Daily life affective dynamics as transdiagnostic predictors of mental health symptoms: An ecological momentary assessment study.

BACKGROUND: Affective dynamics have been identified as a correlate of a broad span of mental health issues, making them key candidate transdiagnostic factors. However, there remains a lack of knowledge about which aspects of affective dynamics - especially as they manifest in the course of daily life - relate to a general risk for mental health issues versus specific symptoms. METHODS: We leverage an ecological momentary assessment (EMA) study design with four measures per day over a two-week period to explore how negative affect levels, inertia, lability, and reactivity to provocation and stress in the course of daily life relate to mental health symptoms in young adults (n = 256) in the domains of anxiety, depression, psychosis-like symptoms, behaviour problems, suicidality, and substance use. RESULTS: Dynamic structural equation modelling (DSEM) suggested that negative affect levels in daily life were associated with depression, anxiety, indirect and proactive aggression, psychosis, anxiety, and self-injury; negative affective lability was associated with depression, physical aggression, reactive aggression, suicidal ideation, and ADHD symptoms; negative affective inertia was associated with depression, anxiety, physical aggression, and cannabis use; and emotional reactivity to provocation was related to physical aggression. LIMITATIONS: The cross-sectional design, the limited span of mental health issues included, and the convenience nature and small size of the sample are limitations. CONCLUSIONS: Findings suggest that a subset of mental health symptoms have shared negative affective dynamics patterns. Longitudinal research is needed to rigorously examine the directionality of the effects underlying the association between affective dynamics and mental health issues.

Examining Maternal Cardiometabolic Markers in Pregnancy on Child Emotional and Behavior Trajectories: Using Growth Curve Models on a Cohort Study.

Background: Poor maternal cardiometabolic health in pregnancy is associated with negative effects on child health outcomes, but there is limited literature on child and adolescent socioemotional outcomes. The study aimed to investigate associations between maternal cardiometabolic markers during pregnancy with child and adolescent socioemotional trajectories. Methods: Growth curve models were run to examine how maternal cardiometabolic markers in pregnancy affected child socioemotional trajectories from ages 4 to 16. Models were adjusted for all pregnancy trimesters and maternal, child, and socioeconomic covariates. This study used the Avon Longitudinal Study of Parents and Children (United Kingdom) cohort. Participants consisted of mother-child pairs (N = 15,133). Maternal predictors of fasting glucose, triglycerides, high-density lipoprotein, low-density lipoprotein, and body mass index were taken from each pregnancy trimester (T1, T2, T3). Child outcomes included emotional problems, conduct problems, and hyperactivity problems from the Strengths and Difficulties Questionnaire. Results: Fully adjusted models showed significant associations between elevated T1 fasting glucose and increased conduct problems, higher T1 body mass index and increased hyperactivity problems, lowered T1 high-density lipoprotein and decreased hyperactivity problems, and elevated T2 triglycerides and increased hyperactivity problems. Conclusions: Maternal cardiometabolic risk is associated with conduct and hyperactivity outcomes from ages 4 to 16. This study suggests that maternal markers of fasting glucose, low-density lipoprotein, high-density lipoprotein, and triglycerides during pregnancy could be added as supplements for clinical measures of risk when predicting child and adolescent socioemotional trajectories.

Maternal metabolic syndrome in pregnancy and child development at age 5: exploring mediating mechanisms using cord blood markers.

BACKGROUND: There is limited evidence on how the classification of maternal metabolic syndrome during pregnancy affects children's developmental outcomes and the possible mediators of this association. This study uses a cohort sample of 12,644 to 13,832 mother-child pairs from the UK Born in Bradford Study to examine the associations between maternal metabolic syndrome classification (MetS) and child development outcomes at age 5, using cord blood markers as candidate mediators. METHODS: Maternal cardiometabolic markers included diabetes, obesity, triglycerides, high-density lipoprotein cholesterol, blood pressure, hypertension, and fasting glucose during pregnancy. Cord blood markers of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, leptin, and adiponectin were used as child mediators. Child outcomes included two starting school variables: British Picture Vocabulary Scale (BPVS) and the Letter Identification Assessment (LID), and five developmental milestone domains from a national UK framework: (1) communication and language (COM); (2) personal, social, and emotional (PSE); (3) physical development (PHY); (4) literacy (LIT); and (5) mathematics (MAT). Mediation models were used to examine the associations between the classification of maternal metabolic syndrome and child developmental milestones. Models were adjusted for potential maternal, socioeconomic, and child confounders such as maternal education, deprivation, and gestational age. RESULTS: In mediation models, significant total effects were found for MetS associations with children's development in the LIT domain at age 5. MetS predicted individual cord blood mediators of lower HDL and increased leptin levels in both adjusted and unadjusted models. Total indirect effects (effects of all mediators combined) for MetS on a child's COM and PSE domain were significant, through all child cord blood mediators of LDL, HDL, triglycerides, adiponectin, and leptin for adjusted models. CONCLUSIONS: The results support the hypothesis that maternal metabolic syndrome classification during pregnancy is associated with some child developmental outcomes at age 5. After adjusting for maternal, child, and environmental covariates, maternal metabolic syndrome classification during pregnancy was associated with children's LIT domain through direct effects of maternal metabolic health and indirect effects of cord blood markers (total effects), and COM and PSE domains via changes only in a child's cord blood markers (total indirect effects).

Maternal infections during pregnancy and child cognitive outcomes.

BACKGROUND: Maternal prenatal infections have been linked to children's neurodevelopment and cognitive outcomes. It remains unclear, however, whether infections occurring during specific vulnerable gestational periods can affect children's cognitive outcomes. The study aimed to examine maternal infections in each trimester of pregnancy and associations with children's developmental and intelligence quotients. The ALSPAC birth cohort was used to investigate associations between maternal infections in pregnancy and child cognitive outcomes. METHODS: Infection data from mothers and cognition data from children were included with the final study sample size comprising 7,410 mother-child participants. Regression analysis was used to examine links between maternal infections occurring at each trimester of pregnancy and children's cognition at 18 months, 4 years, and 8 years. RESULTS: Infections in the third trimester were significantly associated with decreased verbal IQ at age 4 (p < .05, adjusted R2 = 0.004); decreased verbal IQ (p < .01, adjusted R2 = 0.001), performance IQ (p < .01, adjusted R2 = 0.0008), and total IQ at age 8 (p < .01, adjusted R2 = 0.001). CONCLUSION: Results suggest that maternal infections in the third trimester could have a latent effect on cognitive development, only emerging when cognitive load increases over time, though magnitude of effect appears to be small. Performance IQ may be more vulnerable to trimester-specific exposure to maternal infection as compared to verbal IQ. Future research could include examining potential mediating mechanisms on childhood cognition, such as possible moderating effects of early childhood environmental factors, and if effects persist in future cognitive outcomes.

Using network analysis to illuminate the intergenerational transmission of adversity.

Objective: The effects of maternal exposure to adverse childhood experiences (ACEs) may be transmitted to subsequent generations through various biopsychosocial mechanisms. However, studies tend to focus on exploring one or two focal pathways with less attention paid to links between different pathways. Using a network approach, this paper explores a range of core prenatal risk factors that may link maternal ACEs to infant preterm birth (PTB) and low birthweight (LBW). Methods: We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 8379) to estimate two mixed graphical network models: Model 1 was constructed using adverse infant outcomes, biopsychosocial and environmental risk factors, forms of ACEs, and sociodemographic factors. In Model 2, ACEs were combined to represent a threshold ACEs score (≥4). Network indices (i.e., shortest path and bridge expected influence [1-step & 2-step]) were estimated to determine the shortest pathway from ACEs to infant outcomes, and to identify the risk factors that are vital in activating other risk factors and adverse outcomes. Results: Network analyses estimated a mutually reinforcing web of childhood and prenatal risk factors, with each risk connected to at least two other risks. Bridge influence indices suggested that childhood physical and sexual abuse and multiple ACEs were highly interconnected to others risks. Overall, risky health behaviours during pregnancy (i.e., smoking & illicit drug use) were identified as 'active' risk factors capable of affecting (directly and indirectly) other risk factors and contributing to the persistent activation of the global risk network. These risks may be considered priority candidate targets for interventions to disrupt intergenerational risk transmission. Our study demonstrates the promise of network analysis as an approach for illuminating the intergenerational transmission of adversity in its full complexity. HIGHLIGHTS: We took a network approach to assessing links between ACEs and birth outcomes.ACEs, other prenatal risk factors, and birth outcomes had complex inter-connectionsHealth behaviours in pregnancy were indicated as optimal intervention targets.

Objetivo: Los efectos de la exposición materna a experiencias adversas en la infancia (ACEs, en sus siglas en inglés) pueden ser transmitidos a las generaciones posteriores a través de varios mecanismos biopsicosociales. Sin embargo, los estudios tienden a centrarse en la exploración de una o dos vías focales, prestando menos atención a los vínculos entre diferentes vías. Utilizando un abordaje de red, este trabajo explora una serie de factores de riesgo prenatales centrales que pueden vincular las ACEs maternas con el nacimiento prematuro (PTB, en sus siglas en inglés) y el bajo peso al nacer (LBW, en sus siglas en inglés) de los bebés.Métodos: Se utilizaron datos del Estudio Longitudinal de Padres e Hijos de Avon (ALSPAC) (n = 8.379) para estimar dos modelos de red gráfica mixta: El modelo 1 se construyó utilizando los resultados adversos del lactante, los factores de riesgo biopsicosociales y ambientales, las formas de las ACE y los factores sociodemográficos. En el modelo 2, las ACEs se combinaron para representar una puntuación de ACEs umbral (≥ 4). Se estimaron los índices de red (es decir, el camino más corto y la influencia esperada del puente [1 y 2 pasos]) para determinar el camino más corto desde las ACEs hasta los resultados infantiles, y para identificar los factores de riesgo que son vitales para activar otros factores de riesgo y resultados adversos.Resultados: Los análisis de redes estimaron una red de factores de riesgo prenatales y de la infancia que se refuerzan mutuamente, y cada riesgo está conectado con al menos otros dos riesgos. Los índices de influencia de los puentes sugirieron que el abuso físico y sexual en la infancia y los múltiples ACEs estaban altamente interconectados con otros riesgos. En general, las conductas de riesgo para la salud durante el embarazo (es decir, el tabaquismo y el consumo de drogas ilícitas) se identificaron como factores de riesgo "activos" capaces de afectar (directa e indirectamente) a otros factores de riesgo y de contribuir a la activación persistente de la red de riesgo global. Estos riesgos pueden considerarse objetivos candidatos prioritarios para las intervenciones destinadas a interrumpir la transmisión intergeneracional del riesgo. Nuestro estudio demuestra la promesa del análisis de redes como abordaje para iluminar la transmisión intergeneracional de la adversidad en toda su complejidad.

Clinical Outcomes After Ventriculo-Peritoneal Shunting in Patients With Classic vs. Complex NPH.

Objective: Normal pressure hydrocephalus (NPH) is a neurological condition characterized by a clinical triad of gait disturbance, cognitive impairment, and urinary incontinence in conjunction with ventriculomegaly. Other neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and vascular dementia share some overlapping clinical features. However, there is evidence that patients with comorbid NPH and Alzheimer's or Parkinson's disease may still exhibit good clinical response after CSF diversion. This study aims to evaluate clinical responses after ventriculo-peritoneal shunt (VPS) in a cohort of patients with coexisting NPH and neurodegenerative disease. Methods: The study has two components; (i) a pilot study was performed that specifically focused upon patients with Complex NPH and following the inclusion of the Complex NPH subtype into consideration for the clinical NPH programme, (ii) a retrospective snapshot study was performed to confirm and characterize differences between Classic and Complex NPH patients being seen consecutively over the course of 1 year within a working subspecialist NPH clinic. We studied the characteristics of patients with Complex NPH, utilizing clinical risk stratification and multimodal biomarkers. Results: There was no significant difference between responders and non-responders to CSF diversion on comorbidity scales. After VPS insertion, significantly more Classic NPH patients had improved cognition compared to Complex NPH patients (p = 0.005). Improvement in gait and urinary symptoms did not differ between the groups. 26% of the Classic NPH group showed global improvement of the triad, and 42% improved in two domains. Although only 8% showed global improvement of the triad, all Complex NPH patients improved in gait. Conclusions: Our study has demonstrated that the presence of neurodegenerative disorders co-existing with NPH should not be the sole barrier to the consideration of high-volume tap test or lumbar drainage via a specialist NPH programme. Further characterization of distinct cohorts of NPH with differing degrees of CSF responsiveness due to overlay from neurodegenerative or comorbidity risk burden may aid toward more precise prognostication and treatment strategies. We propose a simplistic conceptual framework to describe NPH by its Classic vs. Complex subtypes to promote the clinical paradigm shift toward subspecialist geriatric neurosurgery by addressing needs for rapid screening tools at the clinical-research interface.

Analgesic drug use in pregnancy and neurodevelopment outcomes: an umbrella review.

Emerging evidence from reviews suggests that analgesic drug exposure during pregnancy may contribute to child neurodevelopment outcomes. A comprehensive overview of existing evidence is needed for firm conclusions to inform clinical guidelines. This umbrella review aims to synthesise high-quality evidence on prenatal analgesic drug exposure and risk of ASD and ADHD in children. Seven databases were searched from inception to May 2021 to identify relevant reviews of any design. The AMSTAR 2 and the GRADE quality assessments were used to evaluate risk of bias and heterogeneity. A narrative synthesis approach was used to summarise findings. Five systematic reviews and meta-analyses met the inclusion criteria. All reviews reported significant associations between maternal prenatal acetaminophen use and ADHD outcomes (risk ratio range: 1.08-1.34; no pooled incidence rate), with a potential dose-dependent relationship. Potential sources of heterogeneity included usage timing and dosage. Findings suggest minimisation of prenatal acetaminophen exposure due to risk for ADHD outcomes. Future studies should include assessing potentially interacting mechanisms associating acetaminophen use with future neurodevelopmental outcomes.

The Impact of Multimorbidity Burden, Frailty Risk Scoring, and 3-Directional Morphological Indices vs. Testing for CSF Responsiveness in Normal Pressure Hydrocephalus.

Objective: Multimorbidity burden across disease cohorts and variations in clinico-radiographic presentations within normal pressure hydrocephalus (NPH) confound its diagnosis, and the assessment of its amenability to interventions. We hypothesized that novel imaging techniques such as 3-directional linear morphological indices could help in distinguishing between hydrocephalus vs. non-hydrocephalus and correlate with responsiveness to external lumbar drainage (CSF responsiveness) within NPH subtypes. Methodology: Twenty-one participants with NPH were recruited and age-matched to 21 patients with Alzheimer's Disease (AD) and 21 healthy controls (HC) selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Patients with NPH underwent testing via the NPH programme with external lumbar drainage (ELD); pre- and post-ELD MRI scans were obtained. The modified Frailty Index (mFI-11) was used to stratify the NPH cohort, including Classic and Complex subtypes, by their comorbidity and frailty risks. The quantitative imaging network tool 3D Slicer was used to derive traditional 2-dimensional (2d) linear measures; Evans Index (EI), Bicaudate Index (BCI) and Callosal Angle (CA), along with novel 3-directional (3d) linear measures; z-Evans Index and Brain per Ventricle Ratio (BVR). 3-Dimensional (3D) ventricular volumetry was performed as an independent correlate of ventriculomegaly to CSF responsiveness. Results: Mean age for study participants was 71.14 ± 6.3 years (18, 85.7% males). The majority (15/21, 71.4%) of participants with NPH comprised the Complex subtype (overlay from vascular risk burden and AD); 12/21 (57.1%) were Non-Responders to ELD. Frailty alone was insufficient in distinguishing between NPH subtypes. By contrast, 3d linear measures distinguished NPH from both AD and HC cohorts, but also correlated to CSF responsiveness. The z-Evans Index was the most sensitive volumetric measure of CSF responsiveness (p = 0.012). Changes in 3d morphological indices across timepoints distinguished between Responders vs. Non-Responders to lumbar testing. There was a significant reduction of indices, only in Non-Responders and across multiple measures (z-Evans Index; p = 0.001, BVR at PC; p = 0.024). This was due to a significant decrease in ventricular measurement (p = 0.005) that correlated to independent 3D volumetry (p = 0.008). Conclusion. In the context of multimorbidity burden, frailty risks and overlay from neurodegenerative disease, 3d morphological indices demonstrated utility in distinguishing hydrocephalus vs. non-hydrocephalus and degree of CSF responsiveness. Further work may support the characterization of patients with Complex NPH who would best benefit from the risks of interventions.

The association between analgesic drug use in pregnancy and neurodevelopmental disorders: protocol for an umbrella review.

BACKGROUND: Maternal prenatal health has been shown to be an important influence on children's developmental outcomes, which has led to an increased emphasis on providing more information to support clinical decisions in pregnancy. Several systematic reviews suggest that analgesic drug use during pregnancy may have neurodisruptive properties. However, no firm conclusions have yet been drawn on the associations between prenatal analgesic drug use and children's long-term development of neurodevelopmental disorders such as autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD). Therefore, an umbrella review is proposed for the purpose of examining the associations between maternal analgesic drug use during pregnancy and diagnoses of neurodevelopmental disorders. METHODS: Included systematic reviews will consist of studies examining the effect of maternal prenatal analgesic drug use, specifically ibuprofen, acetaminophen, aspirin, naproxen, diclofenac, and ketoprofen, on children's neurodevelopmental disorder status. Examined drugs were restricted to those readily accessible and frequently used by pregnant women, and with characteristics that allow them to cross the placenta and directly affect fetal development. Outcomes will be restricted to formal clinical diagnoses of ASD and/or ADHD. Two reviewers will independently identify eligible reviews from six databases (e.g., PubMed, EMBASE, PsychINFO) from inception dates of databases to the date of data extraction, and conduct manual searches of reference lists, consultation with field experts, and scan of pre-print archives. Extracted data will also include short qualitative summaries by both reviewers. As part of quality assessment, a standardized measurement tool to assess systematic reviews (AMSTAR 2) will be used. A narrative synthesis is proposed to integrate findings from different, potentially methodologically heterogeneous, studies. DISCUSSION: This umbrella review of associations between maternal prenatal use of analgesic drugs and children's neurodevelopmental disorders could allow for firmer conclusions to be drawn through the synthesis of all relevant published research. The synthesis of findings using high-quality evidence could provide more accurate healthcare information on the long-term effects of analgesic drugs on neurodevelopment, to better guide future clinical decisions during pregnancy. This review will also allow gaps and methodological differences in the literature to be identified, informing recommendations for future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020179216 .

DTI Profiles for Rapid Description of Cohorts at the Clinical-Research Interface.

Normal pressure hydrocephalus (NPH) is a syndrome comprising gait disturbance, cognitive decline and urinary incontinence that is an unique model of reversible brain injury, but it presents as a challenging spectrum of disease cohorts. Diffusion Tensor Imaging (DTI), with its ability to interrogate structural white matter patterns at a microarchitectural level, is a potentially useful tool for the confirmation and characterization of disease cohorts at the clinical-research interface. However, obstacles to its widespread use involve the need for consistent DTI analysis and interpretation tools across collaborator sites. We present the use of DTI profiles, a simplistic methodology to interpret white matter injury patterns based on the morphology of diffusivity parameters. We examined 13 patients with complex NPH, i.e., patients with NPH and overlay from multiple comorbidities, including vascular risk burden and neurodegenerative disease, undergoing extended CSF drainage, clinical assessments, and multi-modal MR imaging. Following appropriate exclusions, we compared the morphology of DTI profiles in such complex NPH patients (n = 12, comprising 4 responders and 8 non-responders) to exemplar DTI profiles from a cohort of classic NPH patients (n = 16) demonstrating responsiveness of white matter injury to ventriculo-peritoneal shunting. In the cohort of complex NPH patients, mean age was 71.3 ± 7.6 years (10 males, 2 females) with a mean MMSE score of 21.1. There were 5 age-matched healthy controls, mean age was 73.4 ± 7.2 years (1 male, 4 females) and mean MMSE score was 26.8. In the exemplar cohort of classic NPH patients, mean age was 74.7 ± 5.9 years (10 males, 6 females) and mean MMSE score was 24.1. There were 9 age-matched healthy controls, mean age was 69.4 ± 9.7 years (4 males, 5 females) and mean MMSE score was 28.6. We found that, despite the challenges of acquiring DTI metrics from differing scanners across collaborator sites and NPH patients presenting as differing cohorts along the spectrum of disease, DTI profiles for responsiveness to interventions were comparable. Distinct DTI characteristics were demonstrated for complex NPH responders vs. non-responders. The morphology of DTI profiles for complex NPH responders mimicked DTI patterns found in predominantly shunt-responsive patients undergoing intervention for classic NPH. However, DTI profiles for complex NPH non-responders was suggestive of atrophy. Our findings suggest that it is possible to use DTI profiles to provide a methodology for rapid description of differing cohorts of disease at the clinical-research interface. By describing DTI measures morphologically, it was possible to consistently compare white matter injury patterns across international collaborator datasets.

The Utility of Developmental Checklists in Parent-held Health Records in Singapore.

OBJECTIVE: The aim of this study was to investigate parents' perceptions of developmental checklists and the child development monitoring schedule in the Singapore health booklet. METHOD: Parents of children aged 2 years 6 months to 3 years 11 months with or without developmental concerns (n = 450) completed a structured interview, and their child's health booklets were reviewed. RESULTS: Most parents reported reading and using the developmental checklists. However, only about half of them attempted the checklists with minimal help from professionals. Approximately 7 in 10 parents of children with developmental concerns found the checklists useful for identifying concerns about their child. Despite positive feedback from parents about the checklists, only about 1 in 4 parents brought their child for a 2 to 3 years developmental monitoring visit at the time of the survey, and the completion rates of the checklists were less than desirable. CONCLUSIONS: Further revisions to the checklists can include simplifying the words and sentences and providing relevant pictures to aid understanding. If the checklists are to be used for screening, standardization of how the checklists are to be completed and how children at risk of developmental delays can be identified on the checklists need to be provided. Parents' awareness of the importance of evaluating their child's development at 9 months, 18 months, and particularly at 2.5 years, needs to be raised. Developmental screening for children at these critical ages can be made mandatory. An electronic version of the health booklet is likely to facilitate implementation of developmental screening in the health care system.