Introduction:
Currently, assessing ADHD treatment response to stimulants relies on rating scales and subjective questionnaires and sometimes a CPT. Such tools fall short of objective, quantifiable ...measurement of effect, especially in natural settings and can result in inconsistent treatment.
Method:
We report results from two studies using a novel proof-of-concept approach. A preliminary trial of 10 individuals used a high-fidelity eye tracker; a second study of 100 individuals used webcams at the participants’ homes.
Results:
Both studies evaluated stimulant effect using reading behavior analysis, being an ADHD symptom that stimulants affect and a major symptom patients want to improve. Both showed a significant change in reading behavior related to medication state, suggesting a clear, objective measure of stimulant effect.
Conclusion:
Using ubiquitous hardware, investigators created a user-friendly treatment assessment platform where individuals can collect their own objective data within minutes in any setting where they have access to a web camera and computer.
In response to mechanical stimuli the freshwater sponge Ephydatia muelleri (Demospongiae, Haplosclerida, Spongillidae) carries out a series of peristaltic-like contractions that is effective in ...expelling clumps of waste material from the aquiferous system. Rates of contraction depend on the region of tissue they are propagating through: 0.3-1 microm s(-1) in the peripheral canals, 1-4 microm s(-1) in central canals, and 6-122 microm s(-1) in the osculum. Faster events include twitches of the entire sponge choanosome and contraction of the sheet-like apical pinacoderm that forms the outer surface of the animal. Contraction events are temporally and spatially coordinated. Constriction of the tip of the osculum leads to dilation of excurrent canals; fields of ostia in the apical pinacoderm close in unison just prior to contraction of the choanosome, apical pinacoderm and osculum. Relaxation returns the osculum, canals and the apical pinacoderm to their normal state, and three such coordinated 'inflation-contraction' responses typically follow a single stimulus. Cells in the mesohyl arrest crawling as a wave of contraction passes, suggesting an extracellular signal may pass between cells. Bundles of actin filaments traverse endopinacocytes of the apical pinacoderm. Actin-dense plaques join actin bundles in adjacent pinacocytes to form continuous tracts spanning the whole sponge. The orchestrated and highly repeatable series of contractions illustrates that cellular sponges are capable of coordinated behavioural responses even in the absence of neurons and true muscle. Propagation of the events through the pinacocytes also illustrates the presence of a functional epithelium in cellular sponges. These results suggest that control over a hydrostatic skeleton evolved prior to the origin of nerves and true muscle.
The view that sponges lack tissue level organisation, epithelia, sensory cells and coordinated behaviour is challenged by recent molecular studies showing the existence in Porifera of molecules and ...proteins that define cell signalling systems in higher order metazoans. Demonstration that freshwater sponges can contract their canals in an organised manner in response to both external and endogenous stimuli prompted us to examine the physiology of the contraction behaviour. Using a combination of digital time-lapse microscopy, high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis, immunocytochemistry and pharmacological manipulations, we tested the role of the diffusible amino acids glutamate and gamma-aminobutyric acid (GABA) and a short-lived diffusible gas, nitric oxide (NO), in triggering or modulating contractions in Ephydatia muelleri. We identified pools of glutamate, glutamine and GABA used to maintain a metabotropic glutamate and GABA receptor signalling system. Glutamate induced contractions and propagation of a stereotypical behaviour inflating and deflating the canal system, acting in a dose-dependent manner. Glutamate-triggered contractions were blocked by the metabatropic glutamate receptor inhibitor AP3 and by incubation of the sponge in an allosteric competitive inhibitor of glutamate, Kynurenic acid. Incubation in GABA inhibited glutamate-triggered contractions of the sponge. Nitric oxide synthase, involved in the formation of the diffusible gas NO, was localised using NADPH-diaphorase to mesenchyme cells in the osculum and pinacoderm. A cGMP assay showed the same cells were labelled suggesting that the NO system is functional. Our findings suggest sponges coordinate behaviour using chemical messenger systems common to other animals.
3-Year Follow-up of the NIMH MTA Study Jensen, Peter S; Arnold, L. Eugene; Swanson, James M ...
Journal of the American Academy of Child and Adolescent Psychiatry,
08/2007, Letnik:
46, Številka:
8
Journal Article
Recenzirano
Objective: In the intent-to-treat analysis of the Multimodal Treatment Study of Children With ADHD (MTA), the effects of medication management (MedMgt), behavior therapy (Beh), their combination ...(Comb), and usual community care (CC) differed at 14 and 24 months due to superiority of treatments that used the MTA medication algorithm (Comb+MedMgt) over those that did not (Beh+CC). This report examines 36-month outcomes, 2 years after treatment by the study ended. Method: For primary outcome measures (attention-deficit/hyperactivity disorder ADHD and oppositional defiant disorder ODD symptoms, social skills, reading scores, impairment, and diagnostic status), mixed-effects regression models and orthogonal contrasts examined 36-month outcomes. Results: At 3 years, 485 of the original 579 subjects (83.8%) participated in the follow-up, now at ages 10 to 13 years, (mean 11.9 years). In contrast to the significant advantage of MedMgt+Comb over Beh+CC for ADHD symptoms at 14 and 24 months, treatment groups did not differ significantly on any measure at 36 months. The percentage of children taking medication greater than 50% of the time changed between 14 and 36 months across the initial treatment groups: Beh significantly increased (14% to 45%), MedMed+Comb significantly decreased (91% to 71%), and CC remained constant (60%-62%). Regardless of their treatment use changes, all of the groups showed symptom improvement over baseline. Notably, initial symptom severity, sex (male), comorbidity, public assistance, and parental psychopathology (ADHD) did not moderate children's 36-month treatment responses, but these factors predicted worse outcomes over 36 months, regardless of original treatment assignment. Conclusions: By 36 months, the earlier advantage of having had 14 months of the medication algorithm was no longer apparent, possibly due to age-related decline in ADHD symptoms, changes in medication management intensity, starting or stopping medications altogether, or other factors not yet evaluated. (Contains 2 tables and 4 figures.)
Participants of the Multimodal Treatment Study of Children with Attention Deficit and Hyperactivity Disorder (ADHD) eight years earlier do not differ significantly in repeated measures or newly ...analyzed variables that include school grades and psychiatric hospitalization. The treatment of childhood ADHD does not predict functioning six to eight years later.
EEG biomarkers have shown promise in predicting non-response to stimulant medication in ADHD and could serve as translational biomarkers. This study aimed to replicate and extend previous EEG ...biomarkers. The international Study to Predict Optimized Treatment for ADHD (iSPOT-A), a multi-center, international, prospective open-label trial, enrolled 336 children and adolescents with ADHD (11.9 yrs; 245 males; prescribed methylphenidate) and 158 healthy children. Treatment response was established after six weeks using the clinician rated ADHD-Rating Scale-IV. Theta/Beta ratio (TBR) and alpha peak frequency (APF) were assessed at baseline as predictors for treatment outcome. No differences between ADHD and controls were found for TBR and APF. 62% of the ADHD group was classified as a responder. Responders did not differ from non-responders in age, medication dosage, and baseline severity of ADHD symptoms. Male-adolescent non-responders exhibited a low frontal APF (Fz: R = 9.2 Hz vs. NR = 8.1 Hz; ES = 0.83), whereas no effects were found for TBR. A low APF in male adolescents was associated with non-response to methylphenidate, replicating earlier work. Our data suggest that the typical maturational EEG changes observed in ADHD responders and controls are absent in non-responders to methylphenidate and these typical changes start emerging in adolescence.
Clinical trials registration: www.clinicaltrials.gov; NCT00863499 (https://clinicaltrials.gov/ct2/show/NCT00863499).
The purpose of this study was to determine if tetrahydrobiopterin (BH4) reduced core symptoms of autism spectrum disorder (ASD).
In this study, 46 children, 3-7 years of age diagnosed with an ASD ...were randomly assigned to double-blind treatment with 20 mg/kg/day BH4 or placebo for 16 weeks. The primary outcome measure was the Clinical Global Impressions Improvement and Severity Scales (CGI-I and CGI-S); secondary outcomes were the Preschool Language Scale-4 (PLS-4), Social Responsiveness Scale (SRS), Aberrant Behavior Checklist (ABC), and Vineland Adaptive Behavior Scales (Vineland).
Overall, no differences were found on global improvement as measured with the CGI-I or CGI-S. Secondary measures indicated significant improvements for BH4 relative to placebo with regard to social awareness, autism mannerisms, hyperactivity, and inappropriate speech. Side effects were minimal and similar between both active medication and placebo.
These results indicate that BH4 offers promise in reducing symptoms of ASD. Clinical Trials.gov Identifier: NCT00850070.
The study compared the neural bases of two cognitive control operations, interference suppression and response inhibition, between children with and children without attention deficit hyperactivity ...disorder (ADHD).
Ten children (7-11 years of age) with combined-type ADHD and 10 comparison subjects matched for age and gender underwent rapid event-related functional magnetic resonance imaging (fMRI) during performance of a modified flanker task. Functional maps were generated through group averaging and performance-based correlational analyses.
Interference suppression in ADHD subjects was characterized by reduced engagement of a frontal-striatal-temporal-parietal network that subserved healthy performance. In contrast, response inhibition performance relied upon different regions in the two groups, frontal-striatal in comparison subjects but right superior temporal in ADHD children.
Alteration in the neural basis of two cognitive control operations in childhood ADHD was characterized by distinct, rather than unitary, patterns of functional abnormality. Greater between-group overlap in the neural network activated for interference suppression than in response inhibition suggests that components of cognitive control are differentially sensitive to ADHD. The ADHD children's inability to activate the caudate nucleus constitutes a core abnormality in ADHD. Observed functional abnormalities did not result from prolonged stimulant exposure, since most children were medication naive.
Objective: To evaluate the hypothesis of stimulant medication effect on physical growth in the follow-up phase of the Multimodal Treatment Study of Children With ADHD. Method: Naturalistic subgroups ...were established based on patterns of treatment with stimulant medication at baseline, 14-, 24-, and 36-month assessments: not medicated (n = 65), newly medicated (n = 88), consistently medicated (n = 70), and inconsistently medicated (n = 147). Analysis of variance was used to evaluate effects of subgroup and assessment time on measures of relative size (z scores) obtained from growth norms. Results: The subgroup x assessment time interaction was significant for z height (p less than 0.005) and z weight (p less than 0.0001), due primarily to divergence of the newly medicated and the not medicated subgroups. These initially stimulant-naive subgroups had z scores significantly greater than 0 at baseline. The newly medicated subgroup showed decreases in relative size that reached asymptotes by the 36-month assessment, when this group showed average growth of 2.0 cm and 2.7 kg less than the not medicated subgroup, which showed slight increases in relative size. Conclusions: Stimulant-naive school-age children with Combined type attention-deficit/hyperactivity disorder were, as a group, larger than expected from norms before treatment but show stimulant-related decreases in growth rates after initiation of treatment, which appeared to reach asymptotes within 3 years without evidence of growth rebound. (Contains 3 tables and 2 figures.)
Objective: To explore the utility of cognitive measures for predicting response of children and adolescents to methylphenidate (MPH). Method: Participants from the International Study to Predict ...Optimized Treatment–in ADHD (iSPOT-A) completed a cognitive test battery prior to receiving 6 weeks of MPH. The responder criterion was a 25% reduction in ADHD-Rating Scale-IV scores. Receiver Operator Characteristics (ROC) classified non-responders from responders with maximal sensitivity and specificity. Results: Overall, 62% of participants responded to MPH. Response rates for ROC-identified groups ranged from 18% to 85%. Non-responders showed compromised cognition related to switching of attention, sustained attention, planning, and impulsivity. One group of responders were 10 years of age or older and had impaired switching of attention and impulsivity; a second group had enhanced switching of attention, normal or higher Continuous Performance Task (CPT) scores, and above average scores on digit span. Conclusion: Cognitive tests may provide a simple, low-cost tool for treatment planning for children and adolescents with ADHD.
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