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Purpose Return to work self-efficacy (RTW-SE) is a strong predictor of return to work (RTW) in employees with mental health problems (MHPs). However, little is known about the development of RTW-SE during the RTW process. In this study, we aimed to identify RTW-SE trajectories in the year following sick leave in employees with MHPs and provided a description of the trajectories in terms of personal and work characteristics, and RTW status. Methods This multi-wave study included 111 employees with MHPs. RTW-SE was measured at baseline, and at 3, 6, and 12 months follow-up with the RTW-SE scale for employees with MHPs. Results Latent class growth analysis revealed six trajectories. In three trajectories employees had increasing RTW-SE scores, namely (class 1) low start, moderate increase, (class 3) moderate start, small increase and (class 5) moderate start, steep increase. The other trajectories were defined by (class 2) persistently high, (class 6) persistently low, and (class 4) decreasing RTW-SE scores over time. Employees across the various trajectories differed significantly with respect to RTW status, and personal and work characteristics measured at baseline, including age, gender, and type of MHP. Less favorable trajectories (class 4 and 6) were characterized by higher age, a higher prevalence of anxiety disorder and lower RTW rates. The most favorable trajectory (class 2) was characterized by a higher proportion of stress-related disorders and less major depression diagnoses. Conclusions Large heterogeneity exists in terms of RTW-SE trajectories in employees with MHPs and significant differences were found across the trajectories regarding personal and work characteristics, and RTW status. Insights into RTW-SE trajectories and their attributes are important to advance more effective and personalized RTW treatment for employees with MHPs.

BackgroundInflammation and metabolic dysregulation are age-related physiological changes and are associated with depressive disorder. We tried to identify subgroups of depressed older patients based on their metabolic-inflammatory profile and examined the course of depression for these subgroups.MethodsThis clinical cohort study was conducted in a sample of 364 depressed older (⩾60 years) patients according to DSM-IV criteria. Severity of depressive symptoms was monitored every 6 months and a formal diagnostic interview repeated at 2-year follow-up. Latent class analyses based on baseline metabolic and inflammatory biomarkers were performed. Adjusted for confounders, we compared remission of depression at 2-year follow-up between the metabolic-inflammatory subgroups with logistic regression and the course of depression severity over 2-years by linear mixed models.ResultsWe identified a ‘healthy’ subgroup (n = 181, 49.7%) and five subgroups characterized by different profiles of metabolic-inflammatory dysregulation. Compared to the healthy subgroup, patients in the subgroup with mild ‘metabolic and inflammatory dysregulation’ (n = 137, 37.6%) had higher depressive symptom scores, a lower rate of improvement in the first year, and were less likely to be remitted after 2-years [OR 0.49 (95% CI 0.26–0.91)]. The four smaller subgroups characterized by a more specific immune-inflammatory dysregulation profile did not differ from the two main subgroups regarding the course of depression.ConclusionsNearly half of the patients with late-life depressions suffer from metabolic-inflammatory dysregulation, which is also associated with more severe depression and a worse prognosis. Future studies should examine whether these depressed older patients benefit from a metabolic-inflammatory targeted treatment.

We investigated preserved episodic recognition memory based on incidental learning of visual associations in Alzheimer's disease (AD). In a cross-sectional design, we analyzed episodic memory score profiles of patients with amnestic mild cognitive impairment (a-MCI) (n = 42) or mild AD (n = 19) who had hippocampal atrophy, and healthy elderly controls (n = 43). The Visual Association Test-Extended served as a measure of episodic memory. Multiple-choice cued recognition was compared with paired associate recall and free recall within groups. Results showed that patients recognized learned material much better compared to when they had to recall material, resulting in large effect sizes (Cohen's d) ranging from 1.3 to 3.5. We conclude that episodic recognition memory based on incidental learning of visual associations is largely preserved when compared to recall in a-MCI and mild AD. This suggests that the episodic memory impairment in AD may be characterized as a retrieval impairment rather than a consolidation impairment, indicating that preserved recognition compared to recall may be compatible with AD being the correct diagnosis. Measuring the episodic memory impairment in AD may benefit from using tests that capture different aspects of memory processes such as incidental learning of visual associations.

BACKGROUND AND OBJECTIVE: After whiplash injury, some patients develop chronic whiplash-associated disorders. The exact pathophysiology of this chronification is still unclear and more knowledge is needed regarding the different post-injury phases. Therefore, studies were searched that examined temporal changes in pain processing, measured by Quantitative Sensory Testing (QST). DATABASES AND DATA TREATMENT: This systematic review searched three electronic databases (Medline, Web of Science and Embase) for articles meeting the eligibility requirements. Risk of bias was assessed according to a modified Newcastle-Ottawa Scale. RESULTS: The 12 included studies presented moderate to good methodological quality. These studies showed altered pain processing within the first month after injury and normalization within 3 months in 59%-78% of the patients. After 3 months, recovery stagnates during the following years. Thermal and widespread mechanical hyperalgesia occur already in the acute phase, but only in eventually non-recovered patients. CONCLUSIONS: Differences in pain processing between recovering and non-recovering patients can be observed already in the acute phase. Early screening for signs of altered pain processing can identify patients with high risk for chronification. These insights in temporal changes show the importance of rehabilitation in the acute phase. Future research should target to develop a standardized (bed-site) QST protocol and collect normative data which could, in relation with self-reported pain parameters, allow clinicians to identify the risk for chronification. SIGNIFICANCE: Altered pain processing is present soon after whiplash injury, but usually recovers within 3 months. Non-recovering patients show little to no improvements in the following years. Differences between recovering and non-recovering patients can be observed by Quantitative Sensory Testing already in the acute phase. Therefore, it is considered a feasible and effective tool that can contribute to the identification of high-risk patients and the prevention of chronification.

The 22q11.2 deletion syndrome (22q11.2DS) is a multisystem disorder with an estimated prevalence of 1:3000 live births. Manifestations show a marked variability in expression and include speech- and language delay, intellectual disability, and neuropsychiatric disorders. We aim to provide an overview of ocular findings in 22q11.2DS in order to optimize recommendations for ophthalmic screening. We combined results from a systematic literature review with results from a multicenter cross-sectional study of patients with 22q11.2DS who were assessed by an ophthalmologist. Our systematic literature search yielded four articles, describing 270 patients. We included 132 patients in our cross-sectional study (median age 8.9 [range 0–56] years). Most reported ocular findings were retinal vascular tortuosity (32%–78%), posterior embryotoxon (22%–50%), eye lid hooding (20%–67%), strabismus (12%–36%), amblyopia (2%–11%), ptosis (4%–6%), and refractive errors, of which hyperopia (6%–48%) and astigmatism (3%–23%) were most common. Visual acuity was (near) normal in most patients (91%–94%). Refractive errors, strabismus, and amblyopia are treatable conditions that are frequently present in patients with 22q11.2DS and should be corrected at an early stage. Therefore, in 22q11.2DS, we recommend ophthalmic and orthoptic screening at the age of 3 years or at diagnosis, and a low-threshold referral in adults.

Different lifestyles have an impact on useful metabolic functions, causing disorders. Different lipids are involved in the metabolic functions that play various vital roles in the body, such as structural components, storage of energy, in signaling, as biomarkers, in energy metabolism, and as hormones. Inter-related disorders are caused when these functions are affected, like diabetes, cancer, infections, and inflammatory and neurodegenerative conditions in humans. During the Covid-19 period, there has been a lot of focus on the effects of metabolic disorders all over the world. Hence, this review collectively reports on research concerning metabolic disorders, mainly cardiovascular and diabetes mellitus. In addition, drug research in lipid metabolism disorders have also been considered. This review explores lipids, metabolism, lipid metabolism disorders, and drugs used for these disorders.

Rationale & Objective The identification of pathogenic variants in genes associated with chronic kidney disease can provide patients and nephrologists with actionable information to guide diagnoses and therapeutic plans. However, many nephrologists do not use genetic testing despite continually lower costs over time and more widespread availability. Study Design We conducted a survey to uncover the perceptions of general adult nephrologists about the utility of and barriers to genetic testing in clinical practice. Setting & Participants The online survey was administered to board-certified nephrologists (n = 10,054) in the United States. Analytical Approach We analyzed demographic characteristics of the survey respondents and their responses in the context of their use of genetic testing in routine clinical practice. Results A total of 149 nephrologists completed the survey, with 72% (107 of 149) reporting any genetic test use in their practice. On average, tests were ordered for 3.8% of their patient population. Thirty-five percent of responses from nephrologists without a history of genetic test use ranked perceived barriers as “extremely significant” compared with 23% of responses from those who had previously used genetic tests. However, both users and nonusers of genetic tests indicated high cost (users: 46%, 49 of 107; nonusers 69%, 29 of 42) and poor availability or lack of ease (users: 33%, 35 of 107; nonusers: 57%; 24 of 42) of genetic testing as the most significant perceived barriers to implementation. Limitations The survey used in this study was not previously validated; additionally, because of the relatively small number of responses, there might have been a selection bias among the responders. Conclusions Although most nephrologists reported using genetic tests in clinical practice, high costs and poor availability or the lack of ease of use were perceived as the most important barriers to routine adoption. These observations indicate that educational programs that cover a range of topics, from genetics of chronic kidney disease to selection of the test, may help mitigate these barriers and enhance the use of genetic testing in nephrology practice.

Background Irritable bowel syndrome (IBS) is a highly prevalent disorder with significant negative impact on quality of life of patients that results in high healthcare use and costs. Improving healthcare outcomes for IBS patients is warranted, however the exact needs of IBS patients with regard to therapy and control of symptoms are unknown. Methods Focus group interviews, using a two-stage model, were performed with twenty-three IBS patients meeting Rome III criteria and one mother of a patient, from four different regions from the Netherlands. Results Twenty-four participants were included of whom majority were female (n = 21), mean age was 43 years, and mean duration of IBS was 18 years. Five categories of patients’ perspectives were identified: clear communication, a multidisciplinary treatment team, centers of expertise, focus on scientific research and information about IBS that is widely available for patients. Conclusions Based on these findings we highlight the need for IBS care givers to take these key items into account in IBS care. These elements aid clinicians, but mostly patients, in coping and management of symptoms and subsequent healthcare outcomes, reducing overall healthcare use and costs.

Objective: Postpartum psychiatric morbidity is one of the most frequent complications of birth, cause of suicides and maternal death.We aimed to determine the prevalence of postpartum depression (PPD) among mothers who gave birth in the last 6 months and alsoassess the risk factors, particularly poor social and spousal support.Patients and Methods: This is a cross-sectional study. We included 303 mothers who gave birth in the last 6 months attendingthree family health centers in a district of Istanbul. Stratified sampling method was used. Edinburgh Postpartum Depression Scale,Postpartum Support Scale, The Scale of Perceived Spousal Support Among Women in Early Postpartum Period were administered.Univariate and multivariate statistical analyses were used.Results: Postpartum depression prevalence was 9.9% among the participants. According to multivariate statistical analysis; while ahigher income (OR : 0.99) and a higher spousal support score (OR: 0.95) were found as protective factors, actively working (OR :8.63),unplanned pregnancy (OR: 3.21), having a first child compared to having two children (OR: 11.20), having low birth weight infant(OR: 8.33) and unmet social support (OR: 1.02) were risk factors for PPD (p

OBJECTIVE: Prenatal exposure to the antiseizure medication (ASM) valproate is associated with an increased risk of congenital malformations, but warnings against the use of valproate in pregnancy were not issued until 2009. The objective was to study how early administrative health registers could have identified the teratogenic risk associated with valproate.METHODS: This was a population-based cohort study of individual-linked data from Danish health care and socioeconomic registers including children born in Denmark between January 1, 1997 and December 31, 2014. Information on ASM use, including valproate, in pregnancy was obtained from the Danish National Prescription Registry. Children identified with major congenital malformations from the Danish National Patient Register and the Danish Register of Causes of Death were included. Using logistic regression models, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for major congenital malformations during the first year of life in children with and without prenatal exposure to ASMs adjusted for potential confounders.RESULTS: Among the 895 507 children (males, 51.3%), 31 790 (3.6%) were diagnosed with a major congenital malformation in the first year of life. In the analyses including children born in 1997, the risk of major congenital malformations among children prenatally exposed to valproate compared with children not exposed to ASMs was increased by a fully adjusted OR (aOR) of 3.95 (95% CI = 1.65-9.47). With the addition of data from the following years, the teratogenic effect of valproate was further substantiated, as the precision of the estimate improved (1997-2014: aOR = 2.44, 95% CI = 1.80-3.30).SIGNIFICANCE: Using Danish health care data, we were able to identify a teratogenic risk associated with prenatal valproate exposure in children born in 1997, which is much earlier than prospective clinical cohorts. Health registry data represent an important tool for early identification of risk associated with drugs in pregnancy.

Contains fulltext : 245998.pdf (Publisher’s version ) (Open Access) Objectives: Frailty marks an increased risk for adverse health outcomes. Since childhood trauma is associated with the onset of physical and mental health diseases during the lifespan, we examined the link between childhood trauma and multidimensional frailty. Method: A cross-sectional study embedded in a clinical cohort study (ROM-GPS) of older (>=60 years) patients (n=182) with a unipolar depressive-, anxiety- and/or somatic symptom disorder according to DSM-criteria referred to specialized geriatric mental health care. Frailty was assessed with the Tilburg Frailty Indicator (TFI), comprising a physical, psychological, and social dimension. Physical, sexual and psychological abuse and emotional neglect before the age of 16 years was measured with a structured interview. Results: Of 182 patients, 103 (56.6%) had experienced any childhood trauma and 154 (84.6%) were frail (TFI sum score >=5). Linear regression analyses, adjusted for lifestyle, psychological and physical-health factors, showed that the presence of any type of childhood trauma was not associated with the TFI sum score, however when considered separately, physical abuse was (ß=0.16, p=.037). Regarding the specific frailty dimensions, any childhood trauma was associated with social frailty (ß=0.18, p=.019), with emotional neglect as main contributor. Conclusion: These findings demonstrate a complex link between different types of childhood trauma and multidimensional frailty among older psychiatric patients. Regarding the three dimensions of frailty, social frailty seems most affected by childhood trauma. This may have been underestimated until now and should receive more attention in clinical care and future research. 7 p.

Background Serious mental illnesses (SMI) such as schizophrenia and bipolar disorder first develop between ages 14 and 25. Once diagnosed, young peoples’ health can deteriorate, and it is therefore vital to detect this early to prevent severe outcomes including hospitalisations and deaths by suicide. The main study aim is to describe and discuss observational studies that examine signs of deterioration in young patients with SMI. Methods A systematic review guided by the published protocol was conducted. Cumulative Index to Nursing and allied Health Literature (CINAHL), MEDLINE, Embase, PsycINFO, Health Management Information Consortium (HMIC) and Web of Science were searched against pre-defined criteria until 1 March 2021. Observational studies were extracted according to design, country, participant, indicator, outcome and main finding categories. Quality was assessed independently using the Newcastle Ottawa Scale (NOS). Results Of the 15,788 publications identified, 5 studies were included and subjected to narrative synthesis. Two indicators of mental health deterioration were identified: cognitive functioning (decline, worsening and poor school/academic performance) and expressed emotion status. Indicators revealed mixed views on predicting deterioration. Worsening cognitive functioning and expressed emotion status significantly predicted medication non-adherence and relapse respectively. However, a decline in cognitive functioning (poor academic performance) was not found to significantly correlate to deaths by suicide. Study quality was mostly poor and associations between indicators and varied outcomes were weak. The heterogeneous nature of the data made comparisons difficult and did not allow for further statistical analysis. Conclusion To our knowledge, this is the first review of observational studies to identify indicators of deterioration in young patients with SMI. Worsening cognitive functioning and expressed emotion status could indicate non-adherence and relapse in young patients with SMI but larger sample sizes in good quality studies are needed. The dearth of observational studies means further research is required to ascertain other indicators of deterioration before serious outcomes occur. Funding This work was supported by the National Institute for Health Research (NIHR) Imperial Patient Safety Translational Research Centre via an NIHR programme grant. The authors are also grateful for support from the NIHR under the Applied Health Research programme for North West London and the NIHR Imperial Biomedical Research Centre. The views expressed in this publication are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Trial registration This systematic review has been registered on PROSPERO (registration number: CRD42017075755).

It is unclear whether testosterone replacement therapy (TRT) in adolescent boys, affected by a range of endocrine diseases that may be associated with hypogonadism, is particularly common. The aim of this study was to assess the contemporary practice of TRT in boys included in the I-DSD Registry. All participating centres in the I-DSD Registry that had boys between 10 and 18 years of age and with a condition that could be associated with hypogonadism were invited to provide further information in 2019. Information on 162 boys was collected from 15 centres that had a median (range) number of 6 boys per centre (1.35). Of these, 30 (19%) from 9 centres were receiving TRT and the median (range) age at the start was 12.6 years (10.8–16.2), with 6 boys (20%) starting at

People with autism spectrum disorders (ASDs) have difficulty with socio-emotional functioning; however, research on facial emotion recognition (FER) remains inconclusive. Individuals with ASD might be using atypical compensatory mechanisms that are exhausted in more complex tasks. This study compared response accuracy and speed on a forced-choice FER task using neutral, happy, sad, disgust, anger, fear and surprise expressions under both timed and non-timed conditions in children with and without ASD ( n = 18). The results showed that emotion recognition accuracy was comparable in the two groups in the non-timed condition. However, in the timed condition, children with ASD were less accurate in identifying anger and surprise compared to children without ASD. This suggests that people with ASD have atypical processing of anger and surprise that might become challenged under time pressure. Understanding these atypical processes, and the environmental factors that challenge them, could be beneficial in supporting socio-emotional functioning in people ASD.

Objective Depression has been associated with metabolomic alterations. Depressive and anxiety disorders are often comorbid diagnoses and are suggested to share etiology. We investigated whether differential metabolomic alterations are present between anxiety and depressive disorders and which clinical characteristics of these disorders are related to metabolomic alterations.Methods Data were from the Netherlands Study of Depression and Anxiety (NESDA), including individuals with current comorbid anxiety and depressive disorders (N = 531), only a current depression (N = 304), only a current anxiety disorder (N = 548), remitted depressive and/or anxiety disorders (N = 897), and healthy controls (N = 634). Forty metabolites from a proton nuclear magnetic resonance lipid-based metabolomics panel were analyzed. First, we examined differences in metabolites between disorder groups and healthy controls. Next, we assessed whether depression or anxiety clinical characteristics (severity and symptom duration) were associated with metabolites.Results As compared to healthy controls, seven metabolomic alterations were found in the group with only depression, reflecting an inflammatory (glycoprotein acetyls; Cohen's d = 0.12, p = 0.002) and atherogenic-lipoprotein-related (e.g., apolipoprotein B: Cohen's d = 0.08, p = 0.03, and VLDL cholesterol: Cohen's d = 0.08, p = 0.04) profile. The comorbid group showed an attenuated but similar pattern of deviations. No metabolomic alterations were found in the group with only anxiety disorders. The majority of metabolites associated with depression diagnosis were also associated with depression severity; no associations were found with anxiety severity or disease duration.Conclusion While substantial clinical overlap exists between depressive and anxiety disorders, this study suggests that altered inflammatory and atherogenic-lipoprotein-related metabolomic profiles are uniquely associated with depression rather than anxiety disorders.

Supplemental digital content is available in the text., Objective This study aimed to examine the association of a mother’s loss of a close relative before or during pregnancy with intellectual disability (ID) in the offspring. Methods We performed a nationwide population-based cohort study based on Danish national registries. All live-born singletons born in Denmark during the 1978–2016 period (n = 2,216,601) were followed up starting from birth to 38 years of age. Log-linear Poisson regression was used to estimate the association between maternal bereavement (the death of an older child, a partner, or a parent 1 year before or during pregnancy) and the risk of ID in the offspring. Results Maternal bereavement during or before pregnancy was associated with an increased risk of ID (incidence rate ratio [IRR] = 1.15; 95% confidence interval [CI] = 1.04–1.28). The risk of ID was increased by 27% when maternal bereavement occurred during pregnancy (IRR = 1.27; 95% CI = 1.08–1.49). When stratifying on the child’s sex, we also observed an increased risk of ID associated with maternal bereavement during pregnancy both for male (IRR = 1.25; 95% CI = 1.02–1.53) and for female (IRR = 1.31; 95% CI = 1.02–1.69), respectively. The IRRs for unnatural death of a relative were also elevated (IRR = 1.22; 95% CI = 0.91–1.64) in general, although the difference was not statistically significant. Conclusions Our findings suggest that prenatal stress due to maternal loss of a close relative may increase the risk of offspring’s ID of both sexes, in particular when the loss happened during pregnancy.

BACKGROUND: Hippocampal alterations are among the most replicated neuroimaging findings across the psychosis spectrum. Moreover, there is strong translational evidence that preserving the maturation of hippocampal networks in mice models prevents the progression of cognitive deficits. However, the developmental trajectory of hippocampal functional connectivity (HFC) and its contribution to psychosis is not well characterized in the human population. 22q11 deletion syndrome (22q11DS) offers a unique model for characterizing early neural correlates of schizophrenia., METHODS: We acquired resting-state functional magnetic resonance imaging in 242 longitudinally repeated scans from 84 patients with 22q11DS (30 with moderate to severe positive psychotic symptoms) and 94 healthy control subjects in the age span of 6 to 32 years. We obtained bilateral hippocampus to whole-brain functional connectivity and employed a novel longitudinal multivariate approach by means of partial least squares correlation to evaluate the developmental trajectory of HFC across groups., RESULTS: Relative to control subjects, patients with 22q11DS failed to increase HFC with frontal regions such as the dorsal part of the anterior cingulate cortex, prefrontal cortex, and supplementary motor area. Concurrently, carriers of the deletion had abnormally higher HFC with subcortical dopaminergic areas. Remarkably, this aberrant maturation of HFC was more prominent during midadolescence and was mainly driven by patients exhibiting subthreshold positive psychotic symptoms., CONCLUSIONS: Our findings suggest a critical period of prefrontal cortex & ndash;hippocampal & ndash;striatal circuit dysmaturation, particularly during late adolescence, which in light of current translation evidence could be a target for short-term interventions to potentially achieve long-lasting rescue of circuit dysfunctions associated with psychosis.

Introduction: Current developments to assess qualitative and quantitative platelet traits in flowed whole-blood are based on microfluidic devices that mostly operate at room temperature. However, operation at physiological temperature (37 degrees;C) may increase the assay's sensitivity, and facilitates the comparison to other platelet function tests of the diagnostic laboratory.Materials and methods: We adapted the conventional microspot-based microfluidic device with a simple thermocoupled pre-heating module. Automated analysis of microscopic images assisted in obtaining five timedependent parameters of thrombus formation over collagen microspots (shear rate 1000 s- 1). These modifications allowed rapid testing of control and patient blood samples at physiological temperature.Results and conclusion: The higher temperature enhanced platelet adhesion and aggregation as well as late thrombus characteristics such as size and contraction, when compared to room temperature. Moreover, assessment at 37 degrees C indicated a time-dependent impairment of the thrombus parameters in blood from patients taking common antiplatelet medication, i.e. aspirin and/or clopidogrel. This pointed to increased contribution of the autocrine platelet agonists thromboxane A2 and ADP in the buildup of contracted thrombi under flow. Overall, this study underlined the advantage of multiparameter assessment of microfluidic thrombus formation in detecting an acquired platelet dysfunction, when operating at physiological temperature. This work may bring microfluidics tests closer to the diagnostic laboratory.Introduction: Current developments to assess qualitative and quantitative platelet traits in flowed whole-blood are based on microfluidic devices that mostly operate at room temperature. However, operation at physiological temperature (37 degrees C) may increase the assay's sensitivity, and facilitates the comparison to other platelet function tests of the diagnostic laboratory.Materials and methods: We adapted the conventional microspot-based microfluidic device with a simple thermocoupled pre-heating module. Automated analysis of microscopic images assisted in obtaining five timedependent parameters of thrombus formation over collagen microspots (shear rate 1000 s- 1). These modifications allowed rapid testing of control and patient blood samples at physiological temperature.Results and conclusion: The higher temperature enhanced platelet adhesion and aggregation as well as late thrombus characteristics such as size and contraction, when compared to room temperature. Moreover, assessment at 37 degrees C indicated a time-dependent impairment of the thrombus parameters in blood from patients taking common antiplatelet medication, i.e. aspirin and/or clopidogrel. This pointed to increased contribution of the autocrine platelet agonists thromboxane A2 and ADP in the buildup of contracted thrombi under flow. Overall, this study underlined the advantage of multiparameter assessment of microfluidic thrombus formation in detecting an acquired platelet dysfunction, when operating at physiological temperature. This work may bring microfluidics tests closer to the diagnostic laboratory.

BACKGROUND: The aim of the study was to evaluate familial Mediterranean fever (FMF) mutation analysis in pediatric patients with inflammatory bowel disease (IBD). The relation between MEFV mutations and chronic inflammatory diseases has been reported previously. METHODS: Children with IBD (334 ulcerative colitis (UC), 224 Crohn’s disease (CD), 39 indeterminate colitis (IC)) were tested for FMF mutations in this multicenter study. The distribution of mutations according to disease type, histopathological findings, and disease activity indexes was determined. RESULTS: A total of 597 children (mean age: 10.8 ± 4.6 years, M/F: 1.05) with IBD were included in the study. In this study, 41.9% of the patients had FMF mutations. E148Q was the most common mutation in UC and CD, and M694V in IC (30.5%, 34.5%, 47.1%, respectively). There was a significant difference in terms of endoscopic and histopathological findings according to mutation types (homozygous/heterozygous) in patients with UC (P < .05). There was a statistically significant difference between colonoscopy findings in patients with or without mutations (P = .031, P = .045, respectively). The patients with UC who had mutations had lower Pediatric Ulcerative Colitis Activity Index (PUCAI) scores than the patients without mutations (P = .007). Conclusion: Although FMF mutations are unrelated to CD patients, but observed in UC patients with low PUCAI scores, it was established that mutations do not have a high impact on inflammatory response and clinical outcome of the disease.

Inborn errors of metabolism (IEMs) are a group of rare genetic disorders which, when emerging later in life, are often characterized by neuropsychiatric manifestations including psychosis. This study aimed to determine whether it would be useful to screen patients presenting with a psychotic disorder for IEMs by a single blood sample using Next Generation Sequencing (NGS), in order to detect rare, treatable causes of psychotic disorders. Blood was drawn from 60 patients with a psychotic disorder, with a duration of illness of less than 5 years. Blood samples were screened for 67 genes using NGS (Illumina® MiSeq sequencing technique). The results were compared to the human reference genome (GoNL, n = 498). The identified variants were classified according to the ACMG classification. For the psychotic patients, 6 variants of a likely pathogenic (class 4, n = 2) or pathogenic (class 5, n = 4) origin were found. As all variants were heterozygous, no patients were considered to be affected by an IEM. For the GoNL control group, 73 variants of a likely pathogenic (class 4, n = 31) or pathogenic (class 5, n = 42) origin were found. All of these found variants were heterozygous. Therefore, these individuals from the control group were considered to be a carrier only. Thus, no patients were identified to have an IEM as an underlying disease using this approach. However, NGS may be useful to detect variants of genes associated with IEMs in an enriched subgroup of psychotic patients.

Background: There are longstanding concerns regarding physical health inequalities for people with psychotic disorders. In recent years concerted efforts have been made to address these. \ud Aims: To examine whether recent national initiatives in England have led to improvements in the physical health of people with schizophrenia and related psychoses. \ud Methods: Secondary analysis of data from multiple rounds of a national audit of services for people with psychosis, conducted over a 9-year period. Proportions of patients in ‘good health’ according to seven discrete measures, and one composite measure derived from national standards, were compared between each round of the audit. \ud Results: The proportion of patients in overall ‘good health’ under the care of ‘Early Intervention in Psychosis’ (EIP) teams increased between 2014 and 2019 (OR=4.65, 95% CI 3.32 to 6.52, P

Aims Little is known about the effects of mental health conditions (MHCs) on the utilization of oral anticoagulation (OAC) therapy in atrial fibrillation (AF) patients. We aimed to assess whether MHCs affect initiation of OAC therapy among AF patients with special focus on non-vitamin K antagonist oral anticoagulants (NOACs). Methods and results The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) registry included all 239 222 patients diagnosed with incident AF during 2007–18 in Finland identified from national registries covering primary to tertiary care and drug purchases. Patients with previous depression, bipolar disorder, anxiety disorder, or schizophrenia diagnosis or a fulfilled psychiatric medication prescription within the year preceding the AF diagnosis were classified to have any MHC. The main outcome was OAC initiation, defined as first fulfilled OAC prescription after AF diagnosis. The patients’ mean age was 72.7 years and 49.8% were female. The prevalence of any MHC was 19.9%. A lower proportion of patients with any MHC compared with those without MHCs were initiated on OAC therapy (64.9% vs. 73.3%, P Conclusion MHCs are common among AF patients, and they are associated with a lower rate of OAC initiation even during the NOAC era.

Objective: Primary immunodeficiencies (PIDs) consist of genetically heterogeneous disorders. The spectrum can include infectious diseases, malignancy, allergy, and autoimmunity. We aimed to analyze the frequency and variety of autoimmune diseases (ADs) in PIDs and describe their clinical and laboratory features. Materials and Methods: Ninety-two patients with PID followed by Ege University Medical Faculty between 2000 and 2017 were enrolled in this retrospective, cross-sectional study. All patients’ medical records were reviewed using the demographic information, type of PIDs and ADs, ADs-related autoantibodies, and basic and immunologic laboratory findings. ADs were diagnosed using clinical and complementary paraclinical findings by an immunologist and/or a subspecialist related to the affected organ or system. Results: We evaluated 50 male and 42 female PID patients with a mean age of 40.92 (18-86). Twenty-nine (32 %) patients (15 females/14 males) with a mean age of 43.8 (19-78) had ADs. In our study group, the most commonly detected type of PID with AD is common variable immune deficiency (CVID) (n=17); followed by combined immune deficiency (CID) (n=3), CTLA4 deficiency (n=2), selective IgA deficiency (sIgAD) (n=2), specific IgG subgroup deficiency (n=1), autoimmune polyglandular syndrome (APS) with hypogammaglobulinemia (n=1), dyskeratosis congenita (DC) (n=1), Osler-Rendu-Weber (ORW) syndrome with CVID-like PID (n=1), and cartilage-hair hypoplasia (CHH) (n=1). According to systematic assessments, ADs resulted in endocrinologic 14%, dermatologic 10.8%, rheumatologic 9.7%, gastroenterological 9.7%, hematological 8.6%, and neurologic disorders 1%. The frequency of ADs was higher in CVID cases than other types of PIDs (p

Objective Despite published guidelines no unified approach to hormone replacement in congenital adrenal hyperplasia (CAH) exists. We aimed to explore geographical and temporal variations in the treatment with glucocorticoids and mineralocorticoids in CAH. Design This retrospective multi-center study, including 31 centers (16 countries), analyzed data from the International-CAH Registry. Methods Data were collected from 461 patients aged 0–18 years with classic 21-hydroxylase deficiency (54.9% females) under follow-up between 1982 and 2018. Type, dose and timing of glucocorticoid and mineralocorticoid replacement were analyzed from 4174 patient visits. Results The most frequently used glucocorticoid was hydrocortisone (87.6%). Overall, there were significant differences between age groups with regards to daily hydrocortisone-equivalent dose for body surface, with the lowest dose (median with interquartile range) of 12.0 (10.0–14.5) mg/m2/day at age 1–8 years and the highest dose of 14.0 (11.6–17.4) mg/m2/day at age 12–18 years. Glucocorticoid doses decreased after 2010 in patients 0–8 years (P < 0.001) and remained unchanged in patients aged 8–18 years. Fludrocortisone was used in 92% of patients, with relative doses decreasing with age. A wide variation was observed among countries with regards to all aspects of steroid hormone replacement. Conclusions Data from the I-CAH Registry suggests international variations in hormone replacement therapy, with a tendency to treatment with high doses in children.

Previously, we established an estimated exposome score for schizophrenia (ES-SCZ) as a cumulative measure of environmental liability for schizophrenia to use in gene–environment interaction studies and for risk stratification in population cohorts. Hereby, we examined the discriminative function of ES-SCZ for identifying individuals diagnosed with schizophrenia spectrum disorder in the general population by measuring the area under the receiver operating characteristic curve (AUC). Furthermore, we compared this ES-SCZ method to an environmental sum score (Esum-SCZ) and an aggregate environmental score weighted by the meta-analytical estimates (Emet-SCZ). We also estimated ORs and Nagelkerke’s R2 for ES-SCZ in association with psychiatric diagnoses and other medical outcomes. ES-SCZ showed a good discriminative function (AUC = 0.84) and statistically significantly performed better than both Esum-SCZ (AUC = 0.80) and Emet-SCZ (AUC = 0.80). At optimal cut point, ES-SCZ showed similar performance in ruling out (LR− = 0.20) and ruling in (LR+ = 3.86) schizophrenia. ES-SCZ at optimal cut point showed also a progressively greater magnitude of association with increasing psychosis risk strata. Among all clinical outcomes, ES-SCZ was associated with schizophrenia diagnosis with the highest OR (2.76, P < .001) and greatest explained variance (R2 = 14.03%), followed by bipolar disorder (OR = 2.61, P < .001, R2 = 13.01%) and suicide plan (OR = 2.44, P < .001, R2 = 12.44%). Our findings from an epidemiologically representative general population cohort demonstrate that an aggregate environmental exposure score for schizophrenia constructed using a predictive modeling approach—ES-SCZ—has the potential to improve risk prediction and stratification for research purposes and may help gain insight into the multicausal etiology of psychopathology.

This study was funded by the Medical Research Council, the European Community’s Seventh Framework Program grant [agreement HEALTH-F2-2009-241909 (Project EU-GEI)], São Paulo Research Foundation (grant 2012/0417-0), the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London, the NIHR BRC at University College London and the Wellcome Trust (grant 101272/Z/12/Z)., Tripoli, G., Quattrone, D., Ferraro, L., Gayer-Anderson, C., Rodriguez, V., La Cascia, C., La Barbera, D., Sartorio, C., Seminerio, F., Tarricone, I., Berardi, D., Szöke, A., Arango, C., Tortelli, A., Llorca, P.-M., De Haan, L., Velthorst, E., Bobes, J., Bernardo, M., Sanjuán, J., Santos, J.L., Arrojo, M., Del-Ben, C.M., Menezes, P.R., Selten, J.-P., Jones, P.B., Jongsma, H.E., Kirkbride, J.B., Lasalvia, A., Tosato, S., Richards, A., O'donovan, M., Rutten, B.P.F., Os, J.V., Morgan, C., Sham, P.C., Murray, R.M., Murray, G.K., Di Forti, M.

Background/aim: Autoimmune bullous diseases, if left untreated, are life-threatening conditions affecting primarily skin and mucous membranes. These blistering disorders are characterized by epidermal or subepidermal detachment. Autoimmunity plays a key role in pathogenesis; therefore, immunosuppressive agents are the treatment of choice. The aim of this study is to document relative frequencies of different autoimmune bullous diseases, patient characteristics, treatment options, and side effects in patients presenting to our bullous skin disease center at İstanbul University, Cerrahpaşa, Cerrahpaşa Medical Faculty. Materials and methods: Medical files were examined retrospectively for all patients with autoimmune bullous diseases who were followed up between 2003 and 2019 at the Bullous Skin Disease Center at İstanbul University, Cerrahpaşa. Results: A total of 346 patient files were examined. Pemphigus vulgaris was the most frequent autoimmune bullous disease, followed by bullous pemphigoid and pemphigus foliaceus, according to our study. There is a general female predominancy for all autoimmune bullous diseases. The most commonly preferred treatment options were high-dose daily corticosteroids. Conclusion: This retrospective study summarizes the patient characteristics, comorbidities, treatment choices, and side effects during 16 years of clinical practice.

Marfan syndrome (MFS) is an autosomal dominant genetic condition that mainly affects connective tissue in many parts of the body. Cardinal manifestations involve the ocular, skeletal, and cardiovascular systems. The diagnosis of MFS relies on the revised Ghent criteria, outlined by international expert opinion to facilitate accurate recognition of this syndrome as well as to improve patient management and counseling. However, it may not always be possible to make a definitive diagnosis according to these criteria in each patient and thus molecular confirmation is necessary in subjects with suspected MFS. This debilitating, if not fatal, disorder is caused by mutations in FBN1, which encodes a major constitutive element of extracellular microfibrils. Here, we present a detailed clinical and molecular analysis of 76 Turkish patients with definitive or suspected MFS diagnosed at our center between 2014 and 2019. We were able to identify a total of 51 different FBN1 variants in our cohort, 31 of which have previously been reported in the relevant scientific literature. The remaining 20 variants have not been documented to date. In one patient, we detected a large deletion including the entire FBN1 gene using the array CGH approach. Currently, there are very few studies on the genotype-phenotype correlation of patients with MFS, and no clear genotype-phenotype maps for MFS have been constructed so far, except for some cases. We believe that our findings will make a rich and peculiar contribution to the elusive genotype-phenotype relationship in MFS, especially in this large and populous ethnic group. WOS:000610028100001 2-s2.0-85099760154 PubMed: 33483584

Background and purpose To determine how the coverage of specialized allied health services for patients with Parkinson's disease (PD) has developed in the Netherlands since the publication of trials that demonstrated cost‐effectiveness. Methods We used healthcare expenditure‐based data on all insured individuals in the Netherlands to determine the annual proportion of patients with PD who received either specialized or generic allied health services (physiotherapy, occupational therapy, speech–language therapy) in 2 calendar years separated by a 5‐year interval (2012 and 2017). Specialized allied health services were delivered through the ParkinsonNet approach, which encompassed professional training and concentration of care among specifically trained professionals. Results Between 2012 and 2017, there was an increase in the number of patients with any physiotherapy (from 17,843 [62% of all patients with PD that year] to 22,282 [68%]), speech–language therapy (from 2171 [8%] to 3378 [10%]), and occupational therapy (from 2813 [10%] to 5939 [18%]). Among therapy‐requiring patients, the percentage who were treated by a specialized therapist rose substantially for physiotherapy (from 36% in 2012 to 62% in 2017; χ2 = 2460.2; p, Following the publication of positive trials, the ParkinsonNet approach was successfully introduced on a nationwide scale in the Netherlands as a cost‐effective intervention for people with Parkinson's disease. The successful wide‐scale implementation of specialized allied healthcare delivery may serve as a template for other healthcare innovations for patients with Parkinson's disease elsewhere.

Objective The aim of this study is to (1) review the digital health tools that have been used in headache studies, and (2) discuss the effectivity and reliability of these tools. Background Many headache patients travel a long and troublesome journey from first symptoms until a meaningful care plan. eHealth, mHealth, and digital therapeutic modalities have been advocated as the way forward to improve patient care. Method Online databases PubMed, Cinahl, and PsycINFO were searched using a predefined search query. A data extraction form was used to gather relevant data elements from the selected papers. Results A total of 39 studies were selected. The studies included 94,127 participants. The majority of studies focused on diaries (N = 27 out of 39). Digital (cognitive) behavioral therapy were also quite common (N = 7 out of 39). Other digital health tool categories were tele-consultations, telemonitoring and patient portals. Conclusion Many digital health tools for headache patients regarding diaries and behavioral/therapeutical treatment are described in scientific research with limited information on effectivity and reliability. Scientific knowledge with regard to other categories such as tele-consultations, patient portals, telemonitoring including medication adherence, online information resources, wearable, symptom checkers, digital peer support is still scarce or missing.

Contains fulltext : 241356.pdf (Publisher’s version ) (Open Access) Centronuclear myopathy (CNM) is a genetically heterogeneous congenital myopathy characterized by muscle weakness, atrophy, and variable degrees of cardiorespiratory involvement. The clinical severity is largely explained by genotype (DNM2, MTM1, RYR1, BIN1, TTN, and other rarer genetic backgrounds), specific mutation(s), and age of the patient. The histopathological hallmark of CNM is the presence of internal centralized nuclei on muscle biopsy. Information on the phenotypical spectrum, subtype prevalence, and phenotype-genotype correlations is limited. To characterize CNM more comprehensively, we retrospectively assessed a national cohort of 48 CNM patients (mean age = 32 ± 24 years, range 0-80, 54% males) from the Netherlands clinically, histologically, and genetically. All information was extracted from entries in the patient's medical records, between 2000 and 2020. Frequent clinical features in addition to muscle weakness and hypotonia were fatigue and exercise intolerance in more mildly affected cases. Genetic analysis showed variants in four genes (18 DNM2, 14 MTM1, 9 RYR1, and 7 BIN1), including 16 novel variants. In addition to central nuclei, histologic examination revealed a large variability of myopathic features in the different genotypes. The identification and characterization of these patients contribute to trial readiness.

Background: Previous studies have suggested that processing of visual contrast information could be altered in major depressive disorder. To clarify the changes at different levels of the visual hierarchy, we behaviourally measured contrast perception in 2 centre-surround conditions, assessing retinal and cortical processing. Methods: As part of a prospective cohort study, our sample consisted of controls (n = 29; 21 female) and patients with unipolar depression, bipolar disorder and borderline personality disorder who had baseline major depressive episodes (n = 111; 74 female). In a brightness induction test that assessed retinal processing, participants compared the perceived luminance of uniform patches (presented on a computer screen) as the luminance of the backgrounds was varied. In a contrast suppression test that assessed cortical processing, participants compared the perceived contrast of gratings, which were presented with collinearly or orthogonally oriented backgrounds. Results: Brightness induction was similar for patients with major depressive episodes and controls (p = 0.60, d = 0.115, Bayes factor = 3.9), but contrast suppression was significantly lower for patients than for controls (p < 0.006, d = 0.663, Bayes factor = 35.2). We observed no statistically significant associations between contrast suppression and age, sex, or medication or diagnostic subgroup. At follow-up (n = 74), we observed some normalization of contrast perception. Limitations: We assessed contrast perception using behavioural tests instead of electrophysiology. Conclusion: The reduced contrast suppression we observed may have been caused by decreased retinal feedforward or cortical feedback signals. Because we observed intact brightness induction, our results suggest normal retinal but altered cortical processing of visual contrast during a major depressive episode. This alteration is likely to be present in multiple types of depression and to partially normalize upon remission.

Virilization is the medical term for describing a female who develops characteristics associated with male hormones (androgens) at any age, or when a newborn girl shows signs of prenatal male hormone exposure at birth. In girls, androgen levels are low during pregnancy and childhood. A first physiologic rise of adrenal androgens is observed at the age of 6 to 8 years and reflects functional activation of the zona reticularis of the adrenal cortex at adrenarche, manifesting clinically with first pubic and axillary hairs. Early adrenarche is known as “premature adrenarche.” It is mostly idiopathic and of uncertain pathologic relevance but requires the exclusion of other causes of androgen excess (eg, nonclassic congenital adrenal hyperplasia) that might exacerbate clinically into virilization. The second modest physiologic increase of circulating androgens occurs then during pubertal development, which reflects the activation of ovarian steroidogenesis contributing to the peripheral androgen pool. However, at puberty initiation (and beyond), ovarian steroidogenesis is normally devoted to estrogen production for the development of secondary female bodily characteristics (eg, breast development). Serum total testosterone in a young adult woman is therefore about 10- to 20-fold lower than in a young man, whereas midcycle estradiol is about 10- to 20-fold higher. But if androgen production starts too early, progresses rapidly, and in marked excess (usually more than 3 to 5 times above normal), females will manifest with signs of virilization such as masculine habitus, deepening of the voice, severe acne, excessive facial and (male typical) body hair, clitoromegaly, and increased muscle development. Several medical conditions may cause virilization in girls and women, including androgen-producing tumors of the ovaries or adrenal cortex, (non)classical congenital adrenal hyperplasia and, more rarely, other disorders (also referred to as differences) of sex development (DSD). The purpose of this article is to describe the clinical approach to the girl with virilization at puberty, focusing on diagnostic challenges. The review is written from the perspective of the case of an 11.5-year-old girl who was referred to our clinic for progressive, rapid onset clitoromegaly, and was then diagnosed with a complex genetic form of DSD that led to abnormal testosterone production from a dysgenetic gonad at onset of puberty. Her genetic workup revealed a unique translocation of an abnormal duplicated Y-chromosome to a deleted chromosome 9, including the Doublesex and Mab-3 Related Transcription factor 1 (DMRT1) gene. Learning Objectives Identify the precise pathophysiologic mechanisms leading to virilization in girls at puberty considering that virilization at puberty may be the first manifestation of an endocrine active tumor or a disorder/difference of sex development (DSD) that remained undiagnosed before and may be life-threatening. Of the DSDs, nonclassical congenital adrenal hyperplasia occurs most often. Provide a step-by-step diagnostic workup plan including repeated and expanded biochemical and genetic tests to solve complex cases. Manage clinical care of a girl virilizing at puberty using an interdisciplinary team approach. Care for complex cases of DSD manifesting at puberty, such as the presented girl with a Turner syndrome-like phenotype and virilization resulting from a complex genetic variation.

BackgroundStudies that assess the role of physical health conditions on separation risk are scarce and mostly lack health information on both partners. It is unclear how the association between physical illness and separation risk varies by type of illness, gender of the ill spouse and age of the couple.MethodsWe used Finnish register data on 127 313 couples to examine how neurological conditions, heart and lung disease, and cancer are associated with separation risk. The data included information on medication, hospitalisations, separations and sociodemographic characteristics. Marital and non-marital cohabiting couples aged 40–70 years were followed from 1998 to 2003 for the onset of health conditions and subsequent separation, and Cox regression was used to examine the associations.ResultsCompared with healthy couples, the HR of separation was elevated by 43% for couples in which both spouses had a physical health condition, by 22% for couples in which only the male spouse had fallen ill, and by 11% for couples in which only the female had fallen ill. Among older couples, the associations between physical illness and separation risk were even clearer. The association with separation risk was strongest for neurological conditions, and after incidence of these conditions among males, separation risk increased over time. Adjustment for sociodemographic characteristics had little effect.ConclusionsOur findings suggest that poor health may largely strain relationships through disability and associated burden of spousal care, and this should be taken into consideration when planning support services for couples with physical health conditions.

This cohort study assesses whether recent stressful life events interact with genetic and environmental liability for schizophrenia in models of mental and physical health in the Dutch adult population.Key PointsQuestionIs the association of adulthood life stress with mental and physical health moderated by polygenic risk and exposome scores for schizophrenia? FindingsThis population-based cohort study of 6646 participants provides novel evidence of the associations of genetic and environmental liability for schizophrenia with mental health in the general population. Both genetic and environmental liability were associated with poor outcomes, particularly mental health, and the association between stressful life events and health outcomes was moderated by exposome score but not polygenic risk score for schizophrenia. MeaningThese findings showing an interaction between adulthood stressful life events and lifetime exposomic liability lend further support to the diathesis-stress model.ImportanceBoth adulthood stressful life events (SLEs) and liability for schizophrenia have been associated with poor mental and physical health in the general population, but their interaction remains to be elucidated to improve population-based health outcomes. ObjectiveTo test whether recent SLEs interact with genetic and environmental liability for schizophrenia in models of mental and physical health. Design, Setting, and ParticipantsThe Netherlands Mental Health Survey and Incidence Study-2 is a population-based prospective cohort study designed to investigate the prevalence, incidence, course, and consequences of mental disorders in the Dutch general population. Participants were enrolled from November 5, 2007, to July 31, 2009, and followed up with 3 assessments during 9 years. Follow-up was completed on June 19, 2018, and data were analyzed from September 1 to November 1, 2019. ExposuresRecent SLEs assessed at each wave and aggregate scores of genetic and environmental liability for schizophrenia: polygenic risk score for schizophrenia (PRS-SCZ) trained using the Psychiatric Genomics Consortium analysis results and exposome score for schizophrenia (ES-SCZ) trained using an independent data set. Main Outcomes and MeasuresIndependent and interacting associations of SLEs with ES-SCZ and PRS-SCZ on mental and physical health assessed at each wave using regression coefficients. ResultsOf the 6646 participants included at baseline, the mean (SD) age was 44.26 (12.54) years, and 3672 (55.25%) were female. The SLEs were associated with poorer physical health (B=-3.22 [95% CI, -3.66 to -2.79]) and mental health (B=-3.68 [95% CI, -4.05 to -3.32]). Genetic and environmental liability for schizophrenia was associated with poorer mental health (ES-SCZ: B=-3.07 [95% CI, -3.35 to -2.79]; PRS-SCZ: B=-0.93 [95% CI, -1.31 to -0.54]). Environmental liability was also associated with poorer physical health (B=-3.19 [95% CI, -3.56 to -2.82]). The interaction model showed that ES-SCZ moderated the association of SLEs with mental (B=-1.08 [95% CI, -1.47 to -0.69]) and physical health (B=-0.64 [95% CI, -1.11 to -0.17]), whereas PRS-SCZ did not. Several sensitivity analyses confirmed these results. Conclusions and RelevanceIn this study, schizophrenia liability was associated with broad mental health outcomes at the population level. Consistent with the diathesis-stress model, exposure to SLEs, particularly in individuals with high environmental liability for schizophrenia, was associated with poorer health. These findings underline the importance of modifiable environmental factors during the life span for population-based mental health outcomes.

Objectives Non-motor symptoms (NMS) are commonly present along with motor impairment in patients with cervical dystonia (CD) and have a significant impact on health-related quality of life (HRQoL). However, the prevalence of NMS and their association with dystonia are still unclear. The aim of our study was to assess the prevalence of depression, anxiety, fatigue, apathy, pain, sleep problems, and excessive daytime sleepiness (EDS) in CD using different evaluation approaches and to explore their association with HRQoL relative to that of motor symptoms.Materials and Methods We enrolled 102 Slovak patients with CD. The severity of both motor and non-motor symptoms was assessed using validated scales. HRQoL was determined by the 36-item Short Form Health Survey (SF-36). Association of NMS with poor HRQoL was assessed using multiple regressions.Results The most frequent NMS in our sample were sleep impairment (67.3%), anxiety (65.5%), general and physical fatigue (57.5% and 52.9%, respectively), depression (47.1%), mental fatigue (31.4%), apathy (30.4%), reduced activity (29.4%), EDS (20.2%), and reduced motivation (18.6%). Univariate analysis showed that NMS, but not motor symptoms, were significantly linked to poor HRQoL, with EDS being most commonly associated with poor HRQoL, followed by disrupted sleep, depression, and fatigue.Conclusions The prevalence of NMS among patients with CD is high, and some NMS are strongly associated with poor HRQoL, while motor impairment was not associated with the severity of NMS or poor HRQoL. Actively diagnosing and treating NMS should therefore be a routine part of the clinical management of patients with CD.

Background Anxiety is frequent in Parkinson's disease (PD) and has a negative impact on disease symptoms and quality of life. The underlying mechanisms remain largely unknown. The aim of this study was to identify anatomical and functional changes associated to PD-related anxiety by comparing the volume, shape and texture of the amygdala, the cortical thickness as well as the functional connectivity (FC) of the fear circuit in patients with and without clinically relevant anxiety. Methods Non-demented PD patients were recruited, and anxiety was quantified using the Parkinson Anxiety Scale. Structural MRI was used to compare cortical thickness and amygdala structure and resting-state functional MRI to compare FC patterns of the amygdala and resting-state functional networks in both groups. Results We included 118 patients: 34 with (A+) and 84 without (A-) clinically relevant anxiety. Clusters of cortical thinning were identified in the bilateral fronto-cingulate and left parietal cortices of the A+ group. The texture and the shape of the left amygdala was different in the A+ group but the overall volume did not differ between groups. FC between the amygdala and the whole brain regions did not differ between groups. The internetwork resting-state FC was higher between the “fear circuit” and salience network in the A+ group. Conclusion Anxiety in PD induces structural modifications of the left amygdala, atrophy of the bilateral fronto-cingulate and the left parietal cortices, and a higher internetwork resting-state FC between the fear circuit and the salience network.

The Strengths and Difficulties Questionnaire (SDQ) is widely used, based on evidence of its value for screening. This evidence primarily regards the single informant total difficulties scale and separate difficulties subscales. We assessed to what degree adolescents’ SDQ profiles that combined all self- and parent-rated subscales were associated with use of care and psychiatric diagnoses, and examined the added value thereof over using only a single informant and the total scale. Cluster analysis was used to identify common SDQ profiles based on self- and parent-reports among adolescents aged 12–17 in mental healthcare (n = 4282), social care (n = 124), and the general population (n = 1293). We investigated associations of the profiles with ‘care use’ and ‘DSM-IV diagnoses’, depending on gender. We identified six common SDQ profiles: five profiles with varying types and severities of reported difficulties, pertaining to 95% of adolescents in care, and one without difficulties, pertaining to 55% of adolescents not in care. The types of reported difficulties in the profiles matched DSM-IV diagnoses for 88% of the diagnosed adolescents. The SDQ profiles were found to be more useful for predicting care use and diagnoses than SDQ scores reported by the adolescent as single informant and the total difficulties scale. The latter indicated the presence of problems among 42–63% of the adolescents in care, missing a substantial number of adolescents with reported emotional difficulties and borderline problem severity. These findings advocate the use of combined self- and parent-rated SDQ score profiles for screening. Electronic supplementary material The online version of this article (10.1007/s00787-020-01667-5) contains supplementary material, which is available to authorized users.

Experiences of sudden and abrupt insight, sometimes termed aha-experiences, are often reported during psychosis. The aha-experience is described as a radical and sudden restructuring, realization o...

Objective To study the impact of gender, puberty, and pregnancy on the expression of POLG disease, one of the most common mitochondrial diseases known. Methods Clinical, laboratory, and genetic data were collected retrospectively from 155 patients with genetically confirmed POLG disease recruited from seven European countries. We used the available data to study the impact of gender, puberty, and pregnancy on disease onset and deterioration. Results We found that disease onset early in life was common in both sexes but there was also a second peak in females around the time of puberty. Further, pregnancy had a negative impact with 10 of 14 women (71%) experiencing disease onset or deterioration during pregnancy. Interpretation Gender clearly influences the expression of POLG disease. While onset very early in life was common in both males and females, puberty in females appeared associated both with disease onset and increased disease activity. Further, both disease onset and deterioration, including seizure aggravation and status epilepticus, appeared to be associated with pregnancy. Thus, whereas disease activity appears maximal early in life with no subsequent peaks in males, both menarche and pregnancy appear associated with disease onset or worsening in females. This suggests that hormonal changes may be a modulating factor. © 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Objective: 22q11.2 deletion syndrome (22q11DS) is among the strongest known genetic risk factors for schizophrenia. Previous studies have reported variable alterations in subcortical brain structures in 22q11DS. To better characterize subcortical alterations in 22q11DS, including modulating effects of clinical and genetic heterogeneity, the authors studied a large multicenter neuroimaging cohort from the ENIGMA 22q11.2 Deletion Syndrome Working Group. Methods: Subcortical structures were measured using harmonized protocols for gross volume and subcortical shape morphometry in 533 individualswith 22q11DS and 330matched healthy control subjects (age range, 6-56 years; 49% female). Results: Compared with the control group, the 22q11DS group showed lower intracranial volume (ICV) and thalamus, putamen, hippocampus, and amygdala volumes and greater lateral ventricle, caudate, and accumbens volumes (Cohen's d values, 20.90 to 0.93). Shape analysis revealed complex differences in the 22q11DS group across all structures. The larger A-D deletion was associated with more extensive shape alterations compared with the smaller A-B deletion. Participants with 22q11DS with psychosis showed lower ICV and hippocampus, amygdala, and thalamus volumes (Cohen's d values, 20.91 to 0.53) compared with participants with 22q11DS without psychosis. Shape analysis revealed lower thickness and surface area across subregions of these structures. Compared with subcortical findings from other neuropsychiatric disorders studied by the ENIGMA consortium, significant convergence was observed between participants with 22q11DS with psychosis and participants with schizophrenia, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. Conclusions: In the largest neuroimaging study of 22q11DS to date, the authors found widespread alterations to subcortical brain structures, which were affected by deletion size and psychotic illness. Findings indicate significant overlap between 22q11DS-associated psychosis, idiopathic schizophrenia, and other severe neuropsychiatric illnesses.

Aim: To determine the frequency of sinopulmonary infections, detect changes in the respiratory system, and measure functional capacity of the lungs in our patients with humoral immunodeficiency. Material and Methods: Fifty-six patients with humoral immunodeficiency were enrolled in this study. The clinical, laboratory, and radiologic data, and pulmonary function tests of the subjects were evaluated from their file records, retrospectively. Results: The distribution of our patients was as follows: 25 patients had common variable immune deficiency, three patients had X-linked agammaglobulinemia, five patients had hyper immunoglobulin M syndrome, 19 patients had deficiency of immunoglobulin G subset, and four patients had selective immunoglobulin A deficiency. The most common symptom of the patients was chronic cough (n=47, 83.9%). The most common pathologies on high-resolution computed tomography of the chest were atelectasis and bronchiectasis (27.7%). The most common pathology in pulmonary function tests was the presence of moderate obstructive patterns along with restrictive patterns (n=6,12.5%). The FEV 1, FVC, and FEF 25-75 values were significantly lower in patients with common variable immunodeficiency compared with the patients who had IgG subset deficiencies (p=0.001, p=0.01, p=0.01). Among the patients who were treated with intravenous immunoglobulin, the age at the diagnosis of immunodeficiency was higher in patients with bronchiectasis (14.2 +/- 8.4 years) compared with those without bronchiectasis (10.1 +/- 11.4 years) (p=0.04). Conclusion: Clinical findings are not sufficient to monitor the structural and functional changes in the respiratory system, and patients should be evaluated using high-resolution computed tomography of the chest and pulmonary function tests. Amaç: Humoral immün yetmezlik tanılı olgularımızda, sinopulmoner enfeksiyonların sıklığı ve bunların sonucunda solunum sisteminde meydana gelen değişikliklerin saptanması ve fonksiyonel akciğer kapasitelerinin ölçülmesi amaçlanmıştır. Gereç ve Yöntemler: Çalışmaya humoral immün yetmezlik tanılı 56 olgu alındı. Olguların dosya kayıtlarından klinik, laboratuvar, radyolojik görüntüleme bulguları ve solunum fonksiyon testi verileri geriye dönük olarak incelendi. Bulgular: Olguların tanılara göre dağılımı; yaygın değişken immün yetmezlik tanılı 25 olgu, X’e bağlı agamaglobulinemi tanılı üç olgu, Hiper immunoglobulin M sendromu tanılı beş olgu, İgG alt grup eksikliği tanılı 19 olgu ve selektif immunoglobulin A eksikliği tanılı dört olgu şeklindedir. Olguların 37’si (%66,1) erkek 19’u (%33,9) kadın, yaş ortalaması 14,1±10,6 yıldı. Olguların en sık yakınması kronik öksürük idi (n=47, %83,9). Akciğerlerin yüksek çözünürlüklü bilgisayarlı tomografilerinde en sık görülen patoloji atelektazi ve bronşiektaziydi (%27,7). Solunum fonksiyon testlerinde en sık görülen anormallik orta obstrüktif ve orta restriktif patern birlikteliğiydi (n=6,%12,5). Solunum fonksiyon testi bulguları ile radyolojik bulguların her zaman tutarlı olmadığı görüldü. İntravenöz immünglobulin alan olgular arasında yaygın değişken immün yetmezlik tanılı olgularda, immünglobulin G alt grup eksikliği olan olgulara göre solunum fonksiyon testlerinde; FEV 1, FVC ve FEF 25–75 değerlerinin anlamlı düşük olduğu saptandı (p=0,001, p=0,01, p=0,01). İntravenöz immünglobulin tedavisi alan olgularda; bronşiektazisi olanların immün yetmezlik tanı yaşı (14,2±8,4 yıl), olmayanlara (10,1±11,4 yıl) göre anlamlı olarak büyüktü (p=0,04). Çıkarımlar: Klinik bulgular solunum sistemindeki yapısal ve fonksiyonel değişiklikleri izlemek için yeterli değildir ve olgular gereğinde akciğer yüksek çözünürlüklü bilgisayarlı tomografi ve solunum fonksiyon testleri ile değerlendirilmelidir.

Aim The present study is aimed at revaluating alexithymia, somatic sensations, resilience and their relationships with suicide ideation in drug naive adult outpatients suffering from first episode major depression (MD). Methods Data of 103 adult outpatients (49 men, 56 women) with a diagnostic and statistical manual of mental disorders, 4th edition, text revision (DSM-IV-TR) diagnosis of MD were analysed. Alexithymia was measured using the 20-item Toronto Alexithymia Scale (TAS-20) and resilience with the 25 items Connor-Davidson Resilience Scale (CD-RISC) whereas depression was evaluated using the 17-item Hamilton Depression Rating Scale, somatic sensations with the Body Sensations Questionnaire and suicide ideation with Scale of Suicide Ideation (SSI). Results Gender comparisons between all demographic and clinical variables showed no significant differences in all variables. Subjects who were found positive for alexithymia showed higher scores on all clinical variables controlling for age, gender and duration of the current episode. In a linear regression model, lower scores on CD-RISC and Difficulty in Identifying Feelings dimension of TAS-20 were significantly predictive of higher scores on SSI. Conclusions Alexithymia and low resilience were significant predictors of increased suicide ideation in a first MD episode. However, study limitations must be considered and future research needs are being discussed.

Aim This study assessed the practice of pica among pregnant women in the Ho Teaching Hospital. Design Descriptive cross-sectional. Methods Systematic sampling technique was used to recruit 286 pregnant women. Questionnaire was used to collect data. Data entered into Statistical Package for Social Sciences for analysis. Result Of the 286 pregnant women, 21.2% and 17.8% considered white clay and ice respectively as nutritious. Prevalence of pica was 47.5%, while 44.9% of pregnant women who practised pica reported they feel uncomfortable when they do not eat pica as 63.3% considered intake of pica as harmful. Among women who received education against pica practice, 49.4% have ever taken pica as 50.9% of them with education on effects of pica were currently engaged in the activity (χ 2 = 1.93 p = .17). Conclusion Health professionals, especially midwives must intensify education on effects of pica among pregnant women.

Funder: FP7 Ideas: European Research Council; doi: http://dx.doi.org/10.13039/100011199; Grant(s): HEALTH-F2-2010-241909, Purpose: The EUropean Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study contains an unparalleled wealth of comprehensive data that allows for testing hypotheses about (1) variations in incidence within and between countries, including by urbanicity and minority ethnic groups; and (2) the role of multiple environmental and genetic risk factors, and their interactions, in the development of psychotic disorders. Methods: Between 2010 and 2015, we identified 2774 incident cases of psychotic disorders during 12.9 million person-years at risk, across 17 sites in 6 countries (UK, The Netherlands, France, Spain, Italy, and Brazil). Of the 2774 incident cases, 1130 cases were assessed in detail and form the case sample for case–control analyses. Across all sites, 1497 controls were recruited and assessed. We collected data on an extensive range of exposures and outcomes, including demographic, clinical (e.g. premorbid adjustment), social (e.g. childhood and adult adversity, cannabis use, migration, discrimination), cognitive (e.g. IQ, facial affect processing, attributional biases), and biological (DNA via blood sample/cheek swab). We describe the methodology of the study and some descriptive results, including representativeness of the cohort. Conclusions: This resource constitutes the largest and most extensive incidence and case–control study of psychosis ever conducted.

Background: Chronotype is an individual's preferred timing of sleep and activity, and is often referred to as a later chronotype (or evening-type) or an earlier chronotype (or morning-type). Having an evening chronotype is associated with more severe depressive and anxiety symptoms. Based on these findings it is has been suggested that chronotype is a stable construct associated with vulnerability to develop depressive or anxiety disorders. To examine this, we test the stability of chronotype over 7 years, and its longitudinal association with the change in severity of depressive and anxiety symptoms. Methods: Data of 1,417 participants with a depressive and/or anxiety disorder diagnosis and healthy controls assessed at the 2 and 9-year follow-up waves of the Netherlands Study of depression and anxiety were used. Chronotype was assessed with the Munich chronotype questionnaire. Severity of depressive and anxiety symptoms were assessed with the inventory of depressive symptomatology and Beck anxiety inventory. Results: Chronotype was found to be moderately stable (r = 0.53) and on average advanced (i.e., became earlier) with 10.8 min over 7 years (p

Purpose: pulmonary involvement is common in adults with scleroderma. The effect of concomitant obstructive sleep apnea (OSA) on risk for pulmonary hypertension in scleroderma is unknown. An enlarged main pulmonary artery diameter (mPAD) derived from chest computer tomography (CT) is a useful predictor of pulmonary hypertension. We addressed the effect of OSA on pulmonary involvement and enlarged mPAD in adults with scleroderma. Methods: all participants underwent pulmonary function testing, carbon monoxide diffusion capacity, chest CT, and overnight sleep recording with home sleep apnea testing. OSA diagnosis was based on an apnea-hypopnea index (AHI) >= 15/h. Oxygen desaturation index (ODI) was also recorded. Scleroderma involvement of the lungs was defined as the Warrick score >= 7 based on the CT findings. Enlarged mPAD was defined as an mPAD >= 29 mm in men and >= 27 mm in women. Results: after exclusions, 62 patients (58 women) were included. OSA was found among 20 (32%), 17/42 (38%) in the limited cutaneous type, and 3/20 (15%) in the diffuse cutaneous type (p = 0.08). Scleroderma involvement of the lungs was observed in 40 participants (65% in OSA vs 64% in no-OSA; n.s.). Enlarged mPAD was measured in 16 participants, 10 of 20 (50%) in the OSA group and 6 of 17 (14%) in the no-OSA group (p = 0.003). OSA was associated with enlarged mPAD (odds ratio 4.7, 95% confidence interval 1.1-20.9; p = 0.042) independent of age, body mass index, and pulmonary involvement. There was a linear relationship between mPAD and AHI (r = 0.37; p = 0.003) as well as ODI (r = 0.41; p < 0.001). Conclusions: in this cohort, OSA was associated with risk for pulmonary hypertension independent of pulmonary involvement. These findings suggest that assessing the effect of therapy for concomitant OSA in patients with scleroderma is warranted., University of Gothenburg

BackgroundPerinatal depression and anxiety are associated with unfavourable child outcomes.AimsTo assess among women with antenatal depression or anxiety the effectiveness of prenatally initiated cognitive–behavioural therapy (CBT) on mother and child compared with care as usual (CAU). Trial registration: Netherlands Trial Register number NTR2242.MethodPregnant women (n= 282) who screened positive for symptoms of depression and/or anxiety were randomised to either CBT (n= 140) or CAU (n= 142). The primary outcome was child behavioural and emotional problems at age 18 months, assessed using the Child Behavior Checklist (CBCL). Secondary outcomes were maternal symptoms during and up to 18 months after pregnancy, neonatal outcomes, mother–infant bonding and child cognitive and motor development at age 18 months.ResultsIn total, 94 (67%) women in the CBT group and 98 (69%) in the CAU group completed the study. The mean CBCL Total Problems score was non-significantly higher in the CBT group than in the CAU group (mean difference: 1.38 (95% CI −1.82 to 4.57);t= 0.85,P= 0.399). No effects on secondary outcomes were observed except for depression and anxiety, which were higher in the CBT group than in the CAU group at mid-pregnancy. Apost hocanalysis of the 98 women with anxiety disorders showed lower infant gestational age at delivery in the CBT than in the CAU group.ConclusionsPrenatally initiated CBT did not improve maternal symptoms or child outcomes among non-help-seeking women with antenatal depression or anxiety. Our findings are not in line with present recommendations for universal screening and treatment for antenatal depression or anxiety, and future work may include the relevance of baseline help-seeking.

Background Dental disorders, of which tooth root abscesses are best documented, are highly prevalent in alpacas. Identification of risk factors can be valuable for prevention of dental disorders in this species. Hypothesis/Objectives To identify risk factors associated with wear abnormalities, malpositioning, diastemata, periodontal disease (PD), and occlusal pulp exposure at the level of the cheek teeth. Animals Two hundred twenty-eight alpacas (Vicugna pacos) from 25 farms. Methods Cross-sectional study. Dental examinations were performed on sedated animals. Risk factors were determined by clinical examination and interview. Multivariable logistic regression was used to identify risk factors for wear abnormalities, malpositioned teeth, diastemata, PD, and occlusal pulp exposure. Results Mandibular swelling was significantly associated with PD (odds ratio [OR], 11.37; 95% confidence interval [CI], 3.27-48.81; P < .001). Nearly 73% of included animals with mandibular swelling concurrently had PD. For every increase in herd size of 1 animal, the risk for PD increased by 2% (95% CI, 1-4%; P = .01). The association between severe stages of PD and body condition score (BCS) indicates a painful situation, impairing animal welfare (P < .001). For each 1-day increase in interval between pasture cleanings, the odds of finding pulp exposure for a single animal was estimated to increase by 1% (95% CI, 0-2%; P = .05). Conclusion and Clinical Importance Simple management tools such as measuring BCS, palpating the mandible for bony swellings, removing feces from pasture on a regular basis and decreasing herd size might help identify animals at risk for dental disorders or prevent their development.

Schizophrenia is a highly polygenic disorder with important contributions from both common and rare risk alleles. We analyzed exome sequencing data for de novo variants (DNVs) in a new sample of 613 schizophrenia trios and combined this with published data to give a total of 3,444 trios. In this new data, loss-of-function (LoF) DNVs were significantly enriched among 3,471 LoF-intolerant genes, which supports previous findings. In the full dataset, genes associated with neurodevelopmental disorders (n = 159) were significantly enriched for LoF DNVs. Within these neurodevelopmental disorder genes, SLC6A1, which encodes a γ-aminobutyric acid transporter, was associated with missense-damaging DNVs. In 1,122 trios for which genome-wide common variant data were available, schizophrenia and bipolar disorder polygenic risk were significantly overtransmitted to probands. Probands carrying LoF or deletion DNVs in LoF-intolerant or neurodevelopmental disorder genes had significantly less overtransmission of schizophrenia polygenic risk than did non-carriers, which provides a second robust line of evidence that these DNVs increase liability to schizophrenia.