Is Attention-Deficit/Hyperactivity Disorder (ADHD) a Dimension or a Category? What Does the Relationship Between ADHD Traits and Psychosocial Quality of Life Tell Us?

OBJECTIVE: The question of whether attention-deficit/hyperactivity disorder (ADHD) is a discrete category or a continuous dimension remains clinically relevant. We report the first examination of this question from the viewpoint of the relationship between ADHD traits and psychosocial quality of life (QoL), and whether the level of QoL declines markedly around a certain high ADHD trait range suggestive of a categorical boundary. METHODS: Parents/caregivers of 1,967 schoolchildren aged 6 to 11 from the general population completed the Pediatric Quality of Life Inventory and the ADHD-Rating Scale IV. Piecewise linear and non-linear regression analyses were performed. RESULTS: No evidence for a non-linear association or an abrupt change in the rate of decrease in QoL was observed in the high end of the ADHD traits continuum. Instead, the relationship was consistent with linearity. CONCLUSION: Psychosocial QoL gradually declines in a linear manner as ADHD trait levels increase providing further support for a dimensional model.

The short-term and long-term adverse effects of melatonin treatment in children and adolescents: a systematic review and GRADE assessment.

Background: Currently, melatonin is used to treat children and adolescents with insomnia without knowing the full extent of the short-term and long-term consequences. Our aim was to provide clinicians and guideline panels with a systematic assessment of serious-and non-serious adverse events seen in continuation of melatonin treatment and the impact on pubertal development and bone health following long-term administration in children and adolescents with chronic insomnia. Methods: We searched PubMed, Embase, Cinahl and PsycINFO via Ovid, up to March 17, 2023, for studies on melatonin treatment among children and adolescents (aged 5-20 years) with chronic insomnia. The language was restricted to English, Danish, Norwegian, and Swedish. Outcomes were non-serious adverse events and serious adverse events assessed 2-4 weeks after initiating treatment and pubertal development and bone health, with no restriction on definition or time of measurement. Observational studies were included for the assessment of long-term outcomes, and serious and non-serious adverse events were assessed via randomised studies. The certainty of the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The protocol is registered with the Danish Health Authority. Findings: We identified 22 randomised studies with 1350 patients reporting on serious-and non-serious adverse events and four observational studies with a total of 105 patients reporting on pubertal development. Melatonin was not associated with serious adverse events, yet the number of patients experiencing non-serious adverse events was increased (Relative risk 1.56, 95% CI 1.01-2.43, 17 studies, I2 = 47%). Three studies reported little or no influence on pubertal development following 2-4 years of treatment, whereas one study registered a potential delay following longer treatment durations (>7 years). These findings need further evaluation due to several methodological limitations. Interpretation: Children who use melatonin are likely to experience non-serious adverse events, yet the actual extent to which melatonin leads to non-serious adverse events and the long-term consequences remain uncertain. This major gap of knowledge on safety calls for caution against complacent use of melatonin in children and adolescents with chronic insomnia and for more research to inform clinicians and guideline panels on this key issue. Funding: The Danish Health Authority. The Parker Institute, Bispebjerg and Frederiksberg Hospital, supported by the Oak Foundation.

Use of melatonin for children and adolescents with chronic insomnia attributable to disorders beyond indication: a systematic review, meta-analysis and clinical recommendation.

Background: Melatonin has become a widely used sleeping aid for young individuals currently not included in existing guidelines. The aim was to develop a recommendation on the use of melatonin in children and adolescents aged 2-20 years, with chronic insomnia due to disorders beyond indication. Methods: We performed a systematic search for guidelines, systematic reviews, and randomised trials (RCTs) in Medline, Embase, Cochrane Library, PsycInfo, Cinahl, Guidelines International Network, Trip Database, Canadian Agency for Drugs and Technologies in Health, American Academy of Sleep Medicine, European Sleep Research Society and Scandinavian Health Authorities databases. A separate search for adverse events was also performed. The latest search for guidelines, systematic reviews, and adverse events was performed on March 17, 2023. The latest search for RCTs was performed on to February 6, 2023. The language was restricted to English, Danish, Norwegian, and Swedish. Eligible participants were children and adolescents (2-20 years of age) with chronic insomnia due to underlying disorders, in whom sleep hygiene practices have been inadequate and melatonin was tested. Studies exclusively on autism spectrum disorders or attention deficit hyperactive disorder were excluded. There were no restrictions on dosage, duration of treatment, time of consumption or release formula. Primary outcomes were quality of sleep, daytime functioning and serious adverse events, assessed at 2-4 weeks post-treatment. Secondary outcomes included total sleep time, sleep latency, awakenings, drowsiness, quality of life, non-serious adverse events, and all-cause dropouts (assessed at 2-4 weeks post-treatment), plus quality of sleep and daytime functioning (assessed at 3-6 months post-treatment). Pooled estimates were calculated using inverse variance random effects model. Statistical heterogeneity was calculated using I2 statistics. Risk of bias was assessed using Cochrane risk of bias tool. Publication bias was assessed using funnel plots. A multidisciplinary guideline panel constructed the recommendation using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The certainty of evidence was considered either high, moderate, low or very low depending on the extent of risk of bias, inconsistency, imprecision, indirectness, or publication bias. The evidence-to-decision framework was used to discuss the feasibility and acceptance of the constructed recommendation and its impact on resources and equity. The protocol is registered with the Danish Health Authority. Findings: We identified 13 RCTs, including 403 patients with a wide range of conditions. Melatonin reduced sleep latency by 14.88 min (95% CI 23.42-6.34, 9 studies, I2 = 60%) and increased total sleep time by 18.97 min (95% CI 0.37-37.57, 10 studies, I2 = 57%). The funnel plot for total sleep time showed no apparent indication of publication bias. No other clinical benefits were found. The number of patients experiencing adverse events was not statistically increased however, safety data was scarce. Certainty of evidence was low. Interpretation: Low certainty evidence supports a moderate effect of melatonin in treating sleep continuity parameters in children and adolescents with chronic insomnia due to primarily medical disorders beyond indication. The off-label use of melatonin for these patients should never be the first choice of treatment, but may be considered by medical specialists with knowledge of the underlying disorder and if non-pharmacological interventions are inadequate. If treatment with melatonin is initiated, adequate follow-up to evaluate treatment effect and adverse events is essential. Funding: The Danish Health Authority. The Parker Institute, Bispebjerg and Frederiksberg Hospital, supported by the Oak Foundation.

Use of melatonin in children and adolescents with idiopathic chronic insomnia: a systematic review, meta-analysis, and clinical recommendation.

Background: Melatonin prescriptions for children and adolescents have increased substantially during the last decade. Existing clinical recommendations focus on melatonin as a treatment for insomnia related to neurodevelopmental disorders. To help guide clinical decision-making, we aimed to construct a recommendation on the use of melatonin in children and adolescents aged 5-20 years with idiopathic chronic insomnia. Methods: A systematic search for guidelines, systematic reviews and randomised controlled trials (RCT) were performed in Medline, Embase, Cochrane Library, PsycInfo, Cinahl, Guidelines International Network, Trip Database, Canadian Agency for Drugs and Technologies in Health, American Academy of Sleep Medicine, European Sleep Research Society and Scandinavian Health Authorities databases. A search for adverse events in otherwise healthy children and adolescents was also performed. The latest search for guidelines, systematic reviews, and adverse events was performed on March 18, 2023. The latest search for RCTs was performed on to February 6, 2023. The language was restricted to English, Danish, Norwegian, and Swedish. Eligible participants were children and adolescents (5-20 years of age) with idiopathic chronic insomnia, in whom sleep hygiene practices have been inadequate and melatonin was tested. There were no restrictions on dosage, duration of treatment, time of consumption, or release formula. Primary outcomes were quality of sleep, daytime functioning and serious adverse events. Secondary outcomes included total sleep time, sleep latency, awakenings, drowsiness, quality of life, all-cause dropouts, and non-serious adverse events. Outcomes were assessed at different time points to assess short-term and long-term effects. Meta-analysis was performed using inverse variance random-effects model and risk of bias was assessed using Cochrane risk of bias tool. If possible, funnel plots would be constructed to investigate publication bias. Heterogeneity was calculated via I2 statistics. A multidisciplinary guideline panel formulated the recommendation according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). The certainty of evidence was considered either high, moderate, low or very low depending on the extent of risk of bias, inconsistency, imprecision, indirectness, or publication bias. The evidence-to-decision framework was subsequently used to discuss the feasibility and acceptance of the constructed recommendation alongside the impact on resources and equity. The protocol is registered with the Danish Health Authority. Findings: We included eight RCTs with 419 children and adolescents with idiopathic chronic insomnia. Melatonin led to a moderate increase in total sleep time by 30.33 min (95% confidence interval (CI) 18.96-41.70, 4 studies, I2 = 0%) and a moderate reduction in sleep latency by 18.03 min (95% CI -26.61 to -9.44, 3 studies, I2 = 0%), both as assessed by sleep diary. No other beneficial effects were found. None of the studies provided information on serious adverse events, yet the number of participants experiencing non-serious adverse events was increased (Relative risk 3.44, 95% CI 1.25-9.42, 4 studies, I2 = 0%). Funnel plots were not constructed due to the low number of studies. The certainty of evidence was very low on the quality of sleep and low for daytime functioning. Interpretation: Evidence of very low certainty shows that benefits are limited and unwanted events are likely when melatonin is used to treat otherwise healthy children and adolescents with chronic insomnia. Melatonin should never be the first choice of treatment for this particular population, yet carefully monitored short-term use may be considered if sleep hygiene practices and non-pharmacological interventions have proven inadequate, and only if daytime function is compromised. Funding: The Danish Health Authority and the Parker Institute, Bispebjerg and Frederiksberg Hospital supported by the Oak Foundation.

Validation of the Weiss Functional Impairment Rating Scale (WFIRS-P) as a Functional Impairment Measure in a General Population of Schoolchildren.

Functional impairment rating scales are few in numbers and have mainly been examined in clinical populations. The Weiss Functional Impairment Rating Scale-Parent report (WFIRS-P) is a case in point. We tested the psychometric properties of the WFIRS-P in the largest general population study to date and for the first time examined the factor structure of the scale in a general population setting. Participants were 2,027 schoolchildren aged 6 to 11. Parents/caregivers completed the WFIRS-P and criterion measures of quality of life, attention-deficit/hyperactivity disorder, and behavioral/emotional symptoms. Confirmatory factor analysis and convergent/divergent validity analyses supported a six-factor structure: family, life skills, self-concept, social activities, and the separation of the school domain into two smaller domains covering school learning and school behavior. Children with and without a history of referral differed significantly on all six domains supporting the external validity. In conclusion, the WFIRS-P was found to generate valid scores in a general population sample.

The factor structure of attention-deficit/hyperactivity disorder in schoolchildren.

BACKGROUND: Most studies support a bifactor model of childhood ADHD with two specific factors. However, several studies have not compared this model with a bifactor model with three specific factors, few have tested the actual strength of the factors, and none have examined whether "talks excessively" should be treated as a hyperactivity versus impulsivity symptom in children with ADHD. AIMS: To examine the factor structure of ADHD symptoms and evaluate the relative strength of potential factors. METHODS: Parent-reports on the ADHD-Rating Scale (ADHD-RS-IV) were collected for 2044 schoolchildren from the general population and 147 children with ADHD from a clinical sample. Single-, two- and three-(correlated and bi-)factor models were tested using confirmatory factor analysis. RESULTS: Most models had a satisfactory fit. However, a correlated three-factor model where "talks excessively" was included as an indicator of impulsivity, and especially a bifactor model with one strong, well-defined general and two/three (ICD-10 defined) weak specific factors fit the data slightly better than the remaining models. CONCLUSIONS: The factor structure is best characterized by a bifactor model with a strong general factor and two/three weaker specific factors. Therefore, we suggest emphasizing the ADHD-RS-IV total score rather than the subscale scores in clinical practice.

How much impairment is required for ADHD? No evidence of a discrete threshold.

BACKGROUND: A diagnosis of attention-deficit/hyperactivity disorder (ADHD) requires the presence of impairment alongside symptoms above a specific frequency and severity threshold. However, the question of whether that symptom threshold represents anything more than an arbitrary cutoff on a continuum of impairment requires further empirical study. Therefore, we present the first study investigating if the relationship between ADHD symptom severity and functional impairment is nonlinear in a way that suggests a discrete, nonarbitrary symptom level threshold associated with a marked step increase in impairment. METHODS: Parent reports on the ADHD-Rating Scale (ADHD-RS-IV), the Weiss Functional Impairment Rating Scale (WFIRS-P), and the Strengths and Difficulties Questionnaire were collected in a general population sample of 1st, 2nd, and 3rd graders (N = 1,914-2,044). RESULTS: Piecewise linear regression analyses and nonlinear regression modeling both demonstrated that the relationship between symptom severity (ADHD-RS-IV total score) and impairment (WFIRS-P mean score) was characterized by a gradual linear increase in impairment with higher symptom severity and no apparent step increase or changing rate of increase in impairment at a certain high ADHD-RS-IV total score level. Controlling for socioeconomic status, sex, and co-occurring conduct and emotional symptoms did not alter these results, though comorbid symptoms had a significant effect on impairment. CONCLUSIONS: There was no clear evidence for a discrete, nonarbitrary symptom severity threshold with regard to impairment. The results highlight the continued need to consider both symptoms and impairment in the diagnosis of ADHD.

Testing the evolutionary advantage theory of attention-deficit/hyperactivity disorder traits.

To reconcile the strong secular persistence of attention-deficit/hyperactivity disorder (ADHD) despite its impairing effects, ADHD traits have been postulated to offer an evolutionary advantage. It has been proposed that such advantages should in particular be observable under time-critical, novel, and resource-depleted conditions requiring response-readiness and high levels of scanning and exploration/foraging. Our objective was to provide the first behavioral test of this hypothesis. Schoolchildren from the general population with no/few (n = 56), mild (n = 50), moderate (n = 48), and severe (n = 48) ADHD traits, defined according to their ADHD-Rating Scale IV (ADHD-RS-IV) total score, participated in an exploratory foraging and response-readiness laboratory test. Here, children searched for coins hidden in locations of varying obscurity in an unfamiliar room for 1 min. Test-performance (number of coins found) adjusted for age, sex, and estimated IQ was analyzed categorically using multiple linear regression analyses and dimensionally by fitting a regression model including the ADHD-RS-IV score as a continuous measure. There were no differences in the mean number of coins between the No/Few (Mean = 7.82), Mild (Mean = 7.76), Moderate (Mean = 7.58), and Severe (Mean = 7.88) groups [F(3,195) = 0.24, p = 0.871]. Furthermore, excluding children with functional impairment, adjusting for verbal working memory and response inhibition, and stratifying for sex did not change these findings. Finally, continuous ADHD traits were not found to be related to test-performance [F(3,195) = 0.73, p = 0.536]. While our results do generally not support the evolutionary advantage theory (i.e., ADHD traits neither conferred an advantage nor a disadvantage), this does not disprove that ADHD traits may have offered advantages via other mechanisms.

Sleep Problems and Daily Functioning in Children With ADHD: An Investigation of the Role of Impairment, ADHD Presentations, and Psychiatric Comorbidity.

OBJECTIVE: Little systematic information is available regarding how sleep problems influence daytime functioning in children with ADHD, as the role of ADHD presentations and comorbidity is unclear. METHOD: In total, 397 children were assessed with the Children's Sleep Habits Questionnaire, the Weiss Functional Impairment Rating Scale, and the ADHD Rating Scale. RESULTS: We found a moderate, positive correlation between sleep problems and impaired functioning in both children with ADHD and in typically developed children. ADHD presentations did not differ significantly with respect to sleep problem profile, but having a comorbid internalizing or autistic disorder lead to higher sleep problem score. CONCLUSION: Sleep problems and impaired daily functioning were more common in children with ADHD, but the overall association between sleep problems and impaired daily functioning was similar in clinical and nonclinical children. Internalizing or autistic comorbid disorders added significantly to the sleep problems.

Disturbed sleep in attention-deficit hyperactivity disorder (ADHD) is not a question of psychiatric comorbidity or ADHD presentation.

Attention-deficit hyperactivity disorder (ADHD) is a heterogeneous psychiatric disorder with three different presentations and high levels of psychiatric comorbidity. Serious sleep complaints are also common, but the role of the presentations and comorbidity in sleep is under-investigated in ADHD. Consequently, the goal of the study was to investigate sleep problems in medicine-naive school-aged children (mean age = 9.6 years) with ADHD compared to controls using objective methods and to examine the role of comorbidity and presentations. Ambulatory polysomnography results suggested that children with ADHD (n = 76) had significantly more sleep disturbances than controls (n = 25), including a larger percentage of rapid eye movement (REM) sleep and more sleep cycles, as well as lower mean sleep efficiency, mean non-REM (NREM) sleep stage 1 and mean NREM sleep stage 3. No significant between-group differences were found on the multiple sleep latency test. Stratifying for comorbidity in the ADHD group did not reveal major differences between groups, but mean sleep latency was significantly longer in children with ADHD and no comorbidity compared to controls (36.1 min; SD = 30.1 versus 22.6 min; SD = 15.2). No differences were found between ADHD presentations. Our results support the presence of night-time sleep disturbances in children with ADHD. Poor sleep does not appear to be attributable to comorbidity alone, nor do sleep disturbances differ within ADHD presentations.