionnaire for the assessment of emotional, physical, and sexual abuse and emotional and physical neglect was administered to 234 patients with definite MS and 885 adults from the general population. RESULTS:After adjusting for sociodemographic factors and current depression, patients with MS scored significantly higher in all Childhood Trauma Questionnaire subscales apart from physical abuse and neglect than adults from the general population. Adjusted odds ratios for these types of childhood trauma were higher in the MS group than in controls, ranging from 2.0 for emotional neglect (95% confidence interval = 1.3-3.2) to 3.4 for emotional abuse (95% confidence interval = 2.0-5.7). Although childhood trauma was not associated with the degree of current MS-related disability, patients with MS with histories of physical and/or sexual abuse had significantly higher relapse rates than patients without early-life stress. CONCLUSIONS:Our findings suggest an association between childhood trauma and MS in this cross-sectional study. Larger prospective longitudinal studies are needed to clarify the relationship between early-life stress and the risk for MS in genetically susceptible individuals.

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

BACKGROUND: The hypothalamic-pituitary-adrenal axis is a major stress response system hypothesized to be involved in the pathogenesis of posttraumatic stress disorder (PTSD). However, few studies have prospectively examined the relationships among pre-exposure hypothalamic-pituitary-adrenal activity, acute stress reactions and PTSD. METHODS: Two hundred ninety-six police recruits were assessed during academy training before critical incident exposure and provided salivary cortisol at first awakening and after 30 minutes. A measure of cortisol awakening response (CAR) was computed as the change in cortisol level from the first to the second collection. At 12, 24, and 36 months following the start of active police service, officers were assessed for peritraumatic distress, peritraumatic dissociation, acute stress disorder (ASD) symptoms, and PTSD symptoms to their self-identified worst duty-related critical incident. Mixed models for repeated measures were used to analyze the effects of CAR on the outcome variables pooled across the three follow-up assessments. RESULTS: After controlling for time of awakening, first awakening cortisol levels, and cumulative critical incident stress exposure, CAR during academy training was associated with greater peritraumatic dissociation, beta = .14, z = 3.49, p < .0001, and greater ASD symptoms during police service assessed at 12, 24, and 36 months, beta = .09, Z = 2.03, p < .05, but not with peritraumatic distress, beta = .03, z = .81, p = .42, or PTSD symptoms, beta = -.004, z = -.09, p = .93. CONCLUSIONS: These findings suggest that greater cortisol response to awakening is a pre-exposure risk factor for peritraumatic dissociation and ASD symptoms during police service

OBJECTIVE: Major depressive disorder (MDD) has been associated with hypercortisolism, reduced glucocorticoid feedback sensitivity, and impaired memory function. In healthy subjects, administration of hydrocortisone impairs declarative memory. The aim of this study was to examine the effects of acute hydrocortisone administration on memory retrieval in MDD patients and healthy controls. We further tested whether the enhancing or impairing effects of hydrocortisone would prevail when it was given after encoding and when delayed retrieval was tested at a time point when glucocorticoid levels were still elevated. METHOD: In a placebo-controlled, double-blind crossover study, 44 patients with DSM-IV MDD and 51 healthy control participants received either placebo or 10 mg of hydrocortisone orally before memory testing. A word list paradigm and the Logical Memory Test from the Wechsler Memory Scale were applied. The study was conducted from April 2008 until April 2010 at sites in Bielefeld and Hamburg, Germany. RESULTS: In both memory tests, patients with MDD performed worse than controls. Healthy controls showed impaired memory performance after hydrocortisone administration compared to placebo. In contrast, hydrocortisone had no effects on memory in MDD patients. Furthermore, in healthy controls we found that administration of hydrocortisone immediately after learning did not lead to an enhanced free recall during increased cortisol levels. CONCLUSIONS: It appears that the impairing effects of hydrocortisone on memory performance are missing in patients with MDD. This might be interpreted in the context of reduced central glucocorticoid receptor functioning

PURPOSE OF REVIEW: The development of acute and posttraumatic stress symptoms after a traumatic event is common and often leads to personal distress, functional impairment, and economic consequences in trauma victims and their loved ones. Hence, the prevention of acute and chronic posttraumatic stress is an important public health priority. This article aims to review the current evidence regarding immediate (within hours) and early (within days and weeks) psychological and behavioral interventions to prevent posttraumatic stress symptoms. RECENT FINDINGS: Acute distress management, psychological debriefing and other immediate unspecific interventions within the first hours following a traumatic event have so far not demonstrated efficacy in preventing posttraumatic stress symptoms. So far, there are no randomized controlled trials (RCTs) that have examined immediate trauma-focused cognitive behavioral interventions. In contrast, some, but not many, studies have shown that cognitive behavioral interventions are efficacious if administered within days or weeks after a traumatic event. For other early interventions after trauma exposure, there is no, or only weak, evidence in support of their efficacy. However, conclusions are limited by the small numbers of trials examining immediate and early interventions. SUMMARY: Today, there is no empirical evidence to support any immediate intervention within hours after the traumatic event to prevent posttraumatic stress symptoms. With regard to early interventions in the first days or weeks after trauma, literature is also sparse, but supports brief cognitive behavioral interventions as a first choice. There is an urgent need for RCTs to examine if behavioral interventions immediately following a traumatic event might be able to reduce the burden of acute and posttraumatic stress symptoms

OBJECTIVE: Depression and fatigue are among the most common symptoms of multiple sclerosis (MS). These symptoms frequently co-occur and partially overlap in MS but their underlying biological substrates are unclear. In this study, the relative role of cytokines and hypothalamic-pituitary-adrenal (HPA) axis activity in depression and fatigue were examined in patients with relapsing-remitting MS (RRMS). METHODS: HPA axis function and frequency of stimulated cytokine (interferon gamma (IFNgamma) and tumour necrosis factor alpha (TNFalpha)) producing T cells was measured cross sectionally in 44 female patients with RRMS. All subjects completed a neurological examination, the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and self-report questionnaires. RESULTS: 10 patients met diagnostic criteria for major depressive disorder (MDD). MS patients with comorbid MDD showed normal morning but elevated evening salivary cortisol levels, resulting in a flattened slope. While a higher frequency of cytokine producing CD8+ T cells was also seen in MS patients with MDD, these markers were more closely associated with fatigue than depression. CONCLUSIONS: This study supports a role for HPA axis hyperactivity in major depression in MS. In addition, inflammatory and neuroendocrine factors may differentially mediate fatigue and depressive symptoms

Post-traumatic stress disorder (PTSD) is associated with elevated catecholamines and increased sympathetic arousal. However, it is unknown whether this condition is a pre-existing vulnerability factor for PTSD or an acquired result of either trauma exposure or the development of PTSD symptoms. We sought to examine if salivary 3-methoxy-4-hydroxy-phenylglycol (MHPG) in response to a laboratory stressor prior to critical incident exposure predicts the development of PTSD symptoms and if early childhood trauma influences this relationship. In a prospective cohort study, 349 urban police officers were assessed during academy training (baseline) and 243 were reassessed 12 months after the start of active duty (follow-up). At baseline, participants observed a video consisting of police critical incidents. Salivary MHPG was measured before and immediately after the challenge, and after 20min recovery. At follow-up, peritraumatic distress and PTSD symptoms were assessed in relationship to the worst critical incident during the past year. Participants with childhood trauma showed a trend towards higher MHPG increase to the challenge. Higher MHPG levels after 20min recovery were associated with both higher levels of peritraumatic distress and PTSD symptoms at follow-up. In a path analysis, elevated MHPG levels predicted higher peritraumatic distress which in turn predicted higher levels of PTSD symptoms while the direct effect of elevated MHPG levels on PTSD symptoms was no longer significant. Prolonged elevation of salivary MHPG in response to a laboratory stressor marks a predisposition to experience higher levels of peritraumatic distress and subsequently more PTSD symptoms following critical incident exposure