Reanalysis of the ß-ν[over ¯]_{e} Angular Correlation Measurement from the aSPECT Experiment with New Constraints on Fierz Interference.

On the basis of revisions of some of the systematic errors, we reanalyzed the electron-antineutrino angular correlation (a coefficient) in free neutron decay inferred from the recoil energy spectrum of the protons which are detected in 4π by the aSPECT spectrometer. With a=-0.104 02(82) the new value differs only marginally from the one published in 2020. The experiment also has sensitivity to b, the Fierz interference term. From a correlated (b,a) fit to the proton recoil spectrum, we derive a limit of b=-0.0098(193) which translates into a somewhat improved 90% confidence interval region of -0.041≤b≤0.022 on this hypothetical term. Tighter constraints on b can be set from a combined [shown as superscript (c)] analysis of the PERKEO III (ß asymmetry) and aSPECT measurement which suggests a finite value of b with b^{(c)}=-0.0181±0.0065 deviating by 2.82σ from the standard model.

Depression, anxiety and PTSD symptoms before and during the COVID-19 pandemic in the UK.

BACKGROUND: The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors. METHOD: Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change. RESULTS: Prospective symptom analyses showed small decreases in depression (PHQ-9: -0.43 points) and anxiety [generalised anxiety disorder scale - 7 items (GAD)-7: -0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status. CONCLUSIONS: We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.

[Gene-based treatment in spinal muscular atrophy]. / Genetisch basierte Therapien bei spinaler Muskelatrophie.

BACKGROUND: The 5q-associated spinal muscular atrophy (SMA) affects ~ 80-120 newborns annually. The disease is characterized by progressive paresis involving the bulbar and respiratory musculatures. The phenotypes are very heterogeneous ranging from severe courses with early death in the first years of life to loss of gait in older age. OBJECTIVE: There are now an increasing number of causally targeted therapies available that can either directly interfere with the transcription of the gene causing the disease or replace the homozygous loss of the SMN1 gene. This work aims to elucidate the current state of therapy in different groups of patients with SMA. MATERIAL AND METHODS: Presentation of clinical trials and basic studies with a focus on patients with disease onset in adulthood. RESULTS: The clinical studies all show improvement or stabilization of motor function; however, in individual cases, the burden of the therapy for severely immobilized patients must be considered in addition to the efficacy in the treatment decision. Even if the drugs show a good safety profile, observations on the long-term efficacy and safety of the new substance classes are still lacking. CONCLUSION: The study landscape shows a good efficacy of the currently approved therapies across all degrees of severity and age groups. Due to the lack of comparative studies, the decision on the appropriate therapy should therefore be made according to an individual risk-benefit assessment.

Neuromodulation and Eating Disorders.

PURPOSE OF REVIEW: We review recent evidence on the use of neuromodulation for treating eating disorders (EDs), including anorexia nervosa, bulimia nervosa and binge eating disorder. We evaluate studies on (a) modern non-invasive methods of brain stimulation, such as transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), (b) electroconvulsive therapy (ECT) and (c) more invasive techniques, including deep brain stimulation (DBS). RECENT FINDINGS: Most reports on the clinical applications of neuromodulation in EDs are limited to case studies, case series and small clinical trials. The majority have focused on severe, enduring and hard-to-treat cases of AN. In this population, data suggest that both rTMS and DBS have therapeutic potential and are safe and acceptable. High-quality clinical trials in different ED populations are needed which investigate different stimulation methods, sites and parameters, the use of neuromodulation as stand-alone and/or adjunctive treatment, as well as the mechanisms of action.

Early weight gain trajectories in first episode anorexia: predictors of outcome for emerging adults in outpatient treatment.

BACKGROUND: Early response to treatment has been shown to be a predictor of later clinical outcomes in eating disorders (EDs). Specifically, early weight gain trajectories in anorexia nervosa (AN) have been shown to predict higher rates of later remission in inpatient treatment. However, no study has, as of yet, examined this phenomenon within outpatient treatment of first episode cases of AN or in emerging adults. METHODS: One hundred seven patients with AN, all between the ages of 16 and 25 and with an illness duration of < 3 years, received treatment via the first episode rapid early intervention in eating disorders (FREED) service pathway. Weight was recorded routinely across early treatment sessions and recovery outcomes (BMI > 18.5 kg/m2 and eating psychopathology) were assessed up to 1 year later. Early weight gain across the first 12 treatment sessions was investigated using latent growth mixture modelling to determine distinct classes of change. Follow-up clinical outcomes and remission rates were compared between classes, and individual and clinical characteristics at baseline (treatment start) were tested as potential predictors. RESULTS: Four classes of early treatment trajectory were identified. Three of these classes (n = 95), though differing in their early change trajectories, showed substantial improvement in clinical outcomes at final follow-up. One smaller class (n = 12), characterised by a 'higher' start BMI (> 17) and no early weight gain, showed negligible improvement 1 year later. Of the three treatment responding groups, levels of purging, depression, and patient reported carer expressed emotion (in the form of high expectations and low tolerance of the patient) determined class membership, although these findings were not significant after correcting for multiple testing. A higher BMI at treatment start was not sufficient to predict optimal clinical outcomes. CONCLUSION: First episode cases of AN treated via FREED fit into four distinct early response trajectory classes. These may represent subtypes of first episode AN patients. Three of these four trajectories included patients with substantial improvements 1 year later. For those in the non-response trajectory class, treatment adjustments or augmentations could be considered earlier, i.e., at treatment session 12.

A key feature of anorexia nervosa (AN) is an unhealthily low body weight. Previous studies show that more weight gained early in inpatient treatment leads to better outcomes. This study tried to see if this was also true for outpatients receiving treatment for the first time. All participants were emerging adults between the ages of 16 and 25 who had been ill for less than 3 years. Weight was recorded across the first 12 weekly treatment sessions. Statistics showed that the patients fit roughly into four different groups in early treatment, each with different starting weights and rates of weight gain in the first 12 treatment sessions. The group a patient belonged to could sometimes be predicted by vomiting behaviours, level of depression, and patients' perception of parental tolerance and expectations at the start of treatment. Out of the four groups, three did relatively well 1 year later, but one small group of patients did not. This small group had a higher starting weight than many of the other groups but did not gain any weight across the first 12 sessions. These patients could benefit from a change or increase in the amount or intensity of treatment after the first 12 treatment sessions.

Comparative efficacy and acceptability of psychological interventions for the treatment of adult outpatients with anorexia nervosa: a systematic review and network meta-analysis.

BACKGROUND: No consistent first-option psychological interventions for adult outpatients with anorexia nervosa emerges from guidelines. We aimed to compare stand-alone psychological interventions for adult outpatients with anorexia nervosa with a specific focus on body-mass index, eating disorder symptoms, and all-cause dropout rate. METHODS: In this systematic review and network meta-analysis, we assessed randomised controlled trials about stand-alone pharmacological or non-pharmacological treatments of adult outpatients with anorexia nervosa, defined according to standardised criteria, with data for at least two timepoints relating to either body-mass index or global eating disorder psychopathology. We searched Cochrane CENTRAL, CINAHL, MEDLINE, and PsychINFO for published and unpublished literature from inception until March 20, 2020. The primary outcomes were the change in body mass index and clinical symptoms, and the secondary outcome was all-cause dropout rate, which were all assessed for treatment as usual, cognitive behavioural therapy (CBT), Maudsley anorexia treatment for adults, family-based treatment, psychodynamic-oriented psychotherapies, a form of CBT targeting compulsive exercise, and cognitive remediation therapy followed by CBT. Global and local inconsistencies for the network meta-analysis were measured, and CINeMA was used to assess the confidence in evidence for primary outcomes. The protocol is registered in PROSPERO (CRD42017064429). FINDINGS: Of 14 003 studies assessed for their title and abstract, 16 (0·1%) randomised controlled trials for psychological treatments were included in the systematic review, of which 13 (0·1%) contributed to the network meta-analysis, with 1047 patients in total (of whom 1020 [97·4%] were female). None of the interventions outperformed treatment as usual in our primary outcomes, but the all-cause dropout rate was lower for CBT than for psychodynamic-oriented psychotherapies (OR 0·54, 95% CI 0·31-0·93). Heterogeneity or inconsistency emerged only for a few comparisons. Confidence in the evidence was low to very low. INTERPRETATION: Compared with treatment as usual, specific psychological treatments for adult outpatients with anorexia nervosa can be associated with modest improvements in terms of clinical course and quality of life, but no reliable evidence supports clear superiority or inferiority of the specific treatments that are recommended by clinical guidelines internationally. Our analysis is based on the best data from existing clinical studies, but these findings should not be seen as definitive or universally applicable. There is an urgent need to fund new research to develop and improve therapies for adults with anorexia nervosa. Meanwhile, to better understand the effects of available treatments, participant-level data should be made freely accessible to researchers to eventually identify whether specific subgroups of patients are more likely to respond to specific treatments. FUNDING: Flinders University, National Institute for Health Research Oxford Health Biomedical Research Centre.

Salivary cortisol response to psychosocial stress in the late evening depends on CRHR1 genotype.

The activation of the hypothalamus-pituitary-adrenal (HPA) axis is induced by stress. Imbalances in this system increase the risk of developing stress related disorders including mental illness. Variants in the single nucleotide polymorphism (SNP) rs110402 of the corticotropin-releasing hormone receptor type I (CRHR1) gene have been shown in interaction with childhood maltreatment to increase the vulnerability to develop depressive symptoms in adulthood. In this study, the direct contribution of polymorphism of the CRHR1 gene (rs110402) to the salivary cortisol response to stress independently from childhood adversity was investigated. Healthy young men between the ages of 18 and 30, free from childhood maltreatment and early trauma, were genotyped (n = 121). To increase the power of the genetic analysis, only homozygous carriers of the common C (n = 31) and of the rare T (n = 21) allele were selected for this study and exposed to a Trier Social Stress Test (TSST) in the late evening (22.30 to 22.40). Salivary samples for the assessment of cortisol and its inactive metabolite cortisone were taken early in the evening (20.00), just before (22.30) and immediately after (22.40) as well as 15 minutes after stress exposure (22.55). Participants with the TT genotype showed higher cortisol levels 15 minutes post stress compared to participants with the CC genotype. No genotype differences were found for cortisone. Interestingly, TT participants reported lower subjective perceived stress levels before the TSST, but not after stress exposure. These results confirm that variants of rs110402 in the CRHR1 gene contribute to an increased stress response. Contrary to previous findings, however, this effect could be observed in subjects reporting no exposure to childhood maltreatment or early trauma.

I.CAN: health coaching provides tailored nutrition and physical activity guidance to people diagnosed with cancer in a rural region in West Gippsland, Australia.

PURPOSE: I.CAN is a program which uses health coaching to provide tailored nutrition and physical activity guidance to people diagnosed with cancer in a rural region in eastern Victoria, Australia. I.CAN builds patients' nutritional knowledge, attitudes and health literacy to healthy eating and weight maintenance and incorporates sustainable and affordable dietary changes into everyday eating patterns. While oncology care identifies patients at risk of malnutrition and weight loss, less attention has been placed on building patient's capacity for healthy lifestyles and behaviours after cancer treatment. METHODS: I.CAN is delivered by a dietitian and exercise physiologist and is offered in three streams, one-on-one consultation, one-one-one and group and group. Paired t tests and chi-square analysis were used to analyse data. RESULTS: At 3-month review, I.CAN participants (1) significantly increased exercise activity from 51 to 86% (p < 0.001) and (2) showed increased trends in positive food choices from 62 to 66%. Importantly, positive food choices for alcohol and processed snacks were maintained, and there were increases in positive food choices for fresh fruit and vegetables, low fat dairy and processed meats. CONCLUSION: I.CAN is an example of a program which can be delivered within a rural setting, with minimal resources, and achieve positive impact for patients. IMPLICATIONS FOR CANCER SURVIVORS: Key to the success of the program is promoting wellness early in the cancer trajectory and providing patients with practical tools, a person-centred and multidisciplinary team approach and a program which is adaptable to the changing needs of the patient and the health service.

Confocal Raman microscopy in life sciences.

Microscopy techniques are widely used in life sciences to study cells and tissues. Fluorescence microscopy, for example, is a very common method in many laboratories. While reliable and strong fluorescence signals are a clear advantage of this method, the labelling procedure with fluorescent dyes, the availability of required antibodies or the potentially necessary genetic modifications of the studied organism all introduce potential complications. By contrast, confocal Raman microscopy is a label-free and non-destructive imaging technique. In contrast to infrared microscopy, it is easily applicable in aqueous environments. Different microscope setups and combinations allow for the examination of various solid and liquid samples, even in their typical environments. The article demonstrates the analyzing capability of confocal Raman microscopy and correlative techniques through application examples of eukaryotic and prokaryotic cells, and cancerous and normal tissues and shows how confocal Raman microscopy provides valuable information for a more comprehensive understanding of the investigated sample.

Correction: Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa.

The fortieth author's name was listed incorrectly. The correct presentation is A Keski-Rahkonen.

The impact of an emotionally expressive writing intervention on eating pathology in female students.

Introduction: Previous research demonstrating emotional influences on eating and weight suggest that emotionally expressive writing may have a significant impact on reducing risk of eating pathology. This study examined the effects of writing about Intensely Positive Experiences on weight and disordered eating during a naturalistic stressor. Method: Seventy-one female students completed an expressive or a control writing task before a period of exams. Both groups were compared on BMI (kg/m2) and the Eating Disorder Examination - Questionnaire (EDE-Q) before the writing task and at 8-week follow-up. A number of secondary analyses were also examined (to identify potential mediators) including measures of attachment, social rank, self-criticism and self-reassurance, stress and mood. Results: There was a significant effect of intervention on changes in the subscales of the EDE-Q (p = .03). Specifically, expressive writers significantly reduced their dietary restraint while those in the control group did not. There was no significant effect of the intervention on changes in BMI or the other subscales of the EDE-Q (Eating, Weight and Shape Concern). There was also no effect of writing on any of the potential mediators in the secondary analyses. Discussion: Emotionally expressive writing may reduce the risk of dietary restraint in women but these findings should be accepted with caution. It is a simple and light touch intervention that has the potential to be widely applied. However, it remains for future research to replicate these results and to identify the mechanisms of action.

Efficacy and safety of single-dose onabotulinumtoxinA in the treatment of symptoms of osteoarthritis of the knee: results of a placebo-controlled, double-blind study.

OBJECTIVE: To evaluate intraarticular onabotulinumtoxinA 400 U and 200 U in reducing symptoms of knee osteoarthritis (OA) in patients with nociceptive pain. DESIGN: A multicenter, double-blind, randomized, placebo-controlled study was conducted in adults with knee OA and a painDETECT questionnaire score of ≤12 (indicating nociceptive pain). Patients were randomized to receive intraarticular onabotulinumtoxinA 400 U or 200 U or placebo (saline) in the study knee on a 1:1:2 ratio and were followed-up for 24 weeks posttreatment. The primary efficacy measure was the daily average numeric rating scale pain score for the study knee over 7 days at week 8. Secondary efficacy measures included the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function scores, the patient global impression of change score and the 7-day average worst pain score. RESULTS: Of the 176 enrolled patients, 158 completed the study. The daily average pain score was reduced by approximately two points for all treatments (week 8); the reduction was sustained throughout follow-up, with no significant between-group difference between onabotulinumtoxinA and placebo (both doses: 0.22 [95% confidence interval (CI): -0.33, 0.76]; 400 U: 0.42 [95% CI: -0.26, 1.10]; 200 U: -0.03 [95% CI: -0.70, 0.64]). Similar results were found for all secondary efficacy measures. Treatment-related adverse events occurred in 3.4% of the pooled onabotulinumtoxinA group and placebo group; none were serious. CONCLUSIONS: There were no significant differences between onabotulinumtoxinA and placebo in reducing average pain score at week 8 compared with baseline in patients with knee OA. No safety concerns were identified. CLINICALTRIALS. GOV IDENTIFIER: NCT02230956.

A multimodal microcharacterisation of trace-element zonation and crystallographic orientation in natural cassiterite by combining cathodoluminescence, EBSD, EPMA and contribution of confocal Raman-in-SEM imaging.

In cassiterite, tin is associated with metals (titanium, niobium, tantalum, indium, tungsten, iron, manganese, mercury). Knowledge of mineral chemistry and trace-element distribution is essential for: the understanding of ore formation, the exploration phase, the feasibility of ore treatment, and disposal/treatment of tailings after the exploitation phase. However, the availability of analytical methods make these characterisations difficult. We present a multitechnical approach to chemical and structural data that includes scanning electron microscopy (SEM)-based imaging and microanalysis techniques such as: secondary and backscattered electrons, cathodoluminescence (CL), electron probe microanalyser (EPMA), electron backscattered diffraction (EBSD) and confocal Raman-imaging integrated in a SEM (RISE). The presented results show the complementarity of the used analytical techniques. SEM, CL, EBSD, EPMA provide information from the interaction of an electron beam with minerals, leading to atomistic information about their composition, whereas RISE, Raman spectroscopy and imaging completes the studies with information about molecular vibrations, which are sensitive to structural modifications of the minerals. The correlation of Raman bands with the presence/absence of Nb, Ta, Fe (heterovalent substitution) and Ti (homovalent substitution) is established at a submicrometric scale. Combination of the different techniques makes it possible to establish a direct link between chemical and crystallographic data of cassiterite.

Advances in the treatment of anorexia nervosa: a review of established and emerging interventions.

BACKGROUND: Anorexia nervosa (AN) is a disabling, deadly and costly mental disorder. Until recently, treatment recommendations were based on expert opinion and limited evidence. The aim of this systematic review is to synthesise recent evidence on established and emerging AN treatments and to forecast trends for future developments. METHODS: We systematically review trials of established treatments and associated process outcome studies from the last 5 years, published since a previous review in this journal. 'Established' treatments were those that are widely used in AN, recommended by guidelines and/or have been tested in at least one large randomised controlled trial. Secondly, we summarise emerging treatments for AN, i.e. those that have only been (or are currently being) tested in proof-of concept, feasibility or pilot trials. RESULTS: We identified 19 published trials of established treatments (15 of high or moderate quality), mostly assessing psychological therapies (n = 17). We also found 11 published trials of emerging treatments, and a total of 34 registered, as yet unpublished trials. Promising emerging treatments include cognitive remediation therapy, exposure therapy and non-invasive neuromodulation. CONCLUSIONS: Evidence generation on the treatment of AN has dramatically accelerated, with our understanding of the role of family-based approaches for adolescents more nuanced and a range of psychological approaches available for the treatment of adults. Evidence on emerging treatments and from forthcoming trials suggests that there is a shift towards more targeted brain-based interventions. Future studies need to focus on elucidating mechanisms of action of treatments and what works best for whom.

Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa.

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10-6), and rs7700147, an intergenic variant (P=2.93 × 10-5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes.

A randomised controlled trial of three psychological treatments for anorexia nervosa.

BACKGROUND: There is a lack of evidence pointing to the efficacy of any specific psychotherapy for adults with anorexia nervosa (AN). The aim of this study was to compare three psychological treatments for AN: Specialist Supportive Clinical Management, Maudsley Model Anorexia Nervosa Treatment for Adults and Enhanced Cognitive Behavioural Therapy. METHOD: A multi-centre randomised controlled trial was conducted with outcomes assessed at pre-, mid- and post-treatment, and 6- and 12-month follow-up by researchers blind to treatment allocation. All analyses were intention-to-treat. One hundred and twenty individuals meeting diagnostic criteria for AN were recruited from outpatient treatment settings in three Australian cities and offered 25-40 sessions over a 10-month period. Primary outcomes were body mass index (BMI) and eating disorder psychopathology. Secondary outcomes included depression, anxiety, stress and psychosocial impairment. RESULTS: Treatment was completed by 60% of participants and 52.5% of the total sample completed 12-month follow-up. Completion rates did not differ between treatments. There were no significant differences between treatments on continuous outcomes; all resulted in clinically significant improvements in BMI, eating disorder psychopathology, general psychopathology and psychosocial impairment that were maintained over follow-up. There were no significant differences between treatments with regard to the achievement of a healthy weight (mean = 50%) or remission (mean = 28.3%) at 12-month follow-up. CONCLUSION: The findings add to the evidence base for these three psychological treatments for adults with AN, but the results underscore the need for continued efforts to improve outpatient treatments for this disorder. Trial Registration Australian New Zealand Clinical Trials Registry (ACTRN 12611000725965) http://www.anzctr.org.au/.

Affect systems, changes in body mass index, disordered eating and stress: an 18-month longitudinal study in women.

Background: Evidence suggests that stress plays a role in changes in body weight and disordered eating. The present study examined the effect of mood, affect systems (attachment and social rank) and affect regulatory processes (self-criticism, self-reassurance) on the stress process and how this impacts on changes in weight and disordered eating. Methods: A large sample of women participated in a community-based prospective, longitudinal online study in which measures of body mass index (BMI), disordered eating, perceived stress, attachment, social rank, mood and self-criticism/reassurance were measured at 6-monthly intervals over an 18-month period. Results: Latent Growth Curve Modelling showed that BMI increased over 18 months while stress and disordered eating decreased and that these changes were predicted by high baseline levels of these constructs. Independently of this, however, increases in stress predicted a reduction in BMI which was, itself, predicted by baseline levels of self-hatred and unfavourable social comparison. Conclusions: This study adds support to the evidence that stress is important in weight change. In addition, this is the first study to show in a longitudinal design, that social rank and self-criticism (as opposed to self-reassurance) at times of difficulty predict increases in stress and, thus, suggests a role for these constructs in weight regulation.

Genotype-phenotype dilemma in a case of sudden cardiac death with the E1053K mutation and a deletion in the SCN5A gene.

Mutations in the cardiac sodium channel gene SCN5A may result in various arrhythmia syndromes such as long QT syndrome type 3 (LQTS), Brugada syndrome (BrS), sick sinus syndrome (SSS), cardiac conduction diseases (CCD) and possibly dilated cardiomyopathy (DCM). In most of these inherited cardiac arrhythmia syndromes the phenotypical expression may range from asymptomatic phenotypes to sudden cardiac death (SCD). A 16-year-old female died during sleep. Autopsy did not reveal any explanation for her death and a genetic analysis was performed. A variant in the SCN5A gene (E1053K) that was previously described as disease causing was detected. Family members are carriers of the same E1053K variant, some even in a homozygous state, but surprisingly did not exhibit any pathological cardiac phenotype. Due to the lack of genotype-phenotype correlation further genetic studies were performed. A novel deletion in the promoter region of SCN5A was identified in the sudden death victim but was absent in other family members. These findings demonstrate the difficulties in interpreting the results of a family-based genetic screening and underline the phenotypic variability of SCN5A mutations.

Intranasal oxytocin reduces provoked symptoms in female patients with posttraumatic stress disorder despite exerting sympathomimetic and positive chronotropic effects in a randomized controlled trial.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a severe psychiatric disease accompanied by neuroendocrine changes such as adrenergic overdrive and hence an elevated cardiovascular morbidity. Current pharmacotherapeutic options for PTSD are less than suboptimal, necessitating the development of PTSD-specific drugs. Although the neuropeptide oxytocin has been repeatedly suggested to be effective in PTSD treatment, there are, to our knowledge, only three studies that have assessed its efficacy on the intensity of PTSD symptoms in PTSD patients - among them one symptom provocation study in male veterans. METHODS: To evaluate for the first time how oxytocin influences the intensity of provoked PTSD symptoms and, furthermore, cardiac control in female PTSD patients, we assessed their psychic and cardiac response to trauma-script exposure with and without oxytocin pretreatment in a double-blind randomized placebo-controlled study. We used a within-subject design to study 35 female PTSD patients who received oxytocin and placebo in a 2-week interval. Furthermore, we performed a small pilot study to get an idea of the relation of the stress-modulated endogenous oxytocin levels and heart rate - we correlated oxytocin serum levels with the heart rate of 10 healthy individuals before and after exposure to the Trier Social Stress Test (TSST). RESULTS: Intranasal oxytocin treatment was followed by a reduction of provoked total PTSD symptoms, in particular of avoidance, and by an elevation in baseline and maximum heart rate together with a drop in the pre-ejection period, a marker for sympathetic cardiac control. Furthermore, we found a positive correlation between endogenous oxytocin levels and heart rate both before and after TSST challenge in healthy control subjects. CONCLUSIONS: This study provides the first evidence that oxytocin treatment reduces the intensity of provoked PTSD symptoms in female PTSD patients. The small size of both samples and the heterogeneity of the patient sample restrict the generalizability of our findings. Future studies have to explore the gender dependency and the tolerability of the oxytocin-mediated increase in heart rate. This randomized controlled trial was retrospectively registered at the German Trials Register (DRKS00009399) on the 02 October 2015.

Perinatal hypothalamic-pituitary-adrenal axis regulation among women with eating disorders and their infants.

BACKGROUND: Psychiatric illness is associated with heightened hypothalamic-pituitary-adrenal (HPA) axis activity during pregnancy which may have long term effects on infant stress regulation. HPA axis regulation has not previously been investigated in women with eating disorders (ED) or their infants during the perinatal period. METHODS: Women were recruited to a prospective longitudinal study in three groups: 1) current or active ED (C-ED=31), 2) past ED (P-ED=29) and healthy control (HC=57). Maternal psychopathology, diurnal cortisol levels, corticotropin-releasing hormone (CRH) and CRH binding protein (CRH-BP) were measured during the third trimester of pregnancy. At eight weeks postpartum infant cortisol was obtained before and after routine immunisations to determine infant hormonal response to a stressful situation. RESULTS: Women with current ED had a significantly lower cortisol decline throughout the day compared to HC, in both adjusted and unadjusted analyses. Lower cortisol decline among women with a current ED were associated with higher levels of psychopathology during pregnancy. Women's cortisol awakening response, CRH and CRH-BP levels did not differ across the three groups. Infants' stress response was also significantly higher among those in the C-ED group, although this effect was attenuated after controlling for confounders. CONCLUSIONS: During pregnancy women with ED have lower cortisol declines, suggestive of blunted diurnal cortisol rhythms. Postnatally, their infants also have a heightened response to stress. This is the first study to identify HPA axis dysfunction in pregnancy in women with ED, and to show an intergenerational effect. Since dysfunctions in HPA activity during childhood may represent a risk factor for psychological and physical health problems later in life, further investigation of the potential long-term implications of these findings is crucial.