Mitigation of a prospective association between early language delay at toddlerhood and ADHD among bilingual preschoolers: Evidence from the GUSTO Cohort

National Research Foundation (NRF) Singapore under its Translational and Clinical Research (TCR) Flagship Programm

Do symptoms of anxiety and/or depression and pain intensity before primary Total knee arthroplasty influence reason for revision? Results of an observational study from the Dutch arthroplasty register in 56,233 patients

Objective: Anxiety, depression and greater pain intensity before total knee arthroplasty (TKA) may increase the probability of revision surgery for remaining symptoms even without clear pathology or technical issues. We aimed to assess whether preoperative anxiety/depression and pain intensity are associated with revision TKA for less clear indications. Methods: Less clear indications for revision were defined after a Delphi process in which consensus was reached among 59 orthopaedic knee experts. We performed a cox regression analyses on primary TKA patients registered in the Dutch Arthroplasty Registry (LROI) who completed the EuroQol 5D 3 L (EQ5D-3 L) anxiety/depression score to examine associations between preoperative anxiety/depression and pain (Numeric Rating Scale (NRS)) with TKA revision for less clear reasons. These analyses were adjusted for age, BMI, sex, smoking, ASA score, EQ5D-3 L thermometer and OKS score. Results: In total, 25.9% patients of the 56,233 included patients reported moderate or severe symptoms of anxiety/depression on the EQ5D-3 L anxiety/depression score. Of those, 615 revisions (45.5%) were performed for less clear reasons for revision (patellar pain, malalignment, instability, progression of osteoarthritis or arthrofibrosis). Not EQ5D-3 L anxiety/depression score, but higher NRS pain at rest and EQ5D-3 L pain score were associated with revision for less clear reason (HR: 1.058, 95% CI 1.019-1.099 & HR: 1.241, 95% CI 1.044-1.476, respectively). Conclusion: Our findings suggest that pain intensity is a risk factor for TKA revision for a less clear reason. The finding that preoperative pain intensity was associated with reason for revision confirms a likely influence of subjective, personal factors on offer and acceptance of TKA revision. The association between anxiety/depression and reason for revision after TKA may also be found when including more specific outcome measures to assess anxiety/depression and we therefore hope to encourage further research on this topic with our study, ideally in a prospective setting. Study design: Longitudinal Cohort Study Level III, Delphi Consensu

Oral contraceptives, depressive and insomnia symptoms in adult women with and without depression

Background: Worldwide, oral contraceptive (OC) use is a very common form of birth control, although it has been associated with symptoms of depression and insomnia. Insomnia is a risk factor for major depressive disorder (MDD) but may also be a symptom of the disorder. Despite the large number of women who use OC, it is yet unknown whether women with previous or current diagnosis of depression are more likely to experience more severe depressive and insomnia symptoms during concurrent OC use than women without diagnosis of depression. Aim: This study examined associations between OC use and concurrent symptoms of depression (including atypical depression) and insomnia as well as between OC and prevalences of concurrent dysthymia and MDD. Participants were adult women with and without a history of MDD or dysthymia. We hypothesized that OC use is associated with concurrent increased severity of depressive symptoms and insomnia symptoms, as well as with an increased prevalence of concurrent diagnoses of dysthymia and MDD. We also hypothesized that a history of MDD or dysthymia moderates the relationship between OC use and depressive and insomnia symptoms. Methods: Measurements from premenopausal adult women from the Netherlands Study of Depression and Anxiety (NESDA) were grouped, based on whether participants were using OC or naturally cycling (NC). OC use, timing and regularity of the menstrual cycle were assessed with a structured interview, self-reported symptoms of depression (including atypical depression), insomnia with validated questionnaires, and MDD and dysthymia with structured diagnostic interviews. Results: We included a total of 1301 measurements in women who reported OC use and 1913 measurements in NC women (mean age 35.6, 49.8% and 28.9% of measurements in women with a previous depression or current depression, respectively). Linear mixed models showed that overall, OC use was neither associated with more severe depressive symptoms (including atypical depressive symptoms), nor with higher prevalence of diagnoses of MDD or dysthymia. However, by disentangling the amalgamated overall effect, within-person estimates indicated increased depressive symptoms and depressive disorder prevalence during OC use, whereas between-person estimated indicated lower depressive symptoms and prevalence of depressive disorders. OC use was consistently associated with more severe concurrent insomnia symptoms, in the overall estimates as well as in the within-person and between-person estimates. Presence of current or previous MDD or dysthymia did not mod-erate the associations between OC use and depressive or insomnia symptoms. Discussion: The study findings showed consistent associations between OC use and more severe insomnia symptoms, but no consistent associations between OC and depressive symptoms or diagnoses. Instead, post-hoc analyses showed that associations between OC and depression differed between within-and between person -estimates. This indicates that, although OC shows no associations on the overall level, some individuals might experience OC-associated mood symptoms. Our findings underscore the importance of accounting for individual differences in experiences during OC use. Furthermore, it raises new questions about mechanisms underlying associations between OC, depression and insomnia.Stress-related psychiatric disorders across the life spa

Prenatal maternal depression alters amygdala functional connectivity in 6-month-old infants

10.1038/tp.2015.3Translational Psychiatry52GUSTO (Growing up towards Healthy Outcomes

Associations Between Eczema and Attention Deficit Hyperactivity Disorder Symptoms in Children

Background: Epidemiological studies suggest a link between eczema and attention deficit hyperactivity disorder (ADHD), but underlying mechanisms have not been examined.Objective: We aim to investigate the association between eczema and subsequent ADHD symptoms in the Growing Up in Singapore Towards healthy Outcomes cohort and explore the role of pro-inflammatory cytokines and gut microbiome.Methods: The modified International Study of Asthma and Allergies in Childhood questionnaire and Computerized Diagnostic Interview Schedule for Children Version IV were administered to assess reported eczema within the first 18 months and presence of ADHD symptoms at 54 months, respectively. Skin prick testing at 18 months, cytokines in maternal blood during pregnancy and cord blood and the mediating role of the gut microbiome at 24 months were assessed.Results: After adjusting for confounders, eczema with or without a positive skin prick test was associated with doubling the risk of ADHD symptoms. No differences in maternal and cord blood cytokines were observed in children with and without eczema, or children with and without ADHD. Gut microbiome dysbiosis was observed in children with eczema and children with ADHD. Children with eczema also had lower gut bacterial Shannon diversity. However, the relationship between eczema and ADHD was not mediated by gut microbiome.Conclusion: Early life eczema diagnosis is associated with a higher risk of subsequent ADHD symptoms in children. We found no evidence for underlying inflammatory mechanism or mediation by gut microbiome dysbiosis. Further research should evaluate other mechanisms underlying the link between eczema and ADHD.Peer reviewe

Pre-Readers at the Alien Zoo: A Preregistered Study of the Predictors of Dyslexia and Linguistic Sound Symbolism in 6-year-olds

Recent studies suggest that multisensory linkages between speech and vision are implicated in the development of dyslexia. Current data only address a relationship in adults with existing diagnoses, but do not inform us about the developmental trajectory of the association. We conducted a pre-registered study of multisensory matching in 388 prereaders in Singapore (Age: 5y 10m) using an adaptation of the bouba-kiki task (the Alien Zoo), and compared children's performance on this task to their earlier scores on measures known to predict dyslexia: phonological awareness, vocabulary size and letter knowledge. As reported elsewhere, children's Alien Zoo scores were lower than adults'(Woon & Styles, 2017a). The language measures were strongly inter-correlated, suggesting persistent language skills across multiple domains, However we found no significant relationship between performance on the Alien Zoo task and any of the predictors of dyslexia. This may mean that the relationship is yet to emerge in this population. The children in this cohort will be tracked and tested at a later time point to establish the developmental trajectory of this relationship

The Effect of Older Sibling, Postnatal Maternal Stress, and Household Factors on Language Development in Two to Four-Year-Old Children

Previous literature has shown that family structure affects language development. Here, factors relating to older siblings (their presence in the house, sex, and age gap), mothers (maternal stress), and household size and residential crowding were assessed to systematically examine the different roles of these factors. Data from mother–child dyads in a Singaporean birth cohort, (677–855 dyads; 52% males; 58% to 61% Chinese, 20% to 24% Malay, 17% to 19% Indian) collected when children were 24, 48, and 54 months old, were analyzed. There was a negative effect of having an older sibling, moderated by the siblings’ age gap, but not by the older sibling’s sex, nor household size or residential crowding. Maternal stress affected language outcomes in some analyses but not others. Implications for understanding the possible effects of family structure on language development are discusse

Maternal Parenting Stress, Child Exuberance, and Preschoolers' Behavior Problems

This study investigated whether child exuberance, an aspect of temperament related to emotion regulation, moderates the well-documented association between high parenting stress and increased risk for internalizing and externalizing problems during the preschool years. At 42 months of age child exuberance was observed in 256 children (47% girls) and maternal self-reports on parenting stress were obtained. At 48 months internalizing and externalizing problems were assessed through reports from both parents. Indeed, higher maternal parenting stress increased the risk for internalizing problems, and this association was more pronounced among children with high levels of exuberance. Existent emotion regulation difficulties in highly exuberant children may further heighten the risk conveyed by an unfavorable caregiving environment for developing internalizing problems

Birth weight and catch up growth are associated with childhood impulsivity in two independent cohorts

Individuals born after intrauterine growth restriction (IUGR) are more impulsive towards palatable foods, but it is not clear 1) if IUGR-related impulsivity is specific for foods and solely based on response inhibition and 2) if the development of impulsivity is due to being born IUGR per se or to growing up fast in the first few years of life (catch up growth). Children were classified in the IUGR group if the birth weight ratio was below 0.85. Delta z score for BMI was used as a measure of catch up growth. In MAVAN (N = 274), impulsivity was measured by the Information Sampling Task from the Cambridge Neuropsychological Test Automated Battery (IST - CANTAB), and in GUSTO using the Sticker Delay Task (N = 327). There is a significant effect of interaction between being born IUGR and the magnitude of catch up growth on the reflection impulsivity from IST-CANTAB at 60 months, in which greater catch up growth associates with greater impulsivity in the IST fixed condition in IUGR children. The finding was reproduced in children from the GUSTO cohort using the Sticker Delay Task. We confirmed that catch up growth interacts with IUGR, having a major role in the development of impulsivity in the first years of life and influencing inhibitory control and decision making processes

Functional and structural networks of lateral and medial orbitofrontal cortex as potential neural pathways for depression in childhood

Background: Converging evidence suggests that the lateral and medial orbitofrontal cortices (lOFC and mOFC) may contribute distinct neural mechanisms in depression. This study investigated the relations of their functional and structural organizations with postnatal maternal depressive symptoms in young children. Methods: Resting-state functional magnetic resonance imaging and structural magnetic resonance imaging were acquired in children at age 4 (n = 199) and 6 years (n = 234). Child's withdrawal behavior problems were assessed using Child's Behavior Checklist. Results: In 4-year-old girls, postnatal maternal depressive symptoms were positively associated with the lOFC functional connectivity with the visual network but negatively with the cognitive control network. The lOFC functional connectivity with the visual network and cerebellum, which was influenced by postnatal maternal depressive symptoms, was also associated with child's withdrawal behavior problems in 6-year-old girls. Moreover, postnatal maternal depressive symptoms were also negatively associated with the mOFC functional connectivity with the cognitive control and motor networks in 4-year-old girls. Furthermore, postnatal maternal depressive symptoms influenced the structural connectivity of left mOFC with the right middle frontal cortex and left inferior temporal cortex in 4-year-old girls. Unlike girls, boys showed that postnatal maternal depressive symptoms selectively impacted the mOFC functional connectivity with the memory system at age 6 years. Conclusion: Our study provided novel evidence on the distinct neural mechanisms of the lOFC and mOFC structural and functional organizations for intergenerational transmission of maternal depression to the offspring. Boys and girls may potentially employ different neural mechanisms to adapt to maternal environment at different timings of early life