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Childhood exposure to social disadvantage is a major risk factor for psychiatric disorders and poor developmental, educational, and occupational outcomes, presumably because adverse exposures alter the neurodevelopmental processes that contribute to risk trajectories. Yet, given the limited social mobility in the United States and other countries, childhood social disadvantage is frequently preceded by maternal social disadvantage during pregnancy, potentially altering fetal brain development during a period of high neuroplasticity through hormonal, microbiome, epigenetic, and immune factors that cross the placenta and fetal blood-brain barrier. The current study examines prenatal social disadvantage to determine whether these exposures in utero are associated with alterations in functional brain networks as early as birth. As part of the Early Life Adversity and Biological Embedding study, mothers were recruited during pregnancy, prenatal social disadvantage was assessed across trimesters, and their healthy, full-term offspring were imaged using resting-state functional magnetic resonance imaging during the first weeks of life. Multivariate machine learning methods revealed that neonatal functional connectivity (FC) varied as a function of prenatal exposure to social disadvantage (n = 261, R = 0.43, R 2 = 0.18), with validation in an independent sample. Alterations in FC associated with prenatal social disadvantage occurred brain-wide and were most pronounced in association networks (fronto-parietal, ventral attention, dorsal attention) and the somatomotor network. Amygdala FC was altered at birth, with a pattern shared across subcortical structures. These findings provide critical insights into how early in development functional networks begin to diverge in the context of social disadvantage and elucidate the functional networks that are most impacted., Competing Interests: Competing interests statement:M.E.R. and D.S. (one of the reviewers) are on a commentary in 2023 as part of two large consortium.

Behavioral inhibition (BI), an early-life temperament characterized by vigilant responses to novelty, is a risk factor for anxiety disorders. In this study, we investigated whether differences in neonatal brain responses to infrequent auditory stimuli relate to children's BI at 1 year of age. Using functional magnetic resonance imaging (fMRI), we collected blood-oxygen-level-dependent (BOLD) data from N = 45 full-term, sleeping neonates during an adapted auditory oddball paradigm and measured BI from n = 27 of these children 1 year later using an observational assessment. Whole-brain analyses corrected for multiple comparisons identified 46 neonatal brain regions producing novelty-evoked BOLD responses associated with children's BI scores at 1 year of age. More than half of these regions ( n = 24, 52%) were in prefrontal cortex, falling primarily within regions of the default mode or frontoparietal networks or in ventromedial/orbitofrontal regions without network assignments. Hierarchical clustering of the regions based on their patterns of association with BI resulted in two groups with distinct anatomical, network, and response-timing profiles. The first group, located primarily in subcortical and temporal regions, tended to produce larger early oddball responses among infants with lower subsequent BI. The second group, located primarily in prefrontal cortex, produced larger early oddball responses among infants with higher subsequent BI. These results provide preliminary insights into brain regions engaged by novelty in infants that may relate to later BI. The findings may inform understanding of anxiety disorders and guide future research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background and Objectives: Children born very preterm (VPT) have high rates of motor disability, but mechanisms for early identification remain limited, especially for children who fall behind in early childhood. This study examines the relationship between functional connectivity (FC) measured at term-equivalent age and motor outcomes at 2 and 5 years., Methods: In this longitudinal observational cohort study, VPT children (gestational age 30 weeks and younger) with and without high-grade brain injury underwent FC MRI at term-equivalent age. Motor development was assessed using the Bayley Scales of Infant Development, Third Edition, at corrected age 2 years and Movement Assessment Battery for Children, Second Edition, at age 5 years. Logistic and negative binomial/Poisson regression models examined relationships between FC measures and 5-year task scores, with and without 2-year scores as covariates. Infants were categorized as "injured" or "uninjured" based on structural MRI findings at term-equivalent age., Results: In the injured group (n = 34), each 1 SD decrease in neonatal left-right motor cortex FC was related to approximately 4× increased odds of being unable to complete a fine motor task at age 5 (log odds = -1.34, p < 0.05). In the uninjured group (n = 41), stronger basal ganglia-motor cortex FC was related to poorer fine motor scores (Est = -0.40, p < 0.05) and stronger cerebellum-motor cortex FC was related to poorer balance and fine motor scores (Est = -0.05 to -0.23, p < 0.05), with balance persisting with adjustment for 2-year scores., Discussion: In VPT children with brain injury, interhemispheric motor cortex FC was related to motor deficits at 5-year assessment, similar to previous findings at 2 years. In uninjured children, FC-measured disruption of the motor system during the neonatal period was associated with motor planning/coordination difficulties that were not apparent on 2-year assessment but emerged at 5 years, suggesting that the neural basis of these deficits was established very early in life. Subsequently, 2-year follow-up may not be sufficient to detect milder motor deficits in VPT children, and they should be monitored for motor difficulties throughout the preschool years. For all VPT children, FC at term-equivalent age has the potential to improve our ability to predict disability before it presents behaviorally., Competing Interests: The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2024 American Academy of Neurology.)

Objective: To examine whether adverse childhood experiences (ACEs) confer risk for socioemotional problems in children born very preterm (VPT)., Study Design: As part of a longitudinal study, 96 infants born VPT at 23-30 weeks of gestation were recruited from a level III neonatal intensive care unit and underwent follow-up at ages 2 and 5 years. Eighty-three full-term (FT) (37-41 weeks gestation) children were recruited from an adjoining obstetric service and the local community. ACEs were assessed with the Child Life Events Scale at age 2 and Preschool Age Psychiatric Assessment at age 5. At age 5, internalizing, externalizing, and attention deficit hyperactivity disorder (ADHD) symptoms were assessed with the Child Behavior Checklist and Conner's Rating Scale-Revised, respectively. Covariates including socioeconomic disadvantage, maternal distress, and parent ADHD symptoms were assessed at the 2- and/or 5-year follow-up. Mediation and moderation analysis, accounting for family clustering, examined associations between birth group, ACEs, and socioemotional outcomes., Results: After covariate adjustment, children born VPT experienced more ACEs (P < .001), particularly medical ACEs (P < .01), and had worse ADHD and internalizing outcomes (P < .05) than full-term children. ACEs mediated the association between birth group and ADHD outcomes (95% CI, 0.11-4.08). There was no evidence of mediation for internalizing outcomes. Higher parent ADHD symptoms (P < .001) and maternal distress (P < .05) were associated with poorer internalizing outcomes., Conclusions: Screening for childhood ACEs should be embedded in the follow-up care of children born VPT and their families. Strategies to screen for and address parent psychosocial functioning may be important to support children's socioemotional development., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate whether parenting or neonatal brain volumes mediate associations between prenatal social disadvantage (PSD) and cognitive/language abilities and whether these mechanisms vary by level of disadvantage., Study Design: Pregnant women were recruited prospectively from obstetric clinics in St Louis, Missouri. PSD encompassed access to social (eg, education) and material (eg, income to needs, health insurance, area deprivation, and nutrition) resources during pregnancy. Neonates underwent brain magnetic resonance imaging. Mother-child dyads (n = 202) returned at age 1 year for parenting observations and at age 2 years for cognition/language assessments (Bayley Scales of Infant and Toddler Development, Third Edition). Generalized additive and mediation models tested hypotheses., Results: Greater PSD associated nonlinearly with poorer cognitive/language scores. Associations between parenting and cognition/language were moderated by disadvantage, such that supportive and nonsupportive parenting behaviors related only to cognition/language in children with lesser PSD. Parenting mediation effects differed by level of disadvantage: both supportive and nonsupportive parenting mediated PSD-cognition/language associations in children with lesser disadvantage, but not in children with greater disadvantage. PSD-associated reductions in neonatal subcortical grey matter (β = 0.19; q = 0.03), white matter (β = 0.23; q = 0.02), and total brain volume (β = 0.18; q = 0.03) were associated with lower cognition, but did not mediate the associations between PSD and cognition., Conclusions: Parenting moderates and mediates associations between PSD and early cognition and language, but only in families with less social disadvantage. These findings, although correlational, suggest that there may be a critical threshold of disadvantage, below which mediating or moderating factors become less effective, highlighting the importance of reducing disadvantage as primary prevention., Competing Interests: Declaration of Competing Interest This study was funded by R01MH113883, K01MH122735, T32NS121881, and T32 MH100019 from the NIH, the March of Dimes Foundation, grant MI-II-2018-725 from the Children's Discovery Institute, grant P50 HD103525 from the Washington University Intellectual and Developmental Disability Research Center, and National Alliance for Research on Schizophrenia & Depression Young Investigator Grant 28521 from the Brain and Behavior Research Foundation, and grant KL2 TR00234. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The brain develops rapidly from the final trimester of gestation through childhood, with cortical surface area expanding greatly in the first decade of life. However, it is unclear exactly where and how cortical surface area changes after birth, or how prematurity affects these developmental trajectories. Fifty-two very preterm (gestational age at birth = 26 ± 1.6 weeks) and 41 full-term (gestational age at birth = 39 ± 1.2 weeks) infants were scanned using structural magnetic resonance imaging at term-equivalent age and again at 9/10 years of age. Individual cortical surface reconstructions were extracted for each scan. Infant and 9/10 cortical surfaces were aligned using anatomically constrained Multimodal Surface Matching (aMSM), a technique that allows calculation of local expansion gradients across the cortical surface for each individual subject. At the neonatal time point, very preterm infants had significantly smaller surface area than their full-term peers ( P < 0.001), but at the age 9/10-year time point, very preterm and full-term children had comparable surface area ( P > 0.05). Across all subjects, cortical expansion by age 9/10 years was most pronounced in frontal, temporal, and supramarginal/inferior parietal junction areas, which are key association cortices ( P Spin < 0.001). Very preterm children showed greater cortical surface area expansion between term-equivalent age and age 9/10 compared to their full-term peers in the medial and lateral frontal areas, precuneus, and middle temporal/banks of the superior sulcus junction ( P < 0.05). Furthermore, within the very preterm group, expansion was highly variable within the orbitofrontal cortex and posterior regions of the brain. By mapping these patterns across the cortex, we identify differences in association cortices that are known to be important for executive functioning, emotion processing, and social cognition. Additional longitudinal work will be needed to understand if increased expansion in very preterm children is adaptive, or if differences persist into adulthood., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

The cerebral cortex comprises discrete cortical areas that form during development. Accurate area parcellation in neuroimaging studies enhances statistical power and comparability across studies. The formation of cortical areas is influenced by intrinsic embryonic patterning as well as extrinsic inputs, particularly through postnatal exposure. Given the substantial changes in brain volume, microstructure, and functional connectivity during the first years of life, we hypothesized that cortical areas in 1-to-3-year-olds would exhibit major differences from those in neonates and progressively resemble adults as development progresses. Here, we parcellated the cerebral cortex into putative areas using local functional connectivity gradients in 92 toddlers at 2 years old. We demonstrated high reproducibility of these cortical regions across 1-to-3-year-olds in two independent datasets. The area boundaries in 1-to-3-year-olds were more similar to adults than neonates. While the age-specific group parcellation fitted better to the underlying functional connectivity in individuals during the first 3 years, adult area parcellations might still have some utility in developmental studies, especially in children older than 6 years. Additionally, we provided connectivity-based community assignments of the parcels, showing fragmented anterior and posterior components based on the strongest connectivity, yet alignment with adult systems when weaker connectivity was included., Competing Interests: Declaration of Competing Interests The authors declared no competing interests directly related to this manuscript.

Environmental influences on brain structure and function during early development have been well-characterized, but whether early environments are associated with the pace of brain development is not clear. In pre-registered analyses, we use flexible non-linear models to test the theory that prenatal disadvantage is associated with differences in trajectories of intrinsic brain network development from birth to three years (n = 261). Prenatal disadvantage was assessed using a latent factor of socioeconomic disadvantage that included measures of mother's income-to-needs ratio, educational attainment, area deprivation index, insurance status, and nutrition. We find that prenatal disadvantage is associated with developmental increases in cortical network segregation, with neonates and toddlers with greater exposure to prenatal disadvantage showing a steeper increase in cortical network segregation with age, consistent with accelerated network development. Associations between prenatal disadvantage and cortical network segregation occur at the local scale and conform to a sensorimotor-association hierarchy of cortical organization. Disadvantage-associated differences in cortical network segregation are associated with language abilities at two years, such that lower segregation is associated with improved language abilities. These results shed light on associations between the early environment and trajectories of cortical development., (© 2024. The Author(s).)

Recent research has reported effects of socioeconomic status on neurobehavioral development as early as infancy, including positive associations between income and brain structure, functional connectivity, and behavior later in childhood (Ramphal, Whalen, et al., 2020; Triplett et al., 2022). This study extends this literature by investigating the relation of maternal prenatal social disadvantage (PSD) to neonatal amygdala and hippocampus functional connectivity and whether socioeconomic-related alterations in functional connectivity subsequently predict behavior at age 12 months in a large, socioeconomically diverse sample ( N = 261 mother-infant dyads). PSD was assessed across gestation; neonatal magnetic resonance imaging was completed within the first weeks of life; and infant internalizing and externalizing symptoms were evaluated using the Infant-Toddler Social and Emotional Assessment at age 12 months. The results showed that PSD was significantly related to neonatal right amygdala and left hippocampus functional connectivity with prefrontal and motor-related regions. Social disadvantage-related right amygdala and left hippocampus functional connectivity with these regions was subsequently related to infant externalizing and internalizing symptoms at age 12 months. Building off an emerging literature exploring prenatal impacts on neonatal functional connectivity, this study further emphasizes the important role of the maternal environment during gestation on infant brain function and its relationship with externalizing and internalizing behavior in the first years of life. The results suggest that the prenatal socioeconomic environment may be a promising target for interventions aimed at improving infant neurobehavioral outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Studies have established that maternal sleep and circadian rhythm disturbances during pregnancy are associated with poor prenatal and perinatal outcomes for mothers and offspring. However, little work has explored its effects on infant sleep or socioemotional outcomes. The current study examined the relationship between maternal sleep and circadian rhythm disturbances during pregnancy and infant sleep and socioemotional outcomes in a diverse sample of N = 193 mothers and their infants (51% White; 52% Female; M age  = 11.95 months). Maternal sleep and circadian rhythms during pregnancy were assessed using self-reports and actigraphy. Mothers reported on infants' sleep and socioemotional outcomes when infants were one year old. When controlling for infant sex, age, gestational age at birth, family income-to-needs ratios, and maternal depression, mothers who reported more sleep problems during pregnancy had infants with more sleep disturbances when they were one year old. Moreover, mothers who had later sleep timing (i.e., went to bed and woke up later, measured via actigraphy) during pregnancy had infants with more dysregulation (e.g., increased feeding difficulties, sensory sensitivities) and externalizing problems, and mothers with increased intra-daily variability in rest-activity rhythms (as measured via actigraphy) had infants with more externalizing problems. Findings suggest that maternal sleep and circadian rhythm disturbances during pregnancy may be a risk factor for infant sleep problems and socioemotional difficulties., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Although limited research suggests that infants can behave prosocially even before their first birthdays, the prevalence and characteristics of early prosocial behaviors remain unexplored. Indeed, very few studies of prosocial development have included 12-month-old infants or examined how prosociality changes across the second year, and none has assessed individual differences in prosocial strategy use. This study investigated prosocial helping behaviors in a racially and socioeconomically diverse sample of 220 11- to 20-month-olds living in the United States (45.5% female; 61% Black; 67.2% low socioeconomic status). At 12 months ( n = 153), > 80% of infants helped an experimenter retrieve out-of-reach items. Modest increases in helping were observed across the second year of life. Individual differences in specific helping strategies were also detected. Infants who helped more by handing an item to an experimenter on one task (rather than placing the item in a target location) also helped more by handing on another task; similar patterns were found with placing. Moreover, the type of strategy was associated with age and sex: older infants and male infants used more placing. The high rates of helping by 12 months of age and the use of individual helping strategies demonstrate that infants have robust prosocial abilities beyond those previously documented. These findings contribute critical information about the typical development of prosocial behaviors in the largest and most racially and socioeconomically diverse sample of infants to date. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Early life adversity is associated with microstructural alterations in white matter regions that subserve language. However, the mediating and moderating pathways between adversities experienced in utero and key neonatal white matter tracts including the corpus callosum (CC), superior longitudinal fasciculus (SLF), arcuate fasciculus (AF), inferior fronto- occipital fasciculus (IFOF), and uncinate on early language outcomes remains unknown., Methods: This longitudinal study includes 160 neonates, oversampled for prenatal exposure to adversity, who underwent diffusion MRI (dMRI) in the first weeks of life. dMRI parameters were obtained using probabilistic tractography in FSL. Maternal Social Disadvantage and Psychosocial Stress was assessed throughout pregnancy. At age 2 years, the Bayley Scales of Infant and Toddler Development-III evaluated language outcomes. Linear regression, mediation, and moderation assessed associations between prenatal adversities and neonatal white matter on language outcomes., Results: Prenatal exposure to Social Disadvantage (p<.001) and Maternal Psychosocial Stress (p<.001) were correlated with poorer language outcomes. When Social Disadvantage and maternal Psychosocial Stress were modeled simultaneously in relation to language outcomes, only Social Disadvantage was significant (p<.001). Independent of Social Disadvantage (p<.001), lower neonatal CC fractional anisotropy (FA) was related to poorer global (p=.02) and receptive (p=.02) language outcomes. CC FA did not mediate the association between Social Disadvantage and language outcomes (indirect effect 95% CIs -0.96-0.15), and there was no interaction between Social Disadvantage and CC FA on language outcomes (p>.05). Bilateral SLF/AF, IFOF, and uncinate were not significant (p>.05)., Conclusions: Prenatal exposure to Social Disadvantage and neonatal CC FA were independently related to language problems by age 2, with no evidence of mediating or moderating associations with language outcomes. These findings elucidate the early neural underpinnings of language development and suggest that the prenatal period may be an important time to provide poverty- reducing support to expectant mothers to promote offspring neurodevelopmental outcomes.

Background: Among presenting conditions in pediatric acute care settings, conduct disorder (CD) is a potentially stigmatizing yet common diagnosis in the setting of behavioral dysregulation requiring psychiatric admission. Concerns exist about over-diagnosis of CD in non-Hispanic Black children relative to White peers and the potential for the CD diagnosis to obfuscate manifestations of co-occurring psychiatric conditions., Methods: We evaluated the number of manuscripts on CD diagnoses that report race and ethnicity and co-occurring mental health characteristics (i.e., history of trauma, attention-deficit hyperactivity disorder [ADHD], or substance use disorders [SUDs]) that are often undertreated in racially minoritized children. Using the keywords "conduct disorder" or "externalizing disorder," we screened peer-reviewed articles in PubMed published from January 2013 to November 2023., Results: We screened 2791 manuscripts for potential inclusion, of which 136 were original research articles with data on children with CD diagnoses. Thirteen articles contained racial and ethnic data for people with CD diagnoses, with the majority illustrating that Black children were overrepresented among those with CD diagnoses. No studies provided details on how race and ethnicity were ascertained and few mentioned racism as a potential explanation for racial disparities in CD diagnoses. No studies contained data collected after 2016, with three studies using data collected as early as 2001-2002. Across all articles, data on co-occurring trauma, ADHD, and SUDs were scarce., Conclusions: The overwhelming majority of studies on CD diagnoses did not provide comprehensive data on race and ethnicity and co-occurring psychiatric disorders in children receiving diagnoses of CD., (© 2024 The Author(s). Psychiatric Research and Clinical Practice published by Wiley Periodicals LLC on behalf of American Psychiatric Association.)

Objective: The objective of this study was to evaluate whether volumetric measurements on early cranial ultrasound (CUS) in high-grade germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) are associated with hydrocephalus and neurodevelopmental metrics., Methods: A retrospective case series analysis of infants with high-grade GMH-IVH admitted to the St. Louis Children's Hospital neonatal intensive care unit between 2007 and 2015 who underwent neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) at 2 years of corrected age was performed. GMH volume, periventricular hemorrhagic infarction volume, and frontotemporal horn ratio were obtained from direct review of neonatal CUS studies. Univariate and multivariable regression models were used to evaluate the association between hemorrhage volumes and hydrocephalus requiring permanent CSF diversion with ventricular shunt or endoscopic third ventriculostomy with or without choroid plexus cauterization and composite Bayley-III cognitive, language, and motor scores., Results: Forty-three infants (29 males, mean gestational age 25 weeks) met the inclusion criteria. The mean age at time of the CUS with the largest hemorrhage volume or first diagnosis of highest grade was 6.2 days. Nineteen patients underwent treatment for hydrocephalus with permanent CSF diversion. In multivariable analyses, larger GMH volume was associated with worse estimated Bayley-III cognitive (left-sided GMH volume: p = 0.048, total GMH volume: p = 0.023) and motor (left-sided GMH volume: p = 0.010; total GMH volume: p = 0.014) scores. Larger periventricular hemorrhagic infarction volume was associated with worse estimated Bayley-III motor scores (each side p < 0.04). Larger left-sided (OR 2.55, 95% CI 1.10-5.88; p = 0.028) and total (OR 1.35, 95% CI 1.01-1.79; p = 0.041) GMH volumes correlated with hydrocephalus. There was no relationship between early ventricular volume and hydrocephalus or neurodevelopmental outcomes., Conclusions: Location-specific hemorrhage volume on early CUS may be prognostic for neurodevelopmental and hydrocephalus outcomes in high-grade GMH-IVH.

Objective: Prenatal exposure to neighborhood crime has been associated with weaker neonatal frontolimbic connectivity; however, associations with early childhood behavior remain unclear. We hypothesized that living in a high-crime neighborhood would be related to higher externalizing symptoms at age 1 and 2 years, over and above other adversities, and that neonatal frontolimbic connectivity and observed parenting behaviors at 1 year would mediate this relationship., Method: Participants included 399 pregnant women, recruited as part of the Early Life Adversity, Biological Embedding, and Risk for Developmental Precursors of Mental Disorders (eLABE) study. Geocoded neighborhood crime data was obtained from Applied Geographic Solution. A total of 319 healthy, non-sedated neonates underwent scanning using resting-state functional magnetic resonance imaging (fMRI) on a Prisma 3T scanner and had ≥10 minutes of high-quality data. Infant-Toddler Socioemotional Assessment Externalizing T scores were available for 274 mothers of 1-year-olds and 257 mothers of 2-year-olds. Observed parenting behaviors were available for 202 parent-infant dyads at 1 year. Multilevel and mediation models tested longitudinal associations., Results: Living in a neighborhood with high violent (β = 0.15, CI = 0.05-0.27, p = .004) and property (β = 0.10, CI = 0.01-0.20, p = .039) crime was related to more externalizing symptoms at 1 and 2 years, controlling for other adversities. Weaker frontolimbic connectivity was also associated with higher externalizing symptoms at 1 and 2 years. After controlling for other adversities, parenting behaviors mediated the specific association between crime and externalizing symptoms, but frontolimbic connectivity did not., Conclusion: These findings provide evidence that early exposure to neighborhood crime and weaker neonatal frontolimbic connectivity may influence later externalizing symptoms, and suggest that parenting may be an early intervention target for families in high-crime areas., Plain Language Summary: This longitudinal study of 399 women and their children found that toddlers who lived in a high crime area during the first 2 years of their lives displayed more externalizing symptoms. Toddlers with weaker frontolimbic brain function at birth also had higher externalizing symptoms at 1 and 2 years. Interestingly, parenting behaviors, but not neonatal brain function, mediated the relationship between neighborhood crime exposure and externalizing symptoms in toddlerhood., Diversity & Inclusion Statement: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work., (Copyright © 2023 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Increasing cannabis use among pregnant people and equivocal evidence linking prenatal cannabis exposure to adverse outcomes in offspring highlights the need to understand its potential impact on pregnancy and child outcomes. Assessing cannabis use during pregnancy remains a major challenge with potential influences of stigma on self-report as well as detection limitations of easily collected biological matrices., Objective: This descriptive study examined the concordance between self-reported (SR) cannabis use and urine drug screen (UDS) detection of cannabis exposure during the first trimester of pregnancy and characterized concordant and discordant groups for sociodemographic factors, modes of use, secondhand exposure to cannabis and tobacco, and alcohol use and cotinine positivity., Study Design: The Cannabis Use During Development and Early Life (CUDDEL) Study is an ongoing longitudinal study that recruits pregnant individuals presenting for obstetric care, who report lifetime cannabis use as well as using (n = 289) or not using cannabis (n = 169) during pregnancy. During the first trimester pregnancy visit, SR of cannabis use and a UDS for cannabis, other illicit drugs and nicotine are acquired from eligible participants, of whom 333 as of 05/01/2023 had both., Results: Using available CUDDEL Study data on both SR and UDS (n = 333; age 26.6 ± 4.7; 88.6% Black; 45.4% below federal poverty threshold; 56.5% with paid employment; 89% with high school education; 22% first pregnancy; 12.3 ± 3.6 weeks gestation), we classified pregnant individuals with SR and UDS data into 4 groups based on concordance (k = 0.49 [95% C.I. 0.40-0.58]) between SR cannabis use and UDS cannabis detection during the first trimester: 1) SR+/UDS+ (n = 107); 2) SR-/UDS- (n = 142); 3) SR+/UDS- (n = 44); 4) SR-/UDS+ (n = 40). Those who were SR+/UDS- reported less frequent cannabis use and fewer hours under the influence of cannabis during their pregnancy. Those who were SR-/UDS+ were more likely to have joined the study at a lower gestational age with 62.5% reporting cannabis use during their pregnancy prior to being aware that they were pregnant. Of the 40 SR-/UDS+ women, 14 (i.e., 35%) reported past month secondhand exposure, or blunt usage. In the subset of individuals with SR and UDS available at trimester 2 (N = 160) and 3 (N = 140), concordant groups were mostly stable and > 50% of those in the discordant groups became concordant by the second trimester. Classifying individuals as exposed or not exposed who were SR+ and/or UDS+ resulted in minor changes in group status based on self-report at screening., Conclusion: Overall, there was moderate concordance between SR and UDS for cannabis use/exposure during pregnancy. Instances of SR+/UDS- discordancy may partially be attributable to lower levels of use that are not detected on UDS. SR-/UDS+ discordancy may arise from recent use prior to knowledge of pregnancy, extreme secondhand exposure, deception, and challenges with completing questionnaires. Acquiring both self-report and biological detection of cannabis use/exposure allows for the examination of convergent evidence. Classifying those who are SR+ and/or UDS+ as individuals who used cannabis during their first trimester after being aware of their pregnancy resulted in only a minor change in exposure status; thus, relying on self-report screening, at least in this population and within this sociocultural context likely provides an adequate approximation of cannabis use during pregnancy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ryan Bogdan, Arpana Agrawal, Cynthia Rogers reports financial support was provided by NIH., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Social anxiety is associated with alterations in socioemotional processing, but the pathophysiology remains poorly understood. Movies present an opportunity to examine more naturalistic socioemotional processing by providing narrative and sensory context to emotion cues. This study aimed to characterize associations between neural response to contextualized social cues and social anxiety symptoms in children., Method: Data from the Healthy Brain Network (final N = 740; age range 5-15 years) were split into discovery and replication samples to maximize generalizability of findings. Associations of parent- and self-reported social anxiety (Screen for Child Anxiety-related Emotional Disorders) with mean differences and person-to-person variability in functional magnetic resonance imaging-measured activation to 2 emotionally dynamic movies were characterized., Results: Though no evidence was found to indicate social anxiety symptoms were associated with mean differences in neural activity to emotional content (fit Spearman rs < 0.09), children with high social anxiety symptoms had higher intersubject activation variability in the posterior cingulate, supramarginal gyrus, and inferior frontal gyrus (Bonferroni familywise error-corrected ps < .05)-regions associated with attention, alertness, and emotion cue processing. Identified regions varied by age group and informant. Across ages, these effects were enhanced for scenes containing greater sensory intensity (brighter, louder, more motion, more vibrance)., Conclusion: These results provide evidence that children with high social anxiety symptoms show high person-to-person variability in the neural processing of sensory aspects of emotional content. These data indicate that children with high social anxiety may require personalized interventions for sensory and emotional difficulties, as the underlying neurology differs from child to child., Diversity & Inclusion Statement: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list., (Copyright © 2023 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Purpose/background: Brexanolone is approved for postpartum depression (PPD) by the United States Food and Drug Administration. Brexanolone has outperformed placebo in clinical trials, but less is known about the efficacy in real-world patients with complex social and medical histories. Furthermore, the impact of brexanolone on large-scale brain systems such as changes in functional connectivity (FC) is unknown., Methods/procedures: We tracked changes in depressive symptoms across a diverse group of patients who received brexanolone at a large medical center. Edinburgh Postnatal Depression Scale (EPDS) scores were collected through chart review for 17 patients immediately prior to infusion through approximately 1 year postinfusion. In 2 participants, we performed precision functional neuroimaging (pfMRI), including before and after treatment in 1 patient. pfMRI collects many hours of data in individuals for precision medicine applications and was performed to assess the feasibility of investigating changes in FC with brexanolone., Findings/results: The mean EPDS score immediately postinfusion was significantly lower than the mean preinfusion score (mean change [95% CI]: 10.76 [7.11-14.40], t (15) = 6.29, P < 0.0001). The mean EPDS score stayed significantly lower at 1 week (mean difference [95% CI]: 9.50 [5.23-13.76], t (11) = 4.90, P = 0.0005) and 3 months (mean difference [95% CI]: 9.99 [4.71-15.27], t (6) = 4.63, P = 0.0036) postinfusion. Widespread changes in FC followed infusion, which correlated with EPDS scores., Implications/conclusions: Brexanolone is a successful treatment for PPD in the clinical setting. In conjunction with routine clinical care, brexanolone was linked to a reduction in symptoms lasting at least 3 months. pfMRI is feasible in postpartum patients receiving brexanolone and has the potential to elucidate individual-specific mechanisms of action., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Pregnant women in poverty may be especially likely to experience sleep and circadian rhythm disturbances, which may have downstream effects on fetal neurodevelopment. However, the associations between sleep and circadian rhythm disturbances, social disadvantage during pregnancy, and neonatal brain structure remains poorly understood. The current study explored the association between maternal sleep and circadian rhythm disturbances during pregnancy and neonatal brain outcomes, examining sleep and circadian rhythm disturbances as a mediator of the effect of social disadvantage during pregnancy on infant structural brain outcomes. The study included 148 mother-infant dyads, recruited during early pregnancy, who had both actigraphy and neuroimaging data. Mothers' sleep was assessed throughout their pregnancy using actigraphy, and neonates underwent brain magnetic resonance imaging in the first weeks of life. Neonatal structural brain outcomes included cortical gray matter, subcortical gray matter, and white matter volumes along with a measure of the total surface area of the cortex. Neonates of mothers who experienced greater inter-daily deviations in sleep duration had smaller total cortical gray and white matter volumes and reduced cortical surface areas. Neonates of mothers who had higher levels of circadian misalignment and later sleep timing during pregnancy showed smaller subcortical gray matter volumes. Inter-daily deviations in sleep duration during pregnancy mediated the association between maternal social disadvantage and neonatal structural brain outcomes. Findings highlight the importance of regularity and rhythmicity in sleep schedules during pregnancy and bring to light the role of chronodisruption as a potential mechanism underlying the deleterious neurodevelopmental effects of prenatal adversity. RESEARCH HIGHLIGHTS: Social disadvantage was associated with sleep and circadian rhythm disturbances during pregnancy, including later sleep schedules, increased variability in sleep duration, circadian misalignment, and a higher proportion of the sleep period spent awake. Maternal sleep and circadian rhythm disturbances during pregnancy were associated with decreased brain volume and reduced cortical surface area in neonates. Maternal inter-daily deviations in sleep duration during pregnancy mediated the association between social disadvantage and neonatal brain volume and cortical surface area., (© 2023 John Wiley & Sons Ltd.)

Importance: Defining basic psychosocial resources to facilitate thriving in the first year of life could tangibly inform policy and enhance child development worldwide., Objective: To determine if key environmental supports measured as a thrive factor (T-factor) in the first year of life positively impact brain, cognitive, and socioemotional outcomes through age 3., Design, Setting, and Participants: This prospective longitudinal cohort study took place at a Midwestern academic medical center from 2017 through 2022. Participants included singleton offspring oversampled for those facing poverty, without birth complications, congenital anomalies, or in utero substance exposures (except cigarettes and marijuana) ascertained prenatally and followed up prospectively for the first 3 years of life. Data were analyzed from March 9, 2023, through January 3, 2024., Exposures: Varying levels of prenatal social disadvantage advantage and a T-factor composed of environmental stimulation, nutrition, neighborhood safety, positive caregiving, and child sleep., Main Outcomes & Measures: Gray and white matter brain volumes and cortical folding at ages 2 and 3 years, cognitive and language abilities at age 3 years measured by the Bayley-III, and internalizing and externalizing symptoms at age 2 years measured by the Infant-Toddler Social and Emotional Assessment., Results: The T-factor was positively associated with child cognitive abilities (β = 0.33; 95% CI, 0.14-0.52), controlling key variables including prenatal social disadvantage (PSD) and maternal cognitive abilities. The T-factor was associated with child language (β = 0.36; 95% CI, 0.24-0.49), but not after covarying for PSD. The association of the T-factor with child cognitive and language abilities was moderated by PSD (β = -0.32; 95% CI, -0.48 to -0.15 and β = -0.36; 95% CI, -0.52 to -0.20, respectively). Increases in the T-factor were positively associated with these outcomes, but only for children at the mean and 1 SD below the mean of PSD. The T-factor was negatively associated with child externalizing and internalizing symptoms over and above PSD and other covariates (β = -0.30; 95% CI, -0.52 to -0.08 and β = -0.32; 95% CI, -0.55 to -0.09, respectively). Increasing T-factor scores were associated with decreases in internalizing symptoms, but only for children with PSD 1 SD above the mean. The T-factor was positively associated with child cortical gray matter above PSD and other covariates (β = 0.29; 95% CI, 0.04-0.54), with no interaction between PSD and T-factor., Conclusions and Relevance: Findings from this study suggest that key aspects of the psychosocial environment in the first year impact critical developmental outcomes including cognitive, brain, and socioemotional development at age 3 years. This suggests that environmental resources and enhancement in the first year of life may facilitate every infant's ability to thrive, setting the stage for a more positive developmental trajectory.

Objective: Resource deprivation is linked to systemic factors that disproportionately impact historically marginalized communities, and theoretical work suggests that resource deprivation may increase risk for bullying behaviors. Bullying perpetration is an intransigent social problem and an early risk factor that perpetuates the school-to-prison pipeline. This study explored how resource deprivation (family- and neighborhood-level metrics) was associated with early childhood bullying behaviors and clinician-rated symptoms of psychopathology, while accounting for other known risk factors (early life stressors, traumatic events, parental arrest, domestic violence)., Method: Participants (306 children, mean age = 4.45 years) were enrolled in a longitudinal study (Preschool Depression Study) where demographics, clinician-rated assessments of psychopathology, and parent reports of social functioning were collected. Measures of bullying behaviors (bullying perpetration, generalized aggression, and victimization) were constructed. A cross-sectional approach was employed, and analyses examined the interrelations between race, bullying-related behaviors, resource deprivation, and psychopathology, while accounting for confounding variables, at the baseline assessment time point., Results: The bullying measure showed acceptable model fit (comparative fit index = 0.956, Tucker-Lewis index = 0.945, root mean square error of approximation = 0.061, standardized root mean residual = 0.052, normed χ 2 ratio = 2). Neighborhood resource deprivation was more strongly associated with bullying perpetration (r = 0.324, p < .001) than generalized aggression (r = 0.236, Williams t 303  = 2.11, p = .036) and remained significant when controlling for other known risk factors (parental arrests, domestic violence, stressors, traumas) and demographic factors. Bullying perpetration was linked with racial category, but the relation was fully mediated by neighborhood resource deprivation. Linear regression including bullying behaviors and symptoms of clinical psychopathology suggested that resource deprivation specifically led to increases in bullying perpetration (t = 2.831, p = .005) and clinician-rated symptoms of conduct disorder (t = 2.827, p = .005), which were attributable to increased rates of resource-driven conduct symptoms (bullies, lies to obtain goods, stolen without confrontation)., Conclusion: Resource deprivation is strongly and specifically associated with increases in bullying perpetration. Children growing up in impoverished neighborhoods show significant increases in resource-driven conduct behaviors, yet interventions often target individual-level factors. These results highlight the need to target social inequity to reduce bullying perpetration and suggest that interventions targeting neighborhoods should be tested to reduce bullying in early childhood., Diversity & Inclusion Statement: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. One or more of the authors of this paper received support from a program designed to increase minority representation in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. We actively worked to promote sex and gender balance in our author group. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list., (Copyright © 2024. Published by Elsevier Inc.)

The development of empathy and prosocial behavior begins in infancy and is likely supported by emotion processing skills. The current study explored whether early emerging deficits in emotion processing are associated with disruptions in the development of empathy and prosociality. We investigated this question in a large, diverse sample of 147, 11- to 20-month-old infants (42% female; 61% Black; 67% low socioeconomic status). Infants completed two observational tasks assessing prosocial helping and one task assessing empathy and prosocial comforting behavior. Infants also completed an eye-tracking task assessing engagement and disengagement with negative emotional faces. Infants who attended less to angry, sad, and fearful faces (i.e., by being slower to look at and/or quicker to look away from negative compared to neutral faces) engaged in fewer helping behaviors, and effect sizes were larger when examining infants' attention toward the eye regions of faces. Additionally, infants who were quicker to look away from the eye regions of angry faces, but not the whole face, displayed less empathy and comforting behaviors. Results suggest that as early as 12 months of age, infants' decreased attention toward negative emotional faces, particularly the eye regions, is associated with less empathy and prosociality during a developmental period in which these abilities are rapidly maturing., (© 2024 International Congress of Infant Studies (ICIS).)

Importance: Children with high callous-unemotional traits are more likely to develop severe and persistent conduct problems; however, the newborn neurobiology underlying early callous-unemotional traits remains unknown. Understanding the neural mechanisms that precede the development of callous-unemotional traits could help identify at-risk children and encourage development of novel treatments., Objective: To determine whether newborn brain function is associated with early-emerging empathy, prosociality, and callous-unemotional traits., Design, Setting, and Participants: In this prospective, longitudinal cohort study, pregnant women were recruited from obstetric clinics in St Louis, Missouri, from September 1, 2017, to February 28, 2020, with longitudinal data collected until March 20, 2023. Mothers were recruited during pregnancy. Newborns underwent brain magnetic resonance imaging shortly after birth. Mothers completed longitudinal follow-up when the children were aged 1, 2, and 3 years., Exposures: The sample was enriched for exposure to socioeconomic disadvantage., Main Outcome and Measure: Functional connectivity between hypothesized brain regions was assessed using newborn-specific networks and voxel-based connectivity analyses. Children's callous-unemotional traits were measured using the Inventory of Callous-Unemotional Traits. Empathy and prosociality were assessed using the Infant and Toddler Socio-Emotional Assessment., Results: A total of 283 children (mean [SD] gestational age, 38 [2] weeks; 159 male [56.2%]; 2 Asian [0.7%], 171 Black [60%], 7 Hispanic or Latino [2.5%], 106 White [38%], 4 other racial or ethnic group [1.4%]) were included in the analysis. Stronger newborn functional connectivity between the cingulo-opercular network (CO) and medial prefrontal cortex (mPFC) was associated with higher callous-unemotional traits at age 3 years (β = 0.31; 95% CI, 0.17-0.41; P < .001). Results persisted when accounting for parental callous-unemotional traits and child externalizing symptoms. Stronger newborn CO-mPFC connectivity was also associated with lower empathy and lower prosociality at ages 1, 2, and 3 years using multilevel models (β = -0.12; 95% CI, -0.21 to -0.04; P = .004 and β = -0.20; 95% CI, -0.30 to -0.10; P < .001, respectively)., Conclusions and Relevance: Newborn functional connectivity was associated with early-emerging empathy, prosociality, and callous-unemotional traits, even when accounting for parental callous-unemotional traits and child externalizing symptoms. Understanding the neurobiological underpinnings of empathy, prosociality, and callous-unemotional traits at the earliest developmental point may help early risk stratification and novel intervention development.

Objective: We provide proof-of-principle for a mental health risk calculator advancing clinical utility of the irritability construct for identification of young children at high risk for common, early onsetting syndromes., Method: Data were harmonized from two longitudinal early childhood subsamples (total N  = 403; 50.1% Male; 66.7% Nonwhite; M age  = 4.3 years). The independent subsamples were clinically enriched via disruptive behavior and violence (Subsample 1) and depression (Subsample 2). In longitudinal models, epidemiologic risk prediction methods for risk calculators were applied to test the utility of the transdiagnostic indicator, early childhood irritability, in the context of other developmental and social-ecological indicators to predict risk of internalizing/externalizing disorders at preadolescence (M age  = 9.9 years). Predictors were retained when they improved model discrimination (area under the receiver operating characteristic curve [AUC] and integrated discrimination index [IDI]) beyond the base demographic model., Results: Compared to the base model, the addition of early childhood irritability and adverse childhood experiences significantly improved the AUC (0.765) and IDI slope (0.192). Overall, 23% of preschoolers went on to develop a preadolescent internalizing/externalizing disorder. For preschoolers with both elevated irritability and adverse childhood experiences, the likelihood of an internalizing/externalizing disorder was 39-66%., Conclusions: Predictive analytic tools enable personalized prediction of psychopathological risk for irritable young children, holding transformative potential for clinical translation.

Prenatal exposure to heightened maternal inflammation has been associated with adverse neurodevelopmental outcomes, including atypical brain maturation and psychiatric illness. In mothers experiencing socioeconomic disadvantage, immune activation can be a product of the chronic stress inherent to such environmental hardship. While growing preclinical and clinical evidence has shown links between altered neonatal brain development and increased inflammatory states in utero, the potential mechanism by which socioeconomic disadvantage differentially impacts neural-immune crosstalk remains unclear. In the current study, we investigated associations between socioeconomic disadvantage, gestational inflammation, and neonatal white matter microstructure in 320 mother-infant dyads over-sampled for poverty. We analyzed maternal serum levels of four cytokines (IL-6, IL-8, IL-10, TNF-α) over the course of pregnancy in relation to offspring white matter microstructure and socioeconomic disadvantage. Higher average maternal IL-6 was associated with very low socioeconomic status (SES; INR < 200% poverty line) and lower neonatal corticospinal fractional anisotropy (FA) and lower uncinate axial diffusivity (AD). No other cytokine was associated with SES. Higher average maternal IL-10 was associated with lower FA and higher radial diffusivity (RD) in corpus callosum and corticospinal tracts, higher optic radiation RD, lower uncinate AD, and lower FA in inferior fronto-occipital fasciculus and anterior limb of internal capsule tracts. SES moderated the relationship between average maternal TNF-α levels during gestation and neonatal white matter diffusivity. When these interactions were decomposed, the patterns indicated that this association was significant and positive among very low SES neonates, whereby TNF-α was inversely and significantly associated with inferior cingulum AD. By contrast, among the more advantaged neonates (lower-to-higher SES [INR ≥ 200% poverty line]), TNF-α was positively and significantly associated with superior cingulum AD. Taken together, these findings suggest that the relationship between prenatal cytokine exposure and white matter microstructure differs as a function of SES. These patterns are consistent with a scenario where gestational inflammation's effects on white matter development diverge depending on the availability of foundational resources in utero., (© 2024. The Author(s).)

The cerebral cortex is organized into distinct but interconnected cortical areas, which can be defined by abrupt differences in patterns of resting state functional connectivity (FC) across the cortical surface. Such parcellations of the cortex have been derived in adults and older infants, but there is no widely used surface parcellation available for the neonatal brain. Here, we first demonstrate that existing parcellations, including surface-based parcels derived from older samples as well as volume-based neonatal parcels, are a poor fit for neonatal surface data. We next derive a set of 283 cortical surface parcels from a sample of n = 261 neonates. These parcels have highly homogenous FC patterns and are validated using three external neonatal datasets. The Infomap algorithm is used to assign functional network identities to each parcel, and derived networks are consistent with prior work in neonates. The proposed parcellation may represent neonatal cortical areas and provides a powerful tool for neonatal neuroimaging studies., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Deficits in emotion intelligence (EI) are a key component of early-childhood callous-unemotional (CU) traits. Children's EI may be influenced by their mother's EI through both familial genetic and environmental mechanisms; however, no study has directly tested the role of maternal EI in the development of CU traits. This study investigated whether maternal EI had a direct relationship with children's CU traits when controlling for the potential influence of parenting affect and other psychiatric diagnoses. Mothers and their 3- to 5-year-old preschoolers (N = 200) were recruited as part of a parent-child interaction-emotion development therapy treatment trial for preschool clinical depression and comorbid psychopathology. Using data collected prior to treatment, regression models tested whether maternal EI was related to children's CU traits, which specific aspects of maternal EI were most strongly associated with CU traits, and whether associations held after accounting for observed parenting affect. Maternal EI (p < 0.005), specifically the ability to understand others' emotions (p < 0.01), was significantly associated with children's CU traits. This relationship was specific, as maternal EI did not predict depression or oppositional defiant disorder. Both maternal EI and observed negative parenting affect were independently and significantly related to CU traits (p < 0.05) in a combined model. Given that maternal EI and observed negative parenting affect were independent predictors of CU traits in preschoolers with comorbid depression, findings suggest that current treatments for CU traits that focus solely on improving parenting could be made more effective by targeting maternal EI and helping mothers better model emotional competence., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Buprenorphine extended-release (XR) is an extended-release monthly injection to treat opioid use disorder (OUD). This retrospective case series includes 15 postpartum patients who were treated with buprenorphine-XR at a single center and reports on their outcomes. The average total daily sublingual buprenorphine dose before initiation of buprenorphine-XR was 16.25 mg (SD±7.76, range 2-32 mg). Overall, 137 total doses of buprenorphine-XR were administered between May 17, 2021, and April 11, 2023. Urine toxicology test results were negative for opioids other than buprenorphine in the majority (80.0%) of patients once appropriate maintenance doses were achieved. Euphoria and intoxication were not reported. A minority of patients (20.0%) discontinued buprenorphine-XR. Although more extensive research is needed before widespread use, buprenorphine-XR may be a favorable treatment for OUD in this high-risk population., Competing Interests: Financial Disclosure Jeannie C. Kelly reports money was paid to her institution from the Barnes-Jewish Foundation St. Louis, PEW Charitable Trusts, NICHD, and the Doris Duke COVID-19 Fund to Retain Clinical Scientists. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Signaling pathways orchestrate fundamental biological processes, including development, regeneration, homeostasis, and disease. Methods to experimentally manipulate signaling are required to understand how signaling is interpreted in these wide-ranging contexts. Molecular optogenetic tools can provide reversible, tunable manipulations of signaling pathway activity with a high degree of spatiotemporal control and have been applied in vitro, ex vivo, and in vivo. These tools couple light-responsive protein domains, such as the blue light homodimerizing light-oxygen-voltage sensing (LOV) domain, with signaling effectors to confer light-dependent experimental control over signaling. This protocol provides practical guidelines for using the LOV-based bone morphogenetic protein (BMP) and Nodal signaling activators bOpto-BMP and bOpto-Nodal in the optically accessible early zebrafish embryo. It describes two control experiments: A quick phenotype assay to determine appropriate experimental conditions, and an immunofluorescence assay to directly assess signaling. Together, these control experiments can help establish a pipeline for using optogenetic tools in early zebrafish embryos. These strategies provide a powerful platform to investigate the roles of signaling in development, health, and physiology.

Objective: To examine profiles of distress of mothers of preterm infants in the neonatal intensive care unit (NICU) and relate profiles to maternal and child outcomes at child age 5 years., Method: A racially and economically diverse sample of mothers (n = 94; 39% African American, 52% White) of preterm infants (≤30 weeks of gestation) completed validated questionnaires assessing depression, anxiety (state and trait), NICU stress, and life stress at NICU discharge of their infant. Mothers reported on their own and their children's symptomatology at child age 5. A latent profile analysis was conducted to categorize maternal symptomatology., Results: Latent profile analysis yielded 4 distinct maternal profiles: low symptomatology, high NICU stress, high depression and anxiety, and high state anxiety. Social determinants of health factors including age, education, neighborhood deprivation, and infant clinical risk distinguished the profiles. Mothers in the high depression and anxiety profile reported more anxiety and life stress at follow-up and reported their children experienced more anxious/depressed symptoms., Conclusion: Existing literature has gaps related to examining multiple dimensions of NICU distress and understanding how patterns of mood/affective symptoms, life stressors, and related social determinants of health factors vary across mothers. In this study, one specific profile of maternal NICU distress demonstrated enduring risks for poorer maternal and child mental health outcomes. This new knowledge underscores sources of disparate health outcomes for mothers of preterm infants and the infants themselves. Universal screening is needed to identify at-risk dyads for poor health outcomes in need of individualized interventions that address both maternal and child well-being., Diversity & Inclusion Statement: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list., (Copyright © 2023 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Health disparities are driven by underlying social disadvantage and psychosocial stressors. However, how social disadvantage and psychosocial stressors lead to adverse health outcomes is unclear, particularly when exposure begins prenatally. Variations in the gut microbiome and circulating proinflammatory cytokines offer potential mechanistic pathways. Here, we interrogate the gut microbiome of mother-child dyads to compare high-versus-low prenatal social disadvantage, psychosocial stressors and maternal circulating cytokine cohorts (prospective case-control study design using gut microbiomes from 121 dyads profiled with 16 S rRNA sequencing and 89 dyads with shotgun metagenomic sequencing). Gut microbiome characteristics significantly predictive of social disadvantage and psychosocial stressors in the mothers and children indicate that different discriminatory taxa and related pathways are involved, including many species of Bifidobacterium and related pathways across several comparisons. The lowest inter-individual gut microbiome similarity was observed among high-social disadvantage/high-psychosocial stressors mothers, suggesting distinct environmental exposures driving a diverging gut microbiome assembly compared to low-social disadvantage/low-psychosocial stressors controls (P = 3.5 × 10 -5 for social disadvantage, P = 2.7 × 10 -15 for psychosocial stressors). Children's gut metagenome profiles at 4 months also significantly predicted high/low maternal prenatal IL-6 (P = 0.029), with many bacterial species overlapping those identified by social disadvantage and psychosocial stressors. These differences, based on maternal social and psychological status during a critical developmental window early in life, offer potentially modifiable targets to mitigate health inequities., (© 2023. Springer Nature Limited.)

Poverty increases the risk of poorer executive function (EF) in children born full-term (FT). Stressors associated with poverty, including variability in parenting behavior, may explain links between poverty and poorer EF, but this remains unclear for children born very preterm (VPT). We examine socioeconomic and parental psychosocial adversity on parenting behavior, and whether these factors independently or jointly influence EF in children born VPT. At age five years, 154 children (VPT = 88, FT = 66) completed parent-child interaction and EF tasks. Parental sensitivity, intrusiveness, cognitive stimulation, and positive and negative regard were coded with the Parent-Child Interaction Rating Scale. Socioeconomic adversity spanned maternal demographic stressors, Income-to-Needs ratio, and Area Deprivation Index. Parents completed measures of depression, anxiety, inattention/hyperactivity, parenting stress, and social-communication interaction (SCI) problems. Parental SCI problems were associated with parenting behavior in parents of children born VPT, whereas socioeconomic adversity was significant in parents of FT children. Negative parenting behaviors, but not positive parenting behaviors, were related to child EF. This association was explained by parental depression/anxiety symptoms and socioeconomic adversity. Results persisted after adjustment for parent and child IQ. Findings may inform research on dyadic interventions that embed treatment for parental mood/affective symptoms and SCI problems to improve childhood EF.

Introduction: Laws regulating substance use in pregnancy are changing and may have unintended consequences on scientific efforts to address the opioid epidemic. Yet, how these laws affect care and research is poorly understood., Methods: We conducted semi-structured qualitative interviews using purposive and snowball sampling of researchers who have engaged pregnant people experiencing substance use. We explored views on laws governing substance use in pregnancy and legal reform possibilities. Interviews were double coded. Data were examined using thematic analysis., Results: We interviewed 22 researchers (response rate: 71 per cent) and identified four themes: (i) harms of punitive laws, (ii) negative legal impacts on research, (iii) proposals for legal reform, and (iv) activism over time., Discussion: Researchers view laws penalizing substance use during pregnancy as failing to treat addiction as a disease and harming pregnant people and families. Respondents routinely made scientific compromises to protect participants. While some have successfully advocated for legal reform, ongoing advocacy is needed., Conclusion: Adverse impacts from criminalizing substance use during pregnancy extend to research on this common and stigmatized problem. Rather than penalizing substance use in pregnancy, laws should approach addiction as a medical issue and support scientific efforts to improve outcomes for affected families., (© The Author(s) 2023. Published by Oxford University Press on behalf of Duke University School of Law, Harvard Law School, Oxford University Press, and Stanford Law School. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Historically, the field of child psychiatry has lagged behind the field of general psychiatry in terms of research innovations and the availability of empirically supported treatment modalities. However, over the last two decades there has been increasing interest in and research focused on the developmental origins of mental disorders examining both neurobiological and psychosocial etiologies.1 This has catalyzed the field leading to advances in understanding the developmental psychopathology of mental disorders and the generation of novel early interventions that have shown significant promise.2-4 Further, catalyzing this effort is new data demonstrating the powerful impact of psychosocial forces on neurodevelopment. New methodologies and discoveries in the basic areas of early childhood developmental psychology have led to a greater appreciation for the emotional and cognitive sophistication of children in the first three years of life. Advances in methods to understand preverbal children's emotional and attentional responses (through measures of eye gaze and suck for example) as well as observational methods to glean a variety of mental health relevant behaviors early in life (e.g. behavioral inhibition, pro-social behaviors and social motivation) have further elucidated and validated these capacities. In addition, measures of neural function using electroencephalogram and evoked response potentials (EEG/ERP) and functional magnetic resonance imaging (fMRI) as early as the neonatal period, with many analysis methods developed at WUSTL, have further informed this domain providing new insight into early brain and behavioral relationships as well as how intervention impact brain function.5-7., (Copyright 2023 by the Missouri State Medical Association.)