Faculty Bibliography

INTRODUCTION/BACKGROUND:People with severe mental illness have poor cardiometabolic health. Commonly used antidepressants and antipsychotics frequently lead to weight gain, which may further contribute to adverse cardiovascular outcomes. AREAS COVERED/METHODS:We searched MEDLINE up to April 2023 for umbrella reviews, (network-)meta-analyses, trials and cohort studies on risk factors, prevention and treatment strategies of weight gain associated with antidepressants/antipsychotics. We developed 10 clinical recommendations. EXPERT OPINION/CONCLUSIONS:To prevent, manage, and treat antidepressant/antipsychotic-related weight gain, we recommend i) assessing risk factors for obesity before treatment, ii) monitoring metabolic health at baseline and regularly during follow-up, iii) offering lifestyle interventions including regular exercise and healthy diet based on patient preference to optimize motivation, iv) considering first-line psychotherapy for mild-moderate depression and anxiety disorders, v) choosing medications based on medications' and patient's weight gain risk, vi) choosing medications based on acute vs long-term treatment, vii) using effective, tolerated medications, viii) switching to less weight-inducing antipsychotics/antidepressants where possible, ix) using early weight gain as a predictor of further weight gain to inform the timing of intervention/switch options, and x) considering adding metformin or glucagon-like peptide-1 receptor agonists, or topiramate (second-line due to potential adverse cognitive effects) to antipsychotics, or aripiprazole to clozapine or olanzapine.

IMPORTANCE/UNASSIGNED:Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are increasingly common. Individuals with NDDs have heightened obesity risks, but long-term data on body mass index (BMI) trends over time in this population are lacking. OBJECTIVE/UNASSIGNED:To assess secular BMI changes from 2004 to 2020 among children with NDDs compared with those without NDDs. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This repeated cross-sectional study used data from the Child and Adolescent Twin Study in Sweden. Children born between January 1, 1992, and December 31, 2010, were screened for neurodevelopmental symptoms using the Autism-Tics, ADHD, and Other Comorbidities inventory between July 2004 and April 2020 when they were 9 or 12 years of age. Data analysis was conducted between September 27, 2023, and January 30, 2024. MAIN OUTCOMES AND MEASURES/UNASSIGNED:BMI percentiles (15th, 50th, and 85th) were modeled using quantile regression and compared between youths with and without NDDs. Secular changes in BMI percentiles over time spanning 2004 to 2020 were evaluated and stratified by NDD subtype. RESULTS/UNASSIGNED:The cohort included 24 969 Swedish twins (12 681 [51%] boys) born between 1992 and 2010, with mean (SD) age of 9 (0.6) years. Of these, 1103 (4%) screened positive for 1 or more NDDs, including ADHD, ASD, and/or learning disability. Results indicated that at the 85th BMI percentile, there was a greater increase in BMI from 2004 to 2020 among youths with NDDs compared with those without NDDs (β for interaction [βint] between NDD status and time, 1.67; 95% CI, 0.39-2.90). The greatest divergence was seen for ASD (βint, 2.12; 95% CI, 1.26-3.70) and learning disability (βint, 1.92; 95% CI, 0.65-3.82). Within the latest cohort (2016-2020), the 85th BMI percentile was 1.99 (95% CI, 1.08-2.89) points higher among children with NDDs compared with those without NDDs. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this repeated cross-sectional study, at the higher end of the BMI distribution, children with NDDs had significantly greater increases in BMI compared with peers without NDDs over a 16-year period, highlighting an increasing risk of overweight over time in youths with NDDs compared with those without NDDs. Targeted obesity prevention efforts for this high-risk population are needed.

We investigated whether SARS-CoV-2 infection is associated with short- and long-term neuropsychiatric sequelae. We used population-based cohorts from the Korean nationwide cohort (discovery; n = 10,027,506) and the Japanese claims-based cohort (validation; n = 12,218,680) to estimate the short-term (<30 days) and long-term (≥30 days) risks of neuropsychiatric outcomes after SARS-CoV-2 infection compared with general population groups or external comparators (people with another respiratory infection). Using exposure-driven propensity score matching, we found that both the short- and long-term risks of developing neuropsychiatric sequelae were elevated in the discovery cohort compared with the general population and those with another respiratory infection. A range of conditions including Guillain-Barré syndrome, cognitive deficit, insomnia, anxiety disorder, encephalitis, ischaemic stroke and mood disorder exhibited a pronounced increase in long-term risk. Factors such as mild severity of COVID-19, increased vaccination against COVID-19 and heterologous vaccination were associated with reduced long-term risk of adverse neuropsychiatric outcomes. The time attenuation effect was the strongest during the first six months after SARS-CoV-2 infection, and this risk remained statistically significant for up to one year in Korea but beyond one year in Japan. The associations observed were replicated in the validation cohort. Our findings contribute to the growing evidence base on long COVID by considering ethnic diversity.

Evidence on the link between developmental coordination disorder (DCD) and obesity and overweight is mixed. Based on a pre-registered protocol (PROSPERO: CRD42023429432), we conducted the first systematic review/meta-analysis on the association between DCD and excessive weight. Web of Science, PubMed and an institutional database aggregator were searched until the 18th of December 2023. We assessed study quality using the Newcastle-Ottawa Scale and study heterogeneity using Q and I2 statistics. Data from 22 studies were combined, comprising 11,330 individuals out of which 1861 had DCD. The main analysis showed a significant association between DCD and higher body weight (OR:1.87, 95 % CI =1.43, 2.44). Meta-regression analyses indicated that the relationship was mediated by age, with stronger effects in studies with higher mean age (p 0.004). We conclude that DCD is associated with obesity and overweight, and this association increases with age. Our study could help to implement targeted prevention and intervention measures.

Stimulants represent the first line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) and are among the most prescribed psychopharmacological treatments. Their mechanism of action at synaptic level has been extensively studied. However, it is less clear how their mechanism of action determines clinically observed benefits. To help bridge this gap, we provide a comprehensive review of stimulant effects, with an emphasis on nuclear medicine and magnetic resonance imaging (MRI) findings. There is evidence that stimulant-induced modulation of dopamine and norepinephrine neurotransmission optimizes engagement of task-related brain networks, increases perceived saliency, and reduces interference from the default mode network. An acute administration of stimulants may reduce brain alterations observed in untreated individuals in fronto-striato-parieto-cerebellar networks during tasks or at rest. Potential effects of prolonged treatment remain controversial. Overall, neuroimaging has fostered understanding on stimulant mechanism of action. However, studies are often limited by small samples, short or no follow-up, and methodological heterogeneity. Future studies should address age-related and longer-term effects, potential differences among stimulants, and predictors of treatment response.

INTRODUCTION/BACKGROUND:Observational studies are fraught with several biases including reverse causation and residual confounding. Overview of reviews of observational studies (ie, umbrella reviews) synthesise systematic reviews with or without meta-analyses of cross-sectional, case-control and cohort studies, and may also aid in the grading of the credibility of reported associations. The number of published umbrella reviews has been increasing. Recently, a reporting guideline for overviews of reviews of healthcare interventions (Preferred Reporting Items for Overviews of Reviews (PRIOR)) was published, but the field lacks reporting guidelines for umbrella reviews of observational studies. Our aim is to develop a reporting guideline for umbrella reviews on cross-sectional, case-control and cohort studies assessing epidemiological associations. METHODS AND ANALYSIS/METHODS:We will adhere to established guidance and prepare a PRIOR extension for systematic reviews of cross-sectional, case-control and cohort studies testing epidemiological associations between an exposure and an outcome, namely Preferred Reporting Items for Umbrella Reviews of Cross-sectional, Case-control and Cohort studies (PRIUR-CCC). Step 1 will be the project launch to identify stakeholders. Step 2 will be a literature review of available guidance to conduct umbrella reviews. Step 3 will be an online Delphi study sampling 100 participants among authors and editors of umbrella reviews. Step 4 will encompass the finalisation of PRIUR-CCC statement, including a checklist, a flow diagram, explanation and elaboration document. Deliverables will be (i) identifying stakeholders to involve according to relevant expertise and end-user groups, with an equity, diversity and inclusion lens; (ii) completing a narrative review of methodological guidance on how to conduct umbrella reviews, a narrative review of methodology and reporting in published umbrella reviews and preparing an initial PRIUR-CCC checklist for Delphi study round 1; (iii) preparing a PRIUR-CCC checklist with guidance after Delphi study; (iv) publishing and disseminating PRIUR-CCC statement. ETHICS AND DISSEMINATION/BACKGROUND:PRIUR-CCC has been approved by The Ottawa Health Science Network Research Ethics Board and has obtained consent (20220639-01H). Participants to step 3 will give informed consent. PRIUR-CCC steps will be published in a peer-reviewed journal and will guide reporting of umbrella reviews on epidemiological associations.

IMPORTANCE/UNASSIGNED:The use of evidence-based standardized outcome measures is increasingly recognized as key to guiding clinical decision-making in mental health. Implementation of these measures into clinical practice has been hampered by lack of clarity on what to measure and how to do this in a reliable and standardized way. OBJECTIVE/UNASSIGNED:To develop a core set of outcome measures for specific neurodevelopmental disorders (NDDs), such as attention-deficit/hyperactivity disorder (ADHD), communication disorders, specific learning disorders, and motor disorders, that may be used across a range of geographic and cultural settings. EVIDENCE REVIEW/UNASSIGNED:An international working group composed of clinical and research experts and service users (n = 27) was convened to develop a standard core set of accessible, valid, and reliable outcome measures for children and adolescents with NDDs. The working group participated in 9 video conference calls and 8 surveys between March 1, 2021, and June 30, 2022. A modified Delphi approach defined the scope, outcomes, included measures, case-mix variables, and measurement time points. After development, the NDD set was distributed to professionals and service users for open review, feedback, and external validation. FINDINGS/UNASSIGNED:The final set recommends measuring 12 outcomes across 3 key domains: (1) core symptoms related to the diagnosis; (2) impact, functioning, and quality of life; and (3) common coexisting problems. The following 14 measures should be administered at least every 6 months to monitor these outcomes: ADHD Rating Scale 5, Vanderbilt ADHD Diagnostic Rating Scale, or Swanson, Nolan, and Pelham Rating Scale IV; Affective Reactivity Index; Children's Communication Checklist 2; Colorado Learning Disabilities Questionnaire; Children's Sleep Habits Questionnaire; Developmental-Disability Children's Global Assessment Scale; Developmental Coordination Disorder Questionnaire; Family Strain Index; Intelligibility in Context Scale; Vineland Adaptive Behavior Scale or Repetitive Behavior Scale-Revised and Social Responsiveness Scale; Revised Child Anxiety and Depression Scales; and Yale Global Tic Severity Scale. The external review survey was completed by 32 professionals and 40 service users. The NDD set items were endorsed by more than 70% of professionals and service users in the open review survey. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The NDD set covers outcomes of most concern to patients and caregivers. Use of the NDD set has the potential to improve clinical practice and research.

OBJECTIVE/UNASSIGNED:To investigate shared and specific neural correlates of cognitive functions in attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), the authors performed a comprehensive meta-analysis and considered a balanced set of neuropsychological tasks across the two disorders. METHODS/UNASSIGNED:A broad set of electronic databases was searched up to December 4, 2022, for task-based functional MRI studies investigating differences between individuals with ADHD or ASD and typically developing control subjects. Spatial coordinates of brain loci differing significantly between case and control subjects were extracted. To avoid potential diagnosis-driven selection bias of cognitive tasks, the tasks were grouped according to the Research Domain Criteria framework, and stratified sampling was used to match cognitive component profiles. Activation likelihood estimation was used for the meta-analysis. RESULTS/UNASSIGNED:After screening 20,756 potentially relevant references, a meta-analysis of 243 studies was performed, which included 3,084 participants with ADHD (676 females), 2,654 participants with ASD (292 females), and 6,795 control subjects (1,909 females). ASD and ADHD showed shared greater activations in the lingual and rectal gyri and shared lower activations in regions including the middle frontal gyrus, the parahippocampal gyrus, and the insula. By contrast, there were ASD-specific greater and lower activations in regions including the left middle temporal gyrus and the left middle frontal gyrus, respectively, and ADHD-specific greater and lower activations in the amygdala and the global pallidus, respectively. CONCLUSIONS/UNASSIGNED:Although ASD and ADHD showed both shared and disorder-specific standardized neural activations, disorder-specific activations were more prominent than shared ones. Functional brain differences between ADHD and ASD are more likely to reflect diagnosis-related pathophysiology than bias from the selection of specific neuropsychological tasks.