Search

Elaine KH Tham,1 Nora Schneider,2 Birit FP Broekman1 1Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore; 2Nestec Ltd., Nestlé Research Center, Lausanne, Switzerland Objective: Infant sleep development is a highly dynamic process occurring in parallel to and in interaction with cognitive and physical growth. This narrative review aims to summarize and discuss recent literature and provide an overview of the relation between infant sleep and cognitive development as well as physical growth.Methods: We conducted online literature search using MEDLINE, Embase, and Cochrane Library databases. We considered original research on humans published in the English language from January 2005 to December 2015. Search terms included “sleep” AND “infant” AND “cognition” OR “memory” OR “executive functioning”, OR “growth” OR “obesity” OR “growth hormone” OR “stunting”, and combinations thereof.Results: Ten studies on infant sleep and cognition were included in this review. Overall, findings indicated a positive association between sleep, memory, language, executive function, and overall cognitive development in typically developing infants and young children. An additional 20 studies support the positive role of infant sleep in physical growth, with the current literature focusing largely on weight gain and obesity rather than healthy growth. Existing evidence in both the domains is mainly based on cross-sectional designs, on association studies, and on parental reports. In contrast, there were limited studies on longitudinal sleep trajectories and intervention effects, or studies have not used more objective sleep measures such as actigraphy and polysomnography.Conclusion: The reviewed studies support a critical and positive role of infant sleep in cognition and physical growth. Future studies should consider key environmental and parental confounders, include a combination of more objective (actigraphy) and subjective measures (sleep diaries and questionnaires), and move towards longitudinal trajectory designs of infant sleep and development. Keywords: infant sleep, cognition, growth

Sleep is dynamic in childhood and studies have shown the relationship between sleep and cognition in children. As the human brain is the most plastic during childhood, the study of longitudinal sleep patterns and neurocognition is an important research area. We aimed to systematically review studies that investigated sleep duration trajectories and cognition in typically-developing children. We searched four databases for articles published between 2003 to October 2023. We included observation studies of children with sleep duration trajectories as a predictor and outcomes related to cognition, memory, language, developmental milestones, intelligence or executive function. We excluded studies where children had atypical development or completed the sleep and neurocognitive assessments after six and 12 years of age respectively. Out of 752 articles identified, 511 were screened and 23 full texts were assessed. The selected studies included three single trajectory and four multiple group trajectories studies. We found associations between both types of trajectories and cognitive development. Overall, children with longer sleep trajectories or more mature sleep pattern with rapid decrease in sleep duration, had better performance scores in developmental assessment tools, and intelligence tests. Findings for language and executive functioning were mixed, whereby some studies found associations and others did not., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Differences in symptom burden, treatment satisfaction and autonomy between patients receiving peritoneal dialysis and haemodialysis could be reflected by a difference in symptom dimensions of anxiety and depression. The aim of this study is to assess differences in prevalence and symptom dimensions of anxiety and depression between patients receiving peritoneal dialysis and haemodialysis., Methods: Baseline data from the Depression Related Factors and Outcomes in Dialysis Patients With Various Ethnicities and Races Study were used. Symptoms of anxiety and depression were measured with the Beck Anxiety Inventory and Beck Depression Inventory- second edition. Linear and logistic regression models were used to compare anxiety and depression total scores and somatic and subjective/cognitive symptom dimension scores between patients receiving peritoneal dialysis and haemodialysis, adjusted for potential confounders., Results: In total, 84 patients receiving peritoneal dialysis and 601 patients receiving haemodialysis were included. Clinically significant symptoms of anxiety and depression were present in respectively 22% and 43% of the patients, with no differences between dialysis modality. Both modalities scored high on the somatic symptom dimensions and on individual somatic items. Almost all patients reported symptoms related to loss of energy and sleep., Conclusion: No differences in symptom dimensions of anxiety and depression were found between patients receiving peritoneal dialysis and haemodialysis. The high prevalence of somatic symptom dimensions in both groups underscores the possible interaction between somatic and psychiatric symptoms in dialysis patients and the need for early recognition and treatment of symptoms of anxiety and depression regardless of treatment modalities.

Objectives: A decrease of both diffusion capacity (DLCO) and Quality of Life (QoL) was reported after discharge in hospitalized COVID-19 pneumonia survivors. We studied three and 6 month outcomes in hospitalized and non-hospitalized patients., Methods: COVID-19 pneumonia survivors ( n = 317) were categorized into non-hospitalized "moderate" cases ( n = 59), hospitalized "severe" cases ( n = 180) and ICU-admitted "critical" cases ( n = 39). We studied DLCO and QoL (Short Form SF-36 health survey) 3 and 6 months after discharge. Data were analyzed using (repeated measures) ANOVA, Kruskal-Wallis or Chi-square test ( p < .05)., Results: At 3 months DLCO was decreased in 44% of moderate-, 56% of severe- and 82% of critical cases ( p < .003). Mean DLCO in critical cases (64±14%) was lower compared to severe (76 ± 17%) and moderate (81±15%) cases ( p < .001). A total of 159/278 patients had a decreased DLCO (<80%), of whom the DLCO improved after 6 months in 45% (71/159). However the DLCO did not normalize in the majority (89%) of the cases (63 ± 10% vs 68±10%; p < .001). At 3 months, compared to critical cases, moderate cases scored lower on SF-36 domain "general health" ( p < .05); both moderate and severe cases scored lower on the domain of "health change" ( p < .05). At 6 months, there were no differences in SF-36 between the subgroups. Compared to 3 months, in all groups "physical functioning" improved; in contrast all groups scored significantly lower on "non-physical" SF-36 domains., Conclusion: Three months after COVID-19 pneumonia, DLCO was still decreased in the more severely affected patients, with an incomplete recovery after 6 months. At 3 months QoL was impaired. At 6 months, while "physical functioning" improved, a decrease in "non-physical" QoL was observed but did not differ between the moderate and severely affected patients.

This study aimed to identify distinct behavioral profiles in a population-based sample of 654 4-year-old children and characterize their relationships with brain functional networks using resting-state functional magnetic resonance imaging data. Young children showed 7 behavioral profiles, including a super healthy behavioral profile with the lowest scores across all Child Behavior CheckList (CBCL) subscales (G1) and other 6 behavioral profiles, respectively with pronounced withdrawal (G2), somatic complaints (G3), anxiety and withdrawal (G4), somatic complaints and withdrawal (G5), the mixture of emotion, withdrawal, and aggression (G6), and attention (G7) problems. Compared with children in G1, children with withdrawal shared abnormal functional connectivities among the sensorimotor networks. Children in emotionally relevant problems shared the common pattern among the attentional and frontal networks. Nevertheless, children in sole withdrawal problems showed a unique pattern of connectivity alterations among the sensorimotor, cerebellar, and salience networks. Children with somatic complaints showed abnormal functional connectivities between the attentional and subcortical networks, and between the language and posterior default mode networks. This study provides novel evidence on the existence of behavioral heterogeneity in early childhood and its associations with specific functional networks that are clinically relevant phenotypes for mental illness and are apparent from early childhood.

Perinatal maternal depressive symptoms influence brain development of offspring. Such effects are particularly notable in the amygdala, a key structure involved in emotional processes. This study investigated whether the functional organization of the amygdala varies as a function of pre- and postnatal maternal depressive symptoms. The amygdala functional network was assessed using resting-state functional magnetic resonance imaging (rs-fMRI) in 128 children at age of 4.4 to 4.8 years. Maternal depressive symptoms were obtained at 26 weeks of gestation, 3 months, 1, 2, 3, and 4.5 years after delivery. Linear regression was used to examine associations between maternal depressive symptoms and the amygdala functional network. Prenatal maternal depressive symptoms were significantly associated with the functional connectivity between the amygdala and the cortico-striatal circuitry, especially the orbitofrontal cortex (OFC), insula, subgenual anterior cingulate (ACC), temporal pole, and striatum. Interestingly, greater pre- than post-natal depressive symptoms were associated with lower functional connectivity of the left amygdala with the bilateral subgenual ACC and left caudate and with lower functional connectivity of the right amygdala with the left OFC, insula, and temporal pole. These findings were only observed in girls but not in boys. Early exposure to maternal depressive symptoms influenced the functional organization of the cortico-striato-amygdala circuitry, which is intrinsic to emotional perception and regulation in girls. This suggests its roles in the transgenerational transmission of vulnerability for socio-emotional problems and depression. Moreover, this study underscored the importance of gender-dependent developmental pathways in defining the neural circuitry that underlies the risk for depression., (© 2017 Wiley Periodicals, Inc.)

This study aimed to examine heterogeneity of neonatal brain network and its prediction to child behaviors at 24 and 48 months of age. Diffusion tensor imaging (DTI) tractography was employed to construct brain anatomical network for 120 neonates. Clustering coefficients of individual structures were computed and used to classify neonates with similar brain anatomical networks into one group. Internalizing and externalizing behavioral problems were assessed using maternal reports of the Child Behavior Checklist (CBCL) at 24 and 48 months of age. The profile of CBCL externalizing and internalizing behaviors was then examined in the groups identified based on the neonatal brain network. Finally, support vector machine and canonical correlation analysis were used to identify brain structures whose clustering coefficients together significantly contribute the variation of the behaviors at 24 and 48 months of age. Four meaningful groups were revealed based on the brain anatomical networks at birth. Moreover, the clustering coefficients of the brain regions that most contributed to this grouping of neonates were significantly associated with childhood internalizing and externalizing behaviors assessed at 24 and 48 months of age. Specially, the clustering coefficient of the right amygdala was associated with both internalizing and externalizing behaviors at 24 months of age, while the clustering coefficients of the right inferior frontal cortex and insula were associated with externalizing behaviors at 48 months of age. Our findings suggested that neural organization established during fetal development could to some extent predict individual differences in behavioral-emotional problems in early childhood. Hum Brain Mapp 38:1362-1373, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objective: Adolescents and adults who are evening-types exhibit shorter sleep duration and more sleep problems than individuals with an earlier chronotype. We hypothesized that already at a preschool age, evening-types would exhibit more sleep problems relative to children who are morning or intermediate chronotypes. The aim of this study was to examine the association between chronotype and sleep problems among preschool children., Methods: We studied a subset of typically-developing 4.5-year-olds taking part in the Growing Up in Singapore Towards healthy Outcomes birth cohort study (n = 244). The Children's Chronotype Questionnaire (CCTQ) was used to categorize children into morning-, intermediate-, and evening-types. Sleep problems were measured using the Children's Sleep Habits Questionnaire (CSHQ), with higher scores corresponding to greater sleep problems. The relation between chronotype, sleep-wake timing, and nocturnal sleep time was also evaluated in a subsample of 117 children using actigraphy recordings with parent-reported sleep diaries., Results: After controlling for potential confounders (maternal education, child's sex, birth order, and ethnicity), a significant main effect of chronotype on sleep problems was observed, in which evening-types exhibited greater CSHQ scores compared to morning- and intermediate-types (all p < 0.001). Actigraphy data in the subsample confirmed that evening-types had later bedtimes (p < 0.001) and get-up times (p = 0.02) during weekdays and weekends, but shorter nocturnal sleep time (p = 0.034) only during weekdays, compared to children who had earlier chronotypes., Conclusions: In preschool children, sleep problems were greater in evening-types compared to morning- and intermediate-types, suggesting that chronotype could be a contributing factor to sleep disturbances in early childhood., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In addition to immediate implications for pregnancy complications, increasing evidence implicates maternal obesity as a major determinant of offspring health during childhood and later adult life. Observational studies provide evidence for effects of maternal obesity on her offspring's risks of obesity, coronary heart disease, stroke, type 2 diabetes, and asthma. Maternal obesity could also lead to poorer cognitive performance and increased risk of neurodevelopmental disorders, including cerebral palsy. Preliminary evidence suggests potential implications for immune and infectious-disease-related outcomes. Insights from experimental studies support causal effects of maternal obesity on offspring outcomes, which are mediated at least partly through changes in epigenetic processes, such as alterations in DNA methylation, and perhaps through alterations in the gut microbiome. Although the offspring of obese women who lose weight before pregnancy have a reduced risk of obesity, few controlled intervention studies have been done in which maternal obesity is reversed and the consequences for offspring have been examined. Because the long-term effects of maternal obesity could have profound public health implications, there is an urgent need for studies on causality, underlying mechanisms, and effective interventions to reverse the epidemic of obesity in women of childbearing age and to mitigate consequences for offspring., Competing Interests: statement KMG reports other from Nestle Nutrition Institute, grants from Abbott Nutrition & Nestec, outside the submitted work; in addition, KMG has a patent Phenotype prediction pending, a patent Predictive use of CpG methylation pending, and a patent Maternal Nutrition Composition pending. SLP reports other from Danone Scientific Advisory Board, other from Nestle Nutrition Institute Scientific Advisory Board, other from ALK Abello, outside the submitted work. The other authors have nothing to disclose., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Research has demonstrated a bilingual advantage in how young children use referential cues such as eye gaze and pointing gesture to locate an object or to categorize objects. This study investigated the use of referential cues (i.e. eye gaze) in fast mapping in three groups of children that differed in their language exposure. One hundred and seven 54-month-old children who were English monolinguals (n = 28), English-Mandarin bilinguals (n = 48), and English-Mandarin bilinguals with exposure to a third language (i.e. trilinguals, n = 31) were assessed with a word learning task using two types of test - a referent test and a mutual exclusivity test. During the task, following the gaze of an adult speaker was needed to be able to indicate the correct referent of a novel word at test. All three groups of children demonstrated successful word learning in explicit selection of and implicit looking time toward the target object during testing. However, bilingual and trilingual children outperformed their monolingual peers in both types of test when they were asked to explicitly select the correct objects. These findings suggest positive effects of bilingualism on children's use of referential cues in fast mapping., (© 2016 John Wiley & Sons Ltd.)

Background: Symptoms of depression and anxiety are common during pregnancy and the postnatal period. A risk factor for mood disorders is poor sleep quality. In this study we investigate the effects of poor subjective prenatal sleep quality on postnatal depressive and anxiety symptoms, independent of prenatal depression or anxiety, amongst pregnant women in the general population., Methods: We analysed data from a subset of women taking part in a prospective cohort study, Growing Up in Singapore towards Healthy Outcomes. The participants completed the Edinburgh Postnatal Depression Scale and State-Trait Anxiety Inventory between 26 and 28 weeks of pregnancy (Time 1) and at 3 months postpartum (Time 2), and the Pittsburgh Sleep Quality Index at Time 1. Logistic regression analyses were used to investigate the associations between subjective prenatal sleep quality and postnatal depressive and anxiety symptoms, while adjusting for prenatal depressive/anxiety symptoms and education., Results: Although borderline-high depressive/anxiety symptoms were the strongest predictors of postnatal depressive/anxiety, independent of this, poor subjective sleep quality during pregnancy was also associated with borderline-high postnatal depressive symptoms, but not with postnatal anxiety., Limitations: Sleep quality and prenatal/postnatal mood were derived from self-reported questionnaires, which may be more susceptible to bias., Conclusion: Although treatment of symptoms of prenatal depression and anxiety will be the most important for reducing postnatal depression and anxiety, in addition to that, future studies may explore treatments improving prenatal sleep quality, particularly for women with antenatal depressive symptoms., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: Analyze the relation of gestational diabetes and maternal blood glucose levels to early cognitive functions in the first two years of life., Methods: In a prospective Singaporean birth cohort study, pregnant women were screened for gestational diabetes at 26-28 weeks gestation using a 75-g oral glucose tolerance test. Four hundred and seventy three children (n = 74 and n = 399 born to mothers with and without gestational diabetes respectively) underwent neurocognitive assessments at 6, 18, and/or 24 month, including electrophysiology during an attentional task and behavioral measures of attention, memory and cognition., Results: Gestational diabetes is related to left hemisphere EPmax amplitude differences (oddball versus standard) at both six (P = 0.039) and eighteen months (P = 0.039), with mean amplitudes suggesting offspring of mothers with gestational diabetes exhibit greater neuronal activity to standard stimuli and less to oddball stimuli. Associations between 2-hour maternal glucose levels and the difference in EPmax amplitude were marginal at 6 months [adjusted β = -0.19 (95% CI: -0.42 to +0.04) μV, P = 0.100] and significant at 18 months [adjusted β = -0.27 (95% CI: -0.49 to -0.06) μV, P = 0.014], and the EPmax amplitude difference (oddball-standard) associated with the Bayley Scales of Infant and toddler Development-III cognitive score at 24 months [β = 0.598 (95% CI: 0.158 to 1.038), P = 0.008]., Conclusion: Gestational diabetes and maternal blood glucose levels are associated with offspring neuronal activity during an attentional task at both six and eighteen months. Such electrophysiological differences are likely functionally important, having been previously linked to attention problems later in life., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: PDG, KMG and YSC have received lecture fees from companies selling nutritional products. They are part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone. The other authors have no competing interests to declare. All competing interests do not alter our adherence to PLOS ONE policies on sharing data and materials.

Maternal antenatal mood is associated with negative infant temperament. This link has not been substantiated in Asian populations. We evaluated the association between antenatal maternal mood and infant temperament among Asian mother-infant pairs. Antenatal maternal depression and anxiety were assessed using the Edinburgh Postnatal Depression Scale (J. Cox, J. Holden, & R. Sagovsky, 1987) and the State-Trait Anxiety Inventory (C. Spielberger, R. Gorsuch, R. Lushene, P. Vagg, & G. Jacobs, 1983), respectively, at 26 weeks of pregnancy and 3 months' postnatally. Infant temperament was evaluated with the Early Infant Temperament Questionnaire (B. Medoff-Cooper, W.B. Carey, & S.C. McDevitt, 1993) at 3 months. Factor analysis was performed to extract culturally relevant categories of temperamental traits. Linear regression was performed to examine the influences of antenatal maternal mood on the factor-model-derived infant temperament. Of the 609 mothers, 11% met risk criteria for depression, 17% for state-anxiety, and 19% for trait-anxiety during pregnancy. Factor analysis yielded three infant temperament factors: Emotionality and Attentional Regulation, Sensory Reactivity, and Regularity and Motor Expression, Cronbach's αs = 0.613, 0.712, and 0.752, respectively. Maternal antenatal state-anxiety, p < .001, and trait anxiety, p = .005, were associated with negative emotionality and poor attentional regulation, especially among Chinese, whereas depression was not, p = .090. There was an association between maternal antenatal anxiety and negative infant temperamental traits in this Asian sample., (© 2016 Michigan Association for Infant Mental Health.)

This study investigated the relationships between pre- and early post-natal maternal depression and their changes with frontal electroencephalogram (EEG) activity and functional connectivity in 6- and 18-month olds, as well as externalizing and internalizing behaviors in 24-month olds (n = 258). Neither prenatal nor postnatal maternal depressive symptoms independently predicted neither the frontal EEG activity nor functional connectivity in 6- and 18-month infants. However, increasing maternal depressive symptoms from the prenatal to postnatal period predicted greater right frontal activity and relative right frontal asymmetry amongst 6-month infants but these finding were not observed amongst 18-month infants after adjusted for post-conceptual age on the EEG visit day. Subsequently increasing maternal depressive symptoms from the prenatal to postnatal period predicted lower right frontal connectivity within 18-month infants but not among 6-month infants after controlling for post-conceptual age on the EEG visit day. These findings were observed in the full sample and the female sample but not in the male sample. Moreover, both prenatal and early postnatal maternal depressive symptoms independently predicted children's externalizing and internalizing behaviors at 24 months of age. This suggests that the altered frontal functional connectivity in infants born to mothers whose depressive symptomatology increases in the early postnatal period compared to that during pregnancy may reflect a neural basis for the familial transmission of phenotypes associated with mood disorders, particularly in girls.

Background: Different maternal psychological states during pregnancy have been associated with wheeze-rhinitis-eczema symptoms in children. However, previous studies were limited and it was unclear whether the type of prenatal psychological state was associated with a particular symptom. We examined the association of maternal depression and anxiety during pregnancy with wheeze-rhinitis-eczema symptoms in infancy., Methods: In a longitudinal birth cohort (GUSTO) of 1152 mother-child pairs, wheeze-rhinitis-eczema symptoms in the infants during the first year of life were collected by parental report. Maternal depressive and anxiety symptoms were assessed at 26 weeks of gestation using the Edinburgh Postnatal Depression Scale (EPDS) and State Trait Anxiety Inventory (STAI). Logistic regression analyses were performed with adjustment for potential confounders., Results: An increased risk of wheezing was found in infants of pregnant women with probable depression (EPDS ≥ 15) [odds ratio (OR) = 1.85 (95% confidence interval (CI) 1.10-3.12)], and an increased risk of rhinitis was associated with maternal anxiety [STAI state ≥ 41: OR = 1.42 (95% CI 1.04-1.93); STAI trait ≥ 43: OR = 1.38 (95% CI 1.01-1.88)]. After adjusting for known risk factors for the development of allergic disease, these associations remained significant [EPDS ≥ 15: adjusted OR = 2.09 (95% CI 1.05-4.19); STAI state ≥ 41: adjusted OR = 1.82 (95% CI 1.17-2.82); STAI trait ≥ 43: adjusted OR = 1.70 (95% CI 1.10-2.61)]. However, maternal psychological states were not associated with infantile eczema., Conclusion: This study suggests that there may be an independent effect of prenatal depression on wheezing and anxiety on rhinitis in infancy., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Mechanisms underlying the profound parental effects on cognitive, emotional and social development in humans remain poorly understood. Studies with nonhuman models suggest variations in parental care affect the limbic system, influential to learning, autobiography and emotional regulation. In some research, nonoptimal care relates to decreases in neurogenesis, although other work suggests early-postnatal social adversity accelerates the maturation of limbic structures associated with emotional learning. We explored whether maternal sensitivity predicts human limbic system development and functional connectivity patterns in a small sample of human infants. When infants were 6 months of age, 20 mother-infant dyads attended a laboratory-based observational session and the infants underwent neuroimaging at the same age. After considering age at imaging, household income and postnatal maternal anxiety, regression analyses demonstrated significant indirect associations between maternal sensitivity and bilateral hippocampal volume at six months, with the majority of associations between sensitivity and the amygdala demonstrating similar indirect, but not significant results. Moreover, functional analyses revealed direct associations between maternal sensitivity and connectivity between the hippocampus and areas important for emotional regulation and socio-emotional functioning. Sensitivity additionally predicted indirect associations between limbic structures and regions related to autobiographical memory. Our volumetric results are consistent with research indicating accelerated limbic development in response to early social adversity, and in combination with our functional results, if replicated in a larger sample, may suggest that subtle, but important, variations in maternal care influence neuroanatomical trajectories important to future cognitive and emotional functioning.

Background: Appetitive traits in childhood such as food responsiveness and enjoyment of food have been associated with body mass index (BMI) in later childhood. However, data on appetitive traits during infancy in relation to BMI in later childhood are sparse. We aimed to relate appetitive traits in infancy to subsequent BMI and weight gain up to 24 months of age., Methods: Data of 210 infants from the Singapore GUSTO mother-offspring cohort was obtained. The Baby Eating Behavior Questionnaire (BEBQ) and the Child Eating Behavior Questionnaire (CEBQ) were administered to mothers when their offspring were aged 3 and 12 months respectively. Height and weight of offspring were measured at ages 3, 6, 9,12,15,18 and 24 months. The association of appetitive traits with both BMI z-score and weight gain were evaluated using multivariate linear regression., Results: Food responsiveness at 3 months was associated with higher BMI from 6 months up to 15 months of age (p < 0.01) and with greater weight gain between 3 and 6 months of age (p = 0.012). Slowness in eating and satiety responsiveness at 3 months was significantly associated with lower BMI at 6 months (p < 0.01) and with less weight gain between 3 to 6 months of age (p = 0.034). None of the appetitive traits at 12 months were significantly associated with BMI or weight gain over any time period., Conclusion: Early assessment of appetitive traits at 3 months of age but not at 12 months of age was associated with BMI and weight gain over the first two years of life., Trial Registration: Clinical Trials identifier NCT01174875.

Objective: Studies have demonstrated a relationship between lower omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) status and anxiety and depression. It is uncertain whether similar associations occur in pregnant women, when anxiety and depression could have long-term effects on the offspring. We examined the associations between plasma LC-PUFA status during pregnancy and perinatal mental health., Method: At 26-28 weeks' gestation, plasma LC-PUFAs were measured in mothers of the Growing Up in Singapore Toward healthy Outcomes (GUSTO) mother-offspring cohort study, who were recruited between June 2009 and September 2010. Maternal symptoms of anxiety and depression were assessed with the State-Trait Anxiety Inventory (STAI) and Edinburgh Postnatal Depression Scale (EPDS) during the same period and at 3 months' postpartum. The STAI-state subscale was used as a continuous measure of current anxiety, while EPDS scores ≥ 15 during pregnancy or ≥ 13 postpartum were indicative of symptoms of probable depression., Results: In adjusted regression analyses (n = 698), lower plasma total omega-3 PUFA concentrations (β = -6.49 STAI-state subscale scores/unit increase of omega-3 fatty acid; 95% CI, -11.90 to -1.08) and higher plasma omega-6:omega-3 PUFA ratios (β = 6.58 scores/unit increase of fatty acid ratio; 95% CI, 1.19 to 12.66), specifically higher arachidonic acid (AA):docosahexaenoic acid, AA:eicosapentaenoic acid, and AA:docosapentaenoic acid ratios, were associated with increased antenatal anxiety (P < .05 for all), but not postpartum anxiety. There was no association between plasma PUFAs and perinatal probable depression., Conclusions: No association was found with probable depression in pregnancy or postpartum. Lower plasma omega-3 fatty acids and higher omega-6:omega-3 fatty acid ratios were associated with higher antenatal anxiety, but not postpartum anxiety. Replication in other studies is needed to confirm the findings and determine the direction of causality., Trial Registration: ClinicalTrials.gov identifier: NCT01174875., (© Copyright 2015 Physicians Postgraduate Press, Inc.)

Background: There is growing research evidence that subclinical autistic traits are elevated in relatives of individuals with autism spectrum disorder (ASD), continuously distributed in the general population and likely to share common etiology with ASD. A number of measures have been developed to assess autistic traits quantitatively in unselected samples. So far, the Quantitative-Checklist for Autism in Toddlers (Q-CHAT) is one of very few measures developed for use with toddlers as young as 18 months, but little is known about its measurement properties and factor structure., Methods: The present study examined internal consistency, factor structure, test-retest stability, and convergent validity of the Q-CHAT in a sample of toddlers in Singapore whose caregivers completed the Q-CHAT at 18 (n = 368) and 24 months (n = 396)., Results: Three factors were derived accounting for 38.1 % of the variance: social/communication traits, non-social/behavioral traits, and a speech/language factor. Internal consistency was suboptimal for the total and speech/language scores, but acceptable for the social/communication and non-social/behavioral factor scores. Scores were generally stable between 18 and 24 months. Convergent validity was found with the Pervasive Developmental Disorders subscale of the Child Behavior Checklist (CBCL) completed by caregivers when their children were 24 months. Q-CHAT total scores in this sample were higher than those reported in other unselected samples from the UK., Conclusions: The Q-CHAT was found to have a three-factor structure, acceptable internal consistency for its two main factor scores (social/communication and non-social/behavioral), normally distributed scores in an unselected sample, and similar structure and measurement properties as those reported in other published studies. Findings are discussed in relation to existing literature and future directions for the validation of the Q-CHAT.

Objective: Antenatal maternal anxiety predicts offspring neurodevelopment and psychopathology, although the degree to which these associations reflect postnatal influences is unclear. To limit this possibility, we assessed newborn neuronal microstructures using diffusion tensor imaging (DTI) and assessed neonatal microstructure variation in relation to antenatal anxiety and in prediction of infant socio-emotional behavior at age 1 year., Method: Dyads were drawn from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) cohort, and included mothers who completed the Speilberger State-Trait Anxiety Inventory (STAI) at 26 weeks gestation (scoring >90, n = 20; scoring <70, n = 34) and their neonates (5-17 days postnatal) who took part in DTI., Results: Antenatal anxiety predicted variation in fractional anisotropy (FA) of regions important to cognitive-emotional responses to stress (i.e., the right insula and dorsolateral prefrontal cortex), sensory processing (e.g., right middle occipital), and socio-emotional function (e.g., the right angular gyrus, uncinate fasciculus, posterior cingulate, and parahippocampus). In a subset of infants with Infant Toddler Socio-Emotional Assessment (ITSEA) data, some of these right lateralized clusters predicted infant internalizing (e.g., insula: β = 0.511, p = .03) but not externalizing behavior 1 year later, although these analyses failed to withstand the correction for multiple comparisons., Conclusion: These findings suggest the need for larger-scale investigations of the role that corticolimbic structures play in regulating cognitive-emotional responses to threat, and potentially in mediating the cross-generational transmission of anxiety, as well as in underscoring the importance of early mother-infant intervention programs., (Copyright © 2015 American Academy of Child and Adolescent Psychiatry. All rights reserved.)

Prenatal maternal depression is associated with alterations in the neonatal amygdala microstructure, shedding light on the timing for the influence of prenatal maternal depression on the brain structure of the offspring. This study aimed to examine the association between prenatal maternal depressive symptomatology and infant amygdala functional connectivity and to thus establish the neural functional basis for the transgenerational transmission of vulnerability for affective disorders during prenatal development. Twenty-four infants were included in this study with both structural magnetic resonance imaging (MRI) and resting-state functional MRI (fMRI) at 6 months of age. Maternal depression was assessed at 26 weeks of gestation and 3 months after delivery using the Edinburgh Postnatal Depression Scale. Linear regression was used to identify the amygdala functional networks and to examine the associations between prenatal maternal depressive symptoms and amygdala functional connectivity. Our results showed that at 6 months of age, the amygdala is functionally connected to widespread brain regions, forming the emotional regulation, sensory and perceptual, and emotional memory networks. After controlling for postnatal maternal depressive symptoms, infants born to mothers with higher prenatal maternal depressive symptoms showed greater functional connectivity of the amygdala with the left temporal cortex and insula, as well as the bilateral anterior cingulate, medial orbitofrontal and ventromedial prefrontal cortices, which are largely consistent with patterns of connectivity observed in adolescents and adults with major depressive disorder. Our study provides novel evidence that prenatal maternal depressive symptomatology alters the amygdala's functional connectivity in early postnatal life, which reveals that the neuroimaging correlates of the familial transmission of phenotypes associated with maternal mood are apparent in infants at 6 months of age.

Early life environments interact with genotype to determine stable phenotypic outcomes. Here we examined the influence of a variant in the brain-derived neurotropic factor (BDNF) gene (Val66Met), which underlies synaptic plasticity throughout the central nervous system, on the degree to which antenatal maternal anxiety associated with neonatal DNA methylation. We also examined the association between neonatal DNA methylation and brain substructure volume, as a function of BDNF genotype. Infant, but not maternal, BDNF genotype dramatically influences the association of antenatal anxiety on the epigenome at birth as well as that between the epigenome and neonatal brain structure. There was a greater impact of antenatal maternal anxiety on the DNA methylation of infants with the methionine (Met)/Met compared to both Met/valine (Val) and Val/Val genotypes. There were significantly more cytosine-phosphate-guanine sites where methylation levels covaried with right amygdala volume among Met/Met compared with both Met/Val and Val/Val carriers. In contrast, more cytosine-phosphate-guanine sites covaried with left hippocampus volume in Val/Val infants compared with infants of the Met/Val or Met/Met genotype. Thus, antenatal Maternal Anxiety × BDNF Val66Met Polymorphism interactions at the level of the epigenome are reflected differently in the structure of the amygdala and the hippocampus. These findings suggest that BDNF genotype regulates the sensitivity of the methylome to early environment and that differential susceptibility to specific environmental conditions may be both tissue and function specific.

Background: Breastfeeding has been shown to enhance global measures of intelligence in children. However, few studies have examined associations between breastfeeding and specific cognitive task performance in the first 2 y of life, particularly in an Asian population., Objective: We assessed associations between early infant feeding and detailed measures of cognitive development in the first 2 y of life in healthy Asian children born at term., Design: In a prospective cohort study, neurocognitive testing was performed in 408 healthy children (aged 6, 18, and 24 mo) from uncomplicated pregnancies (i.e., birth weight >2500 and <4000 g, gestational age ≥37 wk, and 5-min Apgar score ≥9). Tests included memory (deferred imitation, relational binding, habituation) and attention tasks (visual expectation, auditory oddball) as well as the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Children were stratified into 3 groups (low, intermediate, and high) on the basis of breastfeeding duration and exclusivity., Results: After potential confounding variables were controlled for, significant associations and dose-response relations were observed for 4 of the 15 tests. Higher breastfeeding exposure was associated with better memory at 6 mo, demonstrated by greater preferential looking toward correctly matched items during early portions of a relational memory task (i.e., relational binding task: P-trend = 0.015 and 0.050 for the first two 1000-ms time bins, respectively). No effects of breastfeeding were observed at 18 mo. At 24 mo, breastfed children were more likely to display sequential memory during a deferred imitation memory task (P-trend = 0.048), and toddlers with more exposure to breastfeeding scored higher in receptive language [+0.93 (0.23, 1.63) and +1.08 (0.10, 2.07) for intermediate- and high-breastfeeding groups, respectively, compared with the low-breastfeeding group], as well as expressive language [+0.58 (-0.06, 1.23) and +1.22 (0.32, 2.12) for intermediate- and high-breastfeeding groups, respectively] assessed via the BSID-III., Conclusions: Our findings suggest small but significant benefits of breastfeeding for some aspects of memory and language development in the first 2 y of life, with significant improvements in only 4 of 15 indicators. Whether the implicated processes confer developmental advantages is unknown and represents an important area for future research. This trial was registered at www.clinicaltrials.gov as NCT01174875., (© 2015 American Society for Nutrition.)

Objective: Exposure to antenatal maternal anxiety and complex genetic variations may shape fetal brain development. In particular, the catechol-O-methyltransferase (COMT) gene, located on chromosome 22q11.2, regulates catecholamine signaling in the prefrontal cortex and is implicated in anxiety, pain, and stress responsivity. This study examined whether individual single-nucleotide polymorphisms (SNPs) of the COMT gene and their haplotypes moderate the association between antenatal maternal anxiety and in utero cortical development., Method: A total of 146 neonates were genotyped and underwent MRI shortly after birth. Neonatal cortical morphology was characterized using cortical thickness. Antenatal maternal anxiety was assessed using the State-Trait Anxiety Inventory at week 26 of pregnancy., Results: Individual COMT SNPs (val158met, rs737865, and rs165599) modulated the association between antenatal maternal anxiety and the prefrontal and parietal cortical thickness in neonates. Based on haplotype trend regression analysis, findings also showed that among rs737865-val158met-rs165599 haplotypes, the A-val-G (AGG) haplotype probabilities modulated positive associations of antenatal maternal anxiety with cortical thickness in the right ventrolateral prefrontal cortex and the right superior parietal cortex and precuneus. In contrast, the G-met-A (GAA) haplotype probabilities modulated negative associations of antenatal maternal anxiety with cortical thickness in bilateral precentral gyrus and the dorsolateral prefrontal cortex., Conclusions: These results suggest that the association between maternal anxiety and in utero neurodevelopment is modified through complex genetic variation in COMT. Such genetic moderation may explain, in part, the variation in phenotypic outcomes in offspring associated with maternal emotional well-being.

Objective: Understanding healthy brain development in utero is crucial in order to detect abnormal developmental trajectories due to developmental disorders. However, in most studies neuroimaging was done after a significant postnatal period, and in those studies that performed neuroimaging on fetuses, the quality of data has been affected due to complications of scanning during pregnancy. To understand healthy brain development between 37-41 weeks of gestational age, our study assessed the in utero growth of the brain in healthy term born babies with DTI scanning soon after birth., Methods: A cohort of 93 infants recruited from maternity hospitals in Singapore underwent diffusion tensor imaging between 5 to 17 days after birth. We did a cross-sectional examination of white matter microstructure of the brain among healthy term infants as a function of gestational age via voxel-based analysis on fractional anisotropy., Results: Greater gestational age at birth in term infants was associated with larger fractional anisotropy values in early developing brain regions, when corrected for age at scan. Specifically, it was associated with a cluster located at the corpus callosum (corrected p<0.001), as well as another cluster spanning areas of the anterior corona radiata, anterior limb of internal capsule, and external capsule (corrected p<0.001)., Conclusions: Our findings show variation in brain maturation associated with gestational age amongst 'term' infants, with increased brain maturation when born with a relatively higher gestational age in comparison to those infants born with a relatively younger gestational age. Future studies should explore if these differences in brain maturation between 37 and 41 weeks of gestational age will persist over time due to development outside the womb.

Unlabelled: Studies in the general population have proposed links between nutrition and depression, but less is known about the perinatal period. Depletion of nutrient reserves throughout pregnancy and delayed postpartum repletion could increase the risk of perinatal depression. We examined the relationships of plasma folate and vitamin B12 concentrations during pregnancy with perinatal depression. At 26th-28th weeks of gestation, plasma folate and vitamin B12 were measured in women from the GUSTO mother-offspring cohort study in Singapore. Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS) during the same period and at 3-month postpartum. EPDS scores of ≥15 during pregnancy or ≥13 at postpartum were indicative of probable depression. Of 709 women, 7.2% (n = 51) were identified with probable antenatal depression and 10.4% (n = 74) with probable postnatal depression. Plasma folate concentrations were significantly lower in those with probable antenatal depression than those without (mean ± SD; 27.3 ± 13.8 vs 40.4 ± 36.5 nmol/L; p = 0.011). No difference in folate concentrations was observed in those with and without probable postnatal depression. In adjusted regression models, the likelihood of probable antenatal depression decreases by 0.69 for every unit variation (increase) in folate (OR = 0.69 per SD increase in folate; 95% CI: 0.52, 0.94). Plasma vitamin B12 concentrations were not associated with perinatal depression. Lower plasma folate status during pregnancy was associated with antenatal depression, but not with postnatal depression. Replication in other studies is needed to determine the direction of causality between low folate and antenatal depression., Clinical Trial Registry: NCT01174875., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Mental health problems during pregnancy can influence fetal growth. However, studies examining the influence of maternal mental health across the normal range of birth outcomes are uncommon. This study examined the associations between symptoms of maternal depression and anxiety during pregnancy on birth size among term Asian infants., Methods: One thousand forty-eight Asian pregnant women from a cohort Growing Up in Singapore Towards Healthy Outcomes were recruited between 2009 to 2010 at two Singaporean maternity hospitals. At 26 weeks gestation, depressive symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS) and the Beck Depression Inventory II (BDI-II), and anxiety was measured with the Spielberger State-Trait Anxiety Inventory (STAI). Health personnel recorded birthweight, birthlength, gestational age, and head circumference at birth., Results: Nine hundred forty-six women who delivered term infants had complete data. For this sample, the mean birthweight was 3146.6 g [standard deviation (SD) 399.0], the mean birthlength was 48.9 cm (SD 2.0). After controlling for several potential confounders, there was a significant negative association between STAI and birthlength [β = -0.248, confidence interval (CI) [-0.382, -0.115], P < 0.001] and a small negative association between EPDS and birthlength (β = -0.169, CI [-0.305, -0.033], P = 0.02). No associations were found between scores on the EPDS, BDI-II, and STAI with birthweight or head circumference., Conclusions: Our preliminary data suggest that among term infants, anxiety and depressive symptoms are not associated with birthweight, while anxiety and depressive symptoms are associated with a shorter birthlength., (© 2013 John Wiley & Sons Ltd.)

Objective: Fetal growth predicts childhood behavioral problems associated with brain serotonergic systems. We hypothesized that allelic variations in genes involved in serotonergic function would moderate associations between birth weight (BW) and internalizing traits in childhood., Methods: The Child Behavior Checklist was administered to 545 healthy Singaporean children at 8 to 12 years. BW, corrected for gestational age, and candidate single-nucleotide polymorphisms (SNPs) in the TPH2, HTR2A, and SCL6A4 genes were investigated., Results: There was no significant main effect of BW on internalizing T scores (F = 1.08; P = .36). After multiple corrections, significant main effects on internalizing T scores were found for HTR2A rs2296972 (adjusted: F = 2.85; P = .019) and HTR2A rs6313 (adjusted: F = 5.91; P = .0002). Significant interactions were found between BW and SNPs for the TPH2 gene (rs2171363: P = .008; rs7305115: P = .007) and the HTR2A gene (rs2770304: P = .001; rs6313: P = .026) for internalizing T scores. The CC genotype of TPH2 rs2171363, GG genotype of TPH2 rs7305115, CC genotype of HTR2A rs2770304, and CC genotype of HTR2A rs6313 were associated with reduced internalizing scores for children born in the quartile above the midpoint. No significant main effects or interactions were found for SCL6A4 SNPs., Conclusions: These findings suggest that sequence variations in genes involved in serotonergic functions modulate relationships between BW and internalizing traits and might be candidates for plasticity mechanisms that determine individual differences in responses to environmental influences over the course of development.

Objective: Shortened versions of various depression scales have typically been based on conventional techniques such as factor analysis, without simultaneously considering the removal of culturally biased items that show differential item functioning (DIF). The authors recently showed that eight items in the 15-item Geriatric Depression Scale (GDS-15) evidenced DIF, associated with gender, age, ethnicity, and chronic illnesses. By selecting out these items, the authors derived a shortened 7-item GDS and compared it with derivations based on conventional factor analysis and logistic regression techniques and validated its test performance in Asian elderly., Methods: The GDS-15 and Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of major depressive disorder (MDD) was independently administered by interviewers to 4,253 noninstitutionalized community-living elderly subjects aged 60 years and older. Concurrent methods of data reduction and item selection included factor analyses and logistic regression modeling. The GDS-7 was compared with GDS-15 test performance using Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders diagnosis of MDD as gold standard criterion and receiver operating characteristics analysis., Results: After removal of eight DIF items, the derivation was consistent with and complements the results from factor analysis and logistic regression analyses. The short GDS-7 fit a unidimensional model with high explained total variance and demonstrated high sensitivity (0.93) and specificity (0.91) at a cutoff of one-half that was comparable with GDS-15., Conclusions: By removing items with culturally based response bias, the GDS-7 showed excellent scaling and test performance for screening MDD in an Asian elderly population.

Background: The origins of mental disorders arise often in childhood. Early life is a period of unique sensitivity with long lasting effects on mental health. However, the mechanisms for these effects remain unclear., Objective: This thesis describes a variety of studies using a developmental framework to promote greater understanding of the influence of nature (genotypes) and nurture (e.g., environmental risk and protective factors) on outcomes later in childhood., Method: The aim of this thesis is to investigate gene and environmental influences on behavioural, emotional, and cognitive outcomes in different samples from the Netherlands and Singapore, most derived from the general population. We assessed early life influences from a neurobiological, social, and a psychological perspective by using a biopsychosocial framework., Results: Our studies support the hypothesis that all experiences during life, including early experiences in utero, will influence the expression of genes and in the end the mental health of individuals. However, genotypes influencing stress responses are found to be "plastic," which implies that they can be modulated by environmental experiences during life. In line with this, patterns of resilience are found to be context-dependent too., Conclusions: The model of "epigenetic programming" suggests the predictive power of the environment in utero and early childhood on mental health later in life. This association is probably determined by a neurodevelopmental pathway with individual differences in neural and endocrine responses to stress.

Objective: Children react differently to surgeries. The purpose of this study is to examine the stress response in young children after an adenoidectomy and adenotonsillectomy, and whether child characteristics of behavioural and neurophysiological nature can predict this stress response., Methods: In this prospective cohort study 43 children, aged 2-7 years, scheduled for adenoidectomy or adenoitonsillectomy (response rate 43%) were recruited from the Ear, Nose and Throat Department of the Academic Medical Centre in Amsterdam, the Netherlands. Parents completed questionnaires about temperament 4 weeks before surgery, about behaviour and sleeping problems 4 weeks before and 6 weeks after surgery, and about posttraumatic stress symptoms 6 weeks after surgery. Neurophysiological measurements (cortisol and Respiratory Sinus Arrhythmia) were performed 4 weeks before, directly after and 6 weeks after surgery. Results were compared with a control group of healthy children. The data was analysed with paired t-tests and one-way repeated ANOVA., Results: Most children with an indication for an adenoidectomy and adenotonsillectomy had more behavioural and emotional problems before surgery then the control group. After surgery there was an improvement in behaviour and sleep, in respectively 75% and 68% of the children, especially in boys. Posttraumatic stress symptoms were rare. Emotional temperament was associated with more behavioural problems before surgery (r=0.53, P=0.02), after surgery (r=0.38, P<0.000), lower cortisol directly after surgery (r=-0.49, P=0.05) and lower Respiratory Sinus Arrhythmia at follow-up (r=-0.33, P=0.06). Other temperament styles and pre-surgery levels of Respiratory Sinus Arrhythmia and cortisol did not show associations with any behavioural or neurophysiological measures., Conclusions: An adenoidectomy and adenotonsillectomy appear not to be stressful, but rather seems helpful for reducing pre-existing behavioural and emotional problems, possibly associated with the indication for surgery. For those children with an increase of behavioural and sleeping problems after surgery, this can only be partly explained by emotional temperament. There are indications that boys and girls react differently; boys tend to show a better behavioural and emotional improvement after an adenoidectomy and adenotonsillectomy. Other behavioural or neurophysiological child characteristics do not have a predictive value on the outcome., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Objective: Birth parameters have been hypothesized to have an influence on IQ. However, studies within the range of normal birth size have been sparse. With this study we examined the associations between birth length, birth weight, head circumference, and gestational age within the normal birth size range in relation to childhood IQ in Asian children., Methods: A cohort of 1979 of 2913 Asian children aged 7 to 9 years, recruited from 3 schools in Singapore, were followed yearly from 1999 onward. Birth parameters were recorded by health personnel. Childhood IQ was measured with the Raven's Standard Progressive Matrices at ages 8 to 12., Results: The mean IQ score across the sample (n = 1645) was 114.2. After controlling for multiple confounders for every 1-cm increment in birth length, 1 kg in birth weight, or 1 cm in head circumference, there was a corresponding increase in IQ of 0.49 points (P for trend < .001), 2.19 points (P for trend = .007) and .62 points (P for trend = .003), respectively. These associations persisted even after exclusion of premature children and children with extreme weights and head circumferences., Conclusions: Longer birth length, higher birth weight, or larger head circumferences within the normal birth size range are associated with higher IQ scores in Asian children. Our results suggest that antenatal factors reflected in altered rates of growth but within the normative range of pregnancy experiences play a role in generating cognitive potential. This has implications for targeting early intervention and preventative programs.

Objective: Most studies of successful aging have used restricted definitions based on the absence of disability and identified a small number of predictors. The authors aimed to examine whether a broad multidimensional definition of successful aging has good construct validity and identified a wider range of predictors that are relevant for multifaceted interventions., Methods: Cross-sectional and longitudinal data analyses were performed on 1,281 community-living Chinese elderly of 65 years and above in the Singapore Longitudinal Aging Study cohort. Successful aging was measured in multiple dimensions of functioning and wellness: cognitive and affective status, physical health, social functioning and engagement and life satisfaction, and a summary composite measure created across dimensions to form a dichotomous variable. Potential determinants included sociodemographic, psychosocial, behavioral variables., Results: Successful aging was determined in 28.6% of respondents and in multivariate models was significantly (p <0.05) associated with age (OR = 0.90), female gender (OR = 1.37), > or =6 years of education (OR = 2.31), better housing (OR = 1.41), religious or spiritual beliefs (OR = 1.64), physical activities and exercise (OR = 1.90), and low or no nutritional risk (OR = 2.16)., Conclusion: In contrast to findings based on more restricted biomedical definitions of successful aging, a multidimensional definition of successful aging identified more variables including demographic status, psychosocial support, spirituality, and nutrition as salient determinants.

Background: The Geriatric Depression Scale (GDS) is widely used for screening and assessment of major depressive disorder (MDD). Screening scales are often culture-specific and should be evaluated for item response bias (synonymously differential item functioning, DIF) before use in clinical practice and research in a different population. In this study, we examined DIF associated with age, gender, ethnicity and chronic illness in a heterogeneous Asian population in Singapore., Methods: The GDS-15 and Structured Clinical Interview for DSM-IV diagnosis of MDD were independently administered by interviewers on 4253 non-institutionalized community living elderly subjects aged 60 years and above who were users of social service agencies. Multiple Indicator Multiple Cause latent variable modelling was used to identify DIF., Results: We found evidence of significant DIF associated with age, gender, ethnicity and chronic illness for 8 items: dropped many activities and interests, afraid something bad is going to happen, prefer staying home to going out, more problems with memory than most, think it is (not) wonderful to be alive, feel pretty worthless, feel (not) full of energy, feel that situation is hopeless., Limitations: The smaller number of minority Indian and Malay subjects and the self-report of chronic medical illnesses., Conclusions: In a heterogeneous mix of respondents in Singapore, eight items of the GDS-15 showed DIF for age, gender, ethnicity and chronic illness. The awareness and identification of DIF in the GDS-15 provides a rational basis for its use in diverse population groups and guiding the derivation of abbreviated scales.

Although extensive research has already been done on the genetic bases of psychiatric disorders, little is known about polygenetic influences in posttraumatic stress disorder (PTSD). This article reviews molecular genetic studies relating to PTSD that were found in a literature search in Medline, Embase and Web of Science. Association studies have investigated 8 major genotypes in connection with PTSD. They have tested hypotheses involving key candidate genes in the serotonin (5-HTT), dopamine (DRD2, DAT), glucocorticoid (GR), GABA (GABRB), apolipoprotein systems (APOE2), brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY). The studies have produced inconsistent results, many of which may be attributable to methodological shortcomings and insufficient statistical power. The complex aetiology of PTSD, for which experiencing a traumatic event forms a necessary condition, makes it difficult to identify specific genes that substantially contribute to the disorder. Gene-finding strategies are difficult to apply. Interactions between different genes and between them and the environment probably make certain people vulnerable to developing PTSD. Gene-environmental studies are needed that focus more narrowly on specific, distinct endophenotypes and on influences from environmental factors.

Nowadays, cardiopulmonary resuscitation is not routinely discussed with all hospital patients, even though it should be for a number of reasons. First of all, every patient may suffer cardiac arrest, and the overall outcome of a subsequent attempt at resuscitation is difficult to predict. Besides, patients who do not wish to be resuscitated often do not tell that to the physician of their own accord. Patients should therefore be more actively informed and encouraged to express their own preferences. The routine discussion of possible resuscitation gives physicians the opportunity to discuss, determine and delimit the extent of the intended medical procedure. In the literature, communication problems in three different areas can be identified as a cause of the present situation. These are--for both physician and patient--inability, lack of insight and unwillingness to discuss resuscitation. Physicians should be aware of the identified communication problems and deal with them in a professional manner. An understanding of these problems forms the basis for a broader implementation of resuscitation discussions in hospitals.