Examining the interaction between prenatal stress and polygenic risk for attention-deficit/hyperactivity disorder on brain growth in childhood: Findings from the DREAM BIG consortium.

This study explored the interactions among prenatal stress, child sex, and polygenic risk scores (PGS) for attention-deficit/hyperactivity disorder (ADHD) on structural developmental changes of brain regions implicated in ADHD. We used data from two population-based birth cohorts: Growing Up in Singapore Towards healthy Outcomes (GUSTO) from Singapore (n = 113) and Generation R from Rotterdam, the Netherlands (n = 433). Prenatal stress was assessed using questionnaires. We obtained latent constructs of prenatal adversity and prenatal mood problems using confirmatory factor analyses. The participants were genotyped using genome-wide single nucleotide polymorphism arrays, and ADHD PGSs were computed. Magnetic resonance imaging scans were acquired at 4.5 and 6 years (GUSTO), and at 10 and 14 years (Generation R). We estimated the age-related rate of change for brain outcomes related to ADHD and performed (1) prenatal stress by sex interaction models, (2) prenatal stress by ADHD PGS interaction models, and (3) 3-way interaction models, including prenatal stress, sex, and ADHD PGS. We observed an interaction between prenatal stress and ADHD PGS on mean cortical thickness annual rate of change in Generation R (i.e., in individuals with higher ADHD PGS, higher prenatal stress was associated with a lower rate of cortical thinning, whereas in individuals with lower ADHD PGS, higher prenatal stress was associated with a higher rate of cortical thinning). None of the other tested interactions were statistically significant. Higher prenatal stress may promote a slower brain developmental rate during adolescence in individuals with higher ADHD genetic vulnerability, whereas it may promote a faster brain developmental rate in individuals with lower ADHD genetic vulnerability.

The longitudinal impact of pre- and postnatal maternal depression and anxiety on children's cognitive and language development.

We investigated the longitudinal associations among maternal pre- and postnatal depression, maternal anxiety, and children's language and cognitive development followed from 15 to 61 months. Furthermore, we assessed the protective role of children's early print experiences with books against the adverse effect of maternal depression on language development. Data for mothers and children (51.7% boys, 95% White, N = 11,662) were from the Avon Longitudinal Study of Parents and Children. Prenatal maternal depression held an adverse association with child language (ß = -.16, p = .002). Moreover, the risk was greater for girls than boys (ß = .19, p = .02). In addition, prenatal depression was significantly and negatively associated with child verbal intelligence quotient (ß = -.11, p = .02) and performance intelligence quotient (ß = -.12, p = .01). In contrast, postnatal depression or anxiety were not unique predictors of child outcomes. Importantly, children's early experiences with books, as measured by the reported frequency of parent-child shared reading, moderated the negative association between maternal depression and child language development (ß = .30, p < .001). Although modest in size, these findings inform models of child risk and resilience related to maternal psychopathology. The results also have implications for clinical programs as well as for prevention and intervention studies focusing on at-home early literacy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Maternal prenatal depression is associated with dysregulation over the first five years of life moderated by child polygenic risk for comorbid psychiatric problems.

Dysregulation is a combination of emotion, behavior, and attention problems associated with lifelong psychiatric comorbidity. There is evidence for the stability of dysregulation from childhood to adulthood, which would be more fully characterized by determining the likely stability from infancy to childhood. Early origins of dysregulation can further be validated and contextualized in association with environmental and biological factors, such as prenatal stress and polygenic risk scores (PRS) for overlapping child psychiatric problems. We aimed to determine trajectories of dysregulation from 3 months to 5 years (N = 582) in association with maternal prenatal depression moderated by multiple child PRS (N = 232 pairs with available PRS data) in a prenatal cohort. Mothers reported depression symptoms at 24-26 weeks' gestation and child dysregulation at 3, 6, 18, 36, 48, and 60 months. The PRS were for major depressive disorder, attention deficit hyperactivity disorder, cross disorder, and childhood psychiatric problems. Covariates were biological sex, maternal education, and postnatal depression. Analyses included latent classes and regression. Two dysregulation trajectories emerged: persistently low dysregulation (94%), and increasingly high dysregulation (6%). Stable dysregulation emerged at 18 months. High dysregulation was associated with maternal prenatal depression, moderated by PRS for child comorbid psychiatric problems. Males were at greater risk of high dysregulation.

Negative emotionality as a candidate mediating mechanism linking prenatal maternal mood problems and offspring internalizing behaviour.

Negative emotionality (NE) was evaluated as a candidate mechanism linking prenatal maternal affective symptoms and offspring internalizing problems during the preschool/early school age period. The participants were 335 mother-infant dyads from the Maternal Adversity, Vulnerability and Neurodevelopment project. A Confirmatory Bifactor Analysis (CFA) based on self-report measures of prenatal depression and pregnancy-specific anxiety generated a general factor representing overlapping symptoms of prenatal maternal psychopathology and four distinct symptom factors representing pregnancy-specific anxiety, negative affect, anhedonia and somatization. NE was rated by the mother at 18 and 36 months. CFA based on measures of father, mother, child-rated measures and a semistructured interview generated a general internalizing factor representing overlapping symptoms of child internalizing psychopathology accounting for the unique contribution of each informant. Path analyses revealed significant relationships among the general maternal affective psychopathology, the pregnancy- specific anxiety, and the child internalizing factors. Child NE mediated only the relationship between pregnancy-specific anxiety and the child internalizing factors. We highlighted the conditions in which prenatal maternal affective symptoms predicts child internalizing problems emerging early in development, including consideration of different mechanistic pathways for different maternal prenatal symptom presentations and child temperament.

Examining attachment, cortisol secretion, and cognitive neurodevelopment in preschoolers and its predictive value for telomere length at age seven.

Background: Secure attachment reflects caregiver-child relationship in which the caregiver is responsive when support and comforting are needed by the child. This pattern of bond has an important buffering role in the response to stress by the reduction of the negative experience and its associated physiological response. Disruption of the physiological stress system is thought to be a central mechanism by which early care impacts children. Early life stress causes cellular and molecular changes in brain regions associated with cognitive functions that are fundamental for early learning. Methods: The association between attachment, cortisol response before and after the Strange Situation Experiment, and neurodevelopment was examined in a sample of 107 preschoolers at age three. Also, the predictive effect of cortisol reactivity and attachment on telomere length at age seven was investigated in a followed-up sample of 77 children. Results: Children with insecure attachment had higher cortisol secretion and poorer neurodevelopmental skills at age three. A significant cortisol change was observed across the experiment with non-significant interaction with attachment. The attachment and neurodevelopment association was not mediated by cortisol secretion. Preschoolers' attachment and cortisol did not associate nor interacted to predict telomere length at age seven. Conclusion: These findings add evidence to the detrimental effects of insecure attachment as an aggravator of the physiological response to stress and poorer neurodevelopment during the preschool period. Although attachment and cortisol were not predictive of telomere length, intervention policies that promote secure attachment are more likely to positively echo on several health domains.

From temperament and parenting to attachment: a review of the interplay of gene and environment factors in the developmental pathway to attachment.

PURPOSE OF REVIEW: Attachment represents an aspect of the parent-child relationship by encapsulating behaviours and stress management strategies. Although attachment is not considered a measure of psychopathology, some attachment styles place children at higher risk for psychopathologies. The origins of attachment have historically thought to be either parenting-related variables, or temperament. More recently, there has been accumulated evidence of gene × environment interactions in attachment, temperament, and parenting. This review aims to cover shared gene × environment pathways between these variables, introduce recent relevant insights from prenatal programming research, and offer a synthesized developmental cascade model of attachment. RECENT FINDINGS: Carriers of gene polymorphisms related to stress neurobiology respond differently to environments than noncarriers according to two patterns: attachment research shows inconsistent diathesis-stress between gene polymorphisms and environment, and temperament, stress physiology, and prenatal programming research show clear patterns of differential susceptibility. SUMMARY: By synthesizing prenatal and postnatal findings, a model of attachment emerges in which individuals more susceptible to environmental influences are carriers of specific genes, whose endophenotypic markers include stress biology and phenotypic markers include temperament. Intervention should, therefore, focus on parenting and stress regulation strategies for these individuals.

Sharing and Safeguarding Pediatric Data.

Data sharing is key to advancing our understanding of human health and well-being. While issues related to pediatric research warrant strong ethical protections, overly protectionist policies may serve to exclude minors from data sharing initiatives. Pediatric data sharing is critical to scientific research concerning health and well-being, to say nothing of understanding human development generally. For example, large-scale pediatric longitudinal studies, such as those in the DREAM-BIG Consortium, on the influence of prenatal adversity factors on child psychopathology, will provide prevention data and generate future health benefits. Recent initiatives have formulated sound policy to help enable and foster data sharing practices for pediatric research. To help translate these policy initiatives into practice, we discuss how model consent clauses for pediatric research can help address some of the issues and challenges of pediatric data sharing, while enabling data sharing.

Combined polygenic risk scores of different psychiatric traits predict general and specific psychopathology in childhood.

BACKGROUND: Polygenic risk scores (PRSs) operationalize genetic propensity toward a particular mental disorder and hold promise as early predictors of psychopathology, but before a PRS can be used clinically, explanatory power must be increased and the specificity for a psychiatric domain established. To enable early detection, it is crucial to study these psychometric properties in childhood. We examined whether PRSs associate more with general or with specific psychopathology in school-aged children. Additionally, we tested whether psychiatric PRSs can be combined into a multi-PRS score for improved performance. METHODS: We computed 16 PRSs based on GWASs of psychiatric phenotypes, but also neuroticism and cognitive ability, in mostly adult populations. Study participants were 9,247 school-aged children from three population-based cohorts of the DREAM-BIG consortium: ALSPAC (UK), The Generation R Study (Netherlands), and MAVAN (Canada). We associated each PRS with general and specific psychopathology factors, derived from a bifactor model based on self-report and parental, teacher, and observer reports. After fitting each PRS in separate models, we also tested a multi-PRS model, in which all PRSs are entered simultaneously as predictors of the general psychopathology factor. RESULTS: Seven PRSs were associated with the general psychopathology factor after multiple testing adjustment, two with specific externalizing and five with specific internalizing psychopathology. PRSs predicted general psychopathology independently of each other, with the exception of depression and depressive symptom PRSs. Most PRSs associated with a specific psychopathology domain, were also associated with general child psychopathology. CONCLUSIONS: The results suggest that PRSs based on current GWASs of psychiatric phenotypes tend to be associated with general psychopathology, or both general and specific psychiatric domains, but not with one specific psychopathology domain only. Furthermore, PRSs can be combined to improve predictive ability. PRS users should therefore be conscious of nonspecificity and consider using multiple PRSs simultaneously, when predicting psychiatric disorders.

Effectiveness and Predictors of Outcomes in a Psychiatric Day Treatment Program for Elementary-Age.

OBJECTIVE: In this study, we aimed to (1) assess the effectiveness of an intensive multimodal day treatment program in improving externalizing problems and function in elementary-age children and (2) examine 3 predictors of the treatment outcome (i.e., family functioning, baseline severity, and comorbid disorders). METHODS: The sample included 261 children (80.9% boys) between ages of 5 and 12. A retrospective chart review, from 2013 to 2018, and a prospective chart review, from 2018 to 2019, were conducted to extract all relevant data for the present study. Parents and teachers provided reports on children's externalizing problems (i.e., aggressive behavior, attention problems, and rule-breaking behavior) and their level of function across different domains. The level of family functioning was also reported by parents, while clinicians assessed children's severity of disturbance and their diagnoses at intake. RESULTS: Based on both parents' and teachers' reports, children showed significant improvement in their externalizing problems. Moreover, children showed functional improvement at home, at school, with peers, and in hobbies by the end of the program. Based on teacher's reports, children with lower level of severity showed less improvement in their attention problems, and those with comorbid developmental problems showed less improvement in their aggressive and rule-breaking behaviors. Family functioning did not predict any treatment outcome. CONCLUSION: An intensive multimodal day treatment program was effective in reducing the symptoms of externalizing problems in elementary-age children. However, children with less severe difficulties and comorbid developmental problems showed less improvement in their externalizing problems.

Mining Early Life Risk and Resiliency Factors and Their Influences in Human Populations from PubMed: A Machine Learning Approach to Discover DOHaD Evidence.

The Developmental Origins of Health and Disease (DOHaD) framework aims to understand how early life exposures shape lifecycle health. To date, no comprehensive list of these exposures and their interactions has been developed, which limits our ability to predict trajectories of risk and resiliency in humans. To address this gap, we developed a model that uses text-mining, machine learning, and natural language processing approaches to automate search, data extraction, and content analysis from DOHaD-related research articles available in PubMed. Our first model captured 2469 articles, which were subsequently categorised into topics based on word frequencies within the titles and abstracts. A manual screening validated 848 of these as relevant, which were used to develop a revised model that finally captured 2098 articles that largely fell under the most prominently researched domains related to our specific DOHaD focus. The articles were clustered according to latent topic extraction, and 23 experts in the field independently labelled the perceived topics. Consensus analysis on this labelling yielded mostly from fair to substantial agreement, which demonstrates that automated models can be developed to successfully retrieve and classify research literature, as a first step to gather evidence related to DOHaD risk and resilience factors that influence later life human health.

Frequent follow-up of suicidal youth assessed in the emergency room: Long-term trajectory and predictors of suicidality.

Suicide was the second­leading cause of US deaths in 2018 among 15-24-year-olds. Suicide attempts, a risk factor for completions, and suicide ideation have doubled among pediatric emergency room (ER) patients during the past decade. Borderline Personality Disorder (BPD), a comorbid condition, has a 10% suicide rate. We examined the 4-year outcome of a cohort of suicidal adolescents, many also suffering from BPD and having undergone some form of treatment, to identify baseline factors which could inform intervention that would minimize suicidality 4 years post-discharge. METHODS: We conducted a prospective longitudinal study of suicidality at twelve points (four assessment occasions) for 286 suicidal youth presenting to a pediatric ER, most suffering from BPD, with 36 suicide ratings from baseline to 2-, 6- and 48-month follow-up evaluations. We examined the trajectory and predictors of persisting suicidality. RESULTS: Suicidality rapidly decreased within 2 months post-ER-discharge, subsequently remaining low throughout 48 months. Baseline functioning, female sex, stressful life events and BPD impulsiveness were most predictive of persisting suicidality at 48-month follow-up. CONCLUSION: Most suicidal youth, many meeting BPD criteria, no longer feel suicidal 2 months after ER discharge. Management of participants' baseline poor functioning stressful life events and the impulsiveness component of BPD specifically in females could impact suicidality 4 years later, and guide treatment options. The absence of the BPD cognitive and affective subscales as predictors of suicidality at 4-year follow-up may reflect treatment received. Further investigation of treatment effects is warranted and under way.

The Interplay Between Prenatal Adversity, Offspring Dopaminergic Genes, and Early Parenting on Toddler Attentional Function.

Background: Few studies have explored the complex gene-by-prenatal environment-by-early postnatal environment interactions that underlie the development of attentional competence. Here, we examined if variation in dopamine-related genes interacts with prenatal adversity to influence toddler attentional competence and whether this influence is buffered by early positive maternal behavior. Methods: From the Maternal Adversity, Vulnerability and Neurodevelopment cohort, 134 participants (197 when imputing missing data) had information on prenatal adversity (prenatal stressful life events, prenatal maternal depressive symptoms, and birth weight), five dopamine-related genes (DAT1, DRD4, DRD2, COMT, BDNF), observed maternal parenting behavior at 6 months and parent-rated toddler attentional competence at 18 and 24 months. The Latent Environmental and Genetic Interaction (LEGIT) approach was used to examine genes-by-prenatal environment-by-postnatal environment interactions while controlling for sociodemographic factors and postnatal depression. Results: Our hypothesis of a three-way interaction between prenatal adversity, dopamine-related genes, and early maternal parenting behavior was not confirmed. However, consistent two-way interactions emerged between prenatal adversity and dopamine-related genes; prenatal adversity and maternal parenting behavior, and dopamine-related genes and maternal parenting behavior in relation to toddler attentional competence. Significant interaction effects were driven by the DAT1, COMT, and BDNF genotypes; prenatal stressful life events; maternal sensitivity, tactile stimulation, vocalization, and infant-related activities. Conclusions: Multiple dopamine-related genes affected toddler attentional competence and they did so in interaction with prenatal adversity and the early rearing environment, separately. Effects were already visible in young children. Several aspects of early maternal parenting have been identified as potential targets for intervention.

Early life risk and resiliency factors and their influences on developmental outcomes and disease pathways: a rapid evidence review of systematic reviews and meta-analyses.

The Developmental Origins of Health and Disease (DOHaD) framework aims to understand how environmental exposures in early life shape lifecycle health. Our understanding and the ability to prevent poor health outcomes and enrich for resiliency remain limited, in part, because exposure-outcome relationships are complex and poorly defined. We, therefore, aimed to determine the major DOHaD risk and resilience factors. A systematic approach with a 3-level screening process was used to conduct our Rapid Evidence Review following the established guidelines. Scientific databases using DOHaD-related keywords were searched to capture articles between January 1, 2009 and April 19, 2019. A final total of 56 systematic reviews/meta-analyses were obtained. Studies were categorized into domains based on primary exposures and outcomes investigated. Primary summary statistics and extracted data from the studies are presented in Graphical Overview for Evidence Reviews diagrams. There was substantial heterogeneity within and between studies. While global trends showed an increase in DOHaD publications over the last decade, the majority of data reported were from high-income countries. Articles were categorized under six exposure domains: Early Life Nutrition, Maternal/Paternal Health, Maternal/Paternal Psychological Exposure, Toxicants/Environment, Social Determinants, and Others. Studies examining social determinants of health and paternal influences were underrepresented. Only 23% of the articles explored resiliency factors. We synthesized major evidence on relationships between early life exposures and developmental and health outcomes, identifying risk and resiliency factors that influence later life health. Our findings provide insight into important trends and gaps in knowledge within many exposures and outcome domains.

Measuring resilience in children: a review of recent literature and recommendations for future research.

PURPOSE OF REVIEW: Understanding variability in developmental outcomes following exposure to early life adversity (ELA) has been an area of increasing interest in psychiatry, as resilient outcomes are just as prevalent as negative ones. However, resilient individuals are understudied in most cohorts and even when studied, resilience is typically defined as an absence of psychopathology. This review examines current approaches to resilience and proposes more comprehensive and objective ways of defining resilience. RECENT FINDINGS: Of the 36 studies reviewed, the most commonly used measure was the Strengths and Difficulties Questionnaire (n = 6), followed by the Child Behavior Checklist (n = 5), the Resilience Scale for Chinese Adolescents (n = 5), the Rosenberg Self-Esteem Scale (n = 4), and the Child and Youth Resilience Scale (n = 3). SUMMARY: This review reveals that studies tend to rely on self-report methods to capture resilience which poses some challenges. We propose a complementary measure of child resilience that relies on more proactive behavioral and observational indicators; some of our preliminary findings are presented. Additionally, concerns about the way ELA is characterized as well as the influence of genetics on resilient outcomes prompts further considerations about how to proceed with resiliency research.

Maternal Prenatal Mood, Pregnancy-Specific Worries, and Early Child Psychopathology: Findings From the DREAM BIG Consortium.

OBJECTIVE: Few studies have attempted to identify how distinct dimensions of maternal prenatal affective symptoms relate to offspring psychopathology. We defined latent dimensions of women's prenatal affective symptoms and pregnancy-specific worries to examine their association with early offspring psychopathology in three prenatal cohorts. METHOD: Data were used from three cohorts of the DREAM-BIG consortium: Avon Longitudinal Study of Parents and Children (ALSPAC [N = 12,515]), Generation R (N = 6,803), and the Canadian prenatal cohort Maternal Adversity, Vulnerability, and Neurodevelopment (MAVAN [N = 578]). Maternal prenatal affective symptoms and pregnancy-specific worries were assessed using different measures in each cohort. Through confirmatory factor analyses, we determined whether comparable latent dimensions of prenatal maternal affective symptoms existed across the cohorts. We used structural equation models to examine cohort-specific associations between these dimensions and offspring psychopathology at 4 to 8 years of age (general psychopathology, specific internalizing and externalizing previously derived using confirmatory factor analyses). Cohort-based estimates were meta-analyzed using inverse variance-weighing. RESULTS: Four prenatal maternal factors were similar in all cohorts: a general affective symptoms factor and three specific factors-an anxiety/depression factor, a somatic factor, and a pregnancy-specific worries factor. In meta-analyses, both the general affective symptoms factor and pregnancy-specific worries factor were independently associated with offspring general psychopathology. The general affective symptoms factor was further associated with offspring specific internalizing problems. There were no associations with specific externalizing problems. CONCLUSION: These replicated findings of independent and adverse effects for prenatal general affective symptoms and pregnancy-specific worries on child mental health support the need for specific interventions in pregnancy.

Distinguishing differential susceptibility, diathesis-stress, and vantage sensitivity: Beyond the single gene and environment model.

Currently, two main approaches exist to distinguish differential susceptibility from diathesis-stress and vantage sensitivity in Genotype × Environment interaction (G × E) research: regions of significance (RoS) and competitive-confirmatory approaches. Each is limited by its single-gene/single-environment foci given that most phenotypes are the product of multiple interacting genetic and environmental factors. We thus addressed these two concerns in a recently developed R package (LEGIT) for constructing G × E interaction models with latent genetic and environmental scores using alternating optimization. Herein we test, by means of computer simulation, diverse G × E models in the context of both single and multiple genes and environments. Results indicate that the RoS and competitive-confirmatory approaches were highly accurate when the sample size was large, whereas the latter performed better in small samples and for small effect sizes. The competitive-confirmatory approach generally had good accuracy (a) when effect size was moderate and N ≥ 500 and (b) when effect size was large and N ≥ 250, whereas RoS performed poorly. Computational tools to determine the type of G × E of multiple genes and environments are provided as extensions in our LEGIT R package.

Dissecting maternal care: Patterns of maternal parenting in a prospective cohort study.

Parental care has a strong impact on neurodevelopment and mental health in the offspring. Although numerous animal studies have revealed that the parental brain is a highly complex system involving many brain structures and neuroendocrine systems, human maternal parenting as a multidimensional construct with cognitive, emotional, and behavioural components has not been characterised comprehensively. This unique multi-method analysis aimed to examine patterns of self-reported and observed parenting from 6 to 60 months postpartum in a cohort of 496 mothers (mean maternal age = 32 years). Self-report questionnaires assessed motivational components of mothering, parenting stress, parenting-related mood, maternal investment, maternal parenting style, mother-child relationship satisfaction, and mother-child bonding at multiple time points. Observed parenting variables included the Ainsworth Sensitivity Scales at 6 and 18 months, the Behavioral Evaluation Strategies Taxonomies at 6 months, an Etch-A-Sketch cooperation task at 48 months, and the Parent-Child Early Relationship Assessment at 60 months. To examine whether different latent constructs underlie these measures of maternal parenting, we conducted an exploratory factor analysis. Self-report measures of parenting correlated only weakly with behavioural observations. Factor analysis on a subsample (n = 197) revealed four latent factors that each explained from 7% to 11% of the variance in the data (32% total variance explained). Based on the loadings of the instruments, the factors were interpreted as: Supportive Parenting, Self-Enjoyment Parenting, Overwhelmed Parenting, and Affectionate Parenting. These factor scores showed specific associations with maternal education and depressive symptoms, as well as with child outcomes, including maternally reported internalising and externalising behavioural problems, school readiness, and child-reported symptoms of mental health. These findings parallel the complexity of the parental brain, suggesting that maternal parenting consists of multiple components, each of which is associated with different maternal characteristics and child outcomes.

General psychopathology, internalising and externalising in children and functional outcomes in late adolescence.

BACKGROUND: Internalising and externalising problems commonly co-occur in childhood. Yet, few developmental models describing the structure of child psychopathology appropriately account for this comorbidity. We evaluate a model of childhood psychopathology that separates the unique and shared contribution of individual psychological symptoms into specific internalising, externalising and general psychopathology factors and assess how these general and specific factors predict long-term outcomes concerning criminal behaviour, academic achievement and affective symptoms in three independent cohorts. METHODS: Data were drawn from independent birth cohorts (Avon Longitudinal Study of Parents and Children (ALSPAC), N = 11,612; Generation R, N = 7,946; Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN), N = 408). Child psychopathology was assessed between 4 and 8 years using a range of diagnostic and questionnaire-based measures, and multiple informants. First, structural equation models were used to assess the fit of hypothesised models of shared and unique components of psychopathology in all cohorts. Once the model was chosen, linear/logistic regressions were used to investigate whether these factors were associated with important outcomes such as criminal behaviour, academic achievement and well-being from late adolescence/early adulthood. RESULTS: The model that included specific factors for internalising/externalising and a general psychopathology factor capturing variance shared between symptoms regardless of their classification fits well for all of the cohorts. As hypothesised, general psychopathology factor scores were predictive of all outcomes of later functioning, while specific internalising factor scores predicted later internalising outcomes. Specific externalising factor scores, capturing variance not shared by any other psychological symptoms, were not predictive of later outcomes. CONCLUSIONS: Early symptoms of psychopathology carry information that is syndrome-specific as well as indicative of general vulnerability and the informant reporting on the child. The 'general psychopathology factor' might be more relevant for long-term outcomes than specific symptoms. These findings emphasise the importance of considering the co-occurrence of common internalising and externalising problems in childhood when considering long-term impact.

Alternating optimization for G × E modelling with weighted genetic and environmental scores: Examples from the MAVAN study.

Motivated by the goal of expanding currently existing Genotype × Environment interaction (G × E) models to simultaneously include multiple genetic variants and environmental exposures in a parsimonious way, we developed a novel method to estimate the parameters in a G × E model, where G is a weighted sum of genetic variants (genetic score) and E is a weighted sum of environments (environmental score). The approach uses alternating optimization, an iterative process where the genetic score weights, the environmental score weights, and the main model parameters are estimated in turn, assuming the other parameters are constant. This technique can be used to construct relatively complex interaction models that are constrained to a particular structure, and hence contain fewer parameters. We present the model as a 2-way interaction longitudinal mixed model, for which ordinary linear regression is a special case, but it can easily be extended to be compatible with k-way interaction models and generalized linear mixed models. The model is implemented in R (LEGIT package) and using SAS macros (LEGIT_SAS). Through simulations, we demonstrate the power and validity of this approach even with small sample sizes. Furthermore, we present examples from the Maternal Adversity, Vulnerability, and Neurodevelopment (MAVAN) study where we improve significantly upon already existing models using alternating optimization. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The dopamine D4 receptor gene, birth weight, maternal depression, maternal attention, and the prediction of disorganized attachment at 36 months of age: A prospective gene×environment analysis.

BACKGROUND: Efforts to understand the developmental pathways for disorganized attachment reflect the importance of disorganized attachment on the prediction of future psychopathology. The inconsistent findings on the prediction of disorganized attachment from the dopamine D4 receptor (DRD4) gene, birth weight, and maternal depression as well as the evidence supporting the contribution of early maternal care, suggest the importance of exploring a gene by environment model. METHODS: Our sample is from the Maternal Adversity, Vulnerability, and Neurodevelopment project; consisting of 655 mother-child dyads. Birth weight was cross-referenced with normative data to calculate birth weight percentile. Infant DRD4 genotype was obtained with buccal swabs and categorized according to the presence of the 7-repeat allele. Maternal depression was assessed with the Center for Epidemiologic Studies Depression Scale at the prenatal, 6-, 12-, and 24-month assessments. Maternal attention was measured at 6-months using a videotaped session of a 20-min non-feeding interaction. Attachment was assessed at 36-months using the Strange Situation Procedure. RESULTS: The presence of the DRD4 7-repeat allele was associated with less disorganized attachment, ß=-1.11, OR=0.33, p=0.0008. Maternal looking away frequency showed significant interactions with maternal depression at the prenatal assessment, ß=0.003, OR=1.003, p=0.023, and at 24 months, ß=0.004, OR=1.004, p=0.021, as at both time points, women suffering from depression and with frequent looking away behavior had an increased probability of disorganized attachment in their child, while those with less looking away behavior had a decreased probability of disorganized attachment in their child at 36 months. CONCLUSIONS: Our models support the contribution of biological and multiple environmental factors in the complex prediction of disorganized attachment at 36 months.