Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism.

Autism spectrum disorder is a prevalent neurodevelopmental disorder with no established pharmacological treatment for its core symptoms. Although previous literature has shown that single-dose administration of oxytocin temporally mitigates autistic social behaviours in experimental settings, it remains in dispute whether such potentially beneficial responses in laboratories can result in clinically positive effects in daily life situations, which are measurable only in long-term observations of individuals with the developmental disorder undergoing continual oxytocin administration. Here, to address this issue, we performed an exploratory, randomized, double-blind, placebo-controlled, crossover trial including 20 high-functional adult males with autism spectrum disorder. Data obtained from 18 participants who completed the trial showed that 6-week intranasal administration of oxytocin significantly reduced autism core symptoms specific to social reciprocity, which was clinically evaluated by Autism Diagnostic Observation Scale (P = 0.034, PFDR < 0.05, Cohen's d = 0.78). Critically, the improvement of this clinical score was accompanied by oxytocin-induced enhancement of task-independent resting-state functional connectivity between anterior cingulate cortex and dorso-medial prefrontal cortex (rho = -0.60, P = 0.011), which was measured by functional magnetic resonance imaging. Moreover, using the same social-judgement task as used in our previous single-dose oxytocin trial, we confirmed that the current continual administration also significantly mitigated behavioural and neural responses during the task, both of which were originally impaired in autistic individuals (judgement tendency: P = 0.019, d = 0.62; eye-gaze effect: P = 0.03, d = 0.56; anterior cingulate activity: P = 0.00069, d = 0.97; dorso-medial prefrontal activity: P = 0.0014, d = 0.92; all, PFDR < 0.05). Furthermore, despite its longer administration, these effect sizes of the 6-week intervention were not larger than those seen in our previous single-dose intervention. These findings not only provide the evidence for clinically beneficial effects of continual oxytocin administration on the core social symptoms of autism spectrum disorder with suggesting its underlying biological mechanisms, but also highlight the necessity to seek optimal regimens of continual oxytocin treatment in future studies.

Intraventricular cerebrospinal fluid temperature analysis using MR diffusion-weighted imaging thermometry in Parkinson's disease patients, multiple system atrophy patients, and healthy subjects.

PURPOSE: We examined the temperature of the intraventricular cerebrospinal fluid (Tv) in patients with Parkinson's disease (PD) and those with multiple system atrophy (MSA) in comparison with healthy subjects, and we examined normal changes in this temperature with aging. METHODS: Tv was estimated by magnetic resonance (MR) diffusion-weighted imaging (DWI) thermometry in 36 PD patients (19 males, 17 females), 34 MSA patients (17 males, 17 females), 64 age-matched controls (27 men, 37 women), and 114 all-age adult controls (47 men, 67 women; 28-89 years old). The volume of lateral ventricles was also estimated using FreeSurfer in all subjects. Tv and ventricular volume data were compared among the PD and MSA patients and age-matched controls. We also evaluated the relationship between Tv and age in the 114 all-age controls, controlling for ventricular volume. Men and women were analyzed separately. RESULTS: The male PD and MSA patients had significantly higher Tv values compared to the male controls, with no significant difference in ventricular volume among them. There was no significant difference in Tv between the female patients and controls. In the all-age male controls, there was a significant negative correlation between Tv and age controlling for ventricular volume, and this was not observed in the women. CONCLUSION: DWI thermometry is a useful and easy method for demonstrating an altered intracranial environment in male patients and healthy controls, but not in females. DWI thermometry can thus be used to help to explore the pathophysiology of Parkinsonian syndromes and to differentiate individuals affected by neurodegenerative disease with autonomic dysfunction from those without it.

Comparison of white matter integrity between autism spectrum disorder subjects and typically developing individuals: a meta-analysis of diffusion tensor imaging tractography studies.

BACKGROUND: Aberrant brain connectivity, especially with long-distance underconnectivity, has been recognized as a candidate pathophysiology of autism spectrum disorders. However, a number of diffusion tensor imaging studies investigating people with autism spectrum disorders have yielded inconsistent results. METHODS: To test the long-distance underconnectivity hypothesis, we performed a systematic review and meta-analysis of diffusion tensor imaging studies in subjects with autism spectrum disorder. Diffusion tensor imaging studies comparing individuals with autism spectrum disorders with typically developing individuals were searched using MEDLINE, Web of Science and EMBASE from 1980 through 1 August 2012. Standardized mean differences were calculated as an effect size of the tracts. RESULTS: A comprehensive literature search identified 25 relevant diffusion tensor imaging studies comparing autism spectrum disorders and typical development with regions-of-interest methods. Among these, 14 studies examining regions of interest with suprathreshold sample sizes were included in the meta-analysis. A random-effects model demonstrated significant fractional anisotropy reductions in the corpus callosum (P = 0.023, n = 387 (autism spectrum disorders/typically developing individuals: 208/179)), left uncinate fasciculus (P = 0.011, n = 242 (117/125)), and left superior longitudinal fasciculus (P = 0.016, n = 182 (96/86)), and significant increases of mean diffusivity in the corpus callosum (P = 0.006, n = 254 (129/125)) and superior longitudinal fasciculus bilaterally (P = 0.031 and 0.011, left and right, respectively, n = 109 (51/58)), in subjects with autism spectrum disorders compared with typically developing individuals with no significant publication bias. CONCLUSION: The current meta-analysis of diffusion tensor imaging studies in subjects with autism spectrum disorders emphasizes important roles of the superior longitudinal fasciculus, uncinate fasciculus, and corpus callosum in the pathophysiology of autism spectrum disorders and supports the long-distance underconnectivity hypothesis.

Use of an oral effervescent agent in the evaluation of gastric 67Ga uptake.

OBJECTIVE: Gastric uptake of (67)Ga may be observed in patients with no obvious gastric lesions, as well as those with gastric malignancy. The aim of this study was to investigate whether the use of an effervescent agent aids in evaluating gastric (67)Ga uptake. METHODS: Twenty patients having or suspected of having gastric uptake on whole-body (67)Ga scintigrams were studied. Anterior abdominal images were obtained at baseline and after the oral intake of the effervescent agent (gas contrast image). The presence or absence of malignant gastric uptake was judged visually using the baseline image or gas contrast image. The judgment was compared with the clinical diagnosis, and the clinical usefulness of the gas contrast technique was assessed. RESULTS: In all patients, successful distension of the stomach was indicated in the gas contrast image. Clinical assessment showed gastric lesions in six patients (gastric involvement of lymphoma in 3, primary gastric lymphoma in 2, and adenocarcinoma in 1). The gas contrast image yielded accurate judgments of malignant gastric uptake in all patients except one with adenocarcinoma. Imaging after gastric distension induced by the oral effervescent agent contributed to excluding malignant gastric uptake in eight patients and demonstrating malignant gastric uptake in four patients. CONCLUSIONS: Benign gastric uptake may complicate the assessment of gastric lesions in (67)Ga scintigraphy. Additional spot imaging after oral intake of an effervescent agent can aid in evaluating malignant gastric lesions through gastric distension.