Faculty Bibliography

BACKGROUND:To what extent the COVID-19 pandemic and its containment measures influenced mental health in the general population is still unclear. PURPOSE:To assess the trajectory of mental health symptoms during the first year of the pandemic and examine dose-response relations with characteristics of the pandemic and its containment. DATA SOURCES:Relevant articles were identified from the living evidence database of the COVID-19 Open Access Project, which indexes COVID-19-related publications from MEDLINE via PubMed, Embase via Ovid, and PsycInfo. Preprint publications were not considered. STUDY SELECTION:Longitudinal studies that reported data on the general population's mental health using validated scales and that were published before 31 March 2021 were eligible. DATA EXTRACTION:An international crowd of 109 trained reviewers screened references and extracted study characteristics, participant characteristics, and symptom scores at each timepoint. Data were also included for the following country-specific variables: days since the first case of SARS-CoV-2 infection, the stringency of governmental containment measures, and the cumulative numbers of cases and deaths. DATA SYNTHESIS:In a total of 43 studies (331 628 participants), changes in symptoms of psychological distress, sleep disturbances, and mental well-being varied substantially across studies. On average, depression and anxiety symptoms worsened in the first 2 months of the pandemic (standardized mean difference at 60 days, -0.39 [95% credible interval, -0.76 to -0.03]); thereafter, the trajectories were heterogeneous. There was a linear association of worsening depression and anxiety with increasing numbers of reported cases of SARS-CoV-2 infection and increasing stringency in governmental measures. Gender, age, country, deprivation, inequalities, risk of bias, and study design did not modify these associations. LIMITATIONS:The certainty of the evidence was low because of the high risk of bias in included studies and the large amount of heterogeneity. Stringency measures and surges in cases were strongly correlated and changed over time. The observed associations should not be interpreted as causal relationships. CONCLUSION:Although an initial increase in average symptoms of depression and anxiety and an association between higher numbers of reported cases and more stringent measures were found, changes in mental health symptoms varied substantially across studies after the first 2 months of the pandemic. This suggests that different populations responded differently to the psychological stress generated by the pandemic and its containment measures. PRIMARY FUNDING SOURCE:Swiss National Science Foundation. (PROSPERO: CRD42020180049).

To address the issues with the current nomenclature of psychotropic agents, which may be misleading or confusing, the Neuroscience-based Nomenclature (NbN) started being developed in 2009. It was introduced as one approach to the classification of pharmacological treatments based on a medication's putative psychopharmacological mechanisms of action derived from preclinical and clinical studies. In 2018, the NbN-Child & Adolescent (NbN C&A) was released. Since then, the NbN C&A has been refined, and its website and app (https://nbnca.com/) have been implemented. JAACAP encourages its authors and readers to consider utilizing the NbN C&A and to keep abreast of its developments over time. This is in line with the core missions of the Journal: to contribute to the translation and implementation of the most up-to-date science into real-world clinical practice. DIVERSITY & INCLUSION STATEMENT: 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.

In a double-blind randomised controlled trial by Asherson et al., involving prisoners with attention-deficit hyperactivity disorder (ADHD), the rates of response to osmotic-release oral system methylphenidate (OROS-methylphenidate) and placebo were very similar (~50%). I critically discuss this trial against other international literature, highlighting the key issues in the field in terms of clinical practice and research.

Autism spectrum disorder (ASD) substantially contributes to the burden of mental disorders. Improved awareness and changes in diagnostic criteria of ASD may have influenced the diagnostic rates of ASD. However, while data on trends in diagnostic rates in some individual countries have been published, updated estimates of diagnostic rate trends and ASD-related disability at the global level are lacking. Here, we used the Global Burden of Diseases, Injuries, and Risk Factors Study data to address this gap, focusing on changes in prevalence, incidence, and disability-adjusted life years (DALYs) of ASD across the world. From 1990 to 2019, overall age-standardized estimates remained stable globally. Both prevalence and DALYs increased in countries with high socio-demographic index (SDI). However, the age-standardized incidence decreased in some low SDI countries, indicating a need to improve awareness. The male/female ratio decreased between 1990 and 2019, possibly accounted for by increasing clinical attention to ASD in females. Our results suggest that ASD detection in low SDI countries is suboptimal, and that ASD prevention/treatment in countries with high SDI should be improved, considering the increasing prevalence of the disorder. Additionally, growing attention is being paid to ASD diagnosis in females, who might have been left behind by ASD epidemiologic and clinical research previously. ASD burden estimates are underestimated as GBD does not account for mortality in ASD.

Accumulating evidence suggests a higher risk for cardiovascular diseases among individuals with mental disorders, but very little is known about the risk for overall and specific groups of cardiovascular diseases in people with attention-deficit/hyperactivity disorder (ADHD). To fill this knowledge gap, we investigated the prospective associations between ADHD and a wide range of cardiovascular diseases in adults. In a nationwide population-based cohort study, we identified 5,389,519 adults born between 1941 and 1983, without pre-existing cardiovascular diseases, from Swedish registers. The study period was from January 1, 2001 to December 31, 2013. Incident cardiovascular disease events were identified according to ICD codes. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox proportional hazards regression model, with ADHD as a time-varying exposure. After an average 11.80 years of follow-up, 38.05% of individuals with ADHD versus 23.57% of those without ADHD had at least one diagnosis of cardiovascular disease (p<0.0001). ADHD was significantly associated with increased risk of any cardiovascular disease (HR=2.05, 95% CI: 1.98-2.13) after adjusting for sex and year of birth. Further adjustments for education level, birth country, type 2 diabetes mellitus, obesity, dyslipidemia, sleep problems and heavy smoking attenuated the association, which however remained significant (HR=1.84, 95% CI: 1.77-1.91). Further adjustment for psychiatric comorbidities attenuated but could not fully explain the association (HR=1.65, 95% CI: 1.59-1.71). The strongest associations were found for cardiac arrest (HR=2.28, 95% CI: 1.81-2.87), hemorrhagic stroke (HR=2.16, 95% CI: 1.68-2.77), and peripheral vascular disease/arteriosclerosis (HR=2.05, 95% CI: 1.76-2.38). Stronger associations were observed in males and younger adults, while comparable associations were found among individuals with or without psychotropic medications and family history of cardiovascular diseases. These data suggest that ADHD is an independent risk factor for a wide range of cardiovascular diseases. They highlight the importance of carefully monitoring cardiovascular health and developing age-appropriate and individualized strategies to reduce the cardiovascular risk in individuals with ADHD.

INTRODUCTION/BACKGROUND:Pharmacotherapy is an important component of the multimodal treatment of attention-deficit/hyperactivity disorder (ADHD). Cardiovascular safety of medications for ADHD is of concern from a clinical and public health standpoint. We aim to conduct a network meta-analysis (NMA) comparing the effects of available medications for ADHD on blood pressure (diastolic and systolic), heart rate and ECG parameters over the short-term and long-term treatment. METHODS AND ANALYSIS/METHODS:Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines for protocols and NMAs will be followed. We will include parallel group or cross-over randomised controlled trials (RCTs) conducted in patients with a primary diagnosis of ADHD (no age limits). We will search an extensive number of electronic databases (including MEDLINE, CINAHL, CENTRAL, EMBASE, ERIC, PsycINFO, OpenGrey, Web of Science) from their inception and contact study authors/drug manufacturers to gather relevant unpublished information. No language restrictions will be applied. The main outcomes (assessed at 12 weeks, 26 weeks and 52 weeks) will be: (1) change in diastolic and systolic blood pressure (mm Hg); (2) change in heart rate, measured in beats/min; (3) change in any available ECG parameters. We will conduct random effects of NMA using standardised mean differences with 95% CIs for continuous outcomes and ORs with 95% CIs for dichotomous outcomes. We will use the Cochrane risk of bias tool-version 2 to assess the risk of bias of included RCTs and the Confidence In Network Meta-Analysis tool to evaluate the confidence of evidence contributing to each network estimate. Sensitivity analyses will investigate effects at different dose regimens. ETHICS AND DISSEMINATION/BACKGROUND:No institutional review board approval will be necessary. The results of this systematic review and meta-analysis will be presented at national and international conferences and published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER/UNASSIGNED:CRD42021295352.

OBJECTIVE:People with mood disorders have increased risk of comorbid medical diseases versus the general population. It is paramount to identify interventions to improve physical health in this population. METHODS:Umbrella review of meta-analyses of randomised controlled trials (RCTs) on pharmacological/non-pharmacological interventions for physical health outcomes/intolerability-related discontinuation in mood disorders (any age). RESULTS:Ninety-seven meta-analyses were included. Among youths, against placebo, in depression, antidepressants/antipsychotics had higher discontinuation rates; in bipolar depression, olanzapine+fluoxetine worsened total cholesterol (TC)/triglycerides/weight gain (WG) (large ES). In adults with bipolar disorder, olanzapine worsened HbA1c/TC/WG (moderate/large ES); asenapine increased fasting glucose (small ES); quetiapine/cariprazine/risperidone induced WG (small/moderate ES). In bipolar depression, lurasidone was metabolically neutral. In depression, psychological interventions improved physical health-related quality of life (PHQoL) (small ES), fasting glucose/HbA1c (medium/large ES); SSRIs improved fasting glucose/HbA1c, readmission for coronary disease, pain (small ES); quetiapine/aripiprazole/olanzapine induced WG (small to large ES). Exercise improved cardiorespiratory fitness (moderate ES). In the elderly, fluoxetine yielded more detrimental cardiovascular effects than sertraline/escitalopram (large ES); antidepressants were neutral on exercise tolerance and PHQoL. In mixed age groups, in bipolar disorder aripiprazole was metabolically neutral; in depression, SSRIs lowered blood pressure versus placebo and serotonin-noradrenaline reuptake inhibitors (small ES); brexpiprazole augmentation caused WG and was less tolerated (small ES); exercise improved PHQoL (moderate ES). CONCLUSIONS:Some interventions (psychological therapies, exercise and SSRIs) improve certain physical health outcomes in mood disorders, few are neutral, but various pharmacological interventions are associated with negative effects. Evidence from this umbrella review has limitations, should consider evidence from other disorders and should be integrated with recent evidence from individual RCTs, and observational evidence. Effective treatments with either beneficial or physically neutral profiles should be prioritized.

OBJECTIVE:Our objective is to explore the change in the severity of ADHD, ODD and anxiety during a two-month lockdown among children in France and the moderating role of behavioural regulation. METHOD:In 235 children with ADHD, the symptom severity of ADHD, ODD and anxiety was investigated one and two months after the beginning of lockdown, and one month after its end. Behavioural regulation skills were estimated with the Behaviour Regulation Index. RESULTS:ADHD, ODD and anxiety scores were increasing or decreasing depending on BRI. CONCLUSION:Baseline behavioural regulation skills may act as a moderating factor for the persistence of ADHD, ODD and anxiety symptoms related to the lockdown.

Numerous risk factors for mental disorders have been identified. However, we do not know how many disorders we could prevent and to what extent by modifying these risk factors. This study quantifies the Population Attributable Fraction (PAF) of potentially modifiable risk factors for mental disorders. We conducted a PRISMA 2020-compliant (Protocol: https://osf.io/hk2ag ) meta-umbrella systematic review (Web of Science/PubMed/Cochrane Central Register of Reviews/Ovid/PsycINFO, until 05/12/2021) of umbrella reviews reporting associations between potentially modifiable risk factors and ICD/DSM mental disorders, restricted to highly convincing (class I) and convincing (class II) evidence from prospective cohorts. The primary outcome was the global meta-analytical PAF, complemented by sensitivity analyses across different settings, the meta-analytical Generalised Impact Fraction (GIF), and study quality assessment (AMSTAR). Seven umbrella reviews (including 295 meta-analyses and 547 associations) identified 28 class I-II risk associations (23 risk factors; AMSTAR: 45.0% high-, 35.0% medium-, 20.0% low quality). The largest global PAFs not confounded by indication were 37.84% (95% CI = 26.77-48.40%) for childhood adversities and schizophrenia spectrum disorders, 24.76% (95% CI = 13.98-36.49%) for tobacco smoking and opioid use disorders, 17.88% (95% CI = not available) for job strain and depression, 14.60% (95% CI = 9.46-20.52%) for insufficient physical activity and Alzheimer's disease, 13.40% (95% CI = 7.75-20.15%) for childhood sexual abuse and depressive disorders, 12.37% (95% CI = 5.37-25.34%) for clinical high-risk state for psychosis and any non-organic psychotic disorders, 10.00% (95% CI = 5.62-15.95%) for three metabolic factors and depression, 9.73% (95% CI = 4.50-17.30%) for cannabis use and schizophrenia spectrum disorders, and 9.30% (95% CI = 7.36-11.38%) for maternal pre-pregnancy obesity and ADHD. The GIFs confirmed the preventive capacity for these factors. Addressing several potentially modifiable risk factors, particularly childhood adversities, can reduce the global population-level incidence of mental disorders.