Sleep in adults with attention deficit hyperactivity disorder (ADHD) before and during treatment with methylphenidate: a controlled polysomnographic study

STUDY OBJECTIVES: Sleep problems are frequently associated with childhood ADHD, as indicated by numerous polysomnographic investigations showing increased nocturnal movements, reduced sleep efficiency, and decreased percentage of REM sleep (although findings are not consistent over all studies). Data on objective and subjective sleep parameters in adults with ADHD are sparse, and to date the impact of stimulants, the most widely used pharmacological treatment for ADHD, on sleep in adults with ADHD has not been examined. Thus the objectives of our study were to assess objective and subjective sleep parameters in adults with ADHD and the impact of stimulant medication on sleep. DESIGN: Two-group comparison and open-label therapy study. PARTICIPANTS: We enrolled 34 nonmedicated patients with ADHD, of whom 24 were without current comorbid psychiatric disorders, and 34 sex- and gender-matched control subjects without current psychiatric disorders or psychotropic medication. INTERVENTIONS: Ten patients were treated with methylphenidate over > or =26 days with a mean daily dose of 36.7 +/- 11.2 mg. MEASUREMENTS: Polysomnographic recording over 2 consecutive nights as well as assessments of subjective sleep parameters were performed in all patients and controls before treatment and reassessed in those patients receiving methylphenidate. RESULTS: Compared to controls untreated patients showed increased nocturnal activity, reduced sleep efficiency, more nocturnal awakenings and reduced percentage of REM sleep. Treatment with methylphenidate resulted in increased sleep efficiency as well as a subjective feeling of improved restorative value of sleep. CONCLUSIONS: Sleep problems in patients with ADHD continue from childhood to adulthood, with similar objective sleep characteristics in adults and children with ADHD. Medication with methylphenidate appears to have beneficial effects on sleep parameters in adults with ADHD.     

Sleep and sleepiness in children with attention deficit / hyperactivity disorder and controls

The present study assessed the association between habitual sleep patterns and one night of PSG measured sleep with daytime sleepiness in children with ADHD and typically developing children. Eighty‐two children (26 ADHD, 56 typically developing children), between 7 and 11 years, had nighttime sleep recorded using actigraphy over five nights (habitual sleep patterns) and polysomnography during one night (immediate sleep patterns), both within their home environments. Daytime sleepiness was examined using the multiple sleep latency test within a controlled laboratory setting the following day. Using Spearman correlations, the relationships between mean sleep latencies on the multiple sleep latency test and scores on a modified Epworth Sleepiness Scale with polysomnographic measures of sleep quality and architecture and with actigraphic sleep quality measures were examined. Longer sleep latency, measured using polysomnography and actigraphy, was related to longer mean sleep latencies on the multiple sleep latency test in typically developing participants, whereas actigraphic measures of sleep restlessness (time awake and activity during the night), as well as time in slow‐wave sleep, were positively related to mean sleep latency on the multiple sleep latency test in children with ADHD. These results show a differential relationship for children with ADHD and typically developing children between habitual and immediate sleep patterns with daytime sleepiness and suggest that problems initiating and maintaining sleep may be present both in nighttime and daytime sleep.     

Sleep patterns and insomnia among adolescents: a population‐based study

The aim of the current study was to examine sleep patterns and rates of insomnia in a population‐based study of adolescents aged 16–19 years. Gender differences in sleep patterns and insomnia, as well as a comparison of insomnia rates according to DSM‐IV, DSM‐V and quantitative criteria for insomnia (Behav. Res. Ther., 41 , 2003, 427), were explored. We used a large population‐based study in Hordaland county in Norway, conducted in 2012. The sample included 10 220 adolescents aged 16–18 years (54% girls). Self‐reported sleep measurements included bedtime, rise time, time in bed, sleep duration, sleep efficiency, sleep onset latency, wake after sleep onset, rate and frequency and duration of difficulties initiating and maintaining sleep and rate and frequency of tiredness and sleepiness. The adolescents reported short sleep duration on weekdays (mean 6:25 hours), resulting in a sleep deficiency of about 2 h. A majority of the adolescents (65%) reported sleep onset latency exceeding 30 min. Girls reported longer sleep onset latency and a higher rate of insomnia than boys, while boys reported later bedtimes and a larger weekday–weekend discrepancy on several sleep parameters. Insomnia prevalence rates ranged from a total prevalence of 23.8 (DSM‐IV criteria), 18.5 (DSM‐V criteria) and 13.6% (quantitative criteria for insomnia). We conclude that short sleep duration, long sleep onset latency and insomnia were prevalent in adolescents. This warrants attention as a public health concern in this age group.     

Sleep disorders in Taiwanese children with attention deficit/hyperactivity disorder

To assess obstructive sleep apnea syndrome (OSAS) and periodic limb movement disorder (PLMD) in children with attention deficit/hyperactivity disorder (ADHD) compared with a control group. The ADHD was diagnosed based on Diagnostic and Statistical Manual, version IV (DSM-IV) criteria on successively seen elementary school children aged 6-12 years referred to a psychiatric clinic for suspected ADHD. A standardized interview (Kiddie-SADS-E), parents and teacher questionnaires, neuropsychological testing, and nocturnal polysomnography were completed for each child. Eighty-eight children (77 boys) with ADHD and 27 controls were involved in the study. Fifty children with ADHD (56.8%) had an apnea-hypopnea index (AHI) >1 event h(-1) and 17 (19.3%) had an AHI >5 event h(-1). Nine children (10.2%) had a periodic limb movement index (PLMI) >5 events h(-1). There is one child with AHI >1 and none with a PLMI > 5 in the control group. In the test of variables of attention (TOVA), the response time was significantly worse in ADHD with sleep disorders than those without them. The child behavior checklist (CBCL) showed a significant difference between groups in the hyperactivity subscale. The diagnostic criteria for ADHD based on DSM-IV do not differentiate between children with or without sleep disorders. Evaluation of sleep disorders should be considered before starting drug treatment for ADHD.     

注意缺陷多动障碍综合征患儿睡眠结构的初探

目的 探讨注意缺陷多动障碍（ADHD）综合征患儿的睡眠结构，睡眠中痢性放电及睡眠周期性肢体运动（PLMS）的情况；比较ADHD各亚型问睡眠结构的差异。方法 利用多导睡眠监护仪对2005年6月至2006年11月在首都儿科研究所神经科门诊就诊的符合DSM-Ⅳ诊断标准的58例ADHD患儿及30名正常儿童进行整夜睡眠结构监测。结果 ADHD组58例，其中4例睡眠监测未完成，实际完成54例。ADHD组中混合型（ADHD—C）31例（57．4％，31／54），注意缺陷型（ADHD-I）15例（27．8％，15／54），多动／冲动型（ADHD．H）8例（14．8％，8／54）。①与对照组比较，ADHD组快速动眼期（REM）潜伏期短、睡眠潜伏期延长和睡眠效率降低，差异有统计学意义（P〈0．05）；②ADHD-C患儿睡眠Ⅱ期百分比较ADHD-I增加，差异有统计学意义（P〈0．05）；③ADHD组PLMS发生率为37．0％（20／54），对照组PLMS发生率为13．3％（4／30），差异有统计学意义（P〈0．05）；④ADHD组和对照组EEG未见痢性放电。结论 ①ADHD患儿存在REM睡眠结构的改变、入睡困难及睡眠效率降低；②睡眠Ⅱ期百分比的增多可使ADHD-C较ADHD-I有更多和更重的症状；③ADHD患儿睡眠过程中PLMS发生率较对照组显著升高，PLMS也是导致ADHD患儿睡眠质量下降的原因之一。     

The sleep of children with attention deficit hyperactivity disorder on and off methylphenidate: a matched case–control study

In the present study, we assessed the effects of regular use of methylphenidate medication in children diagnosed with attention deficit hyperactivity disorder (ADHD) on sleep timing, duration and sleep architecture. Twenty‐seven children aged 6–12 years meeting diagnostic criteria for Diagnostic and Statistical Manual version IV ADHD and 27 control children matched for age (±3 months) and gender. Two nights of standard polysomnographic (PSG) recordings were conducted. ADHD children were allocated randomly to an on‐ or 48 h off‐methylphenidate protocol for first or second recordings. Control children’s recordings were matched for night, but no medication was used. Mixed modelling was employed in the analyses so that the full data set was used to determine the degree of medication effects. Methylphenidate in ADHD children prolonged sleep onset by an average of 29 min [confidence interval (CI) 11.6, 46.7], reduced sleep efficiency by 6.5% (CI 2.6, 10.3) and shortened sleep by 1.2 h (CI 0.65, 1.9). Arousal indices were preserved. Relative amounts of stages 1, 2 and slow wave sleep were unchanged by medication. Rapid eye movement sleep was reduced (?2.4%) on the medication night, an effect that became non‐significant when control data were incorporated in the analyses. PSG data from ADHD children off‐medication were similar to control data. Our findings suggest that methylphenidate reduces sleep quantity but does not alter sleep architecture in children diagnosed with ADHD. An adequate amount of sleep is integral to good daytime functioning, thus the sleep side effects of methylphenidate may affect adversely the daytime symptoms the drug is targeted to control.     

The involvement of the canonical Wnt‐signaling receptor LRP5 and LRP6 gene variants with ADHD and sexual dimorphism: Association study and meta‐analysis

Wnt‐signaling is one of the most abundant pathways involved in processes such as cell‐proliferation, ‐polarity, and ‐differentiation. Altered Wnt‐signaling has been linked with several neurodevelopmental disorders including attention‐deficit/hyperactivity disorder (ADHD) as well as with cognitive functions, learning and memory. Particularly, lipoprotein receptor‐related protein 5 (LRP5) or LRP6 coreceptors, responsible in the activation of the canonical Wnt‐pathway, were associated with cognitive alterations in psychiatric disorders. Following the hypothesis of Wnt involvement in ADHD, we investigated the association of genetic variations in LRP5 and LRP6 genes with three independent child and adolescent ADHD (cADHD) samples (total 2,917 participants), followed by a meta‐analysis including previously published data. As ADHD is more prevalent in males, we stratified the analysis according to sex and compared the results with the recent ADHD Psychiatric Genomic Consortium (PGC) GWAS. Meta‐analyzing our data including previously published cADHD studies, association of LRP5 intronic rs4988319 and rs3736228 (Ala1330Val) with cADHD was observed among girls (OR = 1.80 with 95% CI = 1.07–3.02, p = .0259; and OR = 2.08 with 95% CI = 1.01–4.46, p = .0026, respectively), whereas in boys association between LRP6 rs2302685 (Val1062Ile) and cADHD was present (OR = 1.66, CI = 1.20–2.31, p = .0024). In the PGC‐ADHD dataset (using pooled data of cADHD and adults) tendency of associations were observed only among females with OR = 1.09 (1.02–1.17) for LRP5 rs3736228 and OR = 1.18 (1.09–1.25) for LRP6 rs2302685. Together, our findings suggest a potential sex‐specific link of cADHD with LRP5 and LRP6 gene variants, which could contribute to the differences in brain maturation alterations in ADHD affected boys and girls, and suggest possible therapy targets.     

Examining for association between candidate gene polymorphisms in the dopamine pathway and attention‐deficit hyperactivity disorder: A family‐based study

Attention‐deficit hyperactivity disorder (ADHD) is a highly heritable childhood‐onset psychiatric condition characterized by developmentally inappropriate inattention, hyperactivity, and impulsiveness. The pathophysiology of ADHD is currently unknown. However, the therapeutic effects of stimulant medication together with findings from animal and neuroimaging studies as well as from several molecular genetic studies of the dopamine receptor D4 gene and dopamine transporter gene have implicated involvement of the dopaminergic system. To test the dopaminergic hypothesis further, we have looked for association between ADHD and alleles of seven dopamine‐related candidate genes using a family‐based association approach in a sample of 150 children diagnosed with ADHD. We tested polymorphisms in genes encoding three dopamine receptors (DRD3, DRD4, and DRD5) and four dopamine‐relevant enzymes: tyrosine hydroxylase [tyrosine hydroxylase (TH)], dopamine beta hydroxylase (DβH), catechol‐O‐methyltransferase (COMT), and monoamine oxidase A (MAOA). We were unable to detect a significant association with any of the polymorphisms genotyped, although there was a trend for preferential transmission of the DRD5 148 bp marker allele and the MAOA 122 bp marker allele. We conclude that none of the alleles we have tested makes a major contribution to ADHD, although much larger samples are required to exclude small effects. © 2001 Wiley‐Liss, Inc.     

Sleep hygiene and actigraphically evaluated sleep characteristics in children with ADHD and chronic sleep onset insomnia

In the present study we investigated sleep hygiene and actigraphically evaluated sleep in 74 medication‐naïve children, aged 6–12 years, with rigorously diagnosed attention‐deficit/hyperactivity disorder (ADHD) and chronic sleep onset insomnia (ADHD‐SOI) and 23 ADHD controls without insomnia (ADHD‐noSOI). Between‐group differences were analysed for lights out (sleep log), actigraphically evaluated sleep onset, sleep latency, total sleep duration, actual sleep time and sleep hygiene as measured with the Children's Sleep Hygiene Scale. We found a significant difference (P < 0.001) in mean (±SD) sleep onset between the ADHD‐SOI group (21:49 ± 0:56 h) and ADHD‐noSOI groups (20:41 ± 0:45 h). Sleep latency was significantly (P < 0.001) longer in ADHD‐SOI (00:53 ± 0:25 h) compared to ADHD‐noSOI (00:26 ± 0:25 h). The difference in total sleep duration between ADHD‐SOI (9:42 ± 0:44 h) and ADHD‐noSOI (10:09 ± 0:43 h) was not significantly different (P = 0.18). The group difference in actual sleep time was also not significant (8:43 ± 0:52 h in ADHD‐SOI versus 9:13 ± 1:16 h; P = 0.40). There was no significant difference (P = 0.17) in mean (±SD) total sleep hygiene score between the ADHD‐SOI (56.4 ± 10.5) and ADHD‐noSOI groups (53.0 ± 10.6). We conclude that there were differences in sleep onset and sleep latency in ADHD children with chronic SOI and those without insomnia; however, sleep hygiene practices were similar and did not relate to sleep characteristics.     

Circadian motor activity affected by stimulant medication in children with attention‐deficit/hyperactivity disorder

Attention‐deficit/hyperactivity disorder (ADHD) is a highly prevalent disorder occurring in approximately 3–5% of school‐aged children. The core symptoms of ADHD are effectively treated with stimulant medications such as methylphenidate; however, there are also negative side effects, including insomnia. It has been suggested that administration of stimulant medication may alter the timing or regularity of circadian motor activity levels. This study aimed to investigate the impact of stimulant medication on the strength and timing of circadian rhythms in 16 stimulant medication‐naïve children with ADHD. Participants were monitored for changes in motor activity during a 3‐week blinded placebo‐controlled medication trial to examine the impact of immediate‐release methylphenidate hydrochloride. Motor activity was measured by actigraphy, and 24‐h activity profiles were analysed using cosinor analyses to identify measurable changes in circadian rhythms. The children in this sample demonstrated significant increases in motor activity during the sleep‐onset latency period. They also showed a significant reduction in relative circadian amplitude and a phase‐delay in the timing of the daily rhythm. Clinicians and parents of children being treated with stimulant medication for ADHD should be aware that stimulant medication may cause disruption of sleep/circadian rhythms. Behavioural strategies to improve sleep may be useful for children experiencing these negative effects from medication.     

Sleep and academic performance in later adolescence: results from a large population‐based study

The aim of the current study was to assess the association between sleep duration and sleep patterns and academic performance in 16–19 year‐old adolescents using registry‐based academic grades. A large population‐based study from Norway conducted in 2012, the youth@hordaland‐survey, surveyed 7798 adolescents aged 16–19 years (53.5% girls). The survey was linked with objective outcome data on school performance. Self‐reported sleep measures provided information on sleep duration, sleep efficiency, sleep deficit and bedtime differences between weekday and weekend. School performance [grade point average (GPA)] was obtained from official administrative registries. Most sleep parameters were associated with increased risk for poor school performance. After adjusting for sociodemographic information, short sleep duration and sleep deficit were the sleep measures with the highest odds of poor GPA (lowest quartile). Weekday bedtime was associated significantly with GPA, with adolescents going to bed between 22:00 and 23:00 hours having the best GPA. Also, delayed sleep schedule during weekends was associated with poor academic performance. The associations were somewhat reduced after additional adjustment for non‐attendance at school, but remained significant in the fully adjusted models. In conclusion, the demonstrated relationship between sleep problems and poor academic performance suggests that careful assessment of sleep is warranted when adolescents are underperforming at school. Future studies are needed on the association between impaired sleep in adolescence and later functioning in adulthood.     

Maternal testosterone in pregnancy and atopic outcomes in childhood

BACKGROUND: In mice, androgens downregulate Th2 cytokine responses, but whether androgen levels during pregnancy might influence the development of allergy in the offspring has not been studied. METHODS: In the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based birth cohort of 14 541 pregnancies, we related maternal blood total testosterone during pregnancy, measured in a subset of the cohort, to allergic outcomes in the offspring, including asthma, hayfever, eczema (n=543) and wheezing (n=532) at 69-81 months, and atopy (positive skin prick test to Dermatophagoides pteronyssinus, cat or grass, n=386) and blood total immunoglobulin E (IgE; n=314) at 7 years. We used logistic and linear regression to analyse binary outcomes and log-transformed IgE, respectively, controlling for potential confounders. RESULTS: Maternal testosterone was negatively associated with total IgE in boys [adjusted geometric mean ratio (GMR), per doubling of testosterone, 0.33 (0.20-0.55), P=0.000038 (n=168)], but not in girls [GMR 1.04 (0.53-2.06), P=0.91 (n=146)], P-value interaction 0.0086. The effect in boys was even stronger in the absence of maternal atopic disease. Testosterone was not associated with skin test positivity or atopic disease in either sex. CONCLUSIONS: Higher testosterone levels in pregnancy are associated with lower IgE production in boys.     

Clinical implications of daytime sleepiness for the academic performance of middle school‐aged adolescents with attention deficit hyperactivity disorder

This study investigated the relative impact of total time slept per night and daytime sleepiness on the academic functioning of 100 middle school‐aged youth (mean age = 11.9) with attention deficit hyperactivity disorder (ADHD). The primary goal of the study was to determine if total time slept per night and/or daytime sleepiness, as measured by youth self‐report on the Pediatric Daytime Sleepiness Scale (PDSS), predicted academic functioning above and beyond symptoms of ADHD and relevant covariates, such as intelligence, achievement scores and parent education level. Self‐reported daytime sleepiness but not self‐reported total time slept per night was associated significantly with all academic outcomes. When examined in a hierarchical regression model, self‐reported daytime sleepiness significantly predicted parent‐rated homework problems and academic impairment and teacher‐rated academic competence above and beyond symptoms of ADHD and relevant covariates, but did not predict grade point average or teacher‐rated academic impairment. The implications of these findings for understanding more clearly the association between ADHD and sleep and the functional implications of this relationship are discussed.     

ADHD risk genes involved in dopamine signaling and metabolism are associated with reduced estimated life expectancy at young adult follow‐up in hyperactive and control children

ADHD is associated with an elevated risk of mortality and reduced estimated life expectancy (ELE) by adulthood. Reduced life expectancy is substantially related to the trait of behavioral disinhibition; a correlate of both ADHD and of several dopamine genes related to dopamine signaling and metabolism. We therefore hypothesized that several ADHD risk genes related to dopamine might also be predictive of reduced ELE. Using a longitudinal study of 131 hyperactive children and 71 control cases followed to young adulthood, we examined whether several polymorphisms involving DRD4, DAT1, and DBH were related to ELE. The homozygous 9/9 allele of DAT1 and the heterozygous allele of DBH TaqI were associated with 5‐ and 2‐year reductions, respectively, in total ELE. They did not operate on ELE through any relationships to ADHD specifically or behavioral disinhibition more generally. Instead, they showed links to alcohol use (DBH), reduced education, smoking, and reduced exercise (DAT1) employed in the computation of ELE. We conclude that polymorphisms of two dopamine genes are linked to reductions in ELE independently of their association with ADHD.     

利他林对注意缺陷多动障碍患儿注意能力影响的ERP研究

目的:探讨注意缺陷多动障碍(ADHD)患儿的视觉空间注意刺激诱发的事件相关电位(ERP)特征,并研究利他林(MPH)对其影响。方法:采用有效提示、无效提示刺激模块对22名ADHD患儿和22名年龄匹配的正常儿童进行ERP检测和记录其行为学表现。ADHD患儿在服MPH前和服MPH后2 h分别接受两次ERP检测。结果:与正常对照组相比,ADHD组在服MPH前,额部N2波潜伏期显著延长(P<0．05),各导联P2、N2波波幅显著降低(P<0．05);服MPH后2 h额部N2波潜伏期显著缩短(P<0．05),各导联波幅显著增高(P<0．05);服MPH后2 h各导联P2、N2波的潜伏期及波幅与正常对照组比较差异无显著意义(P>0．05)。结论:视觉空间注意ERP可以客观检测ADHD患儿注意缺陷的存在及程度,为临床诊断和评价MPH疗效提供了客观依据。     

The impact of daytime sleepiness on the school performance of college students with attention deficit hyperactivity disorder (ADHD): a prospective longitudinal study

This prospective longitudinal study evaluated the impact of daytime sleepiness on the school performance of 62 college students diagnosed comprehensively with attention deficit hyperactivity disorder. The primary goal of the study was to determine if self‐reported daytime sleepiness rated at the beginning of the academic year could predict academic and overall functioning at the end of the academic year while also considering potentially important covariates, including symptoms of inattention, hyperactivity and impulsivity, medication status and whether or not students lived at home or on‐campus. Self‐reported daytime sleepiness predicted longitudinally school maladjustment, overall functional impairment and the number of D and F grades (i.e. poor and failing) students received in courses above and beyond both self‐ and parent‐report of symptoms, but did not predict overall grade point average. Living at home served as a protective factor and was associated with less school maladjustment and overall impairment. Gender was the only significant predictor in the overall grade point average model, with female gender associated with higher overall grades. The implications of these findings for monitoring and treatment of sleep disturbances in college students with attention deficit hyperactivity disorder are discussed.     

Mental health problems in adolescents with delayed sleep phase: results from a large population‐based study in Norway

The aim of the current study was to compare mental health problems, resilience and family characteristics in adolescents with and without delayed sleep phase (DSP) in a population‐based sample. Data were taken from the youth@hordaland‐survey, a large population‐based study in Hordaland County in Norway conducted in 2012. In all, 9338 adolescents aged 16–19 years (53.5% girls) provided self‐reported data on a wide range of instruments assessing mental health symptoms, including depression, anxiety, obsessive–compulsive behaviours, attention deficit hyperactive disorder (ADHD) symptoms, perfectionism, resilience and sleep. Measures of socioeconomic status were also included. Three hundred and six adolescents (prevalence 3.3%) were classified as having DSP [according to the International Classification of Sleep Disorders‐2 (ICSD‐2)] criteria. Adolescents with DSP reported higher levels of depression, anxiety and ADHD symptoms. Adolescents with DSP also exhibited significantly lower levels of resilience. The Cohen's d effect sizes ranged from small [obsessive–compulsive disorder (OCD): d = 0.15] to moderate (inattention: d = 0.71). In the fully adjusted model, the significant predictors of DSP included inattention [odds ratio (OR): 2.11], lack of personal structure (OR: 2.07), low (OR: 1.85) and high (OR: 1.91) paternal education, parents not living together (OR: 1.81), hyperactivity/inattention (OR: 1.71) and poorer family economy (OR: 1.59). In conclusion, the high symptom load across a range of mental health measures suggests that a broad and thorough clinical approach is warranted when adolescents present with DSP.