Catecholaminergic and Cholinergic Neuromodulation in Autism Spectrum Disorder: A Comparison to Attention-Deficit Hyperactivity Disorder

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by social impairments and restricted, repetitive behaviors. Treatment of ASD is notoriously difficult and might benefit from identification of underlying mechanisms that overlap with those disturbed in other developmental disorders, for which treatment options are more obvious. One example of the latter is attention-deficit hyperactivity disorder (ADHD), given the efficacy of especially stimulants in treatment of ADHD. Deficiencies in catecholaminergic systems (dopamine (DA)), norepinephrine (NE)) in ADHD are obvious targets for stimulant treatment. Recent findings suggest that abnormalities in catecholaminergic systems may also be a factor in at least a subgroup of ASD. In this review we scrutinize the evidence for catecholaminergic mechanisms underlying ASD symptoms, and also include in this analysis a third classic ascending arousing system, the acetylcholinergic (ACh) network. We complement this with a comprehensive review of DA-, NE-, and ACh-targeted interventions in ASD, and an exploratory search for potential treatment-response predictors (biomarkers) in ASD, genetically or otherwise. Based on this review and analysis we propose that 1) stimulant treatment may be a viable option for an ASD subcategory, possibly defined by genetic subtyping; 2) cerebellar dysfunction is pronounced for a relatively small ADHD subgroup but much more common in ASD and in both cases may point towards NE- or ACh-directed intervention; 3) deficiency of the cortical salience network is sizable in subgroups of both disorders, and biomarkers such as eye blink rate and pupillometric data may predict the efficacy of targeting this underlying deficiency via DA, NE, or ACh in both ASD and ADHD.

Treatment of Adolescents with Concurrent Substance Use Disorder and Attention-Deficit/Hyperactivity Disorder: A Systematic Review

Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for the development of substance abuse and substance use disorders (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment, and is associated with poor treatment outcomes. In this study, we provide a systematic review of controlled studies on the effectiveness of pharmacological, psychosocial, and complementary treatments of ADHD in adolescents with and without comorbid SUD. In addition, we review the longitudinal association between pharmacotherapy for childhood ADHD and the development of SUD in adolescence and early adulthood. We conducted a systematic review of the research literature published since 2000 using Medline, PsycINFO, and the Cochrane Database of Systematic Reviews databases to select randomized clinical trials, observational studies, and meta-analyses. The quality of the evidence from each study was rated using the SIGN grading system. Based on the limited evidence available, strong clinical recommendations are not justified, but provisionally, we conclude that stimulant treatment in children with ADHD may prevent the development of SUD in adolescence or young adulthood, that high-dose stimulant treatment could be an effective treatment for adolescents with ADHD and SUD comorbidity, that cognitive behavior therapy might have a small beneficial effect in these patients, and that alternative treatments are probably not effective. More studies are needed to draw definitive conclusions that will allow for strong clinical recommendations.

Germination energy and germination of different morphotypes of peas when treated with growth stimulant

The main legume crop, pea, is characterised by various morphotypes: leafy, whiskered, chameleon and other morphotypes. These morphotypes are the result of both selection work and spontaneous mutations. The relevance of the research topic is the effect of various factors, including seed treatment, on the different morphotypes. Six varieties and breeding lines of pea sown by Krasnoyarsk Research Institute of Agriculture were taken for the study: leafy Radomir, Kemchug; with the moustached leaf D-94, Ruslan; and having longitudinal heterophyllia L-19, M-6. This work aims to determine the responsiveness and variability of germination and germination energy, as well as seedling length, recorded during these periods, of different morphotypes of pea varieties and breeding lines to seed treatment with a growth stimulant. The experiment was set up in three replications with the growth stimulant treatment sodium humate and three repetitions of the control variant without remedy. Measurements of seedling length, germination energy and germination were carried out on the 4th and 8th day, respectively. The research revealed that the treatment of pea seeds increased the germination energy by 2,28% and reduced its variation by 0,55%. Chameleon morphotype samples are more responsive to treatment. The variability of the coefficient of variation of the germination energy of pea plants of different morphotypes with and without treatment is less than 10%. Stimulant treatment increases the length of seedlings by 6.34% but does not affect the morphotypes separately. The increase in size at treatment is individual for each sample. The variability of variation in the length of seedlings of control and treated examples is insignificant and unique for each model. But this variability in size decreases throughout the experiment: on the 4th day from 1.63 to 1.36, on the 8th day from 0.98 to 0.95%. In determining the germination rate, it was found that the treatment of pea seeds with a growth stimulant increases it by 3.78%. The growth gain is an individual response of each specimen and is weakly dependent on the morphotype.

Body mass index increase in preschoolers with heterogeneous psychiatric diagnoses treated with risperidone

Objective: Use of risperidone in preschool-aged children is growing, with rising concerns of adverse metabolic consequences. Longitudinal data on risperidone-related weight gain in preschoolers are scarce. We aimed to evaluate changes in body mass index (BMI) that are associated with risperidone treatment in preschoolers. Method: We analyzed naturalistic, longitudinal data on 141 preschool children (112 boys, 29 girls) receiving psychiatric care. Mean patient age at baseline was 5.0 years (SD=0.8) and average follow-up period was 1.3 years (SD=0.8), with >8 mean BMI measurements per patient. We studied the effect of risperidone exposure ( n=78) on age-and-sex-standardized BMI (BMI Z-score) implementing mixed models with random subject intercepts to account for repeated measures, covarying for multiple confounders including demographics, stimulant treatment and psychiatric diagnoses. We employed similar models to study dose and duration effects. Results: Risperidone treatment was significantly associated with an increase in BMI (effect size of exposure=0.45 SD (SE=0.06), t (949)=7.7, p<0.001) covarying for stimulant exposure and other confounders, independent of treatment indication. Females exhibited stronger effects (risperidone treatment × sex interaction t=2.32, p=0.02)). Risperidone daily dose was associated with increase in BMI (for each additional 1 mg, effect size=0.28 SD (SE=0.07), t(419)=3.76, p<0.001). Conclusion: Similar to older populations, risperidone treatment in preschoolers is associated with significant weight gain, with evidence for dose effects. Findings provide critical data that can inform clinicians.

Growth and Yield of Okra Using Bio-Stimulant of Golden Apple Snails Extracts and Fertilizer on Ultisol

Cultivation of okra on ultisol soils having poor physical, chemical and biological soil properties can be improved by administering a bio-stimulant extract of golden snails and combined with NPK fertilizer. This research objective was to study a combination of bio-stimulant treatment of golden apple snail extract and NPK fertilizer dosage in increasing the growth and yield of okra on ultisol soil. This study used a factorial completely randomized design with two factors. The first factor was Bio-stimulant golden apple snails extract consisting of 4 treatment, and the second factor was levels of NPK fertilizer consisting of 3 treatment. Fertilizers had a significant effect on increasing overall plant growth. The bio-stimulant extracts of golden apple snails contain organic materials that can improve physical properties (increasing aggregation, moisture retention, soil hydraulic conductivity), chemical (increasing soil organic carbon content) and biology (increasing soil microbial biomass). The nutrient content in NPK fertilizers can increase nutrients; the availability of nutrients in the soil is balanced and can be absorbed by plants so that the photosynthesis process in plants can run well and increase on growth and yield of okra. The combination of bio-stimulant extract of golden apple snails of 20 mL/L water and NPK fertilizer of 150 kg/ha (1 g/polybag) had the highest resulted in the average value of growth and yield of okra on the ultisol soils.

Patient access to chronic medications during the Covid-19 pandemic: Evidence from a comprehensive dataset of US insurance claims

Patient access and adherence to chronic medications is critical. In this work, we evaluate whether disruptions related to Covid-19 have affected new and existing patients’ access to pharmacological therapies without interruption. We do so by performing a retrospective analysis on a dataset of 9.4 billion US prescription drug claims from 252 million patients from May, 2019 through August, 2020 (about 93% of prescriptions dispensed within those months). Using fixed effect (conditional likelihood) linear models, we evaluate continuity of care, how many days of supply patients received, and the likelihood of discontinuing therapy for drugs from classes with significant population health impacts. Findings indicate that more prescriptions were filled in March 2020 than in any prior month, followed by a significant drop in monthly dispensing. Compared to the pre-Covid era, a patient’s likelihood of discontinuing some medications increased after the spread of Covid: norgestrel-ethinyl estradiol (hormonal contraceptive) discontinuation increased 0.62% (95% CI: 0.59% to 0.65%, p<0.001); dexmethylphenidate HCL (ADHD stimulant treatment) discontinuation increased 2.84% (95% CI: 2.79% to 2.89%, p<0.001); escitalopram oxalate (SSRI antidepressant) discontinuation increased 0.57% (95% CI: 0.561% to 0.578%, p<0.001); and haloperidol (antipsychotic) discontinuation increased 1.49% (95% CI: 1.41% to 1.57%, p<0.001). In contrast, the likelihood of discontinuing tacrolimus (immunosuppressant) decreased 0.15% (95% CI: 0.12% to 0.19%, p<0.001). The likelihood of discontinuing buprenorphine/naloxone (opioid addiction therapy) decreased 0.59% (95% CI: 0.55% to 0.62% decrease, p<0.001). We also observe a notable decline in new patients accessing these latter two therapies. Most US patients were able to access chronic medications during the early months of Covid-19, but still were more likely to discontinue their therapies than in previous months. Further, fewer than normal new patients started taking medications that may be vital to their care. Providers would do well to inquire about adherence and provide prompt, nonjudgmental, re-initiation of medications. From a policy perspective, opioid management programs seem to demonstrate a robust ability to manage existing patients in spite of disruption.