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Identification and Characterization of Influential Factors in Susceptibility to Attention Deficit Hyperactivity Disorder Among Preschool-Aged Children.

ABSTRACT: Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder. Currently, increasing amounts of attention have been focused on the epidemiologic profiling of ADHD in children, viewed as a continuously distributed risk dimension throughout the whole lifespan. This study aimed to identify and characterize potential influential factors susceptible to ADHD-related symptoms among preschool-aged children. A comprehensive questionnaire was self-designed for both children and their parents or guardians and was distributed to 30 kindergartens from Beijing and Hebei, collecting potential influential factors in susceptibility to ADHD. ADHD was assessed by the Conner's Abbreviated Symptom Questionnaire (C-ASQ), and 7,938 children were analyzed. Least absolute shrinkage and selection operator (LASSO) regression and hierarchical degree of adjustment were used to control possible covariates. Five factors, namely, children's secondhand smoking exposure, breastfeeding duration, sleep mode, maternal pregnancy smoking exposure, and parental self-rating for patience, were identified to be independently and significantly associated with ADHD susceptibility. Meanwhile, dose-response relationships were observed between breastfeeding duration, parental self-rating for patience, and ADHD-related symptoms. Finally, a nomogram model was created for predicting ADHD susceptibility based on significant and conventional attributes under each criterion.

SUBMITTER: Deng X

PROVIDER: S-EPMC8841729 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Identification and Characterization of Influential Factors in Susceptibility to Attention Deficit Hyperactivity Disorder Among Preschool-Aged Children.

Deng Xiangling X Yang Min M Wang Shunan S Zhou Bo B Wang Kundi K Zhang Zhixin Z Niu Wenquan W

Frontiers in neuroscience 20220131

Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder. Currently, increasing amounts of attention have been focused on the epidemiologic profiling of ADHD in children, viewed as a continuously distributed risk dimension throughout the whole lifespan. This study aimed to identify and characterize potential influential factors susceptible to ADHD-related symptoms among preschool-aged children. A comprehensive questionnaire was self-designed ...[more]

PMID: 35173570

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Project description:ImportanceAttention-deficit/hyperactivity disorder (ADHD) is diagnosed in approximately 2.4% of preschool-age children. Stimulants are recommended as first-line medication treatment. However, up to 25% of preschool-age children with ADHD are treated with α2-adrenergic agonist medications, despite minimal evidence about their efficacy or adverse effects in this age range.ObjectiveTo determine the frequency of reported improvement in ADHD symptoms and adverse effects associated with α2-adrenergic agonists and stimulant medication for initial ADHD medication treatment in preschool-age children.Design, setting, and participantsRetrospective electronic health record review. Data were obtained from health records of children seen at 7 outpatient developmental-behavioral pediatric practices in the Developmental Behavioral Pediatrics Research Network in the US. Data were abstracted for 497 consecutive children who were younger than 72 months when treatment with an α2-adrenergic agonist or stimulant medication was initiated by a developmental-behavioral pediatrician for ADHD and were treated between January 1, 2013, and July 1, 2017. Follow-up was complete on February 27, 2019.Exposuresα2-Adrenergic agonist vs stimulant medication as initial ADHD medication treatment.Main outcomes and measuresReported improvement in ADHD symptoms and adverse effects.ResultsData were abstracted from electronic health records of 497 preschool-age children with ADHD receiving α2-adrenergic agonists or stimulants. Median child age was 62 months at ADHD medication initiation, and 409 children (82%) were males. For initial ADHD medication treatment, α2-adrenergic agonists were prescribed to 175 children (35%; median length of α2-adrenergic agonist use, 136 days) and stimulants were prescribed to 322 children (65%; median length of stimulant use, 133 days). Improvement was reported in 66% (95% CI, 57.5%-73.9%) of children who initiated α2-adrenergic agonists and 78% (95% CI, 72.4%-83.4%) of children who initiated stimulants. Only daytime sleepiness was more common for those receiving α2-adrenergic agonists vs stimulants (38% vs 3%); several adverse effects were reported more commonly for those receiving stimulants vs α2-adrenergic agonists, including moodiness/irritability (50% vs 29%), appetite suppression (38% vs 7%), and difficulty sleeping (21% vs 11%).Conclusions and relevanceIn this retrospective review of health records of preschool-age children with ADHD treated in developmental-behavioral pediatric practices, improvement was noted in the majority of children who received α2-adrenergic agonists or stimulants, with differing adverse effect profiles between medication classes. Further research, including from randomized clinical trials, is needed to assess comparative effectiveness of α2-adrenergic agonists vs stimulants.

Project description:Intra-subject variability (ISV) is the most consistent behavioral deficit in Attention Deficit Hyperactivity Disorder (ADHD). ISV may be associated with networks involved in sustaining task control (cingulo-opercular network: CON) and self-reflective lapses of attention (default mode network: DMN). The current study examined whether connectivity supporting attentional control is atypical in children with ADHD. Group differences in full-brain connection strength and brain-behavior associations with attentional control measures were examined for the late-developing CON and DMN in 50 children with ADHD and 50 typically-developing (TD) controls (ages 8-12 years). Children with ADHD had hyper-connectivity both within the CON and within the DMN. Full-brain behavioral associations were found for a number of between-network connections. Across both groups, more anti-correlation between DMN and occipital cortex supported better attentional control. However, in the TD group, this brain-behavior association was stronger and occurred for a more extensive set of DMN-occipital connections. Differential support for attentional control between the two groups occurred with a number of CON-DMN connections. For all CON-DMN connections identified, increased between-network anti-correlation was associated with better attentional control for the ADHD group, but worse attentional control in the TD group. A number of between-network connections with the medial frontal cortex, in particular, showed this relationship. Follow-up analyses revealed that these associations were specific to attentional control and were not due to individual differences in working memory, IQ, motor control, age, or scan motion. While CON-DMN anti-correlation is associated with improved attention in ADHD, other circuitry supports improved attention in TD children. Greater CON-DMN anti-correlation supported better attentional control in children with ADHD, but worse attentional control in TD children. On the other hand, greater DMN-occipital anti-correlation supported better attentional control in TD children.

Project description:OBJECTIVE:This was a single-dose, one-period, multicenter, pharmacokinetic (PK) study to evaluate the PK of methylphenidate (MPH) hydrochloride multilayer extended-release capsules (MPH-MLR) in preschool children aged 4 to < 6 years, previously diagnosed with attention-deficit/hyperactivity disorder (ADHD), and on a stable dose of MPH. METHODS:Preschool-aged children (N = 10) received a single oral dose of MPH-MLR (10, 15, or 20 mg) sprinkled over applesauce; a dose equivalent to their pre-enrollment daily dose of MPH. Blood samples for the measurement of MPH concentrations were obtained pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose. No structural model was assumed in the derivation of PK values for analysis. Maximum plasma concentration (Cmax), area under the concentration-time curve (AUC), elimination half-life, clearance (CL), and volume of distribution (Vd) data were compared with a historical group of older children aged 6-11 years (N = 11) and analyzed by bodyweight. Safety (adverse event monitoring, vital signs, electrocardiogram, clinical laboratory testing, physical examination) was assessed. RESULTS:Mean dose-normalized Cmax and area under the curve to the last measurable observation (AUC0-t) values were similar across dose groups, ranging from 0.67 ng/mL/mg (MPH 15 mg) to 0.81 ng/mL/mg (MPH 10 mg) for Cmax/dose, and from 7.80 h × ng/mL/mg (MPH 20 mg) to 8.92 h × ng/mL/mg (MPH 10 mg) for AUC0-t/dose. PK results were integrated into a previously described pharmacostatistical population PK model. Visual predictive check plots showed greater variability in the 6- to 11-year-old group than the 4- to < 6-year-old group, and CL increased with increasing body weight in a greater than dose-proportional manner. Mean CL, normalized for body weight, was constant for all dose groups, ranging from 4.88 L/h/kg to 5.80 L/h/kg. Median time to Cmax ranged from 2.00 to 3.00 h post-dose, and overall, dose-normalized Cmax concentrations indicated greater systemic exposures of MPH-MLR in preschool children aged 4 to < 6 years compared with children aged 6-11 years. Children aged 4 to < 6 years had a lower Vd than children aged 6-11 years. There were no unexpected safety signals. CONCLUSION:The PK of MPH-MLR in preschool children demonstrated the biphasic absorption profile described earlier in older children, and the PK profile in children with ADHD aged 4 to < 6 years was similar to the profile in those aged 6-11 years, apart from a lower Vd and relatively higher systemic MPH levels for children in the preschool group. TRIAL REGISTRATION:Clinicaltrials.gov Identifier: NCT02470234.

Dataset Information

Identification and Characterization of Influential Factors in Susceptibility to Attention Deficit Hyperactivity Disorder Among Preschool-Aged Children.

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Identification and Characterization of Influential Factors in Susceptibility to Attention Deficit Hyperactivity Disorder Among Preschool-Aged Children.

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