Faculty Bibliography

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition in  children and young people worldwide. Robust estimates of its incidence, prevalence, and burden are essential for informing public health policy and planning. Using data from the Global Burden of Disease Study 2021 (GBD 2021), this global population-based analysis assessed ADHD among individuals under 20 years of age across 204 countries and territories from 1990 to 2021. The study examined incidence, prevalence, and disability-adjusted life years (DALYs) associated with ADHD. In 2021, there were an estimated 46,890,733 (95% uncertainty interval [UI]: 32,136,904-67,271,064) prevalent cases and 4,111,621 (2,775,203-5,954,941) incident cases globally in individuals under 20 years. ADHD accounted for 574,979 (294,277-977,557) DALYs, with a global prevalence rate of 1.78% (1.22-2.55%) and an incidence rate of 0.16% (0.11-0.23%). The global DALY rate was 21.8 (11.2-37.1) per 100,000 population. Prevalence and incidence were highest in Australia, with rates of 5.62% (4.16-7.46%) and 0.49% (0.34-0.66%), respectively. Between 1990 and 2021, global prevalence and incidence rates decreased modestly by 6.0 and 5.81%, respectively. Across all GBD regions, prevalence was higher in males than females (2.52 vs 0.99%) and increased with higher socio-demographic index levels. Overall, the GBD 2021 study provides the most comprehensive global estimates of ADHD burden in young people. These findings are important for guiding policymakers and stakeholders, although potential methodological limitations suggest that the prevalence, incidence, and burden of ADHD may be underestimated.

INTRODUCTION/BACKGROUND:A variety of rating scales are currently being used to assess symptom severity and quantify symptoms change in attention-deficit/hyperactivity disorder (ADHD) research and clinical practice. This poses difficulties in interpreting scores from different scales in clinical practice and synthesizing data from studies using different scales. We aimed to develop algorithms for converting scores across the ADHD scales most often used in randomized controlled trials (RCTs) of ADHD medications in children/adolescents and adults, and to develop an online tool for implementing the algorithms. METHODS: RESULTS:We linked six commonly used ADHD scales, such as the ADHD Rating Scale (ADHD-RS-IV; investigator-rated) and the Conners' Parent Rating Scale (CPRS-R:S). Spline models most frequently yielded the lowest prediction error, outperforming alternative conversion algorithms for absolute scores in 6 out of 12 univariable models and 8 out of 12 multivariable models. The tool for scores conversion is available at ADHD_Scale_Conversion_Tool. CONCLUSIONS:Our linkage algorithms enable the comparison and harmonization of findings across studies using different ADHD rating scales. Translating scores across scales improves the interpretability of research findings, facilitates future evidence synthesis across studies, and may support clinical practice. Our online tool supports the practical uptake of our results.

IntroductionBipolar depression is disabling and often inadequately responsive to medication alone. The current efficacy evidence of transcranial magnetic stimulation (TMS) for bipolar depression is conflicting. Therefore, we synthesized randomized controlled trials (RCTs) that tested the efficacy, safety, and tolerability of TMS for bipolar depression.MethodsWe searched MEDLINE/EMBASE/Cochrane/PsycINFO/gray literature (01/10/2025) for RCTs comparing any TMS protocol with sham. Co-primary outcomes were depressive symptoms, all-cause discontinuation; secondary outcomes were response, remission. Risk of bias (RoB) was assessed with RoB-2. Random-effects models estimated standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (95%CI), alongside sensitivity, subgroup, and meta-regression analyses.ResultsNineteen comparisons from 17 RCTs (N = 563; TMS = 293, sham = 270; mean N TMS = 15.4, sham = 15.9; mean duration = 2.40 weeks; RoB "low" = 35%, "some concerns" = 65%) were included. Among trials reporting subtypes (k = 13), 41.8% of participants had bipolar I disorder, and 58.2% had bipolar II disorder. The left dorsolateral prefrontal cortex was the most common target (k = 12). TMS reduced depressive symptoms versus sham (SMD = -0.34; 95%CI = -0.58 to -0.11), with no difference in all-cause discontinuation. TMS was favoured for response (RR = 1.41; 95%CI = 1.10 to 1.80) and remission (RR = 1.54; 95%CI = 1.06 to 2.23). However, these effects were not consistently confirmed in sensitivity or subgroup analyses by RoB, TMS type, stimulation site, or treatment resistance. Overall, 15 comparisons (88.2%) did not show superiority of TMS over sham for depressive symptoms at the individual trial level. No seizures or serious adverse events occurred; adverse events did not differ from sham. Meta-regression suggested a greater number of total pulses was associated with greater depressive symptom reduction (β = -0.018; p = .00017).ConclusionsTMS shows a small meta-analytic antidepressant effect and acceptable tolerability in bipolar depression despite most individual trials being negative. However, subgroups and sensitivity findings did not support TMS as an efficacious treatment at current doses. Further testing via larger RCTs with higher-dose protocols is warranted.

While attention-deficit/hyperactivity disorder (ADHD) medications, particularly stimulants, are among the most effective treatments in psychiatry, there remains a need for novel alternatives, as not all individuals with ADHD respond to or tolerate currently available medications. We aimed to provide an up-to-date overview of randomised controlled trials (RCTs) of agents either not approved for ADHD or approved for ADHD but tested for off-label indications. We updated, using the same methodology, two previous reviews (Cortese et al, 2023 exploring agents in the pipeline for children with ADHD, and Veronesi et al, 2024, focusing on RCTs of novel compounds in adults with ADHD). For the update, we searched ClinicalTrials.gov and the European Union-based EU Clinical Trials registers up to December 14, 2025. Including the RCTs retrieved by the two previous reviews and those from the updated search, we identified a total of 53 eligible RCTs. Of these, 11 reported results in children and adolescents, and 11 in adults. Considering agents with at least two positive trials for ADHD core symptoms without negative trials, only dasotraline, in children, and centanafadine, in adults, emerged as promising (however, the dasotraline development programme was halted in 2020). This review also includes a discussion of opportunities for advancing the development of novel, effective agents and maximising the benefits of currently available options.

It is estimated that, globally, the mean point prevalence of diagnosable mental disorders in children and adolescents is higher than 11%, and around half of cases of major mental disorders have their onset before the age of 18. Mental disorders with onset in childhood or adolescence have an enormous impact on the developing brain, body and personal identity, as well as on the short- and long-term social, educational and functional capacity of individuals. Child and adolescent psychiatry - as a discipline, profession, academic field, and network of clinical services - is still relatively young, with its formal evolution beginning in the 20th century. Therefore, it is not surprising that there are currently many challenges, but also opportunities and expected future developments, in this area. In this paper, we identify and address the core challenges, possible solutions, opportunities, and future directions of child and adolescent psychiatry. In the first part of the paper, challenges and possible solutions are discussed regarding diagnostic issues, stigma, access to care, shortage of mental health professionals, evidence-based treatments, treatment adherence, parental participation/engagement, integration with schools, digital influences and cyberbullying, and war/forced displacement. In the second part, opportunities and developments are addressed that relate to early identification and intervention, resilience, interdisciplinary collaborations, integration with primary care, community-based approaches, use of digital technologies, precision child and adolescent psychiatry, artificial intelligence and related ethical issues, and cultural diversity and competences. Despite the significance and impact of mental disorders in children and adolescents, clinical delivery and research on these conditions remain underfunded and underprioritized, even in high-income countries, with clinical services and prevention/early intervention research receiving minimal investment. Addressing mental health in children and young people requires multi-level strategies beyond individual treatment, including tackling structural and socioeconomic barriers and creating opportunities for strengthening resilience and well-being. A well-trained workforce, adequate policies, and increased public awareness are crucial. Overall, the current gaps demand urgent action and global funding rebalancing to more adequately meet the critical needs of children and young people challenged by mental illness.

Anxiety disorders are the most prevalent mental health conditions worldwide. While their burden in terms of excess mortality is known to be high, a quantitative systematic evaluation of all-cause and cause-specific mortality and suicide attempt risks in people with anxiety or stress-related disorders is lacking. We performed a systematic review and random effects meta-analysis, in which co-primary outcomes were risk ratios (RRs) for all-cause and suicide-related mortality, and secondary outcomes were natural-cause mortality, other cause-specific mortality, and risk of suicide attempt. Sensitivity and meta-regression analyses were conducted. Overall, 165 studies encompassing 7,395,722 people with any anxiety or stress-related disorder and 135,059,023 controls, from 27 different countries across all continents, were included. Compared with the general population, a higher risk of all-cause mortality was associated with any anxiety or stress-related disorder (n=42, RR=1.54, 95% CI: 1.14-2.08, p=0.005), generalized anxiety disorder (n=9, RR=1.48, 95% CI: 1.23-1.78, p<0.001), and post-traumatic stress disorder (PTSD) and other stress-related disorders (n=21, RR=1.39, 95% CI: 1.15-1.67, p<0.001), but not with panic disorder, phobias, and mixed anxiety or stress-related disorders. Suicide mortality was increased in people with any anxiety or stress-related disorder (n=39, RR=2.88, 95% CI: 2.13-3.89, p<0.001), panic disorder (n=3, RR=3.58, 95% CI: 1.39-9.25, p<0.008), mixed anxiety or stress-related disorders (n=27, RR=2.77, 95% CI: 1.89-4.07, p<0.001), PTSD and other stress-related disorders (n=11, RR=3.13, 95% CI: 1.85-5.28, p<0.001), and generalized anxiety disorder (n=3, RR=1.93, 95% CI: 1.17-3.17, p<0.01). Suicide attempt risk was higher than in the general population in people with all anxiety or stress-related disorders, ranging from RR=6.33 (95% CI: 4.08-9.82, n=5) in panic disorder to RR=2.74 (95% CI: 1.72-4.35, n=5) in phobias. Natural-cause mortality was increased in any anxiety or stress-related disorder (n=19, RR=1.25, 95% CI: 1.09-1.44, p=0.002), generalized anxiety disorder (n=5, RR=1.55, 95% CI: 1.19-2.02, p=0.001), mixed anxiety or stress-related disorders (n=8, RR=1.26, 95% CI: 1.02-1.56, p=0.033), and PTSD and other stress-related disorders (n=9, RR=1.17, 95% CI: 1.03-1.33, p=0.019), but not in panic disorder. Cardiovascular-related deaths were increased in any and mixed anxiety or stress-related disorders and in generalized anxiety disorder, while cancer mortality was increased only in generalized anxiety disorder. When analyzing people with vs. without anxiety disorders with samples being matched by comorbid physical or mental disorders, results remained significant for all-cause mortality in generalized anxiety disorder and panic disorder, but not in any or mixed anxiety or stress-related disorders, and in PTSD and stress-related disorders. When compared with other mental disorders, no difference in co-primary outcomes emerged from more than two studies. Publication bias was present across several analyses, but sensitivity analyses largely confirmed the main findings. In meta-regression analyses, more recent data collection mitigated all-cause mortality, while schizophrenia-spectrum and bipolar disorder comorbidity mitigated suicide mortality risk, possibly driven by underlying treatment. This meta-analysis documents a higher all-cause, suicide and natural-cause mortality, and a higher risk of suicide attempt, in people with anxiety or stress-related disorders compared to the general population. Given the high prevalence and the recognized global treatment gap for these disorders, this finding is of great public health concern, and calls for appropriate prevention, screening and treatment strategies. More studies are needed to fill the publication bias gap and to identify modifiable risk or mitigating factors.

BACKGROUND:Optimising the dosage of pharmacological treatments for ADHD is key to maximising their benefits, yet most clinical guidelines provide only limited information on this issue. Dose-effect relationships have not been comprehensively assessed across all ADHD medications and age groups, despite growing concerns about subtherapeutic prescribing. We aimed to estimate dose-effect curves for efficacy and tolerability of ADHD medications (stimulants and non-stimulants) across age groups. METHODS:We conducted a systematic review and dose-effect network meta-analysis of double-blind randomised controlled trials (RCTs) evaluating oral monotherapy (stimulants and non-stimulants) in individuals aged 5 years and older meeting standardised ADHD criteria. Studies involving genetic syndromes, treatment-resistant populations, or withdrawal-phase designs were excluded. We retrieved eligible studies from the MED-ADHD database, updated on Feb 17, 2025, without language restrictions. We included published and unpublished aggregated-level data. The primary outcome was efficacy (measured using validated clinical scales) and the secondary outcome was tolerability (discontinuation due to adverse events). Within-study bias was assessed with the Cochrane Risk of Bias Tool (version 2). We summarised dose-effect associations using a hierarchical Bayesian model with restricted cubic splines. Separate analyses were conducted for children or adolescents (aged <18 years) and adults (aged ≥18 years). The distribution of key effect modifiers was used to examine transitivity of the network. People with lived experience were involved in the conceptualisation and design of the study, and in the interpretation of the findings. The protocol was pre-registered on OSF. FINDINGS/RESULTS:Our 2017 search identified 9948 potential references for inclusion and our Feb 17, 2025 search identified 5148 references. Of these 15 096 references, 8467 were excluded after title and abstract screening, and a further 5862 references were excluded after a full-text read. Of the 767 remaining reports, 164 were included in the systematic review and 113 RCTs (45 in adults and 68 in children and adolescents) were included in the dose-effect network meta-analysis. The 68 RCTs on children and adolescents included 14 138 participants (9981 [70·6%] males and 4157 [29·4%] females) and the 45 RCTs on adults included 11 016 participants (5958 [54·0%] males and 5056 [46·0%] females). Data on ethnicity or race were inconsistently reported across RCTs. We found distinct dose-effect patterns by medication class and age group. In children and adolescents, methylphenidate, amphetamines, and guanfacine showed increasing median efficacy up to 45 mg/day, 25 mg/day and 4 mg/day, respectively, with no evidence of additional benefit at higher doses, although estimates at higher doses were characterised by wide credible intervals. In adults, amphetamines showed a plateau above approximatively 50 mg/day, whereas methylphenidate efficacy increased without evidence of a plateau, possibly due to sparse data. Dose-dependent increases in discontinuation probability due to adverse events were observed for amphetamines (above 25 mg/day for children and 50 mg/day for adults) and methylphenidate (above 50 mg/day for adults, with no clear dose-dependent risk for children). We found no evidence of dose-effect patterns for atomoxetine (in fixed-doses studies) and modafinil. Multiple sensitivity analyses confirmed the robustness of these findings. We found no evidence of intransitivity. INTERPRETATION/CONCLUSIONS:Our findings challenge both therapeutic inertia-accepting suboptimal response without further dose titration-and uncritical dose escalation beyond licensed limits, when potential harms outweigh expected benefits. Our findings can inform clinical guidelines and should support shared decision making regarding ADHD medication dosage. FUNDING/BACKGROUND:National Institute for Health and Care Research (NIHR303122).

The clinical management of a complex disorder such as schizophrenia remains a significant challenge worldwide. This disorder requires a comprehensive, integrated and personalized care that blends multiple approaches, and the real-world availability of multiple resources. We present here the first recommendations addressing the real-world comprehensive care for people with schizophrenia-spectrum psychoses across different approaches, clinical stages, and levels of available resources. The recommendations are based on a critical review of the scientific literature and a collaborative appraisal by numerous clinical academics actively treating people with schizophrenia worldwide, representing various countries and clinical settings, including those in the Global South. Experts by experience were also involved. Our recommendations indicate that the comprehensive care of schizophrenia should involve: a) early detection; b) measurement-based monitoring; c) pharmacological treatments; d) psychological interventions; e) psychosocial interventions (including supported employment, housing and education); f) management of somatic conditions; g) community care; h) inpatient care; i) peer support, self-help, and alternative healing methods; j) population-level prevention, and l) societal-level support. The overarching core recommendation is to implement evidence-based care that addresses disparities across high- to middle/low-resource settings, emphasizing early intervention (and prevention when possible), culturally-sensitive paradigms that leverage the local existing resources, and task-sharing models that involve non-professional health care workers and, if possible, traditional healers. In the future, we expect that scalable and resource-saving, evidence-based digital solutions will help extend and improve care quality and efficiency across all resource settings. However, none of this can be achieved without adequately focusing on and strengthening mental health funding, improving access to care, addressing social determinants of health, and recognizing that care for people at risk for or living with schizophrenia is uneven and in need of improvement across all settings.

Currently, the identification of individuals experiencing suicidal thoughts and behaviours (STBs) rely predominantly on self-report. Previous research on children and young people highlighted an association between difficulties in arousal regulation (reflected, for example, in reduced heart rate variability and altered electrodermal activity patterns) and STBs, but this has not been meta-analytically explored in adults. This systematic review and meta-analysis aimed to quantify the association between STBs and markers of autonomic functioning/regulation in adults. Based on a pre-registered protocol (PROSPERO CRD42024596886), we searched PubMed/MEDLINE, Embase, PsycINFO and Web of Science until 2^nd August 2025 for empirical studies assessing the association between measures of autonomic functioning and/or regulation and STBs in adults. Quality of cross-sectional and cohort studies was assessed through the Newcastle-Ottawa Scale. Pooled effect sizes (Hedge's g) were estimated with random-effects meta-analytic models in R. Out of 2,726 articles screened, 40 studies were included in the systematic review, and 22 in the meta-analyses (6,290 individuals, 28% with STBs). We found reduced heart rate variability in adults with STBs (g = -0.2469, p = 0.0069) but no significant associations between electrodermal activity patterns and STBs (g = -0.2563, p = 0.3953). Our results highlight the connection between reduced cardiac regulation and STBs, providing a rationale for further exploration of cardiac regulation as a potential objective marker for assessing and monitoring STBs in adults. Further research is warranted to understand how these markers can be used in clinical practice to assess and support the management of suicide risk in adults.