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Background: The COVID-19 pandemic and subsequent lockdown measures had serious implications for community-dwelling older people with dementia. While the short-term impacts of the pandemic on this population have been well studied, there is limited research on its long-term impacts. Quantifying the long-term impacts may provide insights into whether healthcare adaptations are needed after the acute phase of the pandemic to balance infection prevention measures with healthcare provision. This study aims to examine patterns of psychotropic drug prescriptions and general practice consultations in community-dwelling older people with dementia during the first two years of the pandemic. Methods: We utilised routine electronic health records from three Dutch academic general practice research networks located in the North, East, and South, between 2019 and 2021. We (1) compared the weekly prescription rates of five groups of psychotropic drugs and two groups of tracer drugs, and weekly general practice consultation rates per 1000 participants, between the first two years of the pandemic and the pre-pandemic phase, (2) calculated changes in these rates during three lockdowns and two relaxation phases relative to the corresponding weeks in 2019, and (3) employed interrupted time series analyses for the prescription rates. Analyses were performed for each region separately. Results: The study population sizes in the North, East, and South between 2019 and 2021 were 1726 to 1916, 93 to 117, and 904 to 960, respectively. Data from the East was excluded from the statistical analyses due to the limited sample size. During the first two years of the pandemic, the prescription rates of psychotropic drugs were either lower or similar to those in the pre-pandemic phase, with differences varying from -2.6‰ to -10.2‰. In contrast, consultation rates during the pandemic were higher than in the pre-pandemic phase, increasing by around 38‰. Conclusions: This study demonstrates a decrease in psychotropic drug prescriptions, but an increase in general practice consultations among community-dwelling older people with dementia during the first two years of the pandemic. However, reasons for the decrease in psychotropic drug prescriptions are unclear due to limited information on the presence of neuropsychiatric symptoms and the appropriateness of prescribing. [ABSTRACT FROM AUTHOR]

Background Recognition of acute diverticulitis is important to determine an adequate management strategy. Differentiating it from other gastrointestinal disorders is challenging as symptoms overlap. Clinical tests might assist the clinician with this diagnostic challenge. Previous reviews have focussed on prognostic questions and imaging examinations in secondary care. Objective To evaluate the diagnostic accuracy of clinical tests feasible in primary care for acute diverticulitis in suspected patients. Method We have systematically searched multiple databases for diagnostic accuracy studies of tests feasible in primary care compared to a reference standard in suspected patients. Two reviewers independently selected studies, extracted data, and assessed study quality with the QUADAS-2 tool. We have meta-analysed the results in the case of more than four studies per index test. Results Seventeen studies were included, all studies were performed in secondary care (median prevalence 48%). Individual signs and symptoms showed a wide range in sensitivity (range 0.00–0.98) and specificity (range 0.08–1.00). Of the four laboratory tests evaluated, CRP >10 mg/l had the highest sensitivity (range 0.89–0.96) with specificity ranging from 0.28 to 0.61. Ultrasound had the highest pooled sensitivity and specificity of 0.92 (95% CI 0.86–0.96) and 0.94 (95% CI 0.88–0.97), respectively. Conclusion None of the studies were performed in primary care. Individual signs and symptoms alone are insufficiently informative for acute diverticulitis diagnosis. CRP showed potential for ruling out and ultrasound had a high diagnostic accuracy. More research is needed about the diagnostic accuracy of these tests in primary care. PROSPERO registration number CRD42021230622 [ABSTRACT FROM AUTHOR]

Introduction: Major depressive disorder (MDD) is common, and recurrence rates are high. Preventive Cognitive Therapy (PCT), has been shown to prolong time to recurrence and reduce risk of recurrence(s) over 2–10 years in patients with recurrent depression. Objective: The aim of the study was to examine the effectiveness of PCT over 20 years on time to first recurrence, cumulative proportion of first recurrences, percentage of depression-free time, mean severity of recurrences, and the number of recurrences within a patient. Methods: Adults remitted from recurrent MDD were randomized to PCT or Treatment As Usual (TAU). Clinical outcomes were assessed using the SCID over 20 years. We used Cox regression analyses, Kaplan-Meier analyses, ANOVA, and negative binomial regression and tested for interaction with the number of previous episodes. Results: There was a significant interaction effect for number of previous episodes with treatment condition on time to first recurrence (Wald[1, n = 172] = 8.840, p = 0.003). For participants with more than 3 previous episodes, the mean time to recurrence was 4.8 years for PCT versus 1.6 years for TAU; the cumulative proportion of first recurrences was 87.5% for PCT and 100% for TAU. For participants with more than 3 previous episodes, exploratory analyses suggest that PCT had 53% less recurrences and percentage of depression-free time was significantly higher compared to TAU. There were no significant effects on mean severity. Conclusions: Up to 20 years, for MDD patients with more than 3 previous episodes, those who received PCT had significantly longer time to a first recurrence and lower recurrence risk and may have less recurrences and more depression-free time compared to TAU. This suggests long term protective effects of PCT up to 20-years. [ABSTRACT FROM AUTHOR]

Background: Preliminary evidence suggests beneficial effects of cognitive remediation in depression. An update of the current evidence is needed. The aim was to systematically assess the effectiveness of cognitive remediation in depression on three outcomes. Methods: The meta-analysis was pre-registered on PROSPERO (CRD42019124316). PubMed, PsycINFO, Embase and Cochrane Library were searched on 2 February 2019 and 8 November 2020 for peer-reviewed published articles. We included randomized and non-randomized clinical trials comparing cognitive remediation to control conditions in adults with primary depression. Random-effects models were used to calculate Hedges' g , and moderators were assessed using mixed-effects subgroup analyses and meta-regression. Main outcome categories were post-treatment depressive symptomatology (DS), cognitive functioning (CF) and daily functioning (DF). Results: We identified 5221 records and included 21 studies reporting on 24 comparisons, with 438 depressed patients receiving cognitive remediation and 540 patients in a control condition. We found a small effect on DS (g = 0.28, 95% CI 0.09–0.46, I 2 40%), a medium effect on CF (g = 0.60, 95% CI 0.37–0.83, I 2 44%) and a small effect on DF (g = 0.22, 95% CI 0.06–0.39, I 2 3%). There were no significant effects at follow-up. Confounding bias analyses indicated possible overestimation of the DS and DF effects in the original studies. Conclusions: Cognitive remediation in depression improves CF in the short term. The effects on DS and DF may have been overestimated. Baseline depressive symptom severity should be considered when administering cognitive remediation. [ABSTRACT FROM AUTHOR]

Copyright of Huisarts En Wetenschap is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Previous studies identified demographic, reproduction-related and psychosocial correlates of suboptimal mother-to-infant bonding. Their joint informative value was still unknown. This study aimed to develop a multivariable model to screen early in pregnancy for suboptimal postnatal mother-to-infant bonding and to transform it into a risk classification model. Methods: Prospective cohort study conducted at 116 midwifery centers between 2010–2014. 634 women reported on the Mother-to-Infant Bonding questionnaire in 2015–2016. A broad range of determinants before 13 weeks of gestation were considered. Missing data were described, analyzed and imputed by multiple imputation. Multivariable logistic regression with backward elimination was used to develop a screening model. The explained variance, the Area Under the Curve of the final model were calculated and a Hosmer and Lemeshow test performed. Finally, we designed a risk classification model. Results: The prevalence of suboptimal mother-to-infant bonding was 11%. The estimated probability of suboptimal mother-to-infant can be calculated: P(MIBS≥4) = 1/(1+exp(-(-4.391+(parity× 0.519)+(Adult attachment avoidance score× 0.040))). The explained variance was 14% and the Area Under the Curve was 0.750 (95%CI 0.690–0.809). The Hosmer and Lemeshow test had a p-value of 0.21. This resulted in a risk classification model. Conclusion: Parity and adult attachment avoidance were the strongest independent determinants. Higher parity and higher levels of adult attachment avoidance are associated with an increased risk of suboptimal mother-to-infant bonding. The model and risk classification model should be externally validated and optimized before use in daily practice. Future research should include an external validation study, a study into the additional value of non-included determinants and finally a study on the impact and feasibility of the screening model. [ABSTRACT FROM AUTHOR]

Background: Previous studies indicated that affect fluctuations, the use of antidepressant medication (ADM), as well as depression during pregnancy might have adverse effects on offspring outcomes. The aim of the current proof-of-principle study is to explore the effect of tapering ADM while receiving online preventive cognitive therapy (PCT) on pregnant women and the offspring as compared to pregnant women continuing ADM. Objectives: We sought to compare positive and negative affect fluctuations in pregnant women receiving online PCT while tapering ADM vs. pregnant women continuing ADM, and to investigate if affect fluctuations in early pregnancy were related to offspring birth weight. Method: An experience sampling methodology (ESM)-trial ran alongside a Dutch randomized controlled trial (RCT) and prospective observational cohort of women using ADM at the start of pregnancy. In the ESM-trial fluctuations of positive and negative affect were assessed in the first 8 weeks after inclusion. Recurrences of depression were assessed up to 12 weeks post-partum, and birth records were used to assess offspring birth weight. The RCT has been registered at the Netherlands Trial Register (NTR4694, https://www.trialregister.nl/trial/4551). Results: In total, 19 pregnant women using ADM at start of their pregnancy participated in the ESM-trial. There were no significant differences in positive and negative affect fluctuations, nor recurrence rates between women receiving PCT while tapering ADM vs. women continuing ADM. We found no association between affect fluctuations, pre-natal depressive symptoms, and birth weight (all p > 0.05). Conclusion: This explorative study showed that tapering ADM while receiving online PCT may protect pregnant women against recurrences of depression and affect fluctuations, without affecting birth weight. There is a high need for more controlled studies focusing on tapering ADM with (online) psychological interventions during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Perinatal depression and anxiety are associated with unfavourable child outcomes.Aims: To 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.Method: Pregnant 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.Results: In 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. A post hoc analysis of the 98 women with anxiety disorders showed lower infant gestational age at delivery in the CBT than in the CAU group.Conclusions: Prenatally 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. [ABSTRACT FROM AUTHOR]

Purpose of Article: In a previous pilot randomized controlled trial including 54 pregnant women with depression, maternal mood improved after Cognitive Behavioural Therapy (CBT) compared to treatment as usual (TAU), showing medium to large effect sizes. The effect persisted up to 9 months postpartum, with infant outcomes also showing medium to large effects favoring CBT in various child domains. This perspective article summarizes the results of a follow-up that was performed approximately 5 years later in the same cohort, assessing the effects of antenatal Cognitive Behavioural Therapy for depression and anxiety on child buccal cell DNA-methylation, brain morphology, behavior and cognition. Findings: Children from the CBT group had overall lower DNA-methylation compared to children from the TAU group. Mean DNA-methylation of all NR3C1 promoter-associated probes did not differ significantly between the CBT and TAU groups. Children from the CBT group had a thicker right lateral occipital cortex and lingual gyrus. In the CBT group, Voxel-Based-Morphometry analysis identified one cluster showing increased gray matter concentration in the right medial temporal lobe, and fixel-based analysis revealed reduced fiber-bundle-cross-section in the Fornix, the Optical Tract, and the Stria Terminalis. No differences were observed in full-scale IQ or Total Problems Score. When the total of hypotheses tests in this study was considered, differences in DNA-methylation and brain measurements were no longer significant. Summary: Our explorative findings suggest that antenatal depression treatment decreases overall child DNA-methylation, increases cortical thickness, and decreases white matter fiber-bundle cross-section in regions involved in cognitive function and the stress response. Nevertheless, larger studies are warranted to confirm our preliminary conclusion that CBT in pregnancy alters neurobiological outcomes in children. Clinical relevance remains unclear as we found no effects of antenatal CBT on child behavior or cognition (yet). [ABSTRACT FROM AUTHOR]

Background: According to cognitive behavioural theory, cognitive factors (i.e. underlying general dysfunctional beliefs and (situation) specific illness beliefs) are theorized to lead to outcomes like anxiety and depression. In clinical practice, general dysfunctional beliefs are generally not tackled directly in short-term-therapy. Aims: The goal of the present study was to investigate the associations of general versus specific illness beliefs on anxiety and depressive symptoms and psychiatric disorders among a subgroup of patients with inflammatory bowel disease (IBD) with poor mental quality of life (QoL). Method: This study concerns cross-sectional data, collected at baseline from a randomized clinical trial. One hundred and eighteen patients, recruited at four Dutch hospitals, with poor QoL (score ≤23 on the mental health subscale of the Short-Form 36-item Health-Survey; SF-36) were included. General dysfunctional beliefs were measured by the Dysfunctional Attitude Scale (DAS), specific illness beliefs by the Illness Perceptions Questionnaire-Revised (IPQ-R), anxiety and depressive symptoms by the Hospital Anxiety and Depression Scale (HADS), and psychiatric disorders by the Structured Clinical Interview for DSM-IV Axis-I Disorders (SCID-I). Results: Univariate analyses showed associations between the level of anxiety and/or depression and general dysfunctional beliefs and four specific illness beliefs (consequences, personal control, emotional representations and treatment control). Among patients with IBD with psychiatric disorders, only the DAS was significantly associated with anxiety and depression (DAS added to IPQ-R and IPQ-R added to DAS). Conclusions: Psychological interventions may have to target general dysfunctional beliefs of patients with IBD with co-morbid psychiatric disorders to be effective. These patients with IBD are especially in need of psychological treatment. [ABSTRACT FROM AUTHOR]

Background: Mother-to-infant bonding is defined as the emotional tie experienced by a mother towards her child, which is considered to be important for the socio-emotional development of the child. Numerous studies on the correlates of both prenatal and postnatal mother-to-infant bonding quality have been published over the last decades. An up-to-date systematic review of these correlates is lacking, however. Objective: To systematically review correlates of prenatal and postnatal mother-to-infant bonding quality in the general population, in order to enable targeted interventions. Methods: MEDLINE, Embase, CINAHL, and PsychINFO were searched through May 2018. Reference checks were performed. Case-control, cross-sectional or longitudinal cohort studies written in English, German, Swedish, Spanish, Norwegian, French or Dutch defining mother-to-infant bonding quality as stipulated in the protocol (PROSPERO CRD42016040183) were included. Two investigators independently reviewed abstracts, full-text articles and extracted data. Methodological quality was assessed using the National Institute of Health Quality Assessment Tool for Observational Cohort and Cross-sectional studies and was rated accordingly as poor, fair or good. Clinical and methodological heterogeneity were examined. Main results: 131 studies were included. Quality was fair for 20 studies, and poor for 111 studies. Among 123 correlates identified, 3 were consistently associated with mother-to-infant bonding quality: 1) duration of gestation at assessment was positively associated with prenatal bonding quality, 2) depressive symptoms were negatively associated with postnatal mother-to-infant bonding quality, and 3) mother-to-infant bonding quality earlier in pregnancy or postpartum was positively associated with mother-to-infant bonding quality later in time. Conclusion: Our review suggests that professionals involved in maternal health care should consider monitoring mother-to-infant bonding already during pregnancy. Future research should evaluate whether interventions aimed at depressive symptoms help to promote mother-to-infant bonding quality. More high-quality research on correlates for which inconsistent results were found is needed. [ABSTRACT FROM AUTHOR]

Objective: Antidepressant medication is commonly used for the prevention of depression recurrence in the perinatal period, yet it is unknown what vulnerability markers may play a role in recurrence. The objective of the current study was to provide a descriptive overview of the associated characteristics of women who experienced a perinatal recurrence of depression despite ongoing antidepressant use, and further, to identify clinically measurable vulnerability markers associated with recurrence. Methods: Eighty-five pregnant women with a history of depression who used antidepressants (e.g. Selective Serotonin Reuptake Inhibitors or Serotonin and Noradrenaline Reuptake Inhibitors) at the start of the study were included. Clinical features, including information on psychiatric history and antidepressant use, were collected throughout the perinatal period (in this study defined as the period between 12 weeks of pregnancy untill three months postpartum). The clinical features of women experiencing recurrence of depression were described in detail. To identify vulnerability markers associated with recurrence of depression, we performed exploratory univariable logistic regression analyses. Results: Eight women (9.4%) experienced a recurrence of depression; two during pregnancy and six in the first 12 weeks postpartum. All women with recurrence of depression had first onset of depression during childhood or adolescence and had at least 2 psychiatric co-morbidities. Identification of vulnerability markers associated with recurrence of depression yielded associations with depressive symptoms around 16 weeks of pregnancy (OR 1.28, 95%CI 1.08–1.52), number of psychiatric co-morbidities (OR 1.89, 95%CI 1.16–3.09) and duration of antidepressant use (OR 1.01, 95%CI 1.00–1.02). Conclusion: Implementing adequate risk assessment in pregnant women who use antidepressants can help identify predictors for recurrence of depression in future studies and thus ultimately lead to improved care. [ABSTRACT FROM AUTHOR]

Introduction Diagnosis and treatment of fractures and dislocations are mostly performed in hospital settings. However, equal care for patients with non-complex fractures or dislocations ('minor trauma care') may be provided in general practice. While substitution of care from secondary to primary care settings is stimulated by governments and insurers, it is unknown what the effects are on patient satisfaction level. Therefore, our primary objective is to determine the effect of minor trauma care delivered in a general practice as compared with a hospital on patient satisfaction. Secondary objectives are to assess the effects on treatment outcomes, cost-effectiveness and time consumption. Methods and analysis In a prospective cohort study, we will include 200 patients aged 12 and over with an X-ray confirmed diagnosis of a non- complex fracture or dislocation out of whom 100 treated in a general practice and 100 in a secondary care hospital, both located in the Netherlands. All treatment procedures and follow-up will be done in accordance to the hospital's standards of trauma care. Study assessments will be performed pre-treatment, and 1, 6 and 12 weeks after treatment. Data collected include demographics, patient satisfaction and patient-reported outcomes including physical functioning, complications, pain scores and treatment-related costs. The primary outcome patient satisfaction measured at 12 weeks will be compared between the settings and additionally multivariable regression will be performed to assess potential confounding effects of unbalanced prognostic factors. Treatment outcomes and time consumption will be analysed following the same approach while costeffectiveness will be assessed using an incremental cost-effectiveness ratio. Subsequently, results will be discussed using focus groups consisting of patients (n=15) and healthcare providers. Ethics and dissemination The Medical Ethics Committee from the University Medical Center Groningen reviewed this study protocol and granted exemption from ethical approval (METc UMCG 2017/277). Study results will be presented at (inter)national conferences and published in peer-reviewed journals. [ABSTRACT FROM AUTHOR]

Background: Depression is common among older adults and is typically treated with antidepressants.Objective: To determine the non-adherence rates to antidepressants among older adults in primary care, based on non-initiation, suboptimal implementation or non-persistence.Methods: We selected all patients aged ≥60 years and diagnosed with depression in 2012, from the Netherlands Institute for Health Services Research (NIVEL) Primary Care Database. Non-initiation was defined as no dispensing within 14 days of the first prescription; suboptimal implementation, as fewer than 80% of the days covered by dispensed dosages; and non-persistence, as discontinuation within 294 days after first dispense. First, we determined the antidepressant non-initiation, suboptimal implementation and non-persistence rates. Second, we examined whether comorbidity and chronic drug use were associated with non-adherence by mixed-effects logistic regression (non-initiation or suboptimal implementation as dependent variables) and a clustered Cox regression (time to non-persistence).Results: Non-initiation, suboptimal implementation and non-persistence rates were 13.5%, 15.2% and 37.1%, respectively. As the number of chronically used drugs increased, the odds of suboptimal implementation (odds ratio, 0.89; 95% confidence interval, 0.83-0.95) and of non-persistence (hazard ratio, 0.87; 95% confidence interval, 0.82-0.92) reduced.Conclusions: Non-adherence to antidepressants is high among older patients with depression in primary care settings. Adherence is better when patients are accustomed to taking larger numbers of prescribed drugs, but this only provides partial explanation of the variance. GPs should be aware of the high rates of non-adherence. Emphasizing the importance of adhering to the optimal length of antidepressant therapy might be prudent first steps to improving adherence. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Late-life depression often coincides with chronic somatic diseases and, consequently, with polypharmacy, which may complicate medical treatment.Objective: To determine the associations between patients diagnosed with late-life depression in primary care and multimorbidity and polypharmacy.Methods: This cross-sectional observational study was performed using 2012 primary care data. Depressed patients aged ≥60 years were compared to age and gender matched patients diagnosed with other psychological diagnoses and mentally healthy controls. Morbidity and prescription data were combined, and regression analyses were performed for the associations between depression and chronic disease and chronic drug use.Results: We included 4477 patients; 1512 had a record of depression, 1457 of other mental health or psychological diagnoses and 1508 were controls. Depressed patients had a 16% [Prevalence Ratio (PR) 1.16; 95% confidence interval (95% CI) 10%-24%] higher rate of chronic somatic disease and higher odds for multimorbidity (OR 1.55; 95% CI 1.33-1.81) compared with controls. No differences existed between depressed patients and patients with other psychological diagnoses. Compared with controls, depressed patients had a 46% (95% CI 39-53%) higher rate of chronic drug use and higher odds for polypharmacy (OR 2.89; 95% CI 2.41-3.47). Depressed patients also had higher rates of chronic drug use and higher odds for polypharmacy compared with patients with other psychological diagnoses (PR 1.26; OR 1.75; both P < 0.001).Conclusions: Late-life depression in primary care patients is associated with more chronic drug use, even beyond the increased rates of comorbid somatic diseases. General practitioners should consider medication reviews to prevent unnecessary drug-related problems in these patients. [ABSTRACT FROM AUTHOR]

Background: The majority of patients with depressive disorders are treated by general practitioners (GPs) and are prescribed antidepressant medication. Patients prefer psychological treatments but they are under-used, mainly due to time constraints and limited accessibility. A promising approach to deliver psychological treatment is blended care, i.e. guided online treatment. However, the cost-effectiveness of blended care formatted as an online psychological treatment supported by the patients' own GP or general practice mental health worker (MHW) in routine primary care is unknown. We aim to demonstrate non-inferiority of blended care compared with usual care in patients with depressive symptoms or a depressive disorder in general practice. Additionally, we will explore the real-time course over the day of emotions and affect, and events within individuals during treatment. Methods: This is a pragmatic non-inferiority trial including 300 patients with depressive symptoms, recruited by collaborating GPs and MHWs. After inclusion, participants are randomized to either blended care or usual care in routine general practice. Blended care consists of the 'Act and Feel' treatment: an eight-week web-based program based on behavioral activation with integrated monitoring of depressive symptomatology and automatized feedback. GPs or their MHWs coach the participants through regular face-to-face or telephonic consultations with at least three sessions. Depressive symptomatology, health status, functional impairment, treatment satisfaction, daily activities and resource use are assessed during a follow-up period of 12 months. During treatment, real-time fluctuations in emotions and affect, and daily events will be rated using ecological momentary assessment. The primary outcome is the reduction of depressive symptoms from baseline to three months follow-up. We will conduct intention-to-treat analyses and supplementary per-protocol analyses. Discussion: This trial will show whether blended care might be an appropriate treatment strategy for patients with depressive symptoms and depressive disorder in general practice. [ABSTRACT FROM AUTHOR]

Aim: To determine whether ataxia rating scales are reliable disease biomarkers for early onset ataxia (EOA).Method: In 40 patients clinically identified with EOA (28 males, 12 females; mean age 15y 3mo [range 5-34y]), we determined interobserver and intraobserver agreement (interclass correlation coefficient [ICC]) and discriminant validity of ataxia rating scales (International Cooperative Ataxia Rating Scale [ICARS], Scale for Assessment and Rating of Ataxia [SARA], and Brief Ataxia Rating Scale [BARS]). Three paediatric neurologists independently scored ICARS, SARA and BARS performances recorded on video, and also phenotyped the primary and secondary movement disorder features. When ataxia was the primary movement disorder feature, we assigned patients to the subgroup 'EOA with core ataxia' (n=26). When ataxia concurred with other prevailing movement disorders (such as dystonia, myoclonus, and chorea), we assigned patients to the subgroup 'EOA with comorbid ataxia' (n=12).Results: ICC values were similar in both EOA subgroups of 'core' and 'comorbid' ataxia (0.92-0.99; ICARS, SARA, and BARS). Independent of the phenotype, the severity of the prevailing movement disorder predicted the ataxia rating scale scores (β=0.83-0.88; p<0.05).Interpretation: In patients with EOA, the reliability of ataxia rating scales is high. However, the discriminative validity for 'ataxia' is low. For adequate interpretation of ataxia rating scale scores, application in uniform movement disorder phenotypes is essential. [ABSTRACT FROM AUTHOR]

Background: Continuation of antidepressant medication (ADM) after remission is widely used to prevent depressive relapse/recurrence. Little is known about predictors of ADM use in terms of adherence, dosage, and successful tapering. The current study aimed to explore beliefs about the causes of depression and recovery (i.e., causal beliefs) and to examine whether they predict ADM use.Methods: The data were drawn from a controlled trial and an extension of this trial with additional experience sampling. In total, 289 remitted patients with recurrent depression (ADM ≥ 6 months) were randomly assigned to Preventive Cognitive Therapy (PCT) with ADM tapering, PCT with maintenance ADM, or maintenance ADM alone. Adherence, ADM dosage, and causal beliefs regarding the first and last depressive episodes were explored via questionnaires.Results: Most patients mentioned stressful life events as cause of depression, although more patients tended to endorse external causes for the first episode and internal causes for the last episode. ADM was most often mentioned as helpful during recovery from both episodes. Over half of all patients were adherent and under half of the patients in the tapering condition were able to complete the taper. Causal beliefs did not predict ADM use.Conclusions: The results suggest that causal beliefs play little role in the use of maintenance ADM. More information is needed on factors contributing to successful tapering. The results must be interpreted with caution as this is not a naturalistic study and the results might be biased toward a more favorable view regarding ADM. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Pelvic organ prolapse is a common condition. There is inconsistency between predictors of unsuccessful pessary fitting in urological/gynaecological clinics. Research in general practice is scarce. The aim was to estimate the proportion of women in general practice with a symptomatic pelvic organ prolapse and unsuccessful pessary fitting, and to identify characteristics associated with unsuccessful pessary fitting. Methods: A cross-sectional study in general practice ( n = 20) was carried out among women (≥55 years) with symptomatic prolapse ( n = 78). Multivariate logistic regression analysis was used to identify predictors of unsuccessful pessary fitting. Results: In total, 33 women (42 %) had unsuccessful pessary fitting. Factors associated with unsuccessful pessary fitting were age (per year, OR 0.93 [95 % CI 0.87-1.00]), body mass index (per kg/m, OR 1.14 [95 % CI 1.00-1.30]), and having underactive pelvic floor muscles (OR 2.60 [95 % CI 0.81-8.36]). Conclusions: Pessary fitting was successful in 58 %, indicating that pessary treatment may be suitable for many, but not for all women in general practice with symptomatic prolapse. The condition of the pelvic floor probably plays a role in the success of pessary fitting, as demonstrated by the association with underactive pelvic floor muscles, and body mass index. The association with age may reflect the higher acceptance of conservative treatments for prolapse in older women. This is the first study on predictive factors for unsuccessful pessary fitting in general practice. Therefore, further research should seek to confirm these associations before we can recommend the use of this information in patient counselling. [ABSTRACT FROM AUTHOR]

Increasingly, evidence has been accumulating emphasizing the importance of looking at bipolar disorder ( BD) from a neurodevelopmental and transdimensional perspective to better understand its origins and its course. In this overview article, the problems facing pathophysiological psychiatric research in BD are addressed and interpreted in the light of brain complexity. Brain complexity can be split into spatial complexity, which constitutes the physiological levels of the central nervous system (i.e., the genetic, molecular, cellular, neuronal circuit and phenomenological levels), and temporal complexity, that is, neurodevelopment. The consequences of this consideration are discussed and suggestions for clinical practice and pathophysiological psychiatric research are made. [ABSTRACT FROM AUTHOR]

Background The Burke-Fahn-Marsden Dystonia Rating Scale is a universally applied instrument for the quantitative assessment of dystonia in both children and adults. However, immature movements by healthy young children may also show 'dystonic characteristics' as a consequence of physiologically incomplete brain maturation. This could implicate that Burke-Fahn-Marsden scale scores are confounded by pediatric age. Objective In healthy young children, we aimed to determine whether physiologically immature movements and postures can induce an age-related effect on Burke-Fahn-Marsden movement and disability scale scores. Methods Nine assessors specializied in movement disorders (3 adult neurologists, 3 pediatric neurologists, and 3 MD/PhD students) independently scored the Burke-Fahn-Marsden movement scale in 52 healthy children (4-16 years of age; 2 boys and 2 girls per year of age). Independent of that, parents scored their children's functional motor development according to the Burke-Fahn-Marsden disability scale in another 52 healthy children (4-16 years of age; 2 boys and 2 girls per year of age). By regression analysis, we determined the association between Burke-Fahn-Marsden movement and disability scales outcomes and pediatric age. Results In healthy children, assessment of physiologically immature motor performances by the Burke-Fahn-Marsden movement and disability scales showed an association between the outcomes of both scales and age (until 16 years and 12 years of age, β = −0.72 and β = −0.60, for Burke-Fahn-Marsden movement and disability scale, respectively [both P < 0.001]). Conclusions The Burke-Fahn-Marsden movement and disability scales are influenced by the age of the child. For accurate interpretation of longitudinal Burke-Fahn-Marsden Dystonia Rating Scale scores in young dystonic children, consideration of pediatric age-relatedness appears advisory. [ABSTRACT FROM AUTHOR]

Low levels of insulin-like growth factor-1 (IGF-1), an essential neurotrophic factor, have been associated with worse cognitive function in older adults. However, few studies have assessed the prospective association of serum IGF-1 with cognitive function. We aimed to determine the association between serum IGF-1 on concurrent and prospective cognitive function in a population sample of men aged 40–80 years. Blood samples were assessed for IGF-1 levels at baseline and neuropsychological assessments were performed at baseline (n = 400) and at follow-up after a mean duration of 8.3 years (n = 286). Linear regression analyses were carried out to determine the associations between quintiles of IGF-1 and cognitive function at the baseline and follow-up visits. Results showed that those in the top quintile of IGF-1 had lower processing capacity and global cognition scores at follow-up after controlling for cognitive function at baseline and other confounding factors. Additional analyses exploring associations with IGF-1 separately in middle-aged and older participants, and with quartiles of IGF-1 produced similar results. In those older than 60 years, high IGF-1 levels were also associated with lower baseline processing capacity. These results suggest that high IGF-1 levels are associated with worse long-term cognition in men. Together with past studies, we suggest that both, high and low levels of IGF-1 may be associated with poor cognitive function and that optimum levels of IGF-1 (quintile 2 and 3 in current study) may be associated with better cognitive function. [ABSTRACT FROM AUTHOR]

Background: Approximately 6.2 % of women in the USA and 3.7 % of women in the UK, use Selective Serotonin Reuptake Inhibitors (SSRIs) during their pregnancies because of depression and/or anxiety. In the Netherlands, this prevalence is around 2 %. Nonetheless, SSRI use during pregnancy is still controversial. On the one hand SSRIs may be toxic to the intrauterine developing child, while on the other hand relapse or recurrence of depression during pregnancy poses risks for both mother and child. Among patients and professionals there is an urgent need for evidence from randomized studies to make rational decisions regarding continuation or tapering of SSRIs during pregnancy. At present, no such studies exist. Methods/Design: 'Stop or Go' is a pragmatic multicentre randomized non-inferiority trial among 200 pregnant women with a gestational age of less than 16 weeks who use SSRIs without clinically relevant depressive symptoms. Women allocated to the intervention group will receive preventive cognitive therapy with gradual, guided discontinuation of SSRIs under medical management (STOP). Women in the control group will continue the use of SSRIs (GO). Primary outcome will be the (cumulative) incidence of relapse or recurrence of maternal depressive disorder (as assessed by the Structured Clinical Interview for DSM disorders) during pregnancy and up to three months postpartum. Secondary outcomes will be child outcome (neonatal outcomes and psychomotor and behavioural outcomes up to 24 months postpartum), and health-care costs. Total study duration for participants will be therefore be 30 months. We specified a non-inferiority margin of 15 % difference in relapse risk. Discussion: This study is the first to investigate the effect of guided tapering of SSRIs with preventive cognitive therapy from early pregnancy onwards as compared to continuation of SSRIs during pregnancy. We will study the effects on both mother and child with a pragmatic approach. Additionally, the study examines cost effectiveness. If non-inferiority of preventive cognitive therapy with guided tapering of SSRIs compared to intended continuation of SSRIs is demonstrated for the primary outcome, this may be the preferential strategy during pregnancy. [ABSTRACT FROM AUTHOR]

Aim: To investigate the interobserver agreement on phenotypic early-onset ataxia (EOA) assessment and to explore whether the Scale for Assessment and Rating of Ataxia (SARA) could provide a supportive marker.Method: Seven movement disorder specialists provided independent phenotypic assessments of potentially ataxic motor behaviour in 40 patients (mean age 15y [range 5-34]; data derived from University Medical Center Groningen medical records 1998-2012). We determined interobserver agreement by Fleiss' kappa. Furthermore, we compared percentage SARA subscores ([subscore/total score]×100%) between 'indisputable' (primary ataxia recognition by at least six observers) and 'mixed' (ataxia recognition, unfulfilling 'indisputable' criteria) EOA phenotypes.Results: Agreement on phenotypic EOA assessment was statistically significant (p<0.001), but of moderate strength (Fleiss' kappa=0.45; 95% CI 0.38-0.51). During mild disease progression, percentage SARA gait subscores discriminated between 'indisputable' and 'mixed' EOA phenotypes. In patients with percentage SARA gait subscores >30%, primary ataxia was more frequently present than in those with subscores <30% (p=0.001).Interpretation: Among movement-disorder professionals from different disciplines, interobserver agreement on phenotypic EOA recognition is of limited strength. SARA gait subscores can provide a supportive discriminative marker between EOA phenotypes. Hopefully, future phenotypic insight will contribute to the inclusion of uniform, high-quality data in international EOA databases. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined whether adding mobile cognitive therapy (M-CT) to treatment as usual (TAU) is clinically superior to TAU alone over 24 months in depressed individuals. Topics covered include the cumulative relapse/recurrence rate after 24 months, the effectiveness of guided and unguided internet-based treatments, and long-term effects of face-to-face preventive cognitive therapy (PCT) and other face-to-face relapse prevention strategies.

Background: Internet-based cognitive therapy with monitoring via text messages (mobile CT), in addition to treatment as usual (TAU), might offer a cost-effective way to treat recurrent depression. Method: Remitted patients with at least 2 previous episodes of depression were randomized to mobile CT in addition to TAU (n = 126) or TAU only (n = 113). A linear mixed model was used to examine the effect of the treatment condition on a 3-month course of depressive symptoms after remission. Both an intention-to-treat analysis (n = 239) and a completer analysis (n = 193) were used. Depressive symptoms were assessed using the Inventory of Depressive Symptomatology (IDS-SR30) at baseline and 1.5 and 3 months after randomization. Results: Residual depressive symptoms showed a small but statistically significant decrease in the intention-to-treat group over 3 months in the mobile CT group relative to the TAU group (difference: -1.60 points on the IDS-SR30 per month, 95% CI = -2.64 to -0.56, p = 0.003). The effect of the treatment condition on the depressive symptomatology at the 3-month follow-up was small to moderate (Cohen's d = 0.44). All analyses among completers (≥5 modules) showed more pronounced treatment effects. Adjustment for unequally distributed variables did not markedly affect the results. Conclusions: Residual depressive symptoms after remission showed a more favorable course over 3 months in the mobile CT group compared to the TAU group. These results are a first indication that mobile CT in addition to TAU is effective in treating recurrently depressed patients in remission. However, demonstration of its long-term effectiveness and replication remains necessary. © 2015 S. Karger AG, Basel. [ABSTRACT FROM AUTHOR]

Aim The aim of the study was to determine whether paediatric ataxia speech subscores are reliably applicable for international early-onset ataxia ( EOA) databases. If so, we reasoned that ataxia speech subscores should be associated with ataxia scores and involve high interobserver agreement, including those for internationally applicable Scale for Assessment and Rating of Ataxia ( SARA) syllable repetition tasks ( SARASRT). Method Three independent paediatric neurologists and a speech therapist scored speech in 52 healthy children (mean age 10y, range 4-16y) and 40 individuals with EOA (mean age 15y, range 5-34y). We compared ataxia speech subscores for the association with age and ataxia scores as well as interobserver reliability. Results In healthy children, ataxia speech subscores were moderately associated with age (International Cooperative Ataxia Rating Scale [ICARS]: r=−0.515; SARA: r=−0.321; p<0.05) and with ataxia scores ( ICARS: r=0.552; SARA: r=0.336; p<0.05), and revealed slight to moderate interobserver agreement ( ICARS-intraclass correlation coefficient [ICC]: 0.380; SARA- ICC: 0.185; SARASRT- ICC: 0.509). In EOA, speech subscores have a strong association with ataxia scores ( ICARS: r=0.735; SARA: r=0.730; p<0.001) and revealed substantial to nearly perfect interobserver agreement ( ICARS- ICC: 0.812; SARA- ICC: 0.854; SARASRT- ICC: 0.724). Interpretation Early-onset ataxia speech subscores are associated with ataxia and also reveal high interobserver agreement, including those internationally applicable to SARASRT. We conclude that SARASRT appears to be applicable for EOA databases. However, before syllable repetition tasks are included, we would advise to wait for the results published by the international Childhood Ataxia and Cerebellar Group. [ABSTRACT FROM AUTHOR]

Background: Childhood adversity may lead to depressive relapse through its long-lasting influence on stress sensitivity. In line with the stress sensitization hypothesis, minor (daily) stress is associated with depressive relapse. Therefore, we examine the impact of childhood adversity on daily stress and its predictive value on prospectively assessed depressive symptoms in recurrently depressed patients. Method: Daily stress was assessed in recurrently depressed adult patients, enrolled into two randomized trials while remitted. The reported intensity and frequency of dependent and independent daily stress was assessed at baseline. Independent stress is externally generated, for example an accident happening to a friend, while dependent stress is internally generated, for example getting into a fight with a neighbor. Hierarchical regression analyses were performed with childhood adversity, independent and dependent daily stress as predictor variables of prospectively measured depressive symptoms after three months of follow-up (n = 138). Results: We found that childhood adversity was not significantly associated with a higher frequency and intensity of daily stress. The intensity of both independent and dependent daily stress was predictive of depressive symptom levels at follow-up (unadjusted models respectively: B = 0.47, t = 2.05, p = 0.041, 95% CI = 0.02–0.92; B = 0.29, t = 2.20, p = 0.028, 95% CI = 0.03–0.55). No associations were found between childhood adversity and depressive symptoms at follow-up. Conclusion: No evidence was found supporting stress sensitization due to the experience of childhood adversity in this recurrently depressed but remitted patient group. Nevertheless, our research indicates that daily stress might be a target for preventive treatment. Trial Registration: Trial A: Nederlands Trial Register Trial B: Nederlands Trial Register [ABSTRACT FROM AUTHOR]

AIM The aim of the study was to determine whether paediatric ataxia speech subscores are reliably applicable for international early-onset ataxia (EOA) databases. If so, we reasoned that ataxia speech subscores should be associated with ataxia scores and involve high interobserver agreement, including those for internationally applicable Scale for Assessment and Rating of Ataxia (SARA) syllable repetition tasks (SARASRT). METHOD Three independent paediatric neurologists and a speech therapist scored speech in 52 healthy children (mean age 10y, range 4–16y) and 40 individuals with EOA (mean age 15y, range 5–34y). We compared ataxia speech subscores for the association with age and ataxia scores as well as interobserver reliability. RESULTS In healthy children, ataxia speech subscores were moderately associated with age (International Cooperative Ataxia Rating Scale [ICARS]: r=–0.515; SARA: r=–0.321; p<0.05) and with ataxia scores (ICARS: r=0.552; SARA: r=0.336; p<0.05), and revealed slight to moderate interobserver agreement (ICARS-intraclass correlation coefficient [ICC]: 0.380; SARA-ICC: 0.185; SARASRT-ICC: 0.509). In EOA, speech subscores have a strong association with ataxia scores (ICARS: r=0.735; SARA: r=0.730; p<0.001) and revealed substantial to nearly perfect interobserver agreement [ICARS-ICC: 0.812; SARA-ICC: 0.854; SARASRT-ICC: 0.724]. INTERPRETATION Early-onset ataxia speech subscores are associated with ataxia and also reveal high interobserver agreement, including those internationally applicable to SARASRT. We conclude that SARASRT appears to be applicable for EOA databases. However, before syllable repetition tasks are included, we would advise to wait for the results published by the international Childhood Ataxia and Cerebellar Group. [ABSTRACT FROM AUTHOR]

Aim To investigate ataxia rating scales in children for reliability and the effect of age and sex. Method Three independent neuropaediatric observers cross-sectionally scored a set of paediatric ataxia rating scales in a group of 52 healthy children (26 males, 26 females) aged 4 to 16 years (mean age 10y 5mo SD 3y 11mo). The investigated scales involved the commonly applied International Cooperative Ataxia Rating Scale ( ICARS), the Scale for Assessment and Rating of Ataxia ( SARA), the Brief Ataxia Rating Scale ( BARS), and PEG-board tests. We investigated the interrelatedness between individual ataxia scales, the influence of age and sex, inter- and intra-observer agreement, and test-retest reliability. Results Spearman's rank correlations revealed strong correlations between ICARS, SARA BARS, and PEG-board test (all p<0.001). ICARS, SARA, BARS and PEG-board test outcomes were age-dependent until 12.5, 10, 11, and 11.5 years of age respectively. Intraclass correlation coefficients ( ICCs) varied between moderate and almost perfect (interobserver agreement: 0.85, 0.72, and 0.69; intraobserver agreement: 0.92, 0.94, and 0.70; and test-retest reliability: 0.95, 0.50, and 0.71; for ICARS, SARA, and BARS respectively). Interobserver variability decreased after the sixth year of life. Interpretation In healthy children, ataxia rating scales are reliable, but should include age-dependent interpretation in children up to 12 years of age. To enable longitudinal interpretation of quantitative ataxia rating scales in children, European paediatric normative values are necessary. [ABSTRACT FROM AUTHOR]

Objectives Existing and previously published datasets were examined for associations between illness and treatment characteristics and monocyte pro-inflammatory gene expression in patients with bipolar disorder ( BD). We hypothesized a priori that increased monocyte pro-inflammatory gene expression would be found more frequently in patients with a lifetime history of psychotic symptoms. Methods Monocyte quantitative polymerase chain reaction and symptom data from 64 patients with BD were collected from three Dutch studies. Regression analyses were performed to analyze the various associations between pro-inflammatory gene expression and clinical features, from which feature-expression heat maps were drawn. Results No associations were found between pro-inflammatory gene expression and lifetime psychotic symptoms, whereas a positive association was identified between subcluster 2 genes and manic symptoms. For several subcluster 1a genes, a negative association was found with age at onset. For most subcluster 2 genes, a positive association was found with the duration of illness. Current use of antidepressants and of anti-epileptic agents was associated with subcluster 2 gene expression, and current use of lithium and antipsychotic agents with subcluster 1a gene expression. Conclusions Our hypothesis that lifetime psychotic features would be associated with pro-inflammatory monocyte gene expression was not confirmed. In an explorative analysis we found: (i) a possible relationship between pro-inflammatory gene expression and manic symptomatology; (ii) a differential immune activation related to age at onset and duration of illness; and (iii) support for the concept of an immune suppressive action of some of the mood-regulating medications. [ABSTRACT FROM AUTHOR]

School environment is an important determinant of psychosocial function and may also be related to mental health. We therefore investigated whether perceived school safety, a simple measure of this environment, is related to mental health problems. In a population-based sample of 11,130 secondary school students, we analysed the relationship of perceived school safety with mental health problems using multiple logistic regression analyses to adjust for potential confounders. Mental health problems were defined using the clinical cut-off of the self-reported Strengths and Difficulties Questionnaire. School safety showed an exposure-response relationship with mental health problems after adjustment for confounders. Odds ratios increased from 2.48 ('sometimes unsafe') to 8.05 ('very often unsafe'). The association was strongest in girls and young and middle-aged adolescents. Irrespective of the causal background of this association, school safety deserves attention either as a risk factor or as an indicator of mental health problems. [ABSTRACT FROM AUTHOR]

Aim: to examine whether the severity of different categories of stressful events is associated with continued smoking and alcohol consumption during mid-pregnancy. Also, we explored the explanation of these associations by anxiety and depressive symptoms during pregnancy. Finally, we studied whether the severity of stressful events was associated with the amount of cigarettes and alcohol used by continued users. Method: we conducted a cross-sectional analysis using data from a population-based prospective cohort study. Pregnant women were recruited via midwifery practices throughout The Netherlands. We analyzed women who continued smoking (n = 113) or quit (n = 290), and women who continued alcohol consumption (n = 124) or quit (n = 1403) during pregnancy. Smoking, alcohol consumption, and perceived severity of stressful events were measured at 19 weeks of gestation. The State Trait Anxiety Inventory and the Edinburgh Postnatal Depression Scale were filled out at 14 weeks of gestation. Odds ratios were calculated as association measures and indicated the relative increase for the odds of continuation of smoking and alcohol consumption for the maximum severity score compared to the minimum score. Findings: severity of the following stressful event categories was associated with continued alcohol consumption: ‘conflict with loved ones’ (OR = 10.4, p<0.01), ‘crime related’ (OR = 35.7, p<0.05), ‘pregnancy-specific’ (OR = 13.4, p<0.05), and the total including all events (OR = 17.2, p<0.05). Adjustment for potential confounders (age, parity and educational level) did not notably change the estimates. There was no association of anxiety and depressive symptoms with continued smoking or alcohol consumption. No associations emerged for continued smoking and severity of stressful events. The amount of cigarettes and alcohol consumption among continued users was not associated with severity of stressful events. Conclusions: Our findings may be relevant for health care providers, in particular midwives and general practitioners. The impact of stressful events may be considered when advising pregnant women on smoking and alcohol consumption. [ABSTRACT FROM AUTHOR]

Objective: To perform a systematic review, and if possible a meta-analysis, to establish whether depressed patients with co-morbid chronic somatic illnesses are a high risk “double trouble” group for depressive recurrence. Method: The databases PubMed, EMbase and PsycINFO were systematically searched until the 4th of December 2012 by using MeSH and free text terms. Additionally, reference lists of retrieved publications and treatment guidelines were reviewed, and experts were consulted. Inclusion criteria were: depression had to be measured at least twice during the study with qualified instruments and the chronic somatic illness had to be assessed by self-report or by a medical professional. Information on depressive recurrence was extracted and additionally risk ratios of recurrence were calculated. Results: The search generated four articles that fulfilled our inclusion criteria. These studies showed no differences in recurrence over one- two- three- and 6.5 years of follow-up for a total of 2010 depressed patients of which 694 patients with a co-morbid chronic somatic illness versus 1316 patients without (Study 1: RR = 0.49, 95% CI, 0.17–1.41 at one year follow-up and RR = 1.37, 95% CI, 0.78–2.41 at two year follow-up; Study 2: RR = 0.94, 95% CI, 0.65–1.36 at two year follow-up; Study 3: RR = 1.15, 95% CI, 0.40–3.27 at one year follow-up; RR = 1.07, 95% CI, 0.48–2.42 at two year follow-up and RR = 0.99, 95% CI,0.55–1.77 at 6.5 years follow-up; Study 4: RR = 1.16, 95% CI, 0.86–1.57 at three year follow-up). Conclusion: We found no association between a heightened risk for depressive recurrence and co-morbid chronic somatic illnesses. There is a need for more longitudinal studies to justify the current specific treatment advice such as long-term pharmacological maintenance treatment for this presumed “double trouble” group. [ABSTRACT FROM AUTHOR]

Background: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning. Methodology/Principal Findings: In 65 bipolar patients cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating version. Saliva cortisol measurements were performed to calculate HPA axis indicators: cortisol awakening response, diurnal slope, the evening cortisol level and the cortisol suppression on the dexamethasone suppression test. Regression analyses of depressive symptoms and cognitive functioning on each HPA axis indicator were performed. In addition we calculated percentages explanation of the association between depressive symptoms and cognition by HPA axis indicators. Depressive symptoms were associated with dysfunction in psychomotor speed, attentional switching and the mean score, as well as with attenuation in diurnal slope value. No association was found between HPA axis activity and cognitive functioning and HPA axis activity did not explain the associations between depressive symptoms and cognition. Conclusions/Significance: As our study is the first one in this field specific for bipolar patients and changes in HPA-axis activity did not seem to explain the association between severity of depressive symptoms and cognitive functioning in bipolar patients, future studies are needed to evaluate other factors that might explain this relationship. [ABSTRACT FROM AUTHOR]

In type 1 diabetes, diabetes-associated autoantibodies, including islet cell antibodies (ICAs), reflect adaptive immunity, while increased serum N(ε)-carboxymethyl-lysine (CML), an advanced glycation end product, is associated with proinflammation. We assessed whether serum CML and autoantibodies predicted type 1 diabetes and to what extent they were determined by genetic or environmental factors. Of 7,287 unselected schoolchildren screened, 115 were ICA(+) and were tested for baseline CML and diabetes autoantibodies and followed (for median 7 years), whereas a random selection (n = 2,102) had CML tested. CML and diabetes autoantibodies were determined in a classic twin study of twin pairs discordant for type 1 diabetes (32 monozygotic, 32 dizygotic pairs). CML was determined by enzyme-linked immunosorbent assay, autoantibodies were determined by radioimmunoprecipitation, ICA was determined by indirect immunofluorescence, and HLA class II genotyping was determined by sequence-specific oligonucleotides. CML was increased in ICA(+) and prediabetic schoolchildren and in diabetic and nondiabetic twins (all P < 0.001). Elevated levels of CML in ICA(+) children were a persistent, independent predictor of diabetes progression, in addition to autoantibodies and HLA risk. In twins model fitting, familial environment explained 75% of CML variance, and nonshared environment explained all autoantibody variance. Serum CML, a glycotoxin, emerged as an environmentally determined diabetes risk factor, in addition to autoimmunity and HLA genetic risk, and a potential therapeutic target. [ABSTRACT FROM AUTHOR]

In type 1 diabetes, diabetes-associated autoantibodies, including islet cell antibodies (ICAs), reflect adaptive immunity, while increased serum Nε-carboxymethyl-lysine (CML), an advanced glycation end product, is associated with proinflammation. We assessed whether serum CML and autoantibodies predicted type 1 diabetes and to what extent they were determined by genetic or environmental factors. Of 7,287 unselected schoolchildren screened, 115 were ICA+ and were tested for baseline CML and diabetes autoantibodies and followed (for median 7 years), whereas a random selection (n = 2,102) had CML tested. CML and diabetes autoantibodies were determined in a classic twin study of twin pairs discordant for type 1 diabetes (32 monozygotic, 32 dizygotic pairs). CML was determined by enzyme-linked immunosorbent assay, autoantibodies were determined by radioimmunoprecipitation, ICA was determined by indirect immunofluorescence, and HLA class II genotyping was determined by sequence-specific oligonucleotides. CML was increased in ICA+ and prediabetic schoolchildren and in diabetic and nondiabetic twins (all P < 0.001). Elevated levels of CML in ICA+ children were a persistent, independent predictor of diabetes progression, in addition to autoantibodies and HLA risk. In twins model fitting, familial environment explained 75% of CML variance, and nonshared environment explained all autoantibody variance. Serum CML, a glycotoxin, emerged as an environmentally determined diabetes risk factor, in addition to autoimmunity and HLA genetic risk, and a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Rationale: Pharmacogenetic studies on antipsychotic-induced movement disorders (MD) in schizophrenia so far have focused mainly on tardive dyskinesia. Only a few examined the more acute antipsychotic-induced MD such as parkinsonism and akathisia. Notably, all MD relate to deregulation of the dopamine system. Objective: This study aimed to replicate previously reported associations in candidate genes for acute and tardive antipsychotic-induced MD in a young Caucasian sample. Methods: In 402 patients (median age 26 years), a total of 13 polymorphisms were genotyped in eight dopamine-related candidate genes selected a priori from the literature (regarding dopamine and serotonin receptors, dopamine degradation, and free radicals scavenging enzymes pathways). Results: Patients with MD used on average a higher haloperidol dose equivalent when compared to those without MD. The prevalence of MD was high and did not differ between first- and second-generation antipsychotics. Significant associations were found between (a) the TaqI_D polymorphism and akathisia (OR = 2.3, p = 0.001 for each extra C-allele) and (b) the −141C polymorphism and tardive dyskinesia (OR = 0.20, p = 0.001 for each extra Del allele). The other polymorphisms were not significantly associated with an MD. Conclusions: Two associations were found between genetic variation TaqI_D and the −141C polymorphisms in the DRD2 gene and antipsychotic-induced MD; one with acute akathisia and one with tardive dyskinesia. These were previously reported to be associated with tardive dyskinesia and acute parkinsonism, respectively. These results suggest that the contribution of these DRD2 gene variants in the vulnerability of antipsychotic-induced MD takes place in a more general or pleiotropic way. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) characteristically presents with asymmetrical symptoms, contralateral to the side of the most extensive cerebral affection. This intriguing asymmetry, even included in the definition for diagnosing PD, however, is still part of a mystery. The relation with handedness as a common indicator of cerebral asymmetry might provide a clue in the search for causal factors of asymmetrical symptom onset in PD. This possible relationship, however, is still under debate. The objective of this study was to establish whether a relation between handedness and dominant PD side exists. We searched for cross-sectional or cohort studies that registered handedness and onset side in PD patients in PubMed, EMBASE, and Web of Science from their first record until 14 February 2011. Data about handedness and dominant PD side was extracted. Authors who registered both but not described their relation were contacted for further information. Odds ratios (ORs) were analyzed with a fixed effect Mantel-Haenszel model. Heterogeneity and indications of publication bias were limited. Our electronic search identified 10 studies involving 4405 asymmetric PD patients. Of the right-handed patients, 2413 (59.5%) had right-dominant and 1644 (40.5%) had left-dominant PD symptoms. For the left-handed patients this relation was reversed, with 142 (40.8%) right-dominant and 206 (59.2%) left-dominant PD symptoms. Overall OR was 2.13 (95% confidence interval [CI], 1.71-2.66). Handedness and symptom dominance in PD are firmly related with each other in such a way that the PD symptoms emerge more often on the dominant hand-side. Possible causal factors are discussed. © 2011 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Rationale: Antipsychotic affinity for the histamine H1 receptor and the muscarinic M3 receptor have been associated with the side effects weight gain, and development of diabetes, respectively. Objectives: We investigated polymorphisms of the histamine H1 ( HRH1) and muscarinic acetylcholine receptor M3 ( CHRM3) receptor genes for an association with body mass index (BMI) and glycated hemoglobin (HbA1c). Methods: We included 430 Caucasian patients with a non-affective psychotic disorder using antipsychotics for at least 3 months. Primary endpoints of the study were cross-sectionally measured BMI and HbA1c; secondary endpoints were obesity and hyperglycaemia. Two single-nucleotide polymorphisms (SNPs) in the HRH1 gene, rs346074 and rs346070, and one SNP in the CHRM3 gene, rs3738435, were genotyped. Our primary hypothesis in this study was an interaction between genotype on BMI and antipsychotic affinity for the H1 and M3 receptor. Results: A significant association of interaction between haplotype rs346074-rs346070 and BMI ( p value 0.025) and obesity ( p value 0.005) in patients using high-H1 affinity antipsychotics versus patients using low-H1 affinity antipsychotics was found. There was no association of CHRM3 gene variant rs3738435 with BMI, and we observed no association with HbA1c or hyperglycaemia in any of the variants. Conclusions: This study, for the first time, demonstrates a significant association between HRH1 variants and BMI in patients with a psychotic disorder using antipsychotics. In future, genotyping of HRH1 variants may help predicting weight gain in patients using antipsychotics. [ABSTRACT FROM AUTHOR]

Objective. To assess the effect of withdrawal of antipsychotic treatment on relapse risk in remitted first-episode schizophrenia patients. Methods. First-episode 1-year stable and remitted outpatients with a schizophrenic disorder were randomly allocated to continuation of their antipsychotic regimen for at least 6 months ( N == 9), or gradual withdrawal ( N == 11). Primary outcome was the difference in cumulative relapse-free survival at 9 months. Results. Recruitment was terminated prematurely on 26 October 2005. The cumulative relapse-free survival was 88% (SE == 0.12) in the continuation and 18% (SE == 0.12) in the discontinuation group ( P == 0.001) at 9 months follow-up. Conclusions. Discontinuation of antipsychotic medication markedly increases the risk of relapse in stable remitted first-episode schizophrenia patients. In future studies the topics of safety monitoring and sampling of patients should receive extra attention. [ABSTRACT FROM AUTHOR]

van der Werf-Eldering MJ, van der Meer L, Burger H, Holthausen EAE, Nolen WA, Aleman A. Insight in bipolar disorder: associations with cognitive and emotional processing and illness characteristics. Bipolar Disord 2011: 13: 343-354. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S. Objective: To investigate the multifactorial relationship between illness insight, cognitive and emotional processes, and illness characteristics in bipolar disorder patients. Methods: Data from 85 euthymic or mildly to moderately depressed bipolar disorder patients were evaluated. Insight was measured using the Mood Disorder Insight Scale (total score and subscale scores: awareness of illness, symptom attribution, and need for treatment). Cognitive and emotional functioning was measured in four domains (processing speed, memory, executive functioning, and emotional learning) in addition to premorbid IQ. Illness characteristics were assessed using the Mini-International Neuropsychiatric Interview, the Questionnaire for Bipolar Disorder, and the Inventory of Depressive Symptomatology-self rating scale. Regression analyses were performed for the whole sample. Post-hoc, interactions with lifetime psychotic features (LPF) were statistically tested and if significant, analyses were repeated for patients with (n = 36) and without (n = 49) LPF separately. Results: In the whole group, better insight was associated with lower processing speed, better memory performance, increased emotional learning, higher level of depressive symptoms, and longer duration of illness. Patients with LPF had worse awareness of illness, but better symptom attribution than patients without LPF. No group differences for need for treatment and overall insight were found. Finally, processing speed significantly predicted subscores for symptom attribution in patients with LPF only. Conclusions: Cognitive functioning as well as impairments in emotional learning and psychotic features independently contributes to impaired insight in bipolar disorder. Processing speed seems to be a key variable in the prediction of insight in patients with LPF and not in patients without LPF. [ABSTRACT FROM AUTHOR]

The present study examined construct equivalence of the teacher Strengths and Difficulties Questionnaire and compared mean scores in an ethnically diverse sample of children living in the Netherlands. Elementary schoolteachers completed the Strengths and Difficulties Questionnaire for 2,185 children aged 6 to 10 years of the four largest ethnic groups in the Netherlands, namely native Dutch (n = 684) and Moroccan (n = 702), Turkish (n = 434), and Surinamese (n = 365) immigrant children. Multigroup confirmatory factor analysis suggested the factor structure of the Strengths and Difficulties Questionnaire to be invariant across children’s ethnicity and gender. Additionally, the factor structure appeared to be similar for Dutch and Surinamese teachers. However, mean scores on emotional problems, hyperactivity, conduct problems, prosocial behavior, and impairment varied significantly according to ethnicity and gender. Mean scores on peer problems differed significantly for boys and girls, but not across ethnicity. Whether mean differences reflect a method bias or actual differences in classroom behaviors is discussed and needs further research. [ABSTRACT FROM PUBLISHER]

Antipsychotics are approved treatment for severe conditions and have serious side effects. Antipsychotics are often prescribed off-label. Although a substantial proportion of antipsychotics are prescribed in primary care, it is largely unknown what motivates the general practitioner (GP) to initiate antipsychotic treatment. Therefore, we sought to examine the relation between pre-defined, licensed as well as off-label, reasons for antipsychotic treatment and the initiation of this treatment by the GP as well as report registration and incidence of antipsychotic treatment in general practice. In a case-control study, 723 patients selected from an electronic database and with a new antipsychotic prescription were compared with 3615 controls receiving any other new prescription. Using logistic regression, six pre-defined categories of International Classification of Primary Care (ICPC) codes ('psychosis', 'depression and anxiety', 'sleeping disorders', 'acute stress and surmenage', 'dementia' and 'somatic indications') were associated with initiating antipsychotic treatment. All, including off-label, categories were significantly related to initiating antipsychotic treatment. The incidence of initiating antipsychotic therapy was 1.28 per 1000 persons per year (95% confidence interval: 1.09, 1.48). GPs registered an ICPC code in 50% and prescribed typical antipsychotics in 90% of the cases. Prescription of atypical antipsychotics increased almost threefold over the study period. The results suggest that GPs prescribe antipsychotics off-label. Despite serious side effects and relatively infrequent occurrence in Dutch general practices, GPs seem imprecise in underpinning and registrating the initiation of antipsychotic treatment. GPs increasingly prescribe atypical antipsychotics although the prescription of typical antipsychotics still dominates. [ABSTRACT FROM AUTHOR]