Faculty Bibliography

Childhood is a period of peak developmental plasticity, involving drastic changes in the maturation of the neural circuitry underlying fear learning. Disruption and atypical development of fear learning are candidate mechanisms underlying child psychopathology. While there is a lack of understanding behind the maturation of fear learning systems in humans, rodent studies in this area delineate the normative development of fear learning systems early in life, and the effects of early threatening and fearful experiences on this developmental trajectory. Here, we review the rodent literature on developmental fear learning, as well as human studies that show translational convergence in typical development and children exposed to early life threat. We identify several gaps in research, including the role that caregivers play in regulating fear learning at different developmental stages and the intergenerational transmission of learned fear. Finally, we provide recommendations on how to address these gaps in a way that would improve our developmental frameworks of fear learning.

Higher predicted brain age difference has been associated with several psychiatric disorders. Generalized anxiety disorder (GAD) is associated with markers of accelerated aging. In this study, we determined brain predicted age difference (PAD) in individuals with GAD and healthy controls (HC) as well as group differences in PAD variability using voxel-wise structural MRI. The training dataset included 3511 controls, and the testing dataset included 1595 individuals with GAD and 4552 HC from the ENIGMA-Anxiety GAD Working Group. A convolutional neural network model using four input modalities per subject and a model ensemble approach was used to predict brain age. The PAD was then calculated by subtracting chronological age from the predicted age. Model performance was consistent with other image-based brain age prediction models with similar accuracy across the training set (mean absolute error (MAE) = 2.95 years) and HC in the testing set (MAE = 2.94). We found no evidence of accelerated brain aging in individuals with GAD compared to individuals without GAD, though we did find evidence for greater variation in PAD for individuals with GAD (Levene's test: W = 442.98, p < 0.001) and evidence for greater variability in PAD of those with GAD over 25 years of age. In several exploratory analyses, we found that symptom severity related significantly to PAD, even after controlling for medication and comorbid diagnoses, echoing previous brain age research. These findings underscore the need for consideration of heterogeneity and dimensionality of psychopathology when examining brain age predicted differences.

BACKGROUNDS/BACKGROUND:The mental health and wellbeing of university students have become increasingly pressing concerns, with rates of psychological distress rising in recent years. This study investigates the factors contributing to psychological distress among university students, focusing on resilience, coping self-efficacy, acculturation, and cultural backgrounds. METHODS:Utilizing a biopsychosocial model, the study examines how sociocultural stressors and individual coping mechanisms interact to influence mental health outcomes. Data were collected from 291 undergraduate domestic and international psychology students at a large urban university in the United States during the Spring 2023 semester. RESULTS:Results indicated that domestic students reported significantly higher levels of psychological distress and life stressors compared to international students. Factors such as stressful life events, resilience, and coping self-efficacy were significantly associated with psychological distress. Acculturation was not directly associated with distress but was linked to coping self-efficacy among international students. Regression analysis revealed that higher numbers of stressful life events, lower resilience, and domestic residence are associated with psychological distress. CONCLUSIONS:The study highlights the importance of protective factors like resilience and coping self-efficacy in managing life stress and adversity among university students. These insights can inform efforts to promote mental health and wellbeing through resilience-building, coping strategy workshops, and community engagement.

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).

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.

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.

Autistic youth visit the emergency department (ED) for psychiatric concerns, including suicidal ideation and behavior, at elevated rates. However, clinicians often report low levels of training and confidence in addressing suicide risk in autistic youth. In this pilot study, clinicians in a pediatric psychiatric emergency service were trained on community- and evidence-informed recommendations to improve suicide-related care for autistic youth and provided with resources to use with autistic youth for a 3-month period. Ratings on attitudes and confidence were obtained from ten providers before and after the training/implementation period and compared. Ratings of feasibility and utility of strategies and resources were obtained from 15 providers after training/implementation and analyzed. While no changes were found across attitudes items, confidence scores were significantly higher after the training/implementation period than before, particularly in the area of suicide risk assessment. Feasibility and utility ratings were generally high, with endorsement patterns aligning with common organizational and systems-level barriers. This pilot study demonstrated that targeted training and evidence-informed recommendations to improve suicide-related care for autistic youth were associated with increased clinician confidence. As research continues in the development of adapted suicide risk assessment tools and management strategies for autistic youth, it is important that both clinical guidance on best practices is provided and that systems-level barriers are addressed.