[Videogame addiction: a danger for only at-risk children or for all children]. / Addiction aux jeux vidéo: des enfants à risque ou un risque pour tous les enfants?

With the rapid growth in the number of children and adolescents having access to videogames, there is a risk of addictive behavior, especially among those with underlying mental illnesses. Yet there is no consensual definition of videogame addiction. Depression, anxiety disorders and hostility are all associated with overuse, but attention-deficit hyperactivity disorder (ADHD) is the most significant predictor.

Search for copy number variants in chromosomes 15q11-q13 and 22q11.2 in obsessive compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a clinically and etiologically heterogeneous syndrome. The high frequency of obsessive-compulsive symptoms reported in subjects with the 22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome) or Prader-Willi syndrome (15q11-13 deletion of the paternally derived chromosome), suggests that gene dosage effects in these chromosomal regions could increase risk for OCD. Therefore, the aim of this study was to search for microrearrangements in these two regions in OCD patients. METHODS: We screened the 15q11-13 and 22q11.2 chromosomal regions for genomic imbalances in 236 patients with OCD using multiplex ligation-dependent probe amplification (MLPA). RESULTS: No deletions or duplications involving 15q11-13 or 22q11.2 were identified in our patients. CONCLUSIONS: Our results suggest that deletions/duplications of chromosomes 15q11-13 and 22q11.2 are rare in OCD. Despite the negative findings in these two regions, the search for copy number variants in OCD using genome-wide array-based methods is a highly promising approach to identify genes of etiologic importance in the development of OCD.

Mutation screening of NOS1AP gene in a large sample of psychiatric patients and controls.

BACKGROUND: The gene encoding carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (NOS1AP) is located on chromosome 1q23.3, a candidate region for schizophrenia, autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD). Previous genetic and functional studies explored the role of NOS1AP in these psychiatric conditions, but only a limited number explored the sequence variability of NOS1AP. METHODS: We analyzed the coding sequence of NOS1AP in a large population (n = 280), including patients with schizophrenia (n = 72), ASD (n = 81) or OCD (n = 34), and in healthy volunteers controlled for the absence of personal or familial history of psychiatric disorders (n = 93). RESULTS: Two non-synonymous variations, V37I and D423N were identified in two families, one with two siblings with OCD and the other with two brothers with ASD. These rare variations apparently segregate with the presence of psychiatric conditions. CONCLUSIONS: Coding variations of NOS1AP are relatively rare in patients and controls. Nevertheless, we report the first non-synonymous variations within the human NOS1AP gene that warrant further genetic and functional investigations to ascertain their roles in the susceptibility to psychiatric disorders.

Temperament and character dimensions associated with clinical characteristics and treatment outcome in attention-deficit/hyperactivity disorder boys.

BACKGROUND: Although differential patterns of temperament and character have been documented in subjects with attention-deficit/hyperactivity disorder (ADHD), few studies have investigated relations between these dimensions, clinical features of ADHD, and treatment outcome. METHODS: Ninety-five boys with ADHD and 87 controls participated in the study; 88.5% of the referred patients were reassessed after optimal titration of methylphendiate treatment. RESULTS: Compared with controls, boys with ADHD showed a temperament profile of high novelty seeking, low reward dependence, and persistence, as well as low scores on both self-determination and cooperativeness character dimensions. No significant differences were found between subjects with ADHD and controls in harm avoidance. Temperament and character traits were related to specific symptom domains and comorbidity but did not predict global severity of ADHD. Persistent and immature children with ADHD were more likely to experience short-term remission.

Reduced 3-O-methyl-dopa levels in OCD patients and their unaffected parents is associated with the low activity M158 COMT allele.

The catechol-O-methyltransferase (COMT) gene is considered as a candidate gene in obsessive-compulsive disorder (OCD). Specifically, the COMT low-activity M158 allele has been suggested to be associated with OCD. However, there is no study reporting that COMT activity is decreased in OCD patients and that the decrease is mediated by the V158M polymorphism. Therefore, the purpose of our study was to assess COMT activity in OCD by measuring plasma levels of 3-O-methyl-dopa (3-OMD), which result from the methylation of levodopa by COMT, and to investigate the relationship between 3-OMD levels and the V158M polymorphism. We also examined whether 3-OMD levels represented an endophenotype, associated with the genetic liability to OCD, by assessing unaffected relatives of OCD patients. We assessed plasma 3-OMD levels in a sample of drug-free OCD probands (n = 34) and their unaffected parents (n = 63), and compared them with controls (n = 85). The COMT V158M polymorphism was genotyped in all participants. Lower plasma 3-OMD levels were found in OCD probands and their unaffected parents compared to controls. The COMT M158 allele was associated with reduced plasma 3-OMD levels in a co-dominant manner, both in OCD probands and their relatives, but not in controls. Our results suggest that COMT activity could act as a limiting factor for the production of 3-OMD in OCD patients and in their relatives. These findings further support a role of COMT in the susceptibility to OCD and provide evidence that 3-OMD levels could represent an endophenotype in OCD.

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.

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.

Psychometric properties of a French version of the junior temperament and character inventory.

The junior temperament and character inventory (JTCI) has been developed for the assessment of temperament and character dimensions in childhood based on Cloninger's model of personality. We evaluated the psychometric proprieties of a French child and parent-rated version of the JTCI based on a previous German version, and assessed the correlations between the JTCI dimension scores and the scores on the child behavior checklist (CBCL) in a community sample of French children and adolescents aged 10-16 years. We used data from 452 child-rated and 233 -parent-rated JCTI. The psychometric properties (internal consistency and external validity in relation to the emotionality activity sociability (EAS) questionnaire) of the French JTCI were adequate in the parent-rated version. The parent-rated JTCI had overall better psychometric qualities than the child-rated version, but for both versions of the JTCI the confirmatory factor analysis showed low fit between the observed data and the original model. Dimensions of the EAS model were significantly correlated with the temperament scales of the JTCI. Further studies are required to improve the psychometric properties of the child-rated JTCI, and to provide insight about lacking fit of our data with the theoretical model.

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.

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.

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

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.

Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with Anorexia nervosa: association with subtype, body-mass index, severity and age of onset.

Anorexia nervosa (AN) affects 0.3% of young girls with a mortality of 6%/decade and is strongly familial with genetic factors. Ghrelin is an upstream regulator of the orexigenic peptides NPY and AgRP and acts as a natural antagonist to leptin's effects on NPY/AgRP-expressing neurons, resulting in an increase in feeding and body weight. Obestatin which counteracts ghrelin action on feeding is derived from the same propeptide than ghrelin. BDNF has been involved in body weight regulation and its Val66Met polymorphism associated with AN. We therefore re-investigated the association between AN and the Leu72Met and Gln90Leu polymorphisms of the prepro-ghrelin/obestatin gene, the Ala67Thr polymorphism of AgRP and the Val66Met polymorphism of BDNF taking into account clinical subtypes (restrictive--ANR--and bingeing/purging--ANB--subtypes). Family trios study of these 4 single nucleotide polymorphisms were performed in 114 probands with AN and both their parents recruited in two specialized French centres. A transmission disequilibrium was observed for the Leu72Met SNP of the preproghrelin gene and for the Ala67Thr SNP of the AgRP gene. When stratified by clinical subtype, these two polymorphisms were preferentially transmitted for the trios with a bingeing/purging proband. An excess of transmission of the Gln90Leu72 preproghrelin/obestatin haplotype in patients with AN was observed. These results do not provide evidence for a preferential transmission of the 66Met allele of BDNF but support the hypothesis that ghrelin and AGRP polymorphisms confers susceptibility to AN. Further simultaneous analysis of genetic variants of the biological determinants of energy metabolism and feeding behaviour in very large populations should contribute to the understanding of the high degree of heritability of eating disorders and to the description of pathophysiological patterns leading to life-threatening conditions in a highly redundant system.

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

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.

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

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.

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

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.

Gaze direction detection in autism spectrum disorder.

Detecting where our partners direct their gaze is an important aspect of social interaction. An atypical gaze processing has been reported in autism. However, it remains controversial whether children and adults with autism spectrum disorder interpret indirect gaze direction with typical accuracy. This study investigated whether the detection of gaze direction toward an object is less accurate in autism spectrum disorder. Individuals with autism spectrum disorder (n = 33) and intelligence quotients-matched and age-matched controls (n = 38) were asked to watch a series of synthetic faces looking at objects, and decide which of two objects was looked at. The angle formed by the two possible targets and the face varied following an adaptive procedure, in order to determine individual thresholds. We found that gaze direction detection was less accurate in autism spectrum disorder than in control participants. Our results suggest that the precision of gaze following may be one of the altered processes underlying social interaction difficulties in autism spectrum disorder.

Sleep and alertness in children with attention-deficit/hyperactivity disorder: a systematic review of the literature.

STUDY OBJECTIVE: To review evidence on sleep and alertness in children with attention-deficit/hyperactivity disorder (ADHD) controlling for potential confounding factors. METHODS: A PubMed search. Studies using ADHD diagnostic criteria other than DSM-III-R or IV and studies not excluding or controlling for psychiatric comorbidity or medication status were not included in the review. Results from objective studies were combined using meta-analysis. RESULTS: From the 46 studies located, 13 were retained. With regard to objective studies, the proportion of subjects who fell asleep during the Multiple Sleep Latency Test, the number of movements in sleep, and the apnea-hypopnea index were significantly higher in children with ADHD than in controls. We found no significant differences in other objective parameters (sleep-onset latency; number of stage changes; percentages of stage 1 sleep, stage 2 sleep, slow-wave sleep, or rapid eye movement sleep; rapid eye movement sleep latency; and sleep efficiency). Limited evidence from subjective studies suggests no significant differences in sleep-onset difficulties and bedtime resistance between children with ADHD and controls, after controlling for comorbidity and medication status. Data on sleep duration, night and morning awakenings, and parasomnias are still very limited. CONCLUSION: Results from our systematic review suggest that children with ADHD have higher daytime sleepiness, more movements in sleep, and higher apnea-hypopnea indexes compared with controls. Given the limited number of studies controlling for confounding factors, further subjective and objective studies are needed to better understand alterations in sleep and alertness in children with ADHD.

Restless legs syndrome triggered by heart surgery.

This report presents the case of a 9-year-old child with a familial history of restless legs syndrome who began to complain of restless legs syndrome symptoms after heart surgery. Hypotheses on the potential interactions between genetic and environmental factors in the development of her restless legs syndrome are discussed. Increasing evidence supports reduced brain iron in the pathophysiology of idiopathic restless legs syndrome. It is possible that the child inherited a compromised brain and peripheral iron regulation, which predisposed her to restless legs syndrome. The interaction between her dysfunctional iron management and her intraoperatory blood loss may have led to a significant decrease in brain iron, triggering restless legs syndrome symptoms. Other factors, such as immobilization and sleep deprivation after surgery, may have contributed to trigger the restless legs syndrome symptoms. If confirmed by further evidence, this patient suggests the need to carefully monitor for restless legs syndrome symptoms in young surgical patients who present with a familial history of restless legs syndrome.