Brain and Cognition 86 (2014) 82–89
Contents lists available at ScienceDirect
Brain and Cognition journal homepage: www.elsevier.com/locate/b&c
The effect of methylphenidate on very low frequency electroencephalography oscillations in adult ADHD Ruth E. Cooper a,⇑, Caroline Skirrow a,1, Charlotte Tye a, Grainne McLoughlin a, Fruhling Rijsdijk a, Tobias Banaschweski b, Daniel Brandeis b, Jonna Kuntsi a, Philip Asherson a a b
King’s College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, UK Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
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Article history: Accepted 4 February 2014 Available online 3 March 2014 Keywords: Attention deficit hyperactivity disorder (ADHD) Electroencephalography (EEG) Very low frequency oscillations (VLFOs) Methylphenidate Default mode network Endophenotype
a b s t r a c t Altered very low-frequency electroencephalographic (VLF-EEG) activity is an endophenotype of ADHD in children and adolescents. We investigated VLF-EEG case-control differences in adult samples and the effects of methylphenidate (MPH). A longitudinal case-control study was conducted examining the effects of MPH on VLF-EEG (.02–0.2 Hz) during a cued continuous performance task. 41 untreated adults with ADHD and 47 controls were assessed, and 21 cases followed up after MPH treatment, with a similar follow-up for 38 controls (mean follow-up = 9.4 months). Cases had enhanced frontal and parietal VLF-EEG and increased omission errors. In the whole sample, increased parietal VLF-EEG correlated with increased omission errors. After controlling for subthreshold comorbid symptoms, VLF-EEG case-control differences and treatment effects remained. Post-treatment, a time by group interaction emerged; VLF-EEG and omission errors reduced to the same level as controls, with decreased inattentive symptoms in cases. Reduced VLF-EEG following MPH treatment provides preliminary evidence that changes in VLF-EEG may relate to MPH treatment effects on ADHD symptoms; and that VLF-EEG may be an intermediate phenotype of ADHD. Further studies of the treatment effect of MPH in larger controlled studies are required to formally evaluate any causal link between MPH, VLF-EEG and ADHD symptoms. Ó 2014 Elsevier Inc. All rights reserved.
1. Introduction Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting 5% of children and 3–4% of adults (Faraone, Biederman, & Mick, 2006; Polanczyk, de Lima, Horta, Biederman, & Rohde, 2007). It is highly heritable (70–80%), indicating the important aetiological role of genetic influences (Asherson & Gurling, 2012). The disorder is associated with cognitive and neurobiological changes (Kuntsi et al., 2010; Paloyelis, Mehta, Kuntsi, & Asherson, 2007; Tye et al., 2012), many of which are seen in unaffected relatives of ADHD probands, indicating their potential role as endophenotypes, indexing genetic risk for ADHD (Gottesman & Gould, 2003). One potential endophenotype of ADHD is the very low frequency component of the electroencephalogram (VLF-EEG:
Contents lists available at ScienceDirect
Brain and Cognition journal homepage: www.elsevier.com/locate/b&c
The effect of methylphenidate on very low frequency electroencephalography oscillations in adult ADHD Ruth E. Cooper a,⇑, Caroline Skirrow a,1, Charlotte Tye a, Grainne McLoughlin a, Fruhling Rijsdijk a, Tobias Banaschweski b, Daniel Brandeis b, Jonna Kuntsi a, Philip Asherson a a b
King’s College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, UK Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
a r t i c l e
i n f o
Article history: Accepted 4 February 2014 Available online 3 March 2014 Keywords: Attention deficit hyperactivity disorder (ADHD) Electroencephalography (EEG) Very low frequency oscillations (VLFOs) Methylphenidate Default mode network Endophenotype
a b s t r a c t Altered very low-frequency electroencephalographic (VLF-EEG) activity is an endophenotype of ADHD in children and adolescents. We investigated VLF-EEG case-control differences in adult samples and the effects of methylphenidate (MPH). A longitudinal case-control study was conducted examining the effects of MPH on VLF-EEG (.02–0.2 Hz) during a cued continuous performance task. 41 untreated adults with ADHD and 47 controls were assessed, and 21 cases followed up after MPH treatment, with a similar follow-up for 38 controls (mean follow-up = 9.4 months). Cases had enhanced frontal and parietal VLF-EEG and increased omission errors. In the whole sample, increased parietal VLF-EEG correlated with increased omission errors. After controlling for subthreshold comorbid symptoms, VLF-EEG case-control differences and treatment effects remained. Post-treatment, a time by group interaction emerged; VLF-EEG and omission errors reduced to the same level as controls, with decreased inattentive symptoms in cases. Reduced VLF-EEG following MPH treatment provides preliminary evidence that changes in VLF-EEG may relate to MPH treatment effects on ADHD symptoms; and that VLF-EEG may be an intermediate phenotype of ADHD. Further studies of the treatment effect of MPH in larger controlled studies are required to formally evaluate any causal link between MPH, VLF-EEG and ADHD symptoms. Ó 2014 Elsevier Inc. All rights reserved.
1. Introduction Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting 5% of children and 3–4% of adults (Faraone, Biederman, & Mick, 2006; Polanczyk, de Lima, Horta, Biederman, & Rohde, 2007). It is highly heritable (70–80%), indicating the important aetiological role of genetic influences (Asherson & Gurling, 2012). The disorder is associated with cognitive and neurobiological changes (Kuntsi et al., 2010; Paloyelis, Mehta, Kuntsi, & Asherson, 2007; Tye et al., 2012), many of which are seen in unaffected relatives of ADHD probands, indicating their potential role as endophenotypes, indexing genetic risk for ADHD (Gottesman & Gould, 2003). One potential endophenotype of ADHD is the very low frequency component of the electroencephalogram (VLF-EEG:
