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

Cortese, Samuele; Angriman, Marco; Maffeis, Claudio; Isnard, Pascale; Konofal, Eric; Lecendreux, Michel; Purper-Ouakil, Diane; Vincenzi, Brenda; Bernardina, Bernardo Dalla; Mouren, Marie-Christine
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.
PMID: 18568858
ISSN: 1040-8398
CID: 1154842

Effects of iron supplementation on attention deficit hyperactivity disorder in children

Konofal, Eric; Lecendreux, Michel; Deron, Juliette; Marchand, Martine; Cortese, Samuele; Zaim, Mohammed; Mouren, Marie Christine; Arnulf, Isabelle
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.
PMID: 18054688
ISSN: 0887-8994
CID: 1154872

Attention-deficit/hyperactivity disorder, Tourette's syndrome, and restless legs syndrome: the iron hypothesis

Cortese, Samuele; Lecendreux, Michel; Bernardina, Bernardo Dalla; Mouren, Marie Christine; Sbarbati, Andrea; Konofal, Eric
Preliminary but increasing evidence suggests that attention-deficit/hyperactivity disorder (ADHD), Tourette's syndrome (TS), and restless legs syndrome (RLS) may be comorbid. In the present article, we hypothesize that ADHD, TS, and RLS may be part of a spectrum, and that iron deficiency contributes to the pathophysiology underlying this spectrum. Iron deficiency might lead to ADHD, RLS and TS symptoms via its impact on the metabolism of dopamine and other catecholamines, which have been involved into the pathophysiology of ADHD, TS, and RLS. We speculate that the catecholaminergic systems are differently impacted in each of the three disorders, contributing to a different specific phenotypic expression of iron deficiency. MRI studies assessing brain iron levels in ADHD, TS, and childhood RLS, as well as genetic studies on the specific molecular pathways involved in iron deficiency, are greatly needed to confirm the iron hypothesis underlying ADHD, TS, and RLS. This body of research may set the basis for controlled trials assessing the effectiveness and tolerability, as well as the most appropriate dose, duration and type (oral vs. intravenous) of iron supplementation. In conclusion, the iron hypothesis may help us progress in the understanding of pathophysiological links between ADHD, RLS, and TS, suggesting that iron supplementation might be effective for all these three impairing conditions.
PMID: 18164140
ISSN: 0306-9877
CID: 1154852

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

Cortese, Samuele; Konofal, Eric; Dalla Bernardina, Bernardo; Mouren, Marie-Christine; Lecendreux, Michel
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.
PMID: 17587509
ISSN: 0306-9877
CID: 1154862

Sleep problems associated with ADHD: a review of current therapeutic options and recommendations for the future

Lecendreux, Michel; Cortese, Samuele
In recent years, there has been a growing interest in sleep problems associated with attention-deficit/hyperactivity disorder (ADHD). The etiology of these sleep problems is multifactorial. In this paper, we review the current literature on the treatment of the most common disorders or factors underlying sleep problems associated with ADHD. In particular, we focus on the management of sleep problems associated with ADHD medications, restless legs syndrome, excessive nocturnal motricity in sleep, sleep disordered breathing, sleep-onset insomnia and psychiatric comorbidities associated with ADHD. Given the paucity of randomized, controlled, double-blinded, placebo-controlled studies, it is hoped that this review will encourage further methodologically sound studies in order to be able to develop treatment guidelines.
PMID: 18052772
ISSN: 1473-7175
CID: 1154882

Parent reports of sleep/alertness problems and ADHD symptoms in a sample of obese adolescents

Cortese, Samuele; Maffeis, Claudio; Konofal, Eric; Lecendreux, Michel; Comencini, Erica; Angriman, Marco; Vincenzi, Brenda; Pajno-Ferrara, Franco; Mouren, Marie-Christine; Dalla Bernardina, Bernardo
OBJECTIVE: Recent evidence suggests an association between obesity and Attention Deficit/Hyperactivity Disorder (ADHD) or ADHD traits. The characteristics of obese subjects with a higher probability of ADHD symptoms are still unclear. We explore the hypothesis that obese adolescents with sleep/alertness problems represent a subgroup at high risk for ADHD traits, independently from associated symptoms of anxiety/depression. The aim of this study was to assess the relationship between parent reports of sleep/alertness problems and ADHD traits in a clinical sample of obese adolescents, controlling for symptoms of anxiety/depression. METHODS: Seventy obese subjects (age range, 10-16 years) were included. The parents filled out the Sleep Disturbance Scale for Children (SDSC), the Conners Parents Rating Scale-Revised (Short Version) (CPRS-R:S), and the Child Behavior Checklist (CBCL). The ADHD Rating Scale (ADHD-RS) was completed by a child psychiatrist. RESULTS: Using multiple regression models controlling for symptoms of anxiety/depression, scores of excessive daytime sleepiness on the SDSC were significantly associated with ADHD traits on the CPRS-R:S as well as on the ADHD-RS. CONCLUSIONS: Obese adolescents described as excessively sleepy by their parents may be at higher risk of ADHD symptoms, independently from symptoms of anxiety/depression. Although the clinician may overlook a potential diagnosis of ADHD in obese adolescents described as sleepy, the results of this study suggest to systematically look for symptoms of ADHD in this subgroup of obese patients. Further studies using objective methods to assess sleep/alertness disturbances are needed to gain insight into the relationship between sleep/alertness disturbances and ADHD in obese individuals.
PMID: 18061748
ISSN: 0022-3999
CID: 1154892

Impact of restless legs syndrome and iron deficiency on attention-deficit/hyperactivity disorder in children

Konofal, Eric; Cortese, Samuele; Marchand, Martine; Mouren, Marie-Christine; Arnulf, Isabelle; Lecendreux, Michel
OBJECTIVE: Increasing evidence suggests a significant comorbidity between attention-deficit/hyperactivity disorder (ADHD) and restless legs syndrome (RLS). Iron deficiency may underlie common pathophysiological mechanisms in subjects with ADHD plus RLS (ADHD+RLS). To date, the impact of iron deficiency, RLS and familial history of RLS on ADHD severity has been scarcely examined in children. These issues are addressed in the present study. METHODS: Serum ferritin levels, familial history of RLS (diagnosed using National Institutes of Health (NIH) criteria) and previous iron supplementation in infancy were assessed in 12 ADHD+RLS children, 10 ADHD children and 10 controls. RLS was diagnosed using NIH-specific pediatric criteria, and ADHD severity was assessed using the Conners' Parent Rating scale. RESULTS: ADHD symptom severity was higher, although not significantly, in children with ADHD+RLS compared to ADHD. The mean serum ferritin levels were significantly lower in children with ADHD than in the control group (p<0.0005). There was a trend for lower ferritin levels in ADHD+RLS subjects versus ADHD. Both a positive family history of RLS and previous iron supplementation in infancy were associated with more severe ADHD scores. CONCLUSIONS: Children with ADHD and a positive family history of RLS appear to represent a subgroup particularly at risk for severe ADHD symptoms. Iron deficiency may contribute to the severity of symptoms. We suggest that clinicians consider assessing children with ADHD for RLS, a family history of RLS, and iron deficiency.
PMID: 17644481
ISSN: 1389-9457
CID: 1154902

Attention-deficit/hyperactivity disorder (ADHD) and binge eating

Cortese, Samuele; Bernardina, Bernardo Dalla; Mouren, Marie-Christine
Attention-deficit/hyperactivity disorder (ADHD) is characterized by a persistent and pervasive pattern of inattention and/or hyperactivity-impulsivity. Emerging data suggest higher than expected rates of binge eating occur in subjects with ADHD. Several hypotheses may explain this newly described comorbidity: 1) inattention and/or impulsivity foster binge eating, 2) ADHD and binge eating share common neurobiological bases, 3) binge eating contributes to ADHD, or 4) psychopathological factors common to both binge eating and ADHD mediate the association. In patients with ADHD and binge eating, both conditions might benefit from common therapeutic strategies. Further research is needed to gain insight into the association between ADHD and binge eating in order to facilitate more appropriate clinical management and, ultimately, a better quality of life for patients with both conditions.
PMID: 17958207
ISSN: 0029-6643
CID: 1154912

Lead and neuroprotection by iron in ADHD [Letter]

Konofal, Eric; Cortese, Samuele
PMCID:1940080
PMID: 17687422
ISSN: 0091-6765
CID: 1154922

Attention-deficit/hyperactivity disorder, binge eating, and obesity [Letter]

Cortese, Samuele; Isnard, Pascale; Dalla Bernardina, Bernardo; Mouren, Marie-Christine
PMID: 17592935
ISSN: 0160-6689
CID: 1154932