Machine Learning Analysis Using RNA Sequencing to Distinguish Neuromyelitis Optica from Multiple Sclerosis and Identify Therapeutic Candidates.

This study aims to identify RNA biomarkers distinguishing neuromyelitis optica (NMO) from relapsing-remitting multiple sclerosis (RRMS) and explore potential therapeutic applications leveraging machine learning (ML). An ensemble approach was developed using differential gene expression analysis and competitive ML methods, interrogating total RNA-sequencing data sets from peripheral whole blood of treatment-naïve patients with RRMS and NMO and healthy individuals. Pathway analysis of candidate biomarkers informed the biological context of disease, transcription factor activity, and small-molecule therapeutic potential. ML models differentiated between patients with NMO and RRMS, with the performance of certain models exceeding 90% accuracy. RNA biomarkers driving model performance were associated with ribosomal dysfunction and viral infection. Regulatory networks of kinases and transcription factors identified biological associations and identified potential therapeutic targets. Small-molecule candidates capable of reversing perturbed gene expression were uncovered. Mitoxantrone and vorinostat-two identified small molecules with previously reported use in patients with NMO and experimental autoimmune encephalomyelitis-reinforced discovered expression signatures and highlighted the potential to identify new therapeutic candidates. Putative RNA biomarkers were identified that accurately distinguish NMO from RRMS and healthy individuals. The application of multivariate approaches in analysis of RNA-sequencing data further enhances the discovery of unique RNA biomarkers, accelerating the development of new methods for disease detection, monitoring, and therapeutics. Integrating biological understanding further enhances detection of disease-specific signatures and possible therapeutic targets.

The role of epigenetic mechanisms in the long-term effects of early-life adversity and mother-infant relationship on physiology and behavior of offspring in laboratory rats and mice.

Maternal care during the early postnatal period of altricial mammals is a key factor in the survival and adaptation of offspring to environmental conditions. Natural variations in maternal care and experimental manipulations with maternal-child relationships modeling early-life adversity (ELA) in laboratory rats and mice have a strong long-term influence on the physiology and behavior of offspring in rats and mice. This literature review is devoted to the latest research on the role of epigenetic mechanisms in these effects of ELA and mother-infant relationship, with a focus on the regulation of hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor. An important part of this review is dedicated to pharmacological interventions and epigenetic editing as tools for studying the causal role of epigenetic mechanisms in the development of physiological and behavioral profiles. A special section of the manuscript will discuss the translational potential of the discussed research.

Statistical and Machine Learning Analysis in Brain-Imaging Genetics: A Review of Methods.

Brain-imaging-genetic analysis is an emerging field of research that aims at aggregating data from neuroimaging modalities, which characterize brain structure or function, and genetic data, which capture the structure and function of the genome, to explain or predict normal (or abnormal) brain performance. Brain-imaging-genetic studies offer great potential for understanding complex brain-related diseases/disorders of genetic etiology. Still, a combined brain-wide genome-wide analysis is difficult to perform as typical datasets fuse multiple modalities, each with high dimensionality, unique correlational landscapes, and often low statistical signal-to-noise ratios. In this review, we outline the progress in brain-imaging-genetic methodologies starting from early massive univariate to current deep learning approaches, highlighting each approach's strengths and weaknesses and elongating it with the field's development. We conclude by discussing selected remaining challenges and prospects for the field.

Associations between telomere length, glucocorticoid receptor gene DNA methylation, volume of stress-related brain structures, and academic performance in middle-school-age children.

Background: The biological embedding theory posits that early life experiences can lead to enduring physiological and molecular changes impacting various life outcomes, notably academic performance. Studying previously revealed and objective biomarkers of early life stress exposure, such as telomere length (TL), glucocorticoid receptor gene DNA methylation (DNAme), and the volume of brain structures involved in the regulation of HPA axis functioning (the hippocampus, the amygdala, and the medial prefrontal cortex), in relation to academic performance is crucial. This approach provides an objective measure that surpasses the limitations of self-reported early life adversity and reveals potential molecular and neurological targets for interventions to enhance academic outcomes. Methods: The participants were 52 children of Mexican or Central American origin aged 11.6-15.6 years. DNA methylation levels and TL were analyzed in three cell sources: saliva, whole blood, and T cells derived from whole blood. Results: Overall, the concordance across three systems of stress-related biomarkers (TL, DNAme, and the brain) was observed to some extent, although it was less pronounced than we expected; no consistency in different cell sources was revealed. Each of the academic domains that we studied was characterized by a unique and distinct complex of associations with biomarkers, both in terms of the type of biomarker, the directionality of the observed effects, and the cell source of biomarkers. Furthermore, there were biomarker-by-sex interaction effects in predicting academic performance measures. Conclusions: Assessed in an understudied youth sample, these preliminary data present new essential evidence for a deepened understanding of the biological mechanisms behind associations between exposure to early life stress and academic performance.

A Dimensional Approach to Discrepancy in Parenting Styles in Russian Families.

We investigated the magnitude and direction of differences in parenting styles as they relate to children's mental health problems, as assessed using the CBCL. The sample consisted of 306 families residing in a large industrial city in Russia. We aimed to expand the cross-cultural literature on parenting styles by assessing a sample of Russian families and analyzing how agreement versus disagreement between self-reported and partner-reported parenting styles related to children's mental health problems. The findings suggested that both congruence and incongruence between parenting styles could be associated with children's mental health problems. When parents agreed about high warmth and matched on lower levels of demandingness, in line with the permissive parenting style, children tended to exhibit maladaptive behavior and externalizing problems. We also registered that children were likely to show low levels of mental health problems when fathers had higher self-reported warmth compared with mothers' reports. In contrast, children whose fathers had higher self-reported demandingness compared with the mothers' reports, exhibited moderate levels of mental health problems. This study expands the existing literature by providing a dimensional approach to children's mental health difficulties in the context of (dis)agreements in the parenting styles within a family.

The Role of Neural and Genetic Processes in Learning to Read and Specific Reading Disabilities: Implications for Instruction.

To learn to read, the brain must repurpose neural systems for oral language and visual processing to mediate written language. We begin with a description of computational models for how alphabetic written language is processed. Next, we explain the roles of a dorsal sublexical system in the brain that relates print and speech, a ventral lexical system that develops the visual expertise for rapid orthographic processing at the word level, and the role of cognitive control networks that regulate attentional processes as children read. We then use studies of children, adult illiterates learning to read, and studies of poor readers involved in intervention, to demonstrate the plasticity of these neural networks in development and in relation to instruction. We provide a brief overview of the rapid increase in the field's understanding and technology for assessing genetic influence on reading. Family studies of twins have shown that reading skills are heritable, and molecular genetic studies have identified numerous regions of the genome that may harbor candidate genes for the heritability of reading. In selected families, reading impairment has been associated with major genetic effects, despite individual gene contributions across the broader population that appear to be small. Neural and genetic studies do not prescribe how children should be taught to read, but these studies have underscored the critical role of early intervention and ongoing support. These studies also have highlighted how structured instruction that facilitates access to the sublexical components of words is a critical part of training the brain to read.

Pediatric Symptom Checklist-17: Factor Structure and Uniform Differential Item Functioning Across Gender and Age in HIV Orphans and Vulnerable Children in Zambia.

This study aimed to investigate the psychometric properties of the Pediatric Symptom Checklist-17 (PSC-17) in a sample of children orphaned or made vulnerable (OVC) by HIV in Zambia. Caregivers of 1,076 OVC (55.1% boys; Mage = 12.91 years) completed the PSC-17. Competing models, including confirmatory factor analysis (CFA), hierarchical CFA, bifactor CFA, exploratory structural equation modeling (ESEM), and bifactor ESEM, were tested to evaluate the optimal factor structure of the PSC-17. Results showed that the bifactor ESEM provided the best approximation of the PSC-17 data with a well-defined general psychosocial problems factor explaining 72% of the reliable variance in the total score and an internalizing factor containing 63% of reliable variance unique from the general factor. The observed overall psychosocial problems score was associated with lower academic achievement and working memory (with small effect sizes), supporting the discriminant validity of score interpretation. Results of multiple indicators multiple causes (MIMIC) analyses revealed that all items functioned equivalently across child gender and age.

Assessing Cognitive Skills in Early Childhood Education Using a Bilingual Early Language Learner Assessment Tool.

In this article, we propose that basic cognitive skills may be fostered and assessed in early childhood educational (pre-K) settings using a technology-based approach to assessment. BELLA (Bilingual English Language Learner Assessment), designed for use with both monolingual (English or Spanish speaking) and bilingual (English and Spanish speaking) children, is designed to attend to cognitive skill development in addition to (pre-)academic knowledge. Specifically, BELLA assesses analytical, creative, and practical thinking in 3-5-year-old children through unique item content and delivery. BELLA is among the first tablet-based pre-K assessments designed to assess cognitive skills needed for the era of the Anthropocene.

Racial/ethnic disparities of the pact in predicting recidivism and court dispositions for justice-involved youth.

OBJECTIVE: Responding to the concern about racial/ethnic disparities (R/ED) in the use of risk assessment instruments (RAIs) in justice systems, previous research has overwhelmingly tested the extent to which RAI scores consistently predict recidivism across race and ethnicity (predictive bias). However, little is known about R/ED in the association between RAI measures and court dispositions (disparate application) for justice-involved youths. This study investigated predictive bias and disparate application of three risk measures-criminal history, social history, and the overall risk level-produced by the Positive Achievement Change Tool (PACT) for White, Black, and Hispanic justice-involved youths. HYPOTHESES: Given the mixed evidence in existing research for predictive bias and lack of evidence for disparate application, we did not make any specific hypothesis but conducted exploratory analyses. From a clinical perspective, however, we anticipated little or no evidence to support predictive bias and disparate application of the PACT among White, Black, and Hispanic youths in the jurisdiction we examined. METHOD: The sample consisted of 5,578 youths (11.4% White, 43.9% Black, and 44.7% Hispanic) who completed the PACT while in the Harris County Juvenile Probation Department, Texas. The outcome variables included recidivism (general and violent reoffending) and court dispositions (deferred adjudication, probation without placement, and probation with placement). We ran a series of moderating binary logistic regression models and moderating ordinal logistic regression models to evaluate predictive bias and disparate application. RESULTS: Race and ethnicity influenced how the criminal history score related to violent recidivism: This compromised the validity of the score as a predictor of recidivism. Moreover, evidence showed that the overall risk of reoffending was associated with harsher sanctioning decisions for Black and Hispanic youths than for White youths. CONCLUSION: Ensuring that RAI results are consistently interpreted and used in informing decisions is as important as ensuring that RAI scores function equally well in predicting recidivism regardless of race and ethnicity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Language: Its Origin and Ongoing Evolution.

With the present paper, we sought to use research findings to illustrate the following thesis: the evolution of language follows the principles of human evolution. We argued that language does not exist for its own sake, it is one of a multitude of skills that developed to achieve a shared communicative goal, and all its features are reflective of this. Ongoing emerging language adaptations strive to better fit the present state of the human species. Theories of language have evolved from a single-modality to multimodal, from human-specific to usage-based and goal-driven. We proposed that language should be viewed as a multitude of communication techniques that have developed and are developing in response to selective pressure. The precise nature of language is shaped by the needs of the species (arguably, uniquely H. sapiens) utilizing it, and the emergence of new situational adaptations, as well as new forms and types of human language, demonstrates that language includes an act driven by a communicative goal. This article serves as an overview of the current state of psycholinguistic research on the topic of language evolution.

Does the Potocki-Lupski Syndrome Convey the Autism Spectrum Disorder Phenotype? Case Report and Scoping Review.

Potocki-Lupski Syndrome (PTLS) is a rare condition associated with a duplication of 17p11.2 that may underlie a wide range of congenital abnormalities and heterogeneous behavioral phenotypes. Along with developmental delay and intellectual disability, autism-specific traits are often reported to be the most common among patients with PTLS. To contribute to the discussion of the role of autism spectrum disorder (ASD) in the PTLS phenotype, we present a case of a female adolescent with a de novo dup(17) (p11.2p11.2) without ASD features, focusing on in-depth clinical, behavioral, and electrophysiological (EEG) evaluations. Among EEG features, we found the atypical peak-slow wave patterns and a unique saw-like sharp wave of 13 Hz that was not previously described in any other patient. The power spectral density of the resting state EEG was typical in our patient with only the values of non-linear EEG dynamics: Hjorth complexity and fractal dimension were drastically attenuated compared with the patient's neurotypical peers. Here we also summarize results from previously published reports of PTLS that point to the approximately 21% occurrence of ASD in PTLS that might be biased, taking into account methodological limitations. More consistent among PTLS patients were intellectual disability and speech and language disorders.

Effects of childhood institutionalization on semantic processing and its neural correlates persist into adolescence and adulthood.

Individuals raised in institutionalized care settings are more likely to demonstrate developmental deficits than those raised in biological families. One domain that is vulnerable to the impoverished environments characteristic of some institutionalized care facilities is language development. We used EEG to assess ERPs and source-localized event-related spectral perturbations (ERSPs) associated with semantic processing at different levels of picture-word conflict and low versus high word frequency. Additionally, we assessed behavioral language ability (a synonyms task) and IQ. Participants (N = 454) were adolescents and adults with a history of institutionalized care (N = 187) or raised in biological families (N = 267), both recruited from secondary educational settings to approximately match the groups on age and education. Results indicate that individuals with a history of institutionalization are less accurate at judging whether semantic information in a spoken word matches an image. Additionally, those with a history of institutionalization show reduced cognitive control of conflict and more reactive N400 ERPs and beta ERSPs when handling picture-word conflict, especially in the left hemisphere. Frontal theta is related to semantic and conflict processing; however, in this study it did not vary with institutionalization.

The global prevalence of autism spectrum disorder: A three-level meta-analysis.

Autism spectrum disorder (ASD) is one the most disabling developmental disorders, imposing an extremely high economic burden. Obtaining as accurate prevalence estimates as possible is crucial to guide governments in planning policies for identification and intervention for individuals with ASD and their relatives. The precision of prevalence estimates can be heightened by summative analyses of the data collected around the world. To that end, we conducted a three-level mixed-effects meta-analysis. A systematic search of the Web of Science, PubMed, EMBASE, and PsycINFO databases from 2000 up to 13 July 2020 was performed, and reference lists of previous reviews and existing databases of prevalence studies were screened. Overall, 79 studies were included in the analysis of ASD and 59-in the analysis of previously existing relevant diagnoses: 30 for Autistic Disorder (AD), 15 for Asperger Syndrome (AS), and 14 for Atypical Autism (AA) and Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS); these research reports covered the period from 1994 to 2019. Pooled prevalence estimates were 0.72% (95% CI = 0.61-0.85) for ASD, 0.25% (95% CI = 0.18-0.33) for AD, 0.13% (95% CI = 0.07-0.20) for AS, and 0.18% (95% CI = 0.10-0.28) for the combined group of AA and PDD-NOS. Estimates were higher (1) for the studies that used records-review surveillance rather than other designs; (2) in North America compared with other geographical regions; and (3) in high-income compared with lower-income countries. The highest prevalence estimates were registered in the USA. There was an increase in autism prevalence estimates over time. The prevalence was also significantly higher for children aged between 6 and 12 years compared to children under the age of 5 and over the age of 13 years. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019131525, identifier CRD42019131525.

Applying Item Response Theory Analysis to the SAVRY in Justice-Involved Youth.

This study investigated item- and test-level functioning of the Structured Assessment of Violence Risk in Youth (SAVRY) and differential item functioning (DIF) across gender and race/ethnicity in justice-involved youth (JIY) using item response theory analysis. Participants were 868 JIY (23.7% female; 26.9% White, 50.9% Black, and 22.2% Hispanic) in pre-trial detention centers in Connecticut. Results obtained from the application of the graded response model showed that the SAVRY items were not equally discriminating JIY with varying levels of the latent trait, with "Poor compliance" as the most discriminating item and "History of self-harm or suicide attempts" as the least discriminating item. At the test level, the SAVRY provided precise (reliable) information about the latent trait for the majority of JIY whose latent trait between two standard deviations below and above the mean. Results of DIF revealed that six items operated inconsistently between White, Black, and Hispanic JIY, among which two items also functioned differentially across gender.

Exploring Genetic and Neural Risk of Specific Reading Disability within a Nuclear Twin Family Case Study: A Translational Clinical Application.

Imaging and genetic studies have characterized biological risk factors contributing to specific reading disability (SRD). The current study aimed to apply this literature to a family of twins discordant for SRD and an older sibling with reading difficulty. Intraclass correlations were used to understand the similarity of imaging phenotypes between pairs. Reading-related genes and brain region phenotypes, including asymmetry indices representing the relative size of left compared to right hemispheric structures, were descriptively examined. SNPs that corresponded between the SRD siblings and not the typically developing (TD) siblings were in genes ZNF385D, LPHN3, CNTNAP2, FGF18, NOP9, CMIP, MYO18B, and RBFOX2. Imaging phenotypes were similar among all sibling pairs for grey matter volume and surface area, but cortical thickness in reading-related regions of interest (ROIs) was more similar among the siblings with SRD, followed by the twins, and then the TD twin and older siblings, suggesting cortical thickness may differentiate risk for this family. The siblings with SRD had more symmetry of cortical thickness in the transverse temporal and superior temporal gyri, while the TD sibling had greater rightward asymmetry. The TD sibling had a greater leftward asymmetry of grey matter volume and cortical surface area in the fusiform, supramarginal, and transverse temporal gyrus. This exploratory study demonstrated that reading-related risk factors appeared to correspond with SRD within this family, suggesting that early examination of biological factors may benefit early identification. Future studies may benefit from the use of polygenic risk scores or machine learning to better understand SRD risk.

Brief Report: Unexpected Bilingualism: A Case of a Russian Child With ASD.

Some children with autism spectrum disorders (ASD) demonstrate unusual islets of abilities or "splinter skills" that represent relative strengths in their development. In this paper we present a clinical case of an 11-year-old Russian boy with ASD who spontaneously acquired the English language. While the child demonstrated language deficits in both English and Russian, the discrepancy between the languages was paradoxical given the lack of exposure to English language. This case study brings into question the importance of a language environment for children with ASD. Alternative pathway to language acquisition is discussed. We hypothesize that that incidental second language acquisition in children with ASD resulting from media exposure could become more frequent with the availability of the Internet.

Cognitive and academic performance of rural Zambian youth exposed to HIV.

Studies focusing on children affected by HIV have shown that they have generally lower academic performance, however, few studies separate children who are HIV exposed and infected (CHEI) and those who are HIV exposed but uninfected (CHEU). Importantly, in rural sub-Saharan Africa, the majority of studies on CHEI and CHEU examine academic performance indirectly based on cognitive test scores. Therefore, studies assessing the effects of HIV on academic achievement directly for CHEI and CHEU are needed. This article evaluates the effects of HIV-infection on cognitive and academic performance by comparing CHEI (n = 82) and CHEU (n = 1045) aged 7-17 years old using cross-sectional data from an ongoing longitudinal study in a rural area of Zambia. Youth completed cognitive and academic assessments; their height and weight were assessed to generate Body Mass Index (BMI). Caregiver questionnaires provided information on youths' years in school and household socio-economic status (SES). Results indicated that while HIV infection status did explain some of the variance in performance between CHEI and CHEU, age, BMI, years of schooling and SES accounted for additional variance. The effect of years of schooling on both cognitive and academic performance demonstrated that CHEI's performance may be greatly improved by consistent school enrollment.

Endogenous oxytocin and human social interactions: A systematic review and meta-analysis.

While there has been an increase in studies investigating the relationship between endogenous oxytocin (OXT) concentrations and human social interactions over the past decades, these studies still seem far from converging, both in methodological terms and in terms of their results. This systematic review and meta-analysis were aimed at a comprehensive evaluation and synthesis of empirical evidence on the relationship between endogenous OXT concentrations and human social interactions by reviewing studies published between 1970 and July 2020 and addressing various related methodological and analytical limitations. Sixty-three studies were included in the qualitative synthesis, and results from 51 studies were pooled in a meta-analysis (n = 3,741 participants). The results indicated that social interaction did not lead to an expected hormonal response in causal designs, either in a pre-post design (g = 0.079) or when comparing experimental conditions with and without social interaction (g = 0.256). However, in correlational designs, the overall mean effect size (ES) of the correlations between indicators of social interaction and OXT concentrations was significantly different from zero (z = 0.137). In both designs, subgroup analyses revealed that studies involving either parent-child interactions, or the utilization of the enzyme-linked immunosorbent assay method for OXT analysis, or unrestricted eating, drinking, or exercise before biofluid collection showed significantly higher than zero mean ESs. This review exposes the observed inconsistencies and suggests that standardized, replicable, and reliable approaches to assessing social interaction and measuring OXT concentrations need to be developed to study neurochemical mechanisms of sociality in humans. (PsycInfo Database Record (c) 2023 APA, all rights reserved).