Blum Kenneth, Dennen Catherine A, Braverman Eric R, Gupta Ashim, Baron David, Downs Bernard William, Bagchi Debasis, Thanos Panayotis, Pollock Maureen, Khalsa Jag, Elman Igor, Bowirrat Abdalla, Badgaiyan Rajendra A
Center for Mental Health and Sports, Psychiatry, Western University Health Sciences, Pomona, USA.
The Kenneth Blum Behavioral & Neurogenetic Institute, Austin, USA.
Open J Immunol. 2022 Sep;12(3):65-75. doi: 10.4236/oji.2022.123004.
Pediatric autoimmune neuropsychiatric disorders associated with group A streptococcal infections (PANDAS) is a concept that is used to characterize a subset of children with neuropsychiatric symptoms, tic disorders, or obsessive-compulsive disorder (OCD), whose symptoms are exacerbated by group A streptococcal (GAS) infection. PANDAS has been known to cause a sudden onset of reward deficiency syndrome (RDS). RDS includes multiple disorders that are characterized by dopaminergic signaling dysfunction in the brain reward cascade (BRC), which may result in addiction, depression, avoidant behaviors, anxiety, tic disorders, and/or OCD. According to research by Blum ., the dopamine receptor D2 (DRD2) gene polymorphisms are important prevalent genetic determinants of RDS. The literature demonstrates that infections like Borrelia and Lyme, as well as other infections like group A beta-hemolytic streptococcal (GABHS), can cause an autoimmune reaction and associated antibodies target dopaminergic loci in the mesolimbic region of the brain, which interferes with brain function and potentially causes RDS-like symptoms/behaviors. The treatment of PANDAS remains controversial, especially since there have been limited efficacy studies to date. We propose an innovative potential treatment for PANDAS based on previous clinical trials using a pro-dopamine regulator known as KB220 variants. Our ongoing research suggests that achieving "dopamine homeostasis" by precision-guided DNA testing and pro-dopamine modulation could result in improved therapeutic outcomes.
与A组链球菌感染相关的儿童自身免疫性神经精神障碍(PANDAS)是一个用于描述具有神经精神症状、抽动障碍或强迫症(OCD)的儿童亚群的概念,其症状会因A组链球菌(GAS)感染而加重。已知PANDAS会导致奖赏缺乏综合征(RDS)突然发作。RDS包括多种以大脑奖赏级联(BRC)中多巴胺能信号功能障碍为特征的疾病,这可能导致成瘾、抑郁、回避行为、焦虑、抽动障碍和/或强迫症。根据布卢姆等人的研究,多巴胺受体D2(DRD2)基因多态性是RDS重要的常见遗传决定因素。文献表明,像伯氏疏螺旋体和莱姆病这样的感染,以及其他如A组β溶血性链球菌(GABHS)感染,可引起自身免疫反应,相关抗体靶向大脑中脑边缘区域的多巴胺能位点,干扰脑功能并可能导致类似RDS的症状/行为。PANDAS的治疗仍存在争议,尤其是因为迄今为止疗效研究有限。我们基于之前使用一种称为KB220变体的多巴胺前体调节剂的临床试验,提出一种针对PANDAS的创新潜在治疗方法。我们正在进行的研究表明,通过精准指导的DNA检测和多巴胺前体调节实现“多巴胺稳态”可能会改善治疗效果。