Faculty Bibliography

OBJECTIVES: It has been suggested that bipolar disorder (BD) with comorbid ADHD represents a distinct clinical phenotype of BD. There are no data regarding potential heterogeneity between BD subjects with a diagnosis of ADHD in childhood whose ADHD remitted in adulthood (cADHD-BD) vs. BD patients with persistent ADHD diagnosis in adulthood (aADHD-BD). This heterogeneity may constitute a confounder in investigations of the nature of the co-occurrence between BD and ADHD. The aim of this paper is to compare BD patients without ADHD, to those with aADHD-BD, and those with cADHD-BD on clinical and temperamental characteristics, hypothesizing that maladaptive temperament will be increased in BD subjects with a stable diagnosis of ADHD in adulthood compared to those whose ADHD remitted. We further hypothesize that maladaptive temperament will be associated with the severity of both illnesses. METHODS: A total of 100 outpatients (aged 18-30 years) with BD in remission were included. The assessment of ADHD was made according to a procedure aimed to reduce potential recall biases. Subjects had to have a parent available and had never been treated with stimulants. Temperamental traits were assessed with the California Child Q-sort (CCQ) and the Early Adolescent Temperament Questionnaire (EATQ). RESULTS: Rate of co-occurrence of ADHD-BD was 18% lifetime and 10% current diagnosis. Patients with ADHD-BD (aADHD-BD+cADHD-BD) reported a significantly earlier onset of mood disorder, higher number of previous mood episodes, and significantly higher impulsivity than BD patients without ADHD. aADHD-BD showed a significantly earlier BD onset, higher number of previous mood episodes, higher impulsivity, decreased Reactive Control and higher Negative Emotionality temperamental scores than cADHD patients. CONCLUSION: Findings suggest that patients with aADHD-BD present a clinical phenotype distinct from that of patients with BD without ADHD or with a childhood ADHD diagnosis that remitted with the age. This appealing hypothesis of a BD-distinct phenotype that can be detected early due to its associated maladaptive temperamental traits requires further investigation in larger samples, supported by neuropsychological, genetic and imaging data.

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.

OBJECTIVE: To perform a meta-analysis of subjective (i.e., based on questionnaires) and objective (i.e., using polysomnography or actigraphy) studies comparing sleep in children with attention-deficit/hyperactivity disorder (ADHD) versus controls. METHOD: We searched for subjective and objective sleep studies (1987-2008) in children with ADHD (diagnosed according to standardized criteria). Studies including subjects pharmacologically treated or with comorbid anxiety/depressive disorders were excluded. RESULTS: Sixteen studies, providing 9 subjective and 15 objective parameters and including a total pooled sample of 722 children with ADHD versus 638 controls, were retained. With regard to subjective items, the meta-analysis indicated that children with ADHD had significantly higher bedtime resistance (z = 6.94, p <.001), more sleep onset difficulties (z = 9.38, p <.001), night awakenings (z = 2.15, p =.031), difficulties with morning awakenings (z = 5.19, p <.001), sleep disordered breathing (z = 2.05, p =.040), and daytime sleepiness (z = 1.96, p =.050) compared with the controls. As for objective parameters, sleep onset latency (on actigraphy), the number of stage shifts/hour sleep, and the apnea-hypopnea index were significantly higher in the children with ADHD compared with the controls (z = 3.44, p =.001; z = 2.43, p =.015; z = 3.47, p =.001, respectively). The children with ADHD also had significantly lower sleep efficiency on polysomnography (z = 2.26, p =.024), true sleep time on actigraphy (z = 2.85, p =.004), and average times to fall asleep for the Multiple Sleep Latency Test (z = 6.37, p <.001) than the controls. CONCLUSIONS: The children with ADHD are significantly more impaired than the controls in most of the subjective and some of the objective sleep measures. These results lay the groundwork for future evidence-based guidelines on the management of sleep disturbances in children with ADHD.

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. METHODS: 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.

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.

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.

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.