Faculty Bibliography
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467
Anxiety, mood, and substance use disorders in adult men and women with and without Attention-Deficit/Hyperactivity Disorder: a substantive and methodological overview
Knowledge on psychiatric comorbidity in adult ADHD is essential for prevention, detection, and treatment of these conditions. This review (1) focuses on large studies (n> 10,000; surveys, claims data, population registries) to identify (a) overall, (b) sex- and (c) age-specific patterns of comorbidity of anxiety disorders (ADs), major depressive disorder (MDD), bipolar disorder (BD) and substance use disorders (SUDs) in adults with ADHD relative to adults without ADHD; and (2) describes methodological challenges relating to establishing comorbidity in ADHD in adults as well as priorities for future research. Meta-analyses (ADHD: n=550,748; no ADHD n=14,546,814) yielded pooled odds ratios of 5.0(CI:3.29-7.46) for AD, 4.5(CI:2.44-8.34) for MDD, 8.7(CI:5.47-13.89) for BD and 4.6(CI:2.72-7.80) for SUDs, indicating strong differences in adults with compared to adults without ADHD. Moderation by sex was not found: high comorbidity held for both men and women with sex-specific patterns as in the general population: higher prevalences of ADs, MDD and BD in women and a higher prevalence of SUDs in men. Insufficient data on different phases of the adult lifespan prevented conclusions on developmental changes in comorbidity. We discuss methodological challenges, knowledge gaps, and future research priorities.
PMID: 37149075
ISSN: 1873-7528
CID: 5470522
Nonstimulant Medications for Attention-Deficit/Hyperactivity Disorder (ADHD) in Adults: Systematic Review and Meta-analysis
BACKGROUND:For some adults with Attention-Deficit/Hyperactivity Disorder (ADHD), nonstimulants need to be considered either as a monotherapy or as an adjunct to stimulants. OBJECTIVES:The objectives of this systematic review and meta-analysis were to assess the efficacy, acceptability, and tolerability of nonstimulants in adults with ADHD. METHODS:Data sources, searches, and study selection were based on a previously published network meta-analysis of randomized clinical trials (RCTs) by Cortese at al. (Lancet Psychiatry 5(9):727-738, 2018), which we updated in March 2022. Specifically, we searched PubMed, BIOSIS Previews, CINAHL, the Cochrane Central Register of Controlled Trials, EMBASE, ERIC, MEDLINE, PsycINFO, OpenGrey, Web of Science Core Collection, ProQuest Dissertations and Theses (UK and Ireland), ProQuest Dissertations and Theses (abstracts and international), and the WHO International Trials Registry Platform, including ClinicalTrials.gov for double-blind RCTs with a placebo arm, lasting at least one week, including adults with a diagnosis of ADHD based on DSM-III, DSM-III-R, DSM-IV(TR), DSM-5 or ICD-9- or 10, and reporting data on efficacy, tolerability (drop-out due to side effects) and acceptability (drop-out due to any cause) of guanfacine, clonidine, or atomoxetine. Additionally, we searched for RCTs of viloxazine extended release (ER), approved for ADHD in 2021. Random-effects meta-analyses were conducted, and the risk of bias for individual RCTs was assessed using the Cochrane Risk of Bias tool. RESULTS:We included 18 studies in the meta-analyses (4308 participants) plus one additional study in the narrative synthesis (374 participants). The meta-analysis showed that atomoxetine (15 RCTs) (Hedge's g = - 0.48, 95% CI [- 0.64; - 0.33]), guanfacine (two RCTs) (Hedge's g = - 0.66, 95% CI [- 0.94; - 0.38]) and viloxazine ER (one RCT) were significantly more efficacious than placebo. Atomoxetine was less well tolerated than placebo, while tolerability of guanfacine and viloxazine ER could not be meta-analysed, since only one study, for each medication, reported on it. CONCLUSIONS:All investigated nonstimulants were more efficacious in the treatment of ADHD in adults, than placebo, while the placebo had better acceptability and tolerability. PROTOCOL:https://osf.io/5vnmt/?view_only=2bf87ed12ba94645babedceeee4c0120 .
PMID: 37166701
ISSN: 1179-1934
CID: 5503362
Cognitive and behavioral profiles in children with autism spectrum disorder with and without Attention-Deficit/hyperactivity disorder
BACKGROUND:Understanding the developmental trajectories of children with autism spectrum disorder (ASD) with and without comorbid ADHD is relevant to tailor care plans. This prospective study assessed, for the first time, cognitive, emotional, behavioral, and learning outcomes in adolescence of children with ASD-ADHD and in those with ASD+ADHD in childhood. Possible predictors of severity of ASD core symptoms in adolescence were also evaluated. METHODS:Forty-five adolescents without intellectual disability, 26 diagnosed in childhood with ASD-ADHD and 19 with ASD+ADHD, were evaluated at baseline (mean age: 8.6 ± 1.3) and at 5-year follow-up (mean age: 12.9 ± 0.9). Parents and teachers completed questionnaires on executive functions, theory of mind (ToM), emotional/behavioral difficulties (EBD), and learning style at both time points.. RESULTS:Overall different developmental trajectories for the two groups were found. In general, deficits in metacognition processes, ToM skills, EBD, and learning abilities were more pronounced in the ASD+ group. Over time, the ASD+ADHD group, but not the ASD-ADHD, tended to improve in EBD and metacognition but their level of development continued to be lower compared with ASD+ADHD. EBD in childhood were significant predictors of autism core symptoms of adolescents. CONCLUSIONS:Our findings highlight the importance of an early identification of comorbid ADHD symptoms in ASD to offer treatment strategies based on specific developmental trajectories.
PMID: 35441444
ISSN: 1475-357x
CID: 5218292
Validation of the Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) questionnaire for adults
BACKGROUND:The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the internal validity of the co-primary outcome, a composite psychopathology "P-score". METHODS:The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r ≥ 0.5 with validated companion questionnaires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed. RESULTS:From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (ω = 0.95). Factor structure was consistent across age and sex. CONCLUSIONS:COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health.
PMCID:9794522
PMID: 36586617
ISSN: 1573-2517
CID: 5442082
Journal of child psychology & psychiatry & allied disciplines. 2023:64(4):641-644.DOI: 10.1111/jcpp.13765
Commentary: The impact of Covid-19 on psychopathology in children and young people worldwide - reflections on Newlove-Delgado et al. (2023)
In the past 3 years, since the beginning of the Covid-19 pandemic, there has been an impressive flourishing body of publications on the impact of the pandemic and related restrictions on the mental health of children and young people. It was about time for a rigorous quantitative evidence synthesis of this large body of research. Newlove-Delgado et al. (J Child Psychol Psychiatry, 2022) took on this challenge by completing a systematic review with meta-analysis of epidemiological studies on the impact of Covid-19 on psychopathology in children and adolescents, featured in the 2023 Annual Research Review series of the Journal. Overall, this meta-analysis shows that the relationship between mental health and Covid-19 pandemic in children and adolescents is complex and, as such, it ought to be addressed by studies using rigorous methods and advanced analytic strategies. Collectively, as a field, we should and could do better with regards to the scope and quality of the studies in this area.
PMID: 36786395
ISSN: 1469-7610
CID: 5431042
We need timely access to mental health data: implications of the Goldacre review
PMID: 36931773
ISSN: 2215-0374
CID: 5470492
Computerized cognitive training in attention-deficit/hyperactivity disorder (ADHD): a meta-analysis of randomized controlled trials with blinded and objective outcomes
This meta-analysis investigated the effects of computerized cognitive training (CCT) on clinical, neuropsychological and academic outcomes in individuals with attention-deficit/hyperactivity disorder (ADHD). The authors searched PubMed, Ovid, and Web of Science until 19th January 2022 for parallel-arm randomized controlled trials (RCTs) using CCT in individuals with ADHD. Random-effects meta-analyses pooled standardized mean differences (SMD) between CCT and comparator arms. RCT quality was assessed with the Cochrane Risk of Bias 2.0 tool (PROSPERO: CRD42021229279). Thirty-six RCTs were meta-analysed, 17 of which evaluated working memory training (WMT). Analysis of outcomes measured immediately post-treatment and judged to be "probably blinded" (PBLIND; trial n = 14) showed no effect on ADHD total (SMD = 0.12, 95%CI[-0.01 to -0.25]) or hyperactivity/impulsivity symptoms (SMD = 0.12, 95%[-0.03 to-0.28]). These findings remained when analyses were restricted to trials (n: 5-13) with children/adolescents, low medication exposure, semi-active controls, or WMT or multiple process training. There was a small improvement in inattention symptoms (SMD = 0.17, 95%CI[0.02-0.31]), which remained when trials were restricted to semi-active controls (SMD = 0.20, 95%CI[0.04-0.37]), and doubled in size when assessed in the intervention delivery setting (n = 5, SMD = 0.40, 95%CI[0.09-0.71]), suggesting a setting-specific effect. CCT improved WM (verbal: n = 15, SMD = 0.38, 95%CI[0.24-0.53]; visual-spatial: n = 9, SMD = 0.49, 95%CI[0.31-0.67]), but not other neuropsychological (e.g., attention, inhibition) or academic outcomes (e.g., reading, arithmetic; analysed n: 5-15). Longer-term improvement (at ~6-months) in verbal WM, reading comprehension, and ratings of executive functions were observed but relevant trials were limited in number (n: 5-7). There was no evidence that multi-process training was superior to working memory training. In sum, CCT led to shorter-term improvements in WM, with some evidence that verbal WM effects persisted in the longer-term. Clinical effects were limited to small, setting specific, short-term effects on inattention symptoms.
PMID: 36977764
ISSN: 1476-5578
CID: 5463182
The future of child and adolescent clinical psychopharmacology: A systematic review of phase 2, 3, or 4 randomized controlled trials of pharmacologic agents without regulatory approval or for unapproved indications
We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (from 01/01/2010-08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia, including also RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥ 1 primary outcome, 43 (18%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥ 1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes.
PMID: 37001575
ISSN: 1873-7528
CID: 5463482
Identification and treatment of individuals with attention-deficit/hyperactivity disorder and substance use disorder: An expert consensus statement
Attention-deficit/hyperactivity disorder (ADHD) often co-occurs with substance use (SU) and/or substance use disorder (SUD). Individuals with concurrent ADHD and SU/SUD can have complex presentations that may complicate diagnosis and treatment. This can be further complicated by the context in which services are delivered. Also, when working with young people and adults with co-existing ADHD and SU/SUD, there is uncertainty among healthcare practitioners on how best to meet their needs. In February 2022, the United Kingdom ADHD Partnership hosted a meeting attended by multidisciplinary experts to address these issues. Following presentations providing attendees with an overview of the literature, group discussions were held synthesizing research evidence and clinical experience. Topics included: (1) A review of substances and reasons for use/misuse; (2) identification, assessment and treatment of illicit SU/SUD in young people and adults with ADHD presenting in community services; and (3) identification, assessment and treatment of ADHD in adults presenting in SU/SUD community and inpatient services. Dis-cussions highlighted inter-service barriers and fragmentation of care. It was concluded that a multimodal and multi-agency approach is needed. The consensus group generated a table of practice recommendations providing guidance on: identification and assessment; pharmacological and psychological treatment; and multi-agency interventions.
PMCID:10075023
PMID: 37033892
ISSN: 2220-3206
CID: 5470512
Predicting childhood and adolescent attention-deficit/hyperactivity disorder onset: a nationwide deep learning approach
Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder with a high degree of psychiatric and physical comorbidity, which complicates its diagnosis in childhood and adolescence. We analyzed registry data from 238,696 persons born and living in Sweden between 1995 and 1999. Several machine learning techniques were used to assess the ability of registry data to inform the diagnosis of ADHD in childhood and adolescence: logistic regression, random Forest, gradient boosting, XGBoost, penalized logistic regression, deep neural network (DNN), and ensemble models. The best fitting model was the DNN, achieving an area under the receiver operating characteristic curve of 0.75, 95% CI (0.74-0.76) and balanced accuracy of 0.69. At the 0.45 probability threshold, sensitivity was 71.66% and specificity was 65.0%. There was an overall agreement in the feature importance among all models (τ > .5). The top 5 features contributing to classification were having a parent with criminal convictions, male sex, having a relative with ADHD, number of academic subjects failed, and speech/learning disabilities. A DNN model predicting childhood and adolescent ADHD trained exclusively on Swedish register data achieved good discrimination. If replicated and validated in an external sample, and proven to be cost-effective, this model could be used to alert clinicians to individuals who ought to be screened for ADHD and to aid clinicians' decision-making with the goal of decreasing misdiagnoses. Further research is needed to validate results in different populations and to incorporate new predictors.
PMCID:10005952
PMID: 36536075
ISSN: 1476-5578
CID: 5431832
