Biomarker Of Attention-deficit/hyperactivity Disorder Research Articles

Using Mobile Electroencephalography and Actigraphy to Diagnose Attention-Deficit/Hyperactivity Disorder: Case-Control Comparison Study.

BackgroundChildren with attention-deficit/hyperactivity disorder (ADHD), a neurobehavioral disorder, display behaviors of inattention, hyperactivity, or impulsivity, which can affect their ability to learn and establish proper family and social relationships. Various tools are currently used by child and adolescent psychiatric clinics to diagnose, evaluate, and collect information and data. The tools allow professional physicians to assess if patients need further treatment, following a thorough and careful clinical diagnosis process.ObjectiveWe aim to determine potential indicators extracted from a mobile electroencephalography (EEG) device (Mindset; NeuroSky) and an actigraph (MotionWatch 8; CamNtech) and to validate them for diagnosis of ADHD. The 3 indicators are (1) attention, measured by the EEG; (2) meditation, measured by the EEG; and (3) activity, measured by the actigraph.MethodsA total of 63 participants were recruited. The case group comprised 40 boys and 9 girls, while the control group comprised 5 boys and 9 girls. The groups were age matched. The test was divided into 3 stages—pretest, in-test, and posttest—with a testing duration of 20 minutes each. We used correlation analysis, repeated measures analysis of variance, and regression analysis to investigate which indicators can be used for ADHD diagnosis.ResultsWith the EEG indicators, the analysis results show a significant correlation of attention with both hit reaction time (RT) interstimulus interval (ISI) change (r=–0.368; P=.003) and hit standard error (SE) ISI change (r=–0.336; P=.007). This indicates that the higher the attention of the participants, the smaller both the hit RT change and the hit SE ISI change. With the actigraph indicator, confidence index (r=0.352; P=.005), omissions (r=0.322; P=.01), hit RT SE (r=0.393; P=.001), and variability (r=0.351; P=.005) were significant. This indicates that the higher the activity amounts, the higher the impulsive behavior of the participants and the more target omissions in the continuous performance test (CPT). The results show that the participants with ADHD present a significant difference in activity amounts (P<0.001). The actigraph outperforms the EEG in screening ADHD.ConclusionsWhen the participants with ADHD are stimulated under restricted conditions, they will present different amounts of activity than in unrestricted conditions due to participants’ inability to exercise control over their concentration. This finding could be a new electronic physiological biomarker of ADHD. An actigraph can be used to detect the amount of activity exhibited and to help physicians diagnose the disorder in order to develop more objective, rapid auxiliary diagnostic tools.

Biomarkers for ADHD: the Present and Future Directions

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders characterized by inattention, impulsivity, diminished executive functions, and hyperactivity. Objective criteria can be used to assess the diagnosis and response of the disease to medications. Several biomarkers belonging to electrophysiological, genetic, peripheral, and miRNA-based biomarkers have shown promise in studies to be an objective aid to clinical diagnostic criteria for the diagnosis of ADHD. This review article focuses on summarizing the existing evidence for different biomarkers that have been studied in the past for diagnosing ADHD.

Novel plasma metabolite markers of attention-deficit/hyperactivity disorder identified using high-performance chemical isotope labelling-based liquid chromatography-mass spectrometry

Objectives Metabolites are the intermediate and final products of biological processes and ultimately reflect the responses of these processes to genetic regulation and environmental perturbations, including those involved in attention deficit/hyperactivity disorder (ADHD). Methods We identified a quantitative profile of plasma metabolites in 58 ADHD patients (mean age 9.0 years, 77.6% males) and 38 healthy control subjects (mean age 10.2 years, 55.3% males) using the high-performance chemical isotope labelling (CIL)-based liquid chromatography-mass spectrometry (LC-MS). Using a volcano plot and orthogonal projections to latent structure-discriminant analysis (OPLS-DA), we determined nine metabolites with differentially expressed levels in ADHD plasma samples. Results Compared to the control group, the plasma levels of guanosine, O-phosphoethanolamine, phenyl-leucine, hypoxanthine, 4-aminohippuric acid, 5-hydroxylysine, and L-cystine appeared increased in the ADHD patients, whilegentisic acid and tryptophyl-phenylalanine were down-regulated in the patients with ADHD. We found that the plasma levels of all nine metabolites were able to discriminate the ADHD group from the control group. Levels of O-phosphoethanolamine, 4-aminohippuric acid, 5-hydroxylysine, L-cystine, tryptophyl-phenylalanine, and gentisic acid were significantly correlated with clinical ADHD symptoms. Conclusions This study is the first to use the CIL-based LC-MS to profile ADHD plasma metabolites, and we identified nine novel metabolite biomarkers of ADHD.

Large epigenome-wide association study of childhood ADHD identifies peripheral DNA methylation associated with disease and polygenic risk burden

Epigenetic variation in peripheral tissues is being widely studied as a molecular biomarker of complex disease and disease-related exposures. To date, few studies have examined differences in DNA methylation associated with attention-deficit hyperactivity disorder (ADHD). In this study, we profiled genetic and methylomic variation across the genome in saliva samples from children (age 7–12 years) with clinically established ADHD (N = 391) and nonpsychiatric controls (N = 213). We tested for differentially methylated positions (DMPs) associated with both ADHD diagnosis and ADHD polygenic risk score, by using linear regression models including smoking, medication effects, and other potential confounders in our statistical models. Our results support previously reported associations between ADHD and DNA methylation levels at sites annotated to VIPR2, and identify several novel disease-associated DMPs (p < 1e–5), although none of them were genome-wide significant. The two top-ranked, ADHD-associated DMPs (cg17478313 annotated to SLC7A8 and cg21609804 annotated to MARK2) are also significantly associated with nearby SNPs (p = 1.2e–46 and p = 2.07e–59), providing evidence that disease-associated DMPs are under genetic control. We also report a genome-wide significant association between ADHD polygenic risk and variable DNA methylation at a site annotated to the promoter of GART and SON (p = 6.71E–8). Finally, we show that ADHD-associated SNPs colocalize with SNPs associated with methylation levels in saliva. This is the first large-scale study of DNA methylation in children with ADHD. Our results represent novel epigenetic biomarkers for ADHD that may be useful for patient stratification, reinforce the importance of genetic effects on DNA methylation, and provide plausible molecular mechanisms for ADHD risk variants.

Multimodal alterations of directed connectivity profiles in patients with attention-deficit/hyperactivity disorders

Functional and effective connectivity measures for tracking brain region interactions that have been investigated using both electroencephalography (EEG) and magnetoencephalography (MEG) bringing up new insights into clinical research. However, the differences between these connectivity methods, especially at the source level, have not yet been systematically studied. The dynamic characterization of coherent sources and temporal partial directed coherence, as measures of functional and effective connectivity, were applied to multimodal resting EEG and MEG data obtained from 11 young patients (mean age 13.2 ± 1.5 years) with attention-deficit/hyperactivity disorder (ADHD) and age-matched healthy subjects. Additionally, machine-learning algorithms were applied to the extracted connectivity features to identify biomarkers differentiating the two groups. An altered thalamo-cortical connectivity profile was attested in patients with ADHD who showed solely information outflow from cortical regions in comparison to healthy controls who exhibited bidirectional interregional connectivity in alpha, beta, and gamma frequency bands. We achieved an accuracy of 98% by combining features from all five studied frequency bands. Our findings suggest that both types of connectivity as extracted from EEG or MEG are sensitive methods to investigate neuronal network features in neuropsychiatric disorders. The connectivity features investigated here can be further tested as biomarkers of ADHD.

Altered kynurenine pathway metabolites in a mouse model of human attention-deficit hyperactivity/autism spectrum disorders: A potential new biological diagnostic marker

Deleterious mutations in patchd1 domain containing 1 (PTCHD1) gene have been identified in patients with intellectual disability and/or autism spectrum disorder (ASD). To clarify the causal relationship between Ptchd1 deficiency and behavioral defects relevant to neurodevelopmental disorders, we generated global Ptchd1 knockout (KO) mice. Ptchd1 KO mice displayed hyperlocomotion, increased impulsivity, and lower recognition memory, which resemble attention-deficit hyperactivity disorder (ADHD)-like behaviors. Acute or chronic treatment with atomoxetine ameliorated almost all behavioral deficits in Pthcd1 KO mice. We next determined possible involvement of the kynurenine pathway (KP) metabolites in neurodevelopmental disorders in Ptchd1 KO mice and assessed the potential of KP metabolites as biomarkers for ADHD and/or ASD. Ptchd1 KO mice showed drastic changes in KP metabolite concentrations in the serum and the brain, indicating that the activated KP is associated with ADHD-like behaviors. Our findings indicate that Ptchd1 KO mice can be used as an animal model of human ADHD and/or ASD, and KP metabolites are potential diagnostic biomarkers for neurodevelopmental disorders.

Gray matter volume and microRNA levels in patients with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder often characterized by gray matter (GM) volume reductions. MicroRNAs, which participate in regulating gene expression, potentially influence neurodevelopment. This study aimed to explore whether differential GM volume is associated with differential miRNA levels in ADHD patients. We recruited a total of 30 drug-naïve patients with ADHD (mean age 10.6years) and 25 healthy controls (mean age 10.6years) that underwent a single session of 3.0-T whole brain structural MRI scanning. RNA samples from the participants' white blood cells were collected to identify the ΔCt values of three miRNAs (miR-30e-5p, miR-126-5p, and miR-140-3p) using the real-time quantitative reverse transcription polymerase chain reaction. In comparison to the control group, ADHD patients demonstrated a significantly lower GM volume in the cingulate gyrus, left middle temporal gyrus, right middle occipital gyrus, left fusiform gyrus, and significantly higher ΔCt values of miR-30e-5p, miR-126-5p, and miR-140-3p. In the ADHD group, the GM volume of cingulate gyrus and left fusiform gyrus was negatively correlated with the ΔCt values of miR-30e-5p, miR-140-3p. The GM volume of left fusiform gyrus was negatively correlated to ADHD behavioral symptoms. Using structural equation modeling (SEM), we observed that the effect of miR-140-3p on hyperactivity/impulsivity symptoms was mediated by left fusiform gyrus. Our findings support that GM volume reduction and miRNA increases may be biomarkers for ADHD in children and adolescents. Expression levels of miRNAs may affect the development of brain structures and further participate in the pathophysiology of ADHD.

Pilot Study: An Ocular Biomarker for Diagnosis of Attention Deficit Hyperactivity Disorder.

ObjectiveBiomarkers of attention deficit hyperactivity disorder (ADHD) are crucial for early diagnosis and intervention, in which the identification of biomarkers in other areas of the body that represent the immature brain of children with ADHD is necessary. The present study aimed to find biomarkers of ADHD in the retina and assessed the relationship between macular thickness of the retina and cortical thickness of the brain in children with ADHD. MethodsTwelve children with ADHD and 13 control children were recruited for the study. To find ocular markers of ADHD, we investigated the correlation between clinical symptoms of ADHD assessed with the Korean ADHD Rating Scale (K-ARS), cortical thickness of the brain, and macular thickness measured with the mean thickness from the Early Treatment Diabetic Retinopathy Study (ETDRS). ResultsChildren with ADHD showed increased macular thicknesses quantified as an ETDRS ring in both eyes, compared to control subjects. Moreover, the right inner ETDRS ring had a positive correlation with K-ARS scores. The ADHD group had an increased ratio of thickness of the right frontal lobe to that of the parietal cortex, compared with the control group. There were positive correlations between the means of the inner ETDRS ring (right) and the left paracentral/right isthmus cingulate thicknesses in the control group. However, there were negative correlations between the means of the inner ETDRS ring (right) and the left frontal pole/right pars triangularis thicknesses in the ADHD group. The results of both groups were at the uncorrected level. ConclusionThe different patterns of macular thickness might represent the immature cortical thickness of the brain in children with ADHD.

Commentary on… the overlapping and distinct resting functional connectivity between autism spectrum disorder and attention-deficit hyperactivity disorder.

Altered neural connectivity in neurodevelopmental disorders is likely subtle, meaning that neuroimaging literature studying development has produced heterogeneous findings. A recent study, published in this issue, illustrates the translational potential of functional connectivity magnetic resonance imaging findings as a biomarker for attention-deficit hyperactivity disorder and autism spectrum disorder. Importantly, it highlights the overlap between disorders, emphasising the need for transdiagnostic and dimensional approaches in neurodevelopment.Declaration of interestNone.

Age-related differences in frontal lobe function in children with ADHD

BackgroundThe neural correlates of executive function disorders are thought to be predominantly localized within the prefrontal cortex (PFC). However, no study to date has investigated changes in this system across different age groups in children with attention deficit hyperactivity disorder (ADHD). Thus, this study aimed to explore changes in PFC function in children with ADHD. MethodsStudy participants included typically developing (TD) children (n = 140) and children with ADHD (n = 67) of primary school age. Behavioral executive functions and their neural basis were evaluated between the TD children and children with ADHD and also across different age periods (younger and older children). To examine executive function, inhibitory control was assessed using the reverse Stroop task, and PFC near-infrared spectroscopic measurements were used to investigate the neural mechanisms involved. ResultsBoth ADHD symptoms and the ability to inhibit color interference improved with age. Compared to TD children, children with ADHD demonstrated decreased activation of the right and middle PFC across all age groups. Interestingly, the left PFC appeared to play a compensatory role. ConclusionChildren with ADHD exhibited changes in PFC function that varied with age. Longitudinal studies are required to assess the potential of using PFC function as an early biomarker of ADHD.

Dehydroepiandrosterone sulfate, free testosterone, and sex hormone-binding globulin on susceptibility to attention-deficit/hyperactivity disorder

The neuroendocrine system may affect the pathophysiology of gender differences in attention deficit/hyperactivity disorder (ADHD). This study examines whether the relationships among dehydroepiandrosterone sulfate (DHEA-S), free testosterone, or sex hormone-binding globulin (SHBG) and ADHD presentations exhibit gender differences. A total of 113 boys and 35 girls with ADHD (all drug naïve) and 46 and 26 healthy control boys and girls, respectively, were recruited. Blood samples were obtained to measure the serum levels of DHEA-S, free testosterone, and SHBG in each child. The Swanson, Nolan, and Pelham Scale for ADHD Version IV (SNAP-IV) was used to evaluate behavioral symptoms and the Wechsler Intelligence Scale for Children–Fourth Edition (WISC-IV) and the Conners’ Continuous Performance Test (CPT) were utilized to assess neurocognitive functions. Patients with ADHD had lower DHEA-S levels than male and female healthy control subjects, and no significant differences were observed in free testosterone and SHBG levels between the patients and the controls. DHEA-S levels were negatively correlated with children’s impulsivity performance in the CPT. SHBG levels were negatively correlated with ADHD behavior symptoms among boys. Free testosterone levels were not significantly correlated with either ADHD clinical symptoms or neuropsychological functions. We propose that DHEA-S serves as a potential biomarker of ADHD and is consistently involved in the pathogenesis of ADHD in both boys and girls. SHBG may be involved in behaviors associated with ADHD in boys. Additional studies with basic scientific measures are warranted to elucidate the relationship between androgen hormones and clinical presentations of ADHD.

Reduced hemispheric asymmetry of brain anatomical networks in attention deficit hyperactivity disorder.

Despite many studies reporting a variety of alterations in brain networks in patients with attention deficit hyperactivity disorder (ADHD), alterations in hemispheric anatomical networks are still unclear. In this study, we investigated topology alterations in hemispheric white matter in patients with ADHD and the relationship between these alterations and clinical features of the illness. Weighted hemispheric brain anatomical networks were first constructed for each of 40 right-handed patients with ADHD and 53 matched normal controls. Then, graph theoretical approaches were utilized to compute hemispheric topological properties. The small-world property was preserved in the hemispheric network. Furthermore, a significant group-by-hemisphere interaction was revealed in global efficiency, local efficiency and characteristic path length, attributed to the significantly reduced hemispheric asymmetry of global and local integration in patients with ADHD compared with normal controls. Specifically, reduced asymmetric regional efficiency was found in three regions. Finally, we found that the abnormal asymmetry of hemispheric brain anatomical network topology and regional efficiency were both associated with clinical features (the Adult ADHD Self-Report Scale and Wechsler Adult Intelligence Scale) in patients. Our findings provide new insights into the lateralized nature of hemispheric dysconnectivity and highlight the potential for using brain network measures of hemispheric asymmetry as neural biomarkers for ADHD and its clinical features.

Aberrant Spatial and Temporal Prefrontal Activation Patterns in Medication-Naïve Adults with ADHD.

Previous near-infrared spectroscopy (NIRS) studies using a verbal fluency task (VFT) have consistently reported that adults with attention-deficit hyperactivity disorder (ADHD) showed significantly smaller oxygenated-hemoglobin [oxy-Hb] activations in the prefrontal cortex (PFC) compared to those in healthy controls (HC). Despite this consistent evidence of brain dysfunction in ADHD, ADHD is currently diagnosed based only on subjective clinical and scoring measures, which are often unreliable. Hence, it is necessary to establish objective neuroimaging biomarkers for ADHD. While most NIRS studies have utilized averaged [oxy-Hb] values during the whole task period for group comparisons, we used a cluster-based non-parametric randomization test to compare the [oxy-Hb] time-course changes with a 0.1-s time resolution between drug-naïve adults with ADHD and HC, which may provide us with more details regarding abnormal prefrontal activation patterns in ADHD. A total of 101 participants, consisting of 63 drug-naïve adult individuals with ADHD and 38 HC, were included in this study. We identified that adults with ADHD showed significantly smaller [oxy-Hb] activations than those in HC at spatially and temporally connected clusters located in the bilateral PFC (more prominent on the left) and temporal brain region (more prominent on the left). We further found that aberrant [oxy-Hb] activation differs according to the time period during the task or according to brain location. Our findings indicate more detailed aberrant prefrontal and temporal activation patterns of ADHD compared with those in previous studies, possibly representing a biological marker for ADHD.

Journal Digest

Journal Digest

Changes in serum levels of kynurenine metabolites in paediatric patients affected by ADHD.

This study aims at determining serum levels of tryptophan and other metabolites of the kynurenine pathway in children with attention deficit hyperactivity disorder (ADHD) compared to healthy controls. Such metabolites interact with glutamate receptors in the central nervous system, potentially modulating mechanisms that are pivotal in ADHD and thus potentially representing peripheral biomarkers of the disorder. We measured serum levels of tryptophan and some metabolites of the kynurenine pathway in 102 children with ADHD and 62 healthy controls by liquid chromatography-tandem mass spectrometry (LC-MS/MS). As compared to healthy controls, children with ADHD showed a reduction in serum levels of anthranilic acid (-60%), kynurenic acid (-11.2%), and xanthurenic acid (-12.5%). In contrast, serum levels of tryptophan (+11.0%) and kynurenine (+48.6%) were significantly enhanced, and levels of quinolinic acid were unchanged in children with ADHD. In a logistic regression model, the presence of ADHD was predicted by low anthranilic acid and high tryptophan levels. These findings support the involvement of the kynurenine pathway in the pathophysiology of ADHD and suggest that anthranilic acid and tryptophan levels should be investigated as potential peripheral biomarker for ADHD.

Thyroid and Cortisol hormones in Attention Deficit Hyperactivity Disorder: A case-control study.

There is paucity of research in the putative role of hormonal biomarkers in Attention Deficit Hyperactivity Disorder (ADHD). The current study aimed to analyze the clinical profile, socio-demographic status, co-morbidity, hormonal biomarkers namely Thyroid hormones and Cortisol in children with ADHD and compare them with healthy controls and to explore the association of the hormonal biomarkers with severity of ADHD. Thirty children with DSM-IV TR diagnosis of ADHD were assessed using semi structured proforma, Conners' Parent Rating Scale revised short (CPRS - R: S) , Mini international neuropsychiatric interview for children and adolescents and Childrens' Global Assessment Scale as well as serum levels of total Triiodothyronine (T3) ,total Thyroxine (T4) , Thyroid Stimulating Hormone (TSH) and Cortisol using chemiluminescent immunometric assay and compared with 30 age- and gender -matched controls. The typical profile of cases of ADHD was of a male with mean age of 9.47 years (S.D=2.43) belonging to Hyperactive subtype of ADHD. Serum T4 was significantly lower in cases compared to controls. No significant difference was found in serum T3, TSH and Cortisol levels. No significant correlation between the CPRS : R-S scores and the hormonal biomarkers. There is need for exploration of Serum T4 as putative biomarker for ADHD with replication in future studies. It may also be important to report the negative finding of Cortisol as a biomarker of ADHD in the context of effective utilization of resources for research with special relevance to resource deficit developing countries.

Hyperactivity in motor response inhibition networks in unmedicated children with attention deficit-hyperactivity disorder

Objectives: Hypo/reduced activity in motor response inhibition (RI) cerebral networks was recently proposed as a promising specific neurobiological marker of attention deficit-hyperactivity disorder (ADHD). Before adopting such a pattern as a key diagnosis tool, we aim to replicate in an independent study the mechanisms underlying reduced RI-related activity in ADHD, after controlling for potentially confounding effects.Methods: In this fMRI study, we investigated the neural networks mediating successful and failed motor RI in children with ADHD and typically developing children (TDC) using the stop-signal task (SST) paradigm.Results: In contrast to hypofrontality predictions, children with ADHD exhibit increased neural activity during successful response inhibition in an RI-related brain network encompassing the indirect and/or hyperdirect pathways between the basal ganglia and cortex. Voxel-based morphometry analyses have further evidenced reduced grey matter volume in the left caudate in children with ADHD, which paralleled higher functional responses. Finally, connectivity analyses disclosed tighter coupling between a set of cortical regions and the right caudate as well as the right IFG, networks involved in successful RI.Conclusions: Hypo/reduced activity in RI cerebral networks in children with ADHD cannot at this time be considered as a systematic biomarker for ADHD.

An integrated feature ranking and selection framework for ADHD characterization.

Today, diagnosis of attention deficit hyperactivity disorder (ADHD) still primarily relies on a series of subjective evaluations that highly rely on a doctor’s experiences and intuitions from diagnostic interviews and observed behavior measures. An accurate and objective diagnosis of ADHD is still a challenge and leaves much to be desired. Many children and adults are inappropriately labeled with ADHD conditions, whereas many are left undiagnosed and untreated. Recent advances in neuroimaging studies have enabled us to search for both structural (e.g., cortical thickness, brain volume) and functional (functional connectivity) abnormalities that can potentially be used as new biomarkers of ADHD. However, structural and functional characteristics of neuroimaging data, especially magnetic resonance imaging (MRI), usually generate a large number of features. With a limited sample size, traditional machine learning techniques can be problematic to discover the true characteristic features of ADHD due to the significant issues of overfitting, computational burden, and interpretability of the model. There is an urgent need of efficient approaches to identify meaningful discriminative variables from a higher dimensional feature space when sample size is small compared with the number of features. To tackle this problem, this paper proposes a novel integrated feature ranking and selection framework that utilizes normalized brain cortical thickness features extracted from MRI data to discriminate ADHD subjects against healthy controls. The proposed framework combines information theoretic criteria and the least absolute shrinkage and selection operator (Lasso) method into a two-step feature selection process which is capable of selecting a sparse model while preserving the most informative features. The experimental results showed that the proposed framework generated the highest/comparable ADHD prediction accuracy compared with the state-of-the-art feature selection approaches with minimum number of features in the final model. The selected regions of interest in our model were consistent with recent brain–behavior studies of ADHD development, and thus confirmed the validity of the selected features by the proposed approach.

Neurobiology of Adult ADHD: Emerging Evidence for Network Dysfunctions.

FIGURE 1. Changes in cortical thickness provide one measure of brain maturation. A large longitudinal study found that for most areas of cortex, children with attention deficit hyperactivity disorder (ADHD) reach peak cortical thickness several years later than typically developing children, supporting presence of developmental delay. The rate of cortical thinning also differed between the group who continued to meet diagnostic criteria into adulthood (persistent ADHD) and those who did not (remitted ADHD). Areas of cortex in which the rate of thinning correlated with adult symptom level (green, more symptoms associated with more thinning) are approximated on medial and lateral simplified representations of cortex. An earlier study also identified multiple areas in which cortex was thinner in adults with persistent ADHD compared with controls (orange). In addition, this study noted some areas of thicker cortex in remitted ADHD when compared with persistent ADHD (blue).

Underarousal in Adult ADHD: How Are Peripheral and Cortical Arousal Related?

In children and adults with attention deficit/hyperactivity disorder (ADHD), a general slowing of spontaneous electroencephalographic (EEG) brain activity and a decrease of event-related potential amplitudes such as the contingent negative variation (CNV) are observed. Additionally, some studies have reported decreased skin conductance level (SCL) in this clinical population leading to the hypothesis of a peripheral hypoarousal, which may be a target of biofeedback treatment in addition to or instead of neurofeedback. To our knowledge, the relationship between SCL and CNV has not been simultaneously investigated in one experiment. Using the theoretical background of the hypoarousal model, this article aims to gain more insight into the differences and correlations of cortical (CNV) and peripheral (SCL) arousal in adults with ADHD. A sample of 23 adults with ADHD and 22 healthy controls underwent an auditory Go-NoGo task with simultaneous 22-channel EEG and SCL recordings. Reaction time (RT) and reaction time variability (RTV) were also measured to assess task performance. Significantly decreased CNV amplitude and significantly higher RTV were observed in the ADHD group, reflecting cortical underarousal and problems with sustained attention. No significant correlation between peripheral underarousal and cortical underarousal was observed in the ADHD group or the control group. The observed cortical underarousal reflected in the decreased CNV supports the notion of a reduced CNV amplitude as a possible biomarker for ADHD. However, the connection between cortical and peripheral arousal is not as clear as is suggested in previous research investigating both separately. Implications of these results for new treatment options for ADHD such as biofeedback are discussed.