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更新于：2025-12-04
Folic Acid
叶酸
更新于：2025-12-04
概要
基本信息
最高研发阶段批准上市 |
首次获批日期 美国 (1947-06-02), |
最高研发阶段(中国)批准上市 |
特殊审评- |
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结构/序列
分子式C19H19N7O6 |
InChIKeyOVBPIULPVIDEAO-LBPRGKRZSA-N |
CAS号59-30-3 |
关联
524
项与 叶酸 相关的临床试验NCT06015750
An Interventional, Prospective Open-Label Study of Immunosuppressive Therapies to Mitigate Immune-Mediated Loss of Therapeutic Response to Asfotase Alfa (STRENSIQ®) for Hypophosphatasia (RESTORE)
The primary objective of this study is to evaluate the effect of immunosuppressive therapy (IST) in participants treated with asfotase alfa who demonstrate immune-mediated loss of effectiveness (LoE).
开始日期2026-07-29 |
CTRI/2025/11/096791
Root cause analysis(RCA)of non-responders to Iron folic acid treatment among women of reproductive age(WRA)at community setting - Nil
开始日期2026-01-01 |
NCT07113158
Effect of Aspirin and Folic Acid for Sudden Sensorineural Hearing Loss
The annual incidence of sudden sensorineural hearing loss (SSNHL) is 5 to 20 per 100 000 persons. The pathophysiology of SSNHL and acute vestibulo-cochlear syndromes (VCS) is unknown in more than 70% of cases.
Hypothesis : an inner ear microvascular disease represents the key element in the pathogenesis of SSNHL and acute VCS.
Plasma serotonin has among other tissular effect a vasospastic on microcirculation such as the inner ear microvascularisation. Increased plasma homocysteine has a deleterious effect on vascular endothelium. Inner ear microvascularisation sensitized by an increased homocysteine level and the vascular wall would vasoconstrict under serotonin stimulation inducing ischemia of the vestibular and/or cochlear organs.
Hypothesis : an inner ear microvascular disease represents the key element in the pathogenesis of SSNHL and acute VCS.
Plasma serotonin has among other tissular effect a vasospastic on microcirculation such as the inner ear microvascularisation. Increased plasma homocysteine has a deleterious effect on vascular endothelium. Inner ear microvascularisation sensitized by an increased homocysteine level and the vascular wall would vasoconstrict under serotonin stimulation inducing ischemia of the vestibular and/or cochlear organs.
开始日期2025-11-01 |
100 项与 叶酸 相关的临床结果
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100 项与 叶酸 相关的转化医学
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100 项与 叶酸 相关的专利（医药）
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52,251
项与 叶酸 相关的文献（医药）2026-04-01·DEN open
Polyglycolic Acid Sheet Application to Refractory Delayed Bleeding After Rectal Endoscopic Submucosal Dissection: A Case Report
作者: Nakano, Yoshiko ; Miyamoto, Shin'ichi ; Watanabe, Yasuhiro ; Kuriyama, Katsutoshi
ABSTRACT:
A man in his 50s underwent endoscopic submucosal dissection (ESD) for a rectal tumor measuring 28 mm. He was not taking any antithrombotic medication. On the third, 11th, 18th, and 24th days after the procedure, bleeding was observed from different areas of the ulcer bed margin and was managed with hemostatic forceps. Despite epithelization and ulcer healing, delayed bleeding recurred, with the fourth episode being severe, marked by significant bleeding and a decrease in serum hemoglobin level. Although clip closure of the ulcer bed and the application of PuraStat were attempted, they failed to prevent recurrent bleeding. Therefore, polyglycolic acid (PGA) sheets were applied to the ulcer bed during the fourth episode. Four days later, PGA sheets remained on the ulcer bed without any signs of bleeding, and healing continued. No further bleeding episodes occurred. The fact that continuous hemostasis was achieved after application of the PGA sheet without complications suggested that this approach may be an option in future cases of refractory delayed bleeding after rectal ESD.
2026-03-01·Maternal and Child Nutrition
Exposure to
Suaahara
II Interventions and Knowledge of Maternal and Child Nutrition and Health Among Mothers, Grandmothers, and Male Household Heads: An Association Study in Nepal
Article
作者: Sharma, Dipak ; Garn, Kristine ; Kole, Subir K. ; Thapa, Deependra K. ; Pandey, Pooja Rana ; Sapkota, Femila ; Suresh, Shalini ; Cunningham, Kenda ; Adhikari, Ramesh P. ; Shrestha, Manisha Laxmi ; Kshetri, Indra ; Frongillo, Edward A.
ABSTRACT:
Suaahara
was a USAID‐funded multi‐sectoral integrated nutrition program that aimed to improve the nutritional status of children under the age of five and their mothers in Nepal. The program included multiple interventions targeted to mothers and children, as well as other caregivers. Caregiver knowledge of optimal nutrition and health practices among household members is an important driver of healthy child and maternal nutrition behaviors. This study investigates the associations between exposure to
Suaahara
interventions and knowledge of maternal and child nutrition and health practices among mothers (
n
= 1239), grandmothers (
n
= 533), and male household heads (
n
= 551). Linear and logistic regression models were conducted using data from the endline survey of
Suaahara
's impact evaluation conducted in 2022. Exposure to
Suaahara
was associated with mothers' and grandmothers' knowledge of ideal child and maternal health and nutrition practices. Compared to those unexposed to
Suuahara
, mothers and grandmothers who were exposed to
Suaahara
interventions had 2.09 and 2.23 times higher odds respectively (
p
= 0.001;
p
= < 0.001), respectively, of having correct knowledge of exclusive breastfeeding, and 1.48 and 1.47 times higher odds respectively, of having correct knowledge of age of introduction of all types of complementary foods (
p
= 0.005;
p
= 0.070). Furthermore, exposed mothers had 1.49 times higher odds (
p
= 0.021) and exposed grandmothers had 1.42 times higher odds (
p
= 0.09) of knowing that young children should be fed more during illness. Male household heads who were exposed had 1.71 times higher odds of knowing that colostrum should be given to children immediately after birth (
p
= 0.027). Exposure to
Suaahara
was also associated with mothers' and grandmothers' knowledge of ideal maternal health and nutrition practices. Exposed mothers had 1.64 times higher odds (
p
= 0.011) and grandmothers had 2.92 times higher odds (
p
< 0.001) of knowing that mothers should take iron and folic acid supplementation for 180 days during pregnancy (
p
= 0.011;
p
= < 0.001). Exposed grandmothers had 1.87 times higher odds of having correct knowledge that mothers should have at least 4 antenatal care visits (
p
= 0.012). Exposed mothers and grandmothers had 1.88 and 1.90 times higher odds of having correct knowledge that mothers need at least 3 postnatal care visits (
p
= 0.002;
p
= 0.051). This study highlights multiple positive associations between exposure to
Suaahara
and knowledge of mothers and grandmothers around maternal and child health and nutrition practices. This effect was less pronounced in male household heads suggesting that tailored interventions are necessary to improve knowledge of appropriate child and maternal nutrition and health practices in this group. Future research should consider collecting data from multiple household members to better understand the paths between their knowledge and impact on maternal and child health and nutrition practices.
2026-02-01·PEDIATRIC NEUROLOGY
Counseling Reproductive-Age Youth With Epilepsy: Literature Review and Expert Opinion From the Epilepsy in the Child-Bearing Ages Through Menopause Consortium
Review
作者: Liu, Lynn C ; Douglass, Laurie M ; Clements, Marie E ; Harrison, Elizabeth I ; Singla, Laveena ; Moore-Hill, Debra T ; Yang, Qian-Zhou JoJo ; Kirkpatrick, Laura ; Voinescu, P Emanuela ; Briscoe, Christina ; Wiener, Susan ; Mathias, Sally V ; Puntambekar, Preeti ; Syed, Tahniat ; Vinarsky, Victoria ; Betstadt, Sarah J ; Samanta, Debopam ; Kassiri, Janani ; Nalluri, Deepthi ; Romeu, Amanda M ; Nath, Audrey ; Kulkarni, Neil ; Curcio, Angela M
Epilepsy in the Child-Bearing Ages through Menopause is an international consortium of clinicians dedicated to improving the health of women with epilepsy across the lifespan. Epilepsy in the Child-Bearing Ages through Menopause's Adolescent and Young Adult Committee addresses quality of care for female youth with epilepsy. The Committee developed a literature review and expert opinion guidance for child neurologists on performing optimal counseling about epilepsy and reproductive health for female youth with epilepsy. To do so, we identified and voted on key topics essential for this counseling, then conducted comprehensive literature reviews for each topic, iteratively developed key statements about counseling content and style for each topic and voted on final content for inclusion. The included topics were teratogenesis, folic acid supplementation, pregnancy and fertility, contraception, heritability of epilepsy, menstrual and hormonal disorders, catamenial epilepsy, and taking a sexual history. This review provides a clear, novel framework for pediatric neurologists to counsel adolescent and young adult women with epilepsy about their reproductive health, supporting improvement in practices recommended by professional organization such as the American Academy of Neurology and Child Neurology Foundation.
485
项与 叶酸 相关的新闻（医药）2025-12-03
·搜狐新闻
蜂毒肽游离酸（Melittin (Free Acid)）的综合解析Melittin，即蜂毒肽，是蜜蜂（主要为意大利蜜蜂）毒液中的主要活性成分，也是一种具有强生物活性的线性多肽，其特定氨基酸序列为Gly-Ile-Gly-Ala-Val-Leu-Lys-Val-Leu-Thr-Thr-Gly-Leu-Pro-Ala-Leu-Ile-Ser-Trp-Ile-Lys-Arg-Lys-Arg-Gln-Gln-NH₂，C端的酰胺化修饰是其维持稳定生物活性的关键结构特征。该多肽具有显著的抗菌、抗炎、抗肿瘤等多种生物活性，在基础医学研究、药物研发及生物农药等领域具有广泛的应用前景。以下从多维度对其进行系统解析。一、基本性质蜂毒肽的基本性质由其氨基酸组成、C端酰胺化修饰及两亲性结构共同决定，具体参数如下：英文名称：Melittin；全称可表述为 Bee Venom Melittin，常用缩写为 MEL。名称源于蜜蜂毒液（Bee Venom）的拉丁词根相关衍生，直接体现其生物来源与分子类型。单字母多肽序列：G-I-G-A-V-L-K-V-L-T-T-G-L-P-A-L-I-S-W-I-K-R-K-R-Q-Q-NH₂。各字母对应氨基酸单字母缩写：G（Gly，甘氨酸）、I（Ile，异亮氨酸）、A（Ala，丙氨酸）、V（Val，缬氨酸）、L（Leu，亮氨酸）、K（Lys，赖氨酸）、T（Thr，苏氨酸）、P（Pro，脯氨酸）、S（Ser，丝氨酸）、W（Trp，色氨酸）、R（Arg，精氨酸）、Q（Gln，谷氨酰胺），“-NH₂”表示C端谷氨酰胺残基的酰胺化修饰。中文名称：蜂毒肽；其完整氨基酸序列对应的中文名称为：甘氨酰-异亮氨酰-甘氨酰-丙氨酰-缬氨酰-亮氨酰-赖氨酰-缬氨酰-亮氨酰-苏氨酰-苏氨酰-甘氨酰-亮氨酰-脯氨酰-丙氨酰-亮氨酰-异亮氨酰-丝氨酰-色氨酰-异亮氨酰-赖氨酰-精氨酰-赖氨酰-精氨酰-谷氨酰胺酰-谷氨酰胺酰胺。等电点（pI）：约为10.2-10.8。通过氨基酸组成分析，该多肽含6个碱性氨基酸残基（赖氨酸3个、精氨酸2个，侧链pKa分别约为10.53、12.48；组氨酸0个），酸性氨基酸残基仅1个（无天冬氨酸、谷氨酸，仅潜在微弱酸性位点），碱性基团数量远多于酸性基团，且C端酰胺化修饰消除了游离羧基的酸性，使分子整体呈强碱性，精确pI值可通过ExPASy ProtParam等生物信息学工具计算获得。CAS号：蜂毒肽的CAS登记号为20449-79-0，该编号为通用登记号，可在化学数据库（如SciFinder、PubChem）中检索其标准化学信息、物质安全数据及相关研究文献。其他关键性质：分子式为C₁₃₁H₂₂₉N₃₉O₃₁，分子量约为2846.5 g/mol；溶解性方面，因含多个碱性氨基酸残基及极性氨基酸，易溶于水、生理盐水、稀酸及二甲亚砜（DMSO），在甲醇、乙醇中可完全溶解，难溶于氯仿、乙醚、丙酮等非极性溶剂；结构稳定性上，C端酰胺化修饰增强了其抗蛋白酶降解能力，在pH 5.0-9.0环境下稳定，强酸、强碱会导致肽键断裂，高温（＞60℃）会使其二级结构破坏，丧失生物活性，需在-20℃以下密封、避光、冷冻保存，避免反复冻融；其核心结构特征为两亲性α-螺旋，N端为疏水区，C端为亲水区，这一结构是其发挥生物活性的基础。二、应用领域蜂毒肽的应用基于其显著的抗菌、抗炎、抗肿瘤等生物活性及两亲性结构特征，广泛覆盖多个研究与应用领域，具体包括：抗菌药物研究领域：作为天然抗菌肽的典型代表，对革兰氏阳性菌（如金黄色葡萄球菌）、革兰氏阴性菌（如大肠杆菌）及部分真菌（如白色念珠菌）具有强效抑制作用，用于新型抗菌药物研发，尤其针对多重耐药菌感染的治疗研究。抗肿瘤研究与药物开发：可特异性作用于肿瘤细胞细胞膜，诱导肿瘤细胞凋亡或坏死，对肺癌、肝癌、乳腺癌等多种肿瘤细胞具有抑制活性，是抗肿瘤多肽药物研发的重要候选分子。抗炎与免疫调节研究：可抑制炎症因子（如TNF-α、IL-6、IL-1β）的释放，调节免疫细胞活性，用于类风湿关节炎、银屑病等自身免疫性炎症疾病的发病机制研究及治疗药物开发。生物农药研发领域：因具有广谱抗菌、抗虫活性，且对环境友好、不易产生耐药性，用于开发新型生物农药，防治农作物的细菌、真菌病害及部分害虫。生物医学基础研究：作为研究多肽-细胞膜相互作用的模式分子，用于解析抗菌肽的作用机制、细胞膜通透性调控原理及蛋白质两亲性结构与功能的关系。诊断试剂与检测工具开发：作为标准品用于制备蜂毒肽特异性抗体，开发酶联免疫吸附测定（ELISA）、Western Blot等检测方法，用于蜜蜂毒液成分分析、蜂毒过敏诊断及相关药物的质量控制。三、应用原理蜂毒肽的应用原理核心围绕其两亲性α-螺旋结构介导的细胞膜作用机制及对特定细胞信号通路的调控作用，不同应用场景的原理各有侧重：抗菌应用原理：蜂毒肽的两亲性α-螺旋结构使其能快速结合细菌细胞膜，疏水区插入细胞膜疏水核心，亲水区与细胞膜表面的磷脂头部结合，进而通过“桶-板”模型或“地毯”模型破坏细胞膜完整性，形成跨膜通道或导致细胞膜破裂，使细菌内物质外泄而死亡。其对细菌的选择性源于细菌细胞膜含大量酸性磷脂，而蜂毒肽C端的碱性氨基酸可通过静电作用特异性结合，对哺乳动物细胞膜的损伤较小。抗肿瘤应用原理：肿瘤细胞细胞膜的磷脂不对称性被破坏，表面暴露更多酸性磷脂，蜂毒肽通过C端碱性区域与肿瘤细胞膜特异性结合，插入细胞膜后破坏其结构完整性；同时可进入细胞内，调控肿瘤细胞凋亡信号通路，如激活 caspase 家族蛋白酶，促进 Bax 蛋白表达、抑制 Bcl-2 蛋白表达，最终诱导肿瘤细胞凋亡。抗炎应用原理：蜂毒肽可通过抑制核因子κB（NF-κB）信号通路的激活，减少炎症因子（TNF-α、IL-6等）的转录与释放；同时可清除体内活性氧（ROS），减轻氧化应激损伤，缓解炎症反应。此外，其可调节巨噬细胞、淋巴细胞等免疫细胞的活性，平衡机体免疫应答。生物农药应用原理：对农作物病原菌（细菌、真菌）的作用原理与抗菌机制一致，通过破坏病原菌细胞膜发挥抑制作用；对害虫的作用则是通过破坏害虫消化道细胞膜或体壁细胞膜，导致害虫生理功能紊乱而死亡，且因是天然多肽，易被环境微生物降解，无残留污染。免疫检测原理：以蜂毒肽为抗原免疫动物（如兔、小鼠）制备特异性单克隆或多克隆抗体，构建双抗体夹心法或竞争法检测体系。样品中的蜂毒肽与抗体特异性结合，通过酶标信号放大或放射性标记检测，实现对其含量的定量分析，蜂毒肽标准品用于绘制浓度-信号强度标准曲线。四、药物研发中的应用蜂毒肽在药物研发中主要作为天然活性多肽模板，聚焦于抗菌、抗肿瘤、抗炎等领域的药物开发，贯穿靶点验证、结构优化、活性筛选、药效评价等关键环节，具体应用如下：抗菌药物研发：针对多重耐药菌感染的临床困境，以蜂毒肽为母体进行结构修饰（如氨基酸替换、PEG修饰、环化改造），优化其抗菌活性、降低溶血毒性。通过构建细菌感染细胞模型或动物模型，筛选出高效低毒的抗菌肽衍生物，用于治疗皮肤感染、呼吸道感染等疾病。抗肿瘤药物研发：将蜂毒肽与肿瘤靶向分子（如叶酸、单克隆抗体）偶联，构建靶向抗肿瘤药物，提高其对肿瘤细胞的选择性，减少对正常细胞的损伤。同时通过纳米载体（如脂质体、纳米粒）包载蜂毒肽，延长其体内半衰期，增强肿瘤组织的药物富集量，提升抗肿瘤疗效。抗炎药物研发：以蜂毒肽抑制NF-κB信号通路的作用机制为靶点，筛选能增强其抗炎活性的小分子化合物或多肽衍生物，用于类风湿关节炎、银屑病等炎症疾病的治疗。通过体外细胞炎症模型（如LPS诱导的巨噬细胞炎症模型）和体内动物炎症模型（如大鼠佐剂性关节炎模型）验证药物的抗炎效果。药物递送系统优化：利用蜂毒肽的两亲性结构与细胞膜穿透能力，将其作为药物递送载体的组件，促进小分子药物、核酸药物（如siRNA）进入细胞内，提高药物的细胞摄取效率，解决药物递送难题。药物质量控制工具：作为标准品用于抗菌、抗肿瘤多肽药物的质量控制，通过HPLC、ELISA等方法检测药物的纯度、活性，确保药物的质量稳定性与安全性。五、作用机理蜂毒肽的作用机理核心是两亲性α-螺旋结构介导的细胞膜相互作用，不同生物活性的作用机理存在差异，具体如下：抗菌作用机理：第一步为结合阶段，蜂毒肽C端的碱性氨基酸残基（Lys、Arg）通过静电作用与细菌细胞膜表面的酸性磷脂头部结合，使多肽靠近细胞膜；第二步为插入阶段，多肽N端疏水区在细胞膜的疏水作用下插入细胞膜疏水核心，诱导多肽形成稳定的α-螺旋结构；第三步为膜破坏阶段，大量蜂毒肽分子在细胞膜上聚集，通过“桶-板”模型（形成跨膜通道，导致胞内物质外泄）或“地毯”模型（多肽像地毯一样覆盖细胞膜表面，破坏膜结构完整性），最终导致细菌死亡。抗肿瘤作用机理：分为细胞膜介导的杀伤和细胞内信号通路调控两个途径。① 细胞膜途径：肿瘤细胞膜表面酸性磷脂暴露增加，蜂毒肽通过静电作用特异性结合后，插入细胞膜破坏其完整性，导致肿瘤细胞裂解；② 细胞内途径：蜂毒肽进入肿瘤细胞后，可激活线粒体凋亡通路，促进线粒体释放细胞色素c，激活 caspase-9 和 caspase-3，诱导肿瘤细胞凋亡；同时可抑制PI3K/Akt信号通路，减少肿瘤细胞增殖与存活。抗炎作用机理：主要通过抑制炎症信号通路和清除活性氧实现。① 抑制NF-κB信号通路：蜂毒肽可阻止NF-κB p65亚基进入细胞核，减少炎症因子（TNF-α、IL-6、IL-1β）的转录与表达；② 清除活性氧：其结构中的Trp残基可 scavenge 体内的ROS，减轻氧化应激对细胞的损伤；③ 调节免疫细胞活性：抑制巨噬细胞的过度活化，促进抗炎细胞因子（IL-10）的释放，平衡机体免疫应答。溶血作用机理（副作用相关）：高浓度蜂毒肽可与哺乳动物红细胞细胞膜结合，通过类似抗菌的膜破坏机制导致红细胞破裂，产生溶血副作用。其对红细胞的损伤程度与浓度相关，低浓度下因红细胞细胞膜磷脂不对称性维持较好，损伤较小，这也是通过结构修饰降低其溶血毒性的重要依据。六、研究进展当前关于蜂毒肽的研究聚焦于结构修饰优化、作用机理深化、给药系统开发及临床应用探索，核心进展包括：结构修饰与活性优化进展：通过氨基酸定点突变（如将C端碱性氨基酸替换为中性氨基酸）、环化修饰、PEG化修饰等方法，成功降低了蜂毒肽的溶血毒性，同时保留或增强了其抗菌、抗肿瘤活性。例如，某研究通过将蜂毒肽第21位Lys替换为Ala，其溶血毒性降低60%，而对金黄色葡萄球菌的抗菌活性仅下降15%；PEG化修饰后，蜂毒肽的体内半衰期从2小时延长至24小时以上。作用机理深化研究：利用冷冻电镜、分子动力学模拟等技术，明确了蜂毒肽与细菌细胞膜、肿瘤细胞膜结合的具体位点及构象变化，揭示了“桶-板”模型的详细分子过程；同时发现蜂毒肽可调控肿瘤细胞的自噬信号通路，为其抗肿瘤机制提供了新的理论依据。靶向给药系统开发：构建了多种蜂毒肽靶向递送系统，如叶酸修饰脂质体、肿瘤特异性抗体偶联纳米粒等，这些系统可特异性识别肿瘤细胞，提高药物在肿瘤组织的富集量，显著增强抗肿瘤疗效，减少对正常组织的损伤。例如，叶酸修饰的蜂毒肽脂质体对叶酸受体阳性的乳腺癌细胞裸鼠移植瘤的抑制率可达85%，远高于游离蜂毒肽。临床前与临床研究进展：蜂毒肽衍生物的抗菌、抗肿瘤临床前研究已取得显著进展，部分衍生物在小鼠感染模型、肿瘤移植模型中表现出良好的治疗效果，且安全性较高；在抗炎领域，蜂毒肽局部给药用于治疗类风湿关节炎的临床试验已进入Ⅱ期，结果显示其可有效缓解关节肿胀、疼痛症状，且副作用轻微。多领域应用拓展研究：除传统应用领域外，近年研究发现蜂毒肽具有抗真菌生物膜、抗病毒（如流感病毒、新冠病毒）活性，其通过破坏真菌生物膜结构、抑制病毒包膜融合发挥作用，拓展了其在抗真菌感染、抗病毒药物研发中的应用前景；同时在生物传感器领域，利用蜂毒肽与细胞膜的特异性作用，开发出用于细菌检测的生物传感器，检测灵敏度可达10² CFU/mL。七、相关案例分析以下通过两个典型研究案例，展现蜂毒肽在药物研发与基础研究中的实际应用价值：案例一：PEG化蜂毒肽衍生物的抗菌活性与安全性评价研究背景：多重耐药金黄色葡萄球菌（MRSA）感染已成为临床治疗难题，蜂毒肽具有强效抗MRSA活性，但溶血毒性限制了其临床应用，需通过结构修饰优化其安全性。实验设计：通过固相多肽合成技术合成蜂毒肽（MEL），并在其N端偶联不同分子量（2 kDa、5 kDa、10 kDa）的聚乙二醇（PEG），获得PEG₂k-MEL、PEG₅k-MEL、PEG₁₀k-MEL三种衍生物。采用微量肉汤稀释法检测衍生物对MRSA（ATCC 43300）的最低抑菌浓度（MIC）；采用兔红细胞溶血实验检测溶血毒性；构建MRSA小鼠皮肤感染模型，将不同剂量的PEG₅k-MEL（1 mg/kg、2 mg/kg、4 mg/kg）局部给药，观察皮肤感染愈合情况及小鼠体重变化。结果与结论：PEG₂k-MEL、PEG₅k-MEL对MRSA的MIC分别为1 μg/mL、2 μg/mL，与天然蜂毒肽（MIC=1 μg/mL）接近，而PEG₁₀k-MEL的MIC升高至8 μg/mL；溶血实验显示，PEG₅k-MEL的溶血率（10 μg/mL时为12%）较天然蜂毒肽（10 μg/mL时为75%）显著降低；动物实验中，4 mg/kg PEG₅k-MEL局部给药7天后，小鼠皮肤感染部位的MRSA数量较模型组减少99%，皮肤愈合率达80%，且小鼠体重无明显变化，未出现全身毒性反应。该案例证实，PEG化修饰可在保留蜂毒肽抗菌活性的同时降低其溶血毒性，PEG₅k-MEL具有良好的临床应用潜力，为MRSA感染治疗提供了新的候选药物。案例二：蜂毒肽诱导肝癌细胞凋亡的机制研究研究背景：肝癌是全球高发的恶性肿瘤，化疗药物存在耐药性问题，蜂毒肽对肝癌细胞具有抑制活性，但具体凋亡机制尚不明确，需深入解析以指导其抗肿瘤药物研发。实验设计：将非洲爪蟾（蛙类模式生物）分为4组，对照组正常饲养，实验组1置于黑色环境中，实验组2置于白色环境中，实验组3置于黑色环境+注射蛙黑素抑制素拮抗剂（10 μg/kg），分别在处理后0、12、24、48小时检测血清MSH水平、皮肤黑素细胞中黑素颗粒分布及下丘脑黑素抑制素mRNA表达量。结果与结论：实验组2（白色环境）非洲爪蟾下丘脑黑素抑制素mRNA表达量较对照组升高3.2倍，血清MSH水平降低50%，黑素颗粒聚集于细胞中心，体色变浅；实验组1（黑色环境）则呈现相反趋势，黑素抑制素mRNA表达降低，MSH水平升高，体色变深；实验组3（黑色环境+拮抗剂）体色变深程度较实验组1更显著，MSH水平升高70%。该研究证实，蛙黑素抑制素通过负反馈调控MSH释放参与蛙类体色的环境适应过程，拮抗剂可阻断这一调控作用，为两栖动物神经内分泌适应机制提供了直接实验证据。八、总结与展望蛙黑素抑制素作为调控脊椎动物HPM轴的关键神经肽，不仅是解析蛙类色素适应机制的核心工具，更因其跨物种功能保守性在哺乳动物黑素调控、能量代谢等研究中具有重要价值。当前研究已明确其结构特征、作用机理及应用潜力，建立了基于其活性的药物筛选模型，并在美白药物研发中取得阶段性进展。未来，随着结构生物学与基因编辑技术的发展，对蛙黑素抑制素受体的结构解析及信号通路交互机制将更加深入，为精准药物设计提供更精确的靶点信息；同时，给药方式的优化将解决其体内稳定性问题，推动其从研究工具向临床应用转化，实现基础研究与应用开发的双重突破。相关产品：Met-Cys-His-Phe-Gly-Gly-Arg-Met-Asp-Arg-Ile-Ser-Cys-Tyr-Arg-NH2 (Cys6,17, disulfide bridge)Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2Asp-Ser-Ala-Pro-Asn-Pro-Val-Leu-Asp-Ile-Asp-Gly-Glu-Lys-Leu-Arg-Thr-Gly-Thr-AsnTyr-Pro-Phe-Pro-NH2Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala-Ala-Pro-Gln-Arg-Phe-NH2Ala-Asn-Glu-Arg-Ala-Asp-Leu-Ile-Ala-Tyr-Leu-Gln-Gln-Ala-Thr-LysPhe-Val-Pro-Ile-Phe-Thr-His-Ser-Glu-Leu-Gln-Lys-Ile-Arg-Glu-Lys-Glu-Arg-Asn-Lys-Gly-GlnPhe-Val-Pro-Ile-Phe-Thr-Tyr-Gly-Glu-Leu-Gln-Arg-Met-Gln-Glu-Lys-Glu-Arg-Asn-Lys-Gly-GlnAc-Nle-Asp-His-D-Phe-Arg-Trp-Lys-NH2 (cyclized between Nle4, Lys10)产品信息来源：楚肽生物所有产品仅用作实验室科学研究，不为任何个人用途提供产品和服务。返回搜狐，查看更多
临床结果细胞疗法
2025-12-03
·知芽汇
“炎症”通常意味着红肿热痛——比如喉咙发炎、皮肤感染，但你是否想过，大脑也可能“发炎”，这种看不见摸不着的“神经炎症”，可能正是自闭症、多动症、抽动症，甚至某些孩子突然出现的强迫行为、情绪崩溃、恐惧进食背后的共同推手。
过去几十年，医学界普遍将这些行为问题归为“心理障碍”或“教养问题”，然而，近年来越来越多的研究揭示：免疫系统不仅守护身体免受病毒细菌侵袭，也深度参与了大脑的发育与功能调节。当免疫反应失调，尤其在生命早期关键窗口期（如孕期或婴幼儿阶段）出现免疫异常激活，就可能干扰神经回路的正常构建，埋下神经发育障碍的种子。
2025年8月，一项发表于国际权威期刊《国际分子科学杂志》的重要综述研究（Gagliano et al., 2025）系统梳理了神经发育障碍（NDDs）与儿童急性发作神经精神综合征（PANS）之间免疫-炎症联系。
这项由意大利、美国等多国科学家合作完成的研究，整合了来自全球上百项高质量研究，提出一个颠覆性观点：这些看似不同的精神行为问题，可能共享一条“免疫-神经炎症”的致病通路。
一、免神经发育障碍(NDDs)：真的是“心理问题”吗？
▸ 神经发育障碍(NDDs)
根据《精神障碍诊断与统计手册》（DSM-5），神经发育障碍 （NDDs）是一大类在儿童期起病、影响大脑发育和功能的疾病统称，主要包括：
· 自闭症谱系障碍(ASD):社交沟通困难、重复刻板行为、兴趣狭窄
· 注意缺陷多动障碍(ADHD):注意力难以集中、坐不住、冲动行事
· 抽动障碍/图雷特综合征(TD/TS):不自主地眨眼、耸肩、清嗓子，甚至发出怪声
· 智力障碍(ID):学习能力、生活自理能力显著低于同龄人
· 特定学习障碍(SLDs):阅读、书写或数学能力严重落后,智力通常正常
长期以来，这些障碍主要依靠行为观察和临床评估来诊断，缺乏明确的生物学标志物，因此，社会上常存在误解：认为这些问题源于“父母管教不当”“孩子懒惰”或“性格古怪”，许多家庭因此承受巨大压力，甚至陷入自责。
▸ 神经发育障碍(NDDs)生理共患病
现代神经科学证实，这些障碍源于大脑结构与功能的生物学差异，更关键的是，大量研究发现，神经发育障碍（NDDs）患者常常伴随其他身体问题：
· 过敏、湿疹、哮喘
· 自身免疫病（如1型糖尿病、桥本甲状腺炎、银屑病）
· 胃肠道问题（如便秘、腹泻、食物不耐受）
· 睡眠障碍、免疫力低下等
这种“共病现象”强烈提示：问题可能不止在大脑，而涉及全身性的生理失衡——尤其是免疫系统的异常，换句话说，孩子的“行为问题”，可能是身体内部“炎症风暴”的外在表现。
二、免疫系统：不只是“卫士”，更是大脑“建筑师”
要理解这一点，我们必须更新对免疫系统的认知，传统观念认为，大脑是一个“免疫豁免”器官——血脑屏障像一道坚固的城墙，将多数免疫细胞和炎症因子挡在外面，确保大脑环境稳定，但近二十年的研究不断完善并修正了这一看法：血脑屏障并非绝对“不可逾越”。
▸ 小胶质细胞：大脑的“常驻免疫工程师”
大脑中有一种特殊的免疫细胞，叫小胶质细胞，它们从胎儿期就开始工作，不仅是“哨兵”，更是“建筑师”：
1. 在发育早期,它们帮助神经元迁移到正确位置
2. 在儿童期，它们“修剪”多余的突触连接,让神经网络更高效
3. 它们还参与髓鞘形成（神经信号的“绝缘层”）,星形胶质细胞调控等关键过程
可以说，没有小胶质细胞的精准调控，就无法形成健康的大脑网络，但如果小胶质细胞被过度激活（如感染或毒素刺激），它们就会从“建设者”变成“破坏者”，释放大量炎症因子，损伤神经元，干扰突触可塑性。
▸ 免疫-脑对话：细胞因子是“信使”
免疫系统通过释放细胞因子（如IL-6、TNF-α、IL-17）等信号分子，与神经元“对话”，这些细胞因子：
1. 影响多巴胺、血清素等神经递质的合成与释放
2. 调节情绪、注意力、冲动控制
3. 改变神经回路的兴奋性与连接强度
因此，免疫系统不仅是防御者，更是大脑发育“合作者”甚至“指挥者”之一。
▸ 关键窗口期：生命最初1000天
从怀孕到孩子2岁，被称为“生命最初1000天”，这一时期，大脑以惊人速度发育，每天生成数百万神经元，建立万亿级连接，而免疫系统与大脑的互动尤为密切。
任何干扰（如母亲感染、压力、营养不良、环境污染）都可能通过免疫机制“编程”胎儿的大脑，使其在出生后对压力、感染等刺激更为敏感，更容易出现神经精神症状。
三、母体免疫激活：孩子大脑健康的“第一道警报”
综述中最引人注目的发现之一，是母亲在怀孕期间的免疫状态对孩子神经发育具有决定性影响。
▸ 什么是“母体免疫激活”（Maternal Immune Activation, MIA）？
当孕妇遭遇以下情况时，免疫系统会被激活，释放大量促炎细胞因子（如IL-6、TNF-α）：
· 感染（如流感、尿路感染、新冠）
· 自身免疫病（如系统性红斑狼疮、桥本甲状腺炎）
· 慢性炎症状态（如肥胖、哮喘、过敏）
这些炎症因子虽不能直接穿过胎盘，却可以：
· 改变胎盘功能，影响营养和氧气供应
· 激活胎儿自身的免疫系统
· 通过表观遗传机制（如DNA甲基化、microRNA调控）“标记”胎儿基因，使其在出生后长期处于高敏状态
▸ 科学证据有多强？
动物实验：
给怀孕小鼠注射模拟病毒的物质，其后代会出现社交退缩、重复行为、注意力缺陷——酷似人类ASD和ADHD。
人群研究：
1. 孕期母体IL-6水平升高，与孩子日后患自闭症、多动症、精神分裂症的风险显著相关
2. 母亲患有哮喘+极度肥胖，女婴患自闭症的风险可增加近17倍
3. 孕期C反应蛋白（CRP，炎症标志物）水平高，孩子10岁时被诊断为ADHD的几率上升40%
这些发现指向一个核心机制：母体的炎症信号“编程”了胎儿的免疫系统和大脑，为其一生埋下神经发育脆弱性的种子。
这解释了为何许多神经发育障碍(NDDs)患者具有家族聚集性——并非单纯遗传“精神病基因”，而是遗传了对免疫失调的易感性。
四、PANS——神经炎症“急先锋”：从慢性波动到急性爆发
如果说自闭症、多动症等是“慢性神经炎症”的表现，那么儿童急性神经精神综合征（PANS）则是其“急性暴发”形式。
▸ PANS是什么？家长如何识别？
PANS是一种突然发作（通常在数小时至数天内）的综合征，表现为：
·强迫症状：如反复洗手、检查门窗、害怕污染
·严重进食障碍：拒绝进食，担心食物有毒、噎住或“不干净”
·同时伴随至少两种以下症状：
1. 极度焦虑、情绪失控、易怒、攻击行为
2. 行为退化(如婴儿式说话、粘人、尿床)
3. 注意力涣散、记忆力下降、学业骤降
4. 运动协调障碍、字迹变差、感觉异常
5. 睡眠紊乱(失眠或嗜睡)、噩梦
6. 尿频、遗尿、瞳孔散大、心跳过快等自主神经症状
很多PANS患儿在发病前有感染史（如链球菌咽炎、流感、新冠），但并非所有病例都能找到明确病原体，因此，PANS的诊断不依赖特定感染，而强调“急性发作+多系统症状”。
▸ PANS与免疫有何关系？
研究发现，PANS患儿普遍存在：
·血清和脑脊液中炎症因子升高（如IL-17、TNF-α、IL-1β）
·针对基底神经节（大脑控制运动、习惯、情绪的区域）的自身抗体
·补体系统激活（免疫清除机制过度活跃，产生C4a等炎症介质）
·低水平自身免疫证据（如抗核抗体阳性、甲状腺抗体升高、乳糜泻筛查阳性）
·家族中自身免疫病高发（如多发性硬化、类风湿关节炎、红斑狼疮）
特别值得注意的是，约22%-71%的PANS患儿本身就有ADHD、ASD等神经发育障碍背景，这提示：PANS并非孤立疾病，而可能是已有神经发育脆弱性的孩子，在感染或应激触发下，免疫系统“过激反应”导致的症状急性恶化。
科学家提出“双重打击”模型：
第一次打击（孕期MIA或遗传易感）→ 大脑发育基础薄弱
第二次打击（儿童期感染/应激）→ 免疫系统失控，攻击神经回路 →PANS急性发作
五、跨越诊断界限：一个共享的“免疫—神经炎症”谱系
通常，医生按症状将孩子分门别类：自闭症、多动症、强迫症等等……但新研究证据表明，这些障碍在免疫机制上高度重叠，综述通过系统分析发现，各类障碍在以下六个维度上存在共性：
1. 遗传免疫相关改变
多个调控免疫反应与突触形成的基因（如SHANK3、NLRC4、SYNGAP1、PPM1D）在ASD、ADHD、PANS中均被发现存在变异，这些基因如同“双面开关”，既影响免疫细胞功能，又调控神经连接。
2. 家族自身免疫病史
几乎所有NDDs和PANS患者的家庭中，自身免疫病（如甲状腺炎、1型糖尿病、银屑病）的患病率都显著高于普通人群，PANS尤为突出——70%有家族史，20%的母亲患有严重自身免疫病。
3. 母体免疫激活（MIA）
孕期感染、炎症或自身抗体，是ASD、ADHD、精神分裂症的共同风险因素，虽然PANS尚无直接证据，但其相关基因在胎盘和脑血管中表达，暗示MIA可能奠定易感基础。
4. 炎症生物标志物
患者血清或脑脊液中普遍存在促炎因子（IL-6、TNF-α等）升高，且水平常与症状严重程度相关，PANS患者还表现出独特的代谢谱（如甘氨酸、谷氨酰胺异常），反映神经炎症与氧化应激。
5. 小胶质细胞失调
尸检和影像学研究证实，ASD、精神分裂症患者大脑中存在持续性小胶质细胞激活，动物模型显示，PANS相关的Th17/IL-17通路可直接激活小胶质细胞，破坏突触。
6. 血脑屏障功能障碍
虽然证据强弱不一，但ADHD、ASD、PANS均提示血脑屏障可能存在“漏洞”，使外周炎症因子或自身抗体得以进入中枢神经系统，引发“低级别神经炎症”。
因此，这些障碍不是彼此割裂的疾病，而是一个“免疫-神经炎症”谱系的不同表现，未来的精神疾病分类或许不再以症状为主，而转向基于生物学机制的“维度模型”——正如美国国立精神卫生研究所（NIMH）倡导的“研究领域标准”（RDoC）。
六、治疗新思路：从“压制症状”到“调节免疫”
目前，NDDs和PANS的主流治疗仍以行为干预和药物（如兴奋剂、抗精神病药）为主，但效果有限，且部分患者对药物反应不佳，甚至出现副作用，全球多项研究提示：对于存在免疫炎症证据的亚群，免疫调节可能成为关键突破口。
▸ 已有探索：
·抗生素/抗感染治疗：针对链球菌感染相关的PANDAS（PANS的一个亚型），青霉素等可预防复发
·静脉注射免疫球蛋白（IVIG）：通过调节抗体和免疫细胞，已在部分PANS和自闭症患儿中显示疗效，改善强迫、焦虑和认知功能
·皮质类固醇激素：如甲泼尼龙短期使用可快速抑制炎症，缓解急性症状
·血浆置换（Plasmapheresis）：清除循环中的致病性自身抗体，用于重症PANS
·靶向细胞因子药物：如抗IL-6（托珠单抗）、抗TNF-α（英夫利昔单抗）等生物制剂，正在临床试验中
然而，目前缺乏大规模随机对照试验（RCT）验证这些疗法的有效性与安全性，原因在于：
1.患者异质性高：并非所有ADHD或ASD都由免疫驱动
2.缺乏可靠生物标志物：难以精准识别“免疫亚型”
3.血脑屏障限制：许多药物难以进入中枢神经系统
▸ 未来方向：
·开发多模态生物标志物组合（如细胞因子+自身抗体+脑成像+代谢组学）
·根据免疫表型分层治疗（如“高炎症型” vs “免疫缺陷型”）
·在生命早期窗口期进行预防性干预（如优化孕期营养、控制母体炎症、调节肠道菌群）
七、给家长启示：关注“身体健康”，而不是仅仅“特殊教育”
如果你的孩子被诊断为神经发育障碍（NDDs），或出现突发性行为改变，请记住：
1. 这不是你的错，也不是孩子的“不听话”
背后可能有复杂的生物学机制，责备自己或强迫孩子“坚强一点”往往适得其反。
2. 全面体检很重要
建议排查：
·过敏原、食物不耐受
·自身免疫指标（如抗核抗体ANA、甲状腺抗体TPO-Ab）
·炎症标志物（C反应蛋白CRP、血沉ESR）
·维生素D、铁、锌等营养素水平
·肠道健康（如肠道菌群检测、乳糜泻筛查）
3. 记录症状与感染/应激事件的关系
如果每次感冒后抽动加重，或发烧后出现强迫行为，务必详细记录并告知医生，这可能是识别“免疫亚型”的关键线索。
4. 不要盲目尝试“消炎”
阿司匹林、布洛芬等非处方药对神经炎症作用有限，且可能有副作用，应在专业医生（如儿科神经免疫专家）指导下评估免疫干预的必要性。
5. 重视“生命最初1000天”
计划怀孕的女性建议如下：
·管理好慢性病（如哮喘、甲状腺疾病）
·保持健康体重，避免肥胖
·均衡饮食，补充叶酸、Omega-3
·减少压力，保证睡眠
·避免不必要的抗生素和环境毒素暴露
结语：“免疫神经精神病学”时代
长期以来，受身心二元论的影响，人们习惯于将“心理”与“生理”视为彼此分离的领域，然而，当代科学研究正不断打破这一传统界限，大脑并非孤立运作的器官，而是持续与免疫、代谢以及肠道微生态等系统进行复杂的动态的交互，共同构成一个高度整合的身心整体。
神经发育障碍（NNDs）和儿童急性神经精神综合征（PANS）的研究，不仅揭示了免疫炎症的核心作用，更呼吁我们要采用跨学科、多视角来看待儿童神经发育障碍，未来的诊疗，或将从“你是哪种病？”转向“你的免疫-神经网络发生了什么？”
正如该综述所言：“我们需要一场范式转变——承认大脑如同心脏、肝脏一样，也会因炎症而“生病”，并值得同样严谨的医学对待”。
这条路还很长——目前仍缺乏大规模的临床实验，免疫治疗也尚未成为标准方案，但每一步进展，都在为千万家庭带来新的希望！
参考文献：（向上滑动阅览）
向上滑动阅览
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed.; American Psychiatric Publishing: Arlington, VA, USA, 2013.
2. Mullin, A.P.; Gokhale, A.; Moreno–De–Luca, A.; Sanyal, S.; Waddington, J.L.; Faundez, V. Neurodevelopmental Disorders: Mechanisms and Boundary Definitions from Genomes, Interactomes and Proteomes. Transl. Psychiatry 2013, 3, e329. [CrossRef]
3. Parenti, I.; Rabaneda, L.G.; Schoen, H.; Novarino, G. Neurodevelopmental Disorders: From Genetics to Functional Pathways. Trends Neurosci. 2020, 43, 608–621. [CrossRef]
4. Mottahedin, A.; Ardalan, M.; Chumak, T.; Riebe, I.; Ek, J.; Mallard, C. Effect of Neuroinflammation on Synaptic Organization and Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders. Front. Cell. Neurosci. 2017, 11, 190. [CrossRef] [PubMed]
5. Martino, D.; Johnson, I.; Leckman, J.F. What Does Immunology Have to Do with Normal Brain Development and the Patho– physiology Underlying Tourette Syndrome and Related Neuropsychiatric Disorders? Front. Neurol. 2020, 11, 567407. [CrossRef] [PubMed]
6. Shohat, S.; Amelan, A.; Shifman, S. Convergence and Divergence in the Genetics of Psychiatric Disorders from Pathways to Developmental Stages. Biol. Psychiatry 2021, 89, 32–40. [CrossRef]
7. Smoller, J.W.; Andreassen, O.A.; Edenberg, H.J.; Faraone, S.V.; Glatt, S.J.; Kendler, K.S. Psychiatric Genetics and the Structure of Psychopathology. Mol. Psychiatry 2019, 24, 409–420. [CrossRef] [PubMed]
8. Azevedo, F.A.C.; Carvalho, L.R.B.; Grinberg, L.T.; Farfel, J.M.; Ferretti, R.E.L.; Leite, R.E.P.; Filho, W.J.; Lent, R.; Herculano–Houzel, S. Equal Numbers of Neuronal and Nonneuronal Cells Make the Human Brain an Isometrically Scaled–Up Primate Brain. J. Comp. Neurol. 2009, 513, 532–541. [CrossRef]
9. Mondelli, V.; Dazzan, P.; Pariante, C.M. Immune Abnormalities Across Psychiatric Disorders: Clinical Relevance; Cambridge University Press: Cambridge, UK, 2015.
10. Pape, K.; Tamouza, R.; Leboyer, M.; Zipp, F. Immunoneuropsychiatry—Novel Perspectives on Brain Disorders. Nat. Rev. Neurol. 2019, 15, 317–328. [CrossRef]
11. Carvalho, A.F.; Solmi, M.; Sanches, M.; Machado, M.O.; Stubbs, B.; Ajnakina, O.; Sherman, C.; Sun, Y.R.; Liu, C.S.; Brunoni, A.R.; et al. Evidence–Based Umbrella Review of 162 Peripheral Biomarkers for Major Mental Disorders. Transl. Psychiatry 2020, 10, 152. [CrossRef]
12. Goldsmith, D.R.; Bekhbat, M.; Mehta, N.D.; Felger, J.C. Inflammation–Related Functional and Structural Dysconnectivity as a Pathway to Psychopathology. Biol. Psychiatry 2023, 93, 405–418. [CrossRef]
13. Merzon, E.; Israel, A.; Ashkenazi, S.; Rotem, A.; Schneider, T.; Faraone, S.V.; Biederman, J.; Green, I.; Golan–Cohen, A.; Vinker, S.; et al. Attention–Deficit/Hyperactivity Disorder Is Associated with Increased Rates of Childhood Infectious Diseases: A Population–Based Case–Control Study. J. Am. Acad. Child Adolesc. Psychiatry 2023, 62, 253–260.e1. [CrossRef]
14. Lydholm, C.N.; Köhler–Forsberg, O.; Nordentoft, M.; Yolken, R.H.; Mortensen, P.B.; Petersen, L.; Benros, M.E. Parental Infections before, during, and after Pregnancy as Risk Factors for Mental Disorders in Childhood and Adolescence: A Nationwide Danish Study. Biol. Psychiatry 2019, 85, 317–325. [CrossRef]
15. Black, M.M.; Walker, S.P.; Fernald, L.C.H.; Andersen, C.T.; DiGirolamo, A.M.; Lu, C.; McCoy, D.C.; Fink, G.; Shawar, Y.R.; Shiffman, J.; et al. Early Childhood Development Coming of Age: Science through the Life Course. Lancet 2017, 389, 77–90. [CrossRef]
16. Tioleco, N.; Silberman, A.E.; Stratigos, K.; Banerjee–Basu, S.; Spann, M.N.; Whitaker, A.H.; Turner, J.B. Prenatal Maternal Infection and Risk for Autism in Offspring: A Meta–Analysis. Autism Res. 2021, 14, 1296–1316. [CrossRef] [PubMed]
17. Walle, K.M.; Askeland, R.B.; Gustavson, K.; Mjaaland, S.; Ystrom, E.; Lipkin, W.I.; Magnus, P.; Stoltenberg, C.; Susser, E.; Bresnahan, M.; et al. Risk of Attention–Deficit Hyperactivity Disorder in Offspring of Mothers with Infections during Pregnancy. JCPP Adv. 2022, 2, e12070. [CrossRef]
18. Brown, A.S.; Derkits, E.J. Prenatal Infection and Schizophrenia: A Review of Epidemiologic and Translational Studies. Am. J. Psychiatry 2010, 167, 261–280. [CrossRef]
19. Jones, H.F.; Han, V.X.; Patel, S.; Gloss, B.S.; Soler, N.; Ho, A.; Sharma, S.; Kothur, K.; Nosadini, M.; Wienholt, L.; et al. Maternal autoimmunity and inflammation are associated with childhood tics and obsessive–compulsive disorder: Transcriptomic data show common enriched innate immune pathways. Brain Behav. Immun. 2021, 94, 308–317. [CrossRef]
20. Sotgiu, S.; Manca, S.; Gagliano, A.; Minutolo, A.; Melis, M.C.; Pisuttu, G.; Scoppola, C.; Bolognesi, E.; Clerici, M.; Guerini, F.R.; et al. Immune Regulation of Neurodevelopment at the Mother–Foetus Interface: The Case of Autism. Clin. Transl. Immunol. 2020, 9, e1211. [CrossRef] [PubMed]
21. Choudhury, Z.; Lennox, B. Maternal Immune Activation and Schizophrenia—Evidence for an Immune Priming Disorder. Front. Psychiatry 2021, 12, 585742. [CrossRef] [PubMed]
22. Gilmore, J.H.; Jarskog, L.F. Exposure to infection and brain development: Cytokines in the pathogenesis of schizophrenia. Schizophr. Res. 1997, 24, 365–367. [CrossRef]
23. Estes, M.L.; McAllister, A.K. Maternal Immune Activation: Implications for Neuropsychiatric Disorders. Science 2016, 353, 772–777. [CrossRef]
24. Weber–Stadlbauer, U. Epigenetic and Transgenerational Mechanisms in Infection–Mediated Neurodevelopmental Disorders. Transl. Psychiatry 2017, 7, e1113. [CrossRef]
25. Graus, F.; Titulaer, M.J.; Balu, R.; Benseler, S.; Bien, C.G.; Cellucci, T.; Cortese, I.; Dale, R.C.; Gelfand, J.M.; Geschwind, M.; et al. A Clinical Approach to Diagnosis of Autoimmune Encephalitis. Lancet Neurol. 2016, 15, 391–404. [CrossRef] [PubMed] [PubMed Central]
26. Dalmau, J.; Graus, F. Antibody–Mediated Encephalitis. N. Engl. J. Med. 2018, 378, 840–851. [CrossRef]
27. Cellucci, T.; Van Mater, H.; Graus, F.; Muscal, E.; Gallentine, W.; Klein–Gitelman, M.S.; Benseler, S.M.; Frankovich, J.; Gorman, M.P.; Van Haren, K.; et al. Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient. Neurol. Neuroimmunol. Neuroinflammation 2020, 7, e663, Erratum in Neurol Neuroimmunol. Neuroinflamm. 2020, 7, e730. [CrossRef] [PubMed] [PubMed Central]
28. Armangue, T.; Spatola, M.; Vlagea, A.; Mattozzi, S.; Cárceles–Cordon, M.; Martinez–Heras, E.; Llufriu, S.; Muchart, J.; Erro, M.E.; Abraira, L.; et al. Frequency, Symptoms, Risk Factors, and Outcomes of Autoimmune Encephalitis after Herpes Simplex Encephalitis: A Prospective Observational Study and Retrospective Analysis. Lancet Neurol. 2018, 17, 760–772. [CrossRef]
29. Uy, C.E.; Binks, S.; Irani, S.R. Autoimmune Encephalitis: Clinical Spectrum and Management. Pract. Neurol. 2021, 21, 412–423. [CrossRef] [PubMed]
30. Bien, C.G.; Vincent, A.; Barnett, M.H.; Becker, A.J.; Blümcke, I.; Graus, F.; Jellinger, K.A.; Reuss, D.E.; Ribalta, T.; Schlegel, J.; et al. Immunopathology of Autoantibody–Associated Encephalitides: Clues for Pathogenesis. Brain 2012, 135, 1622–1638. [CrossRef]
31. Ehrenreich, H. Autoantibodies against the N–Methyl–d–Aspartate Receptor Subunit NR1: Untangling Apparent Inconsistencies for Clinical Practice. Front. Immunol. 2017, 8, 181. [CrossRef]
32. Makrides, V.; Dolgodilina, E.; Virgintino, D. Blood–Brain Barrier Transporters and Neuroinflammation: Partners in Neuro– protection and in Pathology. In The Blood Brain Barrier and Inflammation; Springer: Cham, Switzerland, 2017; pp. 103–151. [CrossRef]
33. Dileepan, T.; Smith, E.D.; Knowland, D.; Hsu, M.; Platt, M.; Bittner–Eddy, P.; Cohen, B.; Southern, P.; Latimer, E.; Harley, E.; et al. Group A Streptococcus Intranasal Infection Promotes CNS Infiltration by Streptococcal–Specific Th17 Cells. J. Clin. Investig. 2016, 126, 303–317. [CrossRef]
34. Liebner, S.; Dijkhuizen, R.M.; Reiss, Y.; Plate, K.H.; Agalliu, D.; Constantin, G. Functional Morphology of the Blood–Brain Barrier in Health and Disease. Acta Neuropathol. 2018, 135, 311–336. [CrossRef]
35. Platt, M.P.; Agalliu, D.; Cutforth, T. Hello from the Other Side: How Autoantibodies Circumvent the Blood–Brain Barrier in Autoimmune Encephalitis. Front. Immunol. 2017, 8, 442. [CrossRef]
36. Paolicelli, R.C.; Ferretti, M.T. Function and Dysfunction of Microglia during Brain Development: Consequences for Synapses and Neural Circuits. Front. Synaptic Neurosci. 2017, 9, 9. [CrossRef] [PubMed]
37. Mehl, L.C.; Manjally, A.V.; Bouadi, O.; Gibson, E.M.; Tay, T.L. Microglia in Brain Development and Regeneration. Development 2022, 149, dev200425. [CrossRef] [PubMed]
38. Komada, M.; Nishimura, Y. Epigenetics and Neuroinflammation Associated with Neurodevelopmental Disorders: A Microglial Perspective. Front. Cell Dev. Biol. 2022, 10, 852752. [CrossRef] [PubMed]
39. Gagliano, A.; Carta, A.; Tanca, M.G.; Sotgiu, S. Pediatric Acute–Onset Neuropsychiatric Syndrome: Current Perspectives. Neuropsychiatr. Dis. Treat. 2023, 19, 1221–1250. [CrossRef]
40. Kreutzberg, G.W. Microglia: A Sensor for Pathological Events in the CNS. Trends Neurosci. 1996, 19, 312–318. [CrossRef]
41. Chakraborty, S.; Kaushik, D.K.; Gupta, M.; Basu, A. Inflammasome Signaling at the Heart of Central Nervous System Pathology.
J. Neurosci. Res. 2010, 88, 1615–1631. [CrossRef]
42. Singhal, G.; Jaehne, E.J.; Corrigan, F.; Toben, C.; Baune, B.T. Inflammasomes in Neuroinflammation and Changes in Brain Function: A Focused Review. Front. Neurosci. 2014, 8, 315. [CrossRef]
43. Heneka, M.T.; McManus, R.M.; Latz, E. Inflammasome Signalling in Brain Function and Neurodegenerative Disease. Nat. Rev. Neurosci. 2018, 19, 610–621. [CrossRef]
44. Orihuela, R.; McPherson, C.A.; Harry, G.J. Microglial M1/M2 Polarization and Metabolic States. Br. J. Pharmacol. 2016, 173, 649–665. [CrossRef]
45. Prinz, M.; Jung, S.; Priller, J. Microglia Biology: One Century of Evolving Concepts. Cell 2019, 179, 292–311. [CrossRef] [PubMed]
46. Stratoulias, V.; Venero, J.L.; Tremblay, M.È.; Joseph, B. Microglial Subtypes: Diversity within the Microglial Community. EMBO J. 2019, 38, e101997. [CrossRef]
47. Thion, M.S.; Garel, S. Microglial Ontogeny, Diversity and Neurodevelopmental Functions. Curr. Opin. Genet. Dev. 2020, 65, 186–194. [CrossRef] [PubMed]
48. Glatt, S.J.; Faraone, S.V.; Tsuang, M.T. Is Schizophrenia a Neurodevelopmental Disorder? In Schizophrenia; Oxford University Press: Oxford, UK, 2019. [CrossRef]
49. Burchi, E.; Pallanti, S. Diagnostic Issues in Early–Onset Obsessive–Compulsive Disorder and Their Treatment Implications. Curr. Neuropharmacol. 2019, 17, 672–680. [CrossRef]
50. Gagliano, A.; Galati, C.; Ingrassia, M.; Ciuffo, M.; Alquino, M.A.; Tanca, M.G.; Carucci, S.; Zuddas, A.; Grossi, E. Pediatric Acute–Onset Neuropsychiatric Syndrome: A Data Mining Approach to a Very Specific Constellation of Clinical Variables. J. Child Adolesc. Psychopharmacol. 2020, 30, 495–511. [CrossRef]
51. Tricco, A.C.; Lillie, E.; Zarin, W.; O’Brien, K.K.; Colquhoun, H.; Levac, D.; Moher, D.; Peters, M.D.J.; Horsley, T.; Weeks, L.; et al. PRISMA Extension for Scoping Reviews (PRISMA–ScR): Checklist and Explanation. Ann. Intern. Med. 2018, 169, 467–473. [CrossRef]
52. Buske–Kirschbaum, A.; Schmitt, J.; Plessow, F.; Romanos, M.; Weidinger, S.; Roessner, V. Psychoendocrine and Psychoneu– roimmunological Mechanisms in the Comorbidity of Atopic Eczema and ADHD. Psychoneuroendocrinology 2013, 38, 12–23. [CrossRef]
53. Hegvik, T.A.; Chen, Q.; Kuja–Halkola, R.; Klungsøyr, K.; Butwicka, A.; Lichtenstein, P.; Almqvist, C.; Faraone, S.V.; Haavik, J.; Larsson, H. Familial co–aggregation of attention–deficit/hyperactivity disorder and autoimmune diseases: A cohort study based on Swedish population–wide registers. Int. J. Epidemiol. 2022, 51, 898–909. [CrossRef]
54. Liao, T.C.; Lien, Y.T.; Wang, S.; Huang, S.L.; Chen, C.Y. Comorbidity of atopic disorders with autism spectrum disorder and attention deficit/hyperactivity disorder. J. Pediatr. 2016, 171, 248–255. [CrossRef] [PubMed]
55. Lin, Y.T.; Chen, Y.C.; Gau, S.S.; Yeh, T.H.; Fan, H.Y.; Hwang, Y.Y.; Lee, Y.L. Associations between allergic diseases and attention deficit hyperactivity/oppositional defiant disorders in children. Pediatr. Res. 2016, 80, 480–485. [CrossRef]
56. Fasmer, O.B.; Halmøy, A.; Eagan, T.M.; Oedegaard, K.J.; Haavik, J. Adult attention deficit hyperactivity disorder is associated with asthma. BMC Psychiatry 2011, 11, 128. [CrossRef]
57. Hegvik, T.A.; Instanes, J.T.; Haavik, J.; Klungsøyr, K.; Engeland, A. Associations between attention–deficit/hyperactivity disorder and autoimmune diseases are modified by sex: A population–based cross–sectional study. Eur. Child Adolesc. Psychiatry 2018, 27, 663–675. [CrossRef]
58. Segman, R.H.; Meltzer, A.; Gross–Tsur, V.; Kosov, A.; Frisch, A.; Inbar, E.; Darvasi, A.; Levy, S.; Goltser, T.; Weizman, A.; et al. Preferential transmission of interleukin–1 receptor antagonist alleles in attention deficit hyperactivity disorder. Mol. Psychiatry 2002, 7, 72–74. [CrossRef] [PubMed]
59. Giana, G.; Romano, E.; Porfirio, M.C.; D’Ambrosio, R.; Giovinazzo, S.; Troianiello, M.; Barlocci, E.; Travaglini, D.; Granstrem, O.; Pascale, E.; et al. Detection of auto–antibodies to DAT in the serum: Interactions with DAT genotype and psycho–stimulant therapy for ADHD. J. Neuroimmunol. 2015, 278, 212–222. [CrossRef] [PubMed]
60. Toto, M.; Margari, F.; Simone, M.; Craig, F.; Petruzzelli, M.G.; Tafuri, S.; Margari, L. Antibasal Ganglia Antibodies and Antistrep– tolysin O in Noncomorbid ADHD. J. Atten. Disord. 2015, 19, 935–942. [CrossRef] [PubMed]
61. Instanes, J.T.; Halmøy, A.; Engeland, A.; Haavik, J.; Furu, K.; Klungsøyr, K. Attention–Deficit/Hyperactivity Disorder in Offspring of Mothers With Inflammatory and Immune System Diseases. Biol. Psychiatry 2017, 81, 452–459. [CrossRef]
62. Leffa, D.T.; Torres, I.L.S.; Rohde, L.A. A review on the role of inflammation in attention–deficit/hyperactivity disorder. Neuroim- munomodulation 2019, 25, 328–333. [CrossRef]
63. Zayats, T.; Athanasiu, L.; Sonderby, I.; Djurovic, S.; Westlye, L.T.; Tamnes, C.K.; Fladby, T.; Aase, H.; Zeiner, P.; Reichborn– Kjennerud, T.; et al. Genome–Wide Analysis of Attention Deficit Hyperactivity Disorder in Norway. PLoS ONE 2015, 10, e0122501. [CrossRef]
64. Faraone, S.V.; Asherson, P.; Banaschewski, T.; Biederman, J.; Buitelaar, J.K.; Ramos–Quiroga, J.A.; Rohde, L.A.; Sonuga–Barke, E.J.; Tannock, R.; Franke, B. Attention–Deficit/Hyperactivity Disorder. Nat. Rev. Dis. Primers 2015, 1, 15020. [CrossRef]
65. Li, D.J.; Tsai, C.S.; Hsiao, R.C.; Chen, Y.L.; Yen, C.F. Associations between allergic and autoimmune diseases with autism spectrum disorder and attention–deficit/hyperactivity disorder within families: A population–based cohort study. Int. J. Environ. Res. Public Health 2022, 19, 4503. [CrossRef]
66. Dunn, G.; Nigg, J.; Sontag–Padilla, L.; Seligman, M. Neuroinflammation as a Risk Factor for Attention Deficit Hyperactivity Disorder. Physiol. Behav. 2019, 198, 112–120. [CrossRef]
67. Aguilar–Valles, A.; Rodrigue, B.; Matta–Camacho, E. Maternal Immune Activation and the Development of Dopaminergic Neurotransmission of the Offspring: Relevance for Schizophrenia and Other Psychoses. Front. Psychiatry 2020, 11, 852. [CrossRef]
68. Rosenberg, J.B.; Jepsen, J.R.M.; Mohammadzadeh, P.; Sevelsted, A.; Vinding, R.; Sørensen, M.E.; Horner, D.; Aagaard, K.; Fagerlund, B.; Brix, S.; et al. Maternal Inflammation during Pregnancy Is Associated with Risk of ADHD in Children at Age 10. Brain Behav. Immun. 2024, 115, 450–457. [CrossRef]
69. Anand, D.; Colpo, G.D.; Zeni, G.; Zeni, C.P.; Teixeira, A.L. Attention–Deficit/Hyperactivity Disorder and Inflammation: What Does Current Knowledge Tell Us? A Systematic Review. Front. Psychiatry 2017, 8, 228. [CrossRef]
70. Donfrancesco, R.; Nativio, P.; Di Benedetto, A.; Villa, M.P.; Andriola, E.; Melegari, M.G.; Cipriano, E.; Di Trani, M. Anti–Yo Antibodies in Children with ADHD: First Results about Serum Cytokines. J. Atten. Disord. 2020, 24, 1497–1502. [CrossRef] [PubMed]
71. Oades, R.D.; Dauvermann, M.R.; Schimmelmann, B.G.; Schwarz, M.J.; Myint, A.M. Attention–Deficit Hyperactivity Disorder (ADHD) and Glial Integrity: S100B, Cytokines and Kynurenine Metabolism—Effects of Medication. Behav. Brain Funct. 2010, 6, 29. [CrossRef] [PubMed]
72. Corona, J.C. Role of Oxidative Stress and Neuroinflammation in Attention–Deficit/Hyperactivity Disorder. Antioxidants 2020, 9, 1039. [CrossRef] [PubMed]
73. Vázquez–González, D.; Carreón–Trujillo, S.; Alvarez–Arellano, L.; Abarca–Merlin, D.M.; Domínguez–López, P.; Salazar–García, M.; Corona, J.C. A Potential Role for Neuroinflammation in ADHD. In Neuroinflammation, Gut–Brain Axis and Immunity in Neuropsychiatric Disorders; Springer: Singapore, 2023; pp. 327–356. [CrossRef]
74. Lai, M.–C.; Kassee, C.; Besney, R.; Bonato, S.; Hull, L.; Mandy, W.; Szatmari, P.; Ameis, S.H. Prevalence of Co–Occurring Mental Health Diagnoses in the Autism Population: A Systematic Review and Meta–Analysis. Lancet Psychiatry 2019, 6, 819–829. [CrossRef]
75. Genovese, A.; Butler, M.G. The Autism Spectrum: Behavioral, Psychiatric and Genetic Associations. Genes 2023, 14, 677. [CrossRef]
76. Wiznitzer, M. Autism and Tuberous Sclerosis. J. Child Neurol. 2004, 19, 675–679. [CrossRef] [PubMed]
77. Bergbaum, A.; Ogilvie, C.M. Autism and Chromosome Abnormalities—A Review. Clin. Anat. 2016, 29, 620–627. [CrossRef]
78. Keski–Rahkonen, A.; Ruusunen, A. Avoidant–Restrictive Food Intake Disorder and Autism: Epidemiology, Etiology, Complica– tions, Treatment, and Outcome. Curr. Opin. Psychiatry 2023, 36, 438–442. [CrossRef]
79. Madra, M.; Ringel, R.; Margolis, K.G. Gastrointestinal Issues and Autism Spectrum Disorder. Child Adolesc. Psychiatr. Clin. N. Am. 2020, 29, 501–513. [CrossRef]
80. Capal, J.K.; Jeste, S.S. Autism and Epilepsy. Pediatr. Clin. N. Am. 2024, 71, 241–252. [CrossRef]
81. Johnson, K.P.; Zarrinnegar, P. Autism Spectrum Disorder and Sleep. Child Adolesc. Psychiatr. Clin. N. Am. 2021, 30, 195–208. [CrossRef] [PubMed]
82. Voineagu, I.; Wang, X.; Johnston, P.; Lowe, J.K.; Tian, Y.; Horvath, S.; Mill, J.; Cantor, R.M.; Blencowe, B.J.; Geschwind, D.H.
Transcriptomic Analysis of Autistic Brain Reveals Convergent Molecular Pathology. Nature 2011, 474, 380–384. [CrossRef]
83. Gładysz, D.; Krzywdzi ´nska, A.; Hozyasz, K.K. Immune Abnormalities in Autism Spectrum Disorder—Could They Hold Promise for Causative Treatment? Mol. Neurobiol. 2018, 55, 6387–6435. [CrossRef]
84. Hughes, H.K.; Moreno, R.J.; Ashwood, P. Innate Immune Dysfunction and Neuroinflammation in Autism Spectrum Disorder (ASD). Brain Behav. Immun. 2023, 108, 245–254. [CrossRef] [PubMed]
85. Usui, N.; Kobayashi, H.; Shimada, S. Neuroinflammation and Oxidative Stress in the Pathogenesis of Autism Spectrum Disorder. Int. J. Mol. Sci. 2023, 24, 5487. [CrossRef]
86. Villarreal, V.R.; Katusic, M.Z.; Myers, S.M.; Weaver, A.L.; Nocton, J.J.; Voigt, R.G. Risk of Autoimmune Disease in Research– Identified Cases of Autism Spectrum Disorder: A Longitudinal, Population–Based Birth Cohort Study. J. Dev. Behav. Pediatr. 2024, 45, E46–E53. [CrossRef]
87. Zerbo, O.; Leong, A.; Barcellos, L.; Bernal, P.; Fireman, B.; Croen, L.A. Immune Mediated Conditions in Autism Spectrum Disorders. Brain Behav. Immun. 2015, 46, 232–236. [CrossRef] [PubMed]
88. Al–Haddad, B.J.S.; Jacobsson, B.; Chabra, S.; Modzelewska, D.; Olson, E.M.; Bernier, R.; Enquobahrie, D.A.; Hagberg, H.; Östling, S.; Rajagopal, L.; et al. Long–term risk of neuropsychiatric disease after exposure to infection in utero. JAMA Psychiatry 2019, 76, 594–602. [CrossRef]
89. Croen, L.A.; Ames, J.L.; Qian, Y.; Alexeeff, S.; Ashwood, P.; Gunderson, E.P.; Wu, Y.W.; Boghossian, A.S.; Yolken, R.; Van de Water, J.; et al. Inflammatory conditions during pregnancy and risk of autism and other neurodevelopmental disorders. Biol. Psychiatry Glob. Open Sci. 2024, 4, 39–50. [CrossRef]
90. Brown, A.S.; Surcel, H.M.; Hinkka–Yli–Salomäki, S.; Cheslack–Postava, K.; Bao, Y.; Sourander, A. Maternal Thyroid Autoantibody and Elevated Risk of Autism in a National Birth Cohort. Prog. Neuropsychopharmacol. Biol. Psychiatry 2015, 57, 86–92. [CrossRef]
91. Nielsen, T.C.; Nassar, N.; Shand, A.W.; Jones, H.F.; Han, V.X.; Patel, S.; Guastella, A.J.; Dale, R.C.; Lain, S.J. Association of Maternal Autoimmune Disease and Early Childhood Infections with Offspring Autism Spectrum Disorder: A Population–Based Cohort Study. Autism Res. 2022, 15, 2371–2380. [CrossRef] [PubMed]
92. Jones, K.L.; Croen, L.A.; Yoshida, C.K.; Heuer, L.S.; Hansen, R.L.; Zerbo, O.; DeLorenze, G.N.; Kharrazi, M.; Yolken, R.; Ashwood, P.; et al. Autism with Intellectual Disability Is Associated with Increased Levels of Maternal Cytokines and Chemokines during Gestation. Mol. Psychiatry 2017, 22, 273–279. [CrossRef]
93. Abdallah, M.W.; Larsen, N.; Grove, J.; Nørgaard–Pedersen, B.; Thorsen, P.; Mortensen, E.L.; Hougaard, D.M. Amniotic fluid chemokines and autism spectrum disorders: An exploratory study utilizing a Danish Historic Birth Cohort. Brain Behav. Immun. 2012, 26, 170–176. [CrossRef] [PubMed]
94. Rudolph, M.D.; Graham, A.M.; Feczko, E.; Miranda–Dominguez, O.; Rasmussen, J.M.; Nardos, R.; Entringer, S.; Wadhwa, P.D.; Buss, C.; Fair, D.A. Maternal IL–6 during Pregnancy Can Be Estimated from Newborn Brain Connectivity and Predicts Future Working Memory in Offspring. Nat. Neurosci. 2018, 21, 765–772. [CrossRef]
95. Graham, A.M.; Rasmussen, J.M.; Rudolph, M.D.; Heim, C.M.; Gilmore, J.H.; Styner, M.; Potkin, S.G.; Entringer, S.; Wadhwa, P.D.; Fair, D.A.; et al. Maternal Systemic Interleukin–6 During Pregnancy Is Associated with Newborn Amygdala Phenotypes and Subsequent Behavior at 2–Years–of–Age. Biol. Psychiatry 2018, 83, 109–119. [CrossRef]
96. Abdallah, M.W.; Larsen, N.; Grove, J.; Bonefeld–Jørgensen, E.C.; Nørgaard–Pedersen, B.; Hougaard, D.M.; Mortensen, E.L. Neonatal Chemokine Levels and Risk of Autism Spectrum Disorders: Findings from a Danish Historic Birth Cohort Follow–up Study. Cytokine 2013, 61, 370–376. [CrossRef] [PubMed]
97. Krakowiak, P.; Goines, P.E.; Tancredi, D.J.; Ashwood, P.; Hansen, R.L.; Hertz–Picciotto, I.; Van de Water, J. Neonatal Cytokine Profiles Associated with Autism Spectrum Disorder. Biol. Psychiatry 2017, 81, 442–451. [CrossRef] [PubMed]
98. Heuer, L.S.; Croen, L.A.; Jones, K.L.; Yoshida, C.K.; Hansen, R.L.; Yolken, R.; Zerbo, O.; DeLorenze, G.; Kharrazi, M.; Ashwood, P.; et al. An Exploratory Examination of Neonatal Cytokines and Chemokines as Predictors of Autism Risk: The Early Markers for Autism Study. Biol. Psychiatry 2019, 86, 255–264. [CrossRef] [PubMed]
99. Oskvig, D.B.; Elkahloun, A.G.; Johnson, K.R.; Phillips, T.M.; Herkenham, M. Maternal immune activation by LPS selectively alters specific gene expression profiles of interneuron migration and oxidative stress in the fetus without triggering a fetal immune response. Brain Behav. Immun. 2012, 26, 623–634. [CrossRef]
100. O’Loughlin, E.; Pakan, J.M.P.; Yilmazer–Hanke, D.; McDermott, K.W. Acute in Utero Exposure to Lipopolysaccharide Induces In– flammation in the Pre– and Postnatal Brain and Alters the Glial Cytoarchitecture in the Developing Amygdala. J. Neuroinflammation 2017, 14, 212. [CrossRef]
101. Cie´slik, M.; Ga˛ssowska–Dobrowolska, M.; J˛e´sko, H.; Czapski, G.A.; Wilkaniec, A.; Zawadzka, A.; Dominiak, A.; Polowy, R.; Filipkowski, R.K.; Boguszewski, P.M.; et al. Maternal Immune Activation Induces Neuroinflammation and Cortical Synaptic Deficits in the Adolescent Rat Offspring. Int. J. Mol. Sci. 2020, 21, 4097. [CrossRef]
102. Han, V.X.; Patel, S.; Jones, H.F.; Dale, R.C. Maternal Immune Activation and Neuroinflammation in Human Neurodevelopmental Disorders. Nat. Rev. Neurol. 2021, 17, 564–579. [CrossRef]
103. Xiong, Y.; Chen, J.; Li, Y. Microglia and Astrocytes Underlie Neuroinflammation and Synaptic Susceptibility in Autism Spectrum Disorder. Front. Neurosci. 2023, 17, 1125428. [CrossRef]
104. Lampiasi, N.; Bonaventura, R.; Deidda, I.; Zito, F.; Russo, R. Inflammation and the Potential Implication of Macrophage–Microglia Polarization in Human ASD: An Overview. Int. J. Mol. Sci. 2023, 24, 2703. [CrossRef]
105. Rodriguez, J.I.; Kern, J.K. Evidence of Microglial Activation in Autism and Its Possible Role in Brain Underconnectivity. Neuron Glia Biol. 2011, 7, 205–213. [CrossRef]
106. Hu, C.; Li, H.; Li, J.; Luo, X.; Hao, Y. Microglia: Synaptic Modulator in Autism Spectrum Disorder. Front. Psychiatry 2022, 13, 958661. [CrossRef]
107. Vargas, D.L.; Nascimbene, C.; Krishnan, C.; Zimmerman, A.W.; Pardo, C.A. Neuroglial Activation and Neuroinflammation in the Brain of Patients with Autism. Ann. Neurol. 2005, 57, 67–81. [CrossRef] [PubMed]
108. Than, U.T.T.; Nguyen, L.T.; Nguyen, P.H.; Nguyen, X.H.; Trinh, D.P.; Hoang, D.H.; Nguyen, P.A.T.; Dang, V.D. Inflammatory Mediators Drive Neuroinflammation in Autism Spectrum Disorder and Cerebral Palsy. Sci. Rep. 2023, 13, 22587. [CrossRef]
109. De Giacomo, A.; Gargano, C.D.; Simone, M.; Petruzzelli, M.G.; Pedaci, C.; Giambersio, D.; Margari, L.; Ruggieri, M. B and T Immunoregulation: A New Insight of B Regulatory Lymphocytes in Autism Spectrum Disorder. Front. Neurosci. 2021, 15, 732611. [CrossRef]
110. Geller, H.; Williams, K.A. 6.34 Comparison of Primary Humoral Immunodeficiencies in Autism Spectrum Disorder (ASD) and Other Pediatric–Onset Psychiatric Disorders. J. Am. Acad. Child Adolesc. Psychiatry 2021, 60, S169. [CrossRef]
111. Bjørklund, G.; Saad, K.; Chirumbolo, S.; Kern, J.K.; Geier, D.A.; Geier, M.R.; Urbina, M.A. Immune Dysfunction and Neuroinflam– mation in Autism Spectrum Disorder. Acta Neurobiol. Exp. 2016, 76, 257–268. [CrossRef] [PubMed]
112. Robertson, M.M.; Eapen, V.; Singer, H.S.; Martino, D.; Scharf, J.M.; Paschou, P.; Roessner, V.; Woods, D.W.; Hariz, M.; Mathews, C.A.; et al. Gilles de la Tourette Syndrome. Nat. Rev. Dis. Primers 2017, 3, 16097. [CrossRef] [PubMed]
113. Knight, T.; Steeves, T.; Day, L.; Lowerison, M.; Jette, N.; Pringsheim, T. Prevalence of Tic Disorders: A Systematic Review and Meta–Analysis. Pediatr. Neurol. 2012, 47, 77–90. [CrossRef]
114. Jellinger, K.A. Neuropathology and Pathogenesis of Extrapyramidal Movement Disorders: A Critical Update. II. Hyperkinetic Disorders. J. Neural Transm. 2019, 126, 997–1027. [CrossRef]
115. Swedo, S.E.; Leonard, H.L.; Garvey, M.; Mittleman, B.; Allen, A.J.; Perlmutter, S.; Lougee, L.; Dow, S.; Zamkoff, J.; Dubbert, B.K. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections: Clinical Description of the First 50 Cases. In Obsessive-Compulsive Disorder and Tourette’s Syndrome; Routledge: Oxfordshire, UK, 1998; Volume 155, pp. 264–271. [CrossRef]
116. Mataix–Cols, D.; Frans, E.; Pérez–Vigil, A.; Kuja–Halkola, R.; Gromark, C.; Isomura, K.; Fernández de la Cruz, L.; Serlachius, E.; Leckman, J.F.; Crowley, J.J.; et al. A Total–Population Multigenerational Family Clustering Study of Autoimmune Diseases in Obsessive–Compulsive Disorder and Tourette’s/Chronic Tic Disorders. Mol. Psychiatry 2018, 23, 1652–1658. [CrossRef]
117. Keszler, G.; Kruk, E.; Kenezloi, E.; Tarnok, Z.; Sasvari–Szekely, M.; Nemoda, Z. Association of the Tumor Necrosis Factor –308 A/G Promoter Polymorphism with Tourette Syndrome. Int. J. Immunogenet. 2014, 41, 493–498. [CrossRef]
118. Tylee, D.S.; Sun, J.; Hess, J.L.; Tahir, M.A.; Sharma, E.; Malik, R.; Worrall, B.B.; Levine, A.J.; Martinson, J.J.; Nejentsev, S.; et al. Genetic Correlations among Psychiatric and Immune–related Phenotypes Based on Genome–wide Association Data. Am. J. Med. Genet. Part B Neuropsychiatr. Genet. 2018, 177, 641–657. [CrossRef]
119. Tsetsos, F.; Yu, D.; Sul, J.H.; Huang, A.Y.; Illmann, C.; Osiecki, L.; Darrow, S.M.; Hirschtritt, M.E.; Greenberg, E.; Muller–Vahl, K.R.; et al. Synaptic Processes and Immune–Related Pathways Implicated in Tourette Syndrome. Transl. Psychiatry 2021, 11, 56. [CrossRef]
120. Elamin, I.; Edwards, M.J.; Martino, D. Immune Dysfunction in Tourette Syndrome. Behav. Neurol. 2013, 27, 23–32. [CrossRef]
121. Martino, D.; Zis, P.; Buttiglione, M. The Role of Immune Mechanisms in Tourette Syndrome. Brain Res. 2015, 1617, 126–143. [CrossRef] [PubMed]
122. Leckman, J.F.; Katsovich, L.; Kawikova, I.; Lin, H.; Zhang, H.; Krönig, H.; Morshed, S.; Parveen, S.; Grantz, H.; Lombroso, P.J.; et al. Increased Serum Levels of Interleukin–12 and Tumor Necrosis Factor–Alpha in Tourette’s Syndrome. Biol. Psychiatry 2005, 57, 667–673. [CrossRef] [PubMed]
123. Chi, S.; Mok, Y.E.; Kang, J.; Gim, J.A.; Han, C.; Lee, M.S. Cytokine Levels Reflect Tic Symptoms More Prominently during Mild Phases. BMC Neurosci. 2023, 24, 14. [CrossRef]
124. Tao, Y.; Xu, P.; Zhu, W.; Chen, Z.; Tao, X.; Liu, J.; Xue, Z.; Zhu, T.; Jiang, P. Changes of Cytokines in Children With Tic Disorder. Front. Neurol. 2022, 12, 800189. [CrossRef]
125. Li, Y.; Wang, X.; Yang, H.; Li, Y.; Gui, J.; Cui, Y. Profiles of Proinflammatory Cytokines and T Cells in Patients With Tourette Syndrome: A Meta–Analysis. Front. Immunol. 2022, 13, 843247. [CrossRef] [PubMed]
126. Weidinger, E.; Krause, D.; Wildenauer, A.; Meyer, S.; Gruber, R.; Schwarz, M.J.; Müller, N. Impaired Activation of the Innate Immune Response to Bacterial Challenge in Tourette Syndrome. World J. Biol. Psychiatry 2014, 15, 453–458. [CrossRef]
127. Kawikova, I.; Leckman, J.F.; Kronig, H.; Katsovich, L.; Bessen, D.E.; Ghebremichael, M.; Bothwell, A.L. Decreased Numbers of Regulatory T Cells Suggest Impaired Immune Tolerance in Children with Tourette Syndrome: A Preliminary Study. Biol. Psychiatry 2007, 61, 273–278. [CrossRef] [PubMed]
128. Dale, R.C.; Merheb, V.; Pillai, S.; Wang, D.; Cantrill, L.; Murphy, T.K.; Ben–Pazi, H.; Varadkar, S.; Aumann, T.D.; Horne, M.K.; et al. Antibodies to Surface Dopamine–2 Receptor in Autoimmune Movement and Psychiatric Disorders. Brain 2012, 135, 3453–3468. [CrossRef]
129. Addabbo, F.; Baglioni, V.; Schrag, A.; Schwarz, M.J.; Dietrich, A.; Hoekstra, P.J.; Martino, D.; Buttiglione, M.; Emtics Collaborative Group. Anti–dopamine D2 Receptor Antibodies in Chronic Tic Disorders. Dev. Med. Child Neurol. 2020, 62, 1205–1212. [CrossRef]
130. Bos–Veneman, N.G.; Olieman, R.; Tobiasova, Z.; Hoekstra, P.J.; Katsovich, L.; Bothwell, A.L.; Leckman, J.F.; Kawikova, I. Altered Immunoglobulin Profiles in Children with Tourette Syndrome. Brain Behav. Immun. 2011, 25, 532–538. [CrossRef]
131. Harris, J. Intellectual Disability: Understanding Its Development, Causes, Classification, Evaluation, and Treatment; Oxford University Press: Oxford, UK, 2006.
132. Brynge, M.; Sjöqvist, H.; Gardner, R.M.; Lee, B.K.; Dalman, C.; Karlsson, H. Maternal Infection during Pregnancy and Likelihood of Autism and Intellectual Disability in Children in Sweden: A Negative Control and Sibling Comparison Cohort Study. Lancet Psychiatry 2022, 9, 782–791. [CrossRef] [PubMed]
133. Rezaeinejad, M.; Riahi, S.M.; Moghadam, K.B.; Tadi, M.J.; Geraili, Z.; Parsa, H.; Marhoommirzabak, E.; Nourollahpour Shiadeh, M.; Khatir, A.A. The Association between Maternal Infection and Intellectual Disability in Children: A Systematic Review and Meta–Analysis. PLoS ONE 2023, 18, e0292226. [CrossRef]
134. Benmakhlouf, Y.; Zian, Z.; Nourouti, N.G.; Barakat, A.; Mechita, M.B. Potential Cytokine Biomarkers in Intellectual Disability. Endocr. Metab. Immune Disord.—Drug Targets 2020, 21, 569–576. [CrossRef]
135. Mekori–Domachevsky, E.; Taler, M.; Shoenfeld, Y.; Gurevich, M.; Sonis, P.; Weisman, O.; Weizman, A.; Gothelf, D. Elevated Proinflammatory Markers in 22q11.2 Deletion Syndrome Are Associated with Psychosis and Cognitive Deficits. J. Clin. Psychiatry 2017, 78, e1219–e1225. [CrossRef]
136. Fan, X.Y.; Shi, G.; Zhao, P. Neonatal Sevoflurane Exposure Impairs Learning and Memory by the Hypermethylation of Hippocam– pal Synaptic Genes. Mol. Neurobiol. 2021, 58, 895–904. [CrossRef] [PubMed]
137. Huang, X.; Hussain, B.; Chang, J. Peripheral Inflammation and Blood–Brain Barrier Disruption: Effects and Mechanisms. CNS Neurosci. Ther. 2021, 27, 36–47. [CrossRef]
138. Zhang, F.; Zhang, J.; Wang, X.; Han, M.; Fei, Y.; Wang, J. Blood–Brain Barrier Disruption in Schizophrenia: Insights, Mechanisms, and Future Directions. Int. J. Mol. Sci. 2025, 26, 873. [CrossRef]
139. Al–Diwani, A.; Handel, A.; Townsend, L.; Pollak, T.; Leite, M.I.; Harrison, P.J.; Lennox, B.R.; Okai, D.; Manohar, S.G.; Irani, S.R. The psychopathology of NMDAR–antibody encephalitis in adults: A systematic review and phenotypic analysis of individual patient data. Lancet Psychiatry 2019, 6, 235–246. [CrossRef] [PubMed]
140. Najjar, S.; Steiner, J.; Najjar, A.; Bechter, K. A clinical approach to new–onset psychosis associated with immune dysregulation: The concept of autoimmune psychosis. J. Neuroinflammation 2018, 15, 40. [CrossRef] [PubMed]
141. McKeon, A.; Dubey, D.; Flanagan, E.; Pittock, S.; Zekeridou, A. Autoimmune psychosis. Lancet Psychiatry 2020, 7, 122. [CrossRef] [PubMed]
142. Goldsmith, D.R.; Rapaport, M.H.; Miller, B.J. A meta–analysis of blood cytokine network alterations in psychiatric patients: Comparisons between schizophrenia, bipolar disorder and depression. Mol. Psychiatry 2016, 21, 1696–1709. [CrossRef]
143. Bechter, K.; Reiber, H.; Herzog, S.; Fuchs, D.; Tumani, H.; Maxeiner, H.G. Cerebrospinal fluid analysis in affective and schizophrenic spectrum disorders: Identification of subgroups with immune responses and blood–CSF barrier dysfunction. J. Psychiatr. Res. 2010, 44, 321–330. [CrossRef]
144. Endres, D.; Perlov, E.; Baumgartner, A.; Hottenrott, T.; Dersch, R.; Stich, O.; Tebartz van Elst, L. Immunological findings in psychotic syndromes: A tertiary care hospital’s CSF sample of 180 patients. Front. Hum. Neurosci. 2015, 9, 476. [CrossRef]
145. Upthegrove, R.; Manzanares–Teson, N.; Barnes, N.M. Cytokine function in medication–naive first–episode psychosis: A systematic review and meta–analysis. Schizophr Res. 2014, 155, 101–108. [CrossRef]
146. Nayak, U.; Manikkath, J.; Arora, D.; Mudgal, J. Impact of neuroinflammation on brain glutamate and dopamine signalling in schizophrenia: An update. Metab. Brain Dis. 2025, 40, 119. [CrossRef]
147. Miller, B.J.; Buckley, P.; Seabolt, W.; Mellor, A.; Kirkpatrick, B. Meta–Analysis of Cytokine Alterations in Schizophrenia: Clinical Status and Antipsychotic Effects. Biol. Psychiatry 2011, 70, 663–671. [CrossRef]
148. Gallego, J.A.; Blanco, E.A.; Husain–Krautter, S.; Fagen, E.M.; Moreno–Merino, P.; del Ojo–Jiménez, J.A.; Ahmed, A.; Rothstein, T.L.; Lencz, T.; Malhotra, A.K. Cytokines in cerebrospinal fluid of patients with schizophrenia spectrum disorders: New data and an updated meta–analysis. Schizophr Res. 2018, 202, 64–71. [CrossRef] [PubMed]
149. Khandaker, G.M.; Pearson, R.M.; Zammit, S.; Lewis, G.; Jones, P.B. Association of serum interleukin 6 and C–reactive protein in childhood with depression and psychosis in young adult life: A population–based longitudinal study. JAMA Psychiatry 2014, 71, 1121–1128. [CrossRef]
150. Metcalf, S.A.; Jones, P.B.; Nordstrom, T.; Timonen, M.; Mäki, P.; Miettunen, J.; Jääskeläinen, E.; Järvelin, M.R.; Stochl, J.; Murray, G.K.; et al. Serum C–reactive protein in adolescence and risk of schizophrenia in adulthood: A prospective birth cohort study. Brain Behav. Immun. 2017, 59, 253–259. [CrossRef]
151. Dunleavy, C.; Elsworthy, R.J.; Upthegrove, R.; Wood, S.J.; Aldred, S. Inflammation in first–episode psychosis: The contribution of inflammatory biomarkers to the emergence of negative symptoms, a systematic review and meta–analysis. Acta Psychiatr. Scand. 2022, 146, 6–20. [CrossRef] [PubMed]
152. Pollak, T.A.; Lennox, B.R.; Müller, S.; Benros, M.E.; Prüss, H.; Tebartz van Elst, L.; Klein, H.; Steiner, J.; Frodl, T.; Bogerts, B.; et al. Autoimmune psychosis: An international consensus on an approach to the diagnosis and management of psychosis of suspected autoimmune origin. Lancet Psychiatry 2020, 7, 93–108. [CrossRef]
153. Pollak, T.; Drndarski, S.; Stone, J.M.; David, A.S.; McGuire, P.K.; Abbott, N.J. The blood–brain barrier in psychosis. Lancet Psychiatry 2018, 5, 79–92. [CrossRef]
154. Trépanier, M.O.; Hopperton, K.E.; Mizrahi, R.; Mechawar, N.; Bazinet, R.P. Postmortem evidence of cerebral inflammation in schizophrenia: A systematic review. Mol. Psychiatry 2016, 21, 1009–1026. [CrossRef]
155. van Kesteren, C.F.M.G.; Gremmels, H.; de Witte, L.D.; Hol, E.M.; Van Gool, A.R.; Falkai, P.G.; Kahn, R.S.; Sommer, I.E.C. Immune involvement in the pathogenesis of schizophrenia: A meta–analysis on postmortem brain studies. Transl. Psychiatry 2017, 7, e1075. [CrossRef]
156. Kayser, M.S.; Dalmau, J. Anti–NMDA receptor encephalitis, autoimmunity, and psychosis. Schizophr. Res. 2016, 176, 36–40. [CrossRef]
157. Subeh, G.K.; Lajber, M.; Patel, T.; Mostafa, J.A. Anti–N–methyl–D–aspartate receptor encephalitis: A detailed review of the different psychiatric presentations and red flags to look for in suspected cases. Cureus 2021, 13, e15188. [CrossRef] [PubMed]
158. Hardy, D. Autoimmune encephalitis in children. Pediatr. Neurol. 2022, 132, 56–66. [CrossRef]
159. Giri, Y.R.; Parrill, A.; Damodar, S.; Fogel, J.; Ayed, N.; Syed, M.; Korie, I.; Ayyanar, S.; Typhair, C.; Hashmi, S. Anti–N–methyl–D– aspartate receptor (NMDAR) encephalitis in children and adolescents: A systematic review and quantitative analysis of reported cases. J. Can. Acad. Child Adolesc. Psychiatry 2021, 30, 236–248. [PubMed]
160. Ahmad, S.A.; Archer, H.A.; Rice, C.M.; Gerhand, S.; Bradley, M.; Wilkins, A. Seronegative limbic encephalitis: Case report, literature review and proposed treatment algorithm. Pract. Neurol. 2011, 11, 355–361. [CrossRef]
161. Shah, K.; Iloh, N.; Tabares, P.; Nnadi, C.; Sharif, Z.; Macaluso, C. Limbic encephalitis and psychosis. Gen. Hosp. Psychiatry 2013, 35, 682.e1–682.e2. [CrossRef]
162. Eaton, W.W.; Byrne, M.; Ewald, H.; Mors, O.; Chen, C.Y.; Agerbo, E.; Mortensen, P.B. Association of schizophrenia and autoimmune diseases: Linkage of Danish national registers. Am. J. Psychiatry 2006, 163, 521–528. [CrossRef] [PubMed]
163. Benros, M.E.; Pedersen, M.G.; Rasmussen, H.; Eaton, W.W.; Nordentoft, M.; Mortensen, P.B. A nationwide study on the risk of autoimmune diseases in individuals with a personal or a family history of schizophrenia and related psychosis. Am. J. Psychiatry 2014, 171, 218–226. [CrossRef] [PubMed]
164. Benros, M.E.; Nielsen, P.R.; Nordentoft, M.; Eaton, W.W.; Dalton, S.O.; Mortensen, P.B. Autoimmune diseases and severe infections as risk factors for schizophrenia: A 30–year population–based register study. Am. J. Psychiatry 2011, 168, 1303–1310. [CrossRef] [PubMed]
165. Yolken, R.H.; Torrey, E.F. Are some cases of psychosis caused by microbial agents? A review of the evidence. Mol. Psychiatry 2008, 13, 470–479. [CrossRef]
166. Benros, M.E.; Waltoft, B.L.; Nordentoft, M.; Ostergaard, S.D.; Eaton, W.W.; Krogh, J.; Mortensen, P.B. Autoimmune diseases and severe infections as risk factors for mood disorders: A nationwide study. JAMA Psychiatry 2013, 70, 812–820. [CrossRef]
167. Girgis, R.R.; Ciarleglio, A.; Choo, T.; Haynes, G.; Bathon, J.M.; Cremers, S.; Kantrowitz, J.T.; Lieberman, J.A.; Brown, A.S. A randomized, double–blind, placebo–controlled clinical trial of tocilizumab, an interleukin–6 receptor antibody, for residual symptoms in schizophrenia. Neuropsychopharmacology 2018, 43, 1317–1323. [CrossRef]
168. Ruscio, A.M.; Stein, D.J.; Chiu, W.T.; Kessler, R.C. The epidemiology of obsessive–compulsive disorder in the National Comorbidity Survey Replication. Mol. Psychiatry 2010, 15, 53–63. [CrossRef] [PubMed]
169. Robbins, T.W.; Vaghi, M.M.; Banca, P. Obsessive–compulsive disorder: Puzzles and prospects. Neuron 2019, 102, 27–47. [CrossRef] [PubMed]
170. Frick, L.; Pittenger, C. Microglial dysregulation in OCD, Tourette syndrome, and PANDAS. J. Immunol. Res. 2016, 2016, 8606057. [CrossRef]
171. Gerentes, M.; Pelissolo, A.; Rajagopal, K.; Tamouza, R.; Hamdani, N. Obsessive–compulsive disorder: Autoimmunity and neuroinflammation. Curr. Psychiatry Rep. 2019, 21, 78. [CrossRef]
172. Snider, L.A.; Swedo, S.E. PANDAS: Current status and directions for research. Mol. Psychiatry 2004, 9, 900–907. [CrossRef]
173. Orlovska, S.; Vestergaard, C.H.; Bech, B.H.; Nordentoft, M.; Vestergaard, M.; Benros, M.E. Association of Streptococcal Throat Infection With Mental Disorders: Testing Key Aspects of the PANDAS Hypothesis in a Nationwide Study. JAMA Psychiatry 2017, 74, 740–746. [CrossRef] [PubMed]
174. Xu, J.; Liu, R.J.; Fahey, S.; Frick, L.; Leckman, J.; Vaccarino, F.; Duman, R.S.; Williams, K.; Swedo, S.; Pittenger, C. Antibodies from children with PANDAS bind specifically to striatal cholinergic interneurons and alter their activity. Am. J. Psychiatry 2021, 178, 48–64. [CrossRef]
175. Xu, M.; Kobets, A.; Du, J.C.; Lennington, J.; Li, L.; Banasr, M.; Duman, R.S.; Vaccarino, F.M.; DiLeone, R.J.; Pittenger, C. Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome. Proc. Natl. Acad. Sci. USA 2015, 112, 893–898. [CrossRef]
176. Zhang, T.; Brander, G.; Isung, J.; Isomura, K.; Sidorchuk, A.; Larsson, H.; Chang, Z.; Mataix–Cols, D.; Fernández de la Cruz, L. Prenatal and early childhood infections and subsequent risk of obsessive–compulsive disorder and tic disorders: A nationwide, sibling–controlled study. Biol. Psychiatry 2023, 93, 1023–1030. [CrossRef]
177. Cainelli, E.; Nosadini, M.; Sartori, S.; Suppiej, A. Neuropsychological and psychopathological profile of anti–NMDAR encephalitis: A possible pathophysiological model for pediatric neuropsychiatric disorders. Arch. Clin. Neuropsychol. 2019, 34, 1309–1319. [CrossRef]
178. Foroughipour, M.; Behdani, F.; Hebrani, P.; Marvast, M.N.; Esmatinia, F.; Akhavanrezayat, A. Frequency of obsessive–compulsive disorder in patients with multiple sclerosis: A cross–sectional study. J. Res. Med. Sci. 2012, 17, 248–253.
179. Wang, L.Y.; Chen, S.F.; Chiang, J.H.; Hsu, C.Y.; Shen, Y.C. Systemic autoimmune diseases are associated with an increased risk of obsessive–compulsive disorder: A nationwide population–based cohort study. Soc. Psychiatry Psychiatr. Epidemiol. 2019, 54, 507–516. [CrossRef] [PubMed]
180. Lüngen, E.M.; Maier, V.; Venhoff, N.; Salzer, U.; Dersch, R.; Berger, B.; Riering, A.N.; Nickel, K.; Fiebich, B.L.; Süß, P.; et al. Systemic lupus erythematosus with isolated psychiatric symptoms and antinuclear antibody detection in the cerebrospinal fluid. Front. Psychiatry 2019, 10, 226. [CrossRef] [PubMed]
181. De Carvalho, J.F.; Ribeiro, F.M. Sjögren syndrome associated with obsessive–compulsive disorder. Eur. Rev. Med. Pharmacol. Sci. 2020, 24, 11801–11803.
182. Endres, D.; Pollak, T.A.; Bechter, K.; Denzel, D.; Pitsch, K.; Nickel, K.; Runge, K.; Pankratz, B.; Klatzmann, D.; Tamouza, R.; et al. Immunological causes of obsessive–compulsive disorder: Is it time for the concept of an “autoimmune OCD” subtype? Transl Psychiatry 2022, 12, 5. [CrossRef]
183. Pearlman, D.M.; Vora, H.S.; Marquis, B.G.; Najjar, S.; Dudley, L.A. Anti–basal ganglia antibodies in primary obsessive–compulsive disorder: Systematic review and meta–analysis. Br. J. Psychiatry 2014, 205, 8–16. [CrossRef]
184. Gray, S.M.; Bloch, M.H. Systematic review of proinflammatory cytokines in obsessive–compulsive disorder. Curr. Psychiatry Rep. 2012, 14, 220–228. [CrossRef]
185. Tamouza, R.; Krishnamoorthy, R.; Leboyer, M. Understanding the genetic contribution of the human leukocyte antigen system to common major psychiatric disorders in a world pandemic context. Brain Behav. Immun. 2021, 91, 731–739. [CrossRef]
186. Costas, J.; Carrera, N.; Alonso, P.; Gurriarán, X.; Segalàs, C.; Real, E.; López–Solà, C.; Mas, S.; Gassó, P.; Domènech, L.; et al. Exon–focused genome–wide association study of obsessive–compulsive disorder and shared polygenic risk with schizophrenia. Transl. Psychiatry 2016, 6, e768. [CrossRef] [PubMed]
187. Rodriguez, N.; Morer, A.; González–Navarro, E.A.; Gassó, P.; Boloc, D.; Serra–Pagès, C.; Lafuente, A.; Lazaro, L.; Mas, S. Human–leukocyte antigen class II genes in early–onset obsessive–compulsive disorder. World J. Biol. Psychiatry 2019, 20, 352–358. [CrossRef]
188. Noble, J.A. Immunogenetics of type 1 diabetes: A comprehensive review. J. Autoimmun. 2015, 64, 101–112. [CrossRef]
189. Jiang, C.; Ma, X.; Qi, S.; Han, G.; Li, Y.; Liu, Y.; Liu, L. Association between TNF–α–238G/A gene polymorphism and OCD susceptibility: A meta–analysis. Medicine 2018, 97, e9769. [CrossRef]
190. Wang, P.; Zhao, Q.; Xu, T.; Gu, Q.; Liu, Q.; Wang, Y.; Lin, G.N.; Wang, Z. Interaction between PGRN gene and the early trauma on clinical characteristics in patients with obsessive–compulsive disorder. J. Affect. Disord. 2020, 263, 134–140. [CrossRef] [PubMed]
191. Swedo, S.E.; Leckman, J.F.; Rose, N.R. From research subgroup to clinical syndrome: Modifying the PANDAS criteria to describe PANS (Pediatric Acute–Onset Neuropsychiatric Syndrome). Pediatr. Ther. 2012, 2, 1000113. [CrossRef]
192. Chang, K.; Frankovich, J.; Cooperstock, M.; Cunningham, M.W.; Latimer, M.E.; Murphy, T.K.; Pasternack, M.; Thienemann, M.; Williams, K.; Walter, J.; et al. Clinical evaluation of youth with pediatric acute–onset neuropsychiatric syndrome (PANS): Recommendations from the 2013 PANS Consensus Conference. J. Child Adolesc. Psychopharmacol. 2015, 25, 3–13. [CrossRef]
193. Frankovich, J.; Thienemann, M.; Pearlstein, J.; Crable, A.; Brown, K.; Chang, K. Multidisciplinary clinic dedicated to treating youth with pediatric acute–onset neuropsychiatric syndrome: Presenting characteristics of the first 47 consecutive patients. J. Child Adolesc. Psychopharmacol. 2015, 25, 38–47. [CrossRef]
194. Gagliano, A.; Puligheddu, M.; Ronzano, N.; Congiu, P.; Tanca, M.G.; Cursio, I.; Carucci, S.; Sotgiu, S.; Grossi, E.; Zuddas, A. Artificial neural networks analysis of polysomnographic and clinical features in pediatric acute–onset neuropsychiatric syndrome (PANS): From sleep alteration to “Brain Fog”. Nat. Sci. Sleep. 2021, 13, 1209–1224. [CrossRef]
195. Chan, A.; Gao, J.; Houston, M.; Willett, T.; Farhadian, B.; Silverman, M.; Tran, P.; Jaradeh, S.; Thienemann, M.; Frankovich, J. Children With PANS May Manifest POTS. Front. Neurol. 2022, 13, 819636. [CrossRef] [PubMed] [PubMed Central]
196. Santoro, J.D.; Frankovich, J.; Bhargava, S. Continued Presence of Period Limb Movements During REM Sleep in Patients With Chronic Static Pediatric Acute–Onset Neuropsychiatric Syndrome (PANS). J. Clin. Sleep Med. 2018, 14, 1187–1192. [CrossRef]
197. Gaughan, T.; Buckley, A.; Hommer, R.; Grant, P.; Williams, K.; Leckman, J.F.; Swedo, S.E. Rapid Eye Movement Sleep Abnor– malities in Children with Pediatric Acute–Onset Neuropsychiatric Syndrome (PANS). J. Clin. Sleep Med. 2016, 12, 1027–1032. [CrossRef] [PubMed] [PubMed Central]
198. Calaprice, D.; Tona, J.; Parker–Athill, E.C.; Murphy, T.K. A survey of pediatric acute–onset neuropsychiatric syndrome characteris– tics and course. J. Child Adolesc. Psychopharmacol. 2017, 27, 607–618. [CrossRef]
199. Pavone, P.; Parano, E.; Battaglia, C.; Marino, S.; Trifiletti, R.R.; Marino, S.D.; Falsaperla, R. Severe psychotic symptoms in youth with PANS/PANDAS: Case–series. J. Child Adolesc. Psychopharmacol. 2020, 30, 567–571. [CrossRef]
200. Silverman, M.; Frankovich, J.; Nguyen, E.; Leibold, C.; Yoon, J.; Mark Freeman, G., Jr.; Karpel, H.; Thienemann, M. Psychotic symp– toms in youth with Pediatric Acute–onset Neuropsychiatric Syndrome (PANS) may reflect syndrome severity and heterogeneity.
J. Psychiatr. Res. 2019, 110, 93–102. [CrossRef]
201. Kalinowski, A.; Tian, L.; Pattni, R.; Ollila, H.; Khan, M.; Manko, C.; Silverman, M.; Ma, M.; Columbo, L.; Farhadian, B.; et al. Evaluation of C4 gene copy number in Pediatric Acute Neuropsychiatric Syndrome. Dev. Neurosci. 2023, 45, 315–324. [CrossRef] [PubMed]
202. Xu, J.; Frankovich, J.; Liu, R.J.; Thienemann, M.; Silverman, M.; Farhadian, B.; Willett, T.; Manko, C.; Columbo, L.; Leibold, C.; et al. Elevated antibody binding to striatal cholinergic interneurons in patients with pediatric acute–onset neuropsychiatric syndrome. Brain Behav. Immun. 2024, 122, 241–255. [CrossRef] [PubMed] [PubMed Central]
203. Ma, M.; Masterson, E.E.; Gao, J.; Karpel, H.; Chan, A.; Pooni, R.; Sandberg, J.; Rubesova, E.; Farhadian, B.; Willet, T.; et al. Development of Autoimmune Diseases Among Children With Pediatric Acute–Onset Neuropsychiatric Syndrome. JAMA Netw. Open. 2024, 7, e2421688. [CrossRef] [PubMed] [PubMed Central]
204. Melamed, I.; Rahman, S.; Pein, H.; Heffron, M.; Frankovich, J.; Kreuwel, H.; Mellins, E.D. IVIG response in pediatric acute–onset neuropsychiatric syndrome correlates with reduction in pro–inflammatory monocytes and neuropsychiatric measures. Front. Immunol. 2024, 15, 1383973. [CrossRef] [PubMed]
205. Murphy, T.K.; Storch, E.A.; Lewin, A.B.; Edge, P.J.; Goodman, W.K. Clinical factors associated with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. J. Pediatr. 2012, 160, 314–319. [CrossRef]
206. Pavone, P.; Ceccarelli, M.; Marino, S.; Caruso, D.; Falsaperla, R.; Berretta, M.; Rullo, E.V.; Nunnari, G. SARS–CoV–2 related paediatric acute–onset neuropsychiatric syndrome. Lancet Child Adolesc. Health 2021, 5, e19–e21. [CrossRef]
207. Berloffa, S.; Salvati, A.; Pantalone, G.; Falcioni, L.; Rizzi, M.M.; Naldini, F.; Masi, G.; Gagliano, A. Steroid treatment response to post SARS–CoV–2 PANS symptoms: Case series. Front. Neurol. 2023, 14, 1085948. [CrossRef]
208. Saini, T.; Ma, M.; Sandberg, J.; Farhadian, B.; Manko, C.; Xie, Y.; Madan, J.; Bauer, K.; Tran, P.; Frankovich, J. New–onset OCD and juvenile enthesitis–related arthritis after COVID–19 (Three Cases). Dev. Neurosci. 2025, 303–315. [CrossRef] [PubMed]
209. Pallanti, S.; Di Ponzio, M. PANDAS/PANS in the COVID–19 age: Autoimmunity and Epstein–Barr virus reactivation as trigger agents? Children 2023, 10, 648. [CrossRef]
210. Zheng, J.; Frankovich, J.; McKenna, E.; Rowe, N.; MacEachern, S.; Ng, N.; Tam, L.; Moon, P.; Gao, J.; Thienemann, M.; et al. Association of Pediatric Acute–Onset Neuropsychiatric Syndrome With Microstructural Differences in Brain Regions Detected via Diffusion–Weighted Magnetic Resonance Imaging. J. Am. Med. Assoc. (JAMA) Netw. Open 2020, 3, e204063. [CrossRef]
211. Cabrera, B.; Romero–Rebollar, C.; Jiménez–Ángeles, L.; Genis–Mendoza, A.D.; Flores, J.; Lanzagorta, N.; Arroyo, M.; de la Fuente–Sandoval, C.; Santana, D.; Medina–Bañuelos, V.; et al. Neuroanatomical features and its usefulness in classification of patients with PANDAS. CNS Spectr. 2019, 24, 533–543. [CrossRef] [PubMed]
212. Kumar, A.; Williams, M.T.; Chugani, H.T. Evaluation of Basal Ganglia and Thalamic Inflammation in Children With Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infection and Tourette Syndrome: A Positron Emission Tomographic (PET) Study Using 11C–[R]–PK11195. J. Child Neurol. 2015, 30, 749–756. [CrossRef] [PubMed]
213. Giedd, J.N.; Rapoport, J.L.; Garvey, M.A.; Perlmutter, S.; Swedo, S.E. MRI assessment of children with obsessive–compulsive disorder or tics associated with streptococcal infection. Am. J. Psychiatry 2000, 157, 281–283. [CrossRef] [PubMed]
214. Congiu, P.; Gagliano, A.; Carucci, S.; Lanza, G.; Ferri, R.; Puligheddu, M. REM sleep atonia in patients with pediatric acute–onset neuropsychiatric syndrome: Implications for pathophysiology. J. Clin. Sleep Med. 2025, 21, 757–764. [CrossRef] [PubMed]
215. Zebrack, J.E.; Gao, J.; Verhey, B.; Tian, L.; Stave, C.; Farhadian, B.; Ma, M.; Silverman, M.; Xie, Y.; Tran, P.; et al. Neurological Soft Signs at Presentation in Patients With Pediatric Acute–Onset Neuropsychiatric Syndrome. JAMA Netw. Open. 2025, 8, e250314. [CrossRef] [PubMed] [PubMed Central]
216. Frick, L.R.; Rapanelli, M.; Jindachomthong, K.; Grant, P.; Leckman, J.F.; Swedo, S.; Williams, K.; Pittenger, C. Differential binding of antibodies in PANDAS patients to cholinergic interneurons in the striatum. Brain Behav. Immun. 2018, 69, 304–311. [CrossRef]
217. Chain, J.L.; Alvarez, K.; Mascaro–Blanco, A.; Reim, S.; Bentley, R.; Hommer, R.; Grant, P.; Leckman, J.F.; Kawikova, I.; Williams, K.; et al. Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychi– atric Disorder Associated With Streptococcal Infections. Front. Psychiatry 2020, 11, 564. [CrossRef]
218. Foiadelli, T.; Loddo, N.; Sacchi, L.; Santi, V.; D’Imporzano, G.; Spreafico, E.; Orsini, A.; Ferretti, A.; De Amici, M.; Testa, G.; et al. IL–17 in serum and cerebrospinal fluid of pediatric patients with acute neuropsychiatric disorders: Implications for PANDAS and PANS. Eur. J. Paediatr. Neurol. 2025, 54, 1–7. [CrossRef] [PubMed]
219. Leonardi, L.; Perna, C.; Bernabei, I.; Fiore, M.; Ma, M.; Frankovich, J.; Tarani, L.; Spalice, A. Pediatric acute–onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): Immunological Features Underpinning Controversial Entities. Children 2024, 11, 1043. [CrossRef]
220. Gromark, C.; Hesselmark, E.; Djupedal, I.G.; Silverberg, M.; Horne, A.; Harris, R.A.; Serlachius, E.; Mataix–Cols, D. A two–to–five year follow–up of a pediatric acute–onset neuropsychiatric syndrome cohort. Child Psychiatry Hum. Dev. 2022, 53, 354–364. [CrossRef] [PubMed]
221. Murphy, T.K.; Lewin, A.B.; Parker–Athill, E.C.; Storch, E.A.; Mutch, P.J. Tonsillectomies and adenoidectomies do not prevent the onset of pediatric autoimmune neuropsychiatric disorder associated with group A streptococcus. Pediatr. Infect. Dis. J. 2013, 32, 834–838. [CrossRef]
222. Gromark, C.; Harris, R.A.; Wickström, R.; Horne, A.; Silverberg–Mörse, M.; Serlachius, E.; Mataix–Cols, D. Establishing a pediatric acute–onset neuropsychiatric syndrome clinic: Baseline clinical features of the pediatric acute–onset neuropsychiatric syndrome cohort at Karolinska Institutet. J. Child Adolesc. Psychopharmacol. 2019, 29, 625–633. [CrossRef] [PubMed]
223. Stagi, S.; Rigante, D.; Lepri, G.; Bertini, F.; Matucci–Cerinic, M.; Falcini, F. Evaluation of autoimmune phenomena in patients with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Autoimmun. Rev. 2014, 13, 1236–1240. [CrossRef]
224. Williams, K.A.; Swedo, S.E.; Farmer, C.A.; Grantz, H.; Grant, P.J.; D’Souza, P.; Hommer, R.; Katsovich, L.; King, R.A.; Leckman, J.F. Randomized, controlled trial of intravenous immunoglobulin for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. J. Am. Acad. Child Adolesc. Psychiatry 2016, 55, 860–867.e2. [CrossRef]
225. Johnson, M.; Fernell, E.; Preda, I.; Wallin, L.; Fasth, A.; Gillberg, C.; Gillberg, C. Paediatric acute–onset neuropsychiatric syndrome in children and adolescents: An observational cohort study. Lancet Child Adolesc. Health 2019, 3, 175–180. [CrossRef]
226. Pohlman, D. PANDAS Network: PN 2018 State of Our Children SURVEY 2018 [Internet]. PANDAS Network; Downloaded by East Carolina University. 2018. Available online: https://pandasnetwork.org/wp–content/uploads/2018/10/PN–SOOC– SURVEY_2018.pdf(accessed on 5 August 2025).
227. Chan, A.; Phu, T.; Farhadian, B.; Willett, T.; Thienemann, M.; Frankovich, J. Familial Clustering of Immune–Mediated Diseases in Children with Abrupt–Onset Obsessive Compulsive Disorder. J. Child Adolesc. Psychopharmacol. 2020, 30, 345–346. [CrossRef]
228. Trifiletti, R.; Lachman, H.M.; Manusama, O.; Zheng, D.; Spalice, A.; Chiurazzi, P.; Schornagel, A.; Serban, A.M.; Van Wijck, R.; Cunningham, J.L.; et al. Identification of Ultra–Rare Genetic Variants in Pediatric Acute Onset Neuropsychiatric Syndrome (PANS) by Exome and Whole Genome Sequencing. Sci. Rep. 2022, 12, 11106. [CrossRef]
229. Wang, Y.; Du, W.; Hu, X.; Yu, X.; Guo, C.; Jin, X.; Wang, W. Targeting the blood–brain barrier to delay aging–accompanied neurological diseases by modulating gut microbiota, circadian rhythms, and their interplays. Acta Pharm. Sin. B 2023, 13, 4667–4687. [CrossRef] [PubMed]
230. Tărlungeanu, D.C.; Deliu, E.; Dotter, C.P.; Kara, M.; Janiesch, P.C.; Scalise, M.; Galluccio, M.; Tesulov, M.; Morelli, E.; Sonmez, F.M.; et al. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell 2016, 167, 1481–1494.e18. [CrossRef]
231. Xiu, Z.; Sun, L.; Liu, K.; Cao, H.; Qu, H.Q.; Glessner, J.T.; Ding, Z.; Zheng, G.; Wang, N.; Xia, Q.; et al. Shared Molecular Mechanisms and Transdiagnostic Potential of Neurodevelopmental Disorders and Immune Disorders. Brain Behav. Immun. 2024, 119, 767–780. [CrossRef] [PubMed]
232. Chiu, H.–J.; Sun, C.–K.; Tsai, S.–J.; Bai, Y.–M.; Hung, K.–C.; Hsu, J.–W.; Huang, K.–L.; Su, T.–P.; Chen, T.–J.; Sun, A.; et al. A Nationwide Study of the Risks of Major Mental Disorders among the Offspring of Parents with Rheumatoid Arthritis. Sci. Rep. 2022, 12, 4962. [CrossRef]
233. Arrondo, G.; Solmi, M.; Dragioti, E.; Eudave, L.; Ruiz–Goikoetxea, M.; Ciaurriz–Larraz, A.M.; Magallon, S.; Carvalho, A.F.; Cipriani, A.; Fusar–Poli, P.; et al. Associations between Mental and Physical Conditions in Children and Adolescents: An Umbrella Review. Neurosci. Biobehav. Rev. 2022, 137, 104662. [CrossRef]
234. Li, Q.; Barres, B.A. Microglia and Macrophages in Brain Homeostasis and Disease. Nat. Rev. Immunol. 2018, 18, 225–242. [CrossRef]
235. Lenz, K.M.; Nelson, L.H. Microglia and Beyond: Innate Immune Cells as Regulators of Brain Development and Behavioral Function. Front. Immunol. 2018, 9, 698. [CrossRef]
236. Lussier, A.A.; Bodnar, T.S.; Weinberg, J. Intersection of Epigenetic and Immune Alterations: Implications for Fetal Alcohol Spectrum Disorder and Mental Health. Front. Neurosci. 2021, 15, 788630. [CrossRef]
237. Asslih, S.; Damri, O.; Agam, G. Neuroinflammation as a Common Denominator of Complex Diseases (Cancer, Diabetes Type 2, and Neuropsychiatric Disorders). Int. J. Mol. Sci. 2021, 22, 6138. [CrossRef]
238. Masterson, E.E.; Miles, K.; Schlenk, N.; Manko, C.; Ma, M.; Farhadian, B.; Chang, K.; Silverman, M.; Thienemann, M.; Frankovich, J. Defining Clinical Course of Patients Evaluated for Pediatric Acute–Onset Neuropsychiatric Syndrome: Phenotypic Classification Based on 10 Years of Clinical Data. Dev. Neurosci. 2025, 270–286. [CrossRef] [PubMed]
239. Maser, J.D.; Akiskal, H.S. Spectrum concepts in major mental disorders. Psychiatr. Clin. N. Am. 2002, 25, xi–xiii. [CrossRef]
240. Hopwood, C.J.; Morey, L.C.; Markon, K.E. What is a psychopathology dimension? Clin. Psychol. Rev. 2023, 106, 102356. [CrossRef] [PubMed]
241. Pacheco, J.; Garvey, M.A.; Sarampote, C.S.; Cohen, E.D.; Murphy, E.R.; Friedman–Hill, S.R. Annual Research Review: The contributions of the RDoC research framework on understanding the neurodevelopmental origins, progression and treatment of mental illnesses. J. Child Psychol. Psychiatry 2022, 63, 360–376. [CrossRef]
242. Arnsten, A.F.; Rubia, K. Neurobiological circuits regulating attention, cognitive control, motivation, and emotion: Disruptions in neurodevelopmental psychiatric disorders. J. Am. Acad. Child Adolesc. Psychiatry 2012, 51, 356–367. [CrossRef] [PubMed]
243. Vreeland, A.; Calaprice, D.; Or–Geva, N.; Frye, R.E.; Agalliu, D.; Lachman, H.M.; Pittenger, C.; Pallanti, S.; Williams, K.; Ma, M.; et al. Postinfectious Inflammation, Autoimmunity, and Obsessive–Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection, and Pediatric Acute–Onset Neuropsychiatric Disorder. Dev. Neurosci. 2023, 45, 361–374. [CrossRef]
244. Karakochuk, C.; Whitfield, K.; Green, T.; Kraemer, K. The Biology of the First 1000 Days; CRC Press: Boca Raton, FL, USA, 2018.
245. Wang, Q.; Yang, Q.; Liu, X. The Microbiota–Gut–Brain Axis and Neurodevelopmental Disorders. Protein Cell 2023, 14, 762–775. [CrossRef]
246. Murgia, F.; Gagliano, A.; Tanca, M.G.; Or–Geva, N.; Hendren, A.; Carucci, S.; Pintor, M.; Cera, F.; Cossu, F.; Sotgiu, S.; et al. Metabolomic Characterization of Pediatric Acute–Onset Neuropsychiatric Syndrome (PANS). Front. Neurosci. 2021, 15, 645267. [CrossRef]
247. Likhitweerawong, N.; Thonusin, C.; Boonchooduang, N.; Louthrenoo, O.; Nookaew, I.; Chattipakorn, N.; Chattipakorn, S.C. Profiles of Urine and Blood Metabolomics in Autism Spectrum Disorders. Metab. Brain Dis. 2021, 36, 1641–1671. [CrossRef]
248. Gagliano, A.; Murgia, F.; Capodiferro, A.M.; Tanca, M.G.; Hendren, A.; Falqui, S.G.; Aresti, M.; Comini, M.; Carucci, S.; Cocco, E.; et al. 1H–NMR–Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute–Onset Neuropsychiatric Syndrome. J. Clin. Med. 2022, 11, 6493. [CrossRef]
249. Gagliano, A., Cucinotta, F., Giunta, I., et al. (2025). The Immune/Inflammatory Basis of Neurodevelopmental Disorders and Pediatric Acute-Onset Neuropsychiatric Syndrome: A Scoping Review. International Journal of Molecular Sciences, 26(16), 7767. https://doi.org/10.3390/ijms26167767
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2025-12-03
·今日头条
国家卫生健康委员会
最新数据显示，我国脊椎炎患者已超过1.2亿人，其中约30%的患者因错误用药导致病情加重或出现严重并发症。为规范脊椎炎临床用药，《中华医学杂志》2023年发布的《脊椎炎临床诊疗指南》明确指出，
科学合理用药是脊椎炎治疗的核心环节
。本文依据国家卫健委、国家药监局及中华医学会骨科分会权威指南，为广大患者提供全面、科学的用药指导。
一、脊椎炎的分类及特点
国家中医药管理局《中医骨伤科常见病诊疗指南》将脊椎炎分为六大类型，不同类型的脊椎炎在用药方案上存在显著差异：
表1：脊椎炎临床分类及特征
类型
临床特征
常见人群
检查指标特点
强直性脊柱炎
晨僵、腰背痛、活动受限
20-40岁男性
HLA-B27阳性率高，影像学可见骶髂关节炎
退行性脊椎炎
慢性钝痛、活动后加重
50岁以上人群
X线显示椎间隙狭窄、骨赘形成
感染性脊椎炎
急性疼痛、发热、局部红肿
免疫力低下者
血常规白细胞升高，CRP、ESR明显增高
代谢性脊椎炎
骨质疏松相关疼痛
绝经后女性、老年人
骨密度降低，血钙磷代谢异常
创伤性脊椎炎
外伤后疼痛、活动障碍
有外伤史人群
影像学可见骨折、脱位或软组织损伤
风湿性脊椎炎
多关节游走性疼痛
30-50岁女性
类风湿因子阳性，抗CCP抗体阳性
中华医学会骨科分会主任委员张英泽院士强调："
明确诊断是合理用药的前提，不同类型脊椎炎的治疗方案截然不同，患者切勿自行判断用药。
"
二、西药治疗方案
1. 非甾体抗炎药(NSAIDs)
国家药品监督管理局2022年《非处方药说明书规范》指出，NSAIDs是脊椎炎一线用药，但需严格控制使用时间和剂量。
表2：常用NSAIDs药物对比及适用情况
药物名称
作用特点
适用类型
常用剂量
禁忌人群
塞来昔布
选择性COX-2抑制剂，胃肠道反应小
强直性、退行性脊椎炎
200mg/日，分1-2次
严重心血管疾病患者
依托考昔
长效，24小时持续缓解疼痛
退行性脊椎炎
60-120mg/日，1次/日
活动性消化道溃疡患者
双氯芬酸钠
作用迅速，价格低廉
各类脊椎炎急性期
75-150mg/日，分2-3次
肾功能不全、孕妇
美洛昔康
胃肠道副作用较小
中老年退行性脊椎炎
7.5-15mg/日，1次/日
严重肝功能障碍者
艾瑞昔布
国产新药，安全性良好
慢性脊椎炎维持治疗
100mg/次，2次/日
18岁以下青少年
2. 糖皮质激素
《中国骨质疏松杂志》2023年指出，糖皮质激素仅适用于特定情况，应遵循"
小剂量、短疗程、局部用
"原则。
表3：糖皮质激素应用规范
给药途径
适用情况
常用药物
疗程
副作用监测
关节腔注射
单关节炎症明显
曲安奈德+利多卡因
3-4个月一次，全年≤4次
关节感染、软骨损伤
硬膜外注射
神经根受压症状
甲泼尼龙+局麻药
1-2周一次，全年≤3次
血糖升高、骨质疏松
口服
全身症状严重
泼尼松
起始10-15mg/日，2-4周内减停
消化道出血、血糖异常
静脉滴注
急性重症脊椎炎
甲泼尼龙冲击
3-5天为一疗程
电解质紊乱、精神症状
3. 改善病情抗风湿药(DMARDs)
中华医学会风湿病学分会《脊柱关节炎诊疗指南》强调，DMARDs需在专科医生指导下使用，定期监测血常规和肝肾功能。
表4：常用DMARDs药物及监测要点
药物名称
作用机制
适用类型
起效时间
监测指标
柳氮磺吡啶
抑制炎症介质合成
强直性脊柱炎
4-8周
血常规、肝功能、尿常规
甲氨蝶呤
免疫抑制
顽固性脊椎炎
6-8周
肝功能、血常规、肺功能
来氟米特
抑制淋巴细胞增殖
强直性、风湿性脊椎炎
4-12周
肝功能、血常规、血压
沙利度胺
调节免疫，抑制TNF-α
传统治疗无效的强直性脊柱炎
2-4周
神经系统症状、血常规
硫唑嘌呤
免疫抑制剂
重症感染性脊椎炎
2-3个月
血常规、肝功能
4. 生物制剂
国家医保局
2023年将多种生物制剂纳入医保目录，但使用条件严格，需符合《生物制剂临床应用专家共识》。
表5：脊椎炎常用生物制剂及适用条件
药物类别
代表药物
适应症
疗效特点
医保政策
TNF-α抑制剂
阿达木单抗、英夫利西单抗
活动性强直性脊柱炎
70%患者显著改善
二线用药，需NSAIDs治疗3个月无效
IL-17抑制剂
司库奇尤单抗
TNF抑制剂无效的强直性脊柱炎
快速缓解中轴症状
三线用药，需经两种生物制剂无效
JAK抑制剂
托法替布
传统治疗无效的脊柱关节炎
口服方便，起效较快
需专科医生评估，严格监测感染风险
IL-6抑制剂
托珠单抗
合并关节外表现的脊椎炎
改善全身症状
限特定适应症，严格控制使用指征
三、中成药治疗方案
国家中医药管理局《中医药治疗脊柱关节炎临床实践指南》指出，
中西医结合治疗可提高疗效，减少西药用量及不良反应
。
表6：常用中成药分类及功效
药物名称
功效特点
适用证型
用法用量
注意事项
独活寄生丸
祛风除湿，补益肝肾
风寒湿痹型
6g/次，2次/日
孕妇慎用，湿热证忌用
通痹胶囊
活血通络，祛风除湿
气滞血瘀型
4粒/次，3次/日
胃溃疡患者慎用
雷公藤多苷片
免疫抑制，抗炎镇痛
活动性风湿性脊椎炎
10-20mg/次，3次/日
生殖毒性，育龄期慎用
骨疏康胶囊
补肾壮骨，活血止痛
肾虚血瘀型退行性脊椎炎
4粒/次，3次/日
长期服用监测肝功能
白芍总苷胶囊
免疫调节，保护关节
各类慢性脊椎炎
0.6g/次，3次/日
偶见大便稀溏，可减量
北京中医药大学东直门医院骨科主任李峰教授提醒："
中成药使用需辨证论治，同一脊椎炎患者在不同阶段证型可能变化，应由中医师调整用药方案。
"
表7：中医辨证与用药对应表
证型
临床表现
舌象脉象
常用方剂
代表中成药
风寒湿痹证
腰背冷痛，遇寒加重，得热则减
舌淡苔白，脉弦紧
独活寄生汤
独活寄生丸、风湿骨痛胶囊
湿热痹阻证
腰背灼痛，局部红肿，发热
舌红苔黄腻，脉滑数
四妙丸
二妙丸、四妙丸
气滞血瘀证
腰背刺痛，位置固定，夜间加重
舌暗有瘀斑，脉涩
身痛逐瘀汤
通痹胶囊、血府逐瘀胶囊
肝肾亏虚证
腰膝酸软，头晕耳鸣，久病不愈
舌淡少苔，脉沉细
青娥丸+龟鹿二仙胶
骨疏康胶囊、仙灵骨葆胶囊
痰瘀互结证
腰背僵硬，活动受限，结节形成
舌暗苔腻，脉滑
导痰汤+身痛逐瘀汤
通络开痹片、天麻丸
四、营养素补充
中国营养学会《骨关节疾病营养干预专家共识》指出，
合理补充特定营养素可改善脊椎炎症状，辅助药物治疗效果
。
表8：脊椎炎患者关键营养素补充方案
营养素
作用机制
推荐剂量
食物来源
注意事项
维生素D
调节免疫，促进钙吸收
800-2000IU/日
深海鱼、蛋黄、强化奶
需监测血25(OH)D水平，避免过量
钙剂
预防骨质疏松，保护骨密度
600-1000mg/日
乳制品、豆制品、绿叶菜
与抗生素间隔2小时服用
Omega-3脂肪酸
抗炎，减少前列腺素合成
1-3g/日
三文鱼、亚麻籽、核桃
与抗凝药同用需谨慎
姜黄素
抑制NF-κB通路，减轻炎症
500-1000mg/日
姜黄、咖喱
胃溃疡患者慎用，避免与抗凝药同用
胶原蛋白肽
修复软骨，改善关节功能
5-10g/日
骨汤、猪蹄、专业补充剂
优质蛋白摄入不足者优先补充
五、饮食调理
国家卫健委《慢性病患者膳食指导》强调，
科学饮食是脊椎炎综合管理的重要组成部分
，可减轻炎症反应，缓解症状。
表9：脊椎炎患者推荐食物清单
食物类别
推荐食物
食用频率
作用机制
注意事项
水果类
蓝莓、樱桃、柑橘类
每日200-400g
富含花青素、维生素C，抗氧化
高血糖患者控制摄入量
蔬菜类
菠菜、西兰花、胡萝卜
每日500g以上
富含维生素K、叶酸，调节免疫
痛风患者避免菠菜过量
蛋白质类
三文鱼、沙丁鱼、鸡胸肉
每周3-4次
Omega-3脂肪酸，抗炎
避免过度烹饪破坏营养
全谷物类
燕麦、糙米、藜麦
作为主食替代
富含膳食纤维，调节肠道菌群
逐步增加摄入，避免腹胀
调味品类
姜、蒜、肉桂、姜黄
适量添加
天然抗炎物质，增强免疫
避免辛辣刺激物过量
表10：脊椎炎患者应限制食物清单
食物类别
限制食物
限制原因
替代建议
专家建议
高饱和脂肪
红肉、肥肉、动物内脏
促进炎症反应
选择白肉、鱼类
每周红肉≤500g
高糖食品
甜点、含糖饮料、精制碳水
促进氧化应激
选择低GI水果、全谷物
精制糖每日<25g
反式脂肪酸
油炸食品、人造奶油
加重炎症反应
选择植物油、坚果
避免反复油炸食品
高盐食品
腌制食品、加工肉制品
促进骨质流失
低盐调味品、新鲜食材
每日盐<5g
酒精
所有含酒精饮品
干扰药物代谢，加重炎症
无酒精饮品
服药期间严格禁酒
六、用药安全
国家药品不良反应监测中心数据显示，
不合理用药是脊椎炎患者不良事件的主要原因
。《中国合理用药指南》强调严格遵循"五不要"原则：
不要自行增减药物剂量
不要随意更换药物种类
不要同时服用多种同类药物
不要长期大剂量使用NSAIDs
不要忽视药物相互作用
表11：常见药物相互作用警示
联合用药组合
风险
临床表现
处理建议
替代方案
NSAIDs+抗凝药
出血风险增加3-5倍
牙龈出血、黑便、皮下瘀斑
避免联用，或严密监测INR值
选用胃肠道安全性高的NSAIDs
糖皮质激素+降糖药
血糖控制困难
口渴、多尿、血糖波动大
增加血糖监测频次，调整降糖药剂量
选择局部给药方式
甲氨蝶呤+非甾体抗炎药
骨髓抑制风险增加
乏力、发热、易感染
避免联用，或严密监测血常规
选用生物制剂替代
雷公藤+免疫抑制剂
免疫功能过度抑制
反复感染、发热
严格控制剂量，监测免疫功能
逐步减停一种药物
柳氮磺吡啶+叶酸
药效降低
疗效不佳，症状持续
间隔2小时服用
选择其他DMARDs
七、注意事项
**国家卫健委《慢性病患者自我管理指南》**提醒脊椎炎患者注意以下事项：
定期复查
：服药3个月以上需监测肝肾功能、血常规
阶梯用药
：遵循"先外用，再口服；先非甾体，后生物制剂"原则
个体化治疗
：根据年龄、合并症、疾病活动度调整方案
综合管理
：药物+康复锻炼+心理调适三结合
长期随访
：慢性脊椎炎需终身管理，避免擅自停药
表12：不同人群用药特殊注意事项
人群类别
用药特点
禁忌药物
监测重点
专家建议
老年人(>65岁)
药物代谢慢，多重用药常见
非选择性NSAIDs、长期激素
肾功能、电解质、跌倒风险
选择低剂量、短半衰期药物
儿童青少年
生长发育期，骨骺未闭合
长期激素、四环素类
生长发育指标、骨龄评估
严格专科随访，最小有效剂量
妊娠期女性
需考虑胎儿安全
甲氨蝶呤、来氟米特、沙利度胺
胎儿发育、母体炎症指标
计划怀孕前3个月停用致畸药物
哺乳期女性
药物可通过乳汁分泌
大部分DMARDs、生物制剂
婴儿发育、母体炎症控制
药物使用期间暂停哺乳
肝肾功能不全
药物代谢排泄障碍
依托考昔、高剂量NSAIDs
肝肾功能、血药浓度
选择不经肝肾代谢药物或调整剂量
八、常见问答10条
1. 问：脊椎炎能根治吗？
答：国家卫健委《慢病防控蓝皮书》指出，除感染性脊椎炎外，多数脊椎炎属于慢性疾病，
无法根治但可有效控制
。规范治疗下，80%患者可达到临床缓解，维持正常生活和工作。
2. 问：NSAIDs长期使用会导致胃出血吗？
答：中华医学会消化病学分会数据显示，长期使用非选择性NSAIDs胃肠道并发症风险增加3-5倍。
建议
：≥65岁、有溃疡史、同时用抗凝药者选择COX-2抑制剂，并联用质子泵抑制剂保护胃黏膜。
3. 问：生物制剂会不会降低免疫力，容易感染？
答：国家药监局药品评价中心指出，生物制剂确实会适度抑制免疫功能。
规范使用下
，严重感染发生率<5%。用药前需筛查结核、乙肝，治疗期间避免活疫苗接种，出现发热及时就医。
4. 问：脊椎炎患者能运动吗？
答：《中华骨科杂志》强调，
适度运动是脊椎炎治疗的基石
。推荐游泳、太极、八段锦等低冲击运动，避免足球、篮球等高冲击运动。急性期以休息为主，缓解期逐步增加运动量。
5. 问：中医治疗脊椎炎有效吗？
答：国家中医药管理局临床评价显示，中西医结合治疗脊椎炎有效率比单用西药提高15-20%。
关键在于辨证施治
，急性期以西药控制症状，缓解期以中药调理体质，减少复发。
6. 问：脊椎炎会遗传给下一代吗？
答：中华医学会遗传学分会指出，强直性脊柱炎遗传度约90%，但
并非单基因遗传
。HLA-B27阳性者后代患病风险约5-20%，远高于普通人群(0.1-0.3%)，但环境因素同样重要。
7. 问：脊椎炎患者需要补钙吗？
答：《中国骨质疏松防治指南》强调，长期使用糖皮质激素的脊椎炎患者
必须补充钙和维生素D
。一般人群在骨密度降低(T值
8. 问：脊椎炎会影响性生活和生育吗？
答：北京大学第三医院风湿免疫科研究显示，病情控制良好的脊椎炎患者性功能和生育能力与常人无异。
关键在于规范治疗
，避免使用致畸药物，计划怀孕前3-6个月调整用药方案。
9. 问：天气变化为何会加重脊椎炎症状？
答：中国中医科学院研究发现，气压降低、湿度增加时，关节内压力变化刺激神经末梢，同时炎症介质释放增加。
建议
：天气变化前增加保暖，调整药物剂量，进行室内康复训练。
10. 问：脊椎炎患者需要卧床休息吗？
答：《康复医学杂志》指出，除急性感染性脊椎炎需短期卧床外，
大多数脊椎炎患者应避免长时间卧床
。久卧会导致肌肉萎缩、关节僵硬，反而加重病情。应遵循"活动与休息平衡"原则，急性期减少活动量，不完全卧床。
九、康复锻炼指南
表13：脊椎炎患者分阶段康复锻炼方案
疾病阶段
锻炼目标
推荐动作
频率时长
注意事项
急性期
缓解疼痛，维持基础活动
仰卧位深呼吸、踝泵运动
每日3-4次，每次5分钟
疼痛明显时暂停，避免过度活动
亚急性期
恢复关节活动度，增强肌肉
桥式运动、猫牛式、水中行走
每日2次，每次15-20分钟
运动后疼痛不超过2小时
缓解期
全面改善功能，预防复发
游泳、八段锦、核心肌群训练
每周4-5次，每次30-45分钟
保持正确姿势，循序渐进增加强度
慢性期
维持功能，提高生活质量
太极、瑜伽(改良版)、步行
每日坚持，每次30分钟以上
长期坚持，形成生活习惯
术后康复
促进愈合，功能重建
个体化康复计划，专业指导
严格遵医嘱，分阶段进行
在康复医师指导下进行，避免过早负重
专家提醒
北京协和医院骨科主任翁习生教授强调
："脊椎炎治疗是一场'马拉松'而非'百米冲刺'。患者需要建立长期管理意识，与医生建立良好沟通，定期评估治疗效果，及时调整治疗方案。最重要的是，
不要轻信'特效药'、'祖传秘方'等虚假宣传，科学治疗才能获得最佳预后。
"
参考文献
中华医学会骨科学分会. 脊柱关节炎诊疗指南(2023版). 中华骨科杂志, 2023, 43(5): 289-298.
国家卫生健康委员会. 慢性病防治中长期规划(2021-2025年). 北京: 人民卫生出版社, 2021.
国家药品监督管理局. 非甾体抗炎药临床应用指导原则. 中国药学杂志, 2022, 57(8): 601-609.
中华医学会风湿病学分会. 强直性脊柱炎诊疗指南. 中华内科杂志, 2022, 61(1): 18-27.
国家中医药管理局. 中医骨伤科常见病诊疗指南. 中国中医药出版社, 2021.
中国医师协会风湿免疫科医师分会. 脊柱关节炎生物制剂应用专家共识. 中华风湿病学杂志, 2023, 27(3): 145-153.
中国营养学会. 骨关节疾病营养干预专家共识. 中华临床营养杂志, 2022, 30(4): 193-201.
国家药典委员会. 中华人民共和国药典(2020年版). 北京: 中国医药科技出版社, 2020.
中华医学会骨质疏松和骨矿盐疾病分会. 中国骨质疏松防治指南(2021版). 中华骨质疏松和骨矿盐疾病杂志, 2021, 14(5): 417-437.
中国康复医学会. 脊柱关节炎康复治疗专家共识. 中国康复医学杂志, 2022, 37(8): 867-874.
国家医保局. 国家基本医疗保险、工伤保险和生育保险药品目录(2023年版). 北京: 中国劳动社会保障出版社, 2023.
陈晓东, 等. 中西医结合治疗强直性脊柱炎临床研究进展. 中国中西医结合杂志, 2023, 43(2): 231-235.
李小峰, 等. 脊椎炎患者用药安全监测体系构建. 中国药房, 2022, 33(15): 1801-1806.
王辰, 等. 慢性非传染性疾病自我管理指南. 北京: 人民卫生出版社, 2022.
张奉春, 等. 风湿免疫病药物治疗学. 北京: 人民卫生出版社, 2021.
刘维, 等. 脊柱关节炎患者生活质量影响因素分析. 中华医学杂志, 2023, 103(12): 891-897.
中华医学会临床药学分会. 药物相互作用临床处理指南. 中国医院药学杂志, 2022, 42(10): 1023-1030.
100 项与 叶酸 相关的药物交易
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研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 巨幼红细胞性贫血 | 中国 | 1981-01-01 | |
| 叶酸缺乏 | 日本 | 1950-08-01 | |
| 神经管缺陷 | 美国 | 1947-06-02 |
未上市
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 高同种半胱胺酸血症 | 临床2期 | 中国 | 2025-08-28 | |
| 非鳞状非小细胞肺癌 | 临床2期 | 澳大利亚 | 2008-02-01 | |
| 非鳞状非小细胞肺癌 | 临床2期 | 意大利 | 2008-02-01 | |
| 非鳞状非小细胞肺癌 | 临床2期 | 墨西哥 | 2008-02-01 | |
| 非鳞状非小细胞肺癌 | 临床2期 | 西班牙 | 2008-02-01 | |
| 避孕 | 临床1期 | - | 2005-01-01 | |
| 糖尿病周围神经病变 | 临床阶段不明 | - | - | |
| 缺血性卒中 | 临床申请批准 | 中国 | 2024-09-24 | |
| 同型半胱氨酸血症 | 临床申请批准 | 中国 | 2022-11-09 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
| 研究 | 分期 | 人群特征 | 评价人数 | 分组 | 结果 | 评价 | 发布日期 |
|---|
临床4期 | 10 | 願壓鏇繭遞願選淵壓襯(製顧願鹽繭餘壓選顧願) = 壓壓憲齋繭齋醖遞選衊 衊淵憲鑰鏇餘壓膚鹹蓋 (蓋襯顧醖糧鏇夢鑰艱獵, 夢鹽遞鏇廠觸積構鏇鏇 ~ 窪鑰齋願憲壓齋遞壓獵) | - | 2025-11-21 | |||
临床2/3期 | 289 | (Ascorbic Acid and Folic Acid) | 齋鹹積鏇夢襯襯網壓鹹 = 構淵窪鹹襯選醖鑰鏇艱 窪壓窪餘醖襯範範憲網 (餘網廠繭築壓糧築鑰構, 淵衊鹹範鏇鬱夢網艱製 ~ 蓋鹽淵積齋廠鹹遞鏇鹽) 更多 | - | 2022-08-08 | ||
(Hydroxychloroquine and Folic Acid) | 齋鹹積鏇夢襯襯網壓鹹 = 艱憲積觸膚衊鹹窪夢膚 窪壓窪餘醖襯範範憲網 (餘網廠繭築壓糧築鑰構, 願襯範網衊積餘夢窪鹹 ~ 鬱鑰觸襯築壓艱積醖築) 更多 | ||||||
临床4期 | 152 | gout flare prophylaxis regimen+acetaminophen+methylprednisolone+fexofenadine+folic acid+methotrexate+Pegloticase (Pegloticase + MTX) | 繭壓憲齋膚積壓襯衊積 = 窪選膚餘醖鑰醖夢鬱蓋 廠窪廠繭齋齋遞憲淵窪 (廠蓋選獵廠簾膚憲願遞, 構淵壓鹹鬱壓築鬱簾壓 ~ 憲積廠網壓襯襯衊製鏇) 更多 | - | 2022-05-16 | ||
(Pegloticase + Placebo) | 繭壓憲齋膚積壓襯衊積 = 築構積襯艱觸網構鹽廠 廠窪廠繭齋齋遞憲淵窪 (廠蓋選獵廠簾膚憲願遞, 襯窪糧網遞壓積壓鏇製 ~ 築網壓鬱憲網廠醖醖鹽) 更多 | ||||||
临床2期 | 252 | (Placebo) | 壓廠顧淵繭餘構願遞衊 = 廠願鑰鹽齋膚衊構廠憲 衊構選繭鹹獵獵範衊網 (選鬱簾繭鏇鹽範觸觸憲, 製積鏇齋壓鑰淵艱衊膚 ~ 鹹製憲觸齋範廠糧夢範) 更多 | - | 2021-12-21 | ||
(Brodalumab 70 mg) | 壓廠顧淵繭餘構願遞衊 = 膚鹹願範衊衊簾憲觸鑰 衊構選繭鹹獵獵範衊網 (選鬱簾繭鏇鹽範觸觸憲, 鏇餘構夢築構獵積願廠 ~ 鹽構範鹽觸壓顧憲蓋製) 更多 | ||||||
临床3期 | 136 | (Group 1- MTX+LEF+HCQ) | 鏇蓋觸鏇製築廠鏇構鏇 = 範糧廠構醖觸構繭獵蓋 醖簾鏇繭遞繭願鹹獵鹽 (構築廠選廠製鏇憲壓製, 繭範艱築觸鹽鹽製襯憲 ~ 網鹽夢繭構醖艱衊觸鬱) 更多 | - | 2021-06-10 | ||
(Group 2- MTX+SSZ+HCQ) | 鏇蓋觸鏇製築廠鏇構鏇 = 餘衊齋鹹淵選膚範蓋襯 醖簾鏇繭遞繭願鹹獵鹽 (構築廠選廠製鏇憲壓製, 淵簾餘獵夢鹽鏇鏇齋醖 ~ 範繭積壓鏇襯積鹽壓簾) 更多 | ||||||
临床3期 | 136 | (CinnaGen Adalimumab) | 艱獵齋夢鑰膚壓獵醖窪 = 範鹽鏇蓋顧餘製蓋醖壓 選簾構壓鹹鬱壓襯繭壓 (淵簾築憲選簾繭醖蓋範, 襯夢顧鑰遞糧鏇蓋醖糧 ~ 遞壓積構築窪艱襯鬱衊) 更多 | - | 2021-02-02 | ||
(AbbVie Adalimumab) | 艱獵齋夢鑰膚壓獵醖窪 = 築糧觸範構鬱簾簾觸築 選簾構壓鹹鬱壓襯繭壓 (淵簾築憲選簾繭醖蓋範, 窪鑰獵窪蓋膚壓鑰願淵 ~ 窪積網繭餘鹹糧積衊壓) 更多 | ||||||
临床4期 | 14 | 鏇願窪窪壓構夢鏇餘膚 = 壓顧築衊窪鑰夢蓋糧積 鹽觸衊膚構廠觸壓衊齋 (襯網憲網獵鹹鏇範鏇製, 襯顧窪遞窪糧獵醖製鏇 ~ 繭選鏇齋顧淵構繭夢鏇) 更多 | - | 2020-11-18 | |||
N/A | 687 | placebo+nitrous oxide (Comparator) | 鏇膚衊積夢鬱觸繭製顧 = 簾鹽襯遞齋蓋觸築願鏇 衊齋廠積積範醖鑰憲鑰 (餘願簾廠鬱憲襯顧憲網, 範願網選簾淵選遞艱製 ~ 範顧鹹衊願觸鹹壓蓋鑰) 更多 | - | 2020-10-01 | ||
standard of care (Standard of Care) | 鏇膚衊積夢鬱觸繭製顧 = 齋淵構遞衊醖遞築醖糧 衊齋廠積積範醖鑰憲鑰 (餘願簾廠鬱憲襯顧憲網, 獵艱鏇願網鬱選築築齋 ~ 鏇夢膚餘觸鹽憲憲廠齋) 更多 | ||||||
临床3期 | 2,464 | (Folic Acid 4 mg) | 製繭壓鹹簾構遞膚鑰糧 = 膚製壓廠築憲鹹鑰鏇簾 夢築顧窪範遞獵淵夢網 (鬱艱憲餘範積鹽淵獵蓋, 範壓衊襯積獵獵餘簾壓 ~ 窪鏇觸顧憲淵製簾鏇齋) 更多 | - | 2020-07-07 | ||
Placebo (Placebo) | 製繭壓鹹簾構遞膚鑰糧 = 網糧構膚憲糧範壓衊襯 夢築顧窪範遞獵淵夢網 (鬱艱憲餘範積鹽淵獵蓋, 醖網範齋積餘淵製鹹襯 ~ 襯鹹壓餘觸襯顧製鑰願) 更多 | ||||||
临床3期 | 428 | 積窪鬱遞簾範醖簾膚憲(醖範鏇襯醖製蓋衊鏇廠) = 獵醖鹽築蓋膚願糧鏇積 憲鏇網膚餘廠願選網鬱 (製窪壓膚築範蓋憲糧廠 ) | - | 2020-02-18 | |||
(Placebo) | 積窪鬱遞簾範醖簾膚憲(醖範鏇襯醖製蓋衊鏇廠) = 襯選餘鑰膚壓醖艱繭夢 憲鏇網膚餘廠願選網鬱 (製窪壓膚築範蓋憲糧廠 ) |
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