Electroencephalographic biomarkers as predictors of methylphenidate response in attention-deficit/hyperactivity disorder

Martijn Arns; Madelon A Vollebregt; Donna Palmer; Chris Spooner; Evian Gordon; Michael Kohn; Simon Clarke; Glen R Elliott; Jan K Buitelaar

doi:10.1016/j.euroneuro.2018.06.002

Electroencephalographic biomarkers as predictors of methylphenidate response in attention-deficit/hyperactivity disorder

Eur Neuropsychopharmacol. 2018 Aug;28(8):881-891. doi: 10.1016/j.euroneuro.2018.06.002. Epub 2018 Jun 22.

Authors

Martijn Arns¹, Madelon A Vollebregt², Donna Palmer³, Chris Spooner⁴, Evian Gordon⁵, Michael Kohn⁶, Simon Clarke⁶, Glen R Elliott⁷, Jan K Buitelaar⁸

Affiliations

¹ Research Institute Brainclinics, Bijleveldsingel 34, 6524 AD Nijmegen, The Netherlands; Department of Experimental Psychology, Utrecht University, Utrecht, The Netherlands. Electronic address: martijn@brainclinics.com.
² Research Institute Brainclinics, Bijleveldsingel 34, 6524 AD Nijmegen, The Netherlands; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.
³ Brain Resource Ltd, Sydney, NSW, Australia; Brain Resource Ltd, San Francisco, CA, USA; Brain Dynamics Center, Sydney Medical School and Westmead Millenium Institute, University of Sydney, NSW, Australia.
⁴ Brain Resource Ltd, Sydney, NSW, Australia.
⁵ Brain Resource Ltd, Sydney, NSW, Australia; Brain Resource Ltd, San Francisco, CA, USA.
⁶ Brain Dynamics Center, Sydney Medical School and Westmead Millenium Institute, University of Sydney, NSW, Australia; CRASH (Centre for Research into Adolescent'S Health) Westmead Hospital, Sydney Australia.
⁷ Children's Health Council, Palo Alto, CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine, CA, USA.
⁸ Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands; Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.

PMID: 29937325
DOI: 10.1016/j.euroneuro.2018.06.002

Abstract

EEG biomarkers have shown promise in predicting non-response to stimulant medication in ADHD and could serve as translational biomarkers. This study aimed to replicate and extend previous EEG biomarkers. The international Study to Predict Optimized Treatment for ADHD (iSPOT-A), a multi-center, international, prospective open-label trial, enrolled 336 children and adolescents with ADHD (11.9 yrs; 245 males; prescribed methylphenidate) and 158 healthy children. Treatment response was established after six weeks using the clinician rated ADHD-Rating Scale-IV. Theta/Beta ratio (TBR) and alpha peak frequency (APF) were assessed at baseline as predictors for treatment outcome. No differences between ADHD and controls were found for TBR and APF. 62% of the ADHD group was classified as a responder. Responders did not differ from non-responders in age, medication dosage, and baseline severity of ADHD symptoms. Male-adolescent non-responders exhibited a low frontal APF (Fz: R = 9.2 Hz vs. NR = 8.1 Hz; ES = 0.83), whereas no effects were found for TBR. A low APF in male adolescents was associated with non-response to methylphenidate, replicating earlier work. Our data suggest that the typical maturational EEG changes observed in ADHD responders and controls are absent in non-responders to methylphenidate and these typical changes start emerging in adolescence.

Clinical trials registration: www.clinicaltrials.gov; NCT00863499 (https://clinicaltrials.gov/ct2/show/NCT00863499).

Keywords: ADHD; Alpha peak frequency; Biomarker; QEEG; Theta.

Publication types

Clinical Trial, Phase IV
Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Attention Deficit Disorder with Hyperactivity / diagnosis
Attention Deficit Disorder with Hyperactivity / drug therapy*
Attention Deficit Disorder with Hyperactivity / physiopathology*
Brain / drug effects
Brain / physiopathology
Central Nervous System Stimulants / pharmacology*
Child
Electroencephalography*
Female
Humans
Male
Methylphenidate / pharmacology*
Prognosis
ROC Curve

Substances

Central Nervous System Stimulants
Methylphenidate

Associated data

ClinicalTrials.gov/NCT00863499