Dataset Information

Translating Discoveries in Attention-Deficit/Hyperactivity Disorder Genomics to an Outpatient Child and Adolescent Psychiatric Cohort.

ABSTRACT:

Objective

Genomic discoveries should be investigated in generalizable child psychiatric samples in order to justify and inform studies that will evaluate their use for specific clinical purposes. In youth consecutively referred for neuropsychiatric evaluation, we examined 1) the convergent and discriminant validity of attention-deficit/hyperactivity disorder (ADHD) polygenic risk scores (PRSs) in relation to DSM-based ADHD phenotypes; 2) the association of ADHD PRSs with phenotypes beyond ADHD that share its liability and have implications for outcome; and 3) the extent to which youth with high ADHD PRSs manifest a distinctive clinical profile.

Method

Participants were 433 youth, ages 7-18 years, from the Longitudinal Study of Genetic Influences on Cognition. We used logistic/linear regression and mixed effects models to examine associations with ADHD-related polygenic variation from the largest ADHD genome-wide association study to date. We replicated key findings in 5,140 adult patients from a local health system biobank.

Results

Among referred youth, ADHD PRSs were associated with ADHD diagnoses, cross-diagnostic ADHD symptoms and academic impairment (odds ratios ∼1.4; R² values ∼2%-3%), as well as cross-diagnostic variation in aggression and working memory. In adults, ADHD PRSs were associated with ADHD and phenotypes beyond the condition that have public health implications. Finally, youth with a high ADHD polygenic burden showed a more severe clinical profile than youth with a low burden (β coefficients ∼.2).

Conclusion

Among child and adolescent outpatients, ADHD polygenic risk was associated with ADHD and related phenotypes as well as clinical severity. These results extend the scientific foundation for studies of ADHD polygenic risk in the clinical setting and highlight directions for further research.

SUBMITTER: Vuijk PJ

PROVIDER: S-EPMC7408479 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Translating Discoveries in Attention-Deficit/Hyperactivity Disorder Genomics to an Outpatient Child and Adolescent Psychiatric Cohort.

Vuijk Pieter J PJ Martin Joanna J Braaten Ellen B EB Genovese Giulio G Capawana Michael R MR O'Keefe Sheila M SM Lee B Andi BA Lind Hannah S HS Smoller Jordan W JW Faraone Stephen V SV Perlis Roy H RH Doyle Alysa E AE

Journal of the American Academy of Child and Adolescent Psychiatry 20190814 8

<h4>Objective</h4>Genomic discoveries should be investigated in generalizable child psychiatric samples in order to justify and inform studies that will evaluate their use for specific clinical purposes. In youth consecutively referred for neuropsychiatric evaluation, we examined 1) the convergent and discriminant validity of attention-deficit/hyperactivity disorder (ADHD) polygenic risk scores (PRSs) in relation to DSM-based ADHD phenotypes; 2) the association of ADHD PRSs with phenotypes beyon ...[more]

PMID: 31421235

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Project description:ObjectivePsychostimulants are partially effective in reducing cognitive dysfunction associated with attention-deficit/hyperactivity disorder (ADHD). Cognitive effects of guanfacine, an alternative treatment, are poorly understood. Given its distinct action on α2A receptors, guanfacine may have different or complementary effects relative to stimulants. This study tested stimulant and guanfacine monotherapies relative to combined treatment on cognitive functions important in ADHD.MethodChildren with ADHD (n = 182; aged 7-14 years) completed an 8-week, double blind, randomized, controlled trial with 3 arms: d-methylphenidate (DMPH), guanfacine (GUAN), or combination treatment with DMPH and GUAN (COMB). A nonclinical comparison group (n = 93) had baseline testing, and a subset was retested 8 weeks later (n = 38). Analyses examined treatment effects in 4 cognitive domains (working memory, response inhibition, reaction time, and reaction time variability) constructed from 20 variables.ResultsThe ADHD group showed impaired working memory relative to the nonclinical comparison group (effect size = -0.53 SD unit). The treatments differed in effects on working memory but not other cognitive domains. Combination treatment improved working memory more than GUAN but was not significantly better than DMPH alone. Treatment did not fully normalize the initial deficit in ADHD relative to the comparison group.ConclusionCombined treatment with DMPH and GUAN yielded greater improvements in working memory than placebo or GUAN alone, but the combined treatment was not superior to DMPH alone and did not extend to other cognitive domains. Although GUAN may be a useful add-on treatment to psychostimulants, additional strategies appear to be necessary to achieve normalization of cognitive function in ADHD.Clinical trial registration informationSingle Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http://clinicaltrials.gov/; NCT00429273.

Project description:BackgroundRegular visit to psychiatric clinic is essential for successful treatment of any psychiatric condition including attention-deficit/hyperactivity disorder (AD/HD). However, cancellation of outpatient appointments in patients with AD/HD, which represents a significant medical loss, has not been systematically investigated to our knowledge.MethodsA systematic chart review was conducted for patients visiting the Shimada Ryoiku medical Center for Challenged Children in Japan at the age of ≤15 years from January to December 2013. The primary outcome measure was the cancellation rate, defined as the number of missed visits divided by the number of scheduled visits. The cancellation rates during 24 months after the first visit were compared between outpatients with AD/HD and other psychiatric disorders, including pervasive developmental disorders (PDD), and developmental coordination disorders and/or communication disorders (DCD-CD). A generalized linear model with binomial distribution was used to examine factors associated with cancellation rates exclusively in the AD/HD group.ResultsWe included 589 patients (mean ± SD age, 5.6 ± 3.4 years; 432 males) in the analysis. The cancellation rate in patients with AD/HD was 12.3% (95% confidence interval [CI]: 10.0-15.1), which was significantly higher than in those with PDD (5.6%, 95% CI: 3.8-8.3) and DCD-CD (5.3%, 95% CI: 3.6-7.8). Prescriptions of osmotic-release oral system-methylphenidate (OROS-MPH) and antipsychotics were associated with fewer cancellations in AD/HD patients (odds ratios: 0.61, 95% CI: 0.39-0.95 and 0.49, 95% CI: 0.25-0.95, respectively), although these significances did not find in the subgroup analysis including only patients with ≥ 6 years old.ConclusionsPatients with AD/HD were more likely to miss appointments compared to those with other psychiatric disorders. The impact of AD/HD medications as well as potential psychiatric symptoms of their parents or caregivers on appointment cancellations needs to be evaluated in more detail in future investigations.

Project description:ImportanceThe association between attention-deficit/hyperactivity disorder (ADHD) and schizophrenia has received increased attention; however, evidence on the association between psychiatric comorbidities and subsequent schizophrenia in patients with ADHD is limited.ObjectiveTo investigate the risk of being diagnosed with schizophrenia in children and adolescents with ADHD considering the presence of psychiatric comorbidity.Design, setting, and participantsThis was a population-based, retrospective cohort study using the Health Insurance Review and Assessment claims database from January 1, 2007, to December 31, 2019. Participants were children and adolescents aged 5 to 19 years who received an ADHD diagnosis between January 1, 2010, and December 31, 2018, in the nationwide claims data of Korea. Data were analyzed from January 2010 to December 2019.Interventions or exposuresThe presence of psychiatric comorbidity was assessed from diagnosis records within 1 year before ADHD diagnosis. Comorbidities were further categorized according to the number of comorbidities and specific comorbid disorders.Main outcomes and measuresCox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs, examining the association between psychiatric comorbidities and the risk of being diagnosed with schizophrenia. Furthermore, the occurrence of psychiatric comorbidity during the follow-up period was explored among patients without psychiatric comorbidity at baseline.ResultsA total of 211 705 patients with newly diagnosed ADHD were included. A total of 157 272 patients (74.3%) were male, and the age of 5 to 9 years showed the highest distribution (115 081 patients [54.4%]). Patients with psychiatric comorbidity had a significantly higher risk of being diagnosed with schizophrenia than those without (adjusted HR, 2.14; 95% CI, 2.05-2.23). The association between schizophrenia and psychiatric comorbidity became progressively greater with the increasing number of comorbidities. Several individual psychiatric disorders showed an association with development of schizophrenia, with ASD, intellectual disability, tic disorder, depression, and bipolar disorder being the top 5 disorders most associated. Furthermore, 3244 patients (73.8%) without psychiatric comorbidities experienced the emergence of other psychiatric disorders before schizophrenia occurrence.Conclusions and relevanceIn this retrospective cohort study involving children and adolescents with ADHD, the presence of psychiatric comorbidity in patients with ADHD was associated with an increased risk of being diagnosed with schizophrenia, with an increased risk observed in multiple comorbidities and a wide variety of comorbidities. These findings highlight the significance of assessing and managing psychiatric comorbidities in patients with ADHD to decrease subsequent schizophrenia risk and allow for early intervention.

Project description:BACKGROUND: Psychostimulants are first line of therapy for paediatric and adolescent AD/HD. The evidence suggests that up to 30% of those prescribed stimulant medications do not show clinically significant outcomes. In addition, many children and adolescents experience side-effects from these medications. As a result, parents are seeking alternate interventions for their children. Complementary and alternative medicine therapies for behavioural disorders such as AD/HD are increasing with as many as 68% of parents having sought help from alternative practitioners, including chiropractors. OBJECTIVE: The review seeks to answer the question of whether chiropractic care can reduce symptoms of inattention, impulsivity and hyperactivity for paediatric and adolescent AD/HD. METHODS: Electronic databases (Cochrane CENTRAL register of Controlled Trials, Cochrane Database of Systematic reviews, MEDLINE, PsycINFO, CINAHL, Scopus, ISI Web of Science, Index to Chiropractic Literature) were searched from inception until July 2009 for English language studies for chiropractic care and AD/HD. Inclusion and exclusion criteria were applied to select studies. All randomised controlled trials were evaluated using the Jadad score and a checklist developed from the CONSORT (Consolidated Standards of Reporting Trials) guidelines. RESULTS: The search yielded 58 citations of which 22 were intervention studies. Of these, only three studies were identified for paediatric and adolescent AD/HD cohorts. The methodological quality was poor and none of the studies qualified using inclusion criteria. CONCLUSIONS: To date there is insufficient evidence to evaluate the efficacy of chiropractic care for paediatric and adolescent AD/HD. The claim that chiropractic care improves paediatric and adolescent AD/HD, is only supported by low levels of scientific evidence. In the interest of paediatric and adolescent health, if chiropractic care for AD/HD is to continue, more rigorous scientific research needs to be undertaken to examine the efficacy and effectiveness of chiropractic treatment. Adequately-sized RCTs using clinically relevant outcomes and standardised measures to examine the effectiveness of chiropractic care verses no-treatment/placebo control or standard care (pharmacological and psychosocial care) are needed to determine whether chiropractic care is an effective alternative intervention for paediatric and adolescent AD/HD.

Project description:ImportanceAppropriate diagnosis of attention-deficit/hyperactivity disorder (ADHD) can improve some short-term outcomes in children and adolescents, but little is known about the association of a diagnosis with their quality of life (QOL).ObjectiveTo compare QOL in adolescents with and without an ADHD diagnosis.Design, setting, and participantsThis cohort study followed an emulated target trial design using prospective, observational data from the Longitudinal Study of Australian Children, a representative, population-based prospective cohort study with biennial data collection from 2006 to 2018 with 8 years of follow-up (ages 6-7 to 14-15 years). Propensity score matching was used to ensure children with and without ADHD diagnosis were well matched on a wide range of variables, including hyperactive/inattentive (H/I) behaviors. Eligible children were born in 1999 to 2000 or 2003 to 2004 and did not have a previous ADHD diagnosis. All incident ADHD cases were matched with controls. Data were analyzed from July 2021 to January 2022.ExposuresIncident parent-reported ADHD diagnosis at age 6 to 7, 8 to 9, 10 to 11, 12 to 13, or 14 to 15.Main outcomes and measuresQuality of life at age 14 to 15 was measured with Child Health Utility 9D (CHU9D) and 8 other prespecified, self-reported measures mapped to the World Health Organization's QOL domains. Pooled regression models were fitted for each outcome, with 95% CIs and P values calculated using bootstrapping to account for matching and repeat observations.ResultsOf 8643 eligible children, a total of 393 adolescents had an ADHD diagnosis (284 [72.2%] boys; mean [SD] age, 10.03 [0.30] years; mean [SD] H/I Strengths and Difficulties Questionnaire score, 5.05 [2.29]) and were age-, sex-, and H/I score-matched with 393 adolescents without ADHD diagnosis at time zero. Compared with adolescents without diagnosis, those with an ADHD diagnosis reported similar QOL on CHU9D (mean difference, -0.03; 95% CI, -0.07 to 0.01; P = .10), general health (mean difference, 0.11; 95% CI, -0.04 to 0.27; P = .15), happiness (mean difference, -0.18; 95% CI, -0.37 to 0.00; P = .05), and peer trust (mean difference, 0.65; 95% CI, 0.00 to 1.30; P = .05). Diagnosed adolescents had worse psychological sense of school membership (mean difference, -2.58; 95% CI, -1.13 to -4.06; P < .001), academic self-concept (mean difference, -0.14; 95% CI, -0.02 to -0.26; P = .02), and self-efficacy (mean difference, -0.20; 95% CI, -0.05 to -0.33; P = .007); displayed more negative social behaviors (mean difference, 1.56; 95% CI, 0.55 to 2.66; P = .002); and were more likely to harm themselves (odds ratio, 2.53; 95% CI, 1.49 to 4.37; P < .001) than adolescents without diagnosis.Conclusions and relevanceIn this cohort study, ADHD diagnosis was not associated with any self-reported improvements in adolescents' QOL compared with adolescents with similar levels of H/I behaviors but no ADHD diagnosis. ADHD diagnosis was associated with worse scores in some outcomes, including significantly increased risk of self-harm. A large, randomized clinical trial with long-term follow-up is needed.

Dataset Information

Translating Discoveries in Attention-Deficit/Hyperactivity Disorder Genomics to an Outpatient Child and Adolescent Psychiatric Cohort.

Objective

Method

Results

Conclusion

Publications

Translating Discoveries in Attention-Deficit/Hyperactivity Disorder Genomics to an Outpatient Child and Adolescent Psychiatric Cohort.

Similar Datasets

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