This is the first large-scale epidemiological meta-analysis that includes all available general population birth, cross-sectional and incidence studies investigating the age at onset of any ICD/DSM-mental disorders. Overall, the global onset of the first mental disorder occurs before age 14 in one-third of individuals, age 18 in almost half (48.4%), and before age 25 in half (62.5%), with a peak/median age at onset of 14.5/18 years across all mental disorders. However, there was significant variability in global age at onset and peak age across mental disorders. These findings can inform the timing and resource allocation regarding early intervention and preventive approaches.

To our best knowledge, this study is the first fully epidemiological and largest [35–38] meta-analysis on age at onset of mental disorders globally. It also represents the most comprehensive approach, encompassing all ICD-11 diagnostic spectra for which we found eligible studies, allowing comparative transdiagnostic analyses across different categories of mental disorders [39, 40]. Furthermore, per protocol, high-quality population-level studies were included that are less likely to be affected by biases, meeting previous methodological recommendations [30]. Moreover, data from all continents of the world were available, providing global estimates on the age at onset of mental disorders. Importantly, the statistical approach of this meta-analysis provides an estimate of age at disorder onset distribution throughout the lifespan, going beyond mere centrality estimates.

The meta-epidemiologic results of this work show that mental disorders have onset when dramatic biological changes in the brain occur, from childhood, through adolescence, to adulthood, that involves grey-matter density, cerebral metabolic rate, synaptic density, white matter growth and myelination [41]. The in-depth, robust epidemiological evidence provided here has several clinical implications. Firstly, the onset of the first mental disorder before age 14, 18 and 25 in one third, half and 62.5% and peak/median age of 15.5/18 years demonstrate that adult mental disorders originate early during the neurodevelopmental phases of life and peak, in pooled mental disorders, by mid to late adolescence [42–44]. Given that mental disorders are one of the five most common ailments leading to morbidity, mortality and dysfunction among young people worldwide [45], the current findings are relevant to policymakers and healthcare providers. These results suggest that the next generation of mental health research should prioritise designing and funding global early interventions [5, 46] and indicated, selective and/or universal preventive interventions for mental disorders during mid/late adolescence and young adulthood that are currently lacking [8].

Secondly, this study provides disorder-specific estimates of age at disorder onset that impacts mental health service configuration and delivery. For about half of mental disorders (Table 2), disorder onset occurs well before age 18. Disorder median age at onset occurred during the neurodevelopment, within age 14 for the vast majority of phobias and separation anxiety, ASD, ADHD, and for more then half in social anxiety disorders. For these disorders, good mental health promotion, along with preventive and early intervention approaches need to target these neurodevelopmental periods, mainly during pre-school and primary school periods. Many of the risk and protective factors that impact the neurodevelopment of individuals with these disorders are known [23, 47–52], and some of them may even impact the pre or perinatal phases [53]. A recent meta-umbrella review (i.e., a synthesis of systematic reviews of meta-analyses) has summarised risk and protective factors (beyond genetics) in a comprehensive atlas [54]. Importantly, targeting the neurodevelopmental phase has the potential to accommodate multi-endpoint numerators across mental disorders that are essential to better justify the denominator of efforts and costs for preventive and early intervention [8]. Higher  median age at disorder onset during the transitional period across adolescence and young adulthood emerged for another larger group of mental disorders, i.e., anorexia nervosa, bulimia nervosa, OCD, binge eating, and cannabis use disorders. For these disorders, good mental health promotion, prevention and early intervention could be delivered in primary and secondary schools [55–57]. A third group with median age at onset in the early adulthood included, schizophrenia, personality, panic and alcohol use disorders, and a fourth group included the remaining disorders that have a median age at onset in the later adulthood, such as PTSD, GAD, depressive and bipolar disorders, and ATPD. Secondary schools and colleges could become the most important setting for mental health promotion, prevention and early intervention across these two groups of mental disorders. Importantly, the diagnosis of personality disorder is artifactually delayed by diagnostic criteria allowing diagnosis after age 18, and clinically relevant symptoms occur earlier.

For all disorders culturally and ethically- sensitive [8] promotion of good mental health (indicated, selective and/or universal) prevention and early intervention should ideally be delivered in an integrated fashion that encompasses schools/colleges, and paediatricians/general practitioners, emergency departments, mental health settings, as well as the general community [60]. Overall, this study shows that any lower age threshold limiting access to mental health promotion campaigns or preventive or early interventions mental health programmes is not supported by meta-epidemiological evidence. Conversely, lower age thresholds that divide the education and training of mental health specialists or clinical services deprive individuals with developmental disorders (or other disorders with early onset) of continuity of care. Divisions fragment pathways to care and continued treatment from childhood through adolescence into adulthood (see below) [58]. Our recommendation for mental health services of the future would allow soft entry points, set no lower age threshold, and loosen lower age intake criteria [59]. For example, an indicated prevention and early intervention model of care for mood disorders, and schizophrenia-spectrum/primary psychotic disorders should ideally integrate low-threshold entry points for individuals of age younger than 18, supplemented by systematic promotion of good mental health, proactive screening for risk of developing specific mental disorders according to peak and median age at onset identified above, and deliver needs-based care [19, 60, 61].

Thirdly, a further, broader clinical implication of these results is that it demonstrates that age 18 as an intake threshold for adult mental health services is artificial and not based on global epidemiological evidence (nor on biological evidence of age when major brain changes occur [41]). To the best of our knowledge, mental health specialist training and mental health services in most parts of the world, including North America, Australia, most European countries, including Italy, Germany, UK, are divided between child/adolescent psychiatry and adult psychiatry. Given that the vast majority of mental disorders diagnoses seen in adulthood show a peak of onset before age 18, such a bifurcated mental health system is not evidence-based and may disadvantage individuals with developmental disorders from accessing and receiving adequate and continuous care [62]. Moreover, most psychiatry training programmes fail to target the transition period from childhood and adolescence to adult psychiatry [63]. Although many mental health services have tried to address this discontinuity of care [63, 64], significant gaps remain. Future mental health reforms could leverage and refine clinical high-risk services for young people at risk of psychosis, which typically accepts referrals aged 14–35 years and therefore provide essential transitional care to this vulnerable young population [15, 17, 58].

This study has several limitations. First, data were too sparse to calculate country-specific estimates. However, the database included many countries worldwide, and, therefore, the estimates provided are largely representative of the global general population. Second, the 95% confidence interval for some estimates were broad since analyses for some disorders were based on few studies. Third, data were heterogeneous, making traditional meta-analytic techniques unfeasible. We, therefore, applied advanced meta-analytic techniques, including bootstrap methods that helped to address this shortcoming and provide unified outcomes across all mental disorders. Fourth, our quality assessment was non-standardised because appropriate validated measures were not available. However, we per-protocol included the highest-quality studies to study age at onset according to previous recommendations [30]. Fifth, the definition of age at disorder onset was heterogeneous; we addressed this issue via sensitivity analyses. Sixth, we were not able to account for and differentiate among comorbid and standalone diagnoses. Sixth, we were not able to account for differences across regions. Finally, caution is needed when comparing peaks (e.g., between symptoms and diagnosis), in particular when the peak curves are different, and when comparing median age at onset across disorders (e-Table 5).