Advanced paternal age and vulnerability to psychotic-like experiences in the offspring

AbstractObjectiveTo investigate whether advanced paternal age is associated with increased psychotic-like experiences (PLEs) and increased sensitivity to Cannabis in the offspring.MethodsA cross-sectional population-based study in 1684 participants aged 18 to 25.ResultsWe found no association of paternal age with PLEs. Only the positive dimension subscale was associated to paternal age, but that could be largely contributed to outliers. Also no increased sensitivity to Cannabis smoking was apparent.ConclusionIn the general population, we did not find robust support for an association between paternal age and vulnerability to PLEs in 18–25year old offspring

A Smartphone Serious Game for Adolescents (Grow It! App):Development, Feasibility, and Acceptance Study

BACKGROUND: Anxiety and mood problems in adolescents often go unnoticed and may therefore remain untreated. Identifying and preventing the development of emotional problems requires monitoring and effective tools to strengthen adolescents' resilience, for example, by enhancing coping skills. OBJECTIVE: This study describes the developmental process, feasibility, and acceptance of Grow It!, a multiplayer serious game app for adolescents aged 12-25 years. The app consists of the experience sampling method (ESM) to monitor thoughts, behaviors, and emotions in daily life to enhance self-insight and daily cognitive behavioral therapy–based challenges to promote adaptive coping. METHODS: Our approach entails an iterative game design process combined with an agile method to develop the smartphone app. The incorporated game features (ie, challenges, chat functionality, and visual representation) in the Grow It! app were co-designed with adolescent end users to increase participant engagement and adherence. RESULTS: The Grow It! app was delivered for Android and iOS in May 2020. Grow It! was offered to adolescents during the COVID-19 crisis between May and December 2020. Participants of the Grow It! COVID-19 study (sample 1: N=685; mean age 16.19, SD 3.11 years; 193/685, 28.2% boys; sample 2: N=1035; mean age 18.78, SD 3.51 years; 193/1035, 18.64% boys) completed 31.5% (13.2/42) to 49.5% (10.4/21) of challenges. Compliance of ESM was suboptimal (35.1/210, 16.7% to 32.5/105, 30.9%). Follow-up questionnaires indicated an overall score of the app of 7.1 out of 10. Moreover, 72.6% (278/383) to 75.6% (487/644) would recommend the app to friends. CONCLUSIONS: To our knowledge, Grow It! is the first gamified ESM app that both measures individual differences in emotional dynamics and offers an integrated cognitive behavioral therapy–based intervention. Our findings support the feasibility and acceptance, and therefore applicability, of the Grow It! app in adolescents. Further iterations of this serious game app will focus on the increase of compliance and on providing participants feedback through their personal mood profiles

The Mood and Resilience in Offspring (MARIO) project:a longitudinal cohort study among offspring of parents with and without a mood disorder

Background:One of the most robust risk factors for developing a mood disorder is having a parent with a mood disorder. Unfortunately, mechanisms explaining the transmission of mood disorders from one generation to the next remain largely elusive. Since timely intervention is associated with a better outcome and prognosis, early detection of intergenerational transmission of mood disorders is of paramount importance. Here, we describe the design of the Mood and Resilience in Offspring (MARIO) cohort study in which we investigate: 1. differences in clinical, biological and environmental (e.g., psychosocial factors, substance use or stressful life events) risk and resilience factors in children of parents with and without mood disorders, and 2. mechanisms of intergenerational transmission of mood disorders via clinical, biological and environmental risk and resilience factors. Methods: MARIO is an observational, longitudinal cohort study that aims to include 450 offspring of parents with a mood disorder (uni- or bipolar mood disorders) and 100-150 offspring of parents without a mood disorder aged 10-25 years. Power analyses indicate that this sample size is sufficient to detect small to medium sized effects. Offspring are recruited via existing Dutch studies involving patients with a mood disorder and healthy controls, for which detailed clinical, environmental and biological data of the index-parent (i.e., the initially identified parent with or without a mood disorder) is available. Over a period of three years, four assessments will take place, in which extensive clinical, biological and environmental data and data on risk and resilience are collected through e.g., blood sampling, face-to-face interviews, online questionnaires, actigraphy and Experience Sampling Method assessment. For co-parents, information on demographics, mental disorder status and a DNA-sample are collected.Discussion: The MARIO cohort study is a large longitudinal cohort study among offspring of parents with and without mood disorders. A unique aspect is the collection of granular data on clinical, biological and environmental risk and resilience factors in offspring, in addition to available parental data on many similar factors. We aim to investigate the mechanisms underlying intergenerational transmission of mood disorders, which will ultimately lead to better outcomes for offspring at high familial risk.</p

The Mood and Resilience in Offspring (MARIO) project:a longitudinal cohort study among offspring of parents with and without a mood disorder

Background:One of the most robust risk factors for developing a mood disorder is having a parent with a mood disorder. Unfortunately, mechanisms explaining the transmission of mood disorders from one generation to the next remain largely elusive. Since timely intervention is associated with a better outcome and prognosis, early detection of intergenerational transmission of mood disorders is of paramount importance. Here, we describe the design of the Mood and Resilience in Offspring (MARIO) cohort study in which we investigate: 1. differences in clinical, biological and environmental (e.g., psychosocial factors, substance use or stressful life events) risk and resilience factors in children of parents with and without mood disorders, and 2. mechanisms of intergenerational transmission of mood disorders via clinical, biological and environmental risk and resilience factors. Methods: MARIO is an observational, longitudinal cohort study that aims to include 450 offspring of parents with a mood disorder (uni- or bipolar mood disorders) and 100-150 offspring of parents without a mood disorder aged 10-25 years. Power analyses indicate that this sample size is sufficient to detect small to medium sized effects. Offspring are recruited via existing Dutch studies involving patients with a mood disorder and healthy controls, for which detailed clinical, environmental and biological data of the index-parent (i.e., the initially identified parent with or without a mood disorder) is available. Over a period of three years, four assessments will take place, in which extensive clinical, biological and environmental data and data on risk and resilience are collected through e.g., blood sampling, face-to-face interviews, online questionnaires, actigraphy and Experience Sampling Method assessment. For co-parents, information on demographics, mental disorder status and a DNA-sample are collected.Discussion: The MARIO cohort study is a large longitudinal cohort study among offspring of parents with and without mood disorders. A unique aspect is the collection of granular data on clinical, biological and environmental risk and resilience factors in offspring, in addition to available parental data on many similar factors. We aim to investigate the mechanisms underlying intergenerational transmission of mood disorders, which will ultimately lead to better outcomes for offspring at high familial risk.</p

Higher cortisol levels may proceed a manic episode and are related to disease severity in patients with bipolar disorder

FSW – Publicaties zonder aanstelling Universiteit Leide

Serum Protein N-Glycosylation Changes with Rheumatoid Arthritis Disease Activity during and after Pregnancy

Proteomic

Lithium Use during Pregnancy and the Risk of Miscarriage

Recent studies have provided new data on the teratogenicity of lithium. Less is known about the risk of miscarriage after lithium use during pregnancy. The aim of this study was to investigate the association between lithium use during pregnancy and miscarriage. Participants were women with bipolar I disorder and one or more pregnancies, of which information on medication use and pregnancy outcome was available (n = 443). The unadjusted odds ratios for miscarriage after lithium use during pregnancy was calculated. Multilevel logistic regression was used to calculate the odds ratio, adjusted for the age at conception and the clustering of pregnancies per woman. Miscarriages occurred in 20.8% of the lithium-exposed pregnancies (16/77), compared with 10.9% of the unexposed pregnancies (40/366) (OR = 2.14; 95% CI: 1.13–4.06). The adjusted odds ratio of miscarriage after lithium use during pregnancy was 2.94 (95% CI: 1.39–6.22). Lithium use during pregnancy may increase the risk of miscarriage

Identification of overlapping but differential binding sites for the high-affinity CXCR3 antagonists NBI-74330

ABSTRACT CXC chemokine receptor CXCR3 and/or its main three ligands CXCL9, CXCL10, and CXCL11 are highly upregulated in a variety of diseases. As such, considerable efforts have been made to develop small-molecule receptor CXCR3 antagonists, yielding distinct chemical classes of antagonists blocking binding and/or function of CXCR3 chemokines. Although it is suggested that these compounds bind in an allosteric fashion, thus far no evidence has been provided regarding the molecular details of their interaction with CXCR3. Using site-directed mutagenesis complemented with in silico homology modeling, we report the binding modes of two high-affinity CXCR3 antagonists of distinct chemotypes: Here we show that NBI-74330 is anchored in the transmembrane minor pocket lined by helices 2 (W2.60, D2.63), 3 (F3.32), and 7 (S7.39, Y7.43), whereas VUF11211 extends from the minor pocket into the major pocket of the transmembrane domains, located between residues in helices 1 (Y1.39), 2 (W2.60), 3 (F3.32), 4 (D4.60), 6 (Y6.51), and 7 (S7.39, Y7.43). Mutation of these residues did not affect CXCL11 binding significantly, confirming the allosteric nature of the interaction of these small molecules with CXCR3. Moreover, the model derived from our in silico-guided studies fits well with the already published structure-activity relationship data on these ligands. Altogether, in this study, we show overlapping, yet different binding sites for two high-affinity CXCR3 antagonists, which offer new opportunities for the structure-based design of allosteric modulators for CXCR3