Background: Risperidone and paliperidone have been the mainstay treatment for schizophrenia and their potential role in neuroprotection could be associated with brain-derived neurotrophic factor (BDNF) and N400 (an event-related brain potential component). So far, different effects on both BDNF and N400 were reported in relation to various antipsychotic treatments. However, few studies have been conducted on the mechanism of risperidone and paliperidone on BDNF and N400. This study aimed to compare the effects of risperidone and paliperidone on BDNF and the N400 component of the event-related brain potential in patients with first-episode schizophrenia.
Methods: Ninety-eight patients with first-episode schizophrenia were randomly divided into the risperidone and paliperidone groups and treated with risperidone and paliperidone, respectively, for 12 weeks. Serum BDNF level, the latency, and amplitude of the N400 event-related potential before and after the treatment and Positive and Negative Syndrome Scale (PANSS) scores were compared between the two groups.
Results: A total of 94 patients were included in the final analysis (47 patients in each group). After the treatment, the serum BDNF levels in both groups increased (all P < 0.01), while no significant difference in serum BDNF level was found between the groups before and after the treatment (all P > 0.05). After the treatment, N400 amplitudes were increased (from 4.73 ± 2.86 μv and 4.51 ± 4.63 μv to 5.35 ± 4.18 μv and 5.52 ± 3.08 μv, respectively) under congruent condition in both risperidone and paliperidone groups (all P < 0.01). Under incongruent conditions, the N400 latencies were shortened in the paliperidone group (from 424.13 ± 110.42 ms to 4.7.41 ± 154.59 ms, P < 0.05), and the N400 amplitudes were increased in the risperidone group (from 5.80 ± 3.50 μv to 7.17 ± 5.51 μv, P < 0.01). After treatment, the total PANSS score in both groups decreased significantly (all P < 0.01), but the difference between the groups was not significant (P > 0.05). A negative correlation between the reduction rate of the PANSS score and the increase in serum BDNF level after the treatment was found in the paliperidone group but not in the risperidone group.
Conclusions: Both risperidone and paliperidone could increase the serum BDNF levels in patients with first-episode schizophrenia and improve their cognitive function (N400 latency and amplitude), but their antipsychotic mechanisms might differ.
新型抗精神病药对首发精神分裂症患者脑源性神经营养因子及N400的影响研究摘要背景：抗精神病药可能通过影响脑源性神经营养因子（BDNF）浓度，对精神分裂症产生治疗作用。然而，对利培酮及其代谢产物帕利哌酮这方面的研究甚少。本文研究比较这两种新型抗精神病药对首发精神分裂症患者血清BDNF以及事件相关脑电位成分（N400）的影响，进一步探讨药物治疗精神分裂症的机制。 方法：98例首发精神分裂症患者随机分为帕利哌酮组与利培酮组（49例/组），采用帕利哌酮及利培酮治疗12周，比较两组治疗前后血清BDNF浓度及N400潜伏期和波幅，同时通过阳性与阴性症状（PANSS）量表对其治疗疗效进行评估。 结果：最终有94例患者纳入统计（每组47例）。抗精神病药治疗后，两组患者血清BDNF浓度均有明显上升（P<0.01），但组间比较未见统计学差异（P>0.05）。治疗后，匹配条件下利培酮和帕利哌酮组患者的N400波幅明显上升（治疗前4.73±2.86 μv, 4.51±4.63 μv, 治疗后 5.35±4.18 μv, 5.52±3.08 μv），具有统计学意义（P<0.01）；在非匹配条件下，帕利哌酮组N400潜伏期缩短（424.13±110.42 ms vs. 407.41±154.59 ms, P<0.05），而利培酮组N400波幅明显增高（5.80±3.50 μv, vs. 7.17±5.51 μv，P<0.01）。治疗后，两组患者PANSS总分均明显下降（P<0.01），而组间比较无显著性差异（P>0.05）。进一步分析发现，帕利哌酮组PANSS减分率与血清BDNF升高值存在正相关，而利培酮组未发现二者间存在相关。 结论：新型抗精神病药物可在不同程度改善首发精神分裂症患者血清BDNF浓度、改善患者认知功能，提高临床治疗疗效，具体机制值得进一步研究。.
Keywords: Brain-Derived Neurotrophic Factor; Cognitive Function; Event-Related Potentials; N400; Schizophrenia.