71 research outputs found

    Response after Infection-Associated Rise in Clozapine Levels in Treatment-Resistant Schizoaffective Disorder

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    The clinical management of patients with treatment-resistant psychotic disorders is still challenging despite years of extensive research. If first-line antipsychotic treatment proves ineffective, clozapine is considered golden standard. Herein, we report on a patient with schizoaffective disorder that initially showed no response to treatment with clozapine and ECT and therefore reached a therapeutic dead end. After an unintentional exposure to supratherapeutic clozapine levels, related to a pneumonia, a significant and persistent reduction of psychotic symptoms occurred. The report suggests a careful reevaluation of the clozapine dose in cases of treatment-resistant psychotic disorders with failed trials of clozapine. Further increase of dose may prove efficacious, although side effects should be closely monitored. Research to determine the upper threshold of clozapine for antipsychotic efficacy is warranted

    Maternal Hypothyroxinemia During Pregnancy and Growth of the Fetal and Infant Head

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    Severe maternal thyroid dysfunction during pregnancy affects fetal brain growth and corticogenesis. This study focused on the effect of maternal hypothyroxinemia during early pregnancy on growth of the fetal and infant head. In a population-based birth cohort, we assessed thyroid status in early pregnancy (median 13.4, 90% range 10.8-17.2), in 4894 women, and measured the prenatal and postnatal head size of their children at 5 time points. Hypothyroxinemia was defined as normal thyroid-stimulating hormone levels and free thyroxine-4 concentrations below the 10th percentile. Statistical analysis was performed using linear generalized estimating equation. Maternal hypothyroxinemia was associated with larger fetal and infant head size (overall estimate beta: 1.38, 95% confidence interval 0.56; 2.19, P = .001). In conclusion, in the general population, even small variations in maternal thyroid function during pregnancy may affect the developing head of the young child

    Maternal Hypothyroxinemia During Pregnancy and Growth of the Fetal and Infant Head

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    Severe maternal thyroid dysfunction during pregnancy affects fetal brain growth and corticogenesis. This study focused on the effect of maternal hypothyroxinemia during early pregnancy on growth of the fetal and infant head. In a population-based birth cohort, we assessed thyroid status in early pregnancy (median 13.4, 90% range 10.8-17.2), in 4894 women, and measured the prenatal and postnatal head size of their children at 5 time points. Hypothyroxinemia was defined as normal thyroid-stimulating hormone levels and free thyroxine-4 concentrations below the 10th percentile. Statistical analysis was performed using linear generalized estimating equation. Maternal hypothyroxinemia was associated with larger fetal and infant head size (overall estimate beta: 1.38, 95% confidence interval 0.56; 2.19, P = .001). In conclusion, in the general population, even small variations in maternal thyroid function during pregnancy may affect the developing head of the young child

    Evaluating changes in functioning and psychological distress in visitors of the @ease youth mental health walk-in centres

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    Background:Highly accessible youth initiatives worldwide aim to prevent worsening of mental health problems, but research into outcomes over time is scarce. Aims:This study aimed to evaluate outcomes and support use in 12- to 15-year-old visitors of the @ease mental health walk-in centres, a Dutch initiative offering free counselling by trained and supervised peers.Method:Data of 754 visitors, collected 2018-2022, included psychological distress (Clinical Outcomes in Routine Evaluation 10 (CORE-10)), social and occupational functioning (Social and Occupational Functioning Assessment Scale (SOFAS)), school absenteeism and support use, analysed with change indicators (first to last visit), and mixed models (first three visits).Results:Among return visitors, 50.5% were female, 79.4% were in tertiary education and 36.9% were born outside of The Netherlands (one-time visitors: 64.7%, 72.9% and 41.3%, respectively). Moreover, 29.9% of return visitors presented with suicidal ideations, 97.1% had clinical psychological distress levels, and 64.1% of the latter had no support in the previous 3 months (one-time visitors: 27.2%, 90.7% and 71.1%, respectively). From visit 1 to 3, psychological distress decreased (β = -3.79, 95% CI -5.41 to -2.18; P &lt; 0.001) and social and occupational functioning improved (β = 3.93, 95% CI 0.51-7.36; P = 0.025). Over an average 3.9 visits, 39.6% improved reliably and 28.0% improved clinically significantly on the SOFAS, which was 28.4% and 8.8%, respectively, on the CORE-10, where 43.2% improved in clinical category. Counselling satisfaction was rated 4.5/5. Conclusions:Reductions in psychological distress, improvements in functioning and high counselling satisfaction were found among @ease visitors, forming a basis for future research with a control group.</p

    Cross-sectional association between metabolic parameters and psychotic-like experiences in a population-based sample of middle-aged and elderly individuals

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    Background: Metabolic alterations are often found in patients with clinical psychosis early in the course of the disorder. Psychotic-like experiences are observed in the general population, but it is unclear whether these are associated with markers of metabolism. Methods: A population-based cohort of 1890 individuals (mean age 58.0 years; 56.3% women) was included. Metabolic parameters were measured by body-mass index (BMI), concentrations of low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C), total cholesterol, triglycerides, and fasting glucose and insulin in blood. Frequency and distress ratings of psychotic-like experiences from the positive symptom dimension of the Community Assessment of Psychic Experience questionnaire were assessed. Cross-sectional associations were analysed using linear regression analyses. Results: Higher BMI was associated with higher frequency of psychotic-like experiences (adjusted mean difference: 0.04, 95% CI 0.02–0.06) and more distress (adjusted mean difference: 0.02, 95% CI 0.01–0.03). Lower LDL-C was associated with more psychotic-like experiences (adjusted mean difference: −0.23, 95% CI −0.40 to −0.06). When restricting the sample to those not using lipid-lowering medication, the results of BMI and LDL-C remained and an association between lower HDL-C and higher frequency of psychotic-like experiences was found (adjusted mean difference: −0.37, 95% CI −0.69 to −0.05). We observed no significant associations between cholesterol, triglycerides, glucose, insulin or homeostatic model assessment and psychotic-like experiences. Conclusions: In a population-based sample of middle-aged and elderly individuals, higher BMI and lower LDL-C were associated with psychotic-like experiences. This suggests that metabolic markers are associated with psychotic-like experiences across the vulnerability spectrum.</p

    Evaluating changes in functioning and psychological distress in visitors of the @ease youth mental health walk-in centres

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    Background:Highly accessible youth initiatives worldwide aim to prevent worsening of mental health problems, but research into outcomes over time is scarce. Aims:This study aimed to evaluate outcomes and support use in 12- to 15-year-old visitors of the @ease mental health walk-in centres, a Dutch initiative offering free counselling by trained and supervised peers.Method:Data of 754 visitors, collected 2018-2022, included psychological distress (Clinical Outcomes in Routine Evaluation 10 (CORE-10)), social and occupational functioning (Social and Occupational Functioning Assessment Scale (SOFAS)), school absenteeism and support use, analysed with change indicators (first to last visit), and mixed models (first three visits).Results:Among return visitors, 50.5% were female, 79.4% were in tertiary education and 36.9% were born outside of The Netherlands (one-time visitors: 64.7%, 72.9% and 41.3%, respectively). Moreover, 29.9% of return visitors presented with suicidal ideations, 97.1% had clinical psychological distress levels, and 64.1% of the latter had no support in the previous 3 months (one-time visitors: 27.2%, 90.7% and 71.1%, respectively). From visit 1 to 3, psychological distress decreased (β = -3.79, 95% CI -5.41 to -2.18; P &lt; 0.001) and social and occupational functioning improved (β = 3.93, 95% CI 0.51-7.36; P = 0.025). Over an average 3.9 visits, 39.6% improved reliably and 28.0% improved clinically significantly on the SOFAS, which was 28.4% and 8.8%, respectively, on the CORE-10, where 43.2% improved in clinical category. Counselling satisfaction was rated 4.5/5. Conclusions:Reductions in psychological distress, improvements in functioning and high counselling satisfaction were found among @ease visitors, forming a basis for future research with a control group.</p

    Determinants of maternal pregnancy one-carbon metabolism and newborn human DNA methylation profiles

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    Maternal one-carbon (1-C) metabolism provides methylgroups for fetal development and programing by DNA methylation as one of the underlying epigenetic mechanisms. We aimed to investigate maternal 1-C biomarkers, folic acid supplement use, and MTHFR C677T genotype as determinants of 1-C metabolism in early pregnancy in association with newborn DNA methylation levels of fetal growth and neurodevelopment candidate genes. The participants were 463 mother-child pairs of Dutch national origin from a large populationbased birth cohort in Rotterdam, The Netherlands. In early pregnancy (median 13.0 weeks, 90% range 10.4-17.1), we assessed the maternal folate and homocysteine blood concentrations, folic acid supplement use, and the MTHFR C677T genotype in mothers and newborns. In newborns, DNA methylation was measured in umbilical cord blood white blood cells at 11 regions of the seven genes: NR3C1, DRD4, 5-HTT, IGF2DMR, H19, KCNQ1OT1, and MTHFR. The associations between the 1-C determinants and DNA methylation were examined using linear mixed models. An association was observed between maternal folate deficiency and lower newborn DNA methylation, which attenuated after adjustment for potential confounders. The maternal MTHFR TT genotype was significantly associated with lower DNA methylation. However, maternal homocysteine and folate concentrations, folic acid supplement use, and the MTHFR genotype in the newborn were not associated with newborn DNA methylation. The maternal MTHFR C677T genotype, as a determinant of folate status and 1-C metabolism, is associated with variations in the epigenome of a selection of genes in newborns. Research on the implications of these variations in methylation on gene expression and health is recommended
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