Genetic, Clinical, and Sociodemographic Factors Associated With Stimulant Treatment Outcomes in ADHD

Brikell, Isabell; Wimberley, Theresa; Albiñana, Clara; Pedersen, Emil Michael; Vilhjálmsson, Bjarni J.; Agerbo, Esben; Demontis, Ditte; Børglum, Anders; Schork, Andrew J.; LaBianca, Sonja; Werge, Thomas; Mors, Ole; Hougaard, David M.; Thapar, Anita; Mortensen, Preben Bo; Dalsgaard, Søren

doi:10.1176/appi.ajp.2020.20121686

Cited by 17 publications

(23 citation statements)

References 51 publications

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“…In more recent years, ADHD is still frequently underdiagnosed or misdiagnosed as other psychiatric conditions such as mood or personality disorders ( 10 ). Even when patients are diagnosed with ADHD as children, many patients lose access to resources when transitioning from child to adult health services ( 11 ) which may contribute to less than half of people with ADHD adhering to stimulant medication ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

The lived experiences of adults with attention-deficit/hyperactivity disorder: A rapid review of qualitative evidence

et al. 2022

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Attention-deficit/hyperactivity disorder (ADHD) is a common condition that frequently persists into adulthood, although research and diagnostic criteria are focused on how the condition presents in children. We aimed to review qualitative research on lived experiences of adults with ADHD to characterize potential ADHD symptomatology in adulthood and provide perspectives on how needs might be better met. We searched three databases for qualitative studies on ADHD. Studies (n = 35) in English that included data on the lived experiences of adults with ADHD were included. These studies covered experiences of receiving a diagnosis as an adult, symptomatology of adult ADHD, skills used to adapt to these symptoms, relationships between ADHD and substance use, patients’ self-perceptions, and participants’ experiences interacting with society. Many of the ADHD symptoms reported in these studies had overlap with other psychiatric conditions and may contribute to misdiagnosis and delays in diagnosis. Understanding symptomatology of ADHD in adults may inform future diagnostic criteria and guide interventions to improve quality of life.

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Section: Introductionmentioning

confidence: 99%

The lived experiences of adults with attention-deficit/hyperactivity disorder: A rapid review of qualitative evidence

et al. 2022

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“…PRS for ADHD was found to predict a favorable response to ADHD medication (MPH or ATX), explaining around 2% of the variance [63]. The aforementioned Danish study did not find the PRS for ADHD to be associated with treatment outcomes [64], consistent with recent evidence that genes implicated in the pathogenesis of ADHD do not overlap with genes encoding targets of stimulants and ATX [67]. However, PRS for bipolar disorder and schizophrenia increased the likelihood of stopping stimulant medication (~5-7% of the variance) [64], mirroring findings that comorbid bipolar or psychotic disorders are associated with poor treatment response and adverse events.…”

Section: Geneticsmentioning

confidence: 85%

“…As large sample sizes are needed in GWAS of complex phenotypes such as medication response, studies including less than 250 participants found no genome-wide significant SNPs tied to medication response [62,63]. More promising results come from a large Danish study that linked genotype data with medical records, allowing a well-powered GWAS of starting (N = 7427) or stopping (N = 3370) MPH treatment or switching to non-stimulants (N = 1137) over 2 years [64]. While no genome-wide significant associations emerged for starting or stopping treatment, a locus on 16q23.3 containing genes associated with many neuropsychiatric phenotypes was associated with switching medications, likely due to poor efficacy.…”

Section: Geneticsmentioning

confidence: 99%

Treatment biomarkers for ADHD: Taking stock and moving forward

et al. 2022

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The development of treatment biomarkers for psychiatric disorders has been challenging, particularly for heterogeneous neurodevelopmental conditions such as attention-deficit/hyperactivity disorder (ADHD). Promising findings are also rarely translated into clinical practice, especially with regard to treatment decisions and development of novel treatments. Despite this slow progress, the available neuroimaging, electrophysiological (EEG) and genetic literature provides a solid foundation for biomarker discovery. This article gives an updated review of promising treatment biomarkers for ADHD which may enhance personalized medicine and novel treatment development. The available literature points to promising pre-treatment profiles predicting efficacy of various pharmacological and non-pharmacological treatments for ADHD. These candidate predictive biomarkers, particularly those based on low-cost and non-invasive EEG assessments, show promise for the future stratification of patients to specific treatments. Studies with repeated biomarker assessments further show that different treatments produce distinct changes in brain profiles, which track treatment-related clinical improvements. These candidate monitoring/response biomarkers may aid future monitoring of treatment effects and point to mechanistic targets for novel treatments, such as neurotherapies. Nevertheless, existing research does not support any immediate clinical applications of treatment biomarkers for ADHD. Key barriers are the paucity of replications and external validations, the use of small and homogeneous samples of predominantly White children, and practical limitations, including the cost and technical requirements of biomarker assessments and their unknown feasibility and acceptability for people with ADHD. We conclude with a discussion of future directions and methodological changes to promote clinical translation and enhance personalized treatment decisions for diverse groups of individuals with ADHD.

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“…Symptoms that are often associated with ADHD such as emotional or affect lability for which the efficacy of current agents is inadequate can serve as the examples for this approach. Summary of findings using genome-wide method ( Mick et al, 2008 ; Pagerols et al, 2018 ; Hegvik et al, 2019 ; Zhong et al, 2020 ; Brikell et al, 2021 ) is also provided in Table 2 .…”

Section: Introductionmentioning

confidence: 99%

Genetics in the ADHD Clinic: How Can Genetic Testing Support the Current Clinical Practice?

2022

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Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a childhood prevalence of 5%. In about two-thirds of the cases, ADHD symptoms persist into adulthood and often cause significant functional impairment. Based on the results of family and twin studies, the estimated heritability of ADHD approximates 80%, suggests a significant genetic component in the etiological background of the disorder; however, the potential genetic effects on disease risk, symptom severity, and persistence are unclear. This article provides a brief review of the genome-wide and candidate gene association studies with a focus on the clinical aspects, summarizing findings of ADHD disease risk, ADHD core symptoms as dimensional traits, and other traits frequently associated with ADHD, which may contribute to the susceptibility to other comorbid psychiatric disorders. Furthermore, neuropsychological impairment and measures from neuroimaging and electrophysiological paradigms, emerging as potential biomarkers, also provide a prominent target for molecular genetic studies, since they lie in the pathway from genes to behavior; therefore, they can contribute to the understanding of the underlying neurobiological mechanisms and the interindividual heterogeneity of clinical symptoms. Beyond the aforementioned aspects, throughout the review, we also give a brief summary of the genetic results, including polygenic risk scores that can potentially predict individual response to different treatment options and may offer a possibility for personalized treatment for the therapy of ADHD in the future.

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Genetic, Clinical, and Sociodemographic Factors Associated With Stimulant Treatment Outcomes in ADHD

Cited by 17 publications

References 51 publications

The lived experiences of adults with attention-deficit/hyperactivity disorder: A rapid review of qualitative evidence

The lived experiences of adults with attention-deficit/hyperactivity disorder: A rapid review of qualitative evidence

Treatment biomarkers for ADHD: Taking stock and moving forward

Genetics in the ADHD Clinic: How Can Genetic Testing Support the Current Clinical Practice?

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