Brain morphometry and estimation of aging brain in subjects with congenital untreated isolated GH deficiency.

PURPOSE: Individuals with isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene have a normal life expectancy and above 50 years of age, similar total cognitive performance, with better attention and executive function than controls. Our objectives were to evaluate their brain morphometry and brain aging using MRI. METHODS: Thirteen IGHD and 14 controls matched by age, sex, and education, were enrolled. Quantitative volumetric data and cortical thickness were obtained by automatic segmentation using Freesurfer software. The volume of each brain region was normalized by the intracranial volume. The difference between the predicted brain age estimated by MRI using a trained neuronal network, and the chronological age, was obtained. p < 0.005 was considered significant and 0.005 < p < 0.05 as a suggestive evidence of difference. RESULTS: In IGHD, most absolute values of cortical thickness and regional brain volumes were similar to controls, but normalized volumes were greater in the white matter in the frontal pole and in the insula bilaterally, and in the gray matter, in the right insula and in left Caudate (p < 0.005 for all comparisons) We also noticed suggestive evidence of a larger volume in IGHD in left thalamus (p = 0.006), right thalamus (p = 0.025), right caudate (p = 0.046) and right putamen (p = 0.013). Predicted brain ages were similar between groups. CONCLUSION: IGHD is primarily associated with similar absolute brain measurements, and a set of larger normalized volumes, and does not appear to alter the process of brain aging.

Cognitive performance during senescence in untreated congenital isolated GH deficiency.

Individuals with untreated isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene from Itabaianinha Brazil have increased insulin sensitivity, normal life expectancy, and an extended health span, i.e. the period of life free from disabilities. We hypothesize that their prolonged health span is accompanied by a delayed cognitive decline in senescence. To test this hypothesis, we have administered the Literacy-Independent Cognitive Assessment (LICA) to 15 IGHD individuals aged over 50 years and 15 controls matched by age, sex, years of education, and percentage of illiteracy. All individuals were negative for HIV and syphilis serology, and there were no differences in serum levels of folate, vitamin B12 and TSH between the two groups, while free T4 was higher in the IGHD group. IGHD subjects had a higher total LICA score than controls, 215 (22.7) vs 204.2 (18.1), without reaching statistical significance. Scores of memory, visuoconstruction, language and calculation were similar between the two groups, with better attention (9.5 (1.4) vs 8.3 (1.1), P = 0.01) and executive function (38.3 (4.8) vs 35.1 (2.5), P = 0.03) scores in IGHD. MANCOVA revealed that group (but no age) had a significant effect on the LICA variables (partial eta squared of 0.455, power of 0.812, P = 0.02). This effect is verified on attention (partial eta squared 0.216, power of 0.749, P = 0.01) and executive function (partial eta squared 0.154, power of 0.570, P = 0.03. In conclusion, IGHD in senescence is associated with similar total cognitive performance but better attention and executive function than controls.

Copeptin response to panic provocation with CO2 in healthy adults.

Repeated panic attacks are the core symptom of panic disorder and severely stressful for patients. Additional to the psychological response, the physiological symptoms are an important aspect of the experienced panic. However, data on the extent of hypothalamic-pituitary-adrenal (HPA)-axis activation during panic attacks is inconsistent. Therefore, in the present study, we aimed at investigating the stress-axis activity in more detail by including Copeptin (CoP) as a stable surrogate parameter for the vasopressinergic hypothalamic activity during experimentally induced panic attacks in healthy adults (N = 21). During a placebo-controlled panic challenge with 35% CO2 compared to normal air inhalation, we measured CoP and the peripheral effector hormones Adrenocorticotropic Releasing Hormone (ACTH) and cortisol in plasma along with the psychological response to panic anxiety. We analyzed hormonal secretion patterns, their correlations and individual panic ratings over time and explored differences between female and male participants. We found a significant CO2-induced increase of CoP plasma levels and psychological panic symptoms after CO2-administration, while no positive correlations of CoP levels with the peripheral HPA-axis hormones and with panic symptoms were present. No differences between female and male participants concerning their psychological response nor their baseline CoP levels, the release of CoP or its increase during the experiment were found. CoP could be a sensitive indicator for an organism's physiologic acute hypothalamic response during stress and panic attacks.

Medication adherence with denosumab in patients with bone metastases from solid tumors treated in routine clinical settings: a retrospective study.

PURPOSE: To describe (non)adherence with denosumab among patients with solid tumors and bone metastases. METHODS: This retrospective, observational study pooled data from two completed prospective, multicenter cohort studies (X-TREME; Study 240) in adult patients with bone metastases from primary breast, prostate, lung, kidney, or other solid cancer types and administered denosumab 120 mg in routine clinical practice in Germany and Central and Eastern Europe. The studies were conducted between May 2012 and May 2017; pooled analysis was completed in August 2021. Medication adherence was described according to a three-component consensus taxonomy: initiation (first-ever administration ≤ 90 days from bone metastasis diagnosis), implementation (actual vs prescribed dosing; optimal implementation = regular/consistent dosing), and persistence (≤ 60-day gap between administrations at 3, 6, 9, and 12 months). Descriptive analyses were conducted for each cancer type. RESULTS: The analysis included 1748 patients with solid tumors and bone metastases. Adherence with denosumab was generally high across the initiation, implementation, and persistence phases. Most patients experienced timely initiation (from 64.4% [kidney cancer] to 81.2% [breast cancer]) and optimal implementation (from 62.4% [lung cancer] to 72.5% [breast cancer]). The proportion of patients who were persistent with treatment at 6 months ranged from 41.4% (lung cancer) to 77.8% (prostate cancer). CONCLUSIONS: This study revealed variations by cancer type in the initiation, implementation, and persistence of denosumab in patients with solid tumors and bone metastases in routine clinical practice. Further cancer-specific studies are warranted to examine the determinants of (non)adherence with denosumab, and potential ways to improve medication adherence.

Rotating Directional Solidification of Ternary Eutectic Microstructures in Bi-In-Sn: A Phase-Field Study.

For the first time, the experimental processing condition of a rotating directional solidification is simulated in this work, by means of a grand-potential-based phase-field model. To simulate the rotating directional solidification, a new simulation setup with a rotating temperature field is introduced. The newly developed configuration can be beneficent for a more precise study of the ongoing adjustment mechanisms during temperature gradient controlled solidification processes. Ad hoc, the solidification of the ternary eutectic system Bi-In-Sn with three distinct solid phases α,ß,δ is studied in this paper. For this system, accurate in situ observations of both directional and rotating directional solidification experiments exist, which makes the system favorable for the investigation. The two-dimensional simulation studies are performed for both solidification processes, considering the reported 2D patterns in the steady state growth of the bulk samples. The desired αßαδ phase ordering repeat unit is obtained within both simulation types. By considering anisotropy of the interfacial energies, experimentally reported tilted lamellae with respect to normal vectors of the solidification front, as well as predominant role of αß anisotropy in tilting phenomenon, are observed. The results are validated by using the Jackson-Hunt analysis and by comparing with the existing experimental data. The convincing agreements indicate the applicability of the introduced method.

Childhood Maltreatment in Individuals With Schizophrenia Spectrum Disorders: The Impact of Cut-Off Scores on Prevalence Rates.

Childhood maltreatment is a common phenomenon in various psychiatric disorders. Accordingly, patients with disorders from the schizophrenia spectrum (SSD) appear to have high prevalence rates of childhood maltreatment. However, the interpretation and comparability of prevalence rates is impeded by methodological weaknesses and differences such as measures and thresholds used in previous studies. Therefore, we aimed to provide and compare systematically captured data on prevalence rates of all common types of childhood maltreatment in patients with SSD using a standardized and well-established questionnaire and the most frequently used thresholds. The sample consisted of 48 patients with a primary diagnosis of SSD. 58.3-77.1% of the sample experienced at least one type of childhood maltreatment. Prevalence rates for physical abuse, physical neglect, and emotional abuse were dependent on the thresholds used, while equal rates were found for emotional neglect and sexual abuse. Physical neglect (46-67%), and emotional abuse (44-48%) were most commonly reported, followed by emotional neglect (38%), physical abuse (25-38%), and sexual abuse (25%). Additionally, high levels of peer victimization were reported by SSD patients. It appears that childhood maltreatment is a common phenomenon in SSD, even though methodological details, especially cut-off scores, have a substantial impact on the prevalence rates that are determined. Therefore, the methodology of studies should be closely examined when drawing conclusions from presented prevalence rates.

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.

[Implementation of Continuity of Care in Everyday Care - A Comparison Between two Psychiatric Hospitals]. / Umsetzung von Behandlungskontinuität im Versorgungsalltag ­ ein Vergleich zwischen zwei psychiatrischen Kliniken 1.

OBJECTIVE: The rigid separation of outpatient and inpatient care in the German health care system prevents continuity of care, although it has been shown to be of great importance for psychiatric patients. This study analyzes continuity of care of a model hospital with a global treatment budget according to §â€Š64b SGB V and constant treatment staff across all settings in comparison to a control hospital with regular financing without such a team. METHODS: In a prospective cohort study with a 20-month observation period, we collected data on continuity of care of 220 model and 215 control clinic patients. RESULTS: The model clinic achieved significant higher continuity of care than the control clinic, both during inpatient treatment at the time of recruitment and across all settings during the observation period. CONCLUSION: A global treatment budget can create the necessary conditions for more flexible psychiatric care and better implementation of continuity of care.

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.

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.

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.

Frequency of atrial thrombus formation in patients with atrial fibrillation under treatment with non-vitamin K oral anticoagulants in comparison to vitamin K antagonists: a systematic review and meta-analysis.

BACKGROUND: To assess the frequency of left atrium/left atrial appendage (LA/LAA) thrombus under treatment with non-vitamin K oral anticoagulants (NOACs) in comparison with vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (AF). METHODS: PubMed, Web of Science™, EMBASE and the Cochrane Library databases were searched for studies comparing NOACs with VKAs in AF patients who underwent diagnostic transoesophageal echocardiography (TEE). RESULTS: A total of four trials were considered eligible and were included in the meta-analysis. Four RCTs comprising n = 2397 AF patients (NOACs: n = 1412, VKAs: n = 985) were included in the meta-analysis. The frequency of LA/LAA thrombus formation under treatment with NOACs was similar to VKAs [odds ratio (OR) 1.14, 95% confidence intervals (95% CIs) 0.97-1.65, p = 0.48]. Both treatment groups revealed an approximately 5% frequency of thrombus formation, although a precise calculation is not possible due to Simpson paradox. Indications of heterogeneity between the included trials were not found (χ2 test p = 0.99, I2 = 0%). CONCLUSIONS: The findings of this meta-analysis suggest that NOACs are similar to VKAs regarding the frequency of LA/LAA thrombus in patients with AF. An unknown number of patients in the original studies did not receive sufficient anticoagulation for at least 3 weeks prior to TEE examination, and therefore the present results should be interpreted with caution. Systematic review registration- http://www.crd.york.ac.uk/PROSPERO . Unique identifier: PROSPERO CRD42017059293.

"Association splitting" versus cognitive remediation in obsessive-compulsive disorder: A randomized controlled trial.

Studies have confirmed the efficacy of the cognitive intervention Association Splitting (AS) in obsessive-compulsive disorder (OCD) when applied as a self-help technique. AS aims to alter symptom-provoking automated cognitive networks of OC-related stimuli by building new or strengthening established but weak neutral associations. The aim of this study was to investigate the acceptance and benefits of therapist-assisted AS as an add-on to cognitive behavioral therapy (CBT). One hundred and nine patients with OCD who were undergoing CBT were randomly assigned to either AS or cognitive remediation (CR). Both groups were assessed at baseline, 4 weeks and 6 months later. The primary measure was the Yale-Brown Obsessive Compulsive Scale. Although patients' acceptance of AS was good, AS was not better than CR regarding overall symptom severity. However, a larger decrease was found from baseline to 6 months follow-up in AS regarding avoidance. Moreover, subsidiary analyses excluding control patients who had obtained information about AS indicated its superiority. Because superiority of AS was found in post hoc analyses excluding control patients who had obtained information on AS, we suggest that contagion effects deserve consideration.

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.

Incidence of left atrial abnormalities under treatment with dabigatran, rivaroxaban, and vitamin K antagonists.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran or rivaroxaban are alternatives to vitamin K antagonists (VKAs) for prevention of stroke and systemic embolism in patients with atrial fibrillation (AF) and atrial flutter (AFL). Incidences of risk factors for left atrium (LA) and left atrial appendage (LAA) thrombus formation, such as dense spontaneous echo contrast (SEC), low LAA velocity (LAAV) <20 cm/s under treatment with dabigatran and rivaroxaban in comparison with VKAs are unknown. METHODS: We studied 306 patients with AF (94 %) and AFL (6 %) undergoing transesophageal echocardiography. Patients received VKAs (n = 138), dabigatran (n = 68), or rivaroxaban (n = 100) for at least 3 weeks prior to investigation. Time in therapeutic range was 67 % for VKA. Mean CHADS2 score and CHA2DS2-VASc score were 1.3 and 2.5, respectively. Left atrial abnormality was defined as either dense SEC, low LAAV <20 cm/s, or thrombus. RESULTS: Any LA abnormality occurred in 9, 3, and 5 % of patients receiving VKA, dabigatran, and rivaroxaban, respectively. The most frequent abnormality was LAA thrombus (VKA: 4 %, dabigatran: 0 %, rivaroxaban: 2 %) and low LAAV of less than 20 cm/s (VKA: 4 %, dabigatran: 1 %, rivaroxaban: 1 %), followed by dense SEC (VKA: 2 %, dabigatran: 1 %, rivaroxaban: 2 %). Results of uni- and multivariate analyses revealed a numerically lower but not significantly different frequency of any LA abnormality under dabigatran (OR 0.4, 95 % Cl 0.08 - 1.88, p = 0.25) and rivaroxaban (OR 0.65, 95 % Cl 0.22 - 1.98, p = 0.45) compared to VKA. CONCLUSION: With respect to the incidence of LA abnormalities, dabigatran and rivaroxaban are not inferior to VKA.

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.

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.