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BackgroundTraumatic events are common globally; however, comprehensive population-based cross-national data on the epidemiology of posttraumatic stress disorder (PTSD), the paradigmatic trauma-related mental disorder, are lacking.MethodsData were analyzed from 26 population surveys in the World Health Organization World Mental Health Surveys. A total of 71 083 respondents ages 18+ participated. The Composite International Diagnostic Interview assessed exposure to traumatic events as well as 30-day, 12-month, and lifetime PTSD. Respondents were also assessed for treatment in the 12 months preceding the survey. Age of onset distributions were examined by country income level. Associations of PTSD were examined with country income, world region, and respondent demographics.ResultsThe cross-national lifetime prevalence of PTSD was 3.9% in the total sample and 5.6% among the trauma exposed. Half of respondents with PTSD reported persistent symptoms. Treatment seeking in high-income countries (53.5%) was roughly double that in low-lower middle income (22.8%) and upper-middle income (28.7%) countries. Social disadvantage, including younger age, female sex, being unmarried, being less educated, having lower household income, and being unemployed, was associated with increased risk of lifetime PTSD among the trauma exposed.ConclusionsPTSD is prevalent cross-nationally, with half of all global cases being persistent. Only half of those with severe PTSD report receiving any treatment and only a minority receive specialty mental health care. Striking disparities in PTSD treatment exist by country income level. Increasing access to effective treatment, especially in low- and middle-income countries, remains critical for reducing the population burden of PTSD.

BACKGROUND: Despite evidence that childhood adversities (CAs) are associated with increased risk of mental disorders, little is known about their associations with disorder-related impairment. We report the associations between CAs and functional impairment associated with 12-month DSM-IV disorders in a national sample. METHOD: We used data from the US National Comorbidity Survey Replication (NCS-R). Respondents completed diagnostic interviews that assessed 12-month DSM-IV disorder prevalence and impairment. Associations of 12 retrospectively reported CAs with impairment among cases (n=2242) were assessed using multiple regression analysis. Impairment measures included a dichotomous measure of classification in the severe range of impairment on the Sheehan Disability Scale (SDS) and a measure of self-reported number of days out of role due to emotional problems in the past 12 months. RESULTS: CAs were positively and significantly associated with impairment. Predictive effects of CAs on the SDS were particularly pronounced for anxiety disorders and were significant in predicting increased days out of role associated with mood, anxiety and disruptive behavior disorders. Predictive effects persisted throughout the life course and were not accounted for by disorder co-morbidity. CAs associated with maladaptive family functioning (MFF; parental mental illness, substance disorder, criminality, family violence, abuse, neglect) were more consistently associated with impairment than other CAs. The joint effects of co-morbid MFF CAs were significantly subadditive. Simulations suggest that CAs account for 19.6% of severely impairing disorders and 17.4% of days out of role. CONCLUSIONS: CAs predict greater disorder-related impairment, highlighting the ongoing clinical significance of CAs at every stage of the life course. [ABSTRACT FROM AUTHOR]

Limited data are available on lifetime prevalence and age-of-onset distributions of psychological disorders and suicidal behaviors among Army personnel. We used simulation methods to approximate such estimates based on analysis of data from a U.S. national general population survey with the sociodemographic profile of U.S. Army personnel. Estimated lifetime prevalence of any Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) anxiety, mood, behavior, or substance disorder in this sample was 53.1% (17.7% for mood disorders, 27.2% for anxiety disorders, 22.7% for behavior disorders, and 14.4% for substance disorders). The vast majority of cases had onsets before the expected age of enlistment if they were in the Army (91.6%). Lifetime prevalence was 14.2% for suicidal ideation, 5.4% for suicide plans, and 4.5% for suicide attempts. The proportion of estimated preenlistment onsets was between 68.4% (suicide plans) and 82.4% (suicidal ideation). Externalizing disorders with onsets before expected age of enlistment and internalizing disorders with onsets after expected age of enlistment significantly predicted postenlistment suicide attempts, with population attributable risk proportions of 41.8% and 38.8%, respectively. Implications of these findings are discussed for interventions designed to screen, detect, and treat psychological disorders and suicidality in the Army. [ABSTRACT FROM AUTHOR]

Background: 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., Methods: 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., Results: 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., Conclusions: 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., (© 2024 Association for Child and Adolescent Mental Health.)

Extensive evidence documents negative consequences of adversity for children's development. Here, we extend such work by looking beyond average effects to consider variation in susceptibility to both threat and deprivation in terms of cognitive and social-emotional development, using an influence-statistic methodology. Data come from the ongoing Avon Longitudinal Study of Parents and Children (N = 14,541, 49.1% female, age range: 6 month to 12 year, race and ethnicity: 97.8% white, 0.4% black, and 0.6% other). With respect to anticipated associations of threat with problem behavior and of deprivation with cognition, results of this pre-registered research revealed that a roughly equal proportion of children proved to be susceptible in a domain-general manner (similarly influenced) and a domain-specific one (dissimilarly influenced). Implications for intervention are considered., (© 2024 The Author(s). Child Development © 2024 Society for Research in Child Development.)

This study investigates (a) age-related differences in how the intensity of stereotyped facial expressions influence the emotion label children, adolescents, and adults assign to that face and (b) how this perceptual sensitivity relates to subclinical symptoms of psychopathology. In 2015-2016, 184 participants aged 4-25 years viewed posed stereotypes of angry, fearful, sad, and happy expressions morphed with neutral expressions at 10%-90% intensity. Thin plate regression smoothing splines were used to chart nonlinear associations between age and the perceptual threshold participants needed to assign the emotion label expected based on cultural consensus. Results suggest that sensitivity to labeling stereotypical happy faces as "happy" peaked by age 4. Sensitivity to perceiving stereotypical angry faces as "angry" increased from ages 4 to 7 and then plateaued. In contrast, sensitivity to perceiving stereotypical fearful and sad faces demonstrated protracted development, not reaching a plateau until ages 15 and 16, respectively. Reduction in selecting the "I don't know" response was the primary driver of these age-related changes. Stereotyped fear expressions required the highest intensity to be labeled as such and showed the most marked change in perceptual threshold across development. Interestingly, lower intensity morphs of stereotypical fear faces were frequently labeled "sad." Furthermore, perceiving lower intensity fear morphs was associated with fewer internalizing and externalizing symptoms in participants aged 7-19. This study describes the development of perceptual sensitivity to labeling stereotypical expressions of emotion according to cultural consensus and shows that how people perceive and categorize ambiguous facial expressions is associated with vulnerability to psychopathology. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Despite significant historical progress toward sex/gender parity in employment status in the United States, women remain more likely to provide domestic labor, creating role competition which may increase depression symptoms. Pro-family employee benefits may minimize the stress of competing roles. We tested whether depressive symptoms were higher among women with competing roles versus without competing roles and whether this effect was greater among women without (vs with) pro-family benefits. Data included employed women (n = 9884 person-years) surveyed across 4 waves (2010, 2015, 2017, and 2019) of the National Longitudinal Survey 1997. Depression symptoms were measured with the 5-item short version of the Mental Health Inventory (MHI-5). The effect of interaction between competing roles and pro-family employee benefits on depressive symptoms was also compared with that of non-family-related benefits, using marginal structural models to estimate longitudinal effects in the presence of time-varying confounding. MHI-5 scores were 0.56 points higher (95% CI, 0.15-0.97) among women in competing roles (vs not). Among women without pro-family benefits, competing roles increased MHI-5 scores by 6.10 points (95% CI, 1.14-11.1). In contrast, there was no association between competing roles and MHI-5 scores among women with access to these benefits (MHI-5 difference = 0.44; 95% CI, -0.2 to 1.0). Results were similar for non-family-related benefits. Dual workplace and domestic labor role competition increases women's depression symptoms, though broad availability of workplace benefits may attenuate that risk. This article is part of a Special Collection on Mental Health., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

The COVID-19 pandemic has presented youth and families with a broad spectrum of unique stressors. Given that adolescents are at increased risk for mental health and emotional difficulties, it is critical to explore family processes that confer resilience for youth in the face of stress. The current study investigated caregiver emotion regulation (ER) as a familial factor contributing to youth ER and risk for psychopathology following stressful life events. In a longitudinal sample of 224 youth ( M age = 12.65 years) and their caregivers, we examined whether caregiver and youth engagement in ER strategies early in the pandemic mediated the associations of pandemic-related stress with youth internalizing and externalizing symptoms six months later. Leveraging serial mediation analysis, we demonstrated that caregiver and youth rumination, but not expressive suppression or cognitive reappraisal, mediated the prospective associations of pandemic-related stress with youth internalizing and externalizing symptoms. Greater exposure to pandemic-related stressors was associated with greater caregiver rumination, which, in turn, related to greater rumination in youth, and higher levels of youth internalizing and externalizing symptoms thereafter. Family interventions that target caregiver ER, specifically rumination, may buffer against the consequences of stress on youth engagement in maladaptive ER strategies and risk for psychopathology.

Objective: Nearly 65% of youth experience trauma, and up to one-third of youth with trauma exposure face profound mental health sequelae. There remains a need to elucidate factors that contribute to psychopathology following trauma exposure, and to optimize interventions for youth who do not benefit sufficiently from existing treatments. Here, we probe safety signal learning (SSL), which is a mechanism of fear reduction that leverages learned safety to inhibit fear in the presence of threat-associated stimuli and has been shown to attenuate fear via a hippocampal-cingulate--specifically, a dorsal anterior cingulate cortex (dACC)--pathway., Method: The present study used behavioral and task-based functional magnetic resonance imaging data to examine age-related associations between interpersonal trauma exposure and the behavioral and neural correlates (ie, activation and functional connectivity) of SSL in a group of 102 youth (aged 9-19 years; 46 female, 56 male) with (n = 52) and without (n = 50) interpersonal trauma exposure. Primary analyses examined anterior hippocampal activation and anterior hippocampus-dACC functional connectivity. Exploratory analyses examined centromedial (CMA) and laterobasal (LBA) amygdala activation and anterior hippocampal, CMA, and LBA functional connectivity with additional anterior cingulate subregions (ie, subgenual anterior cingulate cortex [sgACC] and rostral anterior cingulate cortex [rosACC])., Results: Both youth with and without interpersonal trauma exposure successfully learned conditioned safety, which was determined by using self-report of contingency awareness. Youth with interpersonal trauma exposure (relative to youth in the comparison group) exhibited age-specific patterns of lower hippocampal activation (F 2,96  = 3.75, p FDR  = .049, η p 2  = 0.072), and, in exploratory analyses, showed heightened centromedial amygdala activation (F 1,96  = 5.37, p FDR  = .046, η p 2  = 0.053) and an age-related decrease in hippocampal-sgACC functional connectivity during SSL (F 1,94  = 10.68, p FDR  = .015, η p 2  = 0.102). We also show that hippocampal-sgACC functional connectivity mediated the association between interpersonal trauma exposure and post-traumatic stress disorder symptoms in an age-specific manner in the overall sample., Conclusion: Together, these findings suggest that although age- and trauma-specific differences in the neural correlates of SSL may relate to the development of psychopathology, youth with interpersonal trauma exposure demonstrate successful learning of conditioned safety over time., Diversity & Inclusion Statement: We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. While citing references scientificall`y relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science., (Copyright © 2024. Published by Elsevier Inc.)

Previously institutionalized adolescents show increased risk for psychopathology, though placement into high-quality foster care can partially mitigate this risk. White matter (WM) structure is associated with early institutional rearing and psychopathology in youth. Here we investigate associations between WM structure and psychopathology in previously institutionalized youth. Adolescent psychopathology data were collected using the MacArthur Health and Behavior Questionnaire. Participants underwent diffusion MRI, and data were processed using fixel-based analyses. General linear models investigated interactions between institutionalization groups and psychopathology on fixel metrics. Supplementary analyses also examined the main effects of psychopathology and institutionalization group on fixel metrics. Ever-Institutionalized children included 41 randomized to foster care (Mage=16.6), and 40 to care-as-usual (Mage=16.7)). In addition, 33 participants without a history of institutionalization were included as a reference group (Mage=16.9). Ever-Institutionalized adolescents displayed altered general psychopathology-fixel associations within the cerebellar peduncles, inferior longitudinal fasciculi, corticospinal tract, and corpus callosum, and altered externalizing-fixel associations within the cingulum and fornix. Our findings indicate brain-behavior associations reported in the literature may not be generalizable to all populations. Previously institutionalized youth may develop differential brain development, which in turn leads to altered neural correlates of psychopathology that are still apparent in adolescence., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Charles Zeanah reports a relationship with Irving Harris Foundation that includes: funding grants. Charles Zeanah reports a relationship with The Lumos Foundation that includes: funding grants. Charles Zeanah reports a relationship with The National Heart, Lung, and Blood Institute, NIMH that includes: funding grants. Charles Zeanah reports a relationship with The Substance Abuse and Mental Health Services Administration that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We investigate whether neural, cognitive, and psychopathology phenotypes that are more strongly related to genetic differences are less strongly associated with family- and state-level economic contexts (N = 5374 individuals with 1KG-EUR-like genotypes with 870 twins, from the Adolescent Behavior and Cognitive Development study). We estimated the twin- and SNP-based heritability of each phenotype, as well as its association with an educational attainment polygenic index (EA PGI). We further examined associations with family socioeconomic status (SES) and tested whether SES-related differences were moderated by state cost of living and social safety net programs (Medicaid expansion and cash assistance). SES was broadly associated with cognition, psychopathology, brain volumes, and cortical surface areas, even after controlling for the EA PGI. Brain phenotypes that were more heritable or more strongly associated with the EA PGI were not, overall, less related to SES, nor were SES-related differences in these phenotypes less moderated by macroeconomic context and policy. Informing a long-running theoretical debate, and contra to widespread lay beliefs, results suggest that aspects of child brain development that are more strongly related to genetic differences are not, in general, less associated with socioeconomic contexts and policies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Fear learning is a core component of conceptual models of how adverse experiences may influence psychopathology. Specifically, existing theories posit that childhood experiences involving childhood trauma are associated with altered fear learning processes, while experiences involving deprivation are not. Several studies have found altered fear acquisition in youth exposed to trauma, but not deprivation, although the specific patterns have varied across studies. The present study utilizes a longitudinal sample of children with variability in adversity experiences to examine associations among childhood trauma, fear learning, and psychopathology in youth., Methods: The sample includes 170 youths aged 10-13 years ( M = 11.56, s.d. = 0.47, 48.24% female). Children completed a fear conditioning task while skin conductance responses (SCR) were obtained, which included both acquisition and extinction. Childhood trauma and deprivation severity were measured using both parent and youth report. Symptoms of anxiety, externalizing problems, and post-traumatic stress disorder (PTSD) were assessed at baseline and again two-years later., Results: Greater trauma-related experiences were associated with greater SCR to the threat cue (CS+) relative to the safety cue (CS-) in early fear acquisition, controlling for deprivation, age, and sex. Deprivation was unrelated to fear learning. Greater SCR to the threat cue during early acquisition was associated with increased PTSD symptoms over time controlling for baseline symptoms and mediated the relationship between trauma and prospective changes in PTSD symptoms., Conclusions: Childhood trauma is associated with altered fear learning in youth, which may be one mechanism linking exposure to violence with the emergence of PTSD symptoms in adolescence.

Stressful life events (SLEs) are tightly coupled with the emergence of anxiety and depression symptoms among adolescents, but the mechanisms underlying this relationship remain poorly understood. We investigated within-person fluctuations in emotion regulation as a mechanism linking SLEs and internalizing psychopathology in an intensive longitudinal study. We examined how monthly fluctuations in SLEs were related to engagement in three emotion regulation strategies-acceptance, reappraisal, and rumination-and whether these strategies were associated with changes in internalizing symptoms in adolescents followed for one year (N = 30; n = 355 monthly observations). Bayesian hierarchical models revealed that on months when adolescents experienced more SLEs than was typical for them, they also engaged in more rumination, which, in turn, was associated with higher anxiety and depression symptoms and mediated the prospective relationship between SLEs and internalizing symptoms. In contrast, greater use of acceptance and reappraisal selectively moderated the association between stressors and internalizing symptoms, resulting in stronger links between SLEs and symptoms. These results suggest that emotion regulation strategies play different roles in the stress-psychopathology relationship. Understanding how changes in emotion regulation contribute to increases in internalizing symptoms following experiences of stress may provide novel targets for interventions aimed at reducing stress-related psychopathology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The early stages of the COVID-19 pandemic and associated stay-at-home orders resulted in a stark reduction in daily social interactions for children and adolescents. Given that peer relationships are especially important during this developmental stage, it is crucial to understand the impact of the COVID-19 pandemic on social behavior and risk for psychopathology in children and adolescents. In a longitudinal sample (N=224) of children (7-10y) and adolescents (13-15y) assessed at three strategic time points (before the pandemic, during the initial stay-at-home order period, and six months later after the initial stay-at-home order period was lifted), we examine whether certain social factors protect against increases in stress-related psychopathology during the pandemic, controlling for pre-pandemic symptoms. Youth who reported less in-person and digital socialization, greater social isolation, and less social support had worsened psychopathology during the pandemic. Greater social isolation and decreased digital socialization during the pandemic were associated with greater risk for psychopathology after experiencing pandemic-related stressors. In addition, children, but not adolescents, who maintained some in-person socialization were less likely to develop internalizing symptoms following exposure to pandemic-related stressors. We identify social factors that promote well-being and resilience in youth during this societal event.

Childhood experiences of low socioeconomic status are associated with alterations in neural function in the frontoparietal network and ventral visual stream, which may drive differences in working memory. However, the specific features of low socioeconomic status environments that contribute to these disparities remain poorly understood. Here, we examined experiences of cognitive deprivation (i.e. decreased variety and complexity of experience), as opposed to experiences of threat (i.e. violence exposure), as a potential mechanism through which family income contributes to alterations in neural activation during working memory. As part of a longitudinal study, 148 youth between aged 10 and 13 years completed a visuospatial working memory fMRI task. Early childhood low income, chronicity of low income in early childhood, and current income-to-needs were associated with task-related activation in the ventral visual stream and frontoparietal network. The association of family income with decreased activation in the lateral occipital cortex and intraparietal sulcus during working memory was mediated by experiences of cognitive deprivation. Surprisingly, however, family income and deprivation were not significantly related to working memory performance, and only deprivation was associated with academic achievement in this sample. Taken together, these findings suggest that early life low income and associated cognitive deprivation are important factors in neural function supporting working memory., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: We evaluated whether respiratory sinus arrhythmia (RSA) reactivity and resting RSA-physiological markers reflecting the increase in heart rate with inspiration and decrease during expiration related to parasympathetic influence on the heart-are modifiable and predict symptom change during youth psychotherapy. Methods: Diverse youth ( N  = 158; ages 7-15; 48.1% female) received the Modular Approach to Therapy for Children and completed pre-treatment (pre), post-treatment (post), and 18-months postbaseline (18Mo) assessments. We measured resting RSA, RSA reactivity during stress induction, and psychopathology symptoms. Results: Pre-to-post and pre-to-18Mo, reactivity decreased, and resting RSA increased. Changes in reactivity and resting RSA, separately, did not predict reduced psychopathology. Yet, decreased reactivity combined with increased resting RSA predicted reduced psychopathology over time, suggesting that observed RSA changes were beneficial for some. Higher dosage of a module utilizing slow-breathing, muscle-relaxation, and imagery predicted greater pre-to-18Mo changes in reactivity and resting RSA, whereas a similar module with less emphasis on slow-breathing did not. Conclusions: Findings raise the possibility that youth reactivity and resting RSA could be modifiable during cognitive behavioral therapy and contribute to the amelioration of psychopathology. More studies are needed to determine whether resting RSA and RSA reactivity are modifiable indices of symptom change in slow-breathing practices and psychotherapy., Clinicaltrials.gov Identifier: NCT03153904, registered May 15, 2017.

Conversational turn-taking is a complex communicative skill that requires both linguistic and executive functioning (EF) skills, including processing input while simultaneously forming and inhibiting responses until one's turn. Adult-child turn-taking predicts children's linguistic, cognitive, and socioemotional development. However, little is understood about how disruptions to temporal contingency in turn-taking, such as interruptions and overlapping speech, relate to cognitive outcomes, and how these relationships may vary across developmental contexts. In a longitudinal sample of 275 socioeconomically diverse mother-child dyads (children 50% male, 65% White), we conducted pre-registered examinations of whether the frequency of dyads' conversational disruption during free play when children were 3 years old related to children's executive functioning (EF; 9 months later), self-regulation skills (18 months later), and externalizing psychopathology in early adolescence (age 10-12 years). Contrary to hypotheses, more conversational disruptions significantly predicted higher inhibition skills, controlling for sex, age, income-to-needs (ITN), and language ability. Results were driven by maternal disruptions of the child's speech, and could not be explained by measures of overall talkativeness or interactiveness. Exploratory analyses revealed that ITN moderated these relationships, such that the positive effect of disruptions on inhibition was strongest for children from lower ITN backgrounds. We discuss how adult-driven "cooperative overlap" may serve as a form of engaged participation that supports cognition and behavior in certain cultural contexts., (© 2023 John Wiley & Sons Ltd.)

Recent work demonstrating low test-retest reliability of neural activation during fMRI tasks raises questions about the utility of task-based fMRI for the study of individual variation in brain function. Two possible sources of the instability in task-based BOLD signal over time are noise or measurement error in the instrument, and meaningful variation across time within-individuals in the construct itself-brain activation elicited during fMRI tasks. Examining the contribution of these two sources of test-retest unreliability in task-evoked brain activity has far-reaching implications for cognitive neuroscience. If test-retest reliability largely reflects measurement error, it suggests that task-based fMRI has little utility in the study of either inter- or intra-individual differences. On the other hand, if task-evoked BOLD signal varies meaningfully over time, it would suggest that this tool may yet be well suited to studying intraindividual variation. We parse these sources of variance in BOLD signal in response to emotional cues over time and within-individuals in a longitudinal sample with 10 monthly fMRI scans. Test-retest reliability was low, reflecting a lack of stability in between-person differences across scans. In contrast, within-person, within-session internal consistency of the BOLD signal was higher, and within-person fluctuations across sessions explained almost half the variance in voxel-level neural responses. Additionally, monthly fluctuations in neural response to emotional cues were associated with intraindividual variation in mood, sleep, and exposure to stressors. Rather than reflecting trait-like differences across people, neural responses to emotional cues may be more reflective of intraindividual variation over time. These patterns suggest that task-based fMRI may be able to contribute to the study of individual variation in brain function if more attention is given to within-individual variation approaches, psychometrics-beginning with improving reliability beyond the modest estimates observed here, and the validity of task fMRI beyond the suggestive associations reported here., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Consistent evidence documents powerful effects of social inequality on health, well-being and academic achievement. Yet research on whether social inequality may also be linked to brain structure and function has, until recently, been rare. Here we describe three methodological approaches that can be used to study this question-single site, single study; multi-site, single study; and spatial meta-analysis. We review empirical work that, using these approaches, has observed associations between neural outcomes and structural measures of social inequality-including structural stigma, community-level prejudice, gender inequality, neighbourhood disadvantage and the generosity of the social safety net for low-income families. We evaluate the relative strengths and limitations of these approaches, discuss ethical considerations and outline directions for future research. In doing so, we advocate for a paradigm shift in cognitive neuroscience that explicitly incorporates upstream structural and contextual factors, which we argue holds promise for uncovering the neural correlates of social inequality., (© 2024. Springer Nature Limited.)

Childhood adversity is a common, powerful risk factor for future mental and physical health problems. Appropriately aggregating and categorizing discrete adverse experiences into cumulative indices remains an active area of research and debate in the field of developmental psychopathology. In a recent article by Sisitsky et al. (2013), they report using confirmatory factor analysis and latent profile analysis to categorize participants into "profiles" of childhood adversity. In this commentary, we argue that categorizing dimensions or profiles of childhood adversity based on the tendency of adversities to co-occur is misaligned with dimensional models of adversity, which derive underlying dimensions from their tendency to cumulatively predict certain outcomes rather than adversity co-occurrence. We summarize the history of theories and methods of operationalizing childhood adversity that led to the development of the dimensional model of adversity and psychopathology. We then explain why latent variable approaches, which simply reflect the tendency of adverse experiences to co-occur, are inappropriate for validating any given approach., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Childhood adversity is common and associated with elevated risk for transdiagnostic psychopathology. Reward processing has been implicated in the link between adversity and psychopathology, but whether it serves as a mediator or moderator is unclear. This study examined whether alterations in behavioral and neural reward processing function as a mechanism or moderator of psychopathology outcomes following adversity experiences, including threat (i.e., trauma) and deprivation. A longitudinal community sample of 10-15-year-old youths was assessed across two waves (Wave 1: n = 228; Wave 2: n = 206). Wave 1 assessed adverse experiences, psychopathology symptoms, reward processing on a monetary incentive delay task, and resting-state fMRI. At Wave 2, psychopathology symptoms were reassessed. Greater threat experiences were associated with blunted behavioral reward sensitivity, which, in turn, predicted increases in depression symptoms over time and mediated the prospective association between threat and depression symptoms. In contrast, reward sensitivity moderated the association between deprivation experiences and prospective externalizing symptoms such that the positive association of deprivation with increasing externalizing symptoms was absent for children with high levels of reward sensitivity.

Objective: Ample evidence demonstrates that structural stigma - defined as societal-level conditions, cultural norms, and institutional policies and practices that constrain opportunities, resources, and well-being of stigmatized populations - is associated with psychopathology in adults from marginalized groups. Yet there is limited research on whether structural stigma is similarly associated with internalizing and externalizing symptoms among youth., Method: Structural stigma related to sex, sexual orientation, race, and Latinx ethnicity was measured using indicators of state-level policy and aggregated attitudes. Using data from the Adolescent Brain Cognitive Development (ABCD) Study ( N  = 10,414; M age = 12 years, SD = 0.66; 48% female, 6.8% lesbian, gay, and bisexual (LGB), 13.4% Black, 20% Latinx), we examined associations of structural stigma with internalizing and externalizing symptoms among female, LGB, Black, and Latinx youth., Results: LGB youth living in higher (vs. lower) structural stigma states had elevated levels of internalizing and externalizing symptoms. In lower structural stigma states, there were no differences in externalizing symptoms between LGB and heterosexual youth. Similarly, Latinx youth and females living in higher (vs. lower) structural stigma states had elevated levels of externalizing symptoms. In lower structural stigma states, there were no differences in externalizing symptoms between Latinx youth and non-Latinx White youth. Structural stigma related to race was unrelated to internalizing or externalizing symptoms for Black youth., Conclusions: This study provides novel evidence that macro-level social environments, in the form of structural stigma, contribute to adverse mental health outcomes for marginalized youth and partly explain disparities in externalizing symptoms.

Socioeconomic status (SES) is associated with children's brain and behavioral development. Several theories propose that early experiences of adversity or low SES can alter the pace of neurodevelopment during childhood and adolescence. These theories make contrasting predictions about whether adverse experiences and low SES are associated with accelerated or delayed neurodevelopment. We contextualize these predictions within the context of normative development of cortical and subcortical structure and review existing evidence on SES and structural brain development to adjudicate between competing hypotheses. Although none of these theories are fully consistent with observed SES-related differences in brain development, existing evidence suggests that low SES is associated with brain structure trajectories more consistent with a delayed or simply different developmental pattern than an acceleration in neurodevelopment., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

While the nervous system may be best known as the sensory communication center of an organism, recent research has revealed a myriad of multifaceted roles for both the CNS and PNS from early development to adult regeneration and remodeling. These systems work to orchestrate tissue pattern formation during embryonic development and continue shaping pattering through transitional periods such as metamorphosis and growth. During periods of injury or wounding, the nervous system has also been shown to influence remodeling and wound healing. The neuronal mechanisms responsible for these events are largely conserved across species, suggesting this evidence may be important in understanding and resolving many human defects and diseases. By unraveling these diverse roles, this paper highlights the necessity of broadening our perspective on the nervous system beyond its conventional functions. A comprehensive understanding of the complex interactions and contributions of the nervous system throughout development and adulthood has the potential to revolutionize therapeutic strategies and open new avenues for regenerative medicine and tissue engineering. This review highlights an important role for the nervous system during the patterning and maintenance of complex tissues and provides a potential avenue for advancing biomedical applications.

The COVID-19 pandemic has presented unprecedented challenges for youths and families, dramatically increasing exposure to stressors and stress-related psychopathology. Increasing work has leveraged pre-pandemic neuroimaging data to predict adolescent psychopathology and stress responses during the pandemic, with a particular focus on internalizing symptoms. We review this recent literature on pre-pandemic brain structure and function and adolescent internalizing psychopathology during the pandemic. At present, existing studies have not consistently identified specific alterations in brain structure and function that predict anxiety or depressive symptoms during the pandemic. In contrast, exposure to stress and adversity before and during the pandemic as well as access to peer and family support have emerged as consistent and reliable predictors of youth mental health during the pandemic., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Despite the high prevalence of childhood adversity and well-documented associations with poor academic achievement and psychopathology, effective, scalable interventions remain largely unavailable. Existing interventions targeting growth mindset-the belief that personal characteristics are malleable-have been shown to improve academic achievement and symptoms of psychopathology in youth., Objective: The present study examines growth mindset as a potential modifiable mechanism underlying the associations of two dimensions of childhood adversity-threat and deprivation-with academic achievement and internalizing psychopathology., Participants and Setting: Participants were 408 youth aged 10-18 years drawn from one timepoint of two longitudinal studies of community-based samples recruited to have diverse experiences of childhood adversity., Method: Experiences of threat and deprivation were assessed using a multi-informant, multi-method approach. Youth reported on growth mindset of intelligence and symptoms of anxiety and depression. Parents provided information about youths' academic performance., Results: Both threat and deprivation were independently associated with lower growth mindset, but when accounting for co-occurring adversities, only the association between threat and lower growth mindset remained significant. Lower growth mindset was associated with worse academic performance and greater symptoms of both anxiety and depression. Finally, there was a significant indirect effect of experiences of threat on both lower academic performance and greater symptoms of anxiety through lower growth mindset., Conclusions: Findings suggest that growth mindset could be a promising target for efforts aimed at mitigating the impact of childhood adversity on academic achievement and psychopathology given the efficacy of existing brief, scalable growth mindset interventions., Competing Interests: Declaration of competing interest None., (Copyright © 2022. Published by Elsevier Ltd.)

Strong in-group bonds, facilitated by implicit favoritism for in-group members (i.e., in-group bias), promote mental health across development. Yet, we know little about how the development of in-group bias is shaped by early-life experiences. Childhood violence exposure is known to alter social information processing biases. Violence exposure may also influence social categorization processes, including in-group biases, in ways that influence risk for psychopathology. We examined associations of childhood violence exposure with psychopathology and behavioral and neural indices of implicit and explicit bias for novel groups in children followed longitudinally across three time points from age 5 to 10 years old (n = 101 at baseline; n = 58 at wave 3). To instantiate in-group and out-group affiliations, youths underwent a minimal group assignment induction procedure, in which they were randomly assigned to one of two groups. Youth were told that members of their assigned group shared common interests (in-group) and members of the other group did not (out-group). In pre-registered analyses, violence exposure was associated with lower implicit in-group bias, which in turn was associated prospectively with higher internalizing symptoms and mediated the longitudinal association between violence exposure and internalizing symptoms. During an fMRI task examining neural responses while classifying in-group and out-group members, violence-exposed children did not exhibit the negative functional coupling between vmPFC and amygdala to in-group vs. out-group members that was observed in children without violence exposure. Reduced implicit in-group bias may represent a novel mechanism linking violence exposure with the development of internalizing symptoms., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Macrostructural characteristics, such as cost of living and state-level anti-poverty programs relate to the magnitude of socioeconomic disparities in brain development and mental health. In this study we leveraged data from the Adolescent Brain and Cognitive Development (ABCD) study from 10,633 9-11 year old youth (5115 female) across 17 states. Lower income was associated with smaller hippocampal volume and higher internalizing psychopathology. These associations were stronger in states with higher cost of living. However, in high cost of living states that provide more generous cash benefits for low-income families, socioeconomic disparities in hippocampal volume were reduced by 34%, such that the association of family income with hippocampal volume resembled that in the lowest cost of living states. We observed similar patterns for internalizing psychopathology. State-level anti-poverty programs and cost of living may be confounded with other factors related to neurodevelopment and mental health. However, the patterns were robust to controls for numerous state-level social, economic, and political characteristics. These findings suggest that state-level macrostructural characteristics, including the generosity of anti-poverty policies, are potentially relevant for addressing the relationship of low income with brain development and mental health., (© 2023. The Author(s).)

Experiencing adversity in childhood and adolescence, including stressful life events (SLEs), may accelerate the pace of development, leading to adverse mental and physical health. However, most research on adverse early experiences and biological aging (BA) in youths relies on cross-sectional designs. In 171 youths followed for approximately 2 years, we examined if SLEs over follow-up predicted rate of change in two BA metrics: epigenetic age and Tanner stage. We also investigated if rate of change in BA was associated with changes in depressive symptoms over time. Youths aged 8-16 years at baseline self-reported Tanner stage and depressive symptoms at baseline and follow-up and provided saliva samples for DNA at both assessments. Horvath epigenetic age estimates were derived from DNA methylation data measured with the Illumina EPIC array. At follow-up, contextual threat interviews were administered to youths and caregivers to assess youths' experiences of past-year SLEs. Interviews were objectively coded by an independent rating team to generate a SLE impact score, reflecting the severity of all SLEs occurring over the prior year. Rate of change in BA metrics was operationalized as change in epigenetic age or Tanner stage as a function of time between assessments. Higher objective SLE impact scores over follow-up were related to a greater rate of change in epigenetic age (β = 0.21, p = .043). Additionally, among youths with lower-but not higher-Tanner stage at baseline, there was a positive association of SLE impact scores with rate of change in Tanner stage (Baseline Tanner Stage × SLE Impact Score interaction: β = - 0.21, p = .011). A greater rate of change in epigenetic age was also associated with higher depressive symptom levels at follow-up, adjusting for baseline symptoms (β = 0.15, p = .043). Associations with epigenetic age were similar, although slightly attenuated, when adjusting for epithelial (buccal) cell proportions. Whereas much research in youths has focused on severe experiences of early adversity, we demonstrate that more commonly experienced SLEs during adolescence may also contribute to accelerated BA. Further research is needed to understand the long-term consequences of changes in BA metrics for health., Competing Interests: Declarations of Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Checkpoint immunotherapy (CPI) has increased survival for some patients with advanced-stage bladder cancer (BCa). However, most patients do not respond. Here, we characterized the tumor and immune microenvironment in pre- and post-treatment tumors from the PURE01 neoadjuvant pembrolizumab immunotherapy trial, using a consolidative approach that combined transcriptional and genetic profiling with digital spatial profiling. We identify five distinctive genetic and transcriptomic programs and validate these in an independent neoadjuvant CPI trial to identify the features of response or resistance to CPI. By modeling the regulatory network, we identify the histone demethylase KDM5B as a repressor of tumor immune signaling pathways in one resistant subtype (S1, Luminal-excluded) and demonstrate that inhibition of KDM5B enhances immunogenicity in FGFR3-mutated BCa cells. Our study identifies signatures associated with response to CPI that can be used to molecularly stratify patients and suggests therapeutic alternatives for subtypes with poor response to neoadjuvant immunotherapy., (© 2023. The Author(s).)