Associations between Social Adversity and Biomarkers of Inflammation, Stress, and Aging in Children.

BACKGROUND: Prior work has found relationships between childhood social adversity and biomarkers of stress, but knowledge gaps remain. To help address these gaps, we explored associations between social adversity and biomarkers of inflammation (interleukin-1ß [IL-1ß], IL-6, IL-8, tumor necrosis factor-alpha [TNF-α], and salivary cytokine hierarchical "clusters" based on the three interleukins), neuroendocrine function (cortisol, cortisone, dehydroepiandrosterone, testosterone, and progesterone), neuromodulation (N-arachidonoylethanolamine, stearoylethanolamine, oleoylethanolamide, and palmitoylethanolamide), and epigenetic aging (Pediatric-Buccal-Epigenetic clock). METHODS: We collected biomarker samples of children ages 0-17 recruited from an acute care pediatrics clinic and examined their associations with caregiver-endorsed education, income, social risk factors, and cumulative adversity. We calculated regression-adjusted means for each biomarker and compared associations with social factors using Wald tests. We used logistic regression to predict being in the highest cytokine cluster based on social predictors. RESULTS: Our final sample included 537 children but varied based on each biomarker. Cumulative social adversity was significantly associated with having higher levels of all inflammatory markers and with cortisol, displaying a U-shaped distribution. There were no significant relationships between cumulative social adversity and cortisone, neuromodulation biomarkers or epigenetic aging. CONCLUSION: Our findings support prior work suggesting that social stress exposures contribute to increased inflammation in children. IMPACT: Our study is one of the largest studies examining associations between childhood social adversity and biomarkers of inflammation, neuroendocrine function, neuromodulation, and epigenetic aging. It is one of the largest studies to link childhood social adversity to biomarkers of inflammation, and the first of which we are aware to link cumulative social adversity to cytokine clusters. It is also one of the largest studies to examine associations between steroids and epigenetic aging among children, and one of the only studies of which we are aware to examine associations between social adversity and endocannabinoids among children. CLINICAL TRIAL REGISTRATION: NCT02746393.

Household Social Needs, Emotional Functioning, and Stress in Low-Income Latinx Children and their Mothers.

Latinx families may be particularly vulnerable to emotional dysfunction, due to higher rates of economic hardship and complex social influences in this population. Little is known about the impact of environmental stressors such as unmet social needs and maternal stress on the emotional health of Latinx children from low-income families. We conducted secondary analyses using survey and biomarker data from 432 Latinx children and mothers collected in a separate study. We used binomial and multinomial logistic regression to test if household social needs, or maternal perceived stress or hair cortisol concentration (HCC), predicted child measures of emotional functioning or child HCC, independent of relevant sociodemographic factors. Approximately 40% of children in the sample had symptoms consistent with emotional dysfunction, and over 37% of households reported five or more social needs. High perceived maternal stress predicted higher odds of child emotional dysfunction (OR = 2.15; 95% CI [1.14, 4.04]; p = 0.01), and high maternal HCC was positively associated with high child HCC (OR = 10.60; 95% CI [4.20, 26.74]; p < 0.01). Most individual household social needs, as well as the level of household social need, were not independently associated with child emotional dysfunction or child HCC. Our findings begin to define a framework for understanding emotional health, stress, and resilience when caring for Latinx children and mothers living with high levels of social need, and the need for integrated mental health and social needs screening and interventions in settings that serve this population.

Unmet Social Needs and Patterns of Hair Cortisol Concentration in Mother-Child Dyads.

Background: Mothers and their children demonstrate dyadic synchrony of hypothalamic-pituitary-adrenal (HPA) axis function, likely influenced by shared genetic or environmental factors. Although evidence has shown that chronic stress exposure has physiologic consequences for individuals-including on the HPA axis-minimal research has explored how unmet social needs such as food and housing instability may be associated with chronic stress and HPA axis synchrony in mother-child dyads. Methods: We conducted a secondary analysis of data from 364 mother-child dyads with low-income recruited during a randomized trial conducted in an urban pediatric clinic. We used latent profile analysis (LPA) to identify subgroups based on naturally occurring patterns of within-dyad hair cortisol concentration (HCC). A logistic regression model predicted dyadic HCC profile membership as a function of summative count of survey-reported unmet social needs, controlling for demographic and health covariates. Results: LPA of HCC data from dyads revealed a 2-profile model as the best fit. Comparisons of log HCC for mothers and children in each profile group resulted in significantly "higher dyadic HCC" versus "lower dyadic HCC" profiles (median log HCC for mothers: 4.64 vs 1.58; children: 5.92 vs 2.79, respectively; P < .001). In the fully adjusted model, each one-unit increase in number of unmet social needs predicted significantly higher odds of membership in the higher dyadic HCC profile when compared to the lower dyadic HCC profile (odds ratio = 1.13; 95% confidence interval [1.04-1.23]; P = .01). Conclusion: Mother-child dyads experience synchronous patterns of physiologic stress, and an increasing number of unmet social needs is associated with a profile of higher dyadic HCC. Interventions aimed at decreasing family-level unmet social needs or maternal stress are, therefore, likely to affect pediatric stress and related health inequities; efforts to address pediatric stress similarly may affect maternal stress and related health inequities. Future research should explore the measures and methods needed to understand the impact of unmet social needs and stress on family dyads.

Linking specific biological signatures to different childhood adversities: findings from the HERO project.

BACKGROUND: Although investigations have begun to differentiate biological and neurobiological responses to a variety of adversities, studies considering both endocrine and immune function in the same datasets are limited. METHODS: Associations between proximal (family functioning, caregiver depression, and anxiety) and distal (SES-D; socioeconomic disadvantage) early-life adversities with salivary inflammatory biomarkers (IL-1ß, IL-6, IL-8, and TNF-α) and hair HPA markers (cortisol, cortisone, and dehydroepiandrosterone) were examined in two samples of young U.S. children (N = 142; N = 145). RESULTS: Children exposed to higher SES-D had higher levels of TNF-α (B = 0.13, p = 0.011), IL-1ß (B = 0.10, p = 0.033), and DHEA (B = 0.16, p = 0.011). Higher family dysfunction was associated with higher cortisol (B = 0.08, p = 0.033) and cortisone (B = 0.05, p = 0.003). An interaction between SES-D and family dysfunction was observed for cortisol levels (p = 0.020) whereby children exposed to lower/average levels of SES-D exhibited a positive association between family dysfunction and cortisol levels, whereas children exposed to high levels of SES-D did not. These findings were partially replicated in the second sample. CONCLUSIONS: Our results indicate that these biological response systems may react differently to different forms of early-life adversity. IMPACT: Different forms of early-life adversity have varied stress signatures, and investigations of early-life adversities with inflammation and HPA markers are lacking. Children with higher socioeconomic disadvantage had higher TNF-α, IL-1ß, and DHEA. Higher family dysfunction was associated with higher hair cortisol and cortisone levels, and the association between family dysfunction and cortisol was moderated by socioeconomic disadvantage. Biological response systems (immune and endocrine) were differentially associated with distinct forms of early-life adversities.

O papel da frequência a instituições de educação infantil e de variáveis do ambiente doméstico no desenvolvimento da criança de zero a seis anos / El papel de la asistencia a las instituciones de educación inicial y las variables del entorno familiar en el desarrollo de los niños de cero a seis años / The Role of Attending Child Daycare Institutions and Domestic Environment in the Development of Children from Zero to Six Years of Age

O desenvolvimento infantil é um campo de estudo complexo e deve ser analisado de maneira integrada, considerando os contextos nos quais a criança está in-serida. A frequência a instituições de educação infantil (iei) é indicada pela literatura internacional como um facilitador dos domínios do desenvolvimento, contudo, não há consenso nos dados brasileiros já apresentados. Pontua-se que outras variáveis do ambiente doméstico, como dispor de brinquedos e materiais variados e o tempo de interação com a mãe, possam influenciar nes-sa relação. O objetivo do estudo é comparar crianças que frequentam ou não iei em relação aos domínios do desenvolvimento, considerando grupo etário, tipo de escola e variáveis do ambiente doméstico. Participa-ram 1.843 mães de crianças de quatro a 72 meses, que responderam a um questionário sociodemográfico e ao Inventário Dimensional de Avaliação do Desenvolvi-mento Infantil. Os resultados apontaram que crianças que não frequentam iei apresentaram melhores médias nos domínios Motricidade Ampla e Linguagem Recepti-va em faixas etárias específicas. Dispor de brinquedos e materiais variados e o tempo que a mãe empregava para brincadeiras com a criança demonstraram um impacto positivo em diferentes domínios do desenvolvimento, no entanto, não houve interação com a frequência à iei. Verificou-se que quanto mais horas a mãe dispõe para brincadeiras durante a semana, melhores são as médias alcançadas em diferentes domínios do desenvolvimento de crianças de iei públicas e privadas. Discute-se o papel da educação infantil no desenvolvimento integral da criança, especialmente sobre a qualidade das iei e a necessidade de práticas baseadas em evidências.

El desarrollo infantil es un campo de estudio complejo y debe ser analizado de forma integrada, consideran-do los contextos del niño. La literatura internacional señala a la asistencia a las instituciones de educación infantil (iei) como un facilitador de los dominios del desarrollo, pero, no hay consenso en los datos brasileños. Otras variables del ambiente doméstico, como tener juguetes y materiales diferentes, y el tiempo de interacción con la madre, podrían influir en esta relación. El objetivo del estudio es comparar a los niños que asisten o no a una iei en relación a los dominios de desarrollo, considerando grupo etario, tipo de es-cuela y variables del ambiente del hogar. Participaron 1.843 madres de niños de cuatro a 72 meses, quienes respondieron un cuestionario sociodemográfico y el Inventario Dimensional para la Evaluación del Desarrollo Infantil. Los niños que no asisten a una iei tienen mejores promedios en los dominios Motricidad Gruesa y Lenguaje Receptivo en grupos de edad específicos. Tener diferentes juguetes y materiales, y el tiempo que la madre dedicaba a jugar con el niño demostró un impacto positivo en diferentes dominios, pero, no hubo interacción con la asistencia a una iei. Mientras más horas tiene la madre para jugar durante la semana, mejores son los promedios en los diferentes dominios de desarrollo de los niños con iei pública y privada. Se discute el papel de la educación inicial en el desarrollo integral, especialmente la calidad de la iei y la necesidad de prácticas basadas en evidencias.

Child development is a complex field that should be ana-lyzed comprehensively, considering children's contexts. The international literature indicates attendance to child daycare institutions (cdi) as a facilitator for child development. However, there is no consensus regarding Brazilian data. Other variables of the child's domestic environment, such as having various toys and materials and the time of interaction with the mother, may influence this relationship. This study aimed to compare children attending or not attending cdi regarding developmental domains and considering age group, type of school, and do-mestic environment variables. A total of 1.843 mothers of children aged zero to 72 months participated, answer-ing a sociodemographic questionnaire and the In-ventário Dimensional de Avaliação do Desenvolvimento Infantil (idadi). The results showed that children who did not attend cdi had better averages in Gross Motor Skills and Receptive Language domains in specific age groups. Having a variety of toys and materials and the time the mother spends playing with the child had a positive impact on different developmental domains; however, there was no interaction with attending cdi. It was found that the more hours the mother played with the child during the week, the better the averages achieved in different domains of development for chil-dren attending public or private cdi. The role of early childhood education in integral child development is discussed, especially the quality of cdi and the need for evidence-based practices.

Leptin receptor co-expression gene network moderates the effect of early life adversity on eating behavior in children.

Leptin influences eating behavior. Exposure to early adversity is associated with eating behaviour disorders and metabolic syndrome, but the role of the leptin receptor on this relationship is poorly explored. We investigated whether individual differences in brain region specific leptin receptor (LepR) gene networks could moderate the effects of early adversity on eating behavior and metabolism. We created an expression-based polygenic risk score (ePRS) reflecting variations in the function of LepR gene network in prefrontal cortex and hypothalamus to investigate the interactions between a cumulative index of postnatal adversity on eating behavior in two independent birth cohorts (MAVAN and GUSTO). To explore whether variations in the prefrontal cortex or hypothalamic genetic scores could be associated with metabolic measurements, we also assessed the relationship between LepR-ePRS and fasting blood glucose and leptin levels in a third independent cohort (ALSPAC). We identified significant interaction effects between postnatal adversity and prefrontal-based LepR-ePRS on the Child Eating Behavior Questionnaire scores. In MAVAN, we observed a significant interaction effect on food enjoyment at 48 months (ß = 61.58, p = 0.015) and 72 months (ß = 97.78, p = 0.001); food responsiveness at 48 months (ß = 83.79, p = 0.009) satiety at 48 months (ß = -43.63, p = 0.047). Similar results were observed in the GUSTO cohort, with a significant interaction effect on food enjoyment (ß = 30.48, p = 0.006) food fussiness score (ß = -24.07, p = 0.02) and satiety score at 60 months (ß = -17.00, p = 0.037). No effects were found when focusing on the hypothalamus-based LepR-ePRS on eating behavior in MAVAN and GUSTO cohorts, and there was no effect of hypothalamus and prefrontal cortex based ePRSs on metabolic measures in ALSPAC. Our study indicated that exposure to postnatal adversity interacts with prefrontal cortex LepR-ePRS to moderate eating behavior, suggesting a neurobiological mechanism associated with the development of eating behavior problems in response to early adversity. The knowledge of these mechanisms may guide the understanding of eating patterns associated with risk for obesity in response to fluctuations in stress exposure early in life.

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.

Thrifty-Eating Behavior Phenotype at the Food Court - Programming Goes Beyond Food Preferences.

Introduction: Prenatal growth impairment leads to higher preference for palatable foods in comparison to normal prenatal growth subjects, which can contribute to increased body fat mass and a higher risk for developing chronic diseases in small-for-gestational-age (SGA) individuals throughout life. This study aimed to investigate the effect of SGA on feeding behavior in children and adolescents, as well as resting-state connectivity between areas related to reward, self-control, and value determination, such as orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DL-PFC), amygdala and dorsal striatum (DS). Methods: Caregivers and their offspring were recruited from two independent cohorts in Brazil (PROTAIA) and Canada (MAVAN). Both cohorts included anthropometric measurements, food choice tasks, and resting-state functional magnetic resonance imaging (fMRI) data. Results: In the Brazilian sample (17 ± 0.28 years, n=70), 21.4% of adolescents were classified as SGA. They exhibited lower monetary-related expenditure to buy a snack compared to controls in the food choice test. Decreased functional connectivity (n=40) between left OFC and left DL-PFC; and between right OFC and: left amygdala, right DS, and left DS were observed in the Brazilian SGA participants. Canadian SGA participants (14.9%) had non-significant differences in comparison with controls in a food choice task at 4 years old ( ± 0.01, n=315). At a follow-up brain scan visit (10.21 ± 0.140 years, n=49), SGA participants (28.6%) exhibited higher connectivity between the left OFC and left DL-PFC, also higher connectivity between the left OFC and right DL-PFC. We did not observe significant anthropometric neither nutrients' intake differences between groups in both samples. Conclusions: Resting-state fMRI results showed that SGA individuals had altered connectivity between areas involved in encoding the subjective value for available goods and decision-making in both samples, which can pose them in disadvantage when facing food options daily. Over the years, the cumulative exposure to particular food cues together with the altered behavior towards food, such as food purchasing, as seen in the adolescent cohort, can play a role in the long-term risk for developing chronic non-communicable diseases.

Cognitive Development and Brain Gray Matter Susceptibility to Prenatal Adversities: Moderation by the Prefrontal Cortex Brain-Derived Neurotrophic Factor Gene Co-expression Network.

Background: Previous studies focused on the relationship between prenatal conditions and neurodevelopmental outcomes later in life, but few have explored the interplay between gene co-expression networks and prenatal adversity conditions on cognitive development trajectories and gray matter density. Methods: We analyzed the moderation effects of an expression polygenic score (ePRS) for the Brain-derived Neurotrophic Factor gene network (BDNF ePRS) on the association between prenatal adversity and child cognitive development. A score based on genes co-expressed with the prefrontal cortex (PFC) BDNF was created, using the effect size of the association between the individual single nucleotide polymorphisms (SNP) and the BDNF expression in the PFC. Cognitive development trajectories of 157 young children from the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) cohort were assessed longitudinally in 4-time points (6, 12, 18, and 36 months) using the Bayley-II mental scales. Results: Linear mixed-effects modeling indicated that BDNF ePRS moderates the effects of prenatal adversity on cognitive growth. In children with high BDNF ePRS, higher prenatal adversity was associated with slower cognitive development in comparison with those exposed to lower prenatal adversity. Parallel-Independent Component Analysis (pICA) suggested that associations of expression-based SNPs and gray matter density significantly differed between low and high prenatal adversity groups. The brain IC included areas involved in visual association processes (Brodmann area 19 and 18), reallocation of attention, and integration of information across the supramodal cortex (Brodmann area 10). Conclusion: Cognitive development trajectories and brain gray matter seem to be influenced by the interplay of prenatal environmental conditions and the expression of an important BDNF gene network that guides the growth and plasticity of neurons and synapses.

Salivary cytokine cluster moderates the association between caregivers perceived stress and emotional functioning in youth.

Some individuals exposed to early life stress show evidence of enhanced systemic inflammation and are at greater risk for psychopathology. In the current study, caregivers and their offspring (0-17 years) were recruited at a pediatric clinic visit at the University of California, San Francisco (UCSF). Mothers and seven-year-old children from the Growing Up inSingaporeTowards healthy Outcomes (GUSTO) prospective birth cohort were used as a replication cohort. Caregivers perceived stress was measured to determine potential intergenerational effects on the children's functioning and inflammation levels. Children's emotional functioning in the UCSF cohort was evaluated using the Pediatric Quality of Life (PedsQL) inventory. Child emotional and behavioral functioning was measured using the Child Behavior Checklist (CBCL) in GUSTO. Saliva was collected from the children and salivary levels of IL-6, IL-1ß, IL-8 and TNF-α were measured using an electrochemiluminescent cytokine multiplex panel. Child IL-6, IL-1ß, IL-8 cytokine levels were clustered into low, average, and high cytokine cluster groups using hierarchical cluster analysis. We did not find that salivary cytokine clusters were significantly associated with children's emotional or behavioral function. However, cytokine clusters did significantly moderate the association between increased caregiver perceived stress and reduced child emotional functioning (UCSF cohort) and increased Attention-Deficit-Hyperactivity (ADH) problems (GUSTO cohort, uncorrected Cohen's F2 = 0.02). Using a cytokine clustering technique may be useful in identifying those children exposed to increased caregiver perceived stress that are at risk of emotional and attention deficit hyperactivity problems.

Validation of the short version of the dimensional inventory for child development assessment.

OBJECTIVES: There is a critical need to monitor the development of children around the world, and in Brazil, this need is substantial since there is a paucity of assessment tools. This study aimed to describe the design and provide evidence of reliability and validity for the short version of the Dimensional Inventory for Child Development Assessment (IDADI-short). METHODS: A sample of 1,865 biological mothers of children aged 4-72 months (M = 34.8, SD = 20.20) completed the IDADI to assess Cognitive, socio-emotional, Expressive, and Receptive Language and Communication, Fine and Gross Motor, and Adaptive Behavior development. The psychometric properties of a total of 118 subscales of IDADI were obtained and the IDADI-short age-specific scores were correlated with the original inventory, and criteria variables such as neurodevelopment diagnosis, socioeconomic status, and sex. RESULTS: Item Response Theory analysis, Cronbach's Alpha, and McDonald's Omega indicated excellent internal consistency and optimal participant discrimination after minor alterations. IDADI-short scores were strongly associated with the original inventory, with high sensibility and specificity precision for developmental delays. Significant associations with relevant criteria variables were also observed. CONCLUSION: Findings support the use of IDADI-short as a parental measure of young children's development.

The Revised Mood Rhythm Instrument: A Large Multicultural Psychometric Study.

BACKGROUND: Recent studies with the mood rhythm instrument (MRhI) have shown that the presence of recurrent daily peaks in specific mood symptoms are significantly associated with increased risk of psychiatric disorders. Using a large sample collected in Brazil, Spain, and Canada, we aimed to analyze which MRhI items maintained good psychometric properties across cultures. As a secondary aim, we used network analysis to visualize the strength of the association between the MRhI items. METHODS: Adults (n = 1275) between 18-60 years old from Spain (n = 458), Brazil (n = 415), and Canada (n = 401) completed the MRhI and the self-reporting questionnaire (SRQ-20). Psychometric analyses followed three steps: Factor analysis, item response theory, and network analysis. RESULTS: The factor analysis indicated the retention of three factors that grouped the MRhI items into cognitive, somatic, and affective domains. The item response theory analysis suggested the exclusion of items that displayed a significant divergence in difficulty measures between countries. Finally, the network analysis revealed a structure where sleepiness plays a central role in connecting the three domains. These psychometric analyses enabled a psychometric-based refinement of the MRhI, where the 11 items with good properties across cultures were kept in a shorter, revised MRhI version (MRhI-r). LIMITATIONS: Participants were mainly university students and, as we did not conduct a formal clinical assessment, any potential correlations (beyond the validated SRQ) cannot be ascertained. CONCLUSIONS: The MRhI-r is a novel tool to investigate self-perceived rhythmicity of mood-related symptoms and behaviors, with good psychometric properties across multiple cultures.

Brain structural abnormalities in six major psychiatric disorders: shared variation and network perspectives.

Common brain abnormalities are a possible explanation for comorbidities in psychiatric disorders. Challenges in understanding these conditions are likely due to the paucity of studies able to analyze the extent and regional distribution of shared morphometric abnormalities between disorders. Recently, Opeal et al. presented an elegant rationale to investigate shared and specific morphometric measures of cortical thickness and subcortical gray matter volume between healthy individuals and subjects across six major psychiatric disorders. Although their approach has the potential to systematically portrait shared brain alterations, the chosen principal component analysis solution may not address the central question of the observed shared versus specific brain alterations due to misspecification of the number of components. Given how this misspecification can lead to different conclusions, we reanalyzed Opel et al. data to thoroughly determine the number of factors to be considered, explore the alternative solution, and visualize the patterns of shared brain matter correlations using network analysis. Our approach suggests that a unidimensional solution was appropriate in this situation. The unidimensional solution indicated that brain alterations in autism spectrum disorder (ASD) had a significant negative component loading, suggesting that brain abnormalities found in ASD carry more similarities with major depressive disorder (MDD), bipolar disorder (BD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) than demonstrated by the original work. Network analysis indicated that SCZ had the highest strength, BD the highest closeness, and BD and MDD had the highest betweenness in the network. This work highlights how different component solutions can lead to different conclusions, with important implications for the understanding of overlapped patterns of symptoms among six major psychiatric diseases. The network approach is complementary in indicating central markers of specific psychopathology domains. Investigations using shared-variation and network perspectives are promising for the study of pathophysiological patterns of common brain alterations.

Evidence of validity and reliability of the adaptive functioning scale for intellectual disability (EFA-DI).

Intellectual disability (ID) is a developmental disorder characterized by deficits in intellectual functioning and adaptive behavior. The fifth edition of the Diagnostic and statistical manual of mental disorders (DSM-5) defines adaptive functioning as a severity measure of ID. The availability of tests in the international context to assess this construct has increased in recent years. In Brazil, however, non-systematic assessment of adaptive functioning, such as through observation and interviews, still predominates. The Escala de Funcionamento Adaptativo para Deficiência Intelectual EFA-DI [Adaptive Functioning Scale for Intellectual Disabilities] is a new instrument developed in Brazil to assess the adaptive functioning of 7- to 15-year-old children and support the diagnosis of ID. This study's objectives were to investigate evidence of validity related to the EFA-DI's internal structure, criterion validity, and reliability. The psychometric analyses involved two statistical modeling types, confirmatory factor analysis (CFA) and item response theory analysis (IRT). These results highlight the EFA-DI scale's strong psychometric properties and support its use as a parental report measure of young children's adaptive functioning. Future studies will be conducted to develop norms of interpretation for the EFA-DI. This study is expected to contribute to the fields of psychological assessment and child development in Brazil.

Neurocognitive Impairment in Bipolar Disorder and Associated Factors: Using Population-based Norms and a Strict Criterion for Impairment Definition.

BACKGROUND: Cognitive impairment is often identified in individuals with bipolar disorder and is associated with their functional impairment. However, there is controversy surrounding potential classification methods for impairment in cognitive measures. OBJECTIVE: To examine the proportion of cognitive measures indicating impairment of attention, processing speed, memory, visuoconstructional abilities, and executive functions in individuals with bipolar disorder type I (euthymic) and healthy controls, using a strict criterion for defining impairment. METHODS: We gave 43 individuals with bipolar disorder type I and 17 healthy controls a comprehensive clinical and neuropsychological assessment. All scores were standardized using means and standard deviations according to age. Impaired performance in all cognitive measures was determined using a distribution-based threshold of z=±1645. The effects of the sociodemographic and clinical variables on cognitive performance were examined using multiple stepwise backward regression analyses. RESULTS: Clinically significant cognitive impairment was observed more frequently in the bipolar disorder group, compared to controls, on all measures. From participant factors, we found that level of education and number of manic episodes predicted variation in more cognitive measure scores. DISCUSSION: The use of population-based norms to standardize cognitive measures, and a strict criterion to define cognitive impairment, in individuals with bipolar disorder type 1 and healthy controls resulted in a prevalence of impairment in cognitive domains' frequencies of deficits that fell within the ranges previously reported in meta-analyses. CONCLUSIONS: Clinically introducing population norms and a stringent cognitive impairment criterion can facilitate more accurate measures of cognitive impairment in individuals with bipolar disorder.

Amygdala 5-HTT Gene Network Moderates the Effects of Postnatal Adversity on Attention Problems: Anatomo-Functional Correlation and Epigenetic Changes.

Variations in serotoninergic signaling have been related to behavioral outcomes. Alterations in the genome, such as DNA methylation and histone modifications, are affected by serotonin neurotransmission. The amygdala is an important brain region involved in emotional responses and impulsivity, which receives serotoninergic input. In addition, studies suggest that the serotonin transporter gene network may interact with the environment and influence the risk for psychiatric disorders. We propose to investigate whether/how interactions between the exposure to early life adversity and serotonin transporter gene network in the amygdala associate with behavioral disorders. We constructed a co-expression-based polygenic risk score (ePRS) reflecting variations in the function of the serotonin transporter gene network in the amygdala and investigated its interaction with postnatal adversity on attention problems in two independent cohorts from Canada and Singapore. We also described how interactions between ePRS-5-HTT and postnatal adversity exposure predict brain gray matter density and variation in DNA methylation across the genome. We observed that the expression-based polygenic risk score, reflecting the function of the amygdala 5-HTT gene network, interacts with postnatal adversity, to predict attention and hyperactivity problems across both cohorts. Also, both postnatal adversity score and amygdala ePRS-5-HTT score, as well as their interaction, were observed to be associated with variation in DNA methylation across the genome. Variations in gray matter density in brain regions linked to attentional processes were also correlated to our ePRS score. These results confirm that the amygdala 5-HTT gene network is strongly associated with ADHD-related behaviors, brain cortical density, and epigenetic changes in the context of adversity in young children.

Prefrontal Cortex Dopamine Transporter Gene Network Moderates the Effect of Perinatal Hypoxic-Ischemic Conditions on Cognitive Flexibility and Brain Gray Matter Density in Children.

BACKGROUND: Genetic polymorphisms of the dopamine transporter gene (DAT1) and perinatal complications associated with poor oxygenation are risk factors for attentional problems in childhood and may show interactive effects. METHODS: We created a novel expression-based polygenic risk score (ePRS) reflecting variations in the function of the DAT1 gene network (ePRS-DAT1) in the prefrontal cortex and explored the effects of its interaction with perinatal hypoxic-ischemic-associated conditions on cognitive flexibility and brain gray matter density in healthy children from two birth cohorts-MAVAN from Canada (n = 139 boys and girls) and GUSTO from Singapore (n = 312 boys and girls). RESULTS: A history of exposure to several perinatal hypoxic-ischemic-associated conditions was associated with impaired cognitive flexibility only in the high-ePRS group, suggesting that variation in the prefrontal cortex expression of genes involved in dopamine reuptake is associated with differences in this behavior. Interestingly, this result was observed in both ethnically distinct birth cohorts. Additionally, parallel independent component analysis (MAVAN cohort, n = 40 children) demonstrated relationships between single nucleotide polymorphism-based ePRS and gray matter density in areas involved in executive (cortical regions) and integrative (bilateral thalamus and putamen) functions, and these relationships differ in children from high and low exposure to hypoxic-ischemic-associated conditions. CONCLUSIONS: These findings reveal that the impact of conditions associated with hypoxia-ischemia on brain development and executive functions is moderated by genotypes associated with dopamine signaling in the prefrontal cortex. We discuss the potential impact of innovative genomic and environmental measures for the identification of children at high risk for impaired executive functions.