Distraction versus focusing during VR exposure therapy for acrophobia: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: The therapeutic mechanisms of exposure therapy are not well understood. Research suggests that focusing on the most feared aspect might not be necessary, and that distraction with a low cognitive load (e.g., conversation) might enhance exposure. We aimed at systematically testing the efficacy of exposure therapy with focusing vs. conversational distraction, hypothesizing that distracted exposure would yield superior effects. METHODS: Thirty-eight patients with acrophobia (specific phobia of heights; clinician-determined) (free from relevant somatic or other mental disorders) were randomly assigned (1:1) to one virtual reality (VR) session of either focused (n = 20) or distracted exposure (n = 18). This monocentric trial took place at a psychiatric university hospital. RESULTS: Both conditions resulted in a significant reduction of acrophobic fear and avoidance, and a significant increase of self-efficacy (primary outcome variables). However, condition did not have a significant effect on any of these variables. Effects were stable at four-week follow-up. Heart rate and skin conductance level indicated significant arousal, but did not differ between conditions. LIMITATIONS: Eye-tracking was unavailable, nor did we assess emotions other than fear. Power was limited due to sample size. CONCLUSIONS: A balanced exposure protocol combining attention to fear cues with conversational distraction, while not being superior, might be as effective as focused exposure for acrophobia, at least during the initial stages of exposure therapy. These results support previous findings. This study demonstrates how VR can be exploited for therapy process research, as VR supports dismantling designs and the incorporation of online process measures.

Non-Hunner's Interstitial Cystitis Is Different from Hunner's Interstitial Cystitis and May Be Curable by Uterosacral Ligament Repair.

BACKGROUND: The posterior fornix syndrome (PFS) was first described in 1993 as a predictably occurring group of symptoms: chronic pelvic pain (CPP), urge, frequency, nocturia, emptying difficulties/urinary retention, caused by uterosacral ligament (USL) laxity, and cured by repair thereof. SUMMARY: Our hypothesis was that non-Hunner's interstitial cystitis (IC) and PFS are substantially equivalent conditions. The primary objective was to determine if there was a causal relationship between IC and pelvic organ prolapse (POP). The secondary objective was to assess whether other pelvic symptoms were present in patients with POP-related IC and if so, which ones? How often did they occur? A retrospective study was performed in 198 women who presented with CPP, uterine/apical prolapse (varying degrees), and PFS symptoms, all of whom had been treated by posterior USL sling repair. We compared their PFS symptoms with known definitions of IC, CPP, and bladder symptoms. To check our hypothesis for truth or falsity, we used a validated questionnaire, "simulated operations" (mechanically supporting USLs with a vaginal speculum test to test for reduction of urge and pain), transperineal ultrasound and urodynamics. KEY MESSAGES: 198 patients had CPP and 313 had urinary symptoms which conformed to the definition for non-Hunner's IC. The cure rate after USL sling repair was CPP 74%, urge incontinence 80%, frequency 79.6%, abnormal emptying 53%, nocturia 79%, obstructive defecation 80%. Our findings seem to support our hypothesis that non-Hunner's IC and PFS may be similar conditions; also, non-Hunner IC/BPS may be a separate or lesser disease entity from "Hunner lesion disease". More rigorous scientific investigation, preferably by RCT, will be required.

Atrial natriuretic peptide (ANP) as an endogenous anxiolytic in patients with heart failure? - No replication of previous results showing an inverse association of anxiety and plasma ANP parameters.

OBJECTIVE: An acute anxiolytic-like effect of atrial natriuretic peptide (ANP) has been demonstrated in several preclinical and clinical studies. In a so far singular study (Herrmann-Lingen et al., 2003), patients with congestive heart failure, who pathognomonicly display increased plasma ANP, showed a significant inverse association of anxiety symptoms and pro-ANP levels, giving rise to speculations about ANP as an endogenous anxiolytic. We tried to replicate and extend this preliminary finding. METHODS: In 56 patients suffering from heart failure with reduced left ventricular ejection fraction we measured ANP, mid-regional pro-ANP (MR-proANP) and cyclic guanosine monophosphate (cGMP) as plasma parameters of ANP functioning and characterized anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS) and in addition the State Trait Anxiety Inventory (STAI) for state anxiety. Spearman rank correlation coefficients were calculated. RESULTS: None of our plasma ANP parameters showed a significant association with anxiety symptoms as per HADS ratings. The same picture emerged with STAI state anxiety. ANP, MR-proANP and cGMP significantly correlated with each other. CONCLUSION: In another sample of patients with heart failure we were unable to replicate previous and preliminary cross-sectional findings of low anxiety in subjects with high plasma pro-ANP. Direct measurement of effector hormone ANP and its second messenger as well did not support our hypothesis. Chronically elevated ANP in heart failure might attenuate its potential anxiolytic effects. Longitudinal studies experimentally increasing ANP levels in anxious heart failure patients are needed to test if this approach has clinical psychotropic utility.

Symptoms of voiding dysfunction and other coexisting pelvic floor dysfunctions: the impact of transvaginal, mesh-augmented sacrospinous ligament fixation.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the prevalence for voiding dysfunction and if symptom improvement can be achieved by adequate pelvic floor surgery. METHODS: We evaluated the Propel Study data from 281 women with pelvic organ prolapse (POP) stage 2-4. Bother caused by obstructive micturition, voiding dysfunction, and coexisting pelvic floor symptoms were assessed using the Pelvic Floor Distress Inventory (PFDI) preoperatively and 6, 12, and 24 months after vaginal prolapse repair. Successful reconstruction (Pelvic Organ Prolapse Quantification [POP-Q] stage 0-I throughout the 2-year follow-up at all compartments, "responders"), was compared with all others ("non-responders"). RESULTS: Prevalence of voiding dysfunction was significantly reduced after surgery for all patients with "moderate" to "quite a bit" of bother ("R2") regarding all examined PFDI questions. Defects of the posterior/apical compartment and lower stage defects were found to cause obstructive micturition, which improved significantly after POP surgery. Six months after surgery, the prevalence of R2 for voiding dysfunction symptoms was reduced significantly for responders compared with non-responders. Significant reduction of R2 in patients with rectoceles could be shown for some PFDI questions, whereas the rate was lower in patients with cystoceles. Other pelvic floor symptoms often coexisted in patients with voiding dysfunction symptoms and improved significantly after surgery as well. CONCLUSIONS: Symptoms of voiding dysfunction are frequent in female patients with POP and can significantly improve after vaginal mesh-augmented prolapse repair even for posterior and minor defects. Before counseling patients to undergo POP surgery because of their obstructive symptoms, other causes of voiding dysfunction must first have been ruled out.

The impact of sacrospinous ligament fixation on pre-existing nocturia and co-existing pelvic floor dysfunction symptoms.

INTRODUCTION AND HYPOTHESIS: To evaluate whether nocturia and coexisting pelvic floor symptoms in women with pelvic organ prolapse (POP) can be improved by ligamentous fixation of apical vaginal prolapse to the sacrospinous ligament. METHODS: We evaluated the PROPEL study data from 281 women with pelvic organ prolapse stage > 2. Bothersome nocturia and coexisting pelvic floor symptoms were assessed with the Pelvic Floor Disorder Inventory (PFDI) questionnaire preoperatively and at 6, 12 and 24 months after successful vaginal prolapse repair. Women with successful reconstruction (POP-Q stage < 1 at all compartments throughout the 2-year follow-up), defined as anatomical "responders," were compared to the anatomical "non-responders." RESULTS: Among the patients completing all PFDI questions (N = 277), anatomical responders and non-responders were the groups of interest for our analysis. We found the occurrence rates of "moderate" or "quite a bit" of nocturia was significantly reduced after surgery in all subgroups (48.7% at baseline vs. 19.5% after 24 months). The occurrence of nocturia was halved for responders compared to non-responders (45.4% and 48.3% at baseline vs. 14% and 29.5% after 24 months). Anatomical non-responders still had a relevant improvement of POP-Q stages, especially in the apical compartment. Prevalence rates of co-existing over- and underactive bladder, fecal incontinence, defecation disorders and pain symptoms were also significantly reduced postoperatively. CONCLUSION: Nocturia can be associated with symptomatic POP, with improvements seen following vaginal ligamentous prolapse repair. We caution providers, however, when advising patients of the possible resolution of nocturia following POP reconstruction, that all other traditional etiologies of nocturia must first be ruled out.

Sleep in pituitary insufficient patients compared to patients with depression and healthy controls at baseline and after challenge with CRH.

Sleep disturbances are prevalent in both patients with pituitary insufficiency and with depression. The role of corticotropin releasing hormone (CRH), involved in sleep regulation, has not been fully clarified. Pituitary insufficiency is an ideal model for studying sleep-endocrine effects since no consecutive hormone releases and feedback effects occur after hormone administration. 11 male patients with a chronic insufficiency of the anterior pituitary gland (PI) and under stable hormonal substitution were studied during three consecutive nights in the sleep laboratory. The first night served for adapting to laboratory setting, during the second night placebo was administered and during the third night 4 × 50 µg CRH were injected in pulsatile fashion. Sleep parameters were additionally compared with those of 15 healthy male controls (C) and 15 male patients with depression (D). CRH administration was associated with a numerical increase of wake time (115 ± 15 to 131 ± 13 min) and a decrease of REM sleep (89 ± 8 to 80 ± 8 min), REM latency (69 ± 14 to 55 ± 9 min) and slow wave sleep (66 ± 16 to 57 ± 15 min). Yet, none of these changes reached statistical significance. PI showed a worse sleep profile as compared to both control groups, e.g. indicated by a significantly lower sleep efficiency index (PI:0.80 ± 0.03 vs. C:0.94 ± 0.01 vs. D:0.87 ± 0.03). In conclusion sleep-EEG changes after CRH in PI patients resemble those found in in part in patients with depression. Sleep in anterior pituitary insufficiency was impaired despite full hormonal substitution possibly suggesting an alteration of the receptor organisation of brain structures involved in sleep regulation.

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.

A low cost artisan tension-free tape technique cures pelvic organ prolapse and stress urinary incontinence - proof of concept.

INTRODUCTION: The primary cause of pelvic organ prolapse (POP) is weak cardinal/uterosacral (CL/USL) ligaments and for stress urinary incontinence, weak pubourethral ligaments (PUL). MATERIAL AND METHODS: A 1 cm wide tape cut from a mesh sheet was applied tension-free to reinforce already plicated CL/USLs for cure of prolapse and directly to PUL for cure of stress urinary incontinence (SUI). 40 tapes were inserted, 10 midurethrally for SUI and 30 for 2nd/3rd degree prolapse: 15 to uterosacral ligaments and 15 to cardinal ligaments. RESULTS: At 12 months follow-up there was 72% cure for POP, 70% for SUI and improvement in urge/nocturia symptoms in 82% of patients.At 36 months 8/15 patients were evaluated. Anatomic cure for POP III was 2/4, for POP I-II 6/6. CONCLUSIONS: Though a 'proof of concept' study, our results may be sufficient to provide, in time, an alternative individual pathway for surgeons wishing to provide more certainty to a prolapse repair than 'native tissue' for an individual patient. The method questions whether expensive mesh kits are really necessary: our data though small, actually part of a learning curve, was within 15 percentage points of more sophisticated, more expensive tensioned slings. Intraoperative complications were low with no tape erosions seen at 12 months. Further validation with larger prospective and comparative trials is required.

Copeptin in CCK-4-induced panic in healthy man: Sexual dimorphisms in secretion pattern and panic response, but no correlation of copeptin with panic symptoms.

Copeptin, the C-terminal part of the hypothalamic arginine vaspopressin (AVP) precursor, closely mirrors the production of AVP and was proposed as an easily measured novel marker of the individual stress level in man. First data in male volunteers proposed copeptin as a potential endocrine surrogate marker of cholecystokinin-tetrapeptide (CCK-4)-induced panic. We tried to replicate these pilot data and to extend them to the other sex. 46 healthy human subjects (29 men, 17 women) were given an intravenous bolus of 50 µg CCK-4. Basal and stimulated plasma copeptin was measured and panic symptoms were assessed using the Acute Panic Inventory (API). Basal copeptin was significantly lower in women vs. men, while men showed a significantly higher CCK-4-induced increase of copeptin. In contrast, female subjects displayed a signifcantly higher increase of API ratings by CCK-4. No significant correlations of panic symptoms and copeptin release induced by CCK-4 could be found, neither in man, nor in women, nor in the total sample. A sexual dimorphism in copeptin secretion and in panic response was demonstrated. Prior unexpected findings of copeptin release as an objective read-out of panic could not be replicated. The role of the vasopressinergic system in panic anxiety needs further study in panic patients and in healthy man, using also other panic provocation paradigms.

Cure of Underactive and Overactive Bladder Symptoms in Women by 1,671 Apical Sling Operations Gives Fresh Insights into Pathogenesis and Need for Definition Change.

INTRODUCTION: To check evidence that symptoms identical with those constituting "underactive bladder" (UAB) and "overactive bladder" (OAB) are caused by apical prolapse and cured by repair thereof. MATERIAL AND METHODS: After repair of apical prolapse by mesh tape reinforcement of lax uterosacral ligaments (USL) data form 1,671 women were retrospectively examined to determine the presence of OAB and UAB symptoms and to check, how many were cured surgically. Thereby 3 different techniques were performed: elevate (n = 277), "Posterior IVS" (n = 1,049), and TFS cardinal (CL)/USL (n = 345). RESULTS: Symptoms identical with those comprising UAB and OAB were cured in up to 80% of cases following surgical repair of the CL/USL complex. CONCLUSIONS: These symptoms may be consistent with symptoms of the posterior fornix syndrome, which comprises 4 main symptoms: micturition difficulties, urge/frequency, nocturia, chronic pelvic pain, all consequent on USL laxity. Surgical cure of OAB and UAB is inconsistent with existing definitions, which imply pathogenesis of the detrusor muscle itself. A reconsideration and reformulation of existing definitions may be required. Altering UAB definition to "bladder emptying difficulties" and return to former definitions for OAB such as "detrusor" or "bladder instability" may help to restore compatibility with surgical cure of these conditions.

Clinical score system in the treatment of Cushing's disease: failure to identify discriminative variables from the German Cushing's Registry.

PURPOSE: To develop a multidimensional and integrated clinical scoring instrument, that encompasses, summarizes and weights appropriately the desired clinical benefits of a treatment for Cushing's disease (CD). METHODS: A panel of 42 variables potentially relevant to the clinical course of CD was predefined by endocrinology experts taking into account relevant literature. Variables as well as biochemical disease activity assessed as urinary free cortisol (UFC) levels were evaluated at baseline and at least after 12 months in patients treated between 2012 and 2016 in two Munich-based academic centres of the German Cushing's Registry. The primary endpoint was the identification of variables whose changes from baseline to follow-up visit(s) could characterize well biochemical cured from not cured patients after 12 months. RESULTS: Ninety nine patients with at least two consecutive visits were enrolled. Biochemical data were available for 138 visit-pairs among which UFC was not controlled in 48 (34.8%) and controlled in 90 (65.2%) first visits. In 41 (29.7%) consecutive visits (visit-pairs) changes in biochemical activity categories was observed between visits; concretely: in 17 (12.3%) consecutive visits changing from previously controlled to not controlled, and in 24 (17.4%) from uncontrolled to controlled biochemical activity. Multivariate statistical analyses (especially analyses of variance) based on data of the 138 visit-pairs were performed in order to proof possible effects of biochemical activity on clinical benefits. However, in none of the considered 42 variables corresponding to quality of life-dimensions, laboratory, anthropometric, musculo-skeletal or other clinical areas any statistically significant differences between different categories of biochemical activity were observed. CONCLUSION: It was not possible to provide clinical key parameters in our population of patients with CD discriminating biochemical cured from non-cured patients and to construct a clinical scoring system reflecting clinical treatment benefits.

Can surgical reconstruction of vaginal and ligamentous laxity cure overactive bladder symptoms in women with pelvic organ prolapse?

OBJECTIVE: To examine the extent and intensity of the coexistence of overactive bladder (OAB) symptoms in women with pelvic organ prolapse (POP) and to evaluate the likelihood of OAB symptom improvement after surgical POP reconstruction over a period of 2 years. PATIENTS AND METHODS: The effectiveness of the transvaginal, single-incision 'Elevate' technique for anatomical cure of anterior/apical and posterior/apical vaginal prolapse has been previously reported in a prospective, multicentre study. This technique uses mesh arms attached to the sacrospinous ligaments to recreate apical ligamentous support. Using the same sample population as that used in the multicentre study (n = 281), we conducted the present sub-analysis focusing on estimating the extent of comorbidity between POP and OAB symptoms, as well as the effects of subsequent pelvic floor reconstruction on OAB symptoms over a long period. Assessments of POP and OAB symptom severity before and after surgery at 6, 12 and 24 months were obtained using the Pelvic Floor Distress Inventory (PFDI) questionnaire. RESULTS: Preoperatively, 70% of all POP patients reported moderate to severe OAB symptoms, with almost half (49.5%) noting severe OAB bother ('quite a bit bothersome') for one or more of the classic OAB symptom domains on the PFDI: 'daytime urinary frequency'; 'urinary urgency'; 'urinary urgency incontinence'; and/or 'nocturia'. In fact, across all four OAB symptom domains evaluated, there were significantly more severe symptoms ('quite a bit bothersome') than moderate ('moderately bothersome') or mild ('somewhat bothersome'): 26-31%, 13-21%, and 17-19% of patients, respectively. In patients with symptomatic POP >stage 2, there was no relationship between further degree of prolapse and presence of severity of OAB symptoms; however, patients with POP stage 2 had significantly more complaints regarding the items 'daytime urinary frequency' and 'urinary urgency incontinence' compared with those with stage 3-4 POP. Pelvic floor reconstructive surgery resulted in significant improvement in all OAB symptoms, which seemed to be stable over time. The cure rate of moderate-to-severe OAB complaints ranged between 60% and 80%, which was a durable improvement noted throughout 24 months. CONCLUSION: Results showed that POP was to a high degree accompanied by moderate-to-severe OAB complaints. Significant long-lasting improvements in bothersome OAB symptoms occurred after adequate surgical reconstruction of anterior/apical and posterior/apical vaginal support.

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.

Copeptin - A potential endocrine surrogate marker of CCK-4-induced panic symptoms?

Intravenous cholecystokinin-tetrapeptide (CCK-4) administration reliably and dose-dependently provokes panic anxiety in man, accompanied by adrenocorticotropic hormone (ACTH) and cortisol release. Preclinical findings suggest that behavioral and endocrine effects of CCK-4 are mediated via corticotropin-releasing hormone (CRH) release. Anxiogenic stimulation of the central CCK-receptors in man was shown to increase as well vasopressin (AVP), which acts synergistically with CRH as pituitary-adrenocortical axis stimulator during stress. Copeptin (CoP), the C-terminal part of pre-pro-AVP, is released in an equimolar ratio to AVP. It is more stable in the circulation and easier to determine than AVP and it was found to closely mirror the production of AVP. So far, CoP secretion has not been characterized during panic provocation. In 30 healthy male human subjects, we repeatedly measured CoP in plasma during a panic challenge and studied its correlation to Acute Panic Inventory (API) ratings and plasma ACTH and cortisol. CoP levels correlated positively with the increase in API ratings (r=0.41, p=0.03), while ACTH or cortisol did not (r=0.08, p=0.68 and r=0.12, p=0.53, respectively). CoP levels correlated also positively with ACTH (r=0.48, p=0.009) and cortisol (r=0.48, p=0.01) concentrations throughout the CCK-4 challenge. As expected, we found a positive correlation between plasma ACTH and cortisol levels (r=0.57, p=0.001). A vasopressinergic activation during CCK-4 induced panic was demonstrated, which was correlated positively to panic symptoms and pituitary-adrenocortical release. Our findings suggest a role of CoP as a potential surrogate marker of CCK-4 panic symptoms. Further studies are needed to replicate our results and to further clarify the role of CoP as a stress-sensitive hormone in different panic paradigms as well as in panic patients.

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.

Adrenocorticotropic hormone in serial cerebrospinal fluid in man - Subject to acute regulation by the hypothalamic-pituitary-adrenocortical system?

Acute regulation of adrenocorticotropic hormone (ACTH) in cerebrospinal fluid (CSF) by the hypothalamic-pituitary-adrenocortical system has not been investigated in man. In a pilot study in healthy male volunteers we measured ACTH every twenty minutes in serial CSF for three hours after an intravenous placebo, hydrocortisone (100mg) or insulin (2mg/kg) injection. No acute inhibitory or stimulatory effects of these interventions were discovered. Our results corroborate previous findings in rhesus monkeys. The regulation of CSF ACTH and its potential relevance for behavioral alterations in health and disease (e.g. major depression or anorexia nervosa) in humans need further study.

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.

Overnight suppression of HPA axis after mineraolocorticoid receptor stimulation: A sleep endocrine study.

Nocturnal hyperactivity of hypothalamic-pituitary-adrenal axis (HPA) indicates decreased feedback inhibition with stress-related conditions such as major depression and sleep disorders. To characterize the role of mineralocorticoid (MR) in regulation of HPA axis activity during nocturnal sleep and involvement in sleep architecture, we investigated sleep endocrine effects of the MR agonist fludrocortisone in healthy men after pretreatment with metyrapone to minimize the impact of endogenous cortisol. Subjects (n=8) were treated on three occasions in a single-blinded design in random order with a) metyrapone, b) fludrocortisone after metyrapone, and c) placebo. Polysomnography was recorded and blood samples were drawn for determination of adrenocorticotropic hormone (ACTH) and cortisol during the entire night. After metyrapone administration ACTH was significantly enhanced, while overall nocturnal cortisol secretion remained largely unchanged. Whereas administration of fludrocortisone induced a significant inhibitory effect on basal ACTH and cortisol secretion, no considerable effects on sleep pattern were detectable. While the involvement of MR in sleep regulation needs further study, endocrine findings underline the role of MR in tonic regulation of HPA axis during nocturnal sleep and demonstrate the ability of fludrocortisone to further suppress HPA axis activity overnight. Additional studies would be required to evaluate endocrine and clinical fludrocortisone effects in depressive patients showing HPA hyperactivity.