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Background: Attention-deficit/hyperactivity disorder (ADHD) affects approximately 5% of children globally, with symptoms often persisting into adulthood. While pharmacological interventions are commonly employed for management, understanding the optimal dosing for efficacy and tolerability remains crucial. This study aims to conduct a dose–response network meta-analysis to estimate the efficacy of pharmacological treatments across different doses, aiming to inform clinical decision-making and improve treatment outcomes. Methods: This updated systematic review will include randomized controlled trials evaluating ADHD medication efficacy in children, adolescents, and adults. An updated search from a 2018 NMA will be conducted across multiple electronic databases with no language restrictions, using specific eligibility criteria focused on randomized controlled trials. The primary outcome will assess the severity of ADHD core symptoms, while secondary outcomes will consider treatment tolerability. A dose–response Bayesian hierarchical model will be used to estimate dose–response curves for each medication, identifying optimal dosing strategies. Discussion: With this dose–response network meta-analysis, we aim to better understand the dose–response relationship of pharmacological treatment in ADHD, which could help clinician to the identification of optimal doses. Systematic review registration: OSF https://doi.org/10.17605/OSF.IO/3MY4A. [ABSTRACT FROM AUTHOR]

Background: Attention deficit/hyperactivity disorder (ADHD) entails inattention, impulsivity, and restlessness at a disabling level. The pharmacological treatment of ADHD rests on the use of centrally acting stimulants, such as methylphenidate and D-amphetamine. In some patients, these drugs cause side effects that preclude their use.Case Presentation: We present three adult male, Caucasian, ADHD patients (24, 37, and 43 years old) whose ADHD symptoms improved during treatment with testosterone. The first patient experienced loss of libido during treatment with methylphenidate; for this, he was offered a trial of testosterone. Unexpectedly, his ADHD symptoms improved with testosterone treatment, and this effect continued with testosterone as monotherapy. The two other patients, who also had side effects from centrally acting stimulants, received testosterone monotherapy with similar results. The effect has now continued for 4.5-5 years at the same doses: 10-60 mg testosterone/day, administered as a skin gel. Prior to testosterone treatment, the patients had serum levels of testosterone in the low-normal range: 12-16 nmol/L (age-specific reference range: 10.4-32.6 nmol/L). The testosterone/sex hormone-binding globulin ratio was low in two patients (0.32 and 0.34; age-specific reference range: 0.38-1.1), suggesting low free serum levels of testosterone. Serum testosterone levels and testosterone/sex hormone-binding globulin ratios increased with testosterone treatment in all patients, but remained within reference values.Conclusion: These cases suggest that a moderately reduced serum level of free testosterone may contribute to the ADHD symptoms of some adult male ADHD patients, and that testosterone treatment may be of value for these patients. [ABSTRACT FROM AUTHOR]

Background: Loss of control eating (LOC-E) in youth predicts the later development of full-syndrome binge-eating disorder (BED), and therefore, could be a relevant target for prevention treatments. To develop these treatments, it is important to understand the underlying disease processes and mechanisms. Based on the putative role of neurocognitive impairments in the pathogenesis of LOC-E, treatments that modulate these neurocognitive factors warrant further exploration. For instance, stimulants are an effective treatment for impulsivity in youth with attention deficit/hyperactivity disorder (ADHD) and have been shown to improve symptoms of BED in adults. Notably, stimulants have not been examined as a treatment for LOC-E in youth. To explore this gap, we aim to measure change in LOC-E episodes and secondary outcomes in youth with comorbid ADHD and LOC-E who are being started on stimulants. Methods: We will collect prospective observational data on forty 8-to-13-year-old youth diagnosed with comorbid ADHD and LOC-E who are initiating a stimulant for ADHD. Prior to stimulant initiation, participants will complete baseline measures including LOC-E episode frequency in the last 3 months (primary outcome), and secondary outcomes including disordered eating cognitions, emotions and behaviors, ADHD symptom severity, parental LOC-E, impulsivity and reward sensitivity, and anxiety/mood severity. Outcome measurements will be gathered again at 3-months after initiating the stimulant. Within-patient standardized effect sizes with 95% confidence intervals will be calculated from baseline to 3-month follow-up for all outcomes. Discussion: Many individuals with LOC-E or binge eating do not fully remit over the course of psychotherapy. Whereas psychotherapy may address psychological and sociocultural domains associated with LOC-E, some individuals with neurocognitive impairments (e.g., ADHD) and neurobiological deficits (e.g., low intrasynaptic dopamine or norepinephrine) may benefit from adjunctive treatment that targets those factors. This will be the first study to provide pilot data for future studies that could examine both the effect of stimulants on LOC-E in youth and underlying mechanisms. Trial registration: Trial registration number: NCT05592119 [ABSTRACT FROM AUTHOR]

Background: Attention deficit/hyperactivity disorder (ADHD) is the most common chronic mental and behavioral disorder among children. Some studies showed the lower levels of vitamin D in patients with ADHD compared with the healthy people. Few clinical trials were conducted in this field. The present study will be performed to examine the effect of vitamin D supplementation in children with ADHD.Methods: We will conduct a double-blind, randomized controlled clinical trial to investigate the effect of vitamin D supplementation on brain waves, behavioral performance, serum nitric oxide, malondialdehyde, and high-sensitivity C-reactive protein in 50 patients with ADHD. The intervention group will receive one capsule 50,000 IU vitamin D every week, for 8 weeks. The control group will receive one placebo capsule containing 1000 mg olive oil every week. Electroencephalography will be performed for 10 min using Brain Master Discovery from 19 scalp sites both before the first intervention and the 10 sessions of the therapy. The artifact-free periods of 1-min electroencephalography data will be analyzed for quantitative electroencephalography measures.Discussion: For the first time, this clinical trial will evaluate the effect of vitamin D supplementation on brain waves, serum nitric oxide, malondialdehyde, and high-sensitivity C-reactive protein in patients with ADHD. The results of the present clinical trial will provide a better vision about the vitamin D efficacy in patients with ADHD.Trial Registration: Registered on 5 November 2020 at Iranian Registry of Clinical Trials with code number IRCT20200922048802N1 ( https://www.irct.ir/trial/51410 ). [ABSTRACT FROM AUTHOR]

Background: Prenatal maternal tobacco smoking is a predictor of child attention-deficit/hyperactivity disorder (ADHD) and is associated with offspring telomere length (TL). In this study, we examine the relationship between maternal prenatal smoking, infant TL, and maternal report of early childhood symptoms of ADHD.Methods: One-hundred and eighty-one mother-infant dyads were followed prospectively for the infant's first 18 months of life. Prenatal smoking was assessed from maternal report and medical records. TL was measured from infant buccal swab DNA obtained across the first 18 months of life. ADHD symptoms were obtained from maternal report on the Child Behavior Check List. Multiple regression models tested the relation between prenatal smoking and both ADHD symptoms and infant TL. Additional analyses tested whether the change in infant TL influenced the relation between prenatal smoking and ADHD symptoms.Results: Sixteen percent of mothers reported prenatal smoking. Infant TL at 4, 12, and 18 months of age were correlated. Consistent with previous cross-sectional studies linking shorter offspring TL to maternal prenatal smoking, maternal prenatal smoking predicted greater telomere shortening from four to 18 months of infant age (β = - 5.797, 95% CI [-10.207, -1.386]; p = 0.010). Maternal depression was positively associated with both prenatal smoking (odds ratio (OR): 4.614, 95% CI [1.733, 12.282]; p = 0.002) and child ADHD symptoms (β = 4.713, 95% CI [2.073, 7.354]; p = 0.0006). To prevent confounding, analyses examined the relation between TL, ADHD symptoms, and prenatal smoking only in non-depressed mothers. In non-depressed mothers, infant TL attrition across the first 18 months moderated the relation between smoking and child ADHD.Conclusions: The findings extend previous studies linking prenatal smoking to shorter infant TL by providing data demonstrating the effect on TL trajectory. The relation between prenatal smoking and early infant ADHD symptoms was moderated by the change in TL. The findings provide novel initial evidence suggesting that TL dynamics are one mechanistic pathway influencing the relation between maternal prenatal smoking and ADHD. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that Attention Deficit Hyperactive Disorder (ADHD) affect individuals across their lifespan, especially in relation to employment. The purpose of this review was to synthesize the results from studies examining the prospective association of ADHD diagnosis in childhood and later education, earnings and employment, compared to children without an ADHD diagnosis. A review protocol was prospectively registered with PROSPERO (ID = CRD42019131634). The findings were reported according to the PRISMA guidelines. The systematic review is based on a structured and preplanned analysis of original prospective longitudinal studies. A total of 2505 potential records were identified, two through backward search. Six papers met the inclusion criteria. One paper was assessed as good, four as fair and one as poor quality. The studies indicated that ADHD diagnosis affected the nature of the individual's attachment to the labour market across different labour market attachment outcomes. Adults with persisting symptoms, had significantly more problems at work. Even if ADHD symptoms desist in adulthood, the negative impact of earlier ADHD symptoms can still be seen on occupational outcomes. Significantly fewer probands had a Bachelor's degree compared to controls. Based on one good quality study and four fair quality studies, it is indicated that patients with childhood diagnosed ADHD, generally experience employment of lower quality compared with peers, in relation to income, education and occupational attainment. The overall level of evidence is rated as poor. [ABSTRACT FROM AUTHOR]

Background: Aggressive behavior in children and adolescents may be accounted for by several disruptive behavioral disorders (DBD) including attention-deficit/hyperactive (ADHD), conduct (CD), and oppositional defiant (ODD), disorders and intermittent explosive disorder (IED). The comorbidity among the DBDs is well known, but not its comorbidity with IED. Method: We reanalyzed data from the National Comorbidity Studies (adolescents and adults), and from a large clinical research adult sample, to estimate the comorbidity of IED with each of the DBDs and to explore correlates of these comorbidities. Results: The rate of current comorbidity between IED and the DBDs ranged from 10 to 19%, in adolescents (5–14% in adults) with odds ratios of about five. The onset of ADHD typically appeared before onset of IED while onset ODD and CD more typically appeared before that of IED in adolescents and about equally before or after IED in adults but IED persisted outside the duration window in many (ADHD) or most (ODD, CD) cases. Measures of impulsive aggression severity were highest in those with IED+DBD but relatively low in those with DBD alone while measures of DBD severity were highest in those with DBD alone and in those with IED+DBD. Conclusion: Despite the comorbidity of IED with the DBDs, IED can be separated from the DBDs over time and in terms of severity measures of IED and of DBD. Overall, impulsive aggression varies with IED while DBD behaviors vary with DBD. Based on this, clinicians should consider IED in their differential in the workup of impulsively aggressive children and adolescents. [ABSTRACT FROM AUTHOR]

Background: Widening definitions of health conditions have the potential to affect millions of people and should only occur when there is strong evidence of benefit. In the last version of the Diagnostic and Statistical Manual of Mental Disorders (DSM), the DSM-5 Committee changed the Attention Deficit Hyperactivity Disorder (ADHD) age of onset criterion in two ways: raising the age of symptom onset and removing the requirement for symptoms to cause impairment. Given concerns about ADHD prevalence and treatment rates, we aimed to evaluate the evidence available to support these changes using a recently developed Checklist for Modifying Disease Definitions. Methods: We identified and analysed research informing changes to the DSM-IV-TR ADHD age of onset criterion. We compared this evidence to the evidence recommended in the Checklist for Modifying Disease Definitions. Results: The changes to the DSM-IV-TR age of onset criterion were based on a literature review (publicly available as a 2 page document with online table of included studies), which we appraised as at high risk of bias. Estimates of the change in ADHD prevalence resulting from change to the age of onset criterion were based on a single study that included only a small number of children with ADHD (n = 68) and only assessed the impact of change to the age component of the criterion. No evidence was used by, or available to the Committee regarding the impact on prevalence of removal of the requirement for impairment, or the effect of the criterion changes on diagnostic precision, the prognosis of, or the potential benefits or harms for individuals diagnosed by the new, but not old criterion. Conclusions: The changes to the age of onset criterion were based on minimal research evidence that suffered from either high risk of bias or poor applicability. The minimal documentation available makes it difficult to judge the rigor of the process behind the criterion changes. Use of the Checklist for Modifying Disease Definitions would assist future proposed modifications of the DSM ADHD criteria, provide guidance on the studies needed to inform potential changes and would improve the transparency and documentation of the process. [ABSTRACT FROM AUTHOR]

Background: Attentional disorders (ADD) feature decreased attention span, impulsivity, and over-activity interfering with successful lives. Childhood onset ADD frequently persists to adulthood. Etiology may be hereditary or disease associated. Prevalence is 5% but recognition may be 'overshadowed' by comorbidities (brain injury, mood disorder) thereby escaping formal recognition. Blinded diagnosis by MRI has failed. ADD may not itself manifest a single anatomical pattern of brain abnormality but may reflect multiple, unique responses to numerous and diverse etiologies. Alternatively, a stable ADD-specific brain pattern may be better detected by brain physiology. EEG coherence, measuring cortical connectivity, is used to explore this possibility.Methods: Participants: Ages 2 to 22 years; 347 ADD and 619 neurotypical controls (CON). Following artifact reduction, principal components analysis (PCA) identifies coherence factors with unique loading patterns. Discriminant function analysis (DFA) determines discrimination success differentiating ADD from CON. Split-half and jackknife analyses estimate prospective diagnostic success. Coherence factor loading constitutes an ADD-specific pattern or 'connectome'.  RESULTS: PCA identified 40 factors explaining 50% of total variance. DFA on CON versus ADD groups utilizing all factors was highly significant (p≤0.0001). ADD subjects were separated into medication and comorbidity subgroups. DFA (stepping allowed) based on CON versus ADD without comorbidities or medication treatment successfully classified the correspondingly held out ADD subjects in every instance. Ten randomly generated split-half replications of the entire population demonstrated high-average classification success for each of the left out test-sets (overall: CON, 83.65%; ADD, 90.07%). Higher success was obtained with more restricted age sub-samples using jackknifing: 2-8 year olds (CON, 90.0%; ADD, 90.6%); 8-14 year olds (CON, 96.8%; ADD 95.9%); and 14-20 year-olds (CON, 100.0%; ADD, 97.1%). The connectome manifested decreased and increased coherence. Patterns were complex and bi-hemispheric; typically reported front-back and left-right loading patterns were not observed. Subtemporal electrodes (seldom utilized) were prominently involved.  CONCLUSIONS: Results demonstrate a stable coherence connectome differentiating ADD from CON subjects including subgroups with and without comorbidities and/or medications. This functional 'connectome', constitutes a diagnostic ADD phenotype. Split-half replications support potential for EEG-based ADD diagnosis, with increased accuracy using limited age ranges. Repeated studies could assist recognition of physiological change from interventions (pharmacological, behavioral). [ABSTRACT FROM AUTHOR]

Background: Attention deficit/hyperactivity disorder (ADHD), the most common childhood neurobehavioural disorder, can produce a series of negative effects on children, adolescents, and even adults as well as place a serious economic burden on families and society. However, the prevalence of ADHD is not well understood in China. The goal of this study was to estimate the pooled prevalence of ADHD among children and adolescents in China using a systematic review and meta-analysis. Methods: A systematic literature search was conducted in PubMed, Web of Science, MEDLINE, CNKI, Wanfang, Weipu and CBM databases, and relevant articles published from inception to March 1, 2016, that provided the prevalence of ADHD among children and adolescents in China were reviewed. The risk of bias in individual studies was assessed using the Risk of Bias Tool for prevalence studies. Pooled-prevalence estimates were calculated with a random-effects model. Sources of heterogeneity were explored using subgroup analyses. Results: Sixty-seven studies with a total of 275,502 individuals were included in this study. The overall pooled-prevalence of ADHD among children and adolescents in China was 6.26% (95% CI: 5.36-7.22%) with significant heterogeneity (I² = 99.0%, P < 0.001). The subgroup analyses showed that, the variables "geographic location" and "source of information" partially explained of the heterogeneity in this study (P < 0.05). The prevalence of ADHD-I was the highest of the subtypes, followed by ADHD-HI and ADHD-C. Conclusions: The prevalence of ADHD among children and adolescents in China is generally consistent with the worldwide prevalence and shows that ADHD affects quite a large number of people under 18 years old. However, a nationwide study is needed to provide more accurate estimations. [ABSTRACT FROM AUTHOR]

Background: Patients with a substance use disorder (SUD) and co-occurring attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) often start using substances in an attempt to cope with the stress related to their ADHD or ASD. To improve treatment for these patient groups, it is important to identify and compare the various coping styles between SUD patients with and without ADHD or ASD and with subjects from a general population sample. Methods: Cross-sectional study using the Utrecht Coping List (UCL) in 50 SUD patients, 41 SUD + ADHD patients, 31 SUD + ASD patients and 1,200 railway employees. Results: Compared with the reference group, all three SUD groups showed a significant higher mean on the Palliative reaction, Avoidance, and Passive reaction subscales of the UCL. The scores for all UCL subscales of the SUD and the SUD+ADHD groups were very similar. However, the SUD+ASD group scored higher on Passive reaction and lower on Reassuring thoughts than the SUD and the SUD + ADHD groups and lower on Expression of emotions subscale in comparison with the SUD + ADHD group. Conclusions: Regardless of the presence of a co-occurring disorder, SUD patients reported more palliative, avoidant and passive coping when confronted than people in the general population. In addition, SUD patients with co-occurring ASD were different from other SUD patients in their coping and professionals should take this into account when working on more adaptive coping strategies with these patients. [ABSTRACT FROM AUTHOR]

Background: Attention deficit/hyperactivity disorder (ADHD) often presents as an impairing lifelong condition in adults; yet it is currently underdiagnosed and undertreated in many European countries. This analysis examines the characteristics of adult patients with ADHD in a European (EUR) and non-European (NE) patient population. Methods: Baseline data from the open-label treatment period of a randomized trial of atomoxetine in adult patients with ADHD (N=2017; EUR, n=1217; NE, n=800) were examined. All patients who were enrolled were included in the baseline analyses. Results: The demographics for patients in the EUR and NE groups were comparable. Patients in the EUR group had a somewhat lower percentage of prior exposure to psychostimulants compared with the NE group (32.7% vs. 38.9%, p=.0049). Scores on the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version with adult ADHD prompts (18-item total, inattentive and hyperactive/impulsive subscales, and index) were comparable. The adult ADHD Quality of Life-Life Outlook and Life Productivity domain scores were significantly different between groups (p=.0004). The EuroQol-5 Dimension United Kingdom and United States population-based index scores and Health State score were comparable between groups. Conclusions: Adults with ADHD in Europe present similar demographics and baseline characteristics to those outside Europe and hence, study results outside Europe may be generalizable to patients in Europe. [ABSTRACT FROM AUTHOR]

Background: Reduced executive functions (EF) are commonly associated with developmental conditions (e.g., autism spectrum disorder, ASD; attention deficit/hyperactivity disorder, ADHD), although EF seems to be typical in children with callous unemotional (CU) traits. Regulatory function (RF) is a proposed infant precursor that maps on onto factors driving later EF. Here, we first test whether RF is specifically and negatively associated with ASD and ADHD traits, but not CU traits. Second, we test whether RF can act as a protective factor, by moderating the association between infant markers and subsequent ASD and ADHD traits., Methods: Participants were 79 infants at high (N = 42) and low (N = 37) familial risk for ASD. Data come from the 14-month infant visit (Autism Observational Scale for Infants; AOSI; activity level and RF from the Infant Behavior Questionnaire; IBQ) and the 7-year visit (ASD traits: Social Responsiveness Scale, SRS; ADHD traits: Conners 3, CU traits: Inventory of Callous Unemotional Traits)., Results: Infant RF was negatively associated with later traits of ASD (B = - 0.5, p = 0.01) and ADHD inattention (B = - 0.24, p = 0.02) but not hyperactivity (B = - 0.25, p = 0.10) or CU traits (B = 0.02, p = 0.86). RF moderated the association between infant AOSI score and ASD traits, with a significant effect in those with low RF (B = 0.10, p = 0.006), not high RF (B = 0.01, p = 0.78). Similarly, for ADHD, infant activity level was associated with later ADHD inattention in those with low (B = 0.17, p = 0.04) but not high RF (B = 0.07, p = 0.48). For ADHD hyperactivity symptoms, activity level was predictive at both high and low levels of RF., Conclusions: Strong RF may allow children to compensate for other atypicalities, thus attenuating the association between infant markers and later disorder traits. Whilst infant RF was associated with both ASD and ADHD inattention traits, there was no association with ADHD hyperactivity or CU traits. This suggests that any protective effect may not be universal and emphasises the need for a better understanding of the underlying moderating mechanisms.

Background: Attention deficit/hyperactivity disorder (ADHD), the most common childhood neurobehavioural disorder, can produce a series of negative effects on children, adolescents, and even adults as well as place a serious economic burden on families and society. However, the prevalence of ADHD is not well understood in China. The goal of this study was to estimate the pooled prevalence of ADHD among children and adolescents in China using a systematic review and meta-analysis., Methods: A systematic literature search was conducted in PubMed, Web of Science, MEDLINE, CNKI, Wanfang, Weipu and CBM databases, and relevant articles published from inception to March 1, 2016, that provided the prevalence of ADHD among children and adolescents in China were reviewed. The risk of bias in individual studies was assessed using the Risk of Bias Tool for prevalence studies. Pooled-prevalence estimates were calculated with a random-effects model. Sources of heterogeneity were explored using subgroup analyses., Results: Sixty-seven studies with a total of 275,502 individuals were included in this study. The overall pooled-prevalence of ADHD among children and adolescents in China was 6.26% (95% CI: 5.36-7.22%) with significant heterogeneity (I 2  = 99.0%, P < 0.001). The subgroup analyses showed that, the variables "geographic location" and "source of information" partially explained of the heterogeneity in this study (P < 0.05). The prevalence of ADHD-I was the highest of the subtypes, followed by ADHD-HI and ADHD-C., Conclusions: The prevalence of ADHD among children and adolescents in China is generally consistent with the worldwide prevalence and shows that ADHD affects quite a large number of people under 18 years old. However, a nationwide study is needed to provide more accurate estimations.