Randomized Controlled Trial of Probiotic PS128 in Children with Tourette Syndrome.

Tourette syndrome results from a complex interaction between social-environmental factors, multiple genetic abnormalities, and neurotransmitter disturbances. This study is a double-blinded, randomized controlled trial using probiotics Lactobacillus plantarum PS128 as an intervention to examine if probiotics improve symptoms of children with Tourette syndrome. This study enrolled children aged 5 to 18 years old who fulfilled DSM-V diagnostic criteria for Tourette syndrome. Patients were assessed before initiating the trial, at one month, and at two months after randomization. The primary outcome was evaluated by Yale Global Tic Severity Scale (YGTSS), and the secondary outcome studied the possible comorbidities in these children. The results revealed no significant difference in improvement in YGTSS between the control group and the PS128 group. As for secondary endpoints, an analysis of Conners' Continuous Performance Test (CPT) showed improvement in commission and detectability in the PS128 group. In conclusion, although probiotics may not have tic-reducing effects in children with Tourette syndrome, it may have benefits on comorbidities such as attention deficit and hyperactivity disorder (ADHD). Further studies are needed to clarify the effects of probiotics on the comorbidities of Tourette syndrome children.

Aromatic L-amino acid decarboxylase (AADC) is crucial for brain development and motor functions.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare pediatric neuro-metabolic disease in children. Due to the lack of an animal model, its pathogenetic mechanism is poorly understood. To study the role of AADC in brain development, a zebrafish model of AADC deficiency was generated. We identified an aadc gene homolog, dopa decarboxylase (ddc), in the zebrafish genome. Whole-mount in situ hybridization analysis showed that the ddc gene is expressed in the epiphysis, locus caeruleus, diencephalic catecholaminergic clusters, and raphe nuclei of 36-h post-fertilization (hpf) zebrafish embryos. Inhibition of Ddc by AADC inhibitor NSD-1015 or anti-sense morpholino oligonucleotides (MO) reduced brain volume and body length. We observed increased brain cell apoptosis and loss of dipencephalic catecholaminergic cluster neurons in ddc morphants (ddc MO-injected embryos). Seizure-like activity was also detected in ddc morphants in a dose-dependent manner. ddc morphants had less sensitive touch response and impaired swimming activity that could be rescued by injection of ddc plasmids. In addition, eye movement was also significantly impaired in ddc morphants. Collectively, loss of Ddc appears to result in similar phenotypes as that of ADCC deficiency, thus zebrafish could be a good model for investigating pathogenetic mechanisms of AADC deficiency in children.