Nutritional control of developmental processes.

Nutritional and metabolic cues are integral to animal development. Organisms use them both as sustenance and environmental indicators, fueling, informing and influencing developmental decisions. Classical examples, such as the Warburg effect, clearly illustrate how genetic programs control metabolic changes. However, the way that nutrition and metabolism can also modulate or drive genetic programs to instruct developmental trajectories is much more elusive, owing to several difficulties including uncoupling permissive and instructive functions. Here, we discuss recent advancements in the field that highlight the developmental role of nutritional and metabolic cues across multiple levels of organismal complexity.

Multiscale spatio-temporal dynamics of UBE3A gene in brain physiology and neurodevelopmental disorders.

The UBE3A gene, located in the chromosomal region 15q11-13, is subject to neuron-specific genomic imprinting and it plays a critical role in brain development. Genetic defects of UBE3A cause severe neurodevelopmental disorders, namely the Angelman syndrome (AS) and the 15q11.2-q13.3 duplication syndrome (Dup15q). In the last two decades, the development of in vitro and in vivo models of AS and Dup15q were fundamental to improve the understanding of UBE3A function in the brain. However, the pathogenic mechanisms of these diseases remain elusive and effective treatments are lacking. Recent evidence suggests that UBE3A functions are both spatially and temporally specific, varying across subcellular compartments, brain regions, and neuronal circuits. In the present review, we summarize current knowledge on the role of UBE3A in neuronal pathophysiology under this spatio-temporal perspective. Additionally, we propose key research questions that will be instrumental to better understand the pathogenic mechanisms underpinning AS and Dup15q disorders and provide the rationale to develop novel therapies.

Perinatal adversities as a common factor underlying the association between atypical laterality and neurodevelopmental disorders: A developmental perspective.

Several neurodevelopmental disorders are associated with a higher prevalence of atypical laterality (e.g., left-handedness). Both genetic and non-genetic factors play a role in this association, yet the underlying neurobiological mechanisms are largely unclear. Recent studies have found that stress, mediated by the hypothalamic-pituitary-adrenal (HPA) axis, could be linked to laterality development. These findings provide an opportunity to explore new theoretical perspectives on the association between atypical laterality and neurodevelopmental disorders. This article aims to provide a theoretical framework demonstrating how perinatal adversities could disrupt the typical developmental trajectories of both laterality and neurodevelopment, potentially impacting both the HPA axis and the vestibular system. Additionally, we argue that the relationship between atypical laterality and neurodevelopmental disorders cannot be understood by simply linking genetic and non-genetic factors to a diagnosis, but the developmental trajectories must be considered. Based on these ideas, several perspectives for future research are proposed.

Developmental Trajectories of Transactional Sex and Age-Disparate Relationships During Adolescence: An HPTN 068 Analysis.

Transactional sex and sexual relationships with older partners increase HIV risk in adolescent girls and young women (AGYW), yet little is known about how these behaviors co-evolve over time. We characterize temporal patterns of transactional sex and age-disparate relationships among AGYW in South Africa. Longitudinal data are from a randomized controlled trial (HPTN 068) of school-aged, HIV-negative, AGYW who attended ≥ 3 study visits. We used group-based trajectory modeling to identify trajectories of transactional sex and age-disparate relationships (partner ≥ 5 years older) in the last year and assessed the interrelationship (conditional probability) between both trajectories. At baseline, median age was 14 years, 14.5% of girls were sexually active, and transactional sex (2.1%) and age-disparate relationships were uncommon (2.7%). We identified two trajectories for transactional sex ("low" [81.9%] and "increasing" [18.1%]) and two for age-disparate relationships ("low" [91.7%] and "increasing" [8.3%]). In a separate joint trajectory analysis, nearly a third (28%) had increasing trajectories for both transactional sex and age-disparate relationships, but most (53%) had a low trajectory of both outcomes. Baseline reporting of early sexual debut, depression, and inequitable gender norms were highest in the increasing transactional sex group. Prior pregnancy, early sexual debut, and IPV were highest among those with increasing age-disparate relationships. AGYW who engage in transactional sex or age-disparate partnerships in early adolescence are more likely to experience sustained engagement in both behaviors as they transition to adulthood, increasing HIV risk. Engaging girls early may maximize effectiveness of behavioral and biomedical HIV prevention efforts.

Joint developmental trajectories of internalizing and externalizing problems from mid-childhood to late adolescence and childhood risk factors: Findings from a prospective pre-birth cohort.

There is limited evidence on heterogenous co-developmental trajectories of internalizing (INT) and externalizing (EXT) problems from childhood to adolescence and predictors of these joint trajectories. We utilized longitudinal data from Raine Study participants (n = 2393) to identify these joint trajectories from 5 to 17 years using parallel-process latent class growth analysis and analyze childhood individual and family risk factors predicting these joint trajectories using multinomial logistic regression. Five trajectory classes were identified: Low-problems (Low-INT/Low-EXT, 29%), Moderate Externalizing (Moderate-EXT/Low-INT, 26.5%), Primary Internalizing (Moderate High-INT/Low-EXT, 17.5%), Co-occurring (High-INT/High-EXT, 17%), High Co-occurring (Very High-EXT/High-INT, 10%). Children classified in Co-occurring and High Co-occurring trajectories (27% of the sample) exhibited clinically meaningful co-occurring problem behaviors and experienced more adverse childhood risk-factors than other three trajectories. Compared with Low-problems: parental marital problems, low family income, and absent father predicted Co-occurring and High Co-occurring trajectories; maternal mental health problems commonly predicted Primary Internalizing, Co-occurring, and High Co-occurring trajectories; male sex and parental tobacco-smoking uniquely predicted High Co-occurring membership; other substance smoking uniquely predicted Co-occurring membership; speech difficulty uniquely predicted Primary Internalizing membership; child's temper-tantrums predicted all four trajectories, with increased odds ratios for High Co-occurring (OR = 8.95) and Co-occurring (OR = 6.07). Finding two co-occurring trajectories emphasizes the importance of early childhood interventions addressing comorbidity.

Exploring relative strengths in people with Down syndrome: Spatial thinking and its role in mathematics.

There is convincing evidence that training spatial abilities leads to improved mathematics performance in typically developing (TD) children. However, a lack of information on mathematical development and spatial-mathematical associations in people with Down syndrome (DS) hinders the translation of these interventions. Here, we established developmental trajectories of mathematics and explored whether spatial ability predicts attainment on different mathematics measures in individuals with DS. Participants with DS (n = 36; ages 9-35 years) and TD children (n = 132; ages 4-11 years) completed three groups of tasks: spatial tasks assessing different subdomains of spatial thinking; mathematics tasks assessing early mathematics skills, mathematical reasoning, arithmetic, and geometry; and IQ tasks. The developmental trajectories of mathematics performance against mental age revealed similar starting points of the trajectories and similar rates of development for DS and TD groups. Furthermore, after controlling for verbal skills, spatial skills explained 5.8% to 18.1% of the variation in mathematical performance across different mathematics tasks, and the pattern of spatial-mathematical relations was similar for DS and mental age-matched TD groups. This shows that mathematical development in DS groups appears to mirror that in TD children, indicative of delay only. Strong spatial-mathematical relations were observed for individuals with DS, like those seen for TD participants. This is the vital preliminary knowledge needed to support the design and use of spatial intervention for improving mathematics in individuals with DS.

Developmental trajectories of conduct problems and time-varying peer problems: the Bergen child study.

BACKGROUND: While it is increasingly acknowledged that conduct problems and peer problems often co-occur in development, less is known about the ways in which peer problems may alter the developmental course of conduct problems for distinct subgroups. METHODS: Using data from a large population-based study in Norway (the Bergen Child Study/youth@hordaland; 47.4% males), we estimated group-based trajectories of conduct problems and the presence of time-varying peer problems on the developmental progression of conduct problems between seven and 19 years of age. Risk factors for group membership were also examined. RESULTS: A 3-group model of conduct problems best fit the data (non-engagers, low-engagers, moderate-stable). The presence of peer problems increased the estimated level of conduct problems for both the low-engagers and moderate-stable groups across adolescence. No differences in conduct problems were observed when peer problems were present in childhood or preadolescence for these two groups, nor for the non-engagers group at any point. Being male, having lower perceived economic wellbeing, and lower levels of parental education predicted group membership for the moderate-stable group, whilst lower paternal education predicted membership for the low-engagers group. CONCLUSIONS: Support for developmental 'turning points' was found, suggesting that adolescence is a particularly salient time for those with conduct problems. In particular, the presence of peer problems can increase observed conduct problems at this stage in development.

Placental genomic risk scores and early neurodevelopmental outcomes.

Tracing the early paths leading to developmental disorders is critical for prevention. In previous work, we detected an interaction between genomic risk scores for schizophrenia (GRSs) and early-life complications (ELCs), so that the liability of the disorder explained by genomic risk was higher in the presence of a history of ELCs, compared with its absence. This interaction was specifically driven by loci harboring genes highly expressed in placentae from normal and complicated pregnancies [G. Ursini et al., Nat. Med. 24, 792-801 (2018)]. Here, we analyze whether fractionated genomic risk scores for schizophrenia and other developmental disorders and traits, based on placental gene-expression loci (PlacGRSs), are linked with early neurodevelopmental outcomes in individuals with a history of ELCs. We found that schizophrenia's PlacGRSs are negatively associated with neonatal brain volume in singletons and offspring of multiple pregnancies and, in singletons, with cognitive development at 1 y and, less strongly, at 2 y, when cognitive scores become more sensitive to other factors. These negative associations are stronger in males, found only with GRSs fractionated by placental gene expression, and not found in PlacGRSs for other developmental disorders and traits. The relationship of PlacGRSs with brain volume persists as an anlage of placenta biology in adults with schizophrenia, again selectively in males. Higher placental genomic risk for schizophrenia, in the presence of ELCs and particularly in males, alters early brain growth and function, defining a potentially reversible neurodevelopmental path of risk that may be unique to schizophrenia.

Early risk factors for conduct problem trajectories from childhood to adolescence: the 2004 Pelotas (BRAZIL) Birth Cohort.

Conduct problems are associated with an increased risk of a wide range of physical, mental, and social problems. However, there is still uncertainty about how early risk factors differentiate different developmental patterns of conduct problems and whether findings replicate across diverse social contexts. We aimed to identify developmental trajectories of conduct problems, and test early risk factors, in the 2004 Pelotas Birth Cohort in Brazil. Conduct problems were measured at ages 4, 6, 11, and 15 years from caregiver reports on the Child Behaviour Checklist (CBCL) and Strengths and Difficulties Questionnaire (SDQ). Conduct problem trajectories were estimated using group-based semi-parametric modeling (n = 3938). Multinomial logistic regression was used to examine associations between early risk factors and conduct problem trajectories. We identified four trajectories: three with elevated conduct problems, including early-onset persistent (n = 150; 3.8%), adolescence-onset (n = 286; 17.3%), and childhood-limited (n = 697; 17.7%), and one with low conduct problems (n = 2805; 71.2%). The three elevated conduct problem trajectories were associated with a wide range of sociodemographic risk factors, prenatal smoking, maternal mental health, harsh parenting, childhood trauma, and child neurodevelopmental risk factors. Early-onset persistent conduct problems were particularly associated with trauma, living without a father figure, and attention difficulties. The four trajectories of conduct problems from ages 4 to 15 years in this Brazilian cohort have similar longitudinal patterns to those identified in high-income countries. The results confirm previous longitudinal research and developmental taxonomic theories on the etiology of conduct problems in a Brazilian sample.

Physical activity and psychopathology: are long-term developmental trajectories of physical activity in children and adolescents associated with trajectories of general mental health problems and of attention-deficit hyperactivity (ADHD) symptoms?

A medium-to-high level of physical activity (PA) may have at least a short-term positive effect on psychopathology in children and adolescents. Hence, the objective of this study was to investigate the long-term effects of PA in non-adult age groups on their general mental health problems and/or ADHD symptoms, using trajectories of concurrent development over a period of 10 years. This study employed data from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) collected at three time points (baseline, Wave 1, Wave 2, over 10 years) from 17,640 children and adolescents. Using parent-reported data from the Strengths and Difficulties Questionnaire (SDQ), different developmental trajectories of general mental health problems (SDQ-total) and ADHD symptoms (SDQ-H/I) were identified with latent class mixed models (LCMM) statistics. This was also applied to parent- and self-reported data of three levels of PA. The latter was assessed according to WHO recommendations. The joint probability of class membership for SDQ-total as well as ADHD symptoms with PA was calculated to generate the concurrent developmental trajectories between variables. Results showed a 4-class trajectory model for both SDQ-total and ADHD symptoms among boys and girls. The majority of children and adolescents showed "low general difficulties" and "low ADHD symptoms" over the period of 10 years. Three distinct trajectories in boys and four distinct trajectories in girls were found for PA. Most of the participants showed an "increasing-decreasing activity" trajectory. No statistically significant correlations were found between the different SDQ-total or ADHD symptom trajectories and the trajectories of PA in the two genders. Taken together, our findings did not indicate any significant relationship between waxing and waning PA course over 10 years and various classes of mental health problems for children and adolescents. In contrast to our cross-sectional findings, no steady long-term medium/high-level of PA was present, which could (at least partly) explain the non-significant findings.

John Schulenberg as a developmental scholar and mentor: Personal reflections.

John Schulenberg has had significant impact on developmental science. His conceptual writing and empirical research, grounded in developmental contextualism, emphasized the critical role that developmental transitions play in shaping health risks, especially substance use, across the life course. Schulenberg's integration of developmental concepts with large-scale epidemiological studies, particularly through his leadership in the Monitoring the Future study, provides key insights into how significant life changes-such as school transitions, employment, and relationships-interact to influence well-being across adolescence and early adulthood. He was a fierce advocate for adolescence and young adulthood being critical phases of life, deserving of focused attention and support. John was also a devoted mentor to the next generation of developmental scientists. This commentary reflects on John Schulenberg's legacy, highlighting five of his foundational concepts (developmental tasks, transitions, trajectories, turning points, and timing) and celebrating his role as a generative and joyful mentor. He fostered open intellectual dialog, promoted and celebrated career development, and took pleasure in life inside and outside work, helping early career scientists to develop innovative and impactful research programs. Schulenberg's commitment to positive relationships and celebrating success is an enduring model for future generations of developmental scientists and mentors.

Childhood maltreatment, peer victimization, borderline personality feature, suicidal risk in adolescents: Direct and indirect associations among developmental trajectories.

INTRODUCTION: Childhood maltreatment, peer victimization, and borderline personality traits have all been shown to be linked to suicidal risk. However, there remains a need to illuminate the possible direct and indirect pathways among them from a developmental perspective that could serve as intervention targets. This study thus aimed to investigate the direct and indirect relationships among developmental trajectories of childhood maltreatment, peer victimization, borderline personality feature, and suicidal risk in adolescents. METHODS: A total of 1648 Chinese adolescents (48.12% boys; Mage = 13.69; SD = 0.82) in junior middle schools completed self-report measures on three-time points across 1 year. Latent growth curve modeling was used to evaluate the direct and indirect relationships among the developmental trajectories of the aforementioned study variables. RESULTS: The developmental trajectories of childhood maltreatment, peer victimization, and borderline personality feature were positively and directly related to the developmental trajectory of suicidal risk; and the developmental trajectories of childhood maltreatment, peer victimization were indirectly related to the developmental trajectory of suicidal risk through the mediating effect of the developmental trajectory of borderline personality feature. CONCLUSIONS: The findings elucidated the direct and indirect longitudinal relationships among childhood maltreatment, peer victimization, borderline personality feature, and suicidal risk, highlighting that interventions should target childhood maltreatment, peer victimization, and borderline personality feature to decrease suicidal risk in adolescents with a developmental perspective.

Suicide Risk among Chinese Left-Behind Adolescents: Developmental Trajectories and Multi-Contextual Predictors.

Suicide is prevalent among left-behind youth, a group that has yet to be thoroughly explored in terms of the developmental dynamics of their suicide risk and associated factors. This study adopted a person-centered approach to investigate the developmental trajectories of suicide risk among Chinese left-behind adolescents, along with multi-dimensional predictors. A total of 774 left-behind adolescents (Mage = 13.60, 50.1% female) completed three surveys over a year, with six-month intervals. Result of Latent Class Growth Modeling identified three subgroups with distinct developmental trajectories: High Risk-Escalating (7.6% of participants started at the highest levels with a worsening trend), Risk-Holding (21.6% maintained a stable but risk level starting above the critical threshold), and Low Risk-Diminishing (70.8% started low and continued to decrease). Gender (being a female), increased levels of childhood maltreatment, psychological pain, and depression were risk factors for High Risk-Escalating and/or Risk-Holding trajectories, while increased sense of control and regulatory emotional self-efficacy played protective roles. The findings underscore the malignant developmental patterns of suicide risk among left-behind adolescents. The predictive factors play a crucial role in distinguishing and improving these developmental trajectories.

Peer Bullying Victimization Trajectories for Sexually and Gender Diverse Youth from Early Childhood to Late Adolescence.

Sexually and gender diverse (SGD) youth experience more peer bullying victimization than heterosexual, cisgender youth during adolescence, yet the emergence and persistence of these disparities remain underexplored. Also, it is unclear which factors are associated with these disparities across development, and how these disparities are linked to late adolescent health discrepancies. This study utilized the sample from the Millennium Cohort Study in Britain (N = 10,080; 51.3% assigned female at birth; Mage = 2.28, SDage = 0.46 at Wave 2), in which 23.74% of youth reported non-heterosexual attraction, 21.59% reported non-heterosexual identity, and 1.08% reported gender identity not in line with the sex assigned at birth. Using latent class growth modeling, four peer bullying victimization trajectories were identified, with early peak (7.2%), late childhood peak (6.3%), adolescence onset (12.8%), and low (73.6%) rates of victimization. SGD youth, compared to heterosexual and cisgender youth, were found to have increased odds of being in the victimization-involved classes, especially the adolescence onset class. The study further revealed that SGD youth reported more mental health and relational difficulties in childhood, which were linked to their heightened risk of longer-lasting victimization. Further, long-term victimization was found to partially account for the disparities in health and well-being for SGD youth in late adolescence. In conclusion, SGD youth were more likely to experience longer-lasting bullying victimization during childhood and adolescence, its related mental and relational vulnerabilities were already established in childhood, and such victimization disparities were further linked to their detrimental health and well-being in late adolescence. The design, hypotheses, and target analyses of the current study were preregistered on 21st April 2023 at https://osf.io/f2zxy .

Spatiotemporal Atlas of the Fetal Brain Depicts Cortical Developmental Gradient.

The fetal brains experience rapid and complex development in utero during the second and third trimesters. In utero MRI of the fetal brain in this period enables us to quantify normal fetal brain development in the spatiotemporal domain. In this study, we established a high-quality spatiotemporal atlas between 23 and 38 weeks gestational age (GA) from 90 healthy Chinese human fetuses of both sexes using a pairwise and groupwise registration pipeline. We quantified the fetal cortical morphology indices and characterized their spatiotemporal developmental pattern. The cortical thickness exhibited a biphasic pattern that first increased and then decreased; the curvature fitted well into the Gompertz growth model; sulcal depth increased linearly, while surface area expanded exponentially. The cortical thickness and curvature trajectories consistently pointed to a characteristic time point around GA of 31 weeks. The characteristic GA and growth rate obtained from individual cortical regions suggested a central-to-peripheral developmental gradient, with the earliest development in the parietal lobe, and we also observed a superior-to-inferior gradient within the temporal lobe. These findings may be linked to biophysical events, such as dendritic arborization and thalamocortical fibers ingrowth. The proposed atlas was also compared with an existing fetal atlas from a white/mixed population. Finally, we examined the structural asymmetry of the fetal brains and found extensive asymmetry that dynamically changed with development. The current study depicted a comprehensive profile of fetal cortical development, and the established atlas could be used as a normative reference for neurodevelopmental and diagnostic purposes, especially in the Chinese population.SIGNIFICANCE STATEMENT We generated a high-quality 4D spatiotemporal atlas of the normal fetal brain development from 23 to 38 gestational weeks in a Chinese population and characterized the spatiotemporal developmental pattern of cortical morphology. According to the cortical development trajectories, the fetal cerebral cortex development follows a central-to-peripheral developmental gradient that may be related to the underlying cellular events. The majority of cortical regions already exhibit significant asymmetry during the fetal period.

Developmental trajectories of autistic social traits in the general population.

BACKGROUND: Autistic people show diverse trajectories of autistic traits over time, a phenomenon labelled 'chronogeneity'. For example, some show a decrease in symptoms, whilst others experience an intensification of difficulties. Autism spectrum disorder (ASD) is a dimensional condition, representing one end of a trait continuum that extends throughout the population. To date, no studies have investigated chronogeneity across the full range of autistic traits. We investigated the nature and clinical significance of autism trait chronogeneity in a large, general population sample. METHODS: Autistic social/communication traits (ASTs) were measured in the Avon Longitudinal Study of Parents and Children using the Social and Communication Disorders Checklist (SCDC) at ages 7, 10, 13 and 16 (N = 9744). We used Growth Mixture Modelling (GMM) to identify groups defined by their AST trajectories. Measures of ASD diagnosis, sex, IQ and mental health (internalising and externalising) were used to investigate external validity of the derived trajectory groups. RESULTS: The selected GMM model identified four AST trajectory groups: (i) Persistent High (2.3% of sample), (ii) Persistent Low (83.5%), (iii) Increasing (7.3%) and (iv) Decreasing (6.9%) trajectories. The Increasing group, in which females were a slight majority (53.2%), showed dramatic increases in SCDC scores during adolescence, accompanied by escalating internalising and externalising difficulties. Two-thirds (63.6%) of the Decreasing group were male. CONCLUSIONS: Clinicians should note that for some young people autism-trait-like social difficulties first emerge during adolescence accompanied by problems with mood, anxiety, conduct and attention. A converse, majority-male group shows decreasing social difficulties during adolescence.

Altered developmental trajectories of verbal learning skills in 22q11.2DS: associations with hippocampal development and psychosis.

BACKGROUND: The cognitive profile in 22q11.2 deletion syndrome (22q11.2DS) is often characterized by a discrepancy between nonverbal vs. verbal reasoning skills, in favor of the latter skills. This dissociation has also been observed in memory, with verbal learning skills described as a relative strength. Yet the development of these skills is still to be investigated. We thus aimed to explore verbal learning longitudinally. Furthermore, we explored verbal learning and its respective associations with hippocampal alterations and psychosis, which remain largely unknown despite their high prevalence in 22q11.2DS. METHODS: In total, 332 individuals (173 with 22q11.2DS) aged 5-30 years completed a verbal-paired associates task. Mixed-models regression analyses were conducted to explore developmental trajectories with threefold objectives. First, verbal learning and retention trajectories were compared between 22q11.2DS vs. HC. Second, we examined hippocampal volume development in 22q11.2DS participants with lower vs. higher verbal learning performance. Third, we explored verbal learning trajectories in 22q11.2DS participants with vs. without positive psychotic symptoms and with vs. without a psychotic spectrum disorder (PSD). RESULTS: Our findings first reveal lower verbal learning performance in 22q11.2DS, with a developmental plateau emerging from adolescence. Second, participants with lower verbal learning scores displayed a reduced left hippocampal tail volume. Third, participants with PSD showed a deterioration of verbal learning performance, independently of verbal reasoning skills. CONCLUSION: Our study challenges the current view of preserved verbal learning skills in 22q11.2DS and highlights associations with specific hippocampal alterations. We further identify verbal learning as a novel cognitive marker for psychosis in 22q11.2DS.

Psychosis spectrum features, neurocognition and functioning in a longitudinal study of youth with 22q11.2 deletion syndrome.

BACKGROUND: Neuropsychiatric disorders are common in 22q11.2 Deletion Syndrome (22q11DS) with about 25% of affected individuals developing schizophrenia spectrum disorders by young adulthood. Longitudinal evaluation of psychosis spectrum features and neurocognition can establish developmental trajectories and impact on functional outcome. METHODS: 157 youth with 22q11DS were assessed longitudinally for psychopathology focusing on psychosis spectrum symptoms, neurocognitive performance and global functioning. We contrasted the pattern of positive and negative psychosis spectrum symptoms and neurocognitive performance differentiating those with more prominent Psychosis Spectrum symptoms (PS+) to those without prominent psychosis symptoms (PS-). RESULTS: We identified differences in the trajectories of psychosis symptoms and neurocognitive performance between the groups. The PS+ group showed age associated increase in symptom severity, especially negative symptoms and general nonspecific symptoms. Correspondingly, their level of functioning was worse and deteriorated more steeply than the PS- group. Neurocognitive performance was generally comparable in PS+ and PS- groups and demonstrated a similar age-related trajectory. However, worsening executive functioning distinguished the PS+ group from PS- counterparts. Notably, of the three executive function measures examined, only working memory showed a significant difference between the groups in rate of change. Finally, structural equation modeling showed that neurocognitive decline drove the clinical change. CONCLUSIONS: Youth with 22q11DS and more prominent psychosis features show worsening of symptoms and functional decline driven by neurocognitive decline, most related to executive functions and specifically working memory. The results underscore the importance of working memory in the developmental progression of psychosis.

Psychotic experiences and negative symptoms from adolescence to emerging adulthood: developmental trajectories and associations with polygenic scores and childhood characteristics.

BACKGROUND: Psychotic experiences and negative symptoms (PENS) are common in non-clinical populations. PENS are associated with adverse outcomes, particularly when they persist. Little is known about the trajectories of PENS dimensions in young people, nor about the precursory factors associated with these trajectories. METHODS: We conducted growth mixture modelling of paranoia, hallucinations, and negative symptoms across ages 16, 17, and 22 in a community sample (N = 12 049-12 652). We then described the emergent trajectory classes through their associations with genome-wide polygenic scores (GPS) for psychiatric and educational phenotypes, and earlier childhood characteristics. RESULTS: Three trajectory classes emerged for paranoia, two for hallucinations, and two for negative symptoms. Across PENS, GPS for clinical help-seeking, major depressive disorder, and attention deficit hyperactivity disorder were associated with increased odds of being in the most elevated trajectory class (OR 1.07-1.23). Lower education GPS was associated with the most elevated trajectory class for hallucinations and negative symptoms (OR 0.77-0.91). Conversely for paranoia, higher education GPS was associated with the most elevated trajectory class (OR 1.25). Trajectory class associations were not significant for schizophrenia, obsessive-compulsive disorder, bipolar disorder, or anorexia GPS. Emotional/behaviour problems and life events in childhood were associated with increased odds of being in the most elevated trajectory class across PENS. CONCLUSIONS: Our results suggest latent heterogeneity in the development of paranoia, hallucinations, and negative symptoms in young people that is associated with specific polygenic scores and childhood characteristics.

Single-cell RNA sequencing of the Mongolia sheep testis reveals a conserved and divergent transcriptome landscape of mammalian spermatogenesis.

Spermatogenesis is a highly coordinated and complex process, and is pivotal for transmitting genetic information between mammalian generations. In this study, we investigated the conservation, differences, and biological functions of homologous genes during spermatogenesis in Mongolia sheep, humans, cynomolgus monkey, and mice using single-cell RNA sequencing technology. We compared X chromosome meiotic inactivation events in Mongolia sheep, humans, cynomolgus monkey, and mice to uncover the concerted activity of X chromosome genes. Subsequently, we focused on the dynamics of gene expression, key biological functions, and signaling pathways at various stages of spermatogenesis in Mongolia sheep and humans. Additionally, the ligand-receptor networks of Mongolia sheep and humans in testicular somatic and germ cells at different developmental stages were mapped to reveal conserved germ cell-soma communication using single-cell resolution. These datasets provided novel information and insights to unravel the molecular regulatory mechanisms of Mongolia sheep spermatogenesis and highlight conservation in gene expression during spermatogenesis between Mongolia sheep and humans, providing a foundation for the establishment of a large mammalian disease model of male infertility.