Background: Compared to typically developing individuals, individuals with attention-deficit-hyperactivity disorder (ADHD) are on average more often exposed to stressful conditions (e.g., school failure, family conflicts, financial problems). We hypothesized that high exposure to stress relates to a more persistent and complex (i.e., multi-problem) form of ADHD, while low-stress exposure relates to remitting ADHD over the course of adolescence. Method: Longitudinal data (ages 11, 13, 16, and 19) came from the Tracking Adolescents’ Individual Life Survey (TRAILS). We selected children diagnosed with ADHD (n = 244; 167 males; 77 females) from the TRAILS clinical cohort and children who screened positive (n = 365; 250 males; 115 females) and negative (gender-matched: n = 1222; 831 males; 391 females) for ADHD from the TRAILS general population sample cohort (total n = 1587). Multivariate latent class growth analysis was applied to parent- and self-ratings of stress exposure, core ADHD problems (attention problems, hyperactivity/impulsivity), effortful control, emotion dysregulation (irritability, extreme reactivity, frustration), and internalizing problems (depression, anxiety, somatic complaints). Results: Seven distinct developmental courses in stress exposure and psychopathology were discerned, of which four related to ADHD. Two persistent ADHD courses of severely affected adolescents were associated with very high curvilinear stress exposure peaking in mid-adolescence: (1) Severe combined type with ongoing, severe emotional dysregulation, and (2) combined type with a high and increasing internalization of problems and elevated irritability; two partly remitting ADHD courses had low and declining stress exposure: (3) inattentive type, and (4) moderate combined type, both mostly without comorbid problems. Conclusions: High-stress exposure between childhood and young adulthood is strongly intertwined with a persistent course of ADHD and with comorbid problems taking the form of either severe and persistent emotion dysregulation (irritability, extreme reactivity, frustration) or elevated and increasing irritability, anxiety, and depression. Conversely, low and declining stress exposure is associated with remitting ADHD and decreasing internalizing and externalizing problems. Stress exposure is likely to be a facilitating and sustaining factor in these two persistent trajectories of ADHD with comorbid problems into young adulthood. Our findings suggest that a bidirectional, continuing, cycle of stressors leads to enhanced symptoms, in turn leading to more stressors, and so forth. Consideration of stressful conditions should, therefore, be an inherent part of the diagnosis and treatment of ADHD, to potentiate prevention and interruption of adverse trajectories. Full article

Background: Recent research has shown an increased risk of accidents and injuries in ADHD patients, which could potentially be reduced by stimulant treatment. Therefore, the first aim of our study was to evaluate the prevalence of adult ADHD in a trauma surgery population. The second aim was to investigate accident mechanisms and circumstances which could be specific to ADHD patients, in comparison to the general population. Methods: We screened 905 accident victims for ADHD using the ASRS 18-item self-report questionnaire. The basic demographic data and circumstances of the accidents were also assessed. Results: Prevalence of adult ADHD was found to be 6.18% in our trauma surgery patient sample. ADHD accident victims reported significantly higher rates of distraction, stress and overconfidence in comparison to non-ADHD accident victims. Overconfidence and being in thoughts as causal mechanisms for the accidents remained significantly higher in ADHD patients after correction for multiple comparison. ADHD patients additionally reported a history of multiple accidents. Conclusion: The majority of ADHD patients in our sample had not previously been diagnosed and were therefore not receiving treatment. The results subsequently suggest that general ADHD screening in trauma surgery patients may be useful in preventing further accidents in ADHD patients. Furthermore, psychoeducation regarding specific causal accident mechanisms could be implemented in ADHD therapy to decrease accident incidence rate. Full article

Adaptive behavior requires the adjustment of one’s behavioral repertoire to situational demands. The learning of situationally appropriate choice behavior can be operationalized as a task of Conditional Discrimination Learning (CDL). CDL requires the acquisition of hierarchical reinforcement relations, which may pose a particular challenge for children with Attention Deficit Hyperactivity Disorder (ADHD), particularly in light of documented deficits in short-term/working memory and delay aversion in ADHD. Using an arbitrary Delayed Matching-To-Sample task, we investigated whether children with ADHD (N = 46), relative to Typically Developing children (TD, N = 55), show a deficit in CDL under different choice delays (0, 8, and 16 s) and whether these differences are mediated by short-term/working memory capacity and/or delay aversion. Children with ADHD demonstrated poorer CDL than TD children under 8 and 16-second delays. Non-delayed CDL performance did not differ between groups. CDL differences were not mediated by short-term/working memory performance or delay aversion. Moreover, CDL performance under an 8-second delay was a better predictor of clinical status than short-term/working memory performance or delay aversion. CDL, under conditions of delay, is impaired in children with ADHD. This may lead to difficulties discriminating between different situational demands and adapting behavior according to the prevailing reward contingencies or expectations. Full article

Brain-derived neurotrophic factor (BDNF) facilitates neuronal growth and plasticity, and is crucial for learning and memory. Contactin-1 (CNTN1) is a member of the subfamily of neural immunoglobulin and is involved in the formation of axon connections in the developing nervous system. This cross-sectional study investigates whether BDNF and CNTN1 affect susceptibility to attention deficit/hyperactivity disorder (ADHD). A total of 136 drug-naïve patients with ADHD (108 boys and 28 girls) and 71 healthy controls (45 boys and 26 girls) were recruited. Blood samples were obtained to measure the plasma levels of BDNF and CNTN1 in each child. We found that BDNF levels in the ADHD boys exceeded those in the control boys, but BDNF levels in the ADHD girls were lower than those in the control girls. Boys who had higher BDNF levels performed worse on the Wechsler Intelligence Scale for Children—Fourth Edition, but girls who had higher BDNF levels made fewer omission errors in the Conners’ Continuous Performance Test. However, CNTN1 level did not differ significantly between patients and controls, and were not correlated to ADHD characteristics, regardless of gender. The findings suggest BDNF may influence sex-specific susceptibility to ADHD, but CNTN1 was not associated with ADHD pathophysiology. Full article

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent neuropsychiatric disorders in childhood and adolescence and its diagnosis is based on clinical interviews, symptom questionnaires, and neuropsychological testing. Much research effort has been undertaken to evaluate the usefulness of neurophysiological (EEG) data to aid this diagnostic process. In the current study, we applied deep learning methods on event-related EEG data to examine whether it is possible to distinguish ADHD patients from healthy controls using purely neurophysiological measures. The same was done to distinguish between ADHD subtypes. The results show that the applied deep learning model (“EEGNet”) was able to distinguish between both ADHD subtypes and healthy controls with an accuracy of up to 83%. However, a significant fraction of individuals could not be classified correctly. It is shown that neurophysiological processes indicating attentional selection associated with superior parietal cortical areas were the most important for that. Using the applied deep learning method, it was not possible to distinguish ADHD subtypes from each other. This is the first study showing that deep learning methods applied to EEG data are able to dissociate between ADHD patients and healthy controls. The results show that the applied method reflects a promising means to support clinical diagnosis in ADHD. However, more work needs to be done to increase the reliability of the taken approach. Full article

This study aims to investigate dietary and nutritional biochemistry profiles of attention-deficit/hyperactivity disorder (ADHD) and to explore their potential relationship by path analysis. We enrolled 216 children with ADHD and 216 age-, height- and gender-matched controls from 31 elementary schools in Taiwan. Dietary intake of the participants was assessed using a food frequency questionnaire (FFQ). Fasting blood samples were collected to determine the serum levels of multiple nutritional markers. Moreover, we employed a structural equation model (SEM) to link diet, nutritional markers and ADHD. Compared to healthy control, ADHD children had significantly lower serum levels of vitamin B12, folate, vitamin B6, ferritin concentration, and monounsaturated fatty acids (MUFA), but higher levels of serum saturated fatty acids (SFA), n-6/n-3 fatty acid ratio, and inorganic phosphorous concentration. Children with ADHD had more intake of nutrient-poor foods such as high sugar and high fat foods, and had less intake of vegetable, fruit, protein-rich foods than their counterpart. SEM analysis showed that the poor nutritional biochemistry profiles linked the association between unhealthy dietary patterns and ADHD. In conclusion, an unhealthy dietary pattern may be a predecessor of the poor nutritional biochemistry status, and managing diet and nutrition conditions should be considered to improve ADHD symptoms in children. Full article

Clinical trials in attention-deficit/hyperactivity disorder (ADHD) have typically measured outcome using clinician ratings on the Attention-Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale. Remission has been defined as an endpoint score of less than or equal to 18 on the ADHD-RS-IV (or a mean score of 1). Responders have been defined as patients who achieve a CGI-I score of much or very much improved (1 or 2). There is a lack of agreement in the literature on what percent change in symptoms on the ADHD-RS-IV should be used to define improvement or remission. This study uses data from a clinical trial of a methylphenidate extended release (MPH-MLR; Aptensio XR^®) phase III clinical trial to attempt to determine the percent change of symptoms that best corresponds with improvement and remission. Symptom remission at endpoint (ADHD-RS-IV total score ≤18) was most closely aligned with a ≥46% reduction in ADHD-RS-IV total score. Clinical improvement was most closely aligned with a ≥40% reduction in ADHD-RS-IV total score. The three different measures of outcome were strongly aligned during double blind and open label treatment, and were independent of subtype status. Our data suggest that at least 40% improvement in symptoms is needed to achieve a robust response at endpoint. Full article

Starting from the consolidated relationship between sleep and cognition, we reviewed the available literature on the association between Attention Deficit-Hyperactivity Disorder (ADHD) and sleep. This review analyzes the macrostructural and microstructural sleep features, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria (PRISMA). We included the polysomnographic studies published in the last 15 years. The results of macrostructural parameters are mixed. Almost half of the 18 selected investigations did not find differences between sleep architecture of children with ADHD and controls. Five studies observed that children with ADHD show a longer Rapid Eye Movement (REM) sleep duration than controls. Eight studies included microstructural measures. Remarkable alterations in sleep microstructure of ADHD are related to slow wave activity (SWA) and theta oscillations, respectively, during Non-REM (NREM) and REM sleep. Specifically, some studies found higher SWA in the ADHD group than controls. Similarly, higher theta activity appears to be detrimental for memory performance and inhibitory control in ADHD. These patterns could be interpreted as a maturational delay in ADHD. Also, the increased amount of these activities would be consistent with the hypothesis that the poor sleep could imply a chronic sleep deprivation in children with ADHD, which in turn could affect their cognitive functioning. Full article