Comparative physiological effects of antipsychotic drugs in children and young people: a network meta-analysis.

BACKGROUND: The degree of physiological responses to individual antipsychotic drugs is unclear in children and adolescents. With network meta-analysis, we aimed to investigate the effects of various antipsychotic medications on physiological variables in children and adolescents with neuropsychiatric and neurodevelopmental conditions. METHODS: For this network meta-analysis, we searched Medline, EMBASE, PsycINFO, Web of Science, and Scopus from database inception until Dec 22, 2023, and included randomised controlled trials comparing antipsychotics with placebo in children or adolescents younger than 18 years with any neuropsychiatric and neurodevelopmental condition. Primary outcomes were mean change from baseline to end of acute treatment in bodyweight, BMI, fasting glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, prolactin, heart rate, systolic blood pressure (SBP), and QT interval corrected for heart rate (QTc) for patients receiving either active treatment or placebo. For multigroup trials reporting several doses, we calculated a summary value for each physiological variable for all doses. After transitivity assessment, we fitted frequentist random-effects network meta-analyses for all comparisons in the network. A Kilim plot was used to summarise the results for all treatments and outcomes, providing information regarding the strength of the statistical evidence of treatment effects, using p values. Network heterogeneity was assessed with τ, risk of bias of individual trials was assessed with the Cochrane Collaboration's Tool for Assessing Risk of Bias, and the credibility of findings from each network meta-analysis was assessed with the Confidence in Network Meta-Analysis (CINEMA) app. This study is registered on PROSPERO (CRD42021274393). FINDINGS: Of 6676 studies screened, 47 randomised controlled trials were included, which included 6500 children (mean age 13·29 years, SD 2·14) who received treatment for a median of 7 weeks (IQR 6-8) with either placebo (n=2134) or one of aripiprazole, asenapine, blonanserin, clozapine, haloperidol, lurasidone, molindone, olanzapine, paliperidone, pimozide, quetiapine, risperidone, or ziprasidone (n=4366). Mean differences for bodyweight change gain compared with placebo ranged from -2·00 kg (95% CI -3·61 to -0·39) with molindone to 5·60 kg (0·27 to 10·94) with haloperidol; BMI -0·70 kg/m2 (-1·21 to -0·19) with molindone to 2·03 kg/m2 (0·51 to 3·55) with quetiapine; total cholesterol -0·04 mmol/L (-0·39 to 0·31) with blonanserin to 0·35 mmol/L (0·17 to 0·53) with quetiapine; LDL cholesterol -0·12 mmol/L (-0·31 to 0·07) with risperidone or paliperidone to 0·17 mmol/L (-0·06 to 0·40) with olanzapine; HDL cholesterol 0·05 mmol/L (-0·19 to 0·30) with quetiapine to 0·48 mmol/L (0·18 to 0·78) with risperidone or paliperidone; triglycerides -0·03 mmol/L (-0·12 to 0·06) with lurasidone to 0·29 mmol/L (0·14 to 0·44) with olanzapine; fasting glucose from -0·09 mmol/L (-1·45 to 1·28) with blonanserin to 0·74 mmol/L (0·04 to 1·43) with quetiapine; prolactin from -2·83 ng/mL (-8·42 to 2·75) with aripiprazole to 26·40 ng/mL (21·13 to 31·67) with risperidone or paliperidone; heart rate from -0·20 bpm (-8·11 to 7·71) with ziprasidone to 12·42 bpm (3·83 to 21·01) with quetiapine; SBP from -3·40 mm Hg (-6·25 to -0·55) with ziprasidone to 10·04 mm Hg (5·56 to 14·51) with quetiapine; QTc from -0·61 ms (-1·47 to 0·26) with pimozide to 0·30 ms (-0·05 to 0·65) with ziprasidone. INTERPRETATION: Children and adolescents show varied but clinically significant physiological responses to individual antipsychotic drugs. Treatment guidelines for children and adolescents with a range of neuropsychiatric and neurodevelopmental conditions should be updated to reflect each antipsychotic drug's distinct profile for associated metabolic changes, alterations in prolactin, and haemodynamic alterations. FUNDING: UK Academy of Medical Sciences, Brain and Behaviour Research Foundation, UK National Institute of Health Research, Maudsley Charity, the Wellcome Trust, Medical Research Council, National Institute of Health and Care Research Biomedical Centre at King's College London and South London and Maudsley NHS Foundation Trust, the Italian Ministry of University and Research, the Italian National Recovery and Resilience Plan, and Swiss National Science Foundation.

Effect of maternal eating disorders on mother-infant quality of interaction, bonding and child temperament: A longitudinal study.

AIMS: This study aims to investigate the effect of maternal eating disorders (ED) on mother-infant quality of interaction at 8 weeks and bonding and child temperament at 1 and 2 years postnatally. We also aimed to explore the relationship between maternal ED psychopathology, comorbid psychiatric difficulties, and both mother-infant quality of interaction and bonding in women with ED. Women were recruited to a prospective longitudinal study. By the time of giving birth, the sample consisted of 101 women of the initial 137 (73.7%). Overall, 62 women (ED = 36; HC = 26) participated in the 8-week assessment, 42 (ED = 20; HC = 22) at 1 year, and 78 (ED = 34; HC = 44) at 2 years. Mann-Whitney U Test was used to explore association between maternal ED and mother-infant quality of interaction and between maternal ED and bonding. Spearman correlations were used to explore associations between maternal ED psychopathology, comorbid psychiatric difficulties, and both mother-infant quality of interaction and bonding. RESULTS: We found no differences between early mother-infant interaction and bonding in mothers with ED in comparison to HC. High levels of maternal ED psychopathology were correlated with high anxiety levels, higher negative affectivity, and lower extraversion in children of ED mothers both at 1 and 2 years. Furthermore, high levels of ED psychopathology were also associated with lower effortful control at 1 year. CONCLUSIONS: Findings imply that maternal ED have an impact on child temperament. Future research should focus on resilience and on which protective factors might lead to positive outcomes. These factors can be then used as therapeutic and preventative targets.

Eating disorders, pregnancy and the postnatal period: a review of the recent literature.

PURPOSE OF REVIEW: Eating disorders (ED) are severe psychiatric disorders that affect women in reproductive age. The purpose of this review is to provide an up-to-date overview of the impact of maternal ED on pregnancy and the postnatal period. The clinical implications for identification and management of maternal ED are also discussed. RECENT FINDINGS: In the last 2 years, 15 articles focused on the impact of maternal ED in pregnancy and postpartum. Findings from this review indicate that around 15% of pregnant women are likely to have had an ED at some point in their lifetime, and about 5% have an ED in pregnancy. Although ED symptoms tend to decrease during pregnancy, remission is often only temporary with symptoms typically resurfacing in the postnatal period. Women with ED are prone to psychiatric comorbidities such as depression and anxiety during the perinatal period, with up to a third of women with ED reporting postnatal depression in clinical studies and prevalence ranging between 40% and 66% in general population samples. Furthermore, recent findings continue to highlight that current and prior history of maternal ED are associated with a heightened risk of adverse pregnancy and birth outcomes, most notably preterm birth and adverse birth weight outcomes. SUMMARY: These findings continue to emphasise the clinical importance of early identification and response to maternal ED to mitigate potentially adverse maternal and infant outcomes.

Eating disorders mothers and their children: a systematic review of the literature.

To provide an overview of the impact of maternal eating disorders (ED) on child development in a number of domains including feeding and eating behaviour, neuropsychological profile and cognitive development, psychopathology and temperament. PubMed, Embase and PsychInfo were searched for studies exploring the impact of maternal ED on children between January 1980 and September 2018. Initial search yielded 569 studies. After exclusion, 32 studies were reviewed. Overall, available evidence shows that children of mothers with ED are at increased risk of disturbances in several domains. They exhibit more difficulties in feeding and eating behaviours, display more psychopathological and socio-emotional difficulties, and they are more likely to be described as having a difficult temperament. Maternal ED have an impact on child psychological, cognitive and eating behaviours, and might affect the development of ED in the offspring. Future research should focus on resilience and on which protective factors might lead to positive outcomes. These factors can be then used as therapeutic and preventative targets.

Infant feeding behaviours and attitudes to feeding amongst mothers with eating disorders: A longitudinal study.

This study aims to investigate breastfeeding, infant feeding behaviours, and attitudes to feeding amongst women with eating disorders (ED) and healthy controls (HC). Women with active ED (C-ED; N = 25), past ED (P-ED; N = 28), and HC (N = 46) were recruited in pregnancy and followed up longitudinally. Post-natally infant feeding behaviour was investigated at 8 weeks, 6 months, and 1 year and parental modelling at 1 and 2 years. Women with P-ED and C-ED reported higher concerns about their infant being/becoming overweight compared with HC, respectively, at 8 weeks and 6 months and 6 months only post-partum. Women with P-ED showed less awareness of infant hunger and satiety cues compared with HC at 8 weeks. Despite few differences between ED and HC, both P-ED and C-ED predicted maternal attitudes and worries about child's eating. These are likely to impact on child's growth and later eating behaviours and might impact on the intergenerational transmission of ED.

Associations between eating disorder diagnoses, behaviors, and menstrual dysfunction in a clinical sample.

We explored associations between lifetime eating disorder (ED) diagnoses and behaviors and menstrual dysfunction using logistic regression models. Body mass index (BMI) fully explained differences in the odds of secondary amenorrhea (SA) across diagnoses. Women with dieting behaviors had borderline significantly higher odds of SA than those without after accounting for BMI. We suggest the presence of a strong association between BMI and SA and that dieting might represent a risk factor for SA regardless of BMI and ED diagnosis.

Elevation of Plasma 2-Arachidonoylglycerol Levels in Alzheimer's Disease Patients as a Potential Protective Mechanism against Neurodegenerative Decline.

BACKGROUND: Growing evidence suggests that the endocannabinoid system is involved in the pathogenesis of Alzheimer's disease (AD) and atherosclerosis. OBJECTIVE: The purpose of this study was to investigate the activation of the endocannabinoid system in AD in vivo and the possible intermediate role of atherosclerosis. METHODS: We enrolled 41 patients with probable AD, and 30 age- and gender-matched controls. All subjects underwent: ultrasound examination of cerebral and neck vessels (including intima-media thickness and plaque stenosis evaluation); blood sampling to measure levels of endocannabinoid [anandamide (AEA), 2-arachidonoylglycerol (2-AG)] and endogenous AEA analogues [N-palmitoyl-ethanolamide (PEA); N-oleoyl-ethanolamide]; neuropsychological evaluation and brain MRI (atrophy, white matter hyperintensity volume). RESULTS: 2-AG levels were higher in AD patients compared to controls (Mann-Whitney test p = 0.021). In the AD group, 2-AG correlated to white matter hyperintensity volume (r = 0.415, p = 0.015) and was higher in patients with chronic heart ischemic disease (p = 0.023). In AD patients, 2-AG was also positively related to memory (r = 0.334, p = 0.05) and attention (r = 0.423, p = 0.018) performances. Constructional praxia test scores were lower in patients with higher levels of PEA (r =-0.389, p = 0.019). CONCLUSION: AD patients present high plasma 2-AG levels, also in relation to heart ischemic disease and cerebral leukoaraiosis. This may be a protective mechanism hindering neurodegeneration, but it may also play an ambivalent role on cerebrovascular circulation. The increase in 2-AG and PEA levels observed with ongoing pathological processes may differently modulate cognitive performances.

The safety of serotonin-noradrenaline reuptake inhibitors (SNRIs) in pregnancy and breastfeeding: a comprehensive review.

OBJECTIVE: The present study provides a comprehensive review of the existing literature on the safety of serotonin-noradrenaline reuptake inhibitors (SNRIs) in pregnancy and lactation. METHODS: Studies published in English, reporting the use of SNRIs in pregnant and/or breastfeeding women, were identified by searching MEDLINE/Pubmed, PsycINFO, and EMBASE. RESULTS: Twenty-nine studies were included in the review. Altogether, the initial evidence coming from the reviewed studies suggests a lack of association between SNRIs and an increased risk of major congenital malformations. Conversely, exposure to SNRIs seems to be significantly associated with an increased risk of some perinatal complications. No neonatal adverse events emerged, so far, in the few studies concerning the safety of SNRIs during breastfeeding. CONCLUSIONS: Available data suggest that venlafaxine is relatively safe during pregnancy, in particular as far as major malformations are concerned, whereas considering the small number of studies published, no definitive conclusions can be drawn on its safety during breastfeeding. Because of the few studies so far published, the safety of duloxetine during pregnancy and breastfeeding remains to be well established.