Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan.
Department of Pharmacy, Fukushima Medical University Hospital, Fukushima, Japan.
J Psychiatr Res. 2024 Oct;178:228-235. doi: 10.1016/j.jpsychires.2024.08.012. Epub 2024 Aug 8.
Cognitive dysfunction is a core feature of schizophrenia. Although treatment-resistant schizophrenia (TRS) exhibits wide-ranging neuropsychological deficits, factors defining cognitive prognosis in TRS are unclear. We aimed to clarify the association between cognitive dysfunction and factors, such as plasma concentrations of clozapine (CLZ), N-desmethylclozapine (NDMC), and homovanillic acid (HVA), due to differences in antipsychotic responses in patients with schizophrenia.
This pilot cross-sectional study included 60 Japanese patients (35 with TRS and 25 with non-CLZ antipsychotic responders (AR)). Cognitive function was evaluated using the Brief Assessment of Cognition Short Form (BAC-SF). Plasma concentrations of HVA, CLZ, and NDMC were analyzed by high-performance liquid chromatography.
The cognitive performance of patients with AR was better than that of patients with TRS in all tasks. No significant cognitive differences were detected between the CLZ responders and non-responders. The severity of negative and extrapyramidal symptoms was found to be potentially negatively associated with BAC-SF composite and several subtest scores. In patients with TRS, chlorpromazine equivalents and the CLZ/NDMC ratio were identified as factors negatively associated with Digit Sequencing and the Symbol Coding subtest scores of the BAC-SF, respectively.
Our study suggests that patients with TRS experience worse cognitive dysfunction than those with AR, and CLZ responsiveness in TRS may be not associated with cognitive dysfunction. Additionally, higher chlorpromazine equivalents and the CLZ/NDMC ratio may be associated with severity of cognitive dysfunction in patients with TRS. Further studies are required to clarify the relationship between treatment response and cognitive dysfunction in schizophrenia.
认知功能障碍是精神分裂症的核心特征。尽管治疗抵抗性精神分裂症（TRS）表现出广泛的神经认知缺陷，但定义 TRS 认知预后的因素尚不清楚。我们旨在阐明认知功能障碍与氯氮平（CLZ）、N-去甲基氯氮平（NDMC）和高香草酸（HVA）等因素之间的关联，这些因素与精神分裂症患者的抗精神病反应差异有关。
本研究为一项先导性横断面研究，共纳入 60 例日本患者（35 例为 TRS，25 例为非 CLZ 抗精神病药反应者（AR））。使用简短认知评估量表短式版（BAC-SF）评估认知功能。通过高效液相色谱法分析 HVA、CLZ 和 NDMC 的血浆浓度。
AR 组患者的认知表现优于 TRS 组患者，所有任务均如此。CLZ 反应者和非反应者之间的认知差异无统计学意义。阴性和锥体外系症状的严重程度与 BAC-SF 总分和几个子测试评分呈潜在负相关。在 TRS 患者中，氯丙嗪等效剂量和 CLZ/NDMC 比值分别与 BAC-SF 的数字序列和符号编码子测试评分呈负相关。
本研究表明，TRS 患者的认知功能障碍比 AR 患者更严重，TRS 中的 CLZ 反应性可能与认知功能障碍无关。此外，较高的氯丙嗪等效剂量和 CLZ/NDMC 比值可能与 TRS 患者认知功能障碍的严重程度相关。需要进一步研究以阐明精神分裂症治疗反应与认知功能障碍之间的关系。
