Oxytocin treatment attenuates amygdala activity in autism: a treatment-mechanism study with long-term follow-up

Abstract Intranasal administration of the neuropeptide oxytocin (IN-OT) is increasingly considered as a potential treatment for targeting the core symptoms of autism spectrum disorder (ASD), but the effects of continual use on neural substrates are fairly unexplored and long-term effects are unknown. In this double-blind, randomized, placebo-controlled study, we investigated the effects of single-dose and multiple-dose IN-OT treatment (4 weeks of daily (24 IU) administrations) on brain activity related to processing emotional states. Thirty-eight adult men with ASD (aged between 18 and 35 years) underwent functional magnetic resonance imaging of the posterior superior temporal gyrus (pSTS) and amygdala regions while processing emotional states from point-light biological motion. In line with prior research, a single dose of IN-OT induced a reliable increase in pSTS brain activity during the processing of point-light biological motion, but no consistent long-term changes in pSTS activity were induced after the multiple-dose treatment. In terms of bilateral amygdala, the multiple-dose treatment induced a consistent attenuation in brain activity, which outlasted the period of actual administrations until four weeks and one year post-treatment. Critically, participants with stronger attenuations in amygdala-activity showed greater behavioral improvements, particularly in terms of self-reported feelings of avoidant attachment and social functioning. Together, these observations provide initial insights into the long-lasting neural consequences of chronic IN-OT use on amygdala functioning and provide first indications that the acute versus chronic effects of IN-OT administration may be qualitatively different. Larger studies are however warranted to further elucidate the long-term impact of IN-OT treatment on human neural substrates and its behavioral consequences.

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Efficacy of a Single Dose versus a Multiple Dose Regimen of Mebendazole against Hookworm Infections among School Children: a Randomized Open-label Trial

10.21203/rs.2.19725/v3 ◽

2020 ◽

Author(s):

Tegegne Eshetu ◽

Mulugeta Aemero ◽

Ayalew Jejaw

Keyword(s):

Single Dose ◽

Dose Regimen ◽

Multiple Dose ◽

Open Label ◽

Preventive Chemotherapy ◽

Dose Treatment ◽

School Aged Children ◽

Multiple Dose Regimen ◽

Hookworm Infections

Abstract Background: Despite the existence of a population-based control program using single dose albendazole or mebendazole as a preventive chemotherapy, hookworm transmission remains high. It causes a negative impact on the growth and school performance of children. In connection to this preventive chemotherapy, different studies produced conflicting results. This study aimed at evaluating the efficacy of single (500mg) versus multiple doses (100mg twice a day during three consecutive days) of mebendazole against hookworm infections among school-aged children. Methods: This randomized open-label clinical trial took place among school-aged children (6-14 years old) in Burie and Debre Elias towns, Northwest Ethiopia. Using simple randomization, eligible hookworm-positive children were allocated (1:1) to either a single or multiple dose treatment arms. Stool samples were collected and processed using McMaster method at baseline and follow-up period (14-21 days after treatment). Only laboratory technicians were blinded. The cure and egg reduction rates which were assessed after 14-21 days of treatment were the primary and secondary therapeutic outcome measures against hookworm infections, respectively. An independent t-test was used to compare group means, and logistic regression was used to calculate odds ratio (OR). P-value < 0.05 at 95% CI was considered statistically significant. Result: 108 children, 54 in each treatment arm had completed baseline data and received allocated treatment. 103 children had completed follow-up data records and included for the final efficacy analysis. Cure rate against hookworm was significantly higher in the multiple dose (96.1%) than in the single dose (30.8%) with OR=55.125; 95% CI: 11.92-254.9; P < 0.001. The egg reduction rate in the multiple dose treatment arm (99.5%) was also significantly higher than in the single dose arm (68.9%) with difference t (101) =5.38; 95% CI 230.95-505.36; P < 0.001. Conclusion: The single dose regimen of mebendazole for the treatment of hookworm infections showed poor cure and egg reduction rates, while the multiple dose revealed satisfactory. Although multiple dose regimen administration is a bit more complex than the single dose, we strongly encourage replacing it with multiple dose regimen during deworming programs in hookworm endemic areas. Trial registration: This trial is registered in www.pactr.org, # PACTR201911466695052.

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Pharmacokinetics of Sativex® in Dogs: Towards a Potential Cannabinoid-Based Therapy for Canine Disorders

Biomolecules ◽

10.3390/biom10020279 ◽

2020 ◽

Vol 10 (2) ◽

pp. 279

Author(s):

María Fernández-Trapero ◽

Carmen Pérez-Díaz ◽

Francisco Espejo-Porras ◽

Eva de Lago ◽

Javier Fernández-Ruiz

Keyword(s):

Veterinary Medicine ◽

Single Dose ◽

Multiple Dose ◽

Plasma Concentrations ◽

Beagle Dogs ◽

Blood Samples ◽

Dose Treatment ◽

Pathological Conditions ◽

Sublingual Delivery ◽

Progressive Accumulation

The phytocannabinoid-based medicine Sativex® is currently marketed for the treatment of spasticity and pain in multiple sclerosis patients and is being investigated for other central and peripheral pathological conditions. It may also serve in Veterinary Medicine for the treatment of domestic animals, in particular for dogs affected by different pathologies, including human-like pathological conditions. With the purpose of assessing different dosing paradigms for using Sativex in Veterinary Medicine, we investigated its pharmacokinetics when administered to naïve dogs via sublingual delivery. In the single dose arm of the study, adult Beagle dogs were treated with 3 consecutive sprays of Sativex, and blood samples were collected at 12 intervals up to 24 h later. In the multiple dose arm of the study, Beagle dogs received 3 sprays daily for 14 days, and blood samples were collected for 24 h post final dose. Blood was used to obtain plasma samples and to determine the levels of cannabidiol (CBD), Δ9-tetrahydrocannabinol (Δ9-THC) and its metabolite 11-hydroxy-Δ9-THC. Maximal plasma concentrations of both Δ9-THC (Cmax = 18.5 ng/mL) and CBD (Cmax = 10.5 ng/mL) were achieved 2 h after administration in the single dose condition and at 1 h in the multiple dose treatment (Δ9-THC: Cmax = 24.5 ng/mL; CBD: Cmax = 15.2 ng/mL). 11-hydroxy-Δ9-THC, which is mainly formed in the liver from Δ9-THC, was almost undetected, which is consistent with the use of sublingual delivery. A potential progressive accumulation of both CBD and Δ9-THC was detected following repeated exposure, with maximum plasma concentrations for both cannabinoids being achieved following multiple dose. Neurological status, body temperature, respiratory rate and some hemodynamic parameters were also recorded in both conditions, but in general, no changes were observed. In conclusion, this study demonstrates that single or multiple dose sublingual administration of Sativex to naïve dogs results in the expected pharmacokinetic profile, with maximal levels of phytocannabinoids detected at 1–2 h and suggested progressive accumulation after the multiple dose treatment.

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Rapid changes in functional responsiveness of the 5-HT system after single-dose and multiple-dose treatment with antidepressants: effects of maprotiline and oxaprotiline and its enantiomers

Journal of Psychopharmacology ◽

10.1177/026988118900300102 ◽

1989 ◽

Vol 3 (1) ◽

pp. 7-13 ◽

Cited By ~ 1

Author(s):

A. Delini-Stula ◽

E. Mogilnicka

Keyword(s):

Single Dose ◽

Multiple Dose ◽

Dose Treatment ◽

Rapid Changes ◽

Functional Responsiveness

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Long-term cytogenetic studies of 10 patients with hyperthyroidism after single-dose treatment with radioiodine

Mutation Research/Environmental Mutagenesis and Related Subjects ◽

10.1016/0165-1161(85)90199-2 ◽

1985 ◽

Vol 147 (5) ◽

pp. 316

Author(s):

G. Rittner ◽

G. Schwanitz

Keyword(s):

Single Dose ◽

Dose Treatment ◽

Cytogenetic Studies ◽

Single Dose Treatment

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Brain activity reflects perceptual learning of point-light biological motion

Journal of Vision ◽

10.1167/3.9.81 ◽

2010 ◽

Vol 3 (9) ◽

pp. 81-81

Author(s):

E. D Grossman ◽

C.-Y. Kim ◽

R. Blake

Keyword(s):

Perceptual Learning ◽

Biological Motion ◽

Brain Activity ◽

Point Light

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Pharmacokinetics of mycophenolate mofetil following single-dose intravenous and single- and multiple-dose oral administration and clinicopathologic effects of mycophenolate mofetil following long-term oral administration in healthy horses

American Journal of Veterinary Research ◽

10.2460/ajvr.82.6.502 ◽

2021 ◽

Vol 82 (6) ◽

pp. 502-509

Author(s):

Heather K. Knych ◽

Daniel S. McKemie ◽

Kirsten L. Kanarr ◽

Stephen D. White

Keyword(s):

Mycophenolate Mofetil ◽

Single Dose ◽

Oral Administration ◽

Multiple Dose ◽

Dose Oral

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Neural correlates of experience with CCTV surveillance of naturalistic prosocial and antisocial interactions: a reverse correlation analysis

10.1101/691790 ◽

2019 ◽

Author(s):

Julia A. Gillard ◽

Karin Petrini ◽

Katie Noble ◽

Jesus A. Rodriguez Perez ◽

Frank E. Pollick

Keyword(s):

Eye Movements ◽

Biological Motion ◽

Brain Activity ◽

Real Life ◽

City Centre ◽

Control Group ◽

Reverse Correlation ◽

Movement Data ◽

Cctv Surveillance ◽

Point Light

AbstractPrevious research using reverse correlation to explore the relationship between brain activity and presented image information found that Face Fusiform Area (FFA) activity could be related to the appearance of faces during free viewing of the Hollywood movie “The Good, the Bad, and the Ugly” (Hasson, et al, 2004). We applied this approach to the naturalistic viewing of unedited footage of city-centre closed-circuit television (CCTV) surveillance. Two 300 second videos were used, one containing prosocial activities and the other antisocial activities. Brain activity revealed through fMRI as well as eye movements were recorded while fifteen expert CCTV operators with a minimum of 6 months experience of CCTV surveillance alongside an age and gender matched control group of fifteen novice viewers were scanned while watching the videos. Independent scans functionally localized FFA and posterior Superior Temporal Sulcus (pSTS) activity using faces/houses and intact/scrambled point-light biological motion displays respectively. Reverse correlation revealed peaks in FFA and pSTS brain activity corresponding to the expert and novice eye movements directed towards faces and biological motion across both videos. In contrast, troughs in activation corresponded to camera-induced motion when a clear view of visual targets were temporarily not available. Our findings, validated by the eye movement data, indicate that the predicted modulation of brain activity occurs as a result of salient features of faces and biological motion embedded within the naturalistic stimuli. The examination of expertise revealed that in both pSTS and FFA the novices had significantly more activated timeframes than the experienced observers for the prosocial video. However, no difference was found for the antisocial video. The modulation of brain activity, as well as the effect of expertise gives a novel insight into the underlying visual processes in an applied real-life task.

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Emotional Reactivity to Visual Content as Revealed by ERP Component Clustering

Journal of Psychophysiology ◽

10.1027/0269-8803/a000145 ◽

2015 ◽

Vol 29 (4) ◽

pp. 135-146 ◽

Cited By ~ 3

Author(s):

Miroslaw Wyczesany ◽

Szczepan J. Grzybowski ◽

Jan Kaiser

Keyword(s):

Emotional Reactivity ◽

Brain Activity ◽

Affective State ◽

Occipital Lobe ◽

Stimulus Onset ◽

Emotional States ◽

Neural Basis ◽

Temporoparietal Junction ◽

The Right ◽

The Impact

Abstract. In the study, the neural basis of emotional reactivity was investigated. Reactivity was operationalized as the impact of emotional pictures on the self-reported ongoing affective state. It was used to divide the subjects into high- and low-responders groups. Independent sources of brain activity were identified, localized with the DIPFIT method, and clustered across subjects to analyse the visual evoked potentials to affective pictures. Four of the identified clusters revealed effects of reactivity. The earliest two started about 120 ms from the stimulus onset and were located in the occipital lobe and the right temporoparietal junction. Another two with a latency of 200 ms were found in the orbitofrontal and the right dorsolateral cortices. Additionally, differences in pre-stimulus alpha level over the visual cortex were observed between the groups. The attentional modulation of perceptual processes is proposed as an early source of emotional reactivity, which forms an automatic mechanism of affective control. The role of top-down processes in affective appraisal and, finally, the experience of ongoing emotional states is also discussed.

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