Clinically Oriented Subtyping of Chronic Insomnia of Childhood.

OBJECTIVES: To identify different profiles of pediatric insomnia, based on the most frequent clinical presentations (nocturnal awakenings, difficulty in falling asleep, nocturnal restlessness, early morning awakenings). STUDY DESIGN: A structured parent interview was conducted in 338 children (mean age 21.29 months, SD 10.56) referred by pediatricians because of insomnia resistant to behavioral approaches and common drug treatments. The aim was to assess the characteristics of insomnia in children, together with family sleep-related history. A latent class analysis was run to identify profiles of insomnia. ANOVA and the χ2 test were used to examine differences between profiles. RESULTS: A 3-class model was built by latent class analysis: 17% (n = 58) of children constituted the first class, characterized by difficulties in falling asleep, with restlessness, nocturnal restlessness, and awakenings during the night; the second class, characterized by early morning awakenings, comprised 21% (n = 71) of children; 62% (n = 209) of children fell within the third class because of their high frequency of nocturnal awakenings and difficulties in falling asleep. The first class reported longer sleep latency and the presence of restless legs syndrome and anemia in the family history; depression and/or mood disorders were more frequent in class 2 and allergies and/or food intolerance were more frequent in class 3. CONCLUSIONS: Our study suggests the existence of 3 different phenotypes of insomnia in children, based on clinical, personal, and familial data. The identification of these different phenotypes might help to optimize the assessment and treatment of insomnia in young children.

Practitioner Review: Treatment of chronic insomnia in children and adolescents with neurodevelopmental disabilities.

BACKGROUND: Sleep disturbances, in particular insomnia, represent a common problem in children with neurodevelopmental disabilities (NDDs). Currently, there are no approved medications for insomnia in children by the US Food and Drug Administration or European Medicines Agency and therefore they are prescribed off-label. We critically reviewed pediatric literature on drugs as well as nonpharmacological (behavioral) interventions used for sleep disturbances in children with NDDs. METHODS: PubMed, Ovid (including PsycINFO, Ovid MEDLINE® , and Embase), and Web of Knowledge databases were searched through February 12, 2017, with no language restrictions. Two authors independently and blindly performed the screening. RESULTS: Good sleep practices and behavioral interventions, supported by moderate-to-low level evidence, are the first recommended treatments for pediatric insomnia but they are often challenging to implement. Antihistamine agents, such as hydroxyzine or diphenhydramine, are the most widely prescribed sedatives in the pediatric practice but evidence supporting their use is still limited. An increasing body of evidence supports melatonin as the safest choice for children with NDDs. Benzodiazepines are not recommended in children and should only be used for transient insomnia, especially if daytime anxiety is present. Only few studies have been carried out in children's and adolescents' zolpidem, zaleplon, and eszopiclone, with contrasting results. Limited evidence supports the use of alpha-agonists such as clonidine to improve sleep onset latency, especially in attention deficit/hyperactivity disorder subjects. Tricyclic antidepressants, used in adults with insomnia, are not recommended in children because of their safety profile. Trazodone and mirtazapine hold promise but require further studies. CONCLUSIONS: Here, we provided a tentative guide for the use of drugs for insomnia in children with NDDs. Well-controlled studies employing both objective polysomnography and subjective sleep measures are needed to determine the efficacy, effectiveness, and safety of the currently prescribed pediatric sleep medicines in children with NDDs.

Early and effective treatment of KCNQ2 encephalopathy.

OBJECTIVES: To describe the antiepileptic drug (AED) treatment of patients with early infantile epileptic encephalopathy due to KCNQ2 mutations during the neonatal phase and the first year of life. METHODS: We identified 15 patients and reviewed the electroclinical, neuroimaging, and AED treatment data. RESULTS: Seizure onset was between 1 and 4 days of age with daily tonic asymmetric, focal and clonic seizures in nine patients and status epilepticus in the remaining six. Electroencephalography (EEG) showed multifocal epileptiform abnormalities in nine patients and a burst-suppression pattern in six. All patients were trialed with adequate daily doses of several AEDs before they reached seizure freedom. Six patients (40%) achieved seizure control within 2 weeks of carbamazepine (CBZ) administration and five (33%) were seizure-free with phenytoin (PHT). The last four patients (27%) were successfully treated with topiramate (TPM) (two patients), levetiracetam (LEV) (one), and a combination of LEV with TPM (one). Most patients reached seizure freedom within the first year of life and remained seizure-free thereafter. Twelve patients had moderate-to-severe developmental delay at follow-up. However, the two patients whose seizures ceased within a few days of onset showed only mild cognitive impairment. SIGNIFICANCE: Our findings suggest that drugs acting on sodium channels including CBZ and PHT should be considered as first-line treatment in patients with KCNQ2 encephalopathy. Voltage-gated sodium and potassium channels co-localize at the neuronal membrane. Therefore, the efficacy of drugs acting as sodium-channel blockers could be linked to their modulating effect on both channels. The type of KCNQ2 mutation might influence AED response as well as developmental outcome. Early recognition of KCNQ2 encephalopathy followed by the most appropriate and effective treatment may be important for reducing the neurodevelopmental impairment associated with this disorder.

Sleep in children with neurodevelopmental disabilities.

This review describes recent research in pediatric sleep disorders associated with neurodevelopmental disabilities (NDDs) and their treatment. NDDs affect more than 2% of the general population and represent more than 35% of the total cases of children referred to a neuropsychiatric center for sleep problems. Specific clinical and therapeutic aspects of sleep disorders associated with Down syndrome, Fragile X syndrome, Prader-Willi syndrome, Angelman syndrome, Rett syndrome, Smith-Magenis syndrome, cerebral palsy, and autism spectrum disorders are described. Furthermore, the drugs commonly used for sleep disorders in children with NDDs are described. The review clearly highlighted that children with NDDs are often affected by sleep disorders that require appropriate clinical and therapeutic approach to improve quality of life in both patients and families.

Pediatric insomnia: new insights in clinical assessment and treatment options.

Sleep disorders in children can compromise quality of life of both children and families and chronic sleep deprivations is associated with poorer developmental outcome, overweight and behavioral disturbances. Clinicians should incorporate questions about sleep into their routine health assessment, and the assessment of insomnia should follow a medical approach primary and secondary contributing factors should be assessed, as well as maladaptive behaviors related to sleep. A careful examination of sleep/wake schedule, abnormal movements or behavior during sleep, and daytime consequences of sleep disruption or deprivation is mandatory. Sleeping environment, and bedtime routines should be examined to identify behavioral issues related to sleep. Polysomnography is not routinely indicated for children with insomnia, but actigraphy can give an objective estimation of sleep parameters. The Authors propose a new classification of pediatric insomnia, based on both genetic and clinical aspects, and suggest specific treatment options, including sleep hygiene, behavioral strategies and pharmacological treatment.

Individualized approaches to pediatric chronic insomnia: Advancing precision medicine in sleep disorders.

The manifestations of chronic insomnia undergo age-related changes. In younger infants and children, behavioral insomnia emerges as the most prevalent form and typically responds to behavioral interventions. However, distinct clusters of clinical presentations suggest the presence of various phenotypes, potentially implicating the primary involvement of specific neurotransmitters. These conceptualizations, coupled with genetic studies on pleiotropy and polygenicity, may aid in identifying individuals at risk of persistent insomnia into adulthood and shed light on novel treatment options. In school-age children, the predominant presentation is sleep-onset insomnia, often linked with nighttime fears, anxiety symptoms, poor sleep hygiene, limit-setting issues, and inadequate sleep duration. The manifestations of insomnia in adolescence correlate with the profound changes occurring in sleep architecture, circadian rhythms, and homeostatic processes. The primary symptoms during adolescence include delayed sleep onset, sleep misperception, persistent negative thoughts about sleep, and physiological hyperarousal-paralleling features observed in adult insomnia. An approach centered on distinct presentations may provide a framework for precision-based treatment options. Enhanced comprehension of insomnia's manifestations across diverse developmental stages can facilitate accurate assessment. Efforts to subtype insomnia in childhood align with this objective, potentially guiding the selection of appropriate treatments tailored to individual neurobiological, clinical, and familial features.

Attention-deficit/hyperactivity disorder and impairment in executive functions: a barrier to weight loss in individuals with obesity?

BACKGROUND: An increasing body of research points to a significant association of obesity to Attention-Deficit/Hyperactivity Disorder (ADHD) and deficits in executive functions. There is also preliminary evidence suggesting that children with ADHD may be at risk of obesity in adulthood. DISCUSSION: In this article, we discuss the evidence showing that ADHD and/or deficits in executive functions are a barrier to a successful weight control in individuals enrolled in weight loss programs. Impairing symptoms of ADHD or deficits in executive functions may foster dysregulated eating behaviors, such as binge eating, emotionally-induced eating or eating in the absence of hunger, which, in turn, may contribute to unsuccessful weight loss. ADHD-related behaviors or neurocognitive impairment may also hamper a regular and structured physical activity. There is initial research showing that treatment of comorbid ADHD and executive functions training significantly improve the outcome of obesity in individuals with comorbid ADHD or impairment in executive functions. SUMMARY: Preliminary evidence suggests that comorbid ADHD and deficits in executive functions are a barrier to a successful weight loss in individuals involved in obesity treatment programs. If further methodologically sound evidence confirms this relationship, screening and effectively managing comorbid ADHD and/or executive functions deficits in individuals with obesity might have the potential to reduce not only the burden of ADHD but also the obesity epidemics.

The Italian contribution to pediatric sleep medicine: A scientometric analysis.

We conducted the first scientometric analysis to quantitatively assess the scientific contribution of researchers from Italian institutions in the field of pediatric sleep medicine. We searched Science Citation Index Expanded from Web of Science (WOS) Science Citation up to November 3rd, 2022. Bibliometrix R packages (3.1.4) and CiteSpace (6.0.R2) were used to extract and analyze co-citation reference networks, co-occurring keyword networks, co-authorship network, co-cited institutions, and co-cited journals. We retrieved a total of 2499 documents, published between 1975 and 2022. Co-cited reference networks showed four main clusters of highly cited topics: evidence synthesis of publications on sleep disorders in children and adolescents, sleep and neurological disorders, non-pharmacological treatments of sleep disturbances, and sleep and Covid-19 in youth. Co-occurring keyword networks showed an earlier focus on the neurophysiology of sleep/neurological disorders, followed by a trend on the association of sleep disturbances to neurodevelopmental disorders and behavioral aspects. Co-authorship network showed that Italian researchers in the field of pediatric sleep medicine tend to be highly collaborative internationally. Overall, Italian researchers have provided a crucial contribution to pediatric sleep medicine across a number of specific topics, spanning from neurophysiology to treatment, and from neurological to behavioral/psychopathological aspects.

Increased parental perception of sleep disordered breathing in a cohort of infants with ALTE/BRUE events.

BACKGROUND: An apparent life-threatening event (ALTE) describes an acute, unexpected change in an infant's breathing, aspect, or behavior frightening to the parent or caretaker. According to the new recent terminology, clinicians should use the term brief resolved unexplained event (BRUE) to describe an event occurring in an infant <1 year of age when the observer reports a sudden, brief, and now resolved episode. The aims of the present study in infants were to investigate sleep disturbances in both ALTE event and after their classification according the new BRUE criteria. METHODS: We enrolled (from April to May 2016) 32 consecutive infants referred to our ambulatory for sleep disorders for follow-up after an ALTE episode and 32 pair healthy controls. We administered to parents the adapted questionnaire "Sleep Disturbance Scale for Children - SDSC." RESULTS: Among enrolled infants with ALTE, there were 26 infants in line with the new BRUE definition, of which 10 at low risk and 16 at the high-risk event. CONCLUSIONS: Infants with ALTE and BRUE had more referred-by-parents' sleep symptoms than controls. In particular, sleep disordered breathing wa prevalent in both, requiring a longer follow-up for this disturbance.

Chronic insomnia of early childhood: Phenotypes and pathophysiology.

This paper aims to review the limitations of the current classification of insomnia of early childhood and propose a new conceptual model allowing a better understanding of its pathophysiology. Our hypothesis is that chronic insomnia of childhood has different phenotypical expressions, associated to different pathophysiological mechanisms. Based on a long-lasting experience in evaluating a very large number of children with specific insomnia symptoms (nocturnal awakenings, difficulty in falling asleep, nocturnal restlessness, early morning awakenings) and on published data, we hypothesize that different phenotypes of insomnia might exist with different therapeutic implications. We describe three phenotypes of insomnia in early childhood: a) insomnia with motor restlessness; b) insomnia characterized without difficulties in falling asleep but with long-lasting early morning awakenings; c) insomnia with multiple night awakenings and falling asleep difficulty. This type of categorization might have important implications for treatment, based on the different hypothetical neurotransmitter dysfunctions. The early identification of a phenotype of insomnia might guide to specific behavioral and/or pharmacological interventions with the aim to prevent chronic insomnia.

Association Between Exposure to Pesticides and ADHD or Autism Spectrum Disorder: A Systematic Review of the Literature.

OBJECTIVE: To conduct a systematic review of studies assessing the relationship between exposure to pesticides and ADHD or Autism Spectrum Disorder (ASD). METHODS: Based on a pre-registered protocol in PROPSERO (CRD42018107847), we searched PubMed, Ovid databases, and ISI Web of Knowledge with no date/language/document type restrictions, up to May 2019. The Newcastle Ottawa Scale was used to assess study quality. RESULTS: Among the 29 retained studies, 13 focused on ADHD, 14 on ASD, and two on both disorders. Ten studies reported a significant association between exposure to pesticides and ADHD/ADHD symptoms and 12 studies found a significant association with ASD/ASD traits. The strengths of the association and the possible confounders controlled for varied substantially across studies. CONCLUSION: Whilst there is some evidence suggesting a possible link between pesticides and ADHD/ASD, heterogeneity across studies prevents firm conclusions. We provide methodological indications for future studies.

Impact of intermittently scanned continuous glucose monitoring with alarms on sleep and metabolic outcomes in children and adolescents with type 1 diabetes.

AIMS: Data about sleep quality and quantity are not available in patients with type 1 diabetes (T1D) using intermittently scanned continuous glucose monitoring (isCGM). We questioned whether the isCGM with alarms could fragment sleep in patients and parents, compared to isCGM without alarms. METHODS: A prospective, observational study including 47 child-adolescents with T1D who had experience with isCGM without alarms (Freestyle Libre 1-FSL1). They were asked to wear the isCGM with alarms (Freestyle Libre 2-FSL2) for 14 days. Patients enrolled and their caregiver (s), during a 14 day period with FSL1 and the following 14 days with FSL2, completed psychosocial and sleep-related questionnaires. Furthermore they wore an actigraph that was downloaded to a web platform and processed by the validated and certified algorithm "Dormi®." RESULTS: By the switch to the alarmed FSL2 we found about a 5% increase in Time In Range (from 62.5 to 67.8%), a reduction in time spent in hypoglycemia, number of weekly hypoglycemic events, and coefficient of variation. We did not find significant differences in sleep parameters in patients and their parents; therefore, alarms did not worsen the duration and quality of sleep. A significant improvement in the Quality of Life was perceived by parents using FSL2. CONCLUSIONS: Introduction of alarms in isCGM systems gives, in the short term, an improvement in metabolic control in terms of time in range and reduction in hypoglycemia, without worsening duration and quality of sleep, measured by actigraphy, in children-adolescent and their parents.

Sleep Disorders in Children and Adolescents with Autism Spectrum Disorder: Diagnosis, Epidemiology, and Management.

Sleep problems are a common complaint in children/adolescents with autism spectrum disorder (ASD). Correctly diagnosing and treating sleep problems in individuals with ASD is key, as they can add to the psychosocial burden of the disorder and exacerbate associated symptoms, such as inattention or irritability. Here, we provide an overview of the epidemiology, diagnosis, and management of sleep problems/disorders in children and adolescents with ASD. This narrative review is mainly informed by a systematic search in PubMed and PsycInfo (last search: 10 October 2019) of available pertinent meta-analyses. We also searched for randomized controlled trials (RCTs) published after the search date of available meta-analyses. As for the epidemiology of sleep disorders in ASD, recent meta-analytic evidence shows a pooled prevalence of 13% (95% confidence interval [CI] 9-17) in the ASD population, compared with 3.7% in the general population. In terms of diagnosis of sleep disorders, it should be based on standardized criteria [e.g., the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) or third edition of the International Classification of Sleep Disorders (ICSD)]; clinicians should bear in mind that the communication difficulties presented by individuals with ASD may make the diagnostic process more challenging. Regarding the treatment, a meta-analysis of behavioral interventions, including only three RCTs, found significant effects in terms of increase in total sleep time (24.41 min, 95% CI 5.71-43.11, P = 0.01), decrease in sleep-onset latency (- 18.31 min, 95% CI - 30.84 to - 5.77, P = 0.004), and a significant effect on sleep efficiency (5.59, 95% CI 0.87-10.31, P = 0.02), albeit the risk of bias of the included studies was rated "high" in relation to issues with the blinding. The bulk of the evidence for the pharmacological treatment is for melatonin, with a meta-analysis of five double-blind RCTs showing a large effect size, favoring melatonin, in sleep duration (44 min compared with placebo, Hedge's g 1.07 [95% CI 0.49-1.65]) and sleep-onset latency (39 min compared with placebo, Hedge's g - 2.46 [95% CI - 1.96 to - 2.98]). We conclude that additional RCTs are desperately needed to support the management of sleep disorders in ASD with an evidence-based, precision medicine approach.

Executive functions in preschool children with chronic insomnia.

STUDY OBJECTIVES: Executive functions (EFs) in children with insomnia have not been sufficiently assessed in the literature. This study aimed to describe sleep patterns and habits and EF abilities in preschool children with insomnia, compared to healthy control patients, and to evaluate the relationships between sleep patterns and EFs. METHODS: Two groups of children were recruited: 45 preschoolers with chronic insomnia (28 boys), aged 24-71 months and 167 healthy preschool children (81 boys) aged 24-71 months. Parents of all children completed two questionnaires to assess their children's sleep habits and disturbances, and their EFs with the Behavior Rating Inventory of Executive Function - Preschool Version. RESULTS: Children with chronic insomnia were found to wake up earlier, sleep less during the night, have more nighttime awakenings, and higher nocturnal wakefulness, compared to the control group. The chronic insomnia group showed significant impairment in all the EFs domains. Nocturnal sleep duration, nighttime awakenings, and nocturnal wakefulness correlated with inhibit, plan/organize, working memory, inhibitory self-control, emergent metacognition, and the global executive composite scores in the chronic insomnia group. In the control group, the number of nighttime awakenings correlated with inhibition, inhibitory self-control, and the global executive composite. Regression analyses showed a predominant role of insomnia factor in the association with EFs in both clinical and control groups. CONCLUSIONS: Our findings confirm the link between sleep and "higher level" cognitive functioning. The preschool period represents a critical age during which transient sleep problems also might hamper the development of self-regulation skills and the associated neural circuitry.

Infantile spasms followed by childhood absence epilepsy: A case series.

PURPOSE: Infantile spasms (IS) represent a severe seizure disorder of infancy and early childhood characterized by epileptic spasms along with hypsarrhythmia often accompanied by intellectual disability. According to the current classification and terminology (3) IS can be categorized as known etiology, formerly known as "symptomatic", when an underlying cause has been observed prior to the onset of spasms, or of "unknown cause" with "unfavorable" and "favorable" outcome (previously referred as "cryptogenic" or "idiopathic", respectively). Single reports described children with "unknown cause and favorable outcome" (UC/FO) IS who later developed childhood absence epilepsy (CAE). This study aims to determine the prevalence of CAE following IS. METHODS: a multicenter retrospective chart review was performed; children with UC/FO IS who subsequently developed CAE during follow-up were identified. Eight Italian pediatric epilepsy centers participated in this study. RESULTS: seven out of 24 (29 %) children (3 males) showing a favorable outcome (UC/FO) IS received a second diagnosis of CAE during follow-up. Mean age at IS presentation was 5.8 months (SD ± 0.9). All achieved seizure control of IS at a mean age of 8.5 months (SD ± 1.3) (3 monotherapy, 4 polytherapy). CAE was diagnosed at a mean age of 8.0 years (SD ± 3.0). Six children achieved sustained remission of CAE with valproic acid, whereas 1 child required dual therapy by adding ethosuximide. CONCLUSION: although it is not possible to determine whether the association between UC/FO IS and CAE implies a causality relationship, the later occurrence of CAE in patients with UC/FO IS might support a possible role of thalamo-cortical dysfunction.

Genotype-phenotype correlations in patients with de novo KCNQ2 pathogenic variants.

OBJECTIVE: Early identification of de novo KCNQ2 variants in patients with epilepsy raises prognostic issues toward optimal management. We analyzed the clinical and genetic information from a cohort of patients with de novo KCNQ2 pathogenic variants to dissect genotype-phenotype correlations. METHODS: Patients with de novo KCNQ2 pathogenic variants were identified from Italy, Denmark, and Belgium. Atomic resolution Kv7.2 structures were also generated using homology modeling to map the variants. RESULTS: We included 34 patients with a mean age of 4.7 years. Median seizure onset was 2 days, mainly with focal seizures with autonomic signs. Twenty-two patients (65%) were seizure free at the mean age of 1.2 years. More than half of the patients (17/32) displayed severe/profound intellectual disability; however, 4 (13%) of them had a normal cognitive outcome.A total of 28 de novo pathogenic variants were identified, most missense (25/28), and clustered in conserved regions of the protein; 6 variants recurred, and 7 were novel. We did not identify a relationship between variant position and seizure offset or cognitive outcome in patients harboring missense variants. Besides, recurrent variants were associated with overlapping epilepsy features but also variable evolution regarding the intellectual outcome. CONCLUSIONS: We highlight the complexity of variant interpretation to assess the impact of a class of de novo KCNQ2 mutations. Genetic modifiers could be implicated, but the study paradigms to successfully address the impact of each single mutation need to be developed.

The relationship between body size and depression symptoms in adolescents.

OBJECTIVE: To evaluate the relationship between body size and depressive symptoms, as well as the moderating effects of age, sex, and socioeconomic status (SES), in a sample of young adolescents. STUDY DESIGN: The study group comprised 678 young adolescents (age 11 to 14 years). Body mass index (BMI) z scores were used to estimate body size. Depression symptoms were assessed using the Children's Depression Inventory (CDI). The spline function was used to examine the shape of the relationship between BMI z score and depressive symptoms. RESULTS: In the total sample, CDI scores were lowest for BMI z scores between -1 and -0.5. CDI scores increased progressively for BMI z scores > 0. In boys, CDI scores increased for BMI z scores > 2, whereas in girls, CDI scores increased for BMI z scores > -0.5 and < -1. Age did not have a significant moderating effect. SES had a moderating effect only in boys (P = .011). CONCLUSIONS: The relationship between body size and depressive symptoms in young adolescents is curvilinear and is moderated by sex. Heavier-than-average and underweight girls, as well as obese boys, had the highest depression scores.

Pharmacotherapeutic management of sleep disorders in children with neurodevelopmental disorders.

Introduction: Sleep disturbances are highly prevalent in children with neurodevelopmental disabilities. Without appropriate treatment, sleep disorders can become chronic and last for many years. However, there are no sleep medications approved by the United States Food and Drug Administration and only one has been approved by the European Medicines Agency for pediatric insomnia; thus, most medications are prescribed off-label.Areas covered: In this narrative review, the authors highlight and summarize the most common drugs and supplements used for the treatment of sleep problems in children with neurodevelopmental disabilities. Recommendations are formulated regarding the use of melatonin and melatonin receptor agonists, sedating antidepressants, antipsychotics, antihistamines, gabapentin, clonidine and orexin receptor antagonists, and benzodiazepines and hypnotic benzodiazepine receptor agonists.Expert opinion: The choice of pharmacological agents and their dosage should be individualized taking into consideration multiple factors, including the severity and type of sleep problem and the associated neurological pathology. Melatonin is widely used and safe in children with neurodevelopmental conditions. Gabapentin, clonidine, trazodone, and mirtazapine hold promise but require further study. Supplements (iron, vitamin D, and 5-hydroxytryptophan) might be helpful. Due to the lack of clinical data, there is still uncertainty concerning dosing regimens and tolerability.

Association between inflammatory cytokines and ADHD symptoms in children and adolescents with obesity: A pilot study.

Whilst the association between Attention-Deficit/Hyperactivity Disorder (ADHD) and obesity is supported by meta-analytic evidence, the mechanisms underpinning this link need to be further elucidated. Inflammatory processes may increase the risk of ADHD symptoms in individuals with obesity. This pilot study set out to start testing this hypothesis by assessing the correlation between serum levels of inflammatory cytokines and ADHD symptoms severity in a sample of children and adolescents with obesity. We measured ADHD symptoms severity in 52 children/adolescents with obesity (BMI > 95th centile) with the Conners questionnaire, revised, short version, parent (CPRS-R:S) and teacher (CTRS-R:S) versions. Additionally, a categorical diagnosis of ADHD was established using the Kiddie-SADS-PL. Serum levels of IL-6, Il-10, and TNF-alpha were also obtained. The prevalence of ADHD was 9.6%. We found a significant correlation between IL-6, as well as TNF-alpha, and hyperactivity/impulsivity subscores of the CPRS-R:S and CTRS-R:S, that held even after controlling for BMI and oppositional symptoms. This study provides a rationale for larger, longitudinal studies to gain insight into inflammatory processes underpinning the link between obesity and ADHD. This line of research has the potential to lead to novel, pathophysiologically-based management strategies for individuals with obesity and ADHD.

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.