The future of intergenerational transmission research: A prospective, three-generation approach.

Dr. Dante Cicchetti's pioneering theory and research on developmental psychopathology have been fundamental to the proliferation of research on intergenerational transmission over the last 40 years. In part due to this foundation, much has been learned about continuities and discontinuities in child maltreatment, attachment, parenting, and psychopathology across generations. Looking towards the future, we propose that this field stands to benefit from a prospective, three-generation approach. Specifically, following established prospective, longitudinal cohorts of children over their transition to parenting the next generation will afford the opportunity to investigate the developmental origins of intergenerational transmission. This approach also can address key outstanding questions and methodological limitations in the extant literature related to the confounding of retrospective and prospective measures; examination of mediators and moderators; and investigation of the roles of biology, environment, and their interplay. After considering these advantages, we offer several considerations and recommendations for future research, many of which are broadly applicable to the study of two or more generations. We hope that this discussion will inspire the leveraging of existing prospective cohorts to carry forward Dr. Cicchetti's remarkable contributions, with the ultimate aim to inform the development of preventions and interventions that disrupt deleterious intergenerational cycles.

Impact of FADS genotype on polyunsaturated fatty acid content in human milk extracellular vesicles: A genetic association study.

BACKGROUND: Extracellular vesicles in human milk are critical in supporting newborn growth and development. Bioavailability of dietary extracellular vesicles may depend on the composition of membrane lipids. Single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase gene cluster impact the content of long-chain polyunsaturated fatty acids in human milk phospholipids. This study investigated the relation between variation in FADS1 and FADS2 with the content of polyunsaturated fatty acids in extracellular vesicles from human milk. METHODS: Milk was obtained from a cohort of mothers (N = 70) at 2-4 weeks of lactation. SNPs in the FADS gene locus were determined using pyrosequencing for rs174546 in FADS1 and rs174575 in FADS2. Quantitative lipidomic analysis of polyunsaturated fatty acids in human milk and extracellular vesicles from human milk was completed by gas chromatography-mass spectrometry. RESULTS: The rs174546 and rs174575 genotypes were independent predictors of the arachidonic acid content in extracellular vesicles. The rs174546 genotype also predicted eicosapentaenoic acid and docosahexaenoic acid in extracellular vesicles. The reduced content of long-chain polyunsaturated fatty acids in extracellular vesicles in human milk may be due to lower fatty acid desaturase activity in mothers who are carriers of the A allele in rs174546 or the G allele in rs174575. CONCLUSION: The polyunsaturated fatty acid composition of milk extracellular vesicles is predicted by the FADS genotype. These findings yield novel insights regarding extracellular vesicle content and composition that can inform the design of future research to explore how lipid metabolites impact the bioavailability of human milk extracellular vesicles.

DHEA: a neglected biological signal that may affect fetal and child development.

BACKGROUND: The stress-sensitive maternal hypothalamic-pituitary-adrenal (HPA) axis through the end-product cortisol, represents a primary pathway through which maternal experience shapes fetal development with long-term consequences for child neurodevelopment. However, there is another HPA axis end-product that has been widely ignored in the study of human pregnancy. The synthesis and release of dehydroepiandosterone (DHEA) is similar to cortisol, so it is a plausible, but neglected, biological signal that may influence fetal neurodevelopment. DHEA also may interact with cortisol to determine developmental outcomes. Surprisingly, there is virtually nothing known about human fetal exposure to prenatal maternal DHEA and offspring neurodevelopment. The current study examined, for the first time, the joint impact of fetal exposure to prenatal maternal DHEA and cortisol on infant emotional reactivity. METHODS: Participants were 124 mother-infant dyads. DHEA and cortisol were measured from maternal hair at 15 weeks (early gestation) and 35 weeks (late gestation). Observational assessments of positive and negative emotional reactivity were obtained in the laboratory when the infants were 6 months old. Pearson correlations were used to examine the associations between prenatal maternal cortisol, prenatal maternal DHEA, and infant positive and negative emotional reactivity. Moderation analyses were conducted to investigate whether DHEA might modify the association between cortisol and emotional reactivity. RESULTS: Higher levels of both early and late gestation maternal DHEA were linked to greater infant positive emotional reactivity. Elevated late gestation maternal cortisol was associated with greater negative emotional reactivity. Finally, the association between fetal cortisol exposure and infant emotional reactivity was only observed when DHEA was low. CONCLUSIONS: These new observations indicate that DHEA is a potential maternal biological signal involved in prenatal programming. It appears to act both independently and jointly with cortisol to determine a child's emotional reactivity. Its role as a primary end-product of the HPA axis, coupled with the newly documented associations with prenatal development shown here, strongly calls for the inclusion of DHEA in future investigations of fetal programming.

Temporal relation between pubertal development and peer victimization in a prospective sample of US adolescents.

Peer victimization typically peaks in early adolescence, leading researchers to hypothesize that pubertal timing is a meaningful predictor of peer victimization. However, previous methodological approaches have limited our ability to parse out which puberty cues are associated with peer victimization because gonadal and adrenal puberty, two independent processes, have either been conflated or adrenal puberty timing has been ignored. In addition, previous research has overlooked the possibility of reverse causality-that peer victimization might drive pubertal timing, as it has been shown to do in non-human primates. To fill these gaps, we followed 265 adolescents (47% female) prospectively across three-time points (Mage : T1 = 9.6, T2 = 12.0, T3 = 14.4) and measured self-report peer victimization and self- and maternal-report of gonadal and adrenal pubertal development on the Pubertal Development Scale. Multilevel modeling revealed that females who were further along in adrenal puberty at age 9 were more likely to report peer victimization at age 12 (Cohen's d = 0.25, p = .005). The relation between gonadal puberty status and peer victimization was not significant for either sex. In terms of the reverse direction, the relation between early peer victimization and later pubertal development was not significant in either sex. Overall, our findings suggest that adrenal puberty status, but not gonadal puberty status, predicted peer victimization in females, highlighting the need to separate gonadal and adrenal pubertal processes in future studies.

Annual Research Review: The power of predictability - patterns of signals in early life shape neurodevelopment and mental health trajectories.

The global burden of early life adversity (ELA) is profound. The World Health Organization has estimated that ELA accounts for almost 30% of all psychiatric cases. Yet, our ability to identify which individuals exposed to ELA will develop mental illness remains poor and there is a critical need to identify underlying pathways and mechanisms. This review proposes unpredictability as an understudied aspect of ELA that is tractable and presents a conceptual model that includes biologically plausible mechanistic pathways by which unpredictability impacts the developing brain. The model is supported by a synthesis of published and new data illustrating the significant impacts of patterns of signals on child development. We begin with an overview of the existing unpredictability literature, which has focused primarily on longer patterns of unpredictability (e.g. years, months, and days). We then describe our work testing the impact of patterns of parental signals on a moment-to-moment timescale, providing evidence that patterns of these signals during sensitive windows of development influence neurocircuit formation across species and thus may be an evolutionarily conserved process that shapes the developing brain. Next, attention is drawn to emerging themes which provide a framework for future directions of research including the evaluation of functions, such as effortful control, that may be particularly vulnerable to unpredictability, sensitive periods, sex differences, cross-cultural investigations, addressing causality, and unpredictability as a pathway by which other forms of ELA impact development. Finally, we provide suggestions for prevention and intervention, including the introduction of a screening instrument for the identification of children exposed to unpredictable experiences.

Infant hedonic/anhedonic processing index (HAPI-Infant): Assessing infant anhedonia and its prospective association with adolescent depressive symptoms.

BACKGROUND: Anhedonia, an impairment in the motivation for or experience of pleasure, is a well-established transdiagnostic harbinger and core symptom of mental illness. Given increasing recognition of early life origins of mental illness, we posit that anhedonia should, and could, be recognized earlier if appropriate tools were available. However, reliable diagnostic instruments prior to childhood do not currently exist. METHODS: We developed an assessment instrument for anhedonia/reward processing in infancy, the Infant Hedonic/Anhedonic Processing Index (HAPI-Infant). Exploratory factor and psychometric analyses were conducted using data from 6- and 12-month-old infants from two cohorts (N = 188, N = 212). Then, associations were assessed between infant anhedonia and adolescent self-report of depressive symptoms. RESULTS: The HAPI-Infant (47-items), exhibited excellent psychometric properties. Higher anhedonia scores at 6 (r = 0.23, p < .01) and 12 months (r = 0.19, p < .05) predicted elevated adolescent depressive symptoms, and these associations were stronger than for established infant risk indicators such as negative affectivity. Subsequent analyses supported the validity of short (27-item) and very short (12-item) versions of this measure. LIMITATIONS: The primary limitations of this study are that the HAPI-Infant awaits additional tests of generalizability and of its ability to predict clinical diagnosis of depression. CONCLUSIONS: The HAPI-Infant is a novel, psychometrically strong diagnostic tool suitable for recognizing anhedonia during the first year of life with strong predictive value for later depressive symptoms. In view of the emerging recognition of increasing prevalence of affective disorders in children and adolescents, the importance of the HAPI-Infant in diagnosing anhedonia is encouraging. Early recognition of anhedonia could target high-risk individuals for intervention and perhaps prevention of mental health disorders.

Prenatal Exposure to Maternal Mood Entropy Is Associated With a Weakened and Inflexible Salience Network in Adolescence.

BACKGROUND: Fetal exposure to maternal mood dysregulation influences child cognitive and emotional development, which may have long-lasting implications for mental health. However, the neurobiological alterations associated with this dimension of adversity have yet to be explored. Here, we tested the hypothesis that fetal exposure to entropy, a novel index of dysregulated maternal mood, would predict the integrity of the salience network, which is involved in emotional processing. METHODS: A sample of 138 child-mother pairs (70 females) participated in this prospective longitudinal study. Maternal negative mood level and entropy (an index of variable and unpredictable mood) were assessed 5 times during pregnancy. Adolescents engaged in a functional magnetic resonance imaging task that was acquired between 2 resting-state scans. Changes in network integrity were analyzed using mixed-effect and latent growth curve models. The amplitude of low frequency fluctuations was analyzed to corroborate findings. RESULTS: Prenatal maternal mood entropy, but not mood level, was associated with salience network integrity. Both prenatal negative mood level and entropy were associated with the amplitude of low frequency fluctuations of the salience network. Latent class analysis yielded 2 profiles based on changes in network integrity across all functional magnetic resonance imaging sequences. The profile that exhibited little variation in network connectivity (i.e., inflexibility) consisted of adolescents who were exposed to higher negative maternal mood levels and more entropy. CONCLUSIONS: These findings suggest that fetal exposure to maternal mood dysregulation is associated with a weakened and inflexible salience network. More broadly, they identify maternal mood entropy as a novel marker of early adversity that exhibits long-lasting associations with offspring brain development.

Contact with caregivers is associated with composition of the infant gastrointestinal microbiome in the first 6 months of life.

OBJECTIVES: Little is known about how physical contact at birth and early caregiving environments influence the colonization of the infant gastrointestinal microbiome. We investigated how infant contact with caregivers at birth and within the first 2 weeks of life relates to the composition of the gastrointestinal microbiome in a sample of U.S. infants (n = 60). METHODS: Skin-to-skin and physical contact with caregivers at birth and early caregiving environments were surveyed at 2 weeks postpartum. Stool samples were collected from infants at 2 weeks, 2, 6, and 12 months of age and underwent 16S rRNA sequencing as a proxy for the gastrointestinal microbiome. Associations between early caregiving environments and alpha and beta diversity, and differential abundance of bacteria at the genus level were assessed using PERMANOVA, and negative binomial mixed models in DEseq2. RESULTS: Time in physical contact with caregivers explained 10% of variation in beta diversity at 2 weeks' age. The number of caregivers in the first few weeks of life explained 9% of variation in beta diversity at 2 weeks and the number of individuals in physical contact at birth explained 11% of variation in beta diversity at 6 months. Skin-to-skin contact on the day of birth was positively associated with the abundance of eight genera. Infants held for by more individuals had greater abundance of eight genera. DISCUSSION: Results reveal a potential mechanism (skin-to-skin and physical contact) by which caregivers influence the infant gastrointestinal microbiome. Our findings contribute to work exploring the social transmission of microbes.

Mothers' prenatal distress accelerates adrenal pubertal development in daughters.

Human life history schedules vary, partly, because of adaptive, plastic responses to early-life conditions. Little is known about how prenatal conditions relate to puberty timing. We hypothesized that fetal exposure to adversity may induce an adaptive response in offspring maturational tempo. In a longitudinal study of 253 mother-child dyads followed for 15 years, we investigated if fetal exposure to maternal psychological distress related to children's adrenarche and gonadarche schedules, assessed by maternal and child report and by dehydroepiandrosterone sulfate (DHEA-S), testosterone, and estradiol levels. We found fetal exposure to elevated maternal prenatal psychological distress predicted earlier adrenarche and higher DHEA-S levels in girls, especially first-born girls, and that associations remained after covarying indices of postnatal adversity. No associations were observed for boys or for gonadarche in girls. Adrenarche orchestrates the social-behavioral transition from juvenility to adulthood; therefore, significant findings for adrenarche, but not gonadarche, suggest that prenatal maternal distress instigates an adaptive strategy in which daughters have earlier social-behavioral maturation. The stronger effect in first-borns suggests that, in adverse conditions, it is in the mother's adaptive interest for her daughter to hasten social maturation, but not necessarily sexual maturation, because it would prolong the duration of the daughter allomothering younger siblings. We postulate a novel evolutionary framework that human mothers may calibrate the timing of first-born daughters' maturation in a way that optimizes their own reproductive success.

Across ages and places: Unpredictability of maternal sensory signals and child internalizing behaviors.

BACKGROUND: Patterns of sensory inputs early in life play an integral role in shaping the maturation of neural circuits, including those implicated in emotion and cognition. In both experimental animal models and observational human research, unpredictable sensory signals have been linked to aberrant developmental outcomes, including poor memory and effortful control. These findings suggest that sensitivity to unpredictable sensory signals is conserved across species and sculpts the developing brain. The current study provides a novel investigation of unpredictable maternal sensory signals in early life and child internalizing behaviors. We tested these associations in three independent cohorts to probe the generalizability of associations across continents and cultures. METHOD: The three prospective longitudinal cohorts were based in Orange, USA (n = 163, 47.2 % female, Mage = 1 year); Turku, Finland (n = 239, 44.8 % female, Mage = 5 years); and Irvine, USA (n = 129, 43.4 % female, Mage = 9.6 years). Unpredictability of maternal sensory signals was quantified during free-play interactions. Child internalizing behaviors were measured via parent report (Orange & Turku) and child self-report (Irvine). RESULTS: Early life exposure to unpredictable maternal sensory signals was associated with greater child fearfulness/anxiety in all three cohorts, above and beyond maternal sensitivity and sociodemographic factors. The association between unpredictable maternal sensory signals and child sadness/depression was relatively weaker and did not reach traditional thresholds for statistical significance. LIMITATIONS: The correlational design limits our ability to make causal inferences. CONCLUSIONS: Findings across the three diverse cohorts suggest that unpredictable maternal signals early in life shape the development of internalizing behaviors, particularly fearfulness and anxiety.

Discrimination and adverse birth outcomes among Latina women: The protective role of social support.

OBJECTIVE: Interpersonal discrimination has been associated with adverse birth outcomes among Black populations, but few studies have examined the impact of discrimination among Latinx/Hispanic populations in the United States, especially in conjunction with resources that could be protective. The present study examined (a) if exposure to discrimination is associated with adverse birth outcomes for Latina/Hispanic women and (b) if prenatal social support buffers these links. METHOD: In two independent prospective studies of Latina/Hispanic women in Southern California (N = 84 and N = 102), the relation between maternal experience of discrimination and birth outcomes (length of gestation and birth weight) was examined. Additionally, social support was tested as a moderator of these relations. RESULTS: In both Studies 1 and 2, exposures to discrimination predicted adverse birth outcomes. Specifically, lifetime experiences of major discrimination predicted lower birth weight. Additionally, in Study 2, chronic experiences of everyday discrimination were linked to lower birth weight. In Study 1, major discrimination also predicted shorter gestational length. Importantly, in both studies, the presence of prenatal social support buffered associations between discrimination and poorer birth outcomes. CONCLUSIONS: Findings implicate discrimination as an important risk factor for adverse birth outcomes among women of Latina/Hispanic descent. Further policies, practice, and research on reducing discrimination and enhancing factors that promote resilience such as social support are needed to facilitate healthy births among Latina/Hispanic women, mitigate intergenerational harm of discrimination-related stress, and advance health equity at birth and across the lifespan. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

One size doesn't fit all: Attitudes towards work modify the relation between parental leave length and postpartum depression.

The present study aimed to investigate the relationship between parental leave length and maternal depressive symptoms at six- and twelve-months postpartum and whether this relation was influenced by women's attitudes towards leave, whether leave was paid or unpaid, and the reason they returned to work. The sample included 115 working women recruited during pregnancy as part of a larger longitudinal study. Analyses revealed that maternal attitudes toward leave influenced the association between leave length and depressive symptoms. Specifically, longer leaves were associated with increased depressive symptoms for women who missed their previous activities at work. Furthermore, women who missed work and had leave for 16 weeks or more, exhibited higher depressive symptoms at six- and twelve-months. Last, results also indicated that women who returned to work solely for monetary reasons exhibited more depressive symptoms at six-months postpartum than those who returned to work for other reasons. This study is among the first to show that women's attitudes towards parental leave and their individual reasons for returning to work are important factors to consider that may have potential implications for parental leave policies.

Infant effortful control predicts BMI trajectories from infancy to adolescence.

BACKGROUND: Effortful control, or the regulation of thoughts and behaviour, is a potential target for preventing childhood obesity. OBJECTIVES: To assess effortful control in infancy through late childhood as a predictor of repeated measures of body mass index (BMI) from infancy through adolescence, and to examine whether sex moderates the associations. METHODS: Maternal report of offspring effortful control and measurements of child BMI were obtained at 7 and 8 time points respectively from 191 gestational parent/child dyads from infancy through adolescence. General linear mixed models were used. RESULTS: Effortful control at 6 months predicted BMI trajectories from infancy through adolescence, F(5,338) = 2.75, p = 0.03. Further, when effortful control at other timepoints were included in the model, they added no additional explanatory value. Sex moderated the association between 6-month effortful control and BMI, F(4, 338) = 2.59, p = 0.03, with poorer infant effortful control predicting higher BMI in early childhood for girls, and more rapid increases in BMI in early adolescence for boys. CONCLUSIONS: Effortful control in infancy was associated with BMI over time. Specifically, poor effortful control during infancy was associated with higher BMI in childhood and adolescence. These findings support the argument that infancy may be a sensitive window for the development of later obesity.

Identifying the neural correlates of anticipatory postural control: A novel fMRI paradigm.

Altered postural control in the trunk/hip musculature is a characteristic of multiple neurological and musculoskeletal conditions. Previously it was not possible to determine if altered cortical and subcortical sensorimotor brain activation underlies impairments in postural control. This study used a novel fMRI-compatible paradigm to identify the brain activation associated with postural control in the trunk and hip musculature. BOLD fMRI imaging was conducted as participants performed two versions of a lower limb task involving lifting the left leg to touch the foot to a target. For the supported leg raise (SLR) the leg is raised from the knee while the thigh remains supported. For the unsupported leg raise (ULR) the leg is raised from the hip, requiring postural muscle activation in the abdominal/hip extensor musculature. Significant brain activation during the SLR task occurred predominantly in the right primary and secondary sensorimotor cortical regions. Brain activation during the ULR task occurred bilaterally in the primary and secondary sensorimotor cortical regions, as well as cerebellum and putamen. In comparison with the SLR, the ULR was associated with significantly greater activation in the right premotor/SMA, left primary motor and cingulate cortices, primary somatosensory cortex, supramarginal gyrus/parietal operculum, superior parietal lobule, cerebellar vermis, and cerebellar hemispheres. Cortical and subcortical regions activated during the ULR, but not during the SLR, were consistent with the planning, and execution of a task involving multisegmental, bilateral postural control. Future studies using this paradigm will determine mechanisms underlying impaired postural control in patients with neurological and musculoskeletal dysfunction.

Experiences of COVID-19-Related Racism and Impact on Depression Trajectories Among Racially/Ethnically Minoritized Adolescents.

PURPOSE: In 2020, racially/ethnically minoritized (REMD) youth faced the "dual pandemics" of COVID-19 and racism, both significant stressors with potential for adverse mental health effects. The current study tested whether short- and long-term trajectories of depressive symptoms from before to during the COVID-19 pandemic differed between REMD adolescents who did and did not endorse exposure to COVID-19-era-related racism (i.e., racism stemming from conditions created or exacerbated by the COVID-19 pandemic). METHODS: A community sample of 100 REMD adolescents enrolled in an ongoing longitudinal study of mental health was assessed before and during the COVID-19 pandemic. Participants were 51% girls, mean age = 16, standard deviation = 2.7, and identified as Latinx/Hispanic (48%), Multiethnic (34%), Asian American (12%), and Black (6%). RESULTS: REMD adolescents' depressive symptoms were elevated during the COVID-19 pandemic compared to pre-pandemic levels, and increases were more pronounced over time for those who endorsed exposure to COVID-19-era-related racism. In general, Asian American participants endorsed racism experiences at the highest rates compared to others, including being called names (42%), people acting suspicious around them (33%), and being verbally threatened (17%). Additionally, more than half of Black and Asian American participants reported worry about experiencing racism related to the COVID-19 pandemic, even if they had not experienced it to date. DISCUSSION: REMD adolescents are at increased risk for depressive symptoms related to converging stressors stemming from the COVID-19 pandemic and pandemic-related racism, which has the potential to widen racial/ethnic mental health disparities faced by the REMD youth.

Patterns of Maternal Distress from Pregnancy Through Childhood Predict Psychopathology During Early Adolescence.

Capitalizing on a longitudinal cohort followed from gestation through adolescence (201 mother-child dyads), we investigate the contributions of severity and stability of both maternal depressive and perceived stress symptoms to adolescent psychopathology. Maternal depressive and perceived stress trajectories from pregnancy through adolescence were identified with latent class growth analyses, and associations with adolescent internalizing and externalizing symptoms were examined. For both depression and stress, the most common trajectory group comprised mothers displaying stable and low symptom levels over time, and adolescents of these mothers had the fewest internalizing and externalizing symptoms. Maternal membership to one or more aberrant trajectory groups predicted higher levels of internalizing and externalizing symptoms, determined by both maternal and adolescent self-report. This study indicates that profiles of multiple indicators of maternal psychopathology assessed across childhood, beginning prenatally, can provide critical additional insight into child psychopathology risk.

Intergenerational risk and resilience pathways from discrimination and acculturative stress to infant mental health.

Preconception and prenatal stress impact fetal and infant development, and women of color are disproportionately exposed to sociocultural stressors like discrimination and acculturative stress. However, few studies examine links between mothers' exposure to these stressors and offspring mental health, or possible mitigating factors. Using linear regression, we tested associations between prenatally assessed maternal acculturative stress and discrimination on infant negative emotionality among 113 Latinx/Hispanic, Asian American, Black, and Multiethnic mothers and their children. Additionally, we tested interactions between stressors and potential pre- and postnatal resilience-promoting factors: community cohesion, social support, communalism, and parenting self-efficacy. Discrimination and acculturative stress were related to more infant negative emotionality at approximately 12 months old (M = 12.6, SD = .75). In contrast, maternal report of parenting self-efficacy when infants were 6 months old was related to lower levels of infant negative emotionality. Further, higher levels of parenting self-efficacy mitigated the relation between acculturative stress and negative emotionality. Preconception and prenatal exposure to sociocultural stress may be a risk factor for poor offspring mental health. Maternal and child health researchers, policymakers, and practitioners should prioritize further understanding these relations, reducing exposure to sociocultural stressors, and promoting resilience.

Maternal prenatal cortisol trajectories predict accelerated growth in infancy.

Higher maternal cortisol in pregnancy has been linked to childhood obesity. Much of the previous research has been limited in that cortisol in pregnancy is only measured at one time-point, precluding the ability to examine critical timing effects of prenatal maternal cortisol. To fill this gap, this longitudinal study measured maternal plasma cortisol at 15, 19, 25, and 31 weeks of pregnancy, and assessed infant body mass index percentile (BMIP)1 at birth, 3, 6, 12, and 24 months in 189 mother-infant pairs. Three distinct patterns of maternal cortisol in pregnancy (typical, steep, and flat trajectories) were identified using general growth mixture modeling (GGMM)2 and then used to predict child growth patterns using multilevel modeling. Infants of mothers who had flat cortisol trajectories, characterized by relatively high cortisol in early gestation that plateaus by mid-gestation, experienced more rapid increases in BMIP from birth to 6 months, and had higher BMIPs at 3 and 6 months, than infants whose mothers had the typical slow cortisol rise over gestation, or steep (rapidly accelerating) trajectories. These results suggest that it is not just the total amount of maternal cortisol in pregnancy that shapes early infant growth, but instead the timing and trajectory of prenatal cortisol exposure. To better understand the early origins of obesity risk, future research is needed to investigate the factors that shape mothers' prenatal cortisol trajectories.

Within-subject changes in methylome profile identify individual signatures of early-life adversity, with a potential to predict neuropsychiatric outcome.

Background: Adverse early-life experiences (ELA), including poverty, trauma and neglect, affect a majority of the world's children. Whereas the impact of ELA on cognitive and emotional health throughout the lifespan is well-established, it is not clear how distinct types of ELA influence child development, and there are no tools to predict for an individual child their vulnerability or resilience to the consequences of ELAs. Epigenetic markers including DNA-methylation profiles of peripheral cells may encode ELA and provide a predictive outcome marker. However, the rapid dynamic changes in DNA methylation in childhood and the inter-individual variance of the human genome pose barriers to identifying profiles predicting outcomes of ELA exposure. Here, we examined the relation of several dimensions of ELA to changes of DNA methylation, using a longitudinal within-subject design and a high threshold for methylation changes in the hope of mitigating the above challenges. Methods: We analyzed DNA methylation in buccal swab samples collected twice for each of 110 infants: neonatally and at 12 months. We identified CpGs differentially methylated across time, calculated methylation changes for each child, and determined whether several indicators of ELA associated with changes of DNA methylation for individual infants. We then correlated select dimensions of ELA with methylation changes as well as with measures of executive function at age 5 years. We examined for sex differences, and derived a sex-dependent 'impact score' based on sites that most contributed to the methylation changes. Findings: Setting a high threshold for methylation changes, we discovered that changes in methylation between two samples of an individual child reflected age-related trends towards augmented methylation, and also correlated with executive function years later. Among the tested factors and ELA dimensions, including income to needs ratios, maternal sensitivity, body mass index and sex, unpredictability of parental and household signals was the strongest predictor of executive function. In girls, an interaction was observed between a measure of high early-life unpredictability and methylation changes, in presaging executive function. Interpretation: These findings establish longitudinal, within-subject changes in methylation profiles as a signature of some types of ELA in an individual child. Notably, such changes are detectable beyond the age-associated DNA methylation dynamics. Future studies are required to determine if the methylation profile changes identified here provide a predictive marker of vulnerabilities to poorer cognitive and emotional outcomes.

Early life exposure to unpredictable parental sensory signals shapes cognitive development across three species.

Exposure to early life adversity has long term consequences on cognitive function. Most research has focused on understanding components of early life adversities that contribute to later risk, including poverty, trauma, maltreatment, and neglect. Whereas these factors, in the aggregate, explain a significant proportion of emotional and cognitive problems, there are serious gaps in our ability to identify potential mechanisms by which early life adversities might promote vulnerability or resilience. Here we discuss early life exposure to unpredictable signals from the caretaker as an understudied type of adversity that is amenable to prevention and intervention. We employ a translational approach to discover underlying neurobiological mechanisms by which early life exposure to unpredictable signals sculpts the developing brain. First, we review evidence that exposure to unpredictable signals from the parent during sensitive periods impacts development of neural circuits. Second, we describe a method for characterizing early life patterns of sensory signals across species. Third, we present published and original data illustrating that patterns of maternal care predict memory function in humans, non-human primates, and rodents. Finally, implications are discussed for identifying individuals at risk so that early preventive-intervention can be provided.