Cortisol, DHEA and DHEA-S during exposure therapy in patients with obsessive-compulsive disorder - secretion patterns and prediction of treatment response.

The cortisol response in patients with obsessive-compulsive disorder (OCD) during exposure with response prevention (ERP), a stressful but very effective psychotherapeutic treatment, has shown contradictory findings in three prior studies with low sample sizes. In a larger cohort of 51 patients with OCD we repeatedly measured subjective units of distress (SUD) and the adrenocortical stress hormones cortisol, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) in saliva during the very first session of ERP and on the day before. Expectedly, SUD were increased on the ERP day before the session and further rose during ERP, but salivary cortisol and DHEA were statistically indistinguishable from the comparison condition. Interestingly, DHEA-S was significantly elevated throughout the ERP versus the comparison day, but did not further increase in acute response to ERP. According to an explorative analysis in a subsample, hormone levels on the comparison or the ERP day did not predict anti-OCD treatment response one month later. These results corroborate our prior findings of cortisol non-response despite considerable subjective stress in ERP. The role of DHEA-S in anticipatory anxiety and the effects of augmentative cortisol therapy in ERP need further study.

Impact of physical or sexual childhood abuse on plasma DHEA, DHEA-S and cortisol in a low-dose dexamethasone suppression test and on cardiovascular risk parameters in adult patients with major depression or anxiety disorders.

While the impact of childhood trauma on basal and dynamic cortisol regulation has widely been studied, the most abundant steroid hormones dehydroepiandrosterone (DHEA) and its sulphated derivative DHEA-S have received little attention in this context. One-hundred in-door patients suffering from major depression or an anxiety disorder filled in the Childhood Trauma Questionaire. A low dose dexamethasone suppression test (DST) measuring DHEA, DHEA-S and cortisol was performed. Furthermore, various cardiovascular risk parameters were measured. Forty-six percent of the patients reported a history of substantial physical or sexual childhood abuse. However, no significant differences in plasma DHEA or DHEA-S emerged in the DST between the traumatised group and the remaining patients. Basal plasma cortisol was significantly lower in the childhood trauma group. No impact of childhood trauma history on cardiovascular risk factor profile was detected. Current limited data about DHEA or DHEA-S in patients with childhood trauma are equivocal. Further study using more sophisticated assessment of trauma history and simultaneously measuring a multitude of putative biomarkers of traumatization are needed.

Effects of 35% carbon dioxide (CO2) inhalation in patients with post-traumatic stress disorder (PTSD): A double-blind, randomized, placebo-controlled, cross-over trial.

BACKGROUND: In patients with post-traumatic stress disorder (PTSD) two open pilot studies about the effects of 35% carbon dioxide (CO2) exist. One shows an augmented panicogenic and anxiogenic response (Muhtz et al., 2011), the other does not (Talesnik et al. 2007). We further characterized the CO2 reactivity in PTSD using for the first time placebo-controlled and double-blind conditions. METHODS: In 20 patients with PTSD we assessed panic, anxiety, dissociative and PTSD symptoms after a single vital capacity inhalation of 35% CO2 compared to a placebo gas condition in a within-participant cross-over, placebo-controlled, double-blind and randomized design. RESULTS: Inhalation of 35% CO2 versus placebo provoked significantly increased panic, anxiety, dissociative and PTSD symptoms. The reaction to placebo gas was minimal. Order of inhalation, patients' sex or age did not influence the results. The panic and anxiety response under CO2 was considerably higher in the PTSD patients than in healthy controls from our previous open study. CONCLUSIONS: The results corroborate that our preceding findings of an increased CO2 reactivity in patients with PTSD are not false positive due to the open design or the lack of placebo control. Replication in a larger number of PTSD patients and matched control subjects is needed. The potential role of childhood traumatisation, psychiatric comorbidity, psychotropic medication and trait dissociation in prior contradictory reports should be clarified.

Investigation of implicit avoidance of displacement-related stimuli in offspring of trauma exposed, forcibly-displaced individuals.

There is an ongoing debate as to whether traumatization also affects the close relatives of trauma survivors who have symptoms of PTSD. Although many studies provide evidence favoring a transgenerational transmission, other studies have not found evidence to support this idea. The present study examined whether adult offspring of individuals exposed to trauma during forced displacement with (n=22) and without PTSD (n=24) exhibit an implicit avoidance of stimuli related to the parental trauma compared to children of non-trauma exposed control participants (n=23) using an Approach-Avoidance task (AAT). Offspring participants were requested to push (i.e., avoidance) or pull (i.e., approach) displacement-related and neutral pictures, whereby response direction depended on a non-affective dimension (color of the pictures). Results suggest that the offspring of non-PTSD participants exhibit implicit avoidance of displacement-related stimuli. This rather unexpected finding might either indicate resilience amongst offspring of PTSD participants or that offspring of non-PTSD participants are particularly affected. If these results were to replicate, they suggest that implicit avoidance tendencies amongst the offspring of trauma exposed participants might partially contribute to their heightened PTSD vulnerability. Longitudinal studies are needed to elucidate whether implicit avoidance tendencies are associated with increased stress vulnerability.

Performance in a blocked versus randomized emotional Stroop task in an aged, early traumatized group with and without posttraumatic stress symptoms.

BACKGROUND AND OBJECTIVES: Attentional biases (AB) for trauma-related stimuli have been examined in many studies assessing different trauma samples. In emotional Stroop tasks (EST), blocked and single-trial formats are used almost interchangeably in clinical research. There is reason to believe that different designs yield different results and assess different processes, which, however, has been hardly examined in studies. Furthermore, there is a dearth of information about AB in older trauma survivors with posttraumatic stress symptoms. METHODS: Older adults with (n = 20) and without PTSD symptoms (n = 26) as well as non-traumatized controls (n = 21) completed an EST, in which words were presented both blocked and randomized. RESULTS: Analyses revealed that individuals with PTSD symptoms showed AB for trauma- and depression-related words; however, mode of administration did not significantly influence reaction times. LIMITATIONS: The emotional Stroop task cannot disentangle the underlying cognitive mechanism (i.e., facilitation, interference, avoidance). CONCLUSIONS: PTSD symptoms in older trauma survivors are associated with AB. Overall, participants with PTSD symptoms did not show greater impairment of cognitive control in comparison to both control groups. Results also illustrate that methodological differences between task versions need to be considered more thoroughly.

Age effect on autobiographical memory specificity: A study on autobiographical memory specificity in elderly survivors of childhood trauma.

BACKGROUND AND OBJECTIVES: Post-traumatic stress disorder (PTSD) is accompanied by altered autobiographical memories (AM) of the traumatic incident itself as well as of non-trauma-related events. Several studies have shown that trauma-exposed individuals developing PTSD have a reduced capacity to access specific past events that are not related to the traumatic event compared to those who do not develop PTSD. However, one study including a group of elderly adults did not find significant differences in AM between PTSD and non-PTSD participants. The present study investigated whether PTSD is associated with impaired AM of trauma-related and non-trauma-related memories in the elderly. METHOD: Forty-four elderly participants, displaced during childhood from former German territories after the end of World War II (WWII), were examined. This group comprised 19 participants with and 25 participants without PTSD. These participants were compared to 23 non-traumatized non-displaced elderly participants. RESULTS: PTSD, non-PTSD and non-traumatized participants do not differ significantly in their ability to recall specific memories of their past. Moreover, participants with PTSD did not recall more trauma-related memories than non-PTSD participants. LIMITATIONS: The traumatized participants reached for assessment might represent the most resilient individuals, which might constrain generalizability of our results to other trauma populations. CONCLUSIONS: This study confirms preliminary evidence that PTSD is not associated with AM impairment in the elderly. We suggest that aging may alter the relationship between trauma and AM impairment in traumatized participants with PTSD, which need to be confirmed by longitudinal studies.

Auricular Acupuncture Versus Progressive Muscle Relaxation in Patients with Anxiety Disorders or Major Depressive Disorder: A Prospective Parallel Group Clinical Trial.

Although acupuncture treatment is increasingly in demand among psychiatric patients, to date no studies have investigated the effectiveness of auricular acupuncture (AA) in treating anxiety disorders or major depressive disorder. Thus, this study aimed to compare the effectiveness of AA versus progressive muscle relaxation (PMR), a standardized and accepted relaxation method. We examined 162 patients with a primary diagnosis of anxiety disorder or major depressive disorder, and each patient chose between treatment with AA, executed according to the National Acupuncture Detoxification Association protocol, and treatment with PMR. Each group had treatments twice a week for 4 weeks. Before and after treatment, each participant rated four items on a visual analog scale: anxiety, tension, anger/aggression, and mood. Statistical analyses were performed with the original visual analog scale scores and the Change-Intensity Index, an appropriate indicator of the difference between two values of a variable. Our results show that treatment with AA significantly decreased tension, anxiety, and anger/aggression throughout the 4 weeks, but did not elevate mood. Between AA and PMR, no statistically significant differences were found at any time. Thus, we suggest that both AA and PMR may be useful, equally-effective additional interventions in the treatment of the above-mentioned disorders.

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.

Autobiographical memory in adult offspring of traumatized parents with and without posttraumatic stress symptoms.

The present study examined potential transgenerational effects of trauma on autobiographical memory in adult offspring of elderly participants with and without PTSD symptoms who were exposed to an early trauma during childhood. As traumatization is associated with reduced memory specificity for past events, we hypothesized that offspring of traumatized parents might be exposed to a less elaborative narrative style, which, in turn, might result in less specific autobiographical memories in the offspring. Results show that autobiographical memory specificity did not differ significantly between adult offspring of traumatized elderly participants with PTSD symptoms, without PTSD symptoms, and non-traumatized elderly participants.

Metabotropic glutamate2/3 receptor agonism facilitates autonomic recovery after pharmacological panic challenge in healthy humans.

Group II metabotropic glutamate receptors (mGluR2/3) are suggested to modulate anxiety, arousal, and stress including autonomic control. However, no study has investigated mGluR2/3-related effects on baseline autonomic activity and reactivity to emotional challenge in humans as yet. Using a double-blind, randomized placebo-controlled, cross-over study design, we investigated the influence of a 1-week treatment with the mGluR2/3 agonist LY544344, prodrug of LY354740, on autonomic reactivity to a cholecystokinin tetrapeptide (CCK-4) panic challenge in eight healthy young men. The main outcome measures were time and frequency domain heart rate variability parameters during baseline, CCK-4 challenge, and recovery. There was no evidence for LY544344-mediated effects on baseline and CCK-4 challenge vagal activity, but a significantly lower recovery low frequency (%) and low frequency/high frequency ratio in the LY544344 group, suggesting enhanced autonomic recovery. This pilot study provides first human data indicating that mGluR2/3 agonism is involved in autonomic responsiveness, suggesting an important role of mGluR2/3 in central autonomic regulation.

Mental Health in Offspring of Traumatized Refugees with and without Post-traumatic Stress Disorder.

Intergenerational transmission of psychological trauma and the impact of parental post-traumatic stress disorder (PTSD) on offspring are controversially discussed. We studied 50 offspring (36 women and 14 men, mean age 42.1 years) of refugees who were severely traumatized as children at the end of World War II. From these, 25 of the refugees currently suffered from chronic PTSD, and 25 had no PTSD. Parental PTSD status did not significantly influence mental health [as per the Symptom Checklist (SCL)-90-R] or quality of life (assessed by the 36-item Short-form Health Survey) in their children. In the entire sample, frequency of talking with the mother about the flight correlated with phobic anxiety (r = 0.67, p = 0.03). Interestingly, the stated burden of having a parent with a history of flight significantly (p < 0.05) correlated with almost all subscales of the SCL-90-R. These results in a non-clinical sample do not support a specific role of parental PTSD in intergenerational trauma transmission. Our other remarkable, but preliminary, results need to be studied in larger samples using more subtle interaction or schema analyses. Copyright © 2015 John Wiley & Sons, Ltd.

Investigation of automatic avoidance in displaced individuals with chronic Posttraumatic Stress Disorder (PTSD).

Avoidance of trauma-related stimuli is a key feature of Posttraumatic Stress Disorder (PTSD). However, avoidance has almost exclusively been investigated with explicit measures targeting more strategic aspects of behavior. The aim of the present study was to examine automatic avoidance in older individuals displaced as children at the end of World War II with (n=22) and without PTSD (n=26) and in non-traumatized control participants (n=23) with an Approach-Avoidance Task (AAT). Participants were instructed to respond to the color (gray, brown) of trauma-related, neutral, and control pictures by pushing or pulling a joystick. Groups did not differ significantly as to their behavioral tendencies towards trauma-related pictures. Thus, there was no evidence for automatic avoidance in individuals with PTSD. However, high vigilance was associated with stronger implicit avoidance towards trauma-related pictures in the PTSD group. Several explanations for the non-significant results as well as implications and limitations of the present findings are discussed.

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.

Blunted autonomic reactivity to pharmacological panic challenge under long-term escitalopram treatment in healthy men.

BACKGROUND: Central serotonergic pathways influence brain areas involved in vagal cardiovascular regulation and, thereby, influence sympathetic efferent activity. Selective serotonin reuptake inhibitors (SSRIs) affect multiple serotonergic pathways, including central autonomic pathways. However, only a few studies have assessed SSRI-mediated effects on autonomic reactivity in healthy individuals using heart rate variability (HRV). METHODS: The present study assessed the influence of long-term treatment with escitalopram (ESC) on autonomic reactivity to an intravenous application of 50 µg cholecystokinin tetrapeptide (CCK-4) in 30 healthy young men using a double-blind, placebo (PLA)-controlled, randomized, within-subject cross-over design. Main outcome measures were time- and frequency-domain HRV parameters, assessed at both baseline and immediately after CCK-4 application. RESULTS: Results showed substantial effects for the treatment × CCK-4 challenge interaction with respect to heart rate (p < 0.001; pη(2) = 0.499), SDNN (p < 0.001; pη(2) = 576), RMSSD (p = 0.015; pη(2) = 194), NN50% (p = 0.008; pη(2) = 0.224), and LF% (p = 0.014; pη(2) = 0.196), and moderate effects with respect HF% (p = 0.099; pη(2) = 0.094), with PLA subjects showing a higher increase in HR and SDNN and a higher decrease in RMSSD, NN50, LF and HF than subjects in the ESC condition. Thus, ESC treatment significantly blunted the autonomic reactivity to CCK-4. Secondary analysis indicated no effect of the 5-HTTLPR polymorphism on CCK-4-induced autonomic response. CONCLUSIONS: Our results support findings suggesting an effect of SSRI treatment on autonomic regulation and provide evidence that ESC treatment is associated with blunted autonomic reactivity in healthy men.

The 5-HTTLPR genotype modulates heart rate variability and its adjustment by pharmacological panic challenge in healthy men.

Abnormal serotonin transporter (5-HTT) function and autonomic nervous system (ANS) dysregulation has been proposed in panic disorder. However, in contrast to hypothalamo-pituitary-adrenocortical (HPA) functioning, ANS reactivity during panic response has yet not been investigated in humans with respect to the 5-HTT genotype. The present study assessed the influence of challenging by cholecystokinin tetrapeptide (CCK-4) on heart rate variability (HRV) measures, to monitor autonomic reactivity and its relationship to 5-HTT-linked polymorphic region (5-HTTLPR) genotypes. We hypothesized substantial effects of the 5-HTTLPR genotype on autonomic reactivity. We studied 30 healthy young men, 15 of each with the long/long (l/l) or short/short (s/s) genotype for the 5-HTTLPR. All participants received an intravenous application of 50 µg CCK-4. HRV measures were assessed in both groups at baseline and immediately after CCK-4 application. Our results indicated lower parasympathetic activity in s/s carriers during baseline, time and frequency domain measures. CCK-4 application significantly enhanced the sympathetic tone in both groups, leading to diminished group differences. A significant treatment by genotype effect indicated reduced autonomic reactivity to CCK-4 challenge in the s/s compared to l/l carriers. Our findings show enhanced sympathetic and/or diminished cardiac vagal activity under basal conditions and blunted autonomic reactivity in s/s vs. l/l carriers. Our study provides novel data supporting claims that the s/s genotype represents a genetic vulnerability factor associated with inadequate hyporeactivity to stress and extends current knowledge on the impact of the central serotonergic activity on the sympathoadrenal pathway.

Depression, not PTSD, is associated with attentional biases for emotional visual cues in early traumatized individuals with PTSD.

Using variants of the emotional Stroop task (EST), a large number of studies demonstrated attentional biases in individuals with PTSD across different types of trauma. However, the specificity and robustness of the emotional Stroop effect in PTSD have been questioned recently. In particular, the paradigm cannot disentangle underlying cognitive mechanisms. Transgenerational studies provide evidence that consequences of trauma are not limited to the traumatized people, but extend to close relatives, especially the children. To further investigate attentional biases in PTSD and to shed light on the underlying cognitive mechanism(s), a spatial-cueing paradigm with pictures of different emotional valence (neutral, anxiety, depression, trauma) was administered to individuals displaced as children during World War II (WWII) with (n = 22) and without PTSD (n = 26) as well as to non-traumatized controls (n = 22). To assess whether parental PTSD is associated with biased information processing in children, each one adult offspring was also included in the study. PTSD was not associated with attentional biases for trauma-related stimuli. There was no evidence for a transgenerational transmission of biased information processing. However, when samples were regrouped based on current depression, a reduced inhibition of return (IOR) effect emerged for depression-related cues. IOR refers to the phenomenon that with longer intervals between cue and target the validity effect is reversed: uncued locations are associated with shorter and cued locations with longer RTs. The results diverge from EST studies and demonstrate that findings on attentional biases yield equivocal results across different paradigms. Attentional biases for trauma-related material may only appear for verbal but not for visual stimuli in an elderly population with childhood trauma with PTSD. Future studies should more closely investigate whether findings from younger trauma populations also manifest in older trauma survivors.

Neuropsychological functioning in posttraumatic stress disorder following forced displacement in older adults and their offspring.

The aim of the present study was to investigate neuropsychological performance in an untried trauma sample of older adults displaced during childhood at the end of World War II (WWII) with and without posttraumatic stress disorder (PTSD) as well as transgenerational effects of trauma and PTSD on their offspring. Displaced older adults with (n=20) and without PTSD (n=24) and nondisplaced healthy individuals (n=11) as well as one of their respective offspring were assessed with a large battery of cognitive tests (primarily targeting memory functioning). No evidence for deficits in neuropsychological performance was found in the aging group of displaced people with PTSD. Moreover, no group difference emerged in the offspring groups. Findings may be interpreted as first evidence for a rather resilient PTSD group of older adults that is available for assessment 60 years after displacement.

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.

(Meta)cognitive beliefs in posttraumatic stress disorder following forced displacement at the end of the Second World War in older adults and their offspring.

INTRODUCTION: The aim of the present study was to investigate (meta)cognitive beliefs related to posttraumatic stress disorder (PTSD) in a sample of individuals displaced as children at the end of the Second World War as well as transgenerational effects of trauma and PTSD on the offspring. METHODS: Displaced individuals with (n=20) and without PTSD (n=24) and nondisplaced healthy controls (n=11), as well as one of their adult offspring, were assessed with the Metacognitions Questionnaire (MCQ-30). Older adults, formerly displaced in childhood, were additionally assessed with the Posttraumatic Cognitions Inventory (PTCI). RESULTS: Dysfunctional beliefs (MCQ-30, PTCI) were particularly pronounced in formerly displaced individuals with PTSD, but not in the offspring generation. CONCLUSIONS: The findings suggest that in an aging group of displaced individuals with PTSD dysfunctional beliefs are associated with the disorder. Bias modification may help to attenuate symptomatology. No evidence was found for a transgenerational effect.