BACKGROUND:Certain temperament characteristics, such as low effortful control and high negative affectivity, are linked to an elevated likelihood for later psychopathology. Although genetic vulnerability has been associated with a number of psychiatric conditions, little work has examined the genetic architecture underlying temperament or the genetic overlap between early temperament profiles and later mental health outcomes. The present study examined associations of polygenic scores for anxiety (PGS-Anxiety) and ADHD (PGS-ADHD) with temperament characteristics in a longitudinal sample of children assessed from infancy through age 7 years. METHODS:Analyses were conducted in a sample of children (European Ancestry n = 476; Full Sample [European and other ancestries] N = 606). RESULTS:We observed an age-by-PGS interaction on effortful control. As children aged, there appeared to be stronger negative associations between PGS-ADHD and effortful control. No associations were observed between PGS-Anxiety and negative affectivity. CONCLUSIONS:Overall, the findings suggest some support for associations between genetic underpinnings for externalizing psychopathology and temperament that increase over time.

Postpartum depression impacts 15% of healthy mothers after childbirth, with lasting consequences for the infant and the mother-child relationship. Early diagnosis and intervention are crucial to enhancing mothers’ mental health and promoting a healthy child development. This study investigates the psychometric properties of the Brazilian Edinburgh Postnatal Depression Scale (EPDS). Using a sample of 1,175 Brazilian mothers, data were gathered through online and in-person across four datasets from 2011 to 2020. Confirmatory factor analyses were performed on one-factor, two-factor, and three-factor models, all showing satisfactory fit and internal consistency. Measurement invariance across data collection methods was confirmed, supporting the EPDS’s reliability in both formats. Criterion validity was also evaluated by comparing depressive symptoms before and during the COVID-19 pandemic, with results indicating a significant increase in postpartum depression symptoms. These findings validate the EPDS as a valuable tool for clinical and research purposes within the Brazilian population.

Major depressive disorder (MDD) affects over 300 million people globally. The etiology of MDD is linked to circadian rhythm disruption, including the diurnal pattern of mood, cognition, and physiological processes. The revised Mood Rhythm Instrument (MRhI-r) was developed to assess self-perceived rhythmicity of symptoms and has previously been tested in nonclinical populations. This study evaluates the psychometric properties of the MRhI-r in a clinical MDD sample. Individuals with MDD and healthy controls completed the MRhI-r at baseline and after 2 weeks. Psychometric properties were assessed using confirmatory factor analysis (CFA) of factor structures previously determined in a nonclinical sample, item response theory (IRT), receiver operating characteristic (ROC) curves, internal consistency, and test-retest reliability. Sex differences in symptom peak frequency and timing were assessed within the MDD group. The sample included 102 MDD participants (65% female, ages 17-70, M ± SD = 37 ± 14) and 94 healthy controls (67% female, ages 18-72, M ± SD = 37 ± 15). CFA showed excellent model fit and IRT analysis indicated good item fit. ROC analysis showed a diagnostic threshold of 2.5 with 64% sensitivity and 72% specificity. The MRhI-r scores demonstrated good internal consistency (α = .78, ω = .82) and moderate test-retest reliability (r = 0.69). No sex differences were found in peak frequency or timing within the MDD group. The psychometric properties of the MRhI-r in individuals with MDD support the three-factor model seen in previous studies. This study assesses the psychometric properties of the MRhI-r in a clinical sample, endorsing its use for evaluating symptom rhythmicity in clinically depressed individuals. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Psychiatric disorders are highly prevalent and often co-morbid with metabolic syndrome. Exposure to adversity in early life is a risk factor for both metabolic and behavioral problems, modifying leptin metabolism and signaling. Leptin is not only an energy-balance regulator, being also associated with the development of affective disorders. Our objective was to investigate if individual variations in peripheral leptin receptor (LepR) gene network function moderate the effect of childhood adversity on psychopathology. We created expression-based polygenic scores (ePRS) reflecting genetic variations that affect expression of the liver LepR gene network. We investigated the interaction between the LepR-ePRS and early adversity on mental health outcomes, namely anxiety and depression, in childhood (MAVAN) and adolescence (ALSPAC). In both cohorts, there were interaction effects between early adversity exposure and the liver-based LepR-ePRS, in which adversity was associated with depression only in individuals from the high ePRS group. Our findings suggest that exposure to early adversity is associated with mental health problems in children and adolescents. The liver leptin receptor gene network is an important moderator of these effects, and this may be due to individual differences within metabolic and inflammatory pathways represented by this gene network.

Cardiometabolic and psychiatric disorders often co-exist and share common early life risk factors, such as low birth weight. However, the biological pathways linking early adversity to adult cardiometabolic/psychiatric comorbidity remain unknown. Dopamine (DA) neurotransmission in the striatum is sensitive to early adversity and influences the development of both cardiometabolic and psychiatric diseases. Here we show that a co-expression based polygenic score (ePGS) reflecting individual variations in the expression of the striatal dopamine transporter gene (SLC6A3) network significantly interacts with birth weight to predict psychiatric and cardiometabolic comorbidities in both adults (UK Biobank, N = 225,972) and adolescents (ALSPAC, N = 1188). Decreased birth weight is associated with an increased risk for psychiatric and cardiometabolic comorbidities, but the effect is dependent on a striatal SLC6A3 ePGS, that reflects individual variation in gene expression of genes coexpressed with the SLC6A3 gene in the striatum. Neuroanatomical analyses revealed that SNPs from the striatum SLC6A3 ePGS were significantly associated with prefrontal cortex gray matter density, suggesting a neuroanatomical basis for the link between early adversity and psychiatric and cardiometabolic comorbidity. Our study reveals that psychiatric and cardiometabolic diseases share common developmental pathways and underlying neurobiological mechanisms that includes dopamine signaling in the striatum.

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-1β [IL-1β], 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

BACKGROUND: Early stress increases the risk for psychiatric disorders. Glucocorticoids are stress mediators that regulate transcriptional activity and morphology in the hippocampus, which is implicated in the pathophysiology of multiple psychiatric conditions. We aimed to establish the relevance of hippocampal glucocorticoid-induced transcriptional activity as a mediator of the effects of early life on later psychopathology in humans.METHODS: RNA sequencing was performed with anterior and posterior hippocampal dentate gyrus from adult female macaques (n = 12/group) that were chronically treated with betamethasone (glucocorticoid receptor agonist) or vehicle. Coexpression network analysis identified a preserved gene network in the posterior hippocampal dentate gyrus that was strongly associated with glucocorticoid exposure. The single nucleotide polymorphisms in the genes in this network were used to create an expression-based polygenic score in humans.RESULTS: The expression-based polygenic score significantly moderated the association between early adversity and psychotic disorders in adulthood (UK Biobank, women, n = 44,519) and on child peer relations (ALSPAC [Avon Longitudinal Study of Parents and Children], girls, n = 1666 for 9-year-olds and n = 1594 for 11-year-olds), an endophenotype for later psychosis. Analyses revealed that this network was enriched for glucocorticoid-induced epigenetic remodeling in human hippocampal cells. We also found a significant association between single nucleotide polymorphisms from the expression-based polygenic score and adult brain gray matter density.CONCLUSIONS: We provide an approach for the use of transcriptomic data from animal models together with human data to study the impact of environmental influences on mental health. The results are consistent with the hypothesis that hippocampal glucocorticoid-related transcriptional activity mediates the effects of early adversity on neural mechanisms implicated in psychiatric disorders.

Incorporating functional aspects into polygenic scores may accelerate early diagnosis and the discovery of therapeutic targets. Yet, existing polygenic scores summarize information from genome wide statistical associations between SNPs and phenotypes. We developed the novel biologically informed, expression-based polygenic scores (ePRS or ePGS). The method characterizes tissue specific gene co-expression networks from genome-wide RNA sequencing data and incorporates this information into polygenic scores. Performance and characteristics of the ePGS were compared to traditional polygenic risk score (PRS). We observed that ePGS differs from PRS for aggregating information on; i. the relation between different genes (co-expression); ii. the levels of tissue-specific gene expression; iii. the genetic variation of the target sample; iv. the tissue-specific effect size of the association between genotyping and gene expression; v. the portability across different ancestries. Variations in the ePGS represent individual variations in the expression of a tissue-specific gene co-expression network, and this methodology may profoundly influence the way we study human disease biology.

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-1β, 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-1β ( 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-1β, 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.

The present study aims to investigate the association between type of delivery and breastfeeding in domains of child development, controlling the effect of maternal education and family income. Children aged 4-72 months participated in the research. We used the Dimensional Inventory of Child Development Assessment (IDADI), the Self-Reporting Questionnaire (SRQ-20), and a sociodemographic questionnaire. MANCOVA analyses indicated that there were no statistically significant differences in child development means across IDADI domains comparing vaginal and cesarean delivery as well as breastfed and non-breastfed children's groups. We concluded that controlling confounding variables is an important aspect to consider in future studies.

O desenvolvimento infantil é um campo de estudo complexo e deve ser analisado de maneira integrada, considerando os contextos nos quais a criança está inserida. 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 nessa 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. Participaram 1.843 mães de crianças de quatro a 72 meses, que responderam a um questionário sociodemográfico e ao Inventário Dimensional de Avaliação do Desenvolvimento Infantil. Os resultados apontaram que crianças que não frequentam IEI apresentaram melhores médias nos domínios Motricidade Ampla e Linguagem Receptiva 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.

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.

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 (CDJ) as a facilitator for child develop-ment. 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 rela-tionship. This study aimed to compare children attending or not attending CDJ 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-ventario Dimensional de Avaliacao 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.

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.

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 portray 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 covaried with major depressive disorder (MDD), bipolar disorder (BD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD), a finding not 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.

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 (β = 61.58, p = 0.015) and 72 months (β = 97.78, p = 0.001); food responsiveness at 48 months (β = 83.79, p = 0.009) satiety at 48 months (β = -43.63, p = 0.047). Similar results were observed in the GUSTO cohort, with a significant interaction effect on food enjoyment (β = 30.48, p = 0.006) food fussiness score (β = -24.07, p = 0.02) and satiety score at 60 months (β = -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.

Neuropsychological alterations have been identified in populations heavily exposed to metals with neurotoxic potential, such as manganese (Mn). This study examined the associations between Mn environmental exposure in school-aged children and executive functions, using structural equation modeling. Children, aged between 7 and 12 years (N = 181), were recruited from four elementary schools located in a region that is under the influence of atmospheric emissions from a ferro-manganese alloy plant in the municipality of Simões Filho, Bahia, Brazil. The following cognitive functions were evaluated: Intelligence, Inhibitory Control, Cognitive Flexibility, Verbal and Design Fluency, Verbal and Visual Working Memory and Attention. We performed structural equation modeling to identify the following executive functions latent variables: working memory, inhibitory control and cognitive flexibility. We further analyzed the relations between executive functions and Mn measured in hair (MnH) and toenails (MnTn) with linear mixed models, after controlling for co-variables. A positive effect at the individual level on working memory, inhibition control and cognitive flexibility was observed with MnTn after controlling for co-variables, but no association was found with MnH levels. However, children attending school most environmentally exposed to Mn emissions, which had the highest rate of Mn dust deposition, had the poorest scores on working memory. These findings suggest both benefits and risk of Mn on children's cognitive development.

We thank Lahiri et al. ( 1 Lahiri D.K. Maloney B. Song W. Sokol D.K. Crossing the "birth border" for epigenetic effects. Biol Psychiatry. 2022; 92: e21-e23 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ) for their interest in our recent article in which we describe the potential fetal origins of epigenetic aging ( 2 McGill M.G. Pokhvisneva I. Clappison A.S. McEwen L.M. Beijers R. Tollenaar M.S. et al. Maternal prenatal anxiety and the fetal origins of epigenetic aging. Biol Psychiatry. 2022; 91: 303-312 Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar ). Owing to space constraints, a detailed review of the fetal origins literature was not possible in our original article. We now provide a short historical perspective below. We also direct readers to the following articles, which review the extension of the fetal origins framework to neurodevelopment and mental health phenotypes ( 3 Van den Bergh B.R.H. van den Heuvel M.I. Lahti M. Braeken M. de Rooij S.R. Entringer S. et al. Prenatal developmental origins of behavior and mental health: The influence of maternal stress in pregnancy. Neurosci Biobehav Rev. 2020; 117: 26-64 Crossref PubMed Scopus (376) Google Scholar , 4 O'Donnell K.J. Meaney M.J. Fetal origins of mental health: The Developmental Origins of Health and Disease Hypothesis. Am J Psychiatry. 2017; 174: 319-328 Crossref PubMed Scopus (302) Google Scholar , 5 Lindsay K.L. Buss C. Wadhwa P.D. Entringer S. The interplay between nutrition and stress in pregnancy: Implications for fetal programming of brain development. Biol Psychiatry. 2019; 85: 135-149 Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar , 6 Entringer S. Buss C. Wadhwa P.D. Prenatal stress, development, health and disease risk: A psychobiological perspective-2015 Curt Richter Award Paper. Psychoneuroendocrinology. 2015; 62: 366-375 Crossref PubMed Scopus (177) Google Scholar , 7 Monk C. Lugo-Candelas C. Trumpff C. Prenatal developmental origins of future psychopathology: Mechanisms and pathways. Annu Rev Clin Psychol. 2019; 15: 317-344 Crossref PubMed Scopus (106) Google Scholar , 8 O'Donnell K. O'Connor T.G. Glover V. Prenatal stress and neurodevelopment of the child: Focus on the HPA axis and role of the placenta. Dev Neurosci. 2009; 31: 285-292 Crossref PubMed Scopus (345) Google Scholar , 9 O'Connor T.G. Ciesla A.A. Maternal immune activation hypotheses for human neurodevelopment: Some outstanding questions. Biol Psychiatry Cogn Neurosci Neuroimaging. 2022; 7: 471-479 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar , 10 Glover V. Annual Research Review: Prenatal stress and the origins of psychopathology: An evolutionary perspective. J Child Psychol Psychiatry Allied Discipl. 2011; 52: 356-367 Crossref PubMed Scopus (369) Google Scholar ). Crossing the "Birth Border" for Epigenetic EffectsBiological PsychiatryVol. 92Issue 4PreviewStudying how early life influences late-life outcomes continues to enrich our understanding of neuropsychiatric disorders. Manipulative experiments must be limited to animal models, and longitudinal surveys that unite records data and biological sampling are uncommon. Thus, McGill et al.'s (1) work is a welcome addition to the field. We offer the following analytical and conceptual comments and suggestions. Full-Text PDF

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.