Faculty Bibliography

OBJECTIVE: The objective was to report a case of experienced psychosis during the treatment with methylphenidate (MPH) in a cocaine-dependent adult treated for attention-deficit/hyperactivity disorder (ADHD) with comorbid cocaine dependence. CONCLUSION: ADHD is a frequent comorbidity in substance use disorder (SUD) patients. MPH may be effective in treating ADHD symptoms in SUD patients, thus preventing possible adverse outcomes. Cocaine-induced psychosis may be a risk factor for development of psychosis in the presence of a concurrent treatment with MPH.

Preliminary evidence suggests a possible association between Attention-Deficit/Hyperactivity Disorder and Restless Legs Syndrome with or without Periodic Limb Movements during Sleep. When comorbid, Restless Legs Syndrome/Periodic Limb Movements during Sleep might aggravate Attention-Deficit/Hyperactivity Disorder symptoms. Pharmacological treatment of Attention-Deficit/Hyperactivity Disorder may be associated, at least in some cases, with adverse cardiovascular events, including clinically significant elevation in heart rate and systemic blood pressure. However, the characteristics of patients with Attention-Deficit/Hyperactivity Disorder at risk for cardiovascular events during pharmacological treatment are poorly understood. Here, we hypothesize that Restless Legs Syndrome and/or Periodic Limb Movements during Sleep comorbid with Attention-Deficit/Hyperactivity Disorder increase cardiovascular risk via imbalance in activity of the autonomic nervous system. Such an imbalance of the could be related to alterations of sleep microarchitecture also detected by cyclic alternating pattern analysis. If empirical studies confirm our hypothesis, the clinician would be advised to systematically screen for and effectively treat Restless Legs Syndrome/Periodic Limb Movements during Sleep even before starting treatment with Attention-Deficit/Hyperactivity Disorder drugs. The management of Restless Legs Syndrome/Periodic Limb Movements during Sleep might reduce cardiovascular risk during pharmacological treatment of Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: To explore relationships between basic and translational science research regarding sleep and ADHD in children. METHOD: A multidisciplinary group of experts in pediatric sleep medicine and ADHD convened in November 2010 to summarize the current literature, delineate knowledge gaps, and formulate recommendations regarding future research directions and priorities. RESULTS: Six major research areas of interest were identified: (a) brain centers regulating sleep, arousal, and attention; (b) neurotransmitter systems involved in both sleep and attention regulation; (c) alterations of neural systems regulating sleep in ADHD; (d) phenotypic similarities between behavioral, mood, and cognitive manifestations of insufficient/disrupted sleep and ADHD; (e) hypoarousal and sleepiness in ADHD; and (f) external sleep-wake signals that affect sleep regulation in ADHD. CONCLUSION: An enhanced understanding of the complex mechanisms regulating sleep promotion, wakefulness, and attention may contribute to new insights regarding the core impairments in ADHD and lead to the development of new therapies.

OBJECTIVE: To provide evidence- or consensus-based recommendations concerning the assessment and management of sleep problems in youths with attention-deficit/hyperactivity disorder (ADHD). METHOD: PubMed, Ovid, EMBASE, and Web of Knowledge were searched through October 31, 2012. When no evidence was available, consensus of the authors was achieved. The evidence-level of the recommendations on the management of sleep disturbances was based on the Scottish Intercollegiate Guidelines Network (SIGN) system. RESULTS: A total of 139 original articles on sleep and childhood ADHD were retrieved, including 22 on treatment of sleep disturbances. This review focuses on behaviorally based insomnia, circadian rhythm disorder, sleep-disordered breathing, restless legs syndrome/periodic limb movement disorder, and sleep disturbances due to comorbid psychiatric disorders or ADHD medications. Healthy sleep practices are recommended as the foundation of management strategies. Behavioral interventions should be considered as first-line treatment of insomnia, although further evidence from randomized controlled trials (RCTs) is needed to prove their efficacy in ADHD. Among pharmacological treatments, RCTs support the use of melatonin to reduce sleep-onset delay, whereas there is more limited evidence for other medications. CONCLUSION: Growing empirical evidence is informing assessment/management strategies of sleep problems in youths with ADHD. However, further RCTs are warranted to support current recommendations.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is increasingly conceived as reflecting altered functional and structural brain connectivity. The latter can be addressed with diffusion tensor imaging (DTI). We examined fractional anisotropy (FA), a DTI index related to white matter structural properties, in adult male subjects diagnosed with ADHD in childhood (probands) and matched control subjects without childhood ADHD. Additionally, we contrasted FA among probands with and without current ADHD in adulthood and control subjects. METHODS: Participants were from an original cohort of 207 boys and 178 male control subjects. At 33-year follow-up, analyzable DTI scans were obtained in 51 probands (41.3+/-2.8 yrs) and 66 control subjects (41.2+/-3.1 yrs). Voxel-based FA was computed with tract-based spatial statistics, controlling for multiple comparisons. RESULTS: Probands with childhood ADHD exhibited significantly lower FA than control subjects without childhood ADHD in the right superior and posterior corona radiata, right superior longitudinal fasciculus, and in a left cluster including the posterior thalamic radiation, the retrolenticular part of the internal capsule, and the sagittal stratum (p<.05, corrected). Fractional anisotropy was significantly decreased relative to control subjects in several tracts in both probands with current and remitted ADHD, who did not differ significantly from each other. Fractional anisotropy was not significantly increased in probands in any region. CONCLUSIONS: Decreased FA in adults with childhood ADHD regardless of current ADHD might be an enduring trait of ADHD. White matter tracts with decreased FA connect regions involved in high-level as well as sensorimotor functions, suggesting that both types of processes are involved in the pathophysiology of ADHD.

OBJECTIVE: To compare BMI and obesity rates in fully grown men with and without childhood attention-deficit/hyperactivity disorder (ADHD). We predicted higher BMI and obesity rates in: (1) men with, versus men without, childhood ADHD; (2) men with persistent, versus men with remitted, ADHD; and (3) men with persistent or remitted ADHD versus those without childhood ADHD. METHODS: Men with childhood ADHD were from a cohort of 207 white boys (referred at a mean age of 8.3 years), interviewed blindly at mean ages 18 (FU18), 25 (FU25), and 41 years (FU41). At FU18, 178 boys without ADHD were recruited. At FU41, 111 men with childhood ADHD and 111 men without childhood ADHD self-reported their weight and height. RESULTS: Men with childhood ADHD had significantly higher BMI (30.1 +/- 6.3 vs 27.6 +/- 3.9; P = .001) and obesity rates (41.4% vs 21.6%; P = .001) than men without childhood ADHD. Group differences remained significant after adjustment for socioeconomic status and lifetime mental disorders. Men with persistent (n = 24) and remitted (n = 87) ADHD did not differ significantly in BMI or obesity rates. Even after adjustment, men with remitted (but not persistent) ADHD had significantly higher BMI (B: 2.86 [95% CI: 1.22 to 4.50]) and obesity rates (odds ratio: 2.99 [95% CI: 1.55 to 5.77]) than those without childhood ADHD. CONCLUSIONS: Children with ADHD are at increased risk of obesity as adults. Findings of elevated BMI and obesity rates in men with remitted ADHD require replication.

Activation likelihood estimation (ALE) meta-analyses allow investigators to integrate the results of multiple neuroimaging studies, potentially yielding novel results that may not have been evident in the individual studies. Here, we provide a brief, introductory description of ALE methods for readers without extensive expertise in neuroimaging.

OBJECTIVE: The primary aim of this study was to compare the sleep macroarchitecture of children and adolescents whose mothers have a history of depression with children and adolescents whose mothers do not. METHOD: Polysomnography (PSG) and Holter electroencephalogram (EEG) were used to compare the sleep architecture of 35 children whose mothers had at least one previous depressive episode (19 boys, aged 4-18years, "high-risk" group) and 25 controls (13 males, aged 4-18years, "low-risk" group) whose mothers had never had a depressive episode. The total sleep time, wakefulness after sleep onset (WASO), sleep latency, sleep efficiency, number of awakenings per hour of sleep, percentages of time spent in each sleep stage, rapid eye movement (REM) latency and the depressive symptoms of participants were measured. RESULTS: In children (4-12years old), the high-risk group exhibited significantly more depressive symptoms than controls (P=0.02). However, PSG parameters were not significantly different between high-risk children and controls. In adolescents (13-18years old), the high-risk subjects presented with significantly more depressive symptoms (P=0.003), a significant increase in WASO (P=0.019) and a significant decrease in sleep efficiency compared to controls (P=0.009). CONCLUSION: This study shows that children and adolescents born from mothers with a history of at least one depressive episode had significantly more depressive symptoms than controls. However, only high-risk adolescents presented with concurrent alterations of sleep macroarchitecture.