The relationship between type, timing and duration of exposure to adverse childhood experiences and adolescent self-harm and depression: findings from three UK prospective population-based cohorts.

BACKGROUND: Adverse childhood experiences (ACEs) are well-established risk factors for self-harm and depression. However, despite their high comorbidity, there has been little focus on the impact of developmental timing and the duration of exposure to ACEs on co-occurring self-harm and depression. METHODS: Data were utilised from over 22,000 children and adolescents participating in three UK cohorts, followed up longitudinally for 14-18 years: the Avon Longitudinal Study of Parents and Children (ALSPAC), the Millennium Cohort Study (MCS) and the Environmental Risk (E-Risk) Longitudinal Twin Study. Multinomial logistic regression models estimated associations between each ACE type and a four-category outcome: no self-harm or depression, self-harm alone, depression alone and self-harm with co-occurring depression. A structured life course modelling approach was used to examine whether the accumulation (duration) of exposure to each ACE, or a critical period (timing of ACEs) had the strongest effects on self-harm and depression in adolescence. RESULTS: The majority of ACEs were associated with co-occurring self-harm and depression, with consistent findings across cohorts. The importance of timing and duration of ACEs differed across ACEs and across cohorts. For parental mental health problems, longer duration of exposure was strongly associated with co-occurring self-harm and depression in both ALSPAC (adjusted OR: 1.18, 95% CI: 1.10-1.25) and MCS (1.18, 1.11-1.26) cohorts. For other ACEs in ALSPAC, exposure in middle childhood was most strongly associated with co-occurring self-harm and depression, and ACE occurrence in early childhood and adolescence was more important in the MCS. CONCLUSIONS: Efforts to mitigate the impact of ACEs should start in early life with continued support throughout childhood, to prevent long-term exposure to ACEs contributing to risk of self-harm and depression in adolescence.

PRAME Updated: Diagnostic, Prognostic, and Therapeutic Role in Skin Cancer.

Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the field of skin cancer diagnostics and therapeutics. As a nuclear receptor and transcriptional regulator, PRAME plays a critical role in inhibiting retinoic acid signalling, which is essential for cell differentiation and proliferation. Its aberrant overexpression in various malignancies, particularly cutaneous melanoma, is associated with more aggressive tumour phenotypes, positioning PRAME as both a diagnostic and prognostic marker. In melanoma, PRAME is typically highly expressed, in contrast to its weak or absent expression in benign nevi, thereby improving the accuracy of differential diagnoses. The diagnostic value of PRAME extends to various lesions. It is significantly expressed in uveal melanoma, correlating to an increased risk of metastasis. In acral melanomas, especially those with histopathological ambiguity, PRAME helps to improve diagnostic accuracy. However, its expression in spitzoid and ungual melanocytic lesions is inconsistent and requires a comprehensive approach for an accurate assessment. In soft tissue sarcomas, PRAME may be particularly helpful in differentiating melanoma from clear cell sarcoma, an important distinction due to their similar histological appearance but different treatment approaches and prognosis, or in detecting dedifferentiated and undifferentiated melanomas. In non-melanoma skin cancers such as basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, the variable expression of PRAME can lead to diagnostic complexity. Despite these challenges, the potential of PRAME as a therapeutic target in melanoma is significant. Emerging immunotherapies, including T-cell-based therapies and vaccines targeting PRAME, are being investigated to exploit its cancer-specific expression. Ongoing research into the molecular role and mechanism of action of PRAME in skin cancer continues to open new avenues in both diagnostics and therapeutics, with the potential to transform the management of melanoma and related skin cancers.

The general factor of psychopathology (p): Choosing among competing models and interpreting p.

Over the past 10 years, the general factor of psychopathology, p, has attracted interest and scrutiny. We review the history of the idea that all mental disorders share something in common, p; how we arrived at this idea; and how it became conflated with a statistical representation, the Bi-Factor Model. We then leverage the Environmental Risk (E-Risk) longitudinal twin study to examine the properties and nomological network of different statistical representations of p. We find that p performed similarly regardless of how it was modelled, suggesting that if the sample and content are the same the resulting p factor will be similar. We suggest that the meaning of p is not to be found by dueling over statistical models but by conducting well-specified criterion-validation studies and developing new measurement approaches. We outline new directions to refresh research efforts to uncover what all mental disorders have in common.

Social isolation, loneliness, and inflammation: A multi-cohort investigation in early and mid-adulthood.

Social isolation and loneliness have been associated with poor health and increased risk for mortality, and inflammation might explain this link. We used data from the Danish TRIAGE Study of acutely admitted medical patients (N = 6,144, mean age 60 years), and from two population-representative birth cohorts: the New Zealand Dunedin Longitudinal Study (N = 881, age 45) and the UK Environmental Risk (E-Risk) Longitudinal Twin Study (N = 1448, age 18), to investigate associations of social isolation with three markers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer inflammation marker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to index systemic chronic inflammation. In the TRIAGE Study, socially isolated patients (those living alone) had significantly higher median levels of suPAR (but not CRP or IL-6) compared with patients not living by themselves. Social isolation prospectively measured in childhood was longitudinally associated with higher CRP, IL-6, and suPAR levels in adulthood (at age 45 in the Dunedin Study and age 18 in the E-Risk Study), but only suPAR remained associated after controlling for covariates. Dunedin Study participants who reported loneliness at age 38 or age 45 had elevated suPAR at age 45. In contrast, E-Risk Study participants reporting loneliness at age 18 did not show any elevated markers of inflammation. In conclusion, social isolation was robustly associated with increased inflammation in adulthood, both in medical patients and in the general population. It was associated in particular with systemic chronic inflammation, evident from the consistently stronger associations with suPAR than other inflammation biomarkers.

Characteristics of complex posttraumatic stress disorder (PTSD) in young people with PTSD following multiple trauma exposure.

BACKGROUND: Complex PTSD (CPTSD) is a relatively new diagnosis. The objective of the present study was to investigate how trauma characteristics, comorbid psychopathology and cognitive and social factors experienced by children and adolescents with a posttraumatic stress disorder (PTSD) diagnosis following exposure to multiple traumatic events differs between those who meet the criteria for CPTSD and those who do not. METHOD: The present research used baseline data from the DECRYPT trial (BMJ Open, 2021, 11, e047600). Participants (n = 120) were aged 8-17 years and had exposure to multiple traumas and a PTSD diagnosis. The data collected comprised self-report and parent/caregiver-report questionnaires and interviews. Three primary analyses were conducted, comparing number of trauma types, prevalence of sexual trauma and prevalence of intrafamilial abuse between the CPTSD and PTSD-only groups. A range of comorbid psychopathology and cognitive and social factors were compared between the groups in an exploratory secondary analysis. All analyses were preregistered. RESULTS: The CPTSD group (n = 72, 60%) had a significantly higher frequency of sexual trauma than the PTSD-only group (n = 48, 40%). The groups did not significantly differ on number of trauma types or prevalence of intrafamilial abuse. From the secondary analysis, the CPTSD group were found to have significantly higher scores on measures of negative post-traumatic cognitions, depression and panic. These results were replicated in correlation analyses using a continuous measure of CPTSD symptoms. CONCLUSIONS: A large proportion of youth exposed to multiple traumatic events met criteria for CPTSD. Sexual trauma appears to be related to CPTSD symptoms. Youth with CPTSD appear to have greater severity of comorbid depression and panic symptoms, as well as more negative post-traumatic cognitions. Further investigation could focus on the directionality and mechanisms for these associations.

Transdiagnostic risk of mental disorders in offspring of affected parents: a meta-analysis of family high-risk and registry studies.

The offspring of parents with mental disorders are at increased risk for developing mental disorders themselves. The risk to offspring may extend transdiagnostically to disorders other than those present in the parents. The literature on this topic is vast but mixed. To inform targeted prevention and genetic counseling, we performed a comprehensive, PRISMA 2020-compliant meta-analysis. We systematically searched the literature published up to September 2022 to retrieve original family high-risk and registry studies reporting on the risk of mental disorders in offspring of parents with any type of mental disorder. We performed random-effects meta-analyses of the relative risk (risk ratio, RR) and absolute risk (lifetime, up to the age at assessment) of mental disorders, defined according to the ICD or DSM. Cumulative incidence by offspring age was determined using meta-analytic Kaplan-Meier curves. We measured heterogeneity with the I2 statistic, and risk of bias with the Quality In Prognosis Studies (QUIPS) tool. Sensitivity analyses addressed the impact of study design (family high-risk vs. registry) and specific vs. transdiagnostic risks. Transdiagnosticity was appraised with the TRANSD criteria. We identified 211 independent studies that reported data on 3,172,115 offspring of parents with psychotic, bipolar, depressive, disruptive, attention-deficit/hyperactivity, anxiety, substance use, eating, obsessive-compulsive, and borderline personality disorders, and 20,428,575 control offspring. The RR and lifetime risk of developing any mental disorder were 3.0 and 55% in offspring of parents with anxiety disorders; 2.6 and 17% in offspring of those with psychosis; 2.1 and 55% in offspring of those with bipolar disorder; 1.9 and 51% in offspring of those with depressive disorders; and 1.5 and 38% in offspring of those with substance use disorders. The offspring's RR and lifetime risk of developing the same mental disorder diagnosed in their parent were 8.4 and 32% for attention-deficit/hyperactivity disorder; 5.8 and 8% for psychosis; 5.1 and 5% for bipolar disorder; 2.8 and 9% for substance use disorders; 2.3 and 14% for depressive disorders; 2.3 and 1% for eating disorders; and 2.2 and 31% for anxiety disorders. There were 37 significant transdiagnostic associations between parental mental disorders and the RR of developing a different mental disorder in the offspring. In offspring of parents with psychosis, bipolar and depressive disorder, the risk of the same disorder onset emerged at 16, 5 and 6 years, and cumulated to 3%, 19% and 24% by age 18; and to 8%, 36% and 46% by age 28. Heterogeneity ranged from 0 to 0.98, and 96% of studies were at high risk of bias. Sensitivity analyses restricted to prospective family high-risk studies confirmed the pattern of findings with similar RR, but with greater absolute risks compared to analyses of all study types. This study demonstrates at a global, meta-analytic level that offspring of affected parents have strongly elevated RR and lifetime risk of developing any mental disorder as well as the same mental disorder diagnosed in the parent. The transdiagnostic risks suggest that offspring of parents with a range of mental disorders should be considered as candidates for targeted primary prevention.

Soft Tissue Sarcoma Mimicking Melanoma: A Systematic Review.

BACKGROUND: Sarcoma may show similarities to malignant melanoma in terms of morphologic and immunohistochemical aspects, making it difficult to differentiate between these two neoplasms during the diagnostic process. This systematic review aims to summarize available evidence on cases of sarcoma that were initially diagnosed as melanoma. METHODS: A comprehensive search of the MEDLINE/Pubmed, EMBASE, and SCOPUS databases was conducted through March 2023. We included case series and case reports of sarcoma patients that were initially diagnosed as malignant melanoma. PRISMA guidelines were followed. RESULTS: Twenty-three case reports and four case series with a total of 34 patients were included. The clinical presentation was heterogeneous, and the most involved anatomical regions were lower limbs (24%), head/neck (24%), and upper limbs (21%). IHC positivity was reported for S100 (69%), HMB45 (63%), MelanA (31%), and MiTF (3%). The main reasons for a second assessment were unusual presentation (48%) and uncertain diagnosis (28%). EWSR1 translocation was investigated in 17/34 patients (50%) and found to be positive in 16/17 (94%). The final diagnosis was clear cell sarcoma (50%) or other soft tissue sarcomas (50%). CONCLUSIONS: Melanoma and some histotypes of sarcoma share many similarities. In cases of atypical lesions, a second diagnosis should be considered, and ESWR1 translocation should be investigated.

Associations Between Objective and Subjective Experiences of Childhood Maltreatment and the Course of Emotional Disorders in Adulthood.

Importance: A history of childhood maltreatment is associated with an unfavorable course of illness for emotional disorders. However, the origins and mechanisms underlying these associations are unknown. Objective: To examine the relative associations of objective and subjective measures of childhood maltreatment and continuity in psychopathology with the course of emotional disorders in adulthood. Design, Setting, and Participants: This prospective cohort study followed up until age 40 years participants residing in a metropolitan county of the US Midwest with substantiated records of childhood physical and sexual abuse and/or neglect between 1967 and 1971 and a demographically matched group of participants experiencing no abuse or neglect in childhood. The collected data were analyzed between October 2021 and April 2022. Exposures: The objective experience of childhood maltreatment before age 12 years was prospectively measured through official court records, whereas the subjective experience was measured through retrospective self-report at a mean (SD) age of 29 (3.8) years. Current and previous lifetime psychopathology was also assessed at a mean age of 29 (3.8) years. Main Outcomes and Measures: Symptoms of depression and anxiety were measured at mean (SD) ages of 39.5 (3.5) and 41.2 (3.5) years using Poisson regression models. Results: In a cohort of 1196 participants (582 [48.7%] female and 614 [51.3%] male) followed up to age 40 years, those with objective plus subjective measures of childhood maltreatment had a greater number of subsequent follow-up phases with depression or anxiety than controls (depression: incidence rate ratio [IRR], 2.28 [95% CI, 1.65-3.15]; anxiety: IRR, 2.30 [95% CI, 1.54-3.42]), as did those with subjective-only measures (depression: IRR, 1.49 [95% CI, 1.02-2.18]; anxiety: IRR, 1.58 [95% CI, 0.99-2.52]). In contrast, participants with objective-only measures did not have a greater number of follow-up phases with depression or anxiety (depression: IRR, 1.37 [95% CI, 0.89-2.11]; anxiety: IRR, 1.40 [95% CI, 0.84-2.31]). Current and lifetime psychopathology measured at the time the subjective experience was assessed explained its association with a later course of emotional disorders in participants with subjective-only measures but not in those with objective plus subjective measures. Conclusions and Relevance: In this cohort study, the associations seen between childhood maltreatment and poor course of emotional disorders over the subsequent decade were largely attributable to the subjective experience of maltreatment, which was partly explained by continuity in psychopathology. Modification of the subjective experience of childhood maltreatment could improve the longitudinal course of emotional disorders.

Testing the causal relationships of physical activity and sedentary behaviour with mental health and substance use disorders: a Mendelian randomisation study.

Observational studies suggest that physical activity can reduce the risk of mental health and substance use disorders. However, it is unclear whether this relationship is causal or explained by confounding bias (e.g., common underlying causes or reverse causality). We investigated the bidirectional causal relationship of physical activity (PA) and sedentary behaviour (SB) with ten mental health and substance use disorders, applying two-sample Mendelian Randomisation (MR). Genetic instruments for the exposures and outcomes were derived from the largest available, non-overlapping genome-wide association studies (GWAS). Summary-level data for objectively assessed PA (accelerometer-based average activity, moderate activity, and walking) and SB and self-reported moderate-to-vigorous PA were obtained from the UK Biobank. Data for mental health/substance use disorders were obtained from the Psychiatric Genomics Consortium and the GWAS and Sequencing Consortium of Alcohol and Nicotine Use. MR estimates were combined using inverse variance weighted meta-analysis (IVW). Sensitivity analyses were conducted to assess the robustness of the results. Accelerometer-based average PA was associated with a lower risk of depression (b = -0.043, 95% CI: -0.071 to -0.016, effect size[OR] = 0.957) and cigarette smoking (b = -0.026; 95% CI: -0.035 to -0.017, effect size[ß] = -0.022). Accelerometer-based SB decreased the risk of anorexia (b = -0.341, 95% CI: -0.530 to -0.152, effect size[OR] = 0.711) and schizophrenia (b = -0.230; 95% CI: -0.285 to -0.175, effect size[OR] = 0.795). However, we found evidence of reverse causality in the relationship between SB and schizophrenia. Further, PTSD, bipolar disorder, anorexia, and ADHD were all associated with increased PA. This study provides evidence consistent with a causal protective effect of objectively assessed but not self-reported PA on reduced depression and cigarette smoking. Objectively assessed SB had a protective relationship with anorexia. Enhancing PA may be an effective intervention strategy to reduce depressive symptoms and addictive behaviours, while promoting sedentary or light physical activities may help to reduce the risk of anorexia in at-risk individuals.

Genetic associations with parental investment from conception to wealth inheritance in six cohorts.

Genetic inheritance is not the only way parents' genes may affect children. It is also possible that parents' genes are associated with investments into children's development. We examined evidence for links between parental genetics and parental investments, from the prenatal period through to adulthood, using data from six population-based cohorts in the UK, US and New Zealand, together totalling 36,566 parents. Our findings revealed associations between parental genetics-summarized in a genome-wide polygenic score-and parental behaviour across development, from smoking in pregnancy, breastfeeding in infancy, parenting in childhood and adolescence, to leaving a wealth inheritance to adult children. Effect sizes tended to be small at any given time point, ranging from RR = 1.12 (95% confidence interval (95%CI) 1.09, 1.15) to RR = 0.76 (95%CI 0.72, 0.80) during the prenatal period and infancy; ß = 0.07 (95%CI 0.04, 0.11) to ß = 0.29 (95%CI 0.27, 0.32) in childhood and adolescence, and RR = 1.04 (95%CI 1.01, 1.06) to RR = 1.11 (95%CI 1.07, 1.15) in adulthood. There was evidence for accumulating effects across development, ranging from ß = 0.15 (95%CI 0.11, 0.18) to ß = 0.23 (95%CI 0.16, 0.29) depending on cohort. Our findings are consistent with the interpretation that parents pass on advantages to offspring not only via direct genetic transmission or purely environmental paths, but also via genetic associations with parental investment from conception to wealth inheritance.

Do Children With Attention-Deficit/Hyperactivity Disorder Symptoms Become Socially Isolated? Longitudinal Within-Person Associations in a Nationally Representative Cohort.

Objective: This study examined longitudinal associations between attention-deficit/hyperactivity disorder (ADHD) symptoms and social isolation across childhood. The study tested the direction of this association across time, while accounting for preexisting characteristics, and assessed whether this association varied by ADHD presentation, informant, sex, and socioeconomic status. Method: Participants included 2,232 children from the Environmental Risk (E-Risk) Longitudinal Twin Study. ADHD symptoms and social isolation were measured at ages 5, 7, 10, and 12. Random-intercept cross-lagged panel models were used to assess the directionality of the association across childhood. Results: Children with increased ADHD symptoms were consistently at increased risk of becoming socially isolated later in childhood, over and above stable characteristics (ß = .05-.08). These longitudinal associations were not bidirectional; isolated children were not at risk of worsening ADHD symptoms later on. Children with hyperactive ADHD presentation were more likely to become isolated, compared with inattentive presentation. This was evident in the school setting, as observed by teachers, but not by mothers at home. Conclusion: The study findings highlight the importance of enhancing peer social support and inclusion for children with ADHD, particularly in school settings. This study adds explanatory value beyond traditional longitudinal methods, as the results represent how individual children change over time, relative to their own preexisting characteristics. Diversity & Inclusion Statement: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Editorial: Are Group-Based Interventions Effective for Treating Trauma-Related Psychopathology in Children and Young People?

Trauma-exposed young people are about twice as likely as their unexposed peers to develop mental health problems, which, if left untreated, can have long-term negative consequences.1 There is robust evidence for the effectiveness of individual trauma-focused psychological therapies to improve trauma-related psychopathology, particularly posttraumatic stress disorder (PTSD), in young people.2 However, there are minimal services that provide such specialist treatments in low/middle-income countries where most young people live,3 and services may be severely disrupted at times of extreme stressors, such as war, natural disasters, and other humanitarian crises, when need is greatest.4 Moreover, even in high-income stable regions where child mental health services are established and treatments are available, these health care resources are limited, and can only be accessed by a minority of affected trauma-exposed young people.5 There is therefore a need for research to indicate effective interventions that are more accessible and can be delivered on a greater scale to treat more young people with trauma-related psychopathology.6 The recent meta-analysis by Davis et al.7 focused on the more accessible intervention of group-based psychological treatment for child PTSD symptoms, and found evidence of effectiveness compared with control conditions. The study provides an important advancement in this field, and also highlights the need for further research to better understand how group interventions can be most usefully implemented.

Socioenvironmental Adversity and Adolescent Psychotic Experiences: Exploring Potential Mechanisms in a UK Longitudinal Cohort.

BACKGROUND AND HYPOTHESIS: Children exposed to socioenvironmental adversities (eg, urbanicity, pollution, neighborhood deprivation, crime, and family disadvantage) are more likely to subsequently develop subclinical psychotic experiences during adolescence (eg, hearing voices, paranoia). However, the pathways through which this occurs have not been previously investigated. We hypothesized that cognitive ability and inflammation would partly explain this association. STUDY DESIGN: Data were utilized from the Environmental-Risk Longitudinal Twin Study, a cohort of 2232 children born in 1994-1995 in England and Wales and followed to age 18. Socioenvironmental adversities were measured from birth to age 10 and classified into physical risk (defined by high urbanicity and air pollution) and socioeconomic risk (defined by high neighborhood deprivation, neighborhood disorder, and family disadvantage). Cognitive abilities (overall, crystallized, fluid, and working memory) were assessed at age 12; and inflammatory markers (C-reactive protein, interleukin-6, soluble urokinase plasminogen activator receptor) were measured at age 18 from blood samples. Participants were interviewed at age 18 regarding psychotic experiences. STUDY RESULTS: Higher physical risk and socioeconomic risk were associated with increased odds of psychotic experiences in adolescence. The largest mediation pathways were from socioeconomic risk via overall cognitive ability and crystallized ability, which accounted for ~11% and ~19% of the association with psychotic experiences, respectively. No statistically significant pathways were found via inflammatory markers in exploratory (partially cross-sectional) analyses. CONCLUSIONS: Cognitive ability, especially crystallized ability, may partly explain the association between childhood socioenvironmental adversity and adolescent psychotic experiences. Interventions to support cognitive development among children living in disadvantaged settings could buffer them against developing subclinical psychotic phenomena.

Prevalence of post-traumatic stress disorder and validity of the Impact of Events Scale - Revised in primary care in Zimbabwe, a non-war-affected African country.

BACKGROUND: A critical step in research on the epidemiology of post-traumatic stress disorder (PTSD) in low-resource settings is the validation of brief self-reported psychometric tools available in the public domain, such as the Impact Event Scale - Revised (IES-R). AIMS: We aimed to investigate the validity of the IES-R in a primary healthcare setting in Harare, Zimbabwe. METHOD: We analysed data from a survey of 264 consecutively sampled adults (mean age 38 years; 78% female). We estimated the area under the receiver operating characteristic curve and sensitivity, specificity and likelihood ratios for different cut-off points of the IES-R, against a diagnosis of PTSD made using the Structured Clinical Interview for DSM-IV. We performed factor analysis to evaluate construct validity of the IES-R. RESULTS: The prevalence of PTSD was 23.9% (95% CI 18.9-29.5). The area under the curve for the IES-R was 0.90. At a cut-off of ≥47, the sensitivity of the IES-R to detect PTSD was 84.1 (95% CI 72.7-92.1) and specificity was 81.1 (95% CI 75.0-86.3). Positive and negative likelihood ratios were 4.45 and 0.20, respectively. Factor analysis revealed a two-factor solution, with both factors showing good internal consistency (Cronbach's factor-1 α = 0.95, factor-2 α = 0.76). In a post hoc analysis, we found the brief six-item IES-6 also performed well, with an area under the curve of 0.87 and optimal cut-off of 15. CONCLUSIONS: The IES-R and IES-6 had good psychometric properties and performed well for indicating possible PTSD, but at higher cut-off points than those recommended in the Global North.

The developmental course of loneliness in adolescence: Implications for mental health, educational attainment, and psychosocial functioning.

The present study examined patterns of stability and change in loneliness across adolescence. Data were drawn from the Environmental Risk (E-Risk) Longitudinal Twin Study, a UK population-representative cohort of 2,232 individuals born in 1994 and 1995. Loneliness was assessed when participants were aged 12 and 18. Loneliness showed modest stability across these ages (r = .25). Behavioral genetic modeling indicated that stability in loneliness was explained largely by genetic influences (66%), while change was explained by nonshared environmental effects (58%). Individuals who reported loneliness at both ages were broadly similar to individuals who only reported it at age 18, with both groups at elevated risk of mental health problems, physical health risk behaviors, and education and employment difficulties. Individuals who were lonely only at age 12 generally fared better; however, they were still more likely to finish school with lower qualifications. Positive family influences in childhood predicted reduced risk of loneliness at age 12, while negative peer experiences increased the risk. Together, the findings show that while early adolescent loneliness does not appear to exert a cumulative burden when it persists, it is nonetheless a risk for a range of concomitant impairments, some of which can endure.

A genetically informed Registered Report on adverse childhood experiences and mental health.

Children who experience adversities have an elevated risk of mental health problems. However, the extent to which adverse childhood experiences (ACEs) cause mental health problems remains unclear, as previous associations may partly reflect genetic confounding. In this Registered Report, we used DNA from 11,407 children from the United Kingdom and the United States to investigate gene-environment correlations and genetic confounding of the associations between ACEs and mental health. Regarding gene-environment correlations, children with higher polygenic scores for mental health problems had a small increase in odds of ACEs. Regarding genetic confounding, elevated risk of mental health problems in children exposed to ACEs was at least partially due to pre-existing genetic risk. However, some ACEs (such as childhood maltreatment and parental mental illness) remained associated with mental health problems independent of genetic confounding. These findings suggest that interventions addressing heritable psychiatric vulnerabilities in children exposed to ACEs may help reduce their risk of mental health problems.