Age-associated alterations of brain mitochondria energetics.

The study aimed to explore the role of age-associated elevated cytosolic Ca2+ in changes of brain mitochondria energetic processes. Two groups of rats, young adults (4 months) and advanced old (24 months), were evaluated for potential alterations of mitochondrial parameters, the oxidative phosphorylation (OxPhos), membrane potential, calcium retention capacity, activity of glutamate/aspartate carrier (aralar), and ROS formation. We demonstrated that the brain mitochondria of older animals have a lower resistance to Ca2+ stress with resulting consequences. The suppressed complex I OxPhos and decreased membrane potential were accompanied by reduction of the Ca2+ threshold required for induction of mPTP. The Ca2+ binding sites of mitochondrial aralar mediated a lower activity of old brain mitochondria. The altered interaction between aralar and mPTP may underlie mitochondrial dysregulation leading to energetic depression during aging. At the advanced stages of aging, the declined metabolism is accompanied by the diminished oxidative background.

Magnetic resonance imaging validation of medial transthyroid ultrasound-guided stellate ganglion block: A pilot study.

OBJECTIVE: Ultrasound-guided stellate ganglion block (usSGB) facilitates improved accuracy of needle position and application of lesser volumes of local anesthetic (LA). Approaches of usSGB, however, have not fully been optimized with respect to efficacy and technical convenience. This pilot study examined the anatomical position and spatial distribution of a small volume of LA injectate dispensed by medial transthyroid usSGB via magnetic resonance imaging (MRI) and assessment of its effect on cervical sympathetic nerves. METHODS: Twelve healthy males were tested in a double-blinded within-subject design. In a total of 37 usSGB, 3 ml of LA and saline 0.9% solution were injected intramuscularly into the longus colli muscle (LCM) preventing uncontrollable spread of LA within cervical structures. Immediately after injection, distribution of injectate was traced by MRI. Twenty-four out of the 37 usSGB-injections with 3 ml ropivacaine 1% (verum) and saline 0.9% (placebo) were compared. Efficacy of usSGB was assessed by the appearance of oculosympathetic paresis and increases in skin temperature. RESULTS: All usSGBs were positioned in the proximity of the LCM muscle belly. Most of the axial injectate was distributed within the transversal plane between the middle section of C5 and the upper section of T1 vertebra. Signs of oculosympathetic paresis and skin temperature increase were found exclusively under verum conditions. CONCLUSION: This pilot study demonstrated the feasibility of medial transthyroid usSGB using an out-of-plane technique and a volume of 3 ml of LA. Further studies are required to establish the relative value and safety of this technique compared to other published approaches.

Ethical Pain and Terminal Chaperonage.

Terminal chaperonage embedded in palliative care deeply resonates with human needs and has undergone significant advances in the past decades. At the same time, it is in jeopardy due to austerity measures in healthcare. Its comprehensive translation in philanthropic end-of-life practice necessitates reflection on underlying ethical issues. This chapter addresses ethical aspects arising in pain and terminal chaperonage and deduces important ethical imperatives in the wake of the palliative mandate. The imperatives affect the deployment of resources necessary for a humane pain and terminal chaperonage, one that is to be comprehensive and flexible in design and implementation at the same time. Furthermore, they are concerned with critical implications for dying clients emerging from the idiosyncratic properties of opioids with respect to their potential to induce mental status alterations. Given that living and dying are profoundly mental by nature, the human mind plays a fundamental role in the command of both. Based on this, this chapter also outlines the essentials of terminal thought plasticity and affect catharsis en route to a mindful, decent death. It identifies and advocates eight most fundamental affective, respectively cognitive fields of the human mind, the "Ensemble of the essential eight iridescent fields of relinquishment", whose adaptable, culturally sensitive facilitation in mental management prior to death may have to be considered the core ethical imperative in terminal chaperonage - in true congruence with philanthropic end-of-life care.

Effectiveness, Safety, and Predictive Potential in Ultrasound-Guided Stellate Ganglion Blockades for the Treatment of Sympathetically Maintained Pain.

BACKGROUND: Evaluating the effectiveness of stellate ganglion blockades (SGBs) proves challenging, since the criteria defining a successful blockade are controversial. This may be one reason for the scarcity of studies on this topic, thus forcing clinical guidelines to remain conservative in recommending SGBs. Moreover, factors to predict which patients will benefit from blockade series are not yet available. OBJECTIVES: The objectives of this study were to evaluate through a clinical approach SGBs' effectiveness performed under ultrasound guidance (us-SGB) and to identify factors to predict effectiveness. METHODS: We retrospectively analyzed 809 us-SGBs in 105 patients with complex regional pain syndrome (CRPS) and neuropathic pain syndromes (all potentially including sympathetically maintained pain) regarding pain reduction. Volume and type of local anesthetics, magnitude of pain, temperature of the dorsal hands, heart rate, blood pressure, and occurrence of Horner's syndrome or complications were assessed. RESULTS: Pain reduction after a blockade series was highly significant and showed no significant correlation with change of temperature, vital signs, or Horner's syndrome. For patients with neuropathic pain, the predictive potential for pain reduction following a blockade series lies within the range of pain reduction after the first blockade. In a literature comparison, incidences of complications (hoarseness 3.9%, dysphagia 3.4%, hematoma 0.6%) were lower than in non-ultrasound-guided techniques. CONCLUSIONS: Data indicate that us-SGBs are safe and effective in reducing sympathetically maintained pain in patients with CRPS and neuropathic pain syndromes. Pain reduction after the first blockade may predict total pain reduction after a blockade series. Other clinical measures seem unsuitable to predict effectiveness.

Body-Related Emotions in Posttraumatic Stress Disorder Following Childhood Sexual Abuse.

Traumatic experiences are associated with emotions such as anxiety, shame, guilt, disgust, and anger. For patients who have experienced child sexual abuse, these emotions might be triggered by perceptions of their own body. The aim of this study was to investigate the extent of the association of the body to traumatic experiences and to discern the emotions linked to trauma-associated body areas. Ninety-seven female participants were assigned to four groups: post-traumatic stress disorder following child sexual abuse with co-occurring borderline personality disorder, post-traumatic stress disorder following child sexual abuse without co-occurring borderline personality disorder, borderline personality disorder without post-traumatic stress disorder, and healthy controls. Participants rated 26 body areas regarding their association with trauma and 7 emotions. Emotions were assessed by questionnaires. Results suggest that specific areas of the body are associated with trauma and linked to highly aversive emotions. In post-traumatic stress disorder patients, the areas associated with highly negative emotions were the pubic region and inner thighs. Thus, the patient's body may act as a trigger for traumatic memories.

Ultrasound-guided stellate ganglion blocks combined with pharmacological and occupational therapy in Complex Regional Pain Syndrome (CRPS): a pilot case series ad interim.

OBJECTIVE: This preliminary and retrospective pilot case series examines a treatment concept consisting of ultrasound-guided stellate ganglion blocks (SGBs) combined with pharmacological and occupational therapy in patients with complex regional pain syndrome (CRPS) of the hand. Efficacy of combined treatment concepts and safety of ultrasound-guided SGB have not been sufficiently investigated yet. METHODS: A total number of 156 blocks were evaluated in 16 patients with CRPS in a retrospective analysis. All patients received pharmacotherapy and a standard regimen of occupational therapy offered simultaneously to the SGBs. Changes in both spontaneous and evoked pain levels were assessed by numerical pain rating score before and after the last blockade of a series. Side effects were documented. RESULTS: The overall mean pain reduction was 63.2% regarding spontaneous and 45.3% regarding evoked pain. Mild complications, such as hoarseness or dysphagia, occurred in 13.5% of the blocks (21 SGBs). Serious complications, such as plexus paresis or accidental puncture of vessels or other structures, did not occur. Time between symptom onset and start of treatment did not affect the extent of pain reduction. CONCLUSIONS: The combination of ultrasound-guided SGB and simultaneous pharmacological and occupational therapy showed encouraging treatment results under conditions of this pilot case series. Assessment of efficacy of this combined treatment concept and safety of ultrasound-guided SGB require further prospective clinical studies with larger number of participants.

Body image in patients with posttraumatic stress disorder after childhood sexual abuse and co-occurring eating disorder.

BACKGROUND: Body image is a multidimensional construct with cognitive-affective, behavioral and perceptive components. Survivors of childhood sexual abuse report a disturbance of the cognitive-affective component of their body image but not of the perceptive component. It has not yet been examined whether and how the behavioral component is affected. Also, it is still unknown whether the disturbances might be due to the influence of co-occurring eating disorders. SAMPLING AND METHODS: The cognitive-affective and behavioral components of the body image of 84 female participants with posttraumatic stress disorder (PTSD) after childhood sexual abuse (31 with a co-occurring eating disorder) and 53 healthy participants were assessed via the Dresden Body Image Inventory (Dresdner Körperbildfragebogen-35, DKB-35) and the Body Image Avoidance Questionnaire (BIAQ). RESULTS: PTSD patients reported significantly higher negative scores on all DKB-35 subscales (p < 0.001) and the BIAQ (p = 0.002; p < 0.001). Results remained consistent after accounting for the influence of co-occurring eating disorders (p = 0.021; p = 0.001; p < 0.001). CONCLUSIONS: Results show for the first time that the behavioral component of the body image is impaired in female patients with PTSD in addition to the cognitive-affective component. This is not solely due to a comorbid eating disorder. The effect of established treatments on the body image of PTSD patients should be evaluated and new treatment modules should be developed and tested, if necessary.

Time-dependent alterations of cerebral proteins following short-term normobaric hyperoxia.

Sufficient oxygenation is indispensable for cognitive performance in mammals. In order to assure adequate oxygenation and to prevent hypoxia in medicine or aviation, different approaches of oxygen delivery are realized. With regard to hyperoxia, it is well known that it increases the risk of tissue toxicity and inflammation by generating radical oxygen species. However, this impact of hyperoxia on the expression of specific brain proteins has not been evaluated in detail yet. The present study analyzes time-dependent changes in protein expression in rat brain after a short-term exposure to normobaric hyperoxia. Thirty-six Wistar rats were randomly assigned to six different groups, three normobaric hyperoxia (NH) groups or three normobaric normoxia (NN) groups, each consisting of n = 6 animals. NH animals were exposed to 100% oxygen, NN rats to 21% oxygen, each group for 3 h. One group of NH and one group of NN were killed immediately after the 3 h, one group each after 3 days and one group each after 7 days. Rat brains were removed for analysis and whole brain detergent protein lysates were separated via two-dimensional gel electrophoresis followed by subsequent identification of protein expression alterations by peptide mass fingerprinting using mass spectrometry. Also, a functional network mapping and molecular pathway analysis were carried out. Statistical analysis was performed using analysis of variance (ANOVA) with Bonferroni correction using P < 0.01. Physiological parameters of the animals did not differ significantly between the two groups except for partial oxygen pressure (580 vs. 89 mmHg; P < 0.05). The expression of nine proteins was found to be significantly altered (five up-regulated: GOT1, CCT2, TCP1, G6PD, and ALB; four down-regulated: PEBP1, PRDX2, ENO1, and MDH1). IPA generated a network with eight focus proteins associated with pathways in "cell death, cancer, and signalling". Although hyperoxia was normobaric and induced for only 3 h, significant changes in brain protein expression were detectable immediately after the 3 h, after 3 days, as well as after 7 days. This may indicate effects on brain protein expression take place in the rat brain following a relatively short period of hyperoxia.

Alterations in rat serum proteome and metabolome as putative disease markers in sepsis.

OBJECTIVES: Despite a decreased mortality from sepsis, the absolute number of sepsis-related deaths has actually increased during the last years. At present, there are no biological markers available that can reliably assist early clinical diagnosis and the prompt initiation of therapy. This study investigated the changes in serum protein expression in a coecal ligature and puncture model of rat sepsis at 12, 24, and 48 hours after the induction of sepsis using differential proteomics. METHODS: Sixty-two male Wistar rats were randomly assigned to a sepsis group (coecal ligature and puncture; n = 46) or a sham group (n = 16). Surviving rats were killed 12 hour (n = 6), 24 hour (n = 9), or 48 hour (n = 4) after operation, and their serum lysates were subjected to two-dimensional gel electrophoresis and peptide mass fingerprinting. A systematic functional network mapping and molecular pathway analysis were performed using Ingenuity Pathways Analysis. RESULTS: Septic mortality was 58.7%, but no rat of the sham group was lost. Per gel, an average of 1,082 +/- 10 spots could be discriminated, of which 40 different protein spots were differentially expressed (p < 0.01). From the total of 40, the number of regulated protein spots was 13 (12 hour group) versus 10 (24 hour group) versus 18 (48 hour group). Ingenuity pathways analysis identified 10 of the differential proteins and allocated them to a pathway of tissue inflammation. CONCLUSIONS: The present study quantitatively detected several proteins differentially expressed in acute sepsis. Since a longer time-period was investigated and compared with previous studies, the results may offer new insights into septic organ dysfunction and altered protein pathways. The horizontal analysis of protein expression arrays and systematic biochemical pathways may represent an important new tool for the clinical assessment of septic conditions and support the development of early sepsis markers.

Protein expression differs between neural progenitor cells from the adult rat brain subventricular zone and olfactory bulb.

BACKGROUND: Neural progenitor cells can be isolated from various regions of the adult mammalian brain, including the forebrain structures of the subventricular zone and the olfactory bulb. Currently it is unknown whether functional differences in these progenitor cell populations can already be found on the molecular level. Therefore, we compared protein expression profiles between progenitor cells isolated from the subventricular zone and the olfactory bulb using a proteomic approach based on two-dimensional gel electrophoresis and mass spectrometry. The subventricular zone and the olfactory bulb are connected by the Rostral Migratory Stream (RMS), in which glial fibrillary acidic protein (GFAP)-positive cells guide neuroblasts. Recent literature suggested that these GFAP-positive cells possess neurogenic potential themselves. In the current study, we therefore compared the cultured neurospheres for the fraction of GFAP-positive cells and their morphology of over a prolonged period of time. RESULTS: We found significant differences in the protein expression patterns between subventricular zone and olfactory bulb neural progenitor cells. Of the differentially expressed protein spots, 105 were exclusively expressed in the subventricular zone, 23 showed a lower expression and 51 a higher expression in the olfactory bulb. The proteomic data showed that more proteins are differentially expressed in olfactory bulb progenitors with regard to proteins involved in differentiation and microenvironmental integration, as compared to the subventricular zone progenitors. Compared to 94% of all progenitors of the subventricular zone expressed GFAP, nearly none in the olfactory bulb cultures expressed GFAP. Both GFAP-positive subpopulations differed also in morphology, with the olfactory bulb cells showing more branching. No differences in growth characteristics such as doubling time, and passage lengths could be found over 26 consecutive passages in the two cultures. CONCLUSION: In this study, we describe differences in protein expression of neural progenitor populations isolated from two forebrain regions, the subventricular zone and the olfactory bulb. These subpopulations can be characterized by differential expression of marker proteins. We isolated fractions of progenitor cells with GFAP expression from both regions, but the GFAP-positive cells differed in number and morphology. Whereas in vitro growth characteristics of neural progenitors are preserved in both regions, our proteomic and immunohistochemical data suggest that progenitor cells from the two regions differ in morphology and functionality, but not in their proliferative capacity.

Reduction in rat phosphatidylethanolamine binding protein-1 (PEBP1) after chronic corticosterone treatment may be paralleled by cognitive impairment: a first study.

Chronic stress is associated with hippocampal atrophy and cognitive dysfunction. This study investigates how long-lasting administration of corticosterone as a mimic of experimentally induced stress affects psychometric performance and the expression of the phosphatidylethanolamine binding protein (PEBP1) in the adult hippocampus of one-year-old male rats. Psychometric investigations were conducted in rats before and after corticosterone treatment using a holeboard test system. Rats were randomly attributed to 2 groups (n = 7) for daily subcutaneous injection of either 26.8 mg/kg body weight corticosterone or sesame oil (vehicle control). Treatment was continued for 60 days, followed by cognitive retesting in the holeboard system. For protein analysis, the hippocampal proteome was separated by 2D electrophoresis (2DE) followed by image processing, statistical analysis, protein identification via peptide mass fingerprinting and gel matching and subsequent functional network mapping and molecular pathway analysis. Differential expression of PEBP1 was additionally quantified by Western blot analysis. Results show that chronic corticosterone significantly decreased rat hippocampal PEBP1 expression and induced a working and reference memory dysfunction. From this, we derive the preliminary hypothesis that PEBP1 may be a novel molecular mediator influencing cognitive integrity during chronic corticosterone exposure in rat hippocampus.

Causality of stem cell based neurogenesis and depression--to be or not to be, is that the question?

Mood disorders compose a considerable portion of the worldwide prevailing diseases with high suicide rates and urgent demand for novel therapeutic interventions as efficacious treatment is still lacking. Depression is thought to feature distinct morphological correlatives in the brain and has recently been linked to adult neurogenesis (NG) in the hippocampal formation. Numerous findings give rise to the hypothesis that depression and declining NG in the hippocampus may be causally connected. This implies that depressive symptoms could originate from impairments in NG and, vice versa, that improved NG could mediate antidepressant action and alleviate symptoms. Thus, great hopes rest on the question whether the observed increase in NG following antidepression treatment may have the potential to become a novel drug target and specific mechanism in the development of the next generation of antidepressants that specifically involves targeting of neuropoetic factors in addition to their "traditional" effects as modulators of synaptic transmission. Along the still hypothetical association of depression and NG, however, several controversies and unresolved questions exist with respect to the presently available data and interpretation. This article highlights and summarizes some of the most pressing issues and identifies the crucial ones that await urgent clarification and resolving. Without their reliable answering, the fascinating notion of a neurogenic basis for depression will remain to be greatly speculative.

Alterations in cerebral metabolomics and proteomic expression during sepsis.

The cause of brain dysfunction during sepsis and septic encephalopathy is still under ongoing research. Sepsis induced changes in cerebral protein expression may play a significant role in the understanding of septic encephalopathy. The aim of the present study was to explore cerebral proteome alterations in septic rats. Fifty-six male Wistar rats were randomly assigned to a sepsis group (coecal ligature and puncture, CLP) or a control group (sham). Surviving rats were killed 24 or 48 hours after surgery and whole-brain lysates were used for two-dimensional gel electrophoresis and subsequent protein identification. Differentially expressed proteins were identified by mass spectrometry. Using the Ingenuity Pathways Analysis (IPA) tool, the relationship and interaction between the identified proteins was analyzed. Mortality was 53 % in septic rats. No rat of the control group was lost. More than 1,100 spots per gel were discriminated of which 29 different proteins were significantly (2-fold, P<0.01) changed: 24 proteins down-regulated after 24 hours; two proteins up-regulated and three down-regulated after 48 hours. IPA identified 11 of 35 differentially regulated proteins allocating them to an existing inflammatory pathway. In the analysis of septic rat brains, multiple differentially expressed proteins associated with metabolism, signaling, and cell stress can be identified via proteome analysis, that may help to understand the development of septic encephalopathy.

The effects of sevoflurane anesthesia on rat brain proteins: a proteomic time-course analysis.

BACKGROUND: Recent studies showed changes in cerebral protein expression up to 3 days after desflurane anesthesia in rats. In the present study, we investigated the existence of persisting changes on the proteome level after sevoflurane anesthesia that persisted for as long as 28 days after anesthesia. METHODS: Rats were anesthetized by spontaneous inhalation of 2.4% sevoflurane in air for 3 h. Animals (n = 6 for each group) were killed either directly, 72 h, or 28 days after anesthesia. Brains were removed and subjected to global protein expression profiling based on two-dimensional gel electrophoresis and mass spectrometry. Expression factors were compared to results from untreated conscious animals at each time point. Data were statistically analyzed by ANOVA (P < 0.01) and a cut of more than two-fold change in the expression factor. RESULTS: We found 11 protein spots differentially regulated directly after anesthesia. Seventeen proteins were differentially expressed 72 h after the anesthesia. Only one spot was differentially regulated 28 days after anesthesia. The plausible targets of these differentially regulated proteins can be attributed to synaptic vesicle handling and cell-cell communication. CONCLUSIONS: Sevoflurane induced relevant changes in protein expression profiles directly and 72 h after an anesthesia with 1 MAC. Twenty-eight days after the anesthesia, all proteins except one had returned to baseline levels of abundance.

The heterogeneity of human mesenchymal stem cell preparations--evidence from simultaneous analysis of proteomes and transcriptomes.

OBJECTIVE: Mesenchymal stem cells (MSC) raise high hopes in clinical applications. However, the lack of common standards and a precise definition of MSC preparations remains a major obstacle in research and application of MSC. Whereas surface antigen markers have failed to precisely define this population, a combination of proteomic data and microarray data provides a new dimension for the definition of MSC preparations. METHODS: In our continuing effort to characterize MSC, we have analyzed the differential transcriptome and proteome expression profiles of MSC preparations isolated from human bone marrow under two different expansion media (BM-MSC-M1 and BM-MSC-M2). RESULTS: In proteomics, 136 protein spots were unambiguously identified by MALDI-TOF-MS and corresponding cDNA spots were selected on our "Human Transcriptome cDNA Microarray." Combination of datasets revealed a correlation in differential gene expression and protein expression of BM-MSC-M1 vs BM-MSC-M2. Genes involved in metabolism were more highly expressed in BM-MSC-M1, whereas genes involved in development, morphogenesis, extracellular matrix, and differentiation were more highly expressed in BM-MSC-M2. Interchanging culture conditions for 8 days revealed that differential expression was retained in several genes whereas it was altered in others. CONCLUSION: Our results have provided evidence that homogeneous BM-MSC preparations can reproducibly be isolated under standardized conditions, whereas culture conditions exert a prominent impact on transcriptome, proteome, and cellular organization of BM-MSC.

Changes in the serum proteome of patients with sepsis and septic shock.

BACKGROUND: Sepsis is still the leading cause of death in the intensive care unit. Our goal was to elucidate potential early differences in serum between survivors (SURV) and non-survivors (NON-SURV) on day 28. METHODS: We applied proteomic technology to serum samples of patients with sepsis and septic shock. Serum samples from 18 patients with sepsis and septic shock were obtained during the first 12 h after diagnosis of septic shock. Patients were grouped into SURV and NON-SURV on day 28. RESULTS: Seven patients survived and 11 patients died. Using proteome analysis, two-dimensional gel electrophoresis detected more than 200 spots per gel. A differential protein expression was discovered between SURV and NON-SURV, whereby protein alterations not yet described in sepsis were revealed. CONCLUSIONS: Our results show that proteomic profiling is a useful approach for detecting protein expression dynamics in septic patients, and may bring us closer to achieving a comprehensive molecular profiling compared with genetic studies alone.

Patient survey on Invisalign® treatment comparing [corrected] the SmartTrack® material to the previously used [corrected] aligner material.

OBJECTIVES: In 2013, a novel material SmartTrack® was introduced to replace the previous material used for Invisalign® aligners. We conducted this study to test how this transition was accepted by patients during ongoing Invisalign® treatment. METHODS: We surveyed a total of 72 patients (68 % women, 32 % men, mean age: 29.3 ± 9.2 years) who had worn the new material for a mean of 6 months. They completed a questionnaire with 25 items that compared both materials in terms of pain, pressure upon insertion, comfort, mucosal irritation, phonetics, discoloration, and taste. RESULTS: On a numerical rating scale (NRS) ranging from 0 to 10, the new aligner material was rated by the respondents to cause significantly (p < 0.001) less maximum pain than the old material (2.8 vs. 3.8). Significant reductions were obtained for duration of pain (p < 0.001) and duration of pressure (2.5 vs. 1.9 days; p = 0.001) upon insertion of the aligners. Over 90 % of the respondents indicated less or equal pain during eating, felt that the new material offered a tighter fit, and provided more favorable ratings for impairment, durability, and discoloration. Improved comfort was reported by 50 % of the respondents. CONCLUSIONS: The new material was favorably rated by the patients and showed significant reductions in pain intensity, pain duration, and pressure upon insertion. Important clinical parameters like overall comfort and impairment also were improved. The clinical effectiveness of the new material remains to be investigated.

No evidence for differential dose effects of hydrocortisone on intrusive memories in female patients with complex post-traumatic stress disorder--a randomized, double-blind, placebo-controlled, crossover study.

BACKGROUND: Post-traumatic stress disorder is characterized by intrusive traumatic memories. Presently, a controversial debate is ongoing regarding whether reduced cortisol secretion in post-traumatic stress disorder promotes an automatic retrieval of trauma-associated memories. Hence, a pharmacological elevation of cortisol was proposed to decrease post-traumatic stress disorder symptoms, particularly intrusions. The present study investigated the impact of two different doses of hydrocortisone on automatic memory retrieval using a randomized, double-blind, placebo-controlled, crossover study in 30 inpatients with post-traumatic stress disorder. METHODS: All participants were female and received various psychotropic medications. They were randomly assigned to one of two groups within a crossover design: they received either 1 week placebo followed by 1 week hydrocortisone 10/d, followed by 1 week placebo, followed by hydrocortisone 30 mg/d (15 participants) or 1 week hydrocortisone 30 mg/d, followed by 1 week placebo, followed by 1 week hydrocortisone 10 mg/d, followed by 1 week placebo (15 participants). The outcome measures were the frequency and the intensity of intrusions, the overall symptomatology of post-traumatic stress disorder and the general psychopathology. RESULTS: We did not find any differences in the frequency and the intensity of post-traumatic stress disorder-related intrusions between the 10 mg hydrocortisone, the 30 mg hydrocortisone and the placebo condition. All effect sizes for the hydrocortisone condition vs. placebo were very small. Additionally, the overall symptomatology of post-traumatic stress disorder and the general psychopathology did not differ between the hydrocortisone therapies and placebo. CONCLUSIONS: Our results do not show any effect of the hydrocortisone administration on intrusions in complex post-traumatic stress disorder.