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Person-centred care (PCC) is associated with improved patient well-being and higher levels of satisfaction with care but its impact on individuals living with obesity is not well-established. The main aim of this study was to assess the relationship between PCC and the physical and social well-being of patients living with obesity, as well as their satisfaction with care. This study is based on a cross-sectional, web-based survey administered among a representative panel of Dutch individuals living with obesity. The primary outcomes were physical and social well-being and satisfaction with care. The primary exposure was a rating of overall PCC, encompassing its eight dimensions. In addition, covariates considered in the analyses included sex, age, marital status, education level, body mass index, and chronic illness. The data from a total of 590 participants were analysed using descriptive statistics, correlation analyses, and multiple regression analyses. Among PCC dimensions, participants rated 'access to care' the highest (M 4.1, SD 0.6), while 'coordination of care' (M 3.5, SD 0.8) was rated lower than all other dimensions. Participants' overall PCC ratings were positively correlated with their physical (r = 0.255, P < .001) and social well-being (r = 0.289, P < .001) and their satisfaction with care (r = 0.788, P < .001), as were the separate dimension scores. After controlling for sex, age, marital status, education level, body mass index, and chronic illness in the regression analyses, participants' overall PCC ratings were positively related to their physical (β = 0.24, P < .001) and social well-being (β = 0.26, P < .001), and satisfaction with care (β = 0.79, P < .001). PCC holds promise for improved outcomes among patients living with obesity, both in terms of physical and social well-being, as well as satisfaction with care. This is an important finding, particularly when considering the profound physical, social, and psychological consequences associated with obesity. In addition to highlighting the potential benefits of PCC in the healthcare of individuals living with obesity, the findings offer valuable insights into strategies for further refining the provision of PCC to meet the specific needs of these patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Quality in Health Care.)

Most patients with GNB1 encephalopathy have developmental delay and/or intellectual disability, brain anomalies and seizures. Recently, two cases with GNB1 encephalopathy caused by haploinsufficiency have been reported that also show a Prader-Willi-like phenotype of childhood hypotonia and severe obesity. Here we present three new cases from our expert centre for genetic obesity in which GNB1 truncating and splice variants, probably leading to haploinsufficiency, were identified. They all have obesity, hyperphagia and intellectual deficit. The clinical cases and their weight courses are presented, together with a review of all 68 published cases with GNB1 encephalopathy. Information on weight was not mentioned in most of these articles, so we contacted authors for additional clinical information on weight status and hyperphagia. Of the 42 patients whose weight status we could determine, obesity was present in 8 patients (19%). Obesity is significantly over-represented in the group with truncating and splicing variants. In this group, we see an obesity prevalence of 75%. Since GNB1 has been linked to several key genes in the hypothalamic leptin-melanocortin pathway, which regulates satiety and energy expenditure, our data support the potential association between GNB1 haploinsufficiency and genetic obesity. We also suggest GNB1 is a candidate gene for the known obesity phenotype of the 1p36 microdeletion syndrome given this chromosomal region includes the GNB1 gene. Knowledge of an additional obesity phenotype is important for prognosis, early interventions against obesity and awareness when prescribing weight-inducing medication., (© 2024 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Purpose: The focus of measuring success in obesity treatment is shifting from weight loss to patients' health and quality of life. The objective of this study was to select a core set of patient-reported outcomes and patient-reported outcome measures to be used in clinical obesity care., Materials and Methods: The Standardizing Quality of Life in Obesity Treatment III, face-to-face hybrid consensus meeting, including people living with obesity as well as healthcare providers, was held in Maastricht, the Netherlands, in 2022. It was preceded by two prior multinational consensus meetings and a systematic review., Results: The meeting was attended by 27 participants, representing twelve countries from five continents. The participants included healthcare providers, such as surgeons, endocrinologists, dietitians, psychologists, researchers, and people living with obesity, most of whom were involved in patient representative networks. Three patient-reported outcome measures (patient-reported outcomes) were selected: the Impact of Weight on Quality of Life-Lite (self-esteem) measure, the BODY-Q (physical function, physical symptoms, psychological function, social function, eating behavior, and body image), and the Quality of Life for Obesity Surgery questionnaire (excess skin). No patient-reported outcome measure was selected for stigma., Conclusion: A core set of patient-reported outcomes and patient-reported outcome measures for measuring quality of life in clinical obesity care is established incorporating patients' and experts' opinions. This set should be used as a minimum for measuring quality of life in routine clinical practice. It is essential that individual patient-reported outcome measure scores are shared with people living with obesity in order to enhance patient engagement and shared decision-making., (© 2024. The Author(s).)

Background: Rare genetic obesity commonly features early-onset obesity, hyperphagia, and therapy-resistance to lifestyle interventions. Pharmacotherapy is often required to treat hyperphagia and induce weight loss. We describe clinical outcomes of glucagon-like peptide-1 analogue liraglutide or naltrexone-bupropion treatment in adults with molecularly confirmed genetic obesity (MCGO) or highly suspected for genetic obesity without definite diagnosis (HSGO)., Methods: We conducted a real-world cohort study at the Obesity Center CGG at Erasmus University Center, Rotterdam, Netherlands, between March 19, 2019, and August 14, 2023. All patients with MCGO and HSGO who were treated with either liraglutide or naltrexone-bupropion were included. Liraglutide 3 mg and naltrexone-bupropion were administered according to the manufacturer's protocol. Treatment evaluation occurred short-term, after 12 weeks on maximum or highest-tolerated dose, preceded by the 4-5 week dose escalation phase. Differences in anthropometrics, body composition, metabolic markers, self-reported appetite, eating behaviour, and quality of life (QoL) were evaluated., Findings: Ninety-eight adults were included in the analysis: 23 patients with MCGO and 75 patients with HSGO, with median BMI of 42.0 kg/m 2 (IQR 38.7-48.2) and 43.7 kg/m 2 (IQR 38.0-48.7), respectively. After liraglutide treatment, median weight at evaluation significantly decreased compared to baseline in both groups: -4.7% (IQR -6.0 to -1.5) in patients with MCGO and -5.2% (IQR -8.1 to -3.5) in patients with HSGO. Additionally, improvements were observed in appetite, fat mass, fasting glucose, and HbA1c in both patients with MCGO and with HSGO. Patients with HSGO also reported significant improvements in several domains of QoL and eating behaviour. In patients with MCGO and HSGO treated with naltrexone-bupropion, mean weight at evaluation significantly differed from baseline: -5.2% ± 5.8 in patients with MCGO and -4.4% ± 4.7 in patients with HSGO. Appetite, fat mass, and waist circumference significantly decreased in both groups. Obesity-related comorbidities improved in significant proportions of patients treated with liraglutide or naltrexone-bupropion., Interpretation: In conclusion, our short-term findings show potential of liraglutide and naltrexone-bupropion as treatment options for adults with (a clinical phenotype of) genetic obesity., Funding: MB, EvdA, and EvR are supported by the Elisabeth Foundation, a non-profit foundation supporting academic obesity research., Competing Interests: The institution of MW, CdG, EvdA, and EvR has received funding for clinical trial research from Rhythm Pharmaceuticals, Inc. The current study is not linked to this study. MB and EvR receive personal royalties for the lay book FAT the secret organ. Payment to the institution or personal for scientific and/or educational presentations have been received by EvR. All other authors declare no competing interests., (© 2024 The Author(s).)

Objective: Considering limited evidence on diagnostics of genetic obesity in adults, we evaluated phenotypes of adults with genetic obesity. Additionally, we assessed the applicability of Endocrine Society (ES) recommendations for genetic testing in pediatric obesity., Methods: We compared clinical features, including age of onset of obesity and appetite, between adults with non-syndromic monogenic obesity (MO), adults with syndromic obesity (SO), and adults with common obesity (CO) as control patients., Results: A total of 79 adults with genetic obesity (32 with MO, 47 with SO) were compared with 186 control patients with CO. Median BMI was similar among the groups: 41.2, 39.5, and 38.7 kg/m 2 for patients with MO, SO, and CO, respectively. Median age of onset of obesity was 3 (IQR: 1-6) years in patients with MO, 9 (IQR: 4-13) years in patients with SO, and 21 (IQR: 13-33) years in patients with CO (p < 0.001). Patients with genetic obesity more often reported increased appetite: 65.6%, 68.1%, and 33.9% in patients with MO, SO, and CO, respectively (p < 0.001). Intellectual deficit and autism spectrum disorder were more prevalent in patients with SO (53.2% and 21.3%) compared with those with MO (3.1% and 6.3%) and CO (both 0.0%). The ES recommendations were fulfilled in 56.3%, 29.8%, and 2.7% of patients with MO, SO, and CO, respectively (p < 0.001)., Conclusions: We found distinct phenotypes in adult genetic obesity. Additionally, we demonstrated low sensitivity for detecting genetic obesity in adults using pediatric ES recommendations, necessitating specific genetic testing recommendations in adult obesity care., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Epidemiological results on the link between chronic stress and cancer initiation have been inconsistent. This study examined the relation between chronic biological stress, indicated as hair cortisol (HairF) and hair cortisone (HairE), and cancer incidence, adjusting for metabolic syndrome (MetS) components. We analyzed HairF and HairE samples from 6341 participants from the population-based cohort Lifelines in 2014. A linkage with the Dutch Nationwide Pathology Databank (Palga) provided the cancer incidence from 2015 to 2021. The association between dichotomized HairF and log-transformed HairE (LogHairE) and cancer incidence was estimated using Cox regression. MetS components were evaluated as confounders or moderators. Of the 2776 participants with known HairF levels and no cancer history, 238 developed cancer. The HairF level did not predict cancer incidence (HR: 0.993, 95%CI: 0.740-1.333). No confounders or moderators were identified. Among the 4699 participants with known HairE levels and no cancer history, 408 developed cancer. There was no association between LogHairE and cancer incidence (HR: 1.113, 95%CI: 0.738-1.678). When including age as a confounder and gender as a moderator, LogHairE was statistically significantly associated with cancer incidence (HR: 6.403, 95%CI: 1.110-36.92). In a population-based cohort, chronic biological stress, measured by HairE, was associated with cancer incidence, after controlling for age and gender.

Context: Synthetic glucocorticoids are widely used to treat patients with a broad range of diseases. While efficacious, glucocorticoids can be accompanied by neuropsychiatric adverse effects., Objective: This systematic review and meta-analysis assesses and quantifies the proportion of different neuropsychiatric adverse effects in patients using synthetic glucocorticoids., Methods: Six electronic databases were searched to identify potentially relevant studies. Randomized controlled trials, cohort studies, and cross-sectional studies assessing psychiatric side effects of glucocorticoids measured with validated questionnaires were eligible. Risk of bias was assessed with RoB 2, ROBINS-I, and AXIS appraisal tool. For proportions of neuropsychiatric outcomes, we pooled proportions, and when possible, differences in questionnaire scores between glucocorticoid users and nonusers were expressed as standardized mean differences (SMD). Data were pooled in a random-effects logistic regression model., Results: We included 49 studies with heterogeneity in study populations, type, dose, and duration of glucocorticoids. For glucocorticoid users, meta-analysis showed a proportion of 22% for depression (95% CI, 14%-33%), 11% for mania (2%-46%), 8% for anxiety (2%-25%), 16% for delirium (6%-36%), and 52% for behavioral changes (42%-61%). Questionnaire scores for depression (SMD of 0.80 [95% CI 0.35-1.26]), and mania (0.78 [0.14-1.42]) were higher than in controls, indicating more depressive and manic symptoms following glucocorticoid use., Conclusion: The heterogeneity of glucocorticoid use is reflected in the available studies. Despite this heterogeneity, the proportion of neuropsychiatric adverse effects in glucocorticoid users is high. The most substantial associations with glucocorticoid use were found for depression and mania. Upon starting glucocorticoid treatment, awareness of possible psychiatric side effects is essential. More structured studies on incidence and potential pathways of neuropsychiatric side effects of prescribed glucocorticoids are clearly needed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

In this article we describe how designers can apply storytelling to reduce health-related stigmas. Stigma is a pervasive problem for people with illnesses, such as obesity, and it can persistently hinder coping, treatment, recovery, and prevention. Reducing health-related stigma is complex because it is multi-layered and self-perpetuating, leading to intertwined vicious circles. Interactive storytelling environments can break these vicious circles by delimiting the narrative freedom of stigma actors. We theoretically explain the potential of interactive storytelling environments to reduce stigma through the following seven functions: 1) expose participants to other perspectives, 2) provide a protective frame, 3) intervene in daily conversations, 4) persuade all stigma actors, 5) exchange alternative understandings, 6) elicit understanding and support for stigma victims, and 7) support stigma victims to cope with stigmatization. We elaborate on these functions through a demonstration of an interactive storytelling environment against weight stigma. In conclusion, this article is a call on designers for health and wellbeing, scientists, and practitioners from various disciplines to be sensitive to the pervasiveness of stigma and to collaboratively create destigmatizing storytelling environments., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Introduction: Patients living with obesity often experience weight stigma in healthcare settings, which has worrying consequences for their healthcare experiences. This cross-sectional study aimed to: (1) provide an overview of stigmatising experiences in healthcare settings reported by adults living with varying classes of obesity, (2) identify associations among patient characteristics and perceived weight stigma and (3) investigate the association between perceived weight stigma and person-centred care (PCC)., Methods: Dutch adults living with obesity classes I (body mass index [BMI]: 30 to <35 kg/m 2 ; n = 426), II (BMI: 35 to <40 kg/m 2 ; n = 124) and III (BMI: ≥40 kg/m 2 ; n = 40) completed measures of perceived weight stigma in healthcare settings and PCC. Descriptive, correlational and multivariate analyses were conducted., Results: Of patients living with classes I, II and III obesity, 41%, 59% and 80%, respectively reported experiences of weight stigma in healthcare settings. Younger age, greater obesity severity and the presence of chronic illnesses were associated with greater perceived weight stigma. Greater perceived weight stigma was associated with lower PCC., Conclusion: The results of this study emphasise the significant role of weight stigma in the healthcare experiences of patients living with obesity. Reducing weight stigma is expected to improve PCC and the overall quality of care for these patients. Minimising weight stigma will require efforts across various healthcare domains, including increasing awareness among healthcare professionals about sensitive communication in weight-related discussions., Patient Contribution: Our sample consisted of patients living with obesity. Additionally, patients were involved in the pilot testing and refinement of the PCC instrument., (© 2024 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

The striking link of Cushing's syndrome with the metabolic syndrome (MetS) and cardiovascular disease (CVD) suggests that long-term exposure to extremely high cortisol levels catalyzes cardiometabolic deterioration. However, it remained unclear whether the findings from the extreme glucocorticoid overabundance observed in Cushing's syndrome could be translated into more subtle variations in long-term glucocorticoid levels among the general population, for example, due to chronic stress. Here, we performed a systematic review (PROSPERO: CRD42023425541) of evidence regarding the role of subtle variations in long-term biological stress, measured as levels of scalp hair cortisol (HairF) and cortisone (HairE), in the context of MetS and CVD in adults. We also performed a meta-analysis on the cross-sectional difference in HairF levels between individuals with versus without CVD. Seven studies were included regarding MetS, sixteen regarding CVD, and one regarding both. Most articles indicated a strong, consistent cross-sectional association of higher HairF and HairE levels with CVD, which was confirmed by our meta-analysis for HairF (eight studies, SMD = 0.48, 95% confidence intervals [CIs]: 0.16-0.79, p = 0.0095). Moreover, these relationships appear largely independent of standard risk factors. Age seems relevant as the effect seems stronger in younger individuals. Results regarding the associations of HairF and HairE with MetS were inconsistent. Altogether, long-term biological stress, measured as HairF and HairE, is associated with the presence of CVD, and less consistently with MetS. Prospective studies need to evaluate the directionality of this relationship and determine whether HairF and HairE can be used in addition to standard risk factors in predicting future cardiometabolic deterioration., (© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Context: Turner syndrome (TS) is a rare chromosomal disorder characterized by gonadal dysfunction, short stature, and heart defects, among other features. Women with TS often suffer from severe fatigue, for which they are typically referred to endocrinologists. The diagnostic work-up is generally time-consuming and invasive, and it rarely solves the problem. To prevent the personal and financial burden of unnecessary diagnostic procedures, it is crucial to understand fatigue in TS., Objective: To explore the association between fatigue and endocrine and non-endocrine comorbidities in a-for rare disorders-large group of women with TS., Methods: 170 genetically confirmed women with TS who attended the TS Reference Center underwent a systematic health screening, including a structured interview, complete physical examination, biochemical measurements, perceived stress and fatigue questionnaires, and additional tests when indicated., Results: Median (interquartile range) age was 32.6 (23.9-41.4) years. Severe fatigue was experienced by 1 in 3 women with TS. Liver enzyme disturbances and body mass index were significantly associated with higher fatigue scores. Perceived stress was highly correlated with fatigue., Conclusion: There was no association between fatigue and most endocrine and non-endocrine disorders, which implies that fatigue is only partly explained by somatic disorders. The high correlation between perceived stress and fatigue suggests that TS-related neuropsychological processes may play an important role in the etiology of fatigue in women with TS. We provide a practical algorithm for the endocrine, non-endocrine, and psychological approach to fatigue in women with TS., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: We sought to assess body mass index trajectories of children with genetic obesity to identify optimal early age of onset of obesity (AoO) cut-offs for genetic screening., Study Design: This longitudinal, observational study included growth measurements from birth onward of children with nonsyndromic and syndromic genetic obesity and control children with obesity from a population-based cohort. Diagnostic performance of AoO was evaluated., Results: We describe the body mass index trajectories of 62 children with genetic obesity (29 nonsyndromic, 33 syndromic) and 298 controls. Median AoO was 1.2 years in nonsyndromic genetic obesity (0.4 and 0.6 years in biallelic LEPR and MC4R; 1.7 in heterozygous MC4R); 2.0 years in syndromic genetic obesity (0.9, 2.3, 4.3, and 6.8 years in pseudohypoparathyroidism, Bardet-Biedl syndrome, 16p11.2del syndrome, and Temple syndrome, respectively); and 3.8 years in controls. The optimal AoO cut-off was ≤3.9 years (sensitivity, 0.83; specificity, 0.49; area under the curve, 0.79; P < .001) for nonsyndromic and ≤4.7 years (sensitivity, 0.82; specificity, 0.37; area under the curve, 0.68; P = .001) for syndromic genetic obesity., Conclusions: Optimal AoO cut-off as single parameter to determine which children should undergo genetic testing was ≤3.9 years. In case of older AoO, additional features indicative of genetic obesity should be present to warrant genetic testing. Optimal cut-offs might differ across different races and ethnicities., Competing Interests: Declaration of Competing Interest Supported by the Elisabeth Foundation (project name ObesEcare), a nonprofit foundation supporting academic research. The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Despite preventive measures, the number of people with type 2 diabetes and obesity is increasing. Obesity increases morbidity and mortality in people with type 2 diabetes, making weight loss a cornerstone of treatment. We previously developed a very low energy diet (VLED) intervention that effectively reduced weight in people with type 2 diabetes in the long term. However, this intervention requires considerable time and manpower, which reduces the number of people who can benefit from it. eHealth offers more efficient solutions but has proven to be less effective than face-to-face interventions. Therefore, we want to investigate whether a blended version of our VLED intervention (in which face-to-face contact is partly replaced by an eHealth (mobile) application (E-VLED)) would be more cost-effective than the current face-to-face intervention., Methods: We will conduct a randomised, controlled trial with non-inferiority design in patients with type 2 diabetes and obesity (BMI > 30 kg/m 2 ), aged 18-75 years. The control group will receive the usual care VLED intervention, while the intervention group will receive the E-VLED intervention for 1 year, where face-to-face contact will be partly replaced by an eHealth (mobile) application. The main study endpoint is the difference in weight (% change) between the control and intervention group after 1 year, plus the difference between the total costs (euro) of the treatment in the control and intervention groups. The secondary aims are to investigate the effectiveness of the E-VLED diet intervention regarding cardiovascular risk factors, quality of life, patient satisfaction, compliance, and to study whether there is a difference in effectiveness in pre-specified subgroups. General linear models for repeated measurements will be applied for the statistical analysis of the data., Discussion: We hypothesise that the E-VLED intervention will be equally effective compared to the usual care VLED but lower in costs due to less time invested by the dietician. This will enable to help more people with type 2 diabetes and obesity to effectively lose weight and improve their health-related quality of life., Trial Registration: Netherlands Trial Register, NL7832, registered on 26 June 2019., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: People who give care to autistic individuals (autism-caregivers) experience higher levels of caregiver strain than people who provide care for individuals with other chronic conditions (non-autism-caregivers). This places them at higher risk for psychological, behavioural and physical health concerns. The aim of this study is to delineate psychological, behavioural, and physical aspects of caregiver strain in autism-caregivers compared to non-autism-caregivers., Methods: We included 3354 adult caregivers from the general population in the Netherlands participating in the second assessment (January, 1, 2014-December, 31, 2017) of the Lifelines Cohort. In this cohort study, using multivariable regression adjusted for age, sex, and socioeconomic status, we analysed psychological (anxiety and depression based on a Mini International Neuropsychiatric Interview, and self-reported stress and perceived health), behavioural (questionnaire-assessed physical activity, alcohol use, and smoking), and physical aspects (body mass index, waist circumference, and leukocyte-counts) of caregiver strain in autism-caregivers (n = 722) compared with non-autism-caregivers (n = 2632)., Findings: Autism-caregivers reported more stress (OR 3.61, 95% CI 2.60-4.99). Both anxiety (OR 1.85, 95% CI 1.37-2.49) and depressive disorders (OR 1.83, 95% CI 1.17-2.86) were more common in autism-caregivers than in non-autism-caregivers. Perceived health, physical activity, alcohol use, and smoking were not different between autism- and non-autism-caregivers. In autism-caregivers, lymphocyte- and monocyte-counts were lower than in non-autism-caregivers., Interpretation: In this large cohort, autism-caregivers had worse psychological health than non-autism-caregivers. Moreover, autism-caregiving might be associated with an altered immune balance. These findings underline the higher caregiver strain in autism-caregivers compared to other caregivers. This calls for increased support to autism-caregivers., Funding: Lifelines has been funded by the Dutch government., Competing Interests: The authors declare not having any conflict of interest., (© 2023 The Author(s).)

eHealth has a growing impact on the delivery of healthcare, making health systems more efficient. This study examined the effect of dietary interventions using eHealth compared to face-to-face contact in patients with (pre-) type 2 diabetes (T2D) and who are overweight/obese. Literature databases were searched upon November 2022. Inclusion criteria: randomized controlled trial; duration ≥ 6 months; involving dietary interventions; performed in adults with (pre-) T2D and who are overweight/obese; using eHealth compared to face-to-face contact; and report outcomes on weight loss, glycemic regulation, and/or cost-effectiveness. Selection of articles was performed manually and using ASReviewLab. Fifteen studies were included for data extraction, investigating a wide variety of eHealth interventions. Seven studies reporting on weight loss showed a significant between-group difference (-1.18 to -5.5 kg); five studies showed a trend in favor of the eHealth programs. Eleven studies reported on HbA1c; three found a significant between-group difference (-0.23 to -0.70%) in favor of the eHealth programs and six studies showed non-significant improvements. Interaction with healthcare professionals led to better results of the dietary interventions. Two studies reported incomplete data on cost-effectiveness. In conclusion, eHealth shows better results of dietary interventions in (pre-) T2D patients compared to face-to-face, especially when combined with interaction with healthcare professionals.

Childhood anxiety disorders (CAD) are a common childhood mental disorder and understanding early developmental pathways is key to prevention and early intervention. What is not understood is whether early life stress predictors of CAD might be both mediated by infant cortisol reactivity and moderated by infant attachment status. To address this question, this exploratory study draws on 190 women recruited in early pregnancy and followed together with their children until 4 years of age. Early life stress is operationalized as maternal depression measured using the Structured Clinical Interview for the DSM, Childhood Trauma Questionnaire, Parenting Stress Index, and antenatal maternal hair cortisol concentrations. Infant cortisol reactivity was measured at 12 months together with the Strange Situation Procedure and CAD assessed at 4 years of age using the Preschool Age Psychiatric Assessment. There was no direct association between attachment classification and CAD. Furthermore, infant cortisol reactivity neither mediated nor attachment moderated the association of early life stress predictors and CAD. However, only for infants with organized attachment classifications, higher maternal antenatal depression, and hair cortisol were associated with a higher risk of CAD.

Introduction: Alectinib is a standard-of-care treatment for metastatic ALK+ NSCLC. Weight gain is an unexplored side effect reported in approximately 10%. To prevent or intervene alectinib-induced weight gain, more insight in its extent and etiology is needed., Methods: Change in body composition was analyzed in a prospective series of 46 patients with ALK+ NSCLC, treated with alectinib. Waist circumference, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle were quantified using sliceOmatic software on computed tomography images at baseline, 3 months (3M), and 1 year (1Y). To investigate an exposure-toxicity relationship, alectinib plasma concentrations were quantified. Four patients with more than 10 kg weight gain were referred to Erasmus MC Obesity Center CGG for in-depth analysis (e.g., assessments of appetite, dietary habits, other lifestyle, medical and psychosocial factors, and extensive metabolic and endocrine assessments, including resting energy expenditure)., Results: Mean increase in waist circumference was 9 cm (9.7%, p < 0.001) in 1Y with a 40% increase in abdominal obesity (p = 0.014). VAT increased to 10.8 cm 2 (15.0%, p = 0.003) in 3M and 35.7 cm 2 (39.0%, p < 0.001) in 1Y. SAT increased to 18.8 cm 2 (12.4%, p < 0.001) in 3M and 45.4 cm 2 (33.3%, p < 0.001) in 1Y. The incidence of sarcopenic obesity increased from 23.7% to 47.4% during 1Y of treatment. Baseline waist circumference was a positive predictor of increase in VAT (p = 0.037). No exposure-toxicity relationship was found. In-depth analysis (n = 4) revealed increased appetite in two patients and metabolic syndrome in all four patients., Conclusions: Alectinib may cause relevant increased sarcopenic abdominal obesity, with increases of both VAT and SAT, quickly after initiation. This may lead to many serious metabolic, physical, and mental disturbances in long-surviving patients., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: Human scalp hair is an easily available but complex matrix for determination of cortisone and cortisol, and has been shown to reflect long-term glucocorticoid exposure. Hair glucocorticoid analysis has been used to detect hypo- and hypercortisolism. In this study, we describe the development and validation of a LC-MS/MS method for quantification of cortisone and cortisol in human scalp hair, and provide a novel approach for analysis and interpretation of the results., Methods: Improved sample preparation using pulverization and solid phase extraction allowed for low sample volumes (10 mg). Baseline chromatographic separation without matrix interference was achieved by reversed phase chromatography and MRM measurement in negative ion mode. Run-to-run time was 8 min. Mixed model analyses were performed to create individual patterns of cortisone and cortisol concentrations., Results: Matrix matched calibration curves showed excellent linearity up to 100 pg (analyte)/mg (hair) for both cortisone and cortisol (R 2 >0.995). LLOQ was 1.5 and 1.0 pg/mg for cortisone and cortisol, respectively. Matrix effect was negligible for hair color (recoveries 95-105 %). Cortisone and cortisol concentrations decreased from proximal to distal hair segments, following a predictable, but subject-specific pattern, with less individual variation for cortisone than for cortisol., Conclusions: This improved LC-MS/MS method is able to accurately quantify cortisone and cortisol in human hair with minimum matrix interference. This new way of data analysis and interpretation including individual patterns of cortisone and cortisol will be of help with detection of pathological concentrations in both the high - and the low ranges of glucocorticoids., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Endogenous Cushing's syndrome (CS) is a rare disease characterized by prolonged glucocorticoid excess. Timely diagnosis is critical to allow prompt treatment and limit long-term disease morbidity and risk for mortality. Traditional biochemical diagnostic modalities each have limitations and sensitivities and specificities that vary significantly with diagnostic cutoff values. Biochemical evaluation is particularly complex in patients whose hypercortisolemia fluctuates daily, often requiring repetition of tests to confirm or exclude disease, and when delineating CS from physiologic, nonneoplastic states of hypercortisolism. Lastly, traditional pituitary MRI may be negative in up to 60% of patients with adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (termed "Cushing's disease" [CD]) whereas false positive pituitary MRI findings may exist in patients with ectopic ACTH secretion. Thus, differentiating CD from ectopic ACTH secretion may necessitate dynamic testing or even invasive procedures such as bilateral inferior petrosal sinus sampling. Newer methods may relieve some of the diagnostic uncertainty in CS, providing a more definitive diagnosis prior to subjecting patients to additional imaging or invasive procedures. For example, a novel method of cortisol measurement in patients with CS is scalp hair analysis, a non-invasive method yielding cortisol and cortisone values representing long-term glucocorticoid exposure of the past months. Hair cortisol and cortisone have both shown to differentiate between CS patients and controls with a high sensitivity and specificity. Moreover, advances in imaging techniques may enhance detection of ACTH-secreting pituitary adenomas. While conventional pituitary MRI may fail to identify microadenomas in patients with CD, high-resolution 3T-MRI with 3D-spoiled gradient-echo sequence has thinner sections and superior soft-tissue contrast that can detect adenomas as small as 2 mm. Similarly, functional imaging may improve the identification of ACTH-secreting adenomas noninvasively; Gallium-68-tagged corticotropin-releasing hormone (CRH) combined with PET-CT can be used to detect CRH receptors, which are upregulated on corticotroph adenomas. This technique can delineate functionality of adenomas in patients with CD from patients with ectopic ACTH secretion and false positive pituitary lesions on MRI. Here, we review emerging methods and imaging modalities for the diagnosis of CS, discussing their diagnostic accuracy, strengths and limitations, and applicability to clinical practice., Competing Interests: NA is on the advisory board for Corcept Therapeutics and is a Principal Investigator for institution-directed research grants Chiasm Acromegaly Registry. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2023 Wright, van Rossum, Zan, Werner, Harris, Feelders and Agrawal.)

Background: Weight loss can induce changes in appetite-regulating hormone levels, possibly linked to increases in appetite and weight regain. However, hormonal changes vary across interventions. Here, we studied levels of appetite-regulating hormones during a combined lifestyle intervention (CLI: healthy diet, exercise and cognitive behavioral therapy). Methods: We measured levels of long-term adiposity-related hormones (leptin, insulin, high-molecular-weight (HMW) adiponectin) and short-term appetite hormones (PYY, cholecystokinin, gastric-inhibitory polypeptide, pancreatic polypeptide, FGF21, AgRP) in overnight-fasted serum of 39 patients with obesity. Hormone levels were compared between T0 (baseline), T1 (after 10 weeks) and T2 (end of treatment, 1.5 years). T0-T1 hormone changes were correlated with T1-T2 anthropometric changes. Results: Initial weight loss at T1 was maintained at T2 (-5.0%, p < 0.001), and accompanied by decreased leptin and insulin levels at T1 and T2 (all p < 0.05) compared to T0. Most short-term signals were not affected. Only PP levels were decreased at T2 compared to T0 ( p < 0.05). Most changes in hormone levels during initial weight loss did not predict subsequent changes in anthropometrics, except for T0-T1 decreases in FGF21 levels and T0-T1 increases in HMW adiponectin levels tended to be associated with larger T1-T2 increases in BMI ( p < 0.05 and p = 0.05, respectively). Conclusion: CLI-induced weight loss was associated with changes in levels of long-term adiposity-related hormones towards healthy levels, but not with orexigenic changes in most short-term appetite signals. Our data indicates that the clinical impact of alterations in appetite-regulating hormones during modest weight loss remains questionable. Future studies should investigate potential associations of weight-loss-induced changes in FGF21 and adiponectin levels with weight regain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kuckuck, van der Valk, Scheurink, Lengton, Mohseni, Visser, Iyer, van den Berg and van Rossum.)

We describe the therapeutic journey of a 33-year-old patient with early-onset obesity (BMI 56.7 kg/m 2 ) and hyperphagia due to a likely pathogenic heterozygous melanocortin-4 receptor ( MC4R ) gene variant. She was unsuccessfully treated with several intensive lifestyle interventions, gastric bypass surgery (-40 kg weight loss, followed by +39.8 kg weight regain), liraglutide 3 mg (-3.8% weight loss with sustained hyperphagia), and metformin treatment. However, naltrexone-bupropion treatment led to -48.9 kg (-26.7%) weight loss, of which -39.9 kg (-38.3%) was fat mass, in 17 months of treatment. Importantly, she reported improved hyperphagia and quality of life. We describe the potential beneficial effects of naltrexone-bupropion on weight, hyperphagia, and quality of life in a patient with genetic obesity. This extensive journey shows that various anti-obesity agents can be initiated, subsequently terminated when ineffective and substituted with other anti-obesity agents to identify the most efficient anti-obesity treatment., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Background: Alterations in stress regulation and function of the hypothalamic-pituitary-adrenal (HPA) axis during infancy may be a risk factor for the development of psychopathology later in life. Maternal childhood trauma, depression, anxiety and stressful life events are individually associated with HPA axis dysregulation. Less is known about their interdependent influence on maternal and infant stress regulation in at risk populations. In a sample of mothers with a history of depressive-, and/or anxiety disorders and their infants we explored if a history of maternal childhood trauma, current depressive and anxiety symptomatology, and recent life events were associated with maternal and infant long-term cortisol levels three months postpartum., Methods: Data were available of 89 mothers and 49 infants. All mothers fulfilled criteria for a lifetime depressive or anxiety disorder. Diagnosis was established with a diagnostic interview. Current depressive symptomatology was assessed with the Edinburgh Postnatal Depression Scale (EPDS), current anxiety with the State-Trait Anxiety Inventory (STAI), maternal childhood trauma with the Childhood Trauma Questionnaire (CTQ) and recent life events with the Everyday Problem Checklist (EPC). Maternal and infant hair cortisol concentrations (HCC) were quantified with liquid chromatography with tandem mass spectrometry (LC-MS/MS) three months after birth. Total scores of the CTQ and subscales, EPDS, STAI, and EPC were regressed on maternal and infant HCC using regression analyses. Differences in HCC regarding trauma history were tested with t-tests. Potential confounders were identified and adjusted for., Results: In regression analyses, a positive curvilinear relationship was found between CTQ total score and maternal HCC (n = 83, B = 0.076, SE 0.033, p = .021), but not for current depression (n = 88, B = -0.001, SE 0.011, p = .931), current anxiety (n = 88, B = 0.002, SE 0.004, p = .650) or recent life events (n = 89, B = 0.018, SE 0.032, p = .568). Analyses were adjusted for confounders. A negative linear relationship was found between maternal CTQ score and infant HCC (n = 49, β = -0.264, B = -0.006, SE 0.003, p = .052), but not for current maternal depression (n = 45, β = -0.182, B = -0.011, SE 0.008, p = .164), current maternal anxiety (n = 45, β = -0.209, B = -0.005, SE 0.003, p = .113) or recent life events (n = 46, β = -0.128, B = -0.022, SE 0.023, p = .325). Analyses were adjusted for relevant infant hair characteristics. Specifically, maternal emotional and physical neglect were related to HCC in both mothers and infants., Conclusions: Results suggest that maternal childhood trauma is more prominent in altering maternal and infant long-term cortisol levels than perinatal depressive and anxiety symptomatology or recent life stressors in mothers with a history of depressive and/or anxiety disorders, and their infants. As infants of mothers with psychopathology are at increased risk for later psychiatric disease, future studies should investigate the interplay of possible risk factors for transgenerational transmission, intra-uterine programming of the HPA axis, including (epi-)genetic phenomena, of the HPA axis, and the influence of parenting impairment., Competing Interests: None., (© 2023 The Author(s).)

Background: Obesity is a multifactorial, chronic, progressive disease associated with decreased health-related quality of life, comorbidities, and increased mortality risk. Lifestyle interventions, focusing on dietetics, physical exercise, and behavioral therapy, are a cornerstone of therapy. Despite this very multidisciplinary treatment approach, the definition of treatment success is often based only on a weight loss of ≥ 5%. However, the heterogeneous nature of obesity may necessitate a more comprehensive approach to assessing treatment effects., Objectives: Here, we describe changes in physiological, psychological, and behavioral health after a multidisciplinary combined lifestyle intervention (CLI). Additionally, we investigated whether these changes were related to weight loss., Methods: This prospective observational longitudinal study comprised 96 adults with obesity (73 women, 81 Caucasian) participating in a CLI at the Obesity Center CGG, Erasmus University Medical Center, Rotterdam, the Netherlands. The 1.5-year intervention comprised multidisciplinary professional guidance towards a healthy diet, increased physical activity, and included cognitive behavioral therapy. Physiological health outcomes, psychological well-being, eating behavior, and physical activity were assessed after ten weeks and 1.5 years and compared to baseline., Results: An average of 5.2% weight loss (-6.0 kg) was accompanied by a mean 9.8% decrease in fat mass (-5.9 kg; both P < 0.001) and significant improvements in metabolism, hormonal status, and immune parameters (all P < 0.05). Moreover, we observed decreased psychopathology, increased quality of life, and decreased disordered eating (all P < 0.05). Weight loss correlated with most metabolic changes (all P < 0.05) but not with most psychological/behavioral changes., Conclusions: Combined lifestyle intervention in patients with obesity was accompanied by significant improvements in body weight and body composition along with cardiometabolic, endocrine, immunological, psychological, and behavioral improvements. Interestingly, most changes in psychological and behavioral health occurred independently of weight loss. Obesity treatment success should be evaluated based on a combination of physical and patient-reported outcomes rather than weight loss alone., Competing Interests: Conflict of Interests: All authors are employed by ErasmusMC Medical Center, Rotterdam, the Netherlands, (Copyright © 2022, International Journal of Endocrinology and Metabolism.)

Introduction: To better accommodate patients with obesity, the adoption of a person-centred approach to healthcare seems to be imperative. Eight dimensions are important for person-centred care (PCC): respect for patients' preferences, physical comfort, the coordination of care, emotional support, access to care, the continuity of care, the provision of information and education, and the involvement of family and friends. The aim of this study was to explore the views of patients with obesity on the relative importance of the dimensions of PCC., Methods: Q methodology was used to study the viewpoints of 21 patients with obesity on PCC. Respondents were asked to rank 31 statements about the eight dimensions of PCC by level of personal significance. Using by-person factor analysis, distinct viewpoints were identified. Respondents' comments made while ranking were used to verify and refine the interpretation of the viewpoints., Results: Five distinct viewpoints were identified: (1) 'someone who listens in an unbiased manner', (2) 'everything should run smoothly', (3) 'interpersonal communication is key', (4) 'I want my independence', and (5) 'support for myself and my loved ones'. Viewpoint 1 was supported by the largest number of respondents and explained the most variance in the data, followed by viewpoint 3 and the other viewpoints, respectively., Conclusion: Our findings highlight the need for tailored care in obesity treatment and shed light on aspects of care and support that are most important for patients with obesity., Patient Contribution: Our sample consisted of patients. Patients were also involved in the development of the statement set through pilot testing., (© 2022 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Cushing syndrome results from supraphysiological exposure to glucocorticoids and is associated with significant morbidity and mortality. The pathogenesis includes administration of corticosteroids (exogenous Cushing syndrome) or autonomous cortisol overproduction, whether or not ACTH-dependent (endogenous Cushing syndrome). An early diagnosis of Cushing syndrome is warranted; however, in clinical practice, it is very challenging partly because of resemblance with other common conditions (ie, pseudo-Cushing syndrome). Initial workup should start with excluding local and systemic corticosteroid use. First-line screening tests including the 1-mg dexamethasone suppression test, 24-hour urinary free cortisol excretion, and late-night salivary cortisol measurement should be performed to screen for endogenous Cushing syndrome. Scalp-hair cortisol/cortisone analysis helps in the assessment of long-term glucocorticoid exposure as well as in detection of transient periods of hypercortisolism as observed in cyclical Cushing syndrome. Interpretation of results can be difficult because of individual patient characteristics and hence requires awareness of test limitations. Once endogenous Cushing syndrome is established, measurement of plasma ACTH concentrations differentiates between ACTH-dependent (80%-85%) or ACTH-independent (15%-20%) causes. Further assessment with different imaging modalities and dynamic biochemical testing including bilateral inferior petrosal sinus sampling helps further pinpoint the cause of Cushing's syndrome. In this issue of "Approach to the patient," the diagnostic workup of Cushing syndrome is discussed with answering the questions when to screen, how to screen, and how to differentiate the different causes. In this respect, the latest developments in biochemical and imaging techniques are discussed as well., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Obesity is associated with chronic, low-grade inflammation, which is reflected in altered peripheral blood monocyte characteristics. The aim of this study was to analyze the monocyte subset composition (classical (CM), intermediate (IM) and non-classical monocytes (NCM)), and their inflammatory marker profile (CD14, CD16, CD36, CD45, CD64, CD300e, HLA-DR) in individuals with obesity during a 1.5 year combined lifestyle intervention (CLI), comprising healthy nutrition, increased exercise and behavioral changes., Methods: We analyzed monocyte subset counts and immunophenotypes in 73 individuals with obesity, and associated these to baseline body mass index (BMI) and waist circumference (WC). The measurements were repeated after 10 weeks and at the end of the intervention (1.5 years)., Results: Generally, monocyte subset counts were not associated to BMI or WC at baseline, neither did monocyte counts change during the 1.5 year CLI. Immunophenotypically, higher baseline BMI and WC were associated to lower CD14 and higher CD300e expression by all subsets. During CLI there were remarkable changes in marker profiles: expression of CD14, CD36, CD45 and CD64 significantly decreased in CM and IM, as did CD16 (IM and NCM) (p<0.05). CD300e initially decreased after 10 weeks, but increased sharply at 1.5 years (all subsets). We observed no consistent associations between changes in monocyte characteristics and anthropometric changes., Conclusion: A 1.5 year CLI in individuals with obesity mediates persistent immunophenotypic adaptations related to cellular activation in blood monocytes, whereas changes in subset distribution are limited. Lifestyle-induced changes in the inflammatory profile of monocytes differ from the 'less-severe-obesity'-phenotype, suggesting a novel, 'post-weight-loss' monocyte setpoint., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 van der Valk, Mulder, Kouwenhoven, Nagtzaam, van Rossum, Dik and Leenen.)

Objective: Patients with pro-opiomelanocortin (POMC) defects generally present with early-onset obesity, hyperphagia, hypopigmentation and adrenocorticotropin (ACTH) deficiency. Rodent models suggest that adequate cleavage of ACTH to α-melanocortin-stimulating hormone (α-MSH) and desacetyl-α-melanocortin-stimulating hormone (d-α-MSH) by prohormone convertase 2 at the KKRR region is required for regulating food intake and energy balance., Methods: We present 2 sisters with a novel POMC gene variant, leading to an ACTH defect at the prohormone convertase 2 cleavage site, and performed functional studies of this variant., Results: The patients had obesity, hyperphagia and hypocortisolism, with markerly raised levels of ACTH but unaffected pigmentation. Their ACTH has reduced potency to stimulate the melanocortin (MC) 2 receptor, explaining their hypocortisolism., Conclusion: The hyperphagia and obesity support evidence that adequate cleavage of ACTH to α-MSH and d-α-MSH is also required in humans for feeding control., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The prevalence of nonalcoholic fatty liver disease (NAFLD) and the more severe and inflammatory type, nonalcoholic steatohepatitis (NASH), is increasing rapidly. Especially in high-risk patients, that is those with obesity, metabolic syndrome, and type 2 diabetes mellitus, the prevalence of NAFLD can be as high as 80% while NASH may be present in 20% of these subjects. With the worldwide increase of obesity, it is most likely that these numbers will rise. Since advanced stages of NAFLD and NASH are strongly associated with morbidity and mortality-in particular, cardiovascular disease, liver cirrhosis, and hepatocellular carcinoma-it is of great importance to identify subjects at risk. A great variety of noninvasive tests has been published to diagnose NAFLD and NASH, especially using blood- and imaging-based tests. Liver biopsy remains the gold standard for NAFLD/NASH. This review aims to summarize the different mechanisms leading to NASH and liver fibrosis, the different noninvasive liver tests to diagnose and evaluate patients with severe obesity., (© 2022 World Obesity Federation.)

Background: Pediatric obesity is a multifactorial disease which can be caused by underlying medical disorders arising from disruptions in the hypothalamic leptin-melanocortin pathway, which regulates satiety and energy expenditure., Aim: To investigate and compare resting energy expenditure (REE) and body composition characteristics of children and adolescents with severe obesity with or without underlying medical causes., Methods: This prospective observational study included pediatric patients who underwent an extensive diagnostic workup in our academic centre that evaluated endocrine, non-syndromic and syndromic genetic, hypothalamic, and medication-induced causes of obesity. REE was assessed by indirect calorimetry; body composition by air displacement plethysmography. The ratio between measured REE (mREE) and predicted REE (Schofield equations), REE%, was calculated, with decreased mREE defined as REE% ≤90% and elevated mREE ≥110%. Additionally, the influence of fat-free-mass (FFM) on mREE was evaluated using multiple linear regression., Results: We included 292 patients (146 [50%] with body composition measurements), of which 218 (75%) patients had multifactorial obesity and 74 (25%) an underlying medical cause: non-syndromic and syndromic genetic (n= 29 and 28, respectively), hypothalamic (n= 10), and medication-induced (n= 7) obesity. Mean age was 10.8 ± 4.3 years, 59% were female, mean BMI SDS was 3.8 ± 1.1, indicating severe obesity. Mean REE% was higher in children with non-syndromic genetic obesity (107.4% ± 12.7) and lower in children with hypothalamic obesity (87.6% ± 14.2) compared to multifactorial obesity (100.5% ± 12.6, both p<0.01). In 9 children with pseudohypoparathyroidism type 1a, mean REE% was similar (100.4 ± 5.1). Across all patients, mREE was decreased in 60 (21%) patients and elevated in 69 (24%) patients. After adjustment for FFM, mREE did not differ between patients within each of the subgroups of underlying medical causes compared to multifactorial obesity (all p>0.05)., Conclusions: In this cohort of children with severe obesity due to various etiologies, large inter-individual differences in mREE were found. Consistent with previous studies, almost half of patients had decreased or elevated mREE. This knowledge is important for patient-tailored treatment, e.g. personalized dietary and physical activity interventions and consideration of pharmacotherapy affecting central energy expenditure regulation in children with decreased mREE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abawi, Koster, Welling, Boeters, van Rossum, van Haelst, van der Voorn, de Groot and van den Akker.)

Background: Asthma patients with obesity often have a high disease burden, despite the use of high-dose inhaled corticosteroids (ICS). In contrast to asthmatics with normal weight, the efficacy of ICS in patients with obesity and asthma is often relatively low. Meanwhile, patients do suffer from side effects, such as weight gain, development of diabetes, cataract, or high blood pressure. The relatively poor response to ICS might be explained by the low prevalence of type 2 inflammatory patterns (T2-low) in patients with asthma and obesity. T2-low inflammation is characterized by low eosinophilic count, low Fractional exhaled NO (FeNO), no clinically allergy-driven asthma, and no need for maintenance oral corticosteroids (OCS). We aim to study whether ICS can be safely withdrawn in patients with T2-low asthma and obesity while maintaining an equal level of asthma control. Secondary outcomes focus on the prevalence of 'false-negative' T2-low phenotypes (i.e. T2-hidden) and the effect of ICS withdrawal on parameters of the metabolic syndrome. This study will lead to a better understanding of this poorly understood subgroup and might find new treatable traits., Methods: The STOP trial is an investigator-initiated, multicenter, non-inferiority, open-label, crossover study aiming to assess whether ICS can be safely withdrawn in adults aged 17-75 years with T2-low asthma and obesity (body mass index (BMI) ≥ 30 kg/m 2 ). Patients will be randomly divided into two arms (both n = 60). One arm will start with fixed-dose ICS (control group) and one arm will taper and subsequently stop ICS (intervention group). Patients in the intervention group will remain ICS naïve for ten weeks. After a washout of 4 weeks, patients will crossover to the other study arm. The crossover study takes 36 weeks to complete. Patients will be asked to participate in the extension study, to investigate the long-term metabolic benefits of ICS withdrawal., Discussion: This study yields valuable data on ICS tapering in patients with T2-low asthma and obesity. It informs future guidelines and committees on corticosteroid-sparing algorithms in these patients. Trial registration Netherlands Trial Register, NL8759, registered 2020-07-06, https://www.trialregister.nl/trial/8759 . Protocol version and date: version 2.1, 20 November 2020., (© 2022. The Author(s).)

Introduction: COVID-19 lockdown measures have large impact on lifestyle behaviors and well-being of children. The aim of this mixed-methods study was to investigate the impact of COVID-19 lockdown measures on eating styles and behaviors, physical activity (PA), screen time, and health-related quality of life (HRQoL) in children (0-18 years) with severe obesity., Methods: During the first COVID-19 wave (April 2020), validated questionnaires were completed and semi-structured telephone interviews were conducted with parents of children with severe obesity (adult body mass index [BMI]-equivalent ≥35 kg/m2) and/or with the children themselves. Changes in pre-pandemic versus lockdown scores of the Dutch Eating Behavior Questionnaire Children, Pediatric Quality of Life Inventory, and Dutch PA Questionnaire were assessed. Qualitative analyses were performed according to the Grounded Theory., Results: Ninety families were approached of which 83 families were included. Characteristics of the included children were: mean age 11.2 ± 4.6 years, 52% female, mean BMI SD-score +3.8 ± 1.0. Emotional, restrained, and external eating styles, HRQoL, and (noneducational) screen time did not change on group level (all p > 0.05). However, weekly PA decreased (mean difference -1.9 h/week, p = 0.02) mostly in adolescents. In the majority of children, mean weekly PA decreased to ≤2 h/week. Children with high emotional or external eating scores during lockdown or pre-existent psychosocial problems had the lowest HRQoL (p < 0.01). Qualitative analyses revealed an increased demand for food in a significant proportion of children (n = 21), mostly in children <10 years (19/21). This was often attributed to loss of daily structure and perceived stress. Families who reported no changes (n = 15) or improved eating behaviors (n = 11) attributed this to already existing strict eating schemes that they kept adhering to during lockdown., Conclusion: This study shows differing responses to COVID-19 lockdown measures in children with severe obesity. On group level, PA significantly decreased and in substantial minorities eating styles and HRQoL deteriorated. Children with pre-existent psychosocial problems or pre-pandemic high external or emotional eating scores were most at risk. These children and their families should be targeted by health care professionals to minimize negative physical and mental health consequences., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Introduction: Adult-onset asthma (AOA) is usually more severe compared to childhood onset asthma (CoA). Given the increasing evidence that AoA is associated with obesity, we investigated the relationship of other related metabolic comorbid conditions with AoA compared to CoA., Study Design and Methods: This cross-sectional study compared the metabolic syndrome and lipid derived inflammatory markers in patients with AoA, CoA and age- and sex-matched control subjects without asthma. Participants were asthma patients visiting the outpatient clinic of two teaching hospitals in Rotterdam, The Netherlands. All participants underwent lung function tests, blood tests and physical activity tracking. AoA was defined as asthma age of onset after the age of 18 years. Metabolic syndrome was defined according to the international joint interim statement criteria., Results: Eighty-one participants were included (27 AoA, 25 CoA, 29 controls). AoA was associated with the metabolic syndrome (Odds Ratio = 3.64 95% CI (1.16-11.42) p = 0.03, Nagelkerke R 2  = 0.26), adjusted for age, sex, body mass index and smoking habits. AoA patients had higher median serum IL-6 and leptin-adiponectin (LA) ratio compared to controls (IL-6 (pg/mL): 3.10 [1.11-4.30] vs. 1.13 [0.72-1.58], p = 0.002 and LA ratio (pg/mL): 6.21 [2.45-14.11] vs. 2.24 [0.67-4.71], p = 0.0390). This was not observed in CoA and controls., Conclusion: AoA was associated with the metabolic syndrome and its related pro-inflammatory endocrine and cytokine status. This may suggest adipose tissue derived inflammatory markers play a role in the pathophysiology of AoA., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Higher long-term glucocorticoid levels, measured in scalp hair (HairGC), are associated with obesity. This may represent the state of obesity (perhaps interrelated with chronic immune activation), but could also promote further weight gain. We studied whether hair cortisol (HairF) and hair cortisone (HairE) predict changes in body mass index (BMI) and waist circumference (WC) over time, and assessed the association between HairGC and common immune parameters., Methods: We measured HairGC in 1604 participants of the Netherlands Study of Depression and Anxiety (NESDA), and investigated their associations to BMI, WC, and immune parameters (interleukin-6 (IL-6), C-reactive protein (CRP), and leukocyte subsets). Also, we assessed whether baseline HairGC predict changes in BMI and WC at follow-up (three years later)., Results: In cross-sectional analyses, HairF and HairE were positively associated to BMI (β = 2.06 kg/m 2 , 95% confidence interval (CI)= 1.22-2.90 kg/m 2 ) and β = 2.84 kg/m 2 (95%CI 1.75-3.93 kg/m 2 ) respectively) and WC (β = 5.36 cm (95%CI 3.09-7.62 cm) and β = 8.54 cm (95%CI 5.60-11.48 cm) respectively, all p < 0.001). HairF was also positively associated to IL-6 (β = 0.15 (95%CI 0.003-0.292) p < 0.05) and leukocyte count (β = 0.57 (95%CI 0.234-0.909), p < 0.01), and HairE to IL-6 (β = 0.21 (95%CI 0.016-0.399), p < 0.05). In the longitudinal analyses, higher HairF was associated with yearly increases in BMI (β = 0.58% BMI change per year (95%CI 0.14-1.01%), p = 0.009) and higher HairE with increases in WC (β = 0.84% WC change per year (95%CI 0.02-1.69%), p = 0.049). Adjusting for baseline IL-6 or leukocytes did not change the found associations between HairGC and WC or BMI change., Conclusions: HairGC levels are positively associated to BMI, WC, IL-6 and leukocyte numbers in cross-sectional analyses, and to increases in BMI and WC in longitudinal analyses. Although causality is yet to be proven, higher long-term glucocorticoid levels could represent a relevant risk factor for the development of obesity., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Fetal exposure to cannabis and tobacco during pregnancy leads to adverse fetal and childhood outcomes. We hypothesized that fetal exposure to cannabis and tobacco have persistent programming effects on hypothalamic pituitary adrenal (HPA) axis functioning in childhood. Therefore, we examined the associations of parental cannabis and tobacco use during pregnancy with childhood hair cortisol and cortisone concentrations at 6 years, as biomarkers of long-term HPA-axis functioning., Method: In a population-based prospective birth cohort among 2577 mothers and their children, information of parental cannabis and tobacco use was collected by questionnaires, and maternal urine samples were additionally analyzed to detect cannabis metabolite concentrations. Cortisol and cortisone were measured in hair samples at 6 years. Linear regression analysis with adjustment for several confounders was used to test our hypothesis., Results: As compared to non-exposed children, offspring exposed to cannabis during pregnancy (in combination with tobacco) had higher childhood cortisol concentrations (log-10 transformed difference 0.16, 95 % Confidence Interval 0.04 to 0.28). This association was not mediated by birth weight. No differences in cortisone concentrations among cannabis-exposed children were observed. Maternal tobacco use during pregnancy was not associated with childhood cortisol or cortisone concentrations. Further, paternal cannabis or tobacco use was not associated with childhood cortisol or cortisone concentrations., Conclusions: Our findings suggest that maternal cannabis use, combined with tobacco, during pregnancy is associated with alterations in offspring HPA-axis functioning. Further studies need to replicate these findings, and assess the causality and long-term consequences of these associations., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Exposure to adversity is a risk factor for many mental and somatic health problems. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation is a potential mechanism linking adversity exposure and negative health outcomes. However, associations between adversity exposure and HPA-axis activity have been inconsistent. To understand the impact of adversity on the HPA-axis, we examined associations between early-life and recent adversity with hair cortisol concentration, an indicator of long-term systemic cortisol levels., Methods: We included 1166 adult participants of the Netherlands Study of Depression and Anxiety (NESDA). Hair cortisol was measured in 3 cm of proximal hair, representing cortisol exposure during the previous 3 months. Childhood maltreatment, childhood negative life events, and recent negative life events were retrospectively assessed using interview and self-report questionnaires. Linear regression analyses were performed to assess the associations between childhood maltreatment, childhood life events and recent life events with hair cortisol. Associations with cumulative adversity exposure and with subtypes of childhood maltreatment, childhood and recent negative life events were also investigated, as were interaction effects between adversity and sex, age and psychopathology., Results: Childhood maltreatment (β = 0.034, p = 0.243), childhood life events (β = - 0.017, p = 0.544), and recent life events (β = - 0.021, p = 0.456) were not significantly associated with hair cortisol levels. Subtypes of childhood maltreatment and specific childhood and recent life events were not significantly associated with hair cortisol (p FDR >0.05). There were no significant interaction effects between adversity exposure and sex, age or depression/anxiety diagnostic status on hair cortisol., Conclusions: There were no significant associations between childhood and recent adversity with systemic cortisol levels in adults. Effects of early-life and adult adversity are complex and may not directly impact on long-term systemic cortisol levels as measured in hair., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Maternal psychopathology during pregnancy is associated with negative outcomes in offspring. Increased placental transfer of maternal cortisol may contribute to mediate this association. Hair cortisol concentrations (HCCs) appear to be a good biomarker of long-term prenatal stress exposure. Little is known about the associations between severe maternal psychopathology and perinatal infant HCCs., Aims: We assessed HCCs in the perinatal period in mother-infant dyads with and without severe psychiatric disorders., Method: We examined group differences in HCCs of mother-infant dyads (n = 18) subjected to severe maternal psychiatric disorders versus healthy control dyads (n = 27). We assessed the correlation of HCCs between mother and infant within both groups, and the association between current maternal symptoms and HCCs in patient dyads., Results: Median (interquartile range) and distribution of HCC differed in patients compared with control mothers (U = 468.5, P = 0.03). HCCs in infants of patients did not differ from control infants (U = 250.0, P = 0.67). Subsequently, we found that HCCs within healthy control dyads were correlated (n = 27, r 0.55 (0.14), P = 0.003), but were not within patient dyads (n = 18, r 0.082 (0.13), P = 0.746). HCCs in infants of patients showed a positive correlation with maternal symptoms (n = 16, r = 0.63 (0.06), P = 0.008)., Conclusions: These preliminary findings suggest that infant HCC reflect perinatal stress exposure. In infants, these early differences could influence lifetime hypothalamic-pituitary-adrenal axis functioning, which might be associated with increased susceptibility to later disease.

Introduction: Corticosteroids are widely prescribed and their use has been linked to adverse cardiometabolic outcomes. A pivotal role in the action of corticosteroids is reserved for the glucocorticoid receptor (GR). Here, we assessed the relationship of glucocorticoid sensitivity-altering GR polymorphisms with anthropometrics and metabolic syndrome (MetS) in corticosteroid users., Methods: In this population-based cohort study (Lifelines), we genotyped 10,621 adult participants for GR hypersensitive (1/2 copies BclI and/or N363S) and GR resistant (1/2 copies ER22/23EK and/or 9β) variants. We assessed the relationship between functional GR polymorphisms with BMI, waist circumference (WC), and MetS in users of corticosteroids., Results: Overall corticosteroid use was associated with a significantly higher BMI and WC in GR wild-type (WT) users (BMI, +0.63 kg/m2 [0.09-1.16], p = 0.022; WC, +2.03 cm [0.61-3.44], p = 0.005) and GR hypersensitive (BMI, +0.66 kg/m2 [95% CI, 0.31-1.01]; WC, +2.06 cm [1.13-2.98], both p < 0.001) but not in GR resistant users. Significantly higher WC in GR resistant carriers was observed only for inhaled corticosteroid users. With respect to MetS, again only GR WT users (odds ratio [OR] 1.44 [1.07-1.94], p = 0.017) and GR hypersensitives (OR 1.23 [95% CI, 1.00-1.50], p = 0.046) were more likely to have MetS; even more pronounced in only inhaled corticosteroid users (GR WT users, OR 1.64 [1.06-2.55], p = 0.027; GR hypersensitive users, OR 1.43 [1.08-1.91], p = 0.013)., Conclusions: Polymorphisms associated with increased GR sensitivity and WT GR are related to increased BMI, WC, and an increased MetS presence in corticosteroid users, especially of the inhaled types, when compared to nonusers. The adverse effects of corticosteroid use are less pronounced in users harboring GR resistant polymorphisms., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Background: Prader-Willi syndrome (PWS) is a multisymptomatic, rare, genetic, neurodevelopmental disorder in adults mainly characterized by hyperphagia, cognitive dysfunction, behavioral problems and risk of morbid obesity. Although endocrine insufficiencies are common, hypocortisolism is rare and knowledge on long-term cortisol concentrations is lacking. The aim of this study was to evaluate long-term cortisol levels in PWS by measurements of hair cortisol., Methods: Twenty-nine adults with PWS, 15 men and 14 women, median age 29 years, median BMI 27 kg/m 2 , were included. Scalp hair samples were analyzed for cortisol content using liquid-chromatography tandem-mass spectrometry. In addition, a questionnaire on auxology, medication and stress were included. For comparison, 105 age- and sex-matched participants from the population-based Lifelines Cohort study were included as controls. The mean hair cortisol between the groups were compared and associations between BMI and stress were assessed by a generalized linear regression model., Results: In the PWS group large variations in hair cortisol was seen. Mean hair cortisol was 12.8 ± 25.4 pg/mg compared to 3.8 ± 7.3 pg/mg in controls (p = 0.001). The linear regression model similarly showed higher cortisol levels in patients with PWS, which remained consistent after adjusting for BMI and stress (p = 0.023). Furthermore, hair cortisol increased with BMI (p = 0.012) and reported stress (p = 0.014)., Conclusion: Long-term cortisol concentrations were higher in patients with PWS compared to controls and increased with BMI and stress, suggesting an adequate cortisol response to chronic stress. Hair cortisol demonstrate promising applications in the context of PWS treatment and disease management.

Objective: Posttraumatic stress disorder (PTSD) has been associated with lower circulating cortisol levels in specific subgroups, which have also been found in the offspring of people with PTSD. The analysis of hair cortisol concentrations (HCC) is a recent methodology which is used to assess long-term systemic cortisol levels. We aimed to study veterans with war-related lifetime PTSD and their respective offspring with regards to HCC. We also studied the influence of lifetime major depressive disorder (MDD), war experiences, and childhood adversities on HCC in these groups., Methods: 31 male veterans with PTSD and 28 without PTSD and 69 adult offspring were studied. HCC were quantified by liquid chromatography tandem-mass spectrometry., Results: No differences in HCC were found between veterans with and without PTSD, or between their respective offspring. Veterans without MDD showed a positive association between total war exposure and HCC. Veterans reporting more frequent childhood physical abuse had lower HCC. Veterans-with-PTSD's offspring with MDD had increased HCC compared to offspring without MDD. Offspring's exposure to more frequent childhood physical abuse was negatively associated with HCC in those without MDD., Conclusion: HCC did not appear to constitute a marker of intergenerational heritage of war-related PTSD, except in the case of veteranswith-PTSD's offspring with MDD. Our data suggest that HCC is a marker of adult reported childhood physical abuse.

Background: Regulation of the hypothalamic-pituitary-adrenal (HPA) axis is implicated in the pathogenesis of bipolar disorder (BD). However, the relationship between HPA-activity and disease severity is not fully elucidated. In this pilot study we aimed to explore the temporal relationship between HPA-activity and the risk of a manic episode in BD patients type I, by assessing long-term hair cortisol concentrations (HCC). Second, we explored the relation between HCC and the number of previous episodes., Methods: Hair samples were collected from 45 BD I patients in euthymic or manic state and compared to 17 controls. From each participant, two hair samples of 3 cm length were used to measure long-term cortisol, reflecting retrospect time frames of 1-3 months and 4-6 months respectively prior to sampling., Results: HCC in the BD group was slightly higher than in the control group in both hair segments (p = 0.049 and 0.03; after adjustment for age, sex, BMI and hair washing frequency p = 0.222 and 0.139). A significant peak in hair cortisol was observed prior to a manic episode (p = 0.036). Furthermore, we found a positive correlation between the number of mood episodes HCC (p = 0.03)., Conclusions: Our results indicate that long-term cortisol levels are slightly higher in BD, and in particular elevated in the months prior to a manic relapse. In addition HCC are positively associated with the number of previous mood episodes in the course of BD type I., (Copyright © 2020. Published by Elsevier Ltd.)

Purpose: Central serous chorioretinopathy (CSC), a distinct form of macular degeneration, has been associated with glucocorticoid use and possibly also with an increased endogenous activity of the hypothalamic-pituitary-adrenal (HPA) axis. To estimate long-term glucocorticoid exposure, measurement of hair cortisol concentrations (HCC) has emerged. This cross-sectional study aimed to investigate HCC, as a reflection of chronic endogenous steroid exposure, in a cohort of patients with chronic CSC (cCSC)., Methods: Hair cortisol concentrations (HCC) were determined in 48 patients with cCSC and 230 population-based controls (Lifelines cohort study), not using exogenous corticosteroids., Results: Increased HCC (defined as >10.49 pg/mg) were present in 2 (4%) patients with cCSC and 13 (6%) controls. Mean HCC values were not different between patients and controls, and no difference in HCC was found between patients with active cCSC disease and patients with inactive disease. No correlation between HCC and urinary free cortisol (UFC) levels in patients with cCSC was found., Conclusions: This study shows that HCC in patients with cCSC are not elevated compared to population-based controls, and no association between HCC and cCSC severity was found. This finding questions the previous suggestion that cCSC is associated with increased HPA axis activity. In line, HCC do not seem useful in monitoring cCSC disease activity., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Context: Medical schools are challenged to create academic environments that stimulate students to improve their study progress without compromising their well-being., Objectives: This prospective comparative cohort study investigated the effects of raising Year-1 standards on academic performance and on students' chronic psychological and biological stress levels., Methods: In a Dutch medical school, students within the last Bachelor's degree cohort (n = 410) exposed to the 40/60 (67%) credit Year-1 standard (67%-credit cohort) were compared with students within the first cohort (n = 413) exposed to a 60/60 (100%) credit standard (100%-credit cohort). Main outcome measures were Year-1 pass rate (academic performance), mean score on the Perceived Stress Scale (PSS, psychological stress) and hair cortisol concentration (HCC, biological stress)., Results: Year-1 pass rates were significantly higher in the 100%-credit cohort (odds ratio [OR] 4.65). Interestingly, there was a significant interaction effect (OR 0.46), indicating that raising the standard was more effective for male than for female students. PSS scores (n = 234 [response rate [RR]: 57%] and n = 244 [RR: 59%] in the 67%- and 100%-credit cohorts, respectively) were also significantly higher in the 100%-credit cohort (F (1,474)  = 15.08, P < .001). This applied specifically to female students in the 100%-credit cohort. Levels of HCC (n = 181 [RR: 44%] and n = 162 [RR: 39%] respectively) did not differ between cohorts, but were significantly higher in female students (F (1,332)  = 7.93, P < .01). In separate models including cohort and gender, both PSS score (OR 0.91) and HCC (OR 0.38) were significantly associated with Year-1 performance. Only students with both high PSS scores and high HCC values were significantly at risk of lower Year-1 pass rates (OR 0.27), particularly male students., Conclusions: Raising the Year-1 performance standard increased academic performance, most notably in male students. However, it also increased levels of perceived stress, especially in female students. In particular, the combination of high levels of perceived stress and biological stress, as measured by long-term cortisol, was related to poor academic performance. The study suggests a relationship between raising performance standards and student well-being, with differential effects in male and female students., (© 2020 The Authors. Medical Education published by Association for the Study of Medical Education and John Wiley & Sons Ltd.)

Background: Human scalp hair is a valuable matrix for determining long-term cortisol concentrations, with wide-spread applicability in clinical care as well as research. However, pediatric reference intervals are lacking. The aim of this cross-sectional study is to establish age-adjusted reference intervals for hair cortisol in children and to gain insight into hair growth velocity in children up to 2 years old., Methods: A total of 625 healthy children were enrolled through recruitment in pregnancy, infant-welfare clinics, and school visits. Scalp hair cortisol levels were measured using liquid chromatography-tandem mass spectrometry. Age-adjusted reference intervals were established in children from birth to 18 years old. Hair growth velocity was determined in children 0-2 years of age by measuring hair length at 4- to 10-week intervals., Results: Hair cortisol levels were high (162.4 pg/mg, 2.5th-97.5th percentile: 28.8-961) after birth with a sharp fall in the first 3 months of life. This is followed by lower values until age 6 and then by graduated and subtle higher values to adult concentrations are reached at the age of 18 years (3.0 pg/mg, 2.5th-97.5th percentile: 0.53-17.8). Average hair growth velocity measured in mm/month was significantly lower in infants 0-6 months of age compared to children 12-24 months (3.5 versus 9.4, P < 0.001)., Conclusions: This is the first study to provide age-adjusted reference intervals for hair cortisol in children from 0-18 years. Higher hair cortisol concentrations in infants might be explained by the significantly lower hair growth rate in the first year of life. The establishment of pediatric hair cortisol reference ranges broadens the potential applications of this biomarker in pediatric clinical care., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Use of local corticosteroids, especially the inhaled types, has increasingly been associated with systemic uptake and consequent adverse effects. In this study, we assessed the associations between the use of different corticosteroid types with cognitive and neuropsychiatric adverse effects related to high glucocorticoid exposure., Methods: In 83,592 adults (mean age 44 years, 59% women) of the general population (Lifelines Cohort Study), we analyzed the relationship between corticosteroid use with executive cognitive functioning (Ruff Figural Fluency Test), and presence of mood and anxiety disorders (Mini-International Neuropsychiatric Interview survey). We performed additional exploration for effects of physical quality of life (QoL; RAND-36), and inflammation (high-sensitive C-reactive protein [CRP])., Results: Cognitive scores were lower among corticosteroid users, in particular of systemic and inhaled types, when compared to nonusers. Users of inhaled types showed lower cognitive scores irrespective of physical QoL, psychiatric disorders, and high-sensitive CRP. Overall corticosteroid use was also associated with higher likelihood for mood and anxiety disorders. Users of inhaled corticosteroids were more likely to have mood disorders (OR 1.40 [95% CI 1.19-1.65], p < 0.001) and anxiety disorders (OR 1.19 [95% CI 1.06-1.33], p = 0.002). These findings were independent of physical QoL. A higher likelihood for mood disorders was also found for systemic users whereas nasal and dermal corticosteroid users were more likely to have anxiety disorders., Conclusions: Commonly used local corticosteroids, in particular inhaled types, and systemic corticosteroids are associated with reduced executive cognitive functioning and a higher likelihood of mood and anxiety disorders in the general adult population., (The Author(s). Published by S. Karger AG, Basel.)

Understanding maternal mental health and cortisol regulation across pregnancy and the relationship to the development of the offspring's stress regulation is critical to a range of health outcomes. The aim of this study was to investigate infant and maternal cortisol in women with depression. Data were obtained from 241 pregnant women within the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS), a selected pregnancy cohort study. Depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV) and repeat Edinburgh Postnatal Depression Scale (EPDS). Repeated measures of antidepressant use, stressful events, anxiety symptoms and maternal hair cortisol concentrations (HCC) and infant cortisol at 12 months postpartum in saliva and hair. Socio-emotional outcomes were measured at 12 months by maternal report on the Brief Infant and Toddler Socio-emotional Assessment (BITSEA). This study found that maternal depression was not associated with maternal HCC. Anxiety, stress and antidepressant use were not associated with maternal HCC. Independently, higher maternal 3rd trimester maternal depressive and anxiety symptoms were associated with lower infant cortisol response at 12 months of age. A higher number of postpartum stressful events was associated with lower infant cortisol response. Lower infant stress reactivity was associated with higher externalizing symptoms at 12 months of age. Future studies are required to understand implications for later mental health., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Obesity is a worldwide growing problem. When confronted with obesity, many health care providers focus on direct treatment of the consequences of adiposity. We plead for adequate diagnostics first, followed by an individualized treatment. We provide experience-based and evidence-based practical recommendations (illustrated by clinical examples), to detect potential underlying diseases and contributing factors. Adult patients consulting a doctor for weight gain or obesity should first be clinically assessed for underlying diseases, such as monogenetic or syndromic obesity, hypothyroidism, (cyclic) Cushing syndrome, polycystic ovarian syndrome (PCOS), hypogonadism, growth hormone deficiency, and hypothalamic obesity. The most important alarm symptoms for genetic obesity are early onset obesity, dysmorphic features/congenital malformations with or without intellectual deficit, behavioral problems, hyperphagia, and/or striking family history. Importantly, also common contributing factors to weight gain should be investigated, including medication (mainly psychiatric drugs, (local) corticosteroids, insulin, and specific β-adrenergic receptor blockers), sleeping habits and quality, crash diets and yoyo-effect, smoking cessation, and alcoholism. Other associated conditions include mental factors such as chronic stress or binge-eating disorder and depression.Identifying and optimizing the underlying diseases, contributing factors, and other associated conditions may not only result in more effective and personalized treatment but could also reduce the social stigma for patients with obesity., (© 2019 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Posttraumatic stress disorder (PTSD) is associated with altered hypothalamic-pituitary-adrenal (HPA) axis function. Measurement of hair cortisol concentrations (HCC) allows retrospective assessment of HPA axis regulation over prolonged periods of time. Currently, research investigating HCC in PTSD remains sparse. Previous cross-sectional studies have included only civilian populations, although it is known that trauma type moderates associations between PTSD status and HPA axis function. We investigated differences in HCC between trauma-exposed female police officers with current PTSD (n = 13) and without current and lifetime PTSD (n = 15). To investigate whether HCC was associated with neural correlates of PTSD, we additionally performed exploratory correlational analyses between HCC and amygdala reactivity to negative affective stimuli. We observed significantly lower HCC in participants with PTSD than in participants without PTSD, d = 0.89. Additionally, within participants with PTSD, we observed positive correlations between HCC and right amygdala reactivity to negative affective (vs. happy/neutral) faces, r = .806 (n = 11) and left amygdala reactivity to negative affective (vs. neutral) pictures, r = .663 (n = 10). Additionally, left amygdala reactivity to negative faces was positively correlated with HCC in trauma-exposed controls, r = .582 (n = 13). This indicates that lower HCC is associated with diminished amygdala differentiation between negative affective and neutral stimuli. Thus, we observed lower HCC in trauma-exposed noncivilian women with PTSD compared to those without PTSD, which likely reflects prolonged HPA axis dysregulation. Additionally, HCC was associated with hallmark neurobiological correlates of PTSD, providing additional insights into pathophysiological processes in PTSD., (© 2019 The Authors. Journal of Traumatic Stress published by Wiley Periodicals, Inc. on behalf of International Society for Traumatic Stress Studies.)

Objectives: We aimed to investigate whether five potential functional haplotypes of the glucocorticoid receptor (GR) gene and a single-nucleotide polymorphism of 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) are associated with clinical outcome in ANCA-associated vasculitis., Methods: Patients diagnosed with ANCA-associated vasculitis (n = 241) were genotyped for five polymorphisms of the GR gene and one polymorphism of the HSD11B1 gene. GR gene haplotypes were predicted based on genotyping results. Relapse-free survival, mortality, renal survival, metabolic adverse events and infections were compared between carriers and non-carriers of GR haplotypes and the HSD11B1 genotype., Results: Carriers of haplotype 4 (ER22/23EK + 9β+TthIII1) of GR had a significantly higher 5-year mortality risk [hazard ratio (HR) 4.5 (95% CI 1.6, 12.8)] and had a higher risk of developing end-stage renal disease [HR 7.4 (95% CI 1.9, 28.7)]. Carriers of a minor variant of HSD11B1 more frequently experienced relapse [HR 2.5 (95% CI 1.5, 4.1)] except if they also carried haplotype 1 (BclI) of GR. Homozygous carriers of haplotype 1 had a higher risk of developing dyslipidaemia [HR 4.1 (95% CI 1.8, 9.6)]. The occurrence of infections did not differ between GR haplotypes and HSD11B1 genotypes., Conclusion: Haplotypes 1 and 4 of GR and a polymorphism of the HSD11B1 gene were associated with clinically relevant inflammatory and metabolic outcomes in ANCA-associated vasculitis., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)