Faculty Bibliography

The transition from Child and Adolescent (CAMHS) to Adult Mental Health Services (AMHS) can be challenging. Drawing on the sample of the European MILESTONE project, we explored changes in clinical profiles and treatment outcomes in adolescents transitioning to AMHS over two years, focusing on different pharmacological treatment patterns. The sample (N = 690; mean age: 17.7 years; SD = 0.29) was categorised into three groups based on medication patterns: continuous (Group 1), intermittent (Group 2), and never medicated (Group 3). Participants underwent four evaluations over two years using tools measuring psychopathology and functioning, including the Health of the Nation Outcome Scale for Child and Adolescents (HoNOSCA) and ASEBA Battery. We employed repeated-measures models to analyse clinical rating changes and a two-way mixed ANOVA to assess interaction between time and groups. Group 3 had significantly lower mean HoNOSCA ratings than Groups 1 and 2 (p < 0.001), indicating better mental health. By the last time point (T4), the factors associated with a reduced risk of severe illness included an improvement in the risk of suicide attempts (p = 0.038), enhanced everyday functional skills (p = 0.008), higher quality of life (p = 0.001), and being male (p = 0.020). The ASEBA Battery showed Group 1 had more internalising symptoms, while Group 2 had more externalising symptoms than Group 3. During the transition from CAMHS to AMHS, continuous medication was associated with higher symptom severity than intermittent or no pharmacological treatment. This may reflect either a more severe initial symptomatology requiring sustained pharmacotherapy or a medication-related paradox, whereby symptoms persist or intensify owing to treatment resistance or side effects. TRIAL REGISTRATION: "MILESTONE study" registration: ISRCTN ISRCTN83240263 Registered 23 July 2015; ClinicalTrials.gov NCT03013595 Registered 6 January 2017.

OBJECTIVE:This study aimed at identifying moderators of efficacy of stimulants against placebo to inform personalized recommendations for treatment in preschool children (< 6 years) with attention-deficit/hyperactivity disorder (ADHD). METHOD/METHODS:We acquired individual-level participant data from two randomized placebo-controlled trials (RCTs) of preschool ADHD: MAPPA (8-week methylphenidate, 102 participants, Brazil) and SPD489-347 (6-week lisdexamfetamine, 148 participants, US). We evaluated the moderator and predictor effects of baseline demographic (age, sex, race, ethnicity, maternal educational level) and baseline clinical (ADHD symptom severity, intelligence quotient, number of psychiatric comorbidities) characteristics, as available, on endpoint ADHD symptom severity scores. Data from each study were analyzed separately with linear mixed-effects model for repeated measures. For categorical variables, we also computed treatment effects (i.e., stimulants versus placebo) within subgroups and, when possible, pooled them alongside subgroup data from PATS (5-week methylphenidate, 165 participants, US) in random-effects meta-analyses. RESULTS:Stimulants had greater efficacy against placebo in White children compared to Black children considering data from US studies. Older age was not a moderator of greater efficacy of stimulants against placebo, nor was it associated with worse ADHD symptom severity at endpoint. Greater baseline ADHD symptom severity was associated with higher ADHD symptom severity at endpoint independently of the assigned treatment group. CONCLUSION/CONCLUSIONS:Race, but not older age or baseline ADHD symptom severity, may moderate the efficacy of stimulants for preschool ADHD. Given the post hoc nature of subgroup analyses, the findings should be interpreted as exploratory and viewed as hypothesis for confirmation in future studies.

BACKGROUND/UNASSIGNED:Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition with a multifactorial etiology, many aspects of which remain unclear. Emerging evidence suggests a potential association between ASD and clinical manifestations resulting from hormonal imbalances, henceforth named "steroidopathies." The present study aims to investigate the association between ASD, steroidopathies and altered steroid hormone levels. METHODS/UNASSIGNED:A cohort of 100 individuals aged 9-18 years was examined, comprising 50 autistic individuals (25 males, 25 females) compared to 50 individuals diagnosed with other neuropsychiatric disorders (20 males, 30 females). Data were collected on steroidopathies (including hirsutism, severe acne, irregular menstrual cycles, polycystic ovary syndrome, endometriosis, pubertal disorders) in participants and their first-degree relatives, as well as on maternal pregnancy and delivery complications. Blood samples were analyzed to assess hormonal profiles, including testosterone, estradiol, and vitamin D levels. A multivariate logistic regression analysis was conducted, with ASD status as the dependent variable and hormone levels, steroidopathies and other pregnancy-related conditions as independent variables. Sex and age were included as covariates. RESULTS/UNASSIGNED: = 0.0057). CONCLUSION/UNASSIGNED:These findings support the hypothesis of an association between steroidopathies and altered steroid hormone levels with ASD, suggesting that steroid hormone profiles could potentially serve as early biomarkers in future research. Furthermore, consideration of maternal endocrine health and prenatal exposures may contribute to a better understanding of ASD risk.

A fundamental pillar of science is the estimation of the effect size of associations. However, this task is sometimes difficult and error-prone. To facilitate this process, the R package metaConvert automatically calculates and flexibly converts multiple effect size measures. It applies more than 120 formulas to convert any relevant input data into Cohen's d, Hedges' g, mean difference, odds ratio, risk ratio, incidence rate ratio, correlation coefficient, Fisher's r-to-z transformed correlation coefficient, variability ratio, coefficient of variation ratio, or number needed to treat. Researchers unfamiliar with R can use this software through a browser-based graphical interface (https://metaconvert.org/). We hope this suite will help researchers in the life sciences and other disciplines estimate and convert effect sizes more easily and accurately.

BACKGROUND:Recent epidemiological evidence links early-life obesity and metabolic dysregulation to adult psychosis vulnerability, though a causal relationship remains unclear. Establishing causality in highly heritable psychotic disorders requires 1) demonstrating that early-life metabolic factors mediate between genetic vulnerability and psychosis trajectory, 2) dissecting mechanisms leading to early-life obesity in genetically vulnerable individuals, and 3) clarifying downstream neurodevelopmental pathways linking early-life obesity to psychosis symptoms. METHODS:Here we investigated bidirectional pathways linking behavioral, body mass index (BMI), and neurodevelopmental trajectories in a unique longitudinal cohort of 184 individuals at high genetic risk for psychosis, due to 22q11.2 deletion syndrome (22q11DS), and 182 neurotypical control individuals, followed-up since childhood. We combined repeated BMI measurements with clinical/neurocognitive phenotyping and neuroimaging. We investigated the relationship between BMI trajectories with risk of psychosis and tested whether altered cortical or cerebellar development could underlie this association. RESULTS:Childhood behavioral impulsivity predicted early and progressive deviations in BMI trajectories, mediating the effects of 22q11DS vulnerability to early-life obesity. Chronic BMI increases manifesting during childhood predicted the subsequent emergence of psychosis during late adolescence/early adulthood, mediating the effects of behavioral impulsivity. A dose-effect relationship linked duration of increased BMI status to worsening of motor and cognitive disorganization, a key schizophrenia symptom domain, which was mediated by progressive gray matter volume reductions in posterior-inferior cerebellum. CONCLUSIONS:These findings suggest that metabolic dysregulation associated with obesity may link childhood behavioral impulsivity to psychosis vulnerability in 22q11DS by influencing cerebellar maturation. These findings might support preventive interventions targeting early-life metabolic trajectories in individuals at risk of psychosis.

BACKGROUND:Risky sexual behaviours (RSB) and attention deficit hyperactivity disorder (ADHD) are both major concerns among university students. However, their association remains insufficiently understood. This study aimed to evaluate the relationship between ADHD symptoms and a broad range of RSB in university students. METHODS:A total of 13 085 French students enrolled in the i-Share (Internet-based Students' Health Research Enterprise study (mean age: 20.6 years, SD=2.4) completed self-reported questionnaires assessing ADHD symptoms (Adult Self-Report Scale V.1.1), RSB, sociodemographic characteristics and alcohol and cannabis use. Logistic regression models were used to examine the cross-sectional associations between ADHD symptoms and RSB, adjusting for relevant confounders. RESULTS:A high level of ADHD symptoms was observed in 5.3% of students. In multivariate models, ADHD symptoms were associated with a wide range of RSB, including early first sexual intercourse (adjusted OR (aOR) 1.26; 95% CI 1.06 to 1.51), inconsistent condom use in the last 12 months (aOR 1.26; 95% CI 1.05 to 1.51), diagnosis of a sexually transmitted infection in the last 12 months (aOR 1.60; 95% CI 1.16 to 2.22) and having had multiple sexual partners in the last 12 months (adjusted incidence rate ratio 1.20; 95% CI 1.14 to 1.27). Among female students, ADHD symptoms were associated with lower current use of any form of contraception (aOR 0.59; 95% CI 0.48 to 0.71), and higher odds of having ever used emergency contraception (aOR 1.22; 95% CI 1.02 to 1.47), and having ever had an abortion (aOR 1.77; 95% CI 1.21 to 2.58). CONCLUSIONS:University students with a high level of ADHD symptoms are at increased risk of engaging in a wide range of RSB. Targeted preventive strategies may be particularly beneficial for this population.

INTRODUCTION/UNASSIGNED:Over recent decades, research has identified both overlapping and distinct characteristics, risk factors, and genetic as well as neurobiological correlates associated with Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). This expanding body of evidence is increasingly informing the clinical management of individuals with comorbid ADHD and ASD. AREAS COVERED/UNASSIGNED:Based on a targeted PubMed search conducted up to March 24,2025,24.03.25, prioritizing meta-analyses or umbrella reviews over primary studies (whenever relevant), with terms encompassing autism, assessment, and treatment, this review addresses: 1) Shared and distinct phenotypic characteristics, neuropsychological features, and genetic and neuroimaging correlates of ADHD and ASD; 2) The assessment of individuals presenting with both ASD and ADHD symptoms; 3) Pharmacological and non-pharmacological strategies for the management for individuals with comorbid ASD and ADHD. EXPERT OPINION/UNASSIGNED:The comorbidity of ADHD and ASD should not be overlooked. Nevertheless, before diagnosing comorbid ASD and ADHD, clinicians should perform a thorough differential diagnosis, ensuring that ADHD symptoms are not better explained by ASD. Regarding treatment, further research is warranted to develop personalized approaches, support long-term management strategies, and evaluate real-world outcomes such as quality of life, which are often underrepresented in clinical trials.

OBJECTIVE:To evaluate the association between attention-deficit/hyperactivity disorder (ADHD) and atypical sensory processing patterns. METHOD/METHODS:For this systematic review and meta-analysis, PubMed, Embase, and Web of Science were searched from their inception until June 30, 2024. Studies examining sensory processing patterns using questionnaires in participants with a diagnosis of ADHD compared with healthy controls were included. The study risk of bias was assessed using a modified Newcastle-Ottawa Scale. A random-effects meta-analysis was conducted using R Version 4.3.1 software, considering sensory modulation severity atypicities as the primary outcome. The risk of publication bias was explored, and sensitivity analyses were conducted to test the robustness of findings. RESULTS:= 97%). Heterogeneity was high in all analyses. Only 9 studies were deemed at overall low risk of bias. CONCLUSION/CONCLUSIONS:Even though available ADHD clinical guidelines do not specifically mention the need to assess sensory processing in ADHD, this meta-analysis suggests that this should be systematically explored in the evaluation of children and adults referred for ADHD. PLAIN LANGUAGE SUMMARY/CONCLUSIONS:This systematic review and meta-analysis examined 30 studies including over 5,000 participants to assess the link between attention-deficit/hyperactivity disorder (ADHD) and atypical sensory processing. Findings show that individuals with ADHD experience significantly higher sensory sensitivity, sensory avoidance, sensory seeking, and low sensory registration compared to controls. Given their impact on daily functioning, assessing sensory processing could improve clinical evaluations for both children and adults with ADHD. STUDY REGISTRATION INFORMATION/UNASSIGNED:Association between ADHD and sensory processing disorder: A systematic review and meta-analysis; https://www.crd.york.ac.uk/PROSPERO/view/CRD42022325271. DIVERSITY & INCLUSION STATEMENT/UNASSIGNED:We actively worked to promote sex and gender balance in our author group. 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. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science.

OBJECTIVES/OBJECTIVE:To assess the effects of and related evidence certainty of interventions for attention deficit/hyperactivity disorder (ADHD) across an individual's lifespan, and to develop a continuously updated web platform for people with lived experience of ADHD as a method to disseminate living evidence synthesis for shared decision making. DESIGN/METHODS:Umbrella review and platform for shared decision making. DATA SOURCES/METHODS:Six databases from inception to 19 January 2025. Study authors were contacted for additional information when necessary. ELIGIBILITY CRITERIA FOR SELECTING STUDIES/METHODS:Systematic reviews that used meta-analyses of randomised controlled trials were eligible if they compared a drug or non-drug intervention with a passive control in individuals with a diagnosis of ADHD. Primary outcomes were severity of ADHD symptoms, analysed by rater type (clinician-rated, parent-rated, teacher-rated, or self-rated) and time point (short term (12 weeks, or study endpoint), medium term (26 weeks), and long term (52 weeks)),acceptability (participants dropping out for any reason), and tolerability (participants dropping out owing to any side effects). Secondary outcomes included daily functioning, quality of life, comorbid symptoms, and key side effects (decreased sleep and appetite). DATA SYNTHESIS/RESULTS:Eligible meta-analyses were re-estimated with a standardised statistical approach. Methodological quality was assessed using AMSTAR-2. Evidence certainty was evaluated using an algorithmic version of the GRADE framework, adapted for drug and non-drug interventions. RESULTS:115 of 414 full text articles were deemed eligible and 299 were excluded; the eligible articles comprised 221 unique combinations of participants, interventions, comparators, and outcomes. For each combination, the most recent and methodologically robust meta-analysis was selected for re-estimation, which gave 221 re-estimated meta-analyses in total, derived from 47 meta-analytic reports. In the short term, alpha-2 agonists, amphetamines, atomoxetine, methylphenidate, and viloxazine showed medium to large effect sizes in reducing the severity of ADHD symptoms in children and adolescents, with moderate to high certainty evidence. Methylphenidate showed consistent benefits across raters (standardised mean difference >0.75, 95% confidence interval (CI) 0.56 to 1.03; moderate or high certainty evidence). These interventions showed lower tolerability than the placebo, but this effect was not significant for methylphenidate and atomoxetine. In adults, atomoxetine, cognitive behavioural therapy, methylphenidate (and, when restricting analyses to high quality trials, amphetamines) showed at least moderate certainty evidence of efficacy on ADHD symptoms, with medium effect sizes. Methylphenidate, amphetamines, and atomoxetine had worse tolerability than placebo (methylphenidate, risk ratio 0.50, 95% CI 0.36 to 0.69; amphetamines, 0.40, 0.22 to 0.72; atomoxetine, 0.45, 0.35 to 0.58). Some non-drug interventions (acupuncture and cognitive behavioural therapy in children and adolescents, and mindfulness in adults) showed large effect sizes for ADHD symptoms, but with low certainty evidence. No high certainty, long term evidence was found for any intervention. An online platform showing effects and evidence certainty of each intervention across age groups, time points, and outcomes (https://ebiadhd-database.org/) was developed. CONCLUSIONS:This review provides updated evidence to inform patients, practitioners, and guideline developers how best to manage ADHD symptoms. The online platform should facilitate the implementation of shared decision making in daily practice. TRIAL REGISTRATION/BACKGROUND:Open Science Framework https://osf.io/ugqy6/.