A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis.
A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis.
复制标题
DOI：
10.1038/s41398-020-01095-8
复制
发表时间：
2020-11-30
影响因子：
6.8
通讯作者：
Husain N
中科院分区：
文献类型：
--
作者：
Chaudhry IB;Husain MO;Khoso AB;Husain MI;Buch MH;Kiran T;Fu B;Bassett P;Qurashi I;Ur Rahman R;Baig S;Kazmi A;Corsi-Zuelli F;Haddad PM;Deakin B;Husain N
以精神分裂症为表现的NMDA自身抗体脑炎提示适应性细胞介导的免疫在特发性精神分裂症中的可能作用。然而，据我们所知，还没有免疫抑制剂甲氨蝶呤治疗精神分裂症的试验。我们在一项可行性研究中测试了用于治疗全身性自身免疫性疾病的低剂量甲氨蝶呤在精神分裂症患者中是否可以耐受和有效。从巴基斯坦卡拉奇的住院和门诊机构招募了92名精神分裂症诊断5年内的参与者。他们被随机分配接受每周一次10毫克口服甲氨蝶呤（n = 45）或匹配的安慰剂（n = 47），每天5毫克叶酸，除了治疗照常12周。每组有8人退出。副作用在甲氨蝶呤组中并不明显更常见，而且并不严重。1人出现白细胞减少症。接受甲氨蝶呤治疗的患者阳性症状评分比安慰剂组改善更多（β = −2.5; [95% CI −4.7至−0.4]），而阴性症状不受治疗影响（β = −0.39; [95% CI −2.01至1.23]）。没有免疫生物标志物，但甲氨蝶呤不影响组平均白细胞计数或C反应蛋白。我们的结论是，进一步的研究是可行的，但应集中在亚组确定的神经免疫分析的进展。甲氨蝶呤被认为是在自身免疫性疾病中通过重置免疫信号的系统调节性T细胞控制起作用;我们表明，在中枢神经系统中的类似作用将解释精神分裂症免疫发病机制的其他令人困惑的特征。
NMDA autoantibody encephalitis presenting as schizophrenia suggests the possible role of adaptive cell-mediated immunity in idiopathic schizophrenia. However, to our knowledge there have been no trials of the immune-suppressant methotrexate in schizophrenia. We tested if low-dose methotrexate as used in the treatment of systemic autoimmune disorders would be tolerable and effective in people with schizophrenia in a feasibility study. Ninety-two participants within 5 years of schizophrenia diagnosis were recruited from inpatient and outpatient facilities in Karachi, Pakistan. They were randomised to receive once weekly 10-mg oral methotrexate (n = 45) or matching placebo (n = 47) both with daily 5-mg folic acid, in addition to treatment as usual for 12 weeks. There were eight dropouts per group. Side effects were non-significantly more common in those on methotrexate and were not severe. One person developed leukopenia. Positive symptom scores improved more in those receiving methotrexate than placebo (β = −2.5; [95% CI −4.7 to −0.4]), whereas negative symptoms were unaffected by treatment (β = −0.39; [95% CI −2.01 to 1.23]). There were no immune biomarkers but methotrexate did not affect group mean leucocyte counts or C-reactive protein. We conclude that further studies are feasible but should be focussed on subgroups identified by advances in neuroimmune profiling. Methotrexate is thought to work in autoimmune disorders by resetting systemic regulatory T-cell control of immune signalling; we show that a similar action in the CNS would account for otherwise puzzling features of the immuno-pathogenesis of schizophrenia.
登录
查看更多内容
影响因子：
10.5
作者：
DAVID, A;BUCHANAN, A;ALMEIDA, O
通讯作者：
ALMEIDA, O
影响因子：
3.4
作者：
HALL, RCW
通讯作者：
HALL, RCW
影响因子：
30.8
作者：
Pardiñas AF;Holmans P;Pocklington AJ;Escott-Price V;Ripke S;Carrera N;Legge SE;Bishop S;Cameron D;Hamshere ML;Han J;Hubbard L;Lynham A;Mantripragada K;Rees E;MacCabe JH;McCarroll SA;Baune BT;Breen G;Byrne EM;Dannlowski U;Eley TC;Hayward C;Martin NG;McIntosh AM;Plomin R;Porteous DJ;Wray NR;Caballero A;Geschwind DH;Huckins LM;Ruderfer DM;Santiago E;Sklar P;Stahl EA;Won H;Agerbo E;Als TD;Andreassen OA;Bækvad-Hansen M;Mortensen PB;Pedersen CB;Børglum AD;Bybjerg-Grauholm J;Djurovic S;Durmishi N;Pedersen MG;Golimbet V;Grove J;Hougaard DM;Mattheisen M;Molden E;Mors O;Nordentoft M;Pejovic-Milovancevic M;Sigurdsson E;Silagadze T;Hansen CS;Stefansson K;Stefansson H;Steinberg S;Tosato S;Werge T;GERAD1 Consortium;CRESTAR Consortium;Collier DA;Rujescu D;Kirov G;Owen MJ;O'Donovan MC;Walters JTR
通讯作者：
Walters JTR
影响因子：
--
作者：
Kemmler, G;Hummer, M;Fleischhacher, W
通讯作者：
Fleischhacher, W
自闭症谱系障碍（ASD）、精神分裂症和双相情感障碍中全转录组异构体水平失调
影响因子：
56.9
作者：
Gandal, Michael J.;Zhang, Pan;Geschwind, Daniel H.
通讯作者：
Geschwind, Daniel H.