Social isolation and poor mental health in young people: testing genetic and environmental influences in a longitudinal cohort study.

We assessed genetic and environmental influences on social isolation across childhood and the overlap between social isolation and mental health symptoms including depression symptoms, conduct problems, and psychotic-like experiences from adolescence to young adulthood. Participants included 2,232 children from the Environmental Risk Longitudinal Twin Study. Social isolation was measured at ages 5, 7, 10, 12, and 18. A Cholesky decomposition was specified to estimate the genetic and environmental influences on social isolation across ages 5, 7, 10, and 12. An independent pathway model was used to assess additive genetic (A), shared environmental (C), and non-shared environmental (E) influences on the overlap between social isolation and mental health problems from age 12 to 18. Genetic and non-shared environmental influences accounted for half of the variance in childhood social isolation. Genetic influences contributed to the continuity of social isolation across childhood, while non-shared environmental influences were age-specific. The longitudinal overlap between social isolation and mental health symptoms was largely explained by genetic influences for depression symptoms (r = 0.15-0.24: 82-84% A, 11-12% C, and 5-6% E) and psychotic-like experiences (r = 0.13-0.15: 81-91% A, 0-8% C, and 9-11% E) but not conduct problems (r = 0.13-0.16; 0-42% A, 42-81% C, 16-24% E). Our findings emphasise that rather than a risk factor or an outcome, social isolation is aetiologically intertwined with the experience of poor mental health. An integrative assessment of social isolation could be a helpful indicator of underlying mental health symptoms in young people.

Objective and subjective experiences of childhood maltreatment and their relationships with cognitive deficits: a cohort study in the USA.

BACKGROUND: Cognitive deficits might contribute to the elevated risk of life-course psychopathology observed in maltreated children. Leading theories about the links between childhood maltreatment and cognitive deficits focus on documented exposures (objective experience), but empirical research has largely relied on retrospective self-reports of these experiences (subjective experience), and the two measures identify largely non-overlapping groups. We aimed to test the associations of objective and subjective measures of maltreatment with cognitive abilities within the same individuals. METHODS: We studied a cohort of individuals from the US Midwest with both objective, court-documented evidence of childhood maltreatment and subjective self-reports of individuals' histories at age 29 years. Between the ages of 29 years and 41 years, participants were assessed with a comprehensive set of cognitive tests, including tests of general verbal intelligence (Quick Test and Wide Range Achievement Test-Revised [WRAT]), non-verbal intelligence (Matrix Reasoning Test [MRT]), executive function (Stroop Test and Trail Making Test Part B [TMT-B]), and processing speed (Trail Making Test Part A [TMT-A]). Participants were also assessed for psychopathology (Center for Epidemiologic Studies Depression Scale and Beck Anxiety Inventory). We tested the associations between objective or subjective measures of childhood maltreatment with cognitive functions using ordinary least squares regression. To test whether cognitive deficits could explain previously described associations between different measures of maltreatment and subsequent psychopathology, we re-ran the analyses accounting for group differences in the Quick Test. People with lived experience were not involved in the research or writing process. FINDINGS: The cohort included 1196 individuals (582 [48·7%] female, 614 [51·3%] male; 752 [62·9%] White, 417 [34·9%] Black, 36 [3·8%] Hispanic) who were assessed between 1989 and 2005. Of the 1179 participants with available data, 173 had objective-only measures of childhood maltreatment, 492 had objective and subjective measures, 252 had subjective-only measures, and 262 had no measures of childhood maltreatment. Participants with objective measures of childhood maltreatment showed pervasive cognitive deficits compared with those without objective measures (Quick Test: ß=-7·97 [95% CI -9·63 to -6·30]; WRAT: ß=-7·41 [-9·09 to -5·74]; MRT: ß=-3·86 [-5·86 to -1·87]; Stroop Test: ß=-1·69 [-3·57 to 0·20]; TMT-B: ß=3·66 [1·67 to 5·66]; TMT-A: ß=2·92 [0·86 to 4·98]). The associations with cognitive deficits were specific to objective measures of neglect. In contrast, participants with subjective measures of childhood maltreatment did not differ from those without subjective measures (Quick Test: ß=1·73 [95% CI -0·05 to 3·50]; WRAT: ß=1·62 [-0·17 to 3·40]; MRT: ß=0·19 [-1·87 to 2·24]; Stroop Test: ß=-1·41 [-3·35 to 0·52]; TMT-B: ß=-0·57 [-2·69 to 1·55]; TMT-A: ß=-0·36 [-2·38 to 1·67]). Furthermore, cognitive deficits did not explain associations between different measures of maltreatment and subsequent psychopathology. INTERPRETATION: Previous studies based on retrospective reports of childhood maltreatment have probably grossly underestimated the extent of cognitive deficits in individuals with documented experiences of childhood maltreatment, particularly neglect. Psychopathology associated with maltreatment is unlikely to emerge because of cognitive deficits, but might instead be driven by individual appraisals, autobiographical memories, and associated schemas. FUNDING: National Institute of Justice, National Institute of Mental Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute on Aging, Doris Duke Charitable Foundation, and National Institute for Health and Care Research.

Trajectories of childhood bullying behaviors and conduct problems: Associations with cognitive functioning in a nationally representative cohort study.

Bullying behaviors and conduct problems are two forms of antisocial behavior that frequently co-occur in childhood. However, it remains unclear whether their developmental trajectories are distinct and the extent to which different aspects of cognitive functioning account for their development. We aimed to disentangle the developmental trajectories of bullying behaviors and conduct problems, test their interrelations across childhood, and assess associations with children's early cognitive functioning (executive functions, intelligent quotient [IQ], and theory of mind). Participants included 2,232 children from the Environmental Risk (E-Risk) Longitudinal Twin Study. We performed dual group-based trajectory modeling on combined parent and teacher reports of children's bullying behaviors and conduct problems at 5, 7, 10, and 12 years. We assessed associations with age 5 cognitive functioning using regression analyses. We identified five developmental trajectories for bullying behaviors and four for conduct problems. The developmental course of both behaviors was interrelated most strongly among those with high levels. A subgroup of children was likely to transition from conduct problems to bullying behaviors as they got older. Lower IQ was associated with both antisocial behavior trajectories, whereas lower theory of mind was only associated with conduct problems trajectories. The developmental course of bullying behaviors and conduct problems is distinct but linked across childhood. Interventions targeting bullying behaviors or conduct problems could benefit from more integration and should take into account children's cognitive functioning. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Advances in the Management of Localized Scleroderma: A Systematic Review of Laser Therapy and Injectable Filler Approaches.

Localized scleroderma (LS), commonly known as morphea, presents a significant clinical challenge due to its chronic, inflammatory nature affecting the skin and potentially underlying tissues. This systematic review explores the innovative approach of combining laser therapy and injectable fillers, specifically hyaluronic acid, for the treatment of LS. We conducted a comprehensive literature review following PRISMA guidelines, examining articles from MEDLINE/PubMed to assess the combined efficacy of these treatments in improving both esthetic and functional outcomes for LS patients. The search yielded 64 articles, with six selected for in-depth analysis for a total of nine patients, covering a range of patient demographics and treatment types. Our review highlights cases where fractional CO2 laser therapy promoted long-term tissue remodeling and instances where hyaluronic acid fillers effectively addressed skin atrophy and volume loss, enhancing both immediate and long-lasting esthetic improvements. The synergy between these treatments suggests a promising dual approach, aiming to maximize esthetic outcomes and to improve the quality of life for LS patients. This review underscores the necessity of further research to establish a comprehensive, evidence-based clinical pathway integrating both treatments for managing LS, thereby enhancing patient satisfaction and addressing the multifaceted nature of this challenging dermatological condition.

Research Review: Why do prospective and retrospective measures of maltreatment differ? A narrative review.

BACKGROUND: Childhood maltreatment contributes to a large mental health burden worldwide. Different measures of childhood maltreatment are not equivalent and may capture meaningful differences. In particular, prospective and retrospective measures of maltreatment identify different groups of individuals and are differentially associated with psychopathology. However, the reasons behind these discrepancies have not yet been comprehensively mapped. METHODS: In this review, we draw on multi-disciplinary research and present an integrated framework to explain maltreatment measurement disagreement. RESULTS: We identified three interrelated domains. First, methodological issues related to measurement and data collection methods. Second, the role of memory in influencing retrospective reports of maltreatment. Finally, the motivations individuals may have to disclose, withhold, or fabricate information about maltreatment. CONCLUSIONS: A greater understanding of maltreatment measurement disagreement may point to new ways to conceptualise and assess maltreatment. Furthermore, it may help uncover mechanisms underlying maltreatment-related psychopathology and targets for novel interventions.

Misdiagnosis and Clinical Insights into Acral Amelanotic Melanoma-A Systematic Review.

BACKGROUND: Acral amelanotic melanomas (AAMs), a rare subset of melanomas located on acral sites such as the palms, soles, and subungual areas, are diagnostically challenging due to their lack of typical pigmentation and often benign clinical appearance. Misdiagnosis is common, leading to delays in treatment and potentially worse outcomes. This systematic review aims to synthesise evidence on cases of AAM initially misdiagnosed as other conditions, to better understand their clinical and epidemiological characteristics, diagnostic pitfalls, and management strategies. METHODS: A comprehensive search of the MEDLINE/PubMed, EMBASE, and SCOPUS databases was conducted up to March 2024. Case reports and small case series of AAMs initially misdiagnosed as other conditions were included. Data on patient demographics, clinical presentation, and diagnostic methods were collected and analyzed. RESULTS: Of the 152 records identified, 26 cases from 23 articles met the inclusion criteria. A demographic analysis revealed that the gender distribution appears to be perfectly balanced, with an age range of 38 to 91 years. Misdiagnoses included non-healing ulcers or traumatic lesions (37.5%), benign proliferative lesions (29.2%) and infectious lesions (20.8%). The foot was the most affected site (53.8%). Notably, a histological evaluation was performed in 50% of cases involving the upper extremities, in contrast to only 7.1% of cases involving the foot and 0% of cases of the heel. This discrepancy suggests a reluctance to perform biopsies in the lower extremities, which may contribute to a higher misdiagnosis rate in these areas. CONCLUSIONS: The underutilization of biopsy in the diagnosis of lower extremity lesions contributes significantly to the misdiagnosis and delay in treatment of AAMs. Especially when the clinical assessment and dermoscopy are inconclusive, biopsies of suspicious lesions are essential. Immunohistochemistry and markers such as PRAME are critical in differentiating melanoma from other malignancies such as clear cell sarcoma. This review highlights the need for increased vigilance and a proactive diagnostic approach to increase early detection rates and improve prognostic outcomes.

The lived experience of mental disorders in adolescents: a bottom-up review co-designed, co-conducted and co-written by experts by experience and academics.

We provide here the first bottom-up review of the lived experience of mental disorders in adolescents co-designed, co-conducted and co-written by experts by experience and academics. We screened first-person accounts within and outside the medical field, and discussed them in collaborative workshops involving numerous experts by experience - representing different genders, ethnic and cultural backgrounds, and continents - and their family members and carers. Subsequently, the material was enriched by phenomenologically informed perspectives and shared with all collaborators. The inner subjective experience of adolescents is described for mood disorders, psychotic disorders, attention-deficit/hyperactivity disorder, autism spectrum disorders, anxiety disorders, eating disorders, externalizing disorders, and self-harm behaviors. The recollection of individuals' past histories also indexes the prodromal (often transdiagnostic) features predating the psychiatric diagnosis. The experience of adolescents with mental disorders in the wider society is described with respect to their family, their school and peers, and the social and cultural context. Furthermore, their lived experience of mental health care is described with respect to receiving a diagnosis of mental disorder, accessing mental health support, receiving psychopharmacological treatment, receiving psychotherapy, experiencing peer support and mental health activism, and achieving recovery. These findings can impact clinical practice, research, and the whole society. We hope that this co-designed, co-conducted and co-written journey can help us maintain our commitment to protecting adolescents' fragile mental health, and can help them develop into a healthy, fulfilling and contributing adult life.

Scoping Review: Digital Mental Health Interventions for Children and Adolescents Affected by War.

OBJECTIVE: More than 200 million children and adolescents live in countries affected by violent conflict, are likely to have complex mental health needs, and struggle to access traditional mental health services. Digital mental health interventions have the potential to overcome some of the barriers in accessing mental health support. We performed a scoping review to map existing digital mental health interventions relevant for children and adolescents affected by war, to examine the strength of the evidence base, and to inform the development of future interventions. METHOD: Based on a pre-registered strategy, we systematically searched MEDLINE, Embase, Global Health, APA PsychInfo, and Google Scholar from the creation of each database to September 30, 2022, identifying k = 6,843 studies. Our systematic search was complemented by extensive consultation with experts from the GROW Network. RESULTS: The systematic search identified 6 relevant studies: 1 study evaluating digital mental health interventions for children and adolescents affected by war, and 5 studies for those affected by disasters. Experts identified 35 interventions of possible relevance. The interventions spanned from universal prevention to specialist-guided treatment. Most interventions directly targeted young people and parents or carers/caregivers and were self-guided. A quarter of the interventions were tested through randomized controlled trials. Because most interventions were not culturally or linguistically adapted to relevant contexts, their implementation potential was unclear. CONCLUSION: There is very limited evidence for the use of digital mental health interventions for children and adolescents affected by war at present. The review provides a framework to inform the development of new interventions. DIVERSITY & INCLUSION STATEMENT: We actively worked to promote sex and gender balance in our author group. STUDY PREREGISTRATION INFORMATION: Digital mental health interventions for children and young people affected by war: a scoping review; https://osf.io/; hrny9.

Prospective and Retrospective Measures of Child Maltreatment and Their Association With Psychopathology: A Systematic Review and Meta-Analysis.

Importance: Prospective and retrospective measures of childhood maltreatment identify largely different groups of individuals. However, it is unclear if these measures are differentially associated with psychopathology. Objective: To analyze the associations of prospective and retrospective measures of childhood maltreatment with psychopathology. Data Sources: Based on a preregistered protocol, Embase, PsycInfo, and MEDLINE were searched for peer-reviewed studies published by January 1, 2023, that measured the associations of prospective and retrospective measures of child maltreatment with psychopathology. Study Selection: Titles and abstracts of all articles captured by the search and full texts of potentially eligible studies were independently screened by 2 authors. Observational studies with measures of the association of prospective and retrospective measures of childhood maltreatment with psychopathology were included. Data Extraction and Synthesis: Multiple investigators independently extracted data. Multilevel random-effects meta-analyses were used to pool the results and test predictors of heterogeneity. Main Outcome and Measures: Associations between prospective or retrospective measures of child maltreatment and psychopathology, both unadjusted and adjusted (ie, the association between prospective measures of maltreatment and psychopathology adjusted for retrospective measures, and vice versa), and moderation of these associations by preselected variables. Results: The meta-analyses were based on 24 studies including 15 485 individuals (51.0% female; mean age, 21.3 years at retrospective report). Retrospective measures of childhood maltreatment showed stronger associations with psychopathology relative to prospective measures in both unadjusted analyses (retrospective measures: odds ratio [OR], 2.21; 95%, 1.94-2.42 vs prospective measures: OR, 1.56; 95% CI, 1.39-1.76) and adjusted analyses (retrospective measures: OR, 2.14; 95% CI, 1.90-2.42 vs prospective measures: OR, 1.27; 95% CI, 1.13-1.41). There was no statistically significant moderation of the unadjusted or adjusted associations between prospective measures of child maltreatment and psychopathology. The associations between retrospective measures and psychopathology were stronger when the assessment of psychopathology was based on self-reports and was focused on internalizing or emotional disorders. Conclusions and Relevance: Psychopathology is more strongly associated with retrospective measures-which capture the first-person, subjective appraisal of childhood events reflected in memory recall-compared to prospective measures-which essentially capture third-person accounts of such events. Maltreatment-related psychopathology may be driven by subjective interpretations of experiences, distressing memories, and associated schemas, which could be targeted by cognitive interventions.

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.