榴莲视频

More evidence has emerged that the diuretic drug bumetanide may help treat autism symptoms, a small neuroimaging study showed.

Young children with autism spectrum disorder (ASD) who were treated with bumetanide for three months showed modest improvement in scores for symptom severity -- by about 2 points on the (CARS) -- that was significantly greater than in a control group, according to Fei Li, MD, PhD, of the Shanghai Jiao Tong University School of Medicine in China, and co-authors.

Moreover, these symptom changes were tied to alterations in gamma-aminobutyric acid (GABA)-to-glutamate ratios on magnetic resonance spectroscopy (MRS), they wrote in

"To our knowledge, this is the first study to relate symptom reduction by bumetanide in autism spectrum disorder to the action of brain neurotransmitters using MRS," said co-author Barbara Sahakian, DSc, FMedSci, of the University of Cambridge in England.

"In addition, the study participants were young children -- ages 3 to 6 years -- with moderate and severe ASD," Sahakian told 榴莲视频. "It's important to study young children while their brains are still in development and while there is an opportunity to improve social behavior and engagement in family activities."

Molecular and neural mechanisms of autism are largely unknown, but studies have suggested the disorder may result from brain development alterations during early life, including neuronal excitatory-inhibitory imbalance. This imbalance has been hypothesized to be caused by unsuccessful excitatory-to-inhibitory shift of GABA activity.

Earlier studies have reported that children show modest improvements on autism severity tests after taking bumetanide for three months, and more recently, that bumetanide may decrease autism severity in a .

In this trial, Li and her group studied 3- to 6-year children in China with ASD from April 2016 to April 2019. Autism was assessed with CARS, which rates 15 items including imitation, emotional response, and verbal and non-verbal communication on a 4-point scale (1, 1.5, 2, 2.5, 3, 3.5, and 4).

Children with total CARS scores above 30 were considered to have ASD. In this study, the number of CARS items with a score of 3 or higher also was used to measure symptom severity.

The researchers followed a total of 83 young children: 42 who received 0.5 mg of bumetanide twice a day for three months and 41 who received no treatment. They conducted assessments and MRS scanning at baseline and at three months. MRS was conducted on 38 children in treatment group and 17 in the control group.

Both groups had similar demographic characteristics and CARS scores at baseline were similar (mean 37.40 in the bumetanide arm, 38.15 for controls). At three months, mean CARS scores with bumetanide group declined to 34.51, while the control group had a mean score of 37.27 (t_77.3 = 3.35, P=0.0012; Cohen's d=0.74).

The treatment group also had fewer CARS items with a score of 3 or higher (t_74.6 = 2.88, P=0.0053; Cohen's d=0.63) at three months. Clinical global impression scores also confirmed symptom improvement.

Over three months, GABA-to-glutamate ratios in both the insular cortex and visual cortex decreased more rapidly in the bumetanide group than in the control group. This decrease in GABA-to-glutamate in the insular cortex was associated with symptom improvement among children taking bumetanide.

The most frequent adverse effect with bumetanide was mild polyuria/pollakiuria, which occurred in 15 children and required no treatment. Four patients developed mild hypokalemia; they were given potassium supplements and advised to eat potassium-rich foods, which returned their potassium levels to normal.

These findings are thought-provoking from both clinical and research perspectives, noted Tarek Deeb, PhD, of Tufts University School of Medicine in Boston, who wasn't involved with the study.

"While this supports earlier studies demonstrating bumetanide as a treatment for autistic patients, the reduction in GABA/glutamate ratios in specific brain regions raises interesting questions about how bumetanide actually works," he told 榴莲视频.

Further trials are needed to confirm whether bumetanide can effectively treat autism symptoms, the researchers cautioned. "We need large-scale studies; however, bumetanide may be effective in improving social communication in young children with ASD," Sahakian said.

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