Mechanisms Of Development Research Articles

The development of orofacial complex in bats: Implications for orofacial clefting.

Orofacial morphology in mammals plays a critical role in essential life functions such as feeding and communication, which are influenced by the shapes of these anatomical structures. Bats are known to exhibit highly diversified orofacial morphotypes within their clade, reflecting their varied diets and echolocation behaviors. The presence of bony discontinuities between the premaxilla and maxilla or among the premaxillae is a notable feature of bat orofacial morphology, observed in certain lineages. It is suggested that these unique orofacial morphotypes, not generally found in other mammals, have evolved in relation to dietary adaptations rather than merely for echolocation mode. Until now, the developmental background of the bony discontinuities in the bat orofacial complex has been insufficiently investigated. Here, we present a comparative study of the chondrocranium and epithelial organs in the orofacial complex of three bat species: Cynopterus sphinx, Rhinolophus malayanus, and Vespertilio sinensis. Our observations indicate that the preceding morphogenesis of orofacial cartilage and epithelial structures is remarkably different among these three species. In C. sphinx and V. sinensis, the region forming from the regression of the palatine process of the premaxilla was filled with orofacial cartilage and epithelial structures. We also found that the clefted morphology observed in R. malayanus and V. sinensis was formed via contrastingly divergent developmental processes. Midline clefts among Yangochiroptera have been previously categorized to represent a uniform morphotype, but our study highlights that attributing midline clefts into a singular category should be revisited, advocating for a nuanced categorization of cleft morphology based on their morphogenetic patterns. Further research on the bat orofacial complex may enhance our understanding of bat evolutionary diversification and offer insights into the developmental mechanisms of human cleft palate.

Integration and Differentiation of Transplanted Human iPSC-Derived Retinal Ganglion Cell Precursors in Murine Retinas

Optic neuropathy such as glaucoma, stemming from retinal ganglion cell (RGC) degeneration, is a leading cause of visual impairment. Given the substantial loss of RGCs preceding clinical detection of visual impairment, cell replacement therapy emerges as a compelling treatment strategy. Human-induced pluripotent stem cells (hiPSCs) serve as invaluable tools for exploring the developmental processes and pathological mechanisms associated with human RGCs. Utilizing a 3D stepwise differentiation protocol for retinal organoids, we successfully differentiated RGC precursors from hiPSCs harboring a BRN3B-GFP RGC reporter, verified by GFP expression. Intravitreal transplantation of enriched RGC precursors into healthy or N-methyl-D-aspartate (NMDA)-injured mice demonstrated their survival, migration, and integration into the proper retinal layer, the ganglion cell layer, after 3 weeks. Notably, these transplanted cells differentiated into marker-positive RGCs and extended neurites. Moreover, enhanced cell survival was observed with immunosuppressive and anti-inflammatory treatments of the host prior to transplantation. These data underscore the potential of transplanted RGC precursors as a promising therapeutic avenue for treating degenerative retinal diseases resulting from RGC dysfunction.

The ebony Gene in Silkworm Black Pupae Significantly Affects 30 K Proteins During the Pupal Stage

Background/Objectives: The body color and patterns of insects play important roles in foraging, evading predators, mating, thermoregulation, and environmental adaptation. During the rearing of the QiufengN silkworm strain, a mutant with black pupal cuticle (QiufengNBP) was discovered. Preliminary map-based cloning and sequence analysis indicated that the ebony gene might significantly influence the formation of the black pupa mutant and the expression of 30K proteins. This study aims to determine the function of the ebony gene and its effect on the expression of the 30K protein during the pupal stage; Methods and Results: We employed CRISPR/Cas9 gene-editing technology to knock out the ebony gene in the Nistari strain, resulting in individuals with black pupae, named Nistari Black Pupa (NisBP). This confirmed that the ebony gene plays a crucial role in black pupa formation. Two-dimensional electrophoresis (2-DE) analysis of the pupal cuticle of NisBP and its wild-type Nistari found that the ebony gene has a significant impact on the expression of 30K proteins, which are vital for embryonic development and serve as key storage proteins; Conclusions: This study is the first to demonstrate that the ebony gene affects the expression of 30K proteins, laying the foundation for further research on their functions and providing insights into the developmental mechanisms of silkworms.

Single-cell transcriptomics reveals evolutionary reconfiguration of embryonic cell fate specification in the sea urchin Heliocidaris erythrogramma.

Altered regulatory interactions during development likely underlie a large fraction of phenotypic diversity within and between species, yet identifying specific evolutionary changes remains challenging. Analysis of single-cell developmental transcriptomes from multiple species provides a powerful framework for unbiased identification of evolutionary changes in developmental mechanisms. Here, we leverage a "natural experiment" in developmental evolution in sea urchins, where a major life history switch recently evolved in the lineage leading to Heliocidaris erythrogramma, precipitating extensive changes in early development. Comparative analyses of scRNA-seq developmental time courses from H. erythrogramma and Lytechinus variegatus (representing the derived and ancestral states respectively) reveals numerous evolutionary changes in embryonic patterning. The earliest cell fate specification events and the primary signaling center are co-localized in the ancestral dGRN; remarkably, in H. erythrogramma they are spatially and temporally separate. Fate specification and differentiation are delayed in most embryonic cell lineages, although in some cases, these processes are conserved or even accelerated. Comparative analysis of regulator-target gene co-expression is consistent with many specific interactions being preserved but delayed in H. erythrogramma, while some otherwise widely conserved interactions have likely been lost. Finally, specific patterning events are directly correlated with evolutionary changes in larval morphology, suggesting that they are directly tied to the life history shift. Together, these findings demonstrate that comparative scRNA-seq developmental time courses can reveal a diverse set of evolutionary changes in embryonic patterning and provide an efficient way to identify likely candidate regulatory interactions for subsequent experimental validation.

AgRP neurons mediate activity-dependent development of oxytocin connectivity and autonomic regulation

During postnatal life, leptin specifies neuronal inputs to the paraventricular nucleus of the hypothalamus (PVH) and activates agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus. Activity-dependent developmental mechanisms impact refinement of sensory circuits, but whether leptin-mediated postnatal neuronal activity specifies hypothalamic neural projections is largely unexplored. Here, we used chemogenetics to manipulate the activity of AgRP neurons during a discrete postnatal critical period and evaluated the development of AgRP inputs to the PVH and descending efferent outflow to the dorsal vagal complex (DVC). In leptin-deficient mice, targeting of AgRP neuronal outgrowth to PVH oxytocin neurons was reduced, and despite the lack of leptin receptors found on oxytocin neurons in the PVH, oxytocin-containing connections to the DVC were also impaired. Activation of AgRP neurons during early postnatal life not only normalized AgRP inputs to the PVH but also oxytocin outputs to the DVC in leptin-deficient mice. Blocking AgRP neuron activity during the same postnatal period reduced the density of AgRP inputs to the PVH of wild type mice, as well as the density of oxytocin-containing DVC fibers, and these innervation deficits were associated with dysregulated autonomic function. These findings suggest that leptin-mediated AgRP neuronal activity is required for the development of PVH connectivity and represents a unique activity-dependent mechanism for specification of neural pathways involved in the hypothalamic integration of autonomic responses.

Developmental toxicity and mechanism of dibutyl phthalate on the development of subintestinal vessels in zebrafish

Background: The dibutyl phthalate (DBP) is a member of the phthalate family and is widely used as a plasticizer in daily life and production. However, the influence of DBP on the vascular developmental remains unclear. Methods: In this study, we used zebrafish as a model organism to investigate the effects of DBP on vascular development in vivo. Death curves of zebrafish at different concentrations of DBP exposure and different times incubation were made firstly. Zebrafish embryos after fertilization for 5.5 h were exposed to different concentrations of DBP solution (0, 0.4, 0.8, 1.2 mg/L), the body length, yolk sac absorption area, mortality and heart rate of zebrafish were measured, and the number and area of sprouting of ventral vessels were quantified by transgenic fish system. Reactive oxygen species (ROS) in zebrafish embryos were observed by DCFH-DA staining. Super oxide dimutese (SOD) and catalase (CAT) were determined with ELISA kits. Results: We found that DBP increased the oxidative stress level of zebrafish exposed to DBP, and the genes related to vascular development also increased. Meanwhile, the activities of SOD and CAT were greatly decreased after DBP exposure. In the rescue experiment, we found that the antioxidant astaxanthin and the small molecule VEGF inhibitor ZM-306,416 can reverse the vascular dysplasia caused by DBP. Conclusions: DBP induced vascular developmental toxicity by enhancing oxidative stress levels, activating HIF pathway, and interfering with the expression of vascular development-related pathways in zebrafish, results in the abnormal development of the subintestinal vessels in zebrafish.

Extracellular domains of CATSPERε are essential for CatSper assembly during development and activity modulation in sperm capacitation.

The flagellar-specific Ca 2+ channel CatSper is a multiprotein complex that is critical for successful fertilization by controlling the sperm Ca 2+ signaling in space and time. Large extracellular domains (ECDs) of four single-pass transmembrane subunits, CATSPERβ, γ, δ, and ε, form a unique canopy structure over the pore-forming channel. However, the molecular mechanisms of canopy assembly during development and its physiological function in mature sperm remain unknown. Here, using two genetic mouse models and the biochemical isolation of a bioactive CATSPERε fragment, we report that CATSPERε ECDs are essential for assembling the CatSper canopy, and thus the entire channel complex, and for modulating CatSper function for sperm hyperactivation and fertilization. CATSPERε-deficient males are sterile because their sperm fail to develop hyperactivated motility due to the absence of the entire channel. In transgenic mice overexpressing CATSPERε with truncated ECDs in testicular germ cells, truncated CATSPERε is unable to interact with native CatSper subunits and incorporate into the complex, thus failing to rescue the defective sperm hyperactivation and infertility of Catspere -null males. These findings provide insight into the underlying molecular and developmental mechanisms of CatSper complex assembly and how CatSper channels can be modulated in physiological settings and by therapeutic intervention.

Current concepts regarding developmental mechanisms in diabetic retinopathy in Taiwan

Current concepts regarding developmental mechanisms in diabetic retinopathy in Taiwan

Prospects for the use of perampanel in the treatment of epilepsy in patients with malignant gliomas of the brain

Epilepsy occurs in 35–95% of patients with low-grade malignant cerebral gliomas and in 29–71% of patients with high-grade gliomas. Seizures can be the first manifestation of a malignant cerebral glioma or may develop in the postoperative period and during chemoradiation therapy. This necessitates the use of antiepileptic drugs that can control seizures, ensure seizure prevention, and provide secondary seizure prophylaxis without reducing the effectiveness of anticancer therapy or the patient’s quality of life. The processes of epileptogenesis and oncogenesis are closely interrelated through common developmental mechanisms, with glutamate playing a key role. Increased glutamate secretion is accompanied by elevated expression and activation of its receptors, which raises seizure susceptibility. This is associated with increased levels of brain-derived neurotrophic factor, the number of synapses between peritumoral neurons and glioma cells, and the expression of various growth factors, all of which contribute to tumor progression. In this context, special attention is given to perampanel, a glutamate receptor antagonist and third-generation antiepileptic drug, in the treatment of epilepsy in patients with malignant cerebral gliomas. It has been shown that perampanel not only effectively controls seizures in patients with malignant cerebral gliomas but also suppresses tumor progression. Perampanel can dose-dependently enhance apoptosis and disrupt cell migration in malignant glioma cell lines. A synergistic effect of perampanel in combination with temozolamide has been identified. During chemoradiation therapy, perampanel exerts a protective effect on healthy peritumoral tissues. Adverse drug reactions associated with perampanel use are infrequent and mild. Further research is needed to investigate the anticonvulsant and antitumor efficacy of perampanel for the treatment of epilepsy in patients with malignant brain tumors.

Shared genetic architecture links energy metabolism, behavior and starvation resistance along a power-endurance axis

Abstract Shared developmental, physiological, and molecular mechanisms can generate strong genetic covariances across suites of traits, constraining genetic variability, and evolvability to certain axes in multivariate trait space (“variational modules” or “syndromes”). Such trait suites will not only respond jointly to selection; they will also covary across populations that diverged from one another by genetic drift. We report evidence for such a genetically correlated trait suite that links traits related to energy metabolism along a “power-endurance” axis in Drosophila melanogaster. The “power” pole of the axis is characterized by high potential for energy generation and expenditure—high expression of glycolysis and TCA cycle genes, high abundance of mitochondria, and high spontaneous locomotor activity. The opposite “endurance” pole is characterized by high triglyceride (fat) reserves, locomotor endurance, and starvation resistance (and low values of traits associated with the “power” pole). This trait suite also aligns with the first principal component of metabolome; the “power” direction is characterized by low levels of trehalose (blood sugar) and high levels of some amino acids and their derivatives, including creatine, a compound known to facilitate energy production in muscles. Our evidence comes from six replicate “Selected” populations adapted to a nutrient-poor larval diet regime during 250 generations of experimental evolution and six “Control” populations evolved in parallel on a standard diet regime. We found that, within each of these experimental evolutionary regimes, the above traits strongly covaried along this “power-endurance” axis across replicate populations which diversified by drift, indicating a shared genetic architecture. The two evolutionary regimes also drove divergence along this axis, with Selected populations on average displaced towards the “power” direction compared to Controls. Aspects of this “power-endurance” axis resemble the “pace of life” syndrome and the “thrifty phenotype”; it may have evolved as part of a coordinated organismal response to nutritional conditions.

Nanopore-Based Sequencing of the Full-Length Transcriptome of Male and Female Cleavage-Stage Embryos of the Chinese Mitten Crab (Eriocheir sinensis).

The cleavage stage plays a crucial role in embryo development, characterized by a swift surge in cell proliferation alongside the accurate genetic material transmission to offspring. To delve into the characteristics of sex development during the cleavage stage of embryos, we generated the full-length transcriptome of Eriocheir sinensis male and female cleavage-stage embryos using Oxford Nanopore Technologies (ONT). Notably, this investigation represents the first sequencing effort distinguishing between genders in E. sinensis embryos. In the transcriptome structure analysis, male and female cleavage-stage embryos, while not clustered, exhibited a comparable frequency of alternative splicing (AS) occurrences. We also successfully identified 2875 transcription factors (TFs). The quantitative analysis showed the top 150 genes, in which the highly expressed genes in male embryos predominantly related to protein synthesis and metabolism. Further investigation unveiled 500 differentially expressed genes (DEGs), of which 7 male-biased ribosomal protein genes (RPGs) were particularly noteworthy and further confirmed. These analyses suggest that there may be a more active protein synthesis process in male E. sinensis cleavage-stage embryos. Furthermore, among the 2875 identified TFs, we predicted that 18 TFs could regulate the differentially expressed RPGs, with most TFs belonging to the zf-C2H2 and Homeobox families, which are crucial for embryonic development. During the cleavage stage of E. sinensis, the differential RPGs between genders were intricately linked to energy metabolism. We proposed that these RPGs exert regulatory effects on gene expression in E. sinensis, thereby regulating the difference of development between male and females. Our research sheds light on the developmental mechanisms of E. sinensis during the embryo stage and establishes a groundwork for a deeper understanding of sex development in E. sinensis. The results also provide comprehensive full-length transcriptome data for future gene expression and genetic studies in E. sinensis.

Genetic Analysis of Heterotaxy in a Consanguineous Cohort.

Heterotaxy (HTX) is a group of clinical conditions with a shared pathology of dislocation of one or more organs along the left-right axis. The etiology of HTX is tremendously heterogeneous spanning environmental factors, chromosomal aberrations, mono/oligogenic variants, and complex inheritance. However, in the vast majority of cases, the etiology of HTX remains elusive. Here, we sought to describe the yield of genetic analysis and spectrum of variants in HTX in our highly consanguineous population. Twenty-four affected individuals, from 19 unrelated families, were consecutively recruited. Genetic analysis, with exome sequencing, genome sequencing, or multigene panel, detected 9 unique variants, 7 of which were novel, in 8 genes known to be implicated in autosomal recessive form of HTX (C1orf127, CCDC39, CIROP, DNAAF3, DNAH5, DNAH9, MMP21, and MNS1) providing a yield of 42.1%. Of note, 7 of the 9 variants were homozygous, while 2 were inherited in compound heterozygosity, including a heterozygous CNV deletion. A search for candidate genes in negative cases did not reveal a plausible variant. Our work demonstrates a relatively high yield of genetic testing in HTX in a consanguineous population with an enrichment of homozygous variants. The significant genetic heterogeneity observed herewith underscores the complex developmental mechanisms implicated in the pathogenesis of HTX and supports adopting a genome-wide analysis in the diagnostic evaluation of HTX.

Self-injury and suicidal behaviors in high-risk adolescents: Distal predictors, proximal correlates, and interactive effects of impulsivity and emotion dysregulation.

Suicide rates are rising among U.S. youth, yet our understanding of developmental mechanisms associated with increased suicide risk is limited. One high-risk pathway involves an interaction between heritable trait impulsivity and emotion dysregulation (ED). Together, these confer increased vulnerability to nonsuicidal self-injury (NSSI), suicide ideation (SI), and suicide attempts (SAs). Previous work, however, has been limited to homogeneous samples. We extend the Impulsivity × ED hypothesis to a more diverse sample of adolescents (N = 344, ages 12-15 at Baseline, 107 males and 237 females) who were treated for major depression and assessed four times over two years. In multilevel models, the impulsivity × ED interaction was associated with higher levels and worse trajectories of NSSI, SI, and SAs. As expected, stressful life events were also associated with poorer trajectories for all outcomes, and NSSI was associated with future and concurrent SI and SAs. These findings extend one developmental pathway of risk for self-harming and suicidal behaviors to more diverse adolescents, with potential implications for prevention.

Caregiver-child Neural Synchrony: Magic, Mirage, or Developmental Mechanism?

Young children transition in and out of more and less synchronous states with their caregivers across physiology, behavior, and brain activity, but what do these synchronous periods mean? One body of caregiver-child two-brain studies using fNIRS finds that individual, familial, and moment-to-moment behavioral and contextual factors are correlated with caregiver-child neural synchrony, while a separate body of literature finds that neural synchrony is associated with positive child outcomes. Taken together, it is tempting to conclude that caregiver-child neural synchrony may act as a key developmental mechanism linking children’s experiences to their healthy development, but many questions remain. In this brief review, we synthesize key findings and open questions from two-brain caregiver-child studies using functional near-infrared spectroscopy (fNIRS), which is uniquely well-suited for use with caregivers and children, but also laden with unique constraints. Throughout, we highlight key questions and best practice recommendations to optimize two-brain fNIRS to examine these critical developmental mechanisms from assumptions guiding study design to final analysis. We particularly emphasize the need to consider immediate and global stressors as context for interpretation of neural synchrony findings, and the need for full inclusion of socioeconomically and racially diverse families in future studies.

Clarifying the place of p300 in the empirical structure of psychopathology over development.

Psychophysiology can help elucidate the structure and developmental mechanisms of psychopathology, consistent with the Research Domain Criteria initiative. Cross-sectional research using categorical diagnoses indicates that P300 is an electrocortical endophenotype indexing genetic vulnerability to externalizing problems. However, current diagnostic systems' limitations impede a precise understanding of risk. The Hierarchical Taxonomy of Psychopathology (HiTOP) overcomes these limitations by delineating reliable dimensions ranging in specificity from broad spectra to narrow syndromes. The current study used a HiTOP-aligned approach to clarify P300's associations with a higher-order externalizing factor versus syndrome-specific manifestations within externalizing and internalizing spectra during middle and late adolescence. Participants from the Minnesota Twin Family Study's Enrichment Sample contributed psychophysiological and clinical data at age 14 (N = 930) and follow-up clinical data at age 17 (N = 913). Blunted target P300 at age 14 was selectively associated with externalizing as manifested at age 17 at the superspectrum level (rather than specific externalizing syndromes). Unlike in prior work, target P300 amplitude was positively associated with age 17 depressive symptoms (once controlling for standard stimuli). No association was observed with lifetime symptoms of childhood externalizing or depression evident by age 14. The results indicate that blunted target P300 elucidates specific risk for the development of late-adolescent/young-adult expressions of general externalizing, over and above symptoms evident by middle adolescence. Additionally, the findings speak to the synergistic utility of studying HiTOP-aligned dimensions using multiple measurement modalities to build a more comprehensive understanding of the development of psychopathology. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Prenatal maternal immune activation predicts observed fearfulness in infancy.

Fear reactivity is an early emerging temperament trait that predicts longer term behavioral and health outcomes. The current analysis tests the hypothesis, an extension of prior research on maternal immune activation (MIA), that the prenatal maternal immune system is a reliable predictor of observed fear reactivity in infancy. The analysis is based on a prospective longitudinal cohort study that collected data from the first trimester and conducted observational assessments of temperament at approximately 12 months of age (n = 281 infants). MIA was assessed from immune biomarkers measured in maternal blood at each trimester; infant temperament was assessed using the Laboratory Temperament Assessment Battery assessment at 12 months; covariates included family and sociodemographic factors. Patterns of inflammatory markers across gestation reliably predicted observed temperament: elevated prenatal MIA was associated with high fear reactivity to novel stimuli. The findings provide novel evidence of prenatal origins of fear reactivity and suggest developmental mechanisms that may underlie early emerging individual differences in child temperament. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Microcell-mediated chromosome transfer between non-identical human iPSCs

Microcell-mediated chromosome transfer (MMCT) is anticipated as a unique strategy to manipulate numbers of chromosomes, including the generation of hyperaneuploidy syndrome models with human induced pluripotent stem cells (hiPSCs). Mouse A9/Chinese hamster ovary (CHO) cell libraries of human monochromosomal hybrids as chromosome donor cells frequently show chromosomal rearrangement in the components. The generation of a new A9/CHO library is time-consuming and laborious. Here, we developed an MMCT method using hiPSCs as chromosome donor and recipient cells, through micronucleation using paclitaxel and reversine. Membrane fusion during the MMCT was mediated through interactions between the ecotropic viral envelope transiently expressed in chromosome donor cells and mCAT-1 in chromosome recipient cells. This approach involved tagging Chr21 and ChrY by CRISPR/Cas9 and transferring human/mouse artificial chromosomes, Chr21, ChrX, and ChrY, wherein there are no previous reports demonstrating a full-length introduction. Thus, a strategy that combined CRISPR/Cas9-mediated chromosome tagging and MMCT from hiPSCs as chromosome donor cells to hiPSCs as recipient cells systematically produced isogenic disease model hiPSCs with hyperaneuploidy. This approach allows the study of rare diseases and promises to provide new insights into early developmental mechanisms by introducing a comprehensive set of influential chromosomes/regions into hiPSCs.

Cutis Verticis Gyrata Differential Diagnosis: Clinical Case

Background. Cutis verticis gyrata is rare benign scalp disorder characterized by excessive skin and subcutaneous tissue proliferation and hypertrophy. Nowadays, there are three forms of this disease with various developmental mechanisms and associated manifestations. Clinical case description. This article presents the patient admitted with diagnosis and clinical picture of pachydermia, who underwent surgical excision of scalp abnormal tissues. However, the diagnosis of giant congenital melanocytic nevus was established according to the results of clinical examination. Later it was confirmed by histological and immunohistological studies. Moreover, pathogenic variants in the NRAS gene were not revealed. Conclusion. This case demonstrates the complexity of differential diagnosis of pachydermia that leads to careful examination of patients with morphogenetic studies of affected tissues samples.

Identifying cognitive, affective, and developmental mechanisms linking threat and deprivation with adolescent psychopathology.

The mechanisms linking early-life adversity with psychopathology over the life-course are complex. In this prospective study, we collectively examined cognitive, affective, and developmental mediators previously found to individually link childhood threat and deprivation experiences to adolescent psychopathology to identify the most potent mechanisms. Data came from a community sample of 227 children (mean child age 11.5 ± 0.5 years, 48.5% female) from the Seattle metro area with recruitment designed to reflect diversity in family income. Candidate mechanisms included self-rated pubertal development and task-measured attention bias to threat, emotion regulation, theory of mind, fear learning, inhibitory control, language ability, reasoning, and reward sensitivity. Using a high-dimensional mediation approach, we determined which mediating pathways linking threat and deprivation to psychopathology persisted after controlling for all candidate mechanisms associated with psychopathology. Models additionally controlled for the child's age, sex, early-childhood emotional and behavioral symptoms, poverty, and maternal depression. Blunted reward sensitivity mediated the prospective relationship between threat and internalizing psychopathology, explaining 17.25% (95% CI 1.08%, 69.96%) of this association. Advanced pubertal development was associated with increases in internalizing and externalizing symptoms (standardized associations of 0.16 (95% CI 0.03, 0.29) and 0.17 (95% CI 0.05, 0.29), respectively), but not with adversity. Although deprivation was strongly related to psychopathology, no mechanisms were empirically identified. In a well-characterized community sample, we isolated reward sensitivity as a robust mediator of the prospective association between early-life threat and adolescent internalizing psychopathology. Interventions aimed at bolstering reward sensitivity may mitigate the impact of early-life threat experiences on internalizing problems.

An Examination of Underlying Domains in Childhood Adversity: A Scoping Review of Studies Conducting Factor Analyses on Adverse Childhood Experiences.

There is an abundance of research linking experiences of childhood adversity to negative physical and mental health outcomes. Areas that remain to be explored and expanded upon include the ideal set of events for inclusion in measures of childhood adversity and testing the models of risk (e.g., cumulative, specificity, dimensional). In the current paper, we performed a scoping review to develop a comprehensive list of studies that conducted factor analyses of childhood adversity measures. There were 89 articles that met the inclusion criteria; trends in the underlying factor structures are reported. Highly associated yet distinct constructs of adversity have demonstrated empirical utility in predicting outcomes in dozens of studies, with consensus that physical abuse, emotional abuse, sexual abuse, physical and emotional neglect, and household dysfunction offer important predictive value to understanding developmental mechanisms of change. We endorse revisions to one commonly used scale that could offer researchers a consistent and psychometrically robust measure of adversity.