Short Research Article: Impact of a prolonged lockdown on the symptoms of paediatric ADHD and common associated disorders.

OBJECTIVE: Our objective is to explore the change in the severity of ADHD, ODD and anxiety during a two-month lockdown among children in France and the moderating role of behavioural regulation. METHOD: In 235 children with ADHD, the symptom severity of ADHD, ODD and anxiety was investigated one and two months after the beginning of lockdown, and one month after its end. Behavioural regulation skills were estimated with the Behaviour Regulation Index. RESULTS: ADHD, ODD and anxiety scores were increasing or decreasing depending on BRI. CONCLUSION: Baseline behavioural regulation skills may act as a moderating factor for the persistence of ADHD, ODD and anxiety symptoms related to the lockdown.

Cross-sectional case-control study of the relationships between pharyngeal compliance and heart rate variability indices in childhood obstructive sleep apnoea.

A combination of noradrenergic and antimuscarinic agents reduces the apnea-hypopnea index (AHI) in adult patients with obstructive sleep apnoea (OSA) via reduced upper airway collapsibility, suggesting that a shift in the sympathovagal balance improves OSA. The objectives of our present case-control study were to assess heart rate variability (HRV) indices in the stages of sleep in children with and without OSA to evaluate OSA-induced sleep HRV modifications and to assess whether increased collapsibility measured during wakefulness is associated with reduced sympathetic activity during non-rapid eye movement (NREM) sleep. Three groups of 15 children were matched by sex, age, z-score of body mass index and ethnicity: non-OSA (obstructive AHI [OAHI] <2 events/hr), mild (OAHI ≥2 to <5 events/hr) or moderate-severe (OAHI ≥5 events/hr) OSA. Pharyngeal compliance was measured during wakefulness using acoustic pharyngometry. HRV indices (time and frequency domain variables) were calculated on 5-min electrocardiography recordings from polysomnography during wakefulness, NREM and REM sleep in periods free of any event. As compared to children without OSA, those with OSA (n = 30) were characterised by increased compliance and no physiological parasympathetic tone increase in REM sleep. Children with increased pharyngeal compliance (n = 21) had a higher OAHI due to higher AHI in NREM sleep, whereas their sympathetic tone was lower than that of those with normal compliance (n = 24). In conclusion, children with increased pharyngeal compliance exhibit decreased sympathetic tone associated with increased AHI in NREM sleep. Therapeutics directed at sympathovagal balance modifications should be tested in childhood OSA.

Practitioner Review: Current best practice in the use of parent training and other behavioural interventions in the treatment of children and adolescents with attention deficit hyperactivity disorder.

BACKGROUND: Behavioural interventions are recommended for use with children and young people with attention deficit hyperactivity disorder (ADHD); however, specific guidance for their implementation based on the best available evidence is currently lacking. METHODS: This review used an explicit question and answer format to address issues of clinical concern, based on expert interpretation of the evidence with precedence given to meta-analyses of randomised controlled trials. RESULTS: On the basis of current evidence that takes into account whether outcomes are blinded, behavioural intervention cannot be supported as a front-line treatment for core ADHD symptoms. There is, however, evidence from measures that are probably blinded that these interventions benefit parenting practices and improve conduct problems which commonly co-occur with ADHD, and are often the main reason for referral. Initial positive results have also been found in relation to parental knowledge, children's emotional, social and academic functioning - although most studies have not used blinded outcomes. Generic and specialised ADHD parent training approaches - delivered either individually or in groups - have reported beneficial effects. High-quality training, supervision of therapists and practice with the child, may improve outcomes but further evidence is required. Evidence for who benefits the most from behavioural interventions is scant. There is no evidence to limit behavioural treatments to parents with parenting difficulties or children with conduct problems. There are positive effects of additive school-based intervention for the inattentive subtype. Targeting parental depression may enhance the effects of behavioural interventions. CONCLUSIONS: Parent training is an important part of the multimodal treatment of children with ADHD, which improves parenting, reduces levels of oppositional and noncompliant behaviours and may improve other aspects of functioning. However, blinded evidence does not support it as a specific treatment for core ADHD symptoms. More research is required to understand how to optimise treatment effectiveness either in general or for individual patients and explore potential barriers to treatment uptake and engagement. In terms of selecting which intervention formats to use, it seems important to acknowledge and respond to parental treatment preferences.

Research review: the role of diet in the treatment of attention-deficit/hyperactivity disorder--an appraisal of the evidence on efficacy and recommendations on the design of future studies.

BACKGROUND: The efficacy of three dietary treatments for ADHD has been repeatedly tested in randomized controlled trials (RCTs). These interventions are restricted elimination diets (RED), artificial food colour elimination (AFCE) and supplementation with free fatty acids (SFFA). There have been three systematic reviews and associated meta-analyses of the RCTs for each of these treatments. SCOPE: The aim of this review is to critically appraise the studies on the dietary treatments of ADHD, to compare the various meta-analyses of their efficacy that have been published and to identify where the design of such RCTs could be improved and where further investigations are needed. FINDINGS: The meta-analyses differ in the inclusion and exclusion criteria applied to potentially eligible studies. The range of average effect sizes in standard deviation units is RED (0.29-1.2), AFCE (0.18-0.42) and SFFA (0.17-0.31). The methodology of many of the trials on which the meta-analyses are based is weak. CONCLUSIONS: Nevertheless, there is evidence from well-conducted studies for a small effect of SFFA. Restricted elimination diets may be beneficial, but large-scale studies are needed on unselected children, using blind assessment and including assessment of long-term outcome. Artificial food colour elimination is a potentially valuable treatment but its effect size remains uncertain, as does the type of child for whom it is likely to be efficacious. There are additional dietary supplements that have been used with children with ADHD. A systematic search identified 11 RCTs that investigated the effects of these food supplements. Despite positive results for some individual trials, more studies are required before conclusions can be reached on the value in reducing ADHD symptoms of any of these additional supplements.

From past to future: 50 years of pharmacological interventions to treat narcolepsy.

The history of narcolepsy research began with the pioneering work of Jean-Baptiste-Édouard Gélineau in the late 19th century. In the 1880s, Gélineau introduced the term "narcolepsy" to describe a condition characterized by sudden and uncontrollable episodes of sleep. His clinical descriptions laid the foundation for our understanding of this complex disorder. Over the last half-century, the pharmacological landscape for narcolepsy treatment has evolved remarkably, shifting from merely managing symptoms to increasingly targeting its underlying pathophysiology. By the 1930s, treatments such as ephedrine and amphetamine were introduced to alleviate excessive daytime sleepiness, marking significant advancements in narcolepsy management. These stimulants provided temporary relief, helping patients maintain wakefulness during the day. As research progressed, the focus shifted towards understanding the disorder's underlying mechanisms. The discovery of orexin (also known as hypocretin) in the late 1990s revolutionized the field. This breakthrough underscored the importance of orexin in regulating sleep-wake cycles and provided new targets for pharmacological intervention. Looking ahead, the future of narcolepsy pharmacotherapy is poised for further innovation. The ongoing exploration of orexin receptor agonists and the potential development of neuroprotective therapeutic targets underscore a promising horizon. Emerging research into the genetic and immunological underpinnings of narcolepsy opens new avenues for personalized medicine approaches and the identification of biomarkers for more precise treatment strategies. Additionally, the refinement of existing treatments through improved delivery systems and the investigation of combination therapies offer opportunities for enhanced efficacy and improved quality of life for patients with narcolepsy.

Association of Parent-Rated Sleep Disturbances With Attention-Deficit/Hyperactivity Disorder Symptoms: 9-Year Follow-up of a Population-Based Cohort Study.

OBJECTIVE: Symptoms of attention-deficit/hyperactivity disorder (ADHD) and sleep disturbances frequently co-occur, and can result in significant functional impairments that worsen quality of life. Despite a growing number of studies focusing on the association between sleep disturbances and ADHD symptoms over the last 20 years, the directionality of this association from childhood to early adulthood remains unclear. METHOD: A sample of French parents (n = 1,055) were followed-up over a 9-year period. At children mean ages of 9, 13, and 18 years, parents were interviewed about their children's ADHD symptoms and sleep disturbances. Random-intercept cross-lagged panel models assessed the directionality of the association from childhood to early adulthood. RESULTS: Parent-reported sleep disturbances at a mean age of 13 years predicted increased ADHD symptoms 5 years later. Additional analyses suggested that this effect might be limited to inattentive symptoms, and that ADHD symptoms at a mean age of 9 predicted increased sleep disturbances 4 years later. CONCLUSION: The present study provides evidence of a directional longitudinal association between parent-reported sleep disturbances and ADHD symptoms from adolescence to early adulthood. Our results highlight the importance of identifying sleep disturbances and ADHD symptoms for the design of preventive interventions. Future studies investigating this association in children with a clinical diagnosis of ADHD have the potential to provide important information for clinical practice.

Adjustment to lockdown in children and adolescents with narcolepsy in France.

STUDY OBJECTIVES: The goal of the current study was to explore the effect of a 2-month quarantine on children and adolescents with narcolepsy and to describe the changes in their sleep, mood, and metabolism during this period. METHODS: The study involved 77 patients aged 7 to 23 years with a diagnosis of narcolepsy. Participants had to answer multiple-choice questions to characterize the changes and modifications in their own habits and state of health. RESULTS: Participants reported changes in daytime sleep, nighttime sleep schedules, treatment intake, food intake, weight, and amount of screen time. Most patients reported deterioration in their memory and attention abilities as well as a decrease in their work efficiency. Mood appeared to be less affected, although it deteriorated in less than one-third of the participants who reported feeling sad more often. CONCLUSIONS: The prolonged and complete lockdown seemed to have an effect on children and adolescents with narcolepsy, and changes are often considered by the participants to depend on or to determine an overall quality of adaptation to the situation. This study highlights the importance of maintaining and strengthening time markers in individuals with narcolepsy and should help to establish guidelines that would apply in future quarantine situations. CITATION: de Laclause AP, Konofal E, Bokov P, Delclaux C, Lecendreux M. Adjustment to lockdown in children and adolescents with narcolepsy in France. J Clin Sleep Med. 2022;18(9):2247-2252.

Cross-sectional study of loop gain abnormalities in childhood obstructive sleep apnea syndrome.

STUDY OBJECTIVES: We aimed to assess ventilatory control in typically developing children with and without obstructive sleep apnea (OSA). METHODS: Otherwise healthy children referred for suspicion of OSA were recruited. In addition to polysomnography, we analyzed loop, controller and plant gains (ie, LG, CG, and PG), which reflect the stability of control, chemoreceptor sensitivity and the pulmonary control of blood gases in response to changes in ventilation, respectively, from tidal breathing recordings during wakefulness. Two bivariate (ventilation, end-tidal CO2: one unconstrained and one constrained) and one trivariate (plus end-tidal oxygen) unconstrained model were used to assess model consistency and oxygen chemosensitivity. RESULTS: In sum, 54 children (median age 11.6 years) were included. Children with OSA (n = 19, [obstructive apnea-hypopnea index] OAHI ≥2.h-1) had a higher plant gain compared with those without OSA (n = 35), and it was positively correlated with apnea hypopnea index (AHI) (r2 = 0.10, p < 0.020). The two models showed consistent results. The bivariate constrained model showed that children with OAHI ≥5.h-1 showed an increased steady-state plant gain compared with children with OAHI <5.h-1. The trivariate model did not show evidence of any abnormality of oxygen chemosensitivity. CONCLUSION: Plant gain may contribute to OSA pathophysiology in children, and therapies directed at its reduction should be tested.

Restless legs syndrome, rapid eye movement sleep behavior disorder, and hypersomnia in patients with two parkin mutations.

Parkin gene mutations cause a juvenile parkinsonism. Patients with these mutations may commonly exhibit REM sleep behaviour disorders, but other sleep problems (insomnia, sleepiness, restless legs syndrome) have not been studied. The aim of this study was to evaluate the sleep-wake phenotype in patients with two parkin mutations, compared with patients with idiopathic Parkinson's disease (iPD). Sleep interview and overnight video-polysomnography, followed by multiple sleep latency tests, were assessed in 11 consecutive patients with two parkin mutations (aged 35-60 years, from seven families) and 11 sex-matched patients with iPD (aged 51-65 years). Sleep complaints in the parkin group included insomnia (73% patients versus 45% in the iPD group), restless legs syndrome (45%, versus none in the iPD group, P = 0.04), and daytime sleepiness (45%, versus 54% in the iPD group). Of the parkin patients, 45% had REM sleep without atonia, but only 9% had a definite REM sleep behavior disorder. All sleep measures were similar in the parkin and iPD groups. Two parkin siblings had a central hypersomnia, characterized by mean daytime sleep latencies of 3 min, no sleep onset REM periods, and normal nighttime sleep. Although the patients with two parkin mutations were young, their sleep phenotype paralleled the clinical and polygraphic sleep recording abnormalities reported in iPD, except that restless legs syndrome was more prevalent and secondary narcolepsy was absent.

Periodic leg movements and REM sleep without atonia in Parkinson's disease with camptocormia.

Camptocormia (a flexion of the trunk that only appears when standing or walking) affects a minority of patients with Parkinson's disease (PD). As it responds poorly to levodopa and is associated with reduced midbrain and pons volume, it may result from non-dopaminergic, brainstem lesions. As several sleep abnormalities in PD also result from non-dopaminergic brainstem lesions, we monitored sleep in 24 non-demented PD patients with (n = 12) and without (n = 12) camptocormia and in 12 controls. Nearly half (42%) patients with camptocormia had abnormal periodic leg movement indices (>15/h), versus 17% patients without camptocormia and 8% of controls (p = 0.02). In addition, the percentage of enhanced muscle activity during REM sleep (measured on the chin and on the limb muscles) tended to be higher in patients with than without camptocormia (51 +/- 39% vs. 20 +/- 25%, p = 0.06). The other sleep and REM sleep characteristics (sleep and REM sleep onset latencies, sleep time and sleep stage percentages, REMs density, arousal, and apnea-hypopnea indices) were not different between these two PD groups. Lesions causing this axial dystonia may spare the sleep systems but affect the control of movements during sleep.

Effectiveness of ropinirole for RLS and depressive symptoms in an 11-year-old girl.

An 11-year-old girl was referred for an irresistible urge to move her legs associated with uncomfortable sensations. She was diagnosed with definite Restless Legs Syndrome (RLS) according to 2003 NIH criteria. The IRLSSG severity scale score was 31 (very severe). The girl also presented with dysthymic disorder according to DSM-IV criteria, as confirmed by the semi-structured interview Kiddie-SADS-PL. The score on the Children Depression Inventory (CDI) was in the clinical range (21). The total score on the Sleep Disturbance Scale for Children (SDSC) was 100. A standard PSG revealed a periodic limb movement index of 16.5, indicating that the child also presented with Periodic Limb Movements Disorder. The girl was treated with ropinirole (a D2/D3 dopamine agonist). After 3 months of treatment (0.50mg/day at 8.00 PM), RLS, as well as depressive symptoms, remarkably improved, as suggested by the improvement in the IRLSSG severity and CDI scores (14 and 4, respectively). No side effects were reported. The total score on the SDSC also improved (73). The PLM index did not remarkably change. We strongly recommend double blind, randomized, controlled studies to gain insight into the effective treatment strategies for RLS and depression when they coexist in children.

Two early descriptions of restless legs syndrome and periodic leg movements by Boissier de Sauvages (1763) and Gilles de la Tourette (1898).

Boissier de Sauvages de La Croix and Gilles de la Tourette, French neurologists, noticed that patients with "anxiety in the lower limbs, shooting pain, tingling legs" may have an insomnia "at the time of wake-sleep transition [and] experience sudden jerks in the lower limbs." Their descriptions confirm that the clinical features of RLS were previously described in French literature in the 18th century.

Dopamine dysregulation syndrome in a patient with restless legs syndrome.

A middle-aged architect, suffering from familial, idiopathic, levodopa-responsive restless legs syndrome (RLS) progressively abused levodopa for 10 years, to the point of taking 20 tablets/day (4000 mg/day) for 6 months. Such abuse (possibly linked to the rewarding effect of dopamine) has been recently monitored in the context of Parkinson's disease (PD) (the "dopamine dysregulation syndrome"). Physicians who now routinely treat RLS patients with dopaminergic agents should be aware of this abuse potential. This case also constitutes an experimental model. As levodopa abuse has only been described in patients with PD, it was suspected to be promoted by central dopamine depletion (with consequent sensitization of dopamine receptors). This idea should be revised because functional imaging showed that this RLS patient had no dopamine depletion. Later, he had no impulse disorders (no gambling, hypersexuality, excessive shopping), which occur with dopamine agonists, suggesting that levodopa abuse and impulse disorders can result through different mechanisms.

Sleep disturbances and serum ferritin levels in children with attention-deficit/hyperactivity disorder.

BACKGROUND: A subset of children with attention-deficit/hyperactivity disorder (ADHD) may present with impairing sleep disturbances. While preliminary evidence suggests that iron deficiency might be involved into the pathophysiology of daytime ADHD symptoms, no research has been conducted to explore the relationship between iron deficiency and sleep disturbances in patients with ADHD. The aim of this study was to assess the association between serum ferritin levels and parent reports of sleep disturbances in a sample of children with ADHD. SUBJECTS: Sixty-eight consecutively referred children (6-14 years) with ADHD diagnosed according to DSM-IV criteria using the semi-structured interview Kiddie-SADS-PL. MEASURES: parents filled out the Sleep Disturbance Scale for Children (SDSC) and the Conners Parent Rating Scale (CPRS). Serum ferritin levels were determined using the Tinaquant method. RESULTS: Compared to children with serum ferritin levels >or=45 microg/l, those with serum ferritin levels <45 microg/l had significantly higher scores on the SDSC subscale "Sleep wake transition disorders" (SWTD) (P = 0.042), which includes items on abnormal movements in sleep, as well as significantly higher scores on the CPRS-ADHD index (P = 0.034). The mean scores on the other SDSC subscales did not significantly differ between children with serum ferritin >or=45 and <45 microg/l. Serum ferritin levels were inversely correlated to SWTD scores (P = 0.043). CONCLUSION: Serum ferritin levels <45 microg/l might indicate a risk for sleep wake transition disorders, including abnormal sleep movements, in children with ADHD. Our results based on questionnaires set the basis for further actigraphic and polysomnographic studies on nighttime activity and iron deficiency in ADHD. Research in this field may suggest future trials of iron supplementation (possibly in association with ADHD medications) for abnormal sleep motor activity in children with ADHD.

A 9-Year Follow-Up of Attention-Deficit/Hyperactivity Disorder in a Population Sample.

BACKGROUND: Prior follow-up studies of attention-deficit/hyperactivity disorder (ADHD) have mostly been from North America. They have provided a good deal of information about ADHD, but whether these results generalize to population samples and to other countries is not certain. Most prior studies have also not assessed predictors of possible new onsets of ADHD in non-ADHD youth or the validity of subthreshold forms of the disorder. METHODS: 1,012 families were recruited at baseline, when a telephone interview assessed a child in the 6-12 years age range. The interview covered symptoms of ADHD, conduct disorder, and oppositional defiant disorder as well as family living situation, school performance, sleep disturbance, eating habits, use of supplemental iron, and history of ADHD treatment. Nine years later, the persistence of ADHD and its impairments and the emergence of new conditions were assessed. DSM-5 diagnostic criteria were used to diagnose ADHD. RESULTS: 492 of the 1,012 participants seen at baseline were followed up 9 years later, at a mean age of 18 years. At follow-up, 16.7% of the children diagnosed with ADHD at baseline met full criteria for ADHD and 11.1% met criteria for subthreshold ADHD, yielding a persistence rate of 27.8%. Among children not diagnosed with ADHD at baseline, 1.1% met criteria for ADHD at follow-up. The persistence of ADHD and new onsets of ADHD were predicted by several baseline clinical features and by a family history of ADHD. CONCLUSIONS: We replicated predictors of the persistence of ADHD found in prior studies and provide new data about predictors of new ADHD onsets in the population. Our findings about subthreshold ADHD support a dimensional conceptualization of the disorder, highlighting the potential clinical utility of a subthreshold diagnostic category. This study also contributes to the ongoing debate regarding adult-onset ADHD.

The utility of acoustic pharyngometry and rhinometry in pediatric obstructive sleep apnea syndrome.

OBJECTIVE: Our objective was to evaluate the usefulness of acoustic pharyngometry and rhinometry in assessing obstructive sleep apnea (OSA) syndrome in children. PATIENTS/METHODS: Patients who were hospitalized for polysomnography underwent acoustic pharyngometry and rhinometry in sitting and supine positions to measure anatomical (pharyngeal and nasopharyngeal) volumes and collapsibility characteristics (reduction of pharyngeal volume, estimated pharyngeal compliance, and reduction of nasopharyngeal volume). RESULTS: In this study, we prospectively enrolled 103 children (median age, 10.4 years; 47 girls). Measures obtained from rhinometry correlated with height and were further height-normalized whereas measures obtained from pharyngometry did not correlate with height. Sleep apnea was ruled out in 51 subjects, while 52 children fulfilled OSA criteria (35 with obstructive apnea-hypopnea index ≥ 2 and < 5.h-1 [mild] and 17 with an index ≥ 5). The three groups differed on the z-score of BMI, the reduction of pharyngeal volume when supine, the estimated pharyngeal compliance and the supine normalized nasopharyngeal volume. These four factors linearly correlated with the apnea index even though children without OSA and mild OSA were found to be similar overall. A multivariate analysis with apnea index as the dependent variable and BMI z-score, neck circumference, mean pharyngeal area in supine position, estimated pharyngeal compliance and normalized nasopharyngeal volume as independent variables, showed that only BMI z-score and estimated compliance remained independent predictors of obstructive apnea (r2 value = 0.25, p < 0.0001). CONCLUSION: An increase in pharyngeal compliance is an independent risk factor of OSA syndrome in children; it can be measured using acoustic pharyngometry while awake.

Attention-deficit/hyperactivity disorder (ADHD) and obesity: a systematic review of the literature.

Recent studies suggest a possible comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD) and obesity. To gain insight into this potential association, we performed a systematic review of the literature excluding case reports, non-empirical studies, and studies not using ADHD diagnostic criteria. Empirically based evidence suggests that obese patients referred to obesity clinics may present with higher than expected prevalence of ADHD. Moreover, all reviewed studies indicate that subjects with ADHD are heavier than expected. However, data on the prevalence of obesity in subjects with ADHD are still limited. As for the mechanisms underlying the potential association between ADHD and obesity, ADHD might lead to obesity via abnormal eating behaviors, impulsivity associated with binge eating might contribute to ADHD in obese patients, or, alternatively, both obesity and ADHD might be the expression of common underlying neurobiological dysfunctions, at least in a subset of subjects. In patients with obesity and ADHD, both conditions might benefit from common therapeutic strategies. Further empirically based studies are needed to understand the potential comorbidity between obesity and ADHD, as well as the possible mechanisms underlying this association. This might allow a more appropriate clinical management and, ultimately, a better quality of life for patients with both obesity and ADHD.

Effects of iron supplementation on attention deficit hyperactivity disorder in children.

Iron deficiency has been suggested as a possible contributing cause of attention deficit hyperactivity disorder (ADHD) in children. This present study examined the effects of iron supplementation on ADHD in children. Twenty-three nonanemic children (aged 5-8 years) with serum ferritin levels <30 ng/mL who met DSM-IV criteria for ADHD were randomized (3:1 ratio) to either oral iron (ferrous sulfate, 80 mg/day, n = 18) or placebo (n = 5) for 12 weeks. There was a progressive significant decrease in the ADHD Rating Scale after 12 weeks on iron (-11.0 +/- 13.9; P < 0.008), but not on placebo (3.0 +/- 5.7; P = 0.308). Improvement on Conners' Parent Rating Scale (P = 0.055) and Conners' Teacher Rating Scale (P = 0.076) with iron supplementation therapy failed to reach significance. The mean Clinical Global Impression-Severity significantly decreased at 12 weeks (P < 0.01) with iron, without change in the placebo group. Iron supplementation (80 mg/day) appeared to improve ADHD symptoms in children with low serum ferritin levels suggesting a need for future investigations with larger controlled trials. Iron therapy was well tolerated and effectiveness is comparable to stimulants.

Alertness and feeding behaviors in ADHD: does the hypocretin/orexin system play a role?

Increasing evidence has suggested that patients with attention-deficit/hyperactivity disorder (ADHD) may present with a deficit of alertness and sleep disturbances. Recent studies have also pointed out a previously underestimated association between ADHD and abnormal eating behaviors, including binge eating. Since sleep/alertness disturbances and eating disorders may significantly increase the functional impairment of ADHD, gaining insight into their pathophysiology as well as into their treatment is of relevance to provide a better clinical management of patients suffering from ADHD. The hypocretin/orexin system comprises two distinct peptides, located in the hypothalamus, which are involved in several homeostatic functions. In particular, it has been suggested that hypocretin/orexin neurons located in perifornical and dorsomedial hypothalamic nuclei increase arousal, whereas those located in the lateral hypothalamus are primarily implicated in reward processing, stimulating feeding and other reward seeking behaviors. Given the involvement of the hypocretin/orexin system in the control of alertness and reward seeking (including feeding), we hypothesize that hypocretin/orexin neurons located in perifornical and dorsomedial hypothalamic areas are hypoactivated, while those located in the lateral hypothalamus are overactivated in patients with ADHD. If confirmed by further neurophysiological, imaging, and genetics studies, our hypothesis may help us progress in the understanding of the complex pathophysiology of ADHD. This might set the basis for the study of novel molecules, acting on the hypocretin/orexin system, aimed at increasing wakefulness and reducing binge eating and other abnormal reward seeking behaviors in patients with ADHD. We also suggest future studies on the potential therapeutic role of other molecules which have a complex interplay with the hypocretin/orexin system, such as the histamine H(1) receptor agonists, the histamine H(3) receptor antagonists, and the neuropeptide Y receptor antagonists. All this body of research would provide a tremendous opportunity to improve the quality of life of patients with ADHD by means of pathophysiologically oriented treatment.

Does excessive daytime sleepiness contribute to explaining the association between obesity and ADHD symptoms?

Recent studies suggest a significant association between obesity and attention-deficit/hyperactivity disorder (ADHD). The factors underlying this newly described comorbidity are still unclear and unexplored. In the present article, we propose that excessive daytime sleepiness (EDS) contributes to explaining the association between ADHD and obesity. The background for this hypothesis comes from studies on the association between ADHD and EDS, as well as from investigations on EDS in obese individuals. Available studies suggest that ADHD behaviours are significantly associated with EDS. Moreover, increasing evidence indicates that obesity is significantly associated with EDS independently of sleep-disordered breathing (SDB) or any other sleep disorders. Given the relationship between EDS and ADHD behaviors, we hypothesize that the higher than expected rates of EDS in obese individuals contribute to explaining the association between obesity and ADHD behaviors. We further speculate on the role of the brain derived neurotrophic factor (BDNF) and other molecules such as the proinflammatory cytokines IL-6 and TNF-alpha. Our hypothesis generates potentially relevant clinical and therapeutic implications. From a clinical standpoint, it may suggest to systematically look for ADHD symptoms (including hyperactivity and impulsivity) in obese patients described as sleepy. With regard to the therapeutic implications, we suggest that wake-promoting agents with anorexigenic effect, such as mazindol, might be particularly indicated for the treatment of ADHD symptoms in obese patients, since they might address both ADHD symptoms and weight reduction. In conclusion, considering the burden that ADHD adds to obesity, we believe that further studies on the comorbidity between obesity and ADHD are necessary. Research on the role of EDS might allow advancements in this field, suggesting a more effective management and, ultimately, a better quality of life of patients with both obesity and ADHD.