Electrophysiological and Clinical Predictors of Methylphenidate, Guanfacine, and Combined Treatment Outcomes in Children With Attention-Deficit/Hyperactivity Disorder

Michelini, Giorgia; Lenartowicz, Agatha; Vera, Juan Diego; Bilder, Robert M.; McGough, James J.; McCracken, James T.; Loo, Sandra K.

doi:10.1016/j.jaac.2022.08.001

Cited by 3 publications

(5 citation statements)

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“…Classifiers and machine learning algorithms are becoming particularly popular approaches to handle high dimensionality and maximize predictive accuracy of biomarkers [3,136]. The few studies that adopted these multivariate methods to predict treatment response at the level of individual subjects have used small sample sizes, which are known to be highly sensitive to overfitting [20,57,137]. Moreover, most studies did not examine whether biomarker profiles explain clinically useful variance over and above routinely-collected information such as baseline ADHD symptoms, comorbidities and neuropsychological functioning.…”

Section: Discussionmentioning

confidence: 99%

“… Luo et al [ 56 ] China 121 0 M = 8.9, range= 7.1–12.3 83% Not reported 3-month remote computerized cognitive, NF, and combined training, RCT Relative alpha power during rest Pre-training relative alpha power correlated positively with ADHD improvements. Michelini et al [ 57 ] USA 207 (all medication naïve or medication free for >5 times half-lives) 0 M = 10.1, SD = 2.1 68% 83% 8-week MPH, GUAN, MPH + GUAN, RCT Event-related midfrontal beta power localized in the ACC during the Sternberg spatial working memory task with encoding, maintenance and retrieval phases Weaker mid-frontal beta power modulations across task phases predicted greater ADHD improvements with MPH + GUAN. Stronger mid-frontal beta power modulations predicted clinical improvements with GUAN (during retrieval) and binary response with MPH (during encoding).…”

Section: Predictive Biomarkersmentioning

confidence: 99%

Section: Predictive Biomarkersmentioning

confidence: 99%

“…Given the relatively inconclusive evidence on neurofeedback efficacy for ADHD at the group level [53][54][55], these studies may help to identify biologically-distinct ADHD subgroups who respond better to this treatment. Only a few studies tested EEG predictors of more than one type of treatment [52,56,57]. An 8-week randomized controlled trial (RCT) comparing MPH, guanfacine and their combination found that event-related EEG power profiles during a working memory task showed treatment-specific associations with clinical improvements [57].…”

Section: Eegmentioning

confidence: 99%

“…Only a few studies tested EEG predictors of more than one type of treatment [52,56,57]. An 8-week randomized controlled trial (RCT) comparing MPH, guanfacine and their combination found that event-related EEG power profiles during a working memory task showed treatment-specific associations with clinical improvements [57]. Specifically, better treatment outcome was predicted by weaker mid-frontal beta power modulations localized in the anterior cingulate cortex (ACC) in children treated with combined MPH + guanfacine, but by stronger modulations in children treated with MPH or guanfacine.…”

Section: Eegmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Predictive Biomarkersmentioning

confidence: 99%

Section: Predictive Biomarkersmentioning

confidence: 99%

Section: Eegmentioning

confidence: 99%

Section: Eegmentioning

confidence: 99%

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Treatment biomarkers for ADHD: Taking stock and moving forward

et al. 2022

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Noradrenergic Modulation of Learned and Innate Behaviors in Dopamine Transporter Knockout Rats by Guanfacine

Volnova

Kurzina²,

Belskaya³

et al. 2023

Biomedicines

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Investigation of the precise mechanisms of attention deficit and hyperactivity disorder (ADHD) and other dopamine-associated conditions is crucial for the development of new treatment approaches. In this study, we assessed the effects of repeated and acute administration of α2A-adrenoceptor agonist guanfacine on innate and learned forms of behavior of dopamine transporter knockout (DAT-KO) rats to evaluate the possible noradrenergic modulation of behavioral deficits. DAT-KO and wild type rats were trained in the Hebb–Williams maze to perform spatial working memory tasks. Innate behavior was evaluated via pre pulse inhibition (PPI). Brain activity of the prefrontal cortex and the striatum was assessed. Repeated administration of GF improved the spatial working memory task fulfillment and PPI in DAT-KO rats, and led to specific changes in the power spectra and coherence of brain activity. Our data indicate that both repeated and acute treatment with a non-stimulant noradrenergic drug lead to improvements in the behavior of DAT-KO rats. This study further supports the role of the intricate balance of norepinephrine and dopamine in the regulation of attention. The observed compensatory effect of guanfacine on the behavior of hyperdopaminergic rats may be used in the development of combined treatments to support the dopamine–norepinephrine balance.

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