Emsley R, Asmal L, du Plessis S, Chiliza B, Phahladira L, Kilian S
Department of Psychiatry, Faculty of Medicine and Health Sciences,Stellenbosch University,Cape Town,South Africa.
Psychol Med. 2017 Sep;47(12):2187-2196. doi: 10.1017/S0033291717000642. Epub 2017 Mar 28.
Progressive brain volume reductions have been described in schizophrenia, and an association with antipsychotic exposure has been reported.
We compared percentage changes in grey and white matter volume from baseline to month 12 in 23 previously antipsychotic-naïve patients with a first episode of schizophrenia or schizophreniform disorder who were treated with the lowest effective dose of flupenthixol decanoate depot formulation, with 53 matched healthy individuals. Total antipsychotic dose was precisely calculated and its relationship with brain volume changes investigated. Relationships between volumetric changes and treatment were further investigated in terms of treatment response (changes in psychopathology and functionality) and treatment-related adverse-events (extrapyramidal symptoms and weight gain).
Excessive cortical volume reductions were observed in patients [-4.6 (6.6)%] v. controls [-1.12 (4.0)%] (p = 0.009), with no significant group differences for changes in subcortical grey matter and white matter volumes. In a multiple regression model, the only significant predictor of cortical volume change was total antipsychotic dose received (p = 0.04). Cortical volume change was not significantly associated with the changes in psychopathology, functionality, extrapyramidal symptoms and body mass index or age, gender and duration of untreated psychosis.
Brain volume reductions associated with antipsychotic treatment are not restricted to poor outcome patients and occur even with the lowest effective dose of antipsychotic. The lack of an association with poor treatment response or treatment-related adverse effects counts against cortical volume reductions reflecting neurotoxicity, at least in the short term. On the other hand, the volume reductions were not linked to the therapeutic benefits of antipsychotics.
精神分裂症患者存在进行性脑容量减少的情况，且有报道称其与抗精神病药物暴露有关。
我们比较了23例既往未使用过抗精神病药物、首次发作精神分裂症或精神分裂症样障碍且接受最低有效剂量癸酸氟奋乃静长效注射剂治疗的患者，与53例匹配的健康个体从基线到第12个月时灰质和白质体积的百分比变化。精确计算了抗精神病药物的总剂量，并研究了其与脑容量变化的关系。还根据治疗反应（精神病理学和功能的变化）以及治疗相关不良事件（锥体外系症状和体重增加）进一步研究了体积变化与治疗之间的关系。
与对照组相比，患者出现了过度的皮质体积减少[-4.6（6.6）%]对比对照组[-1.12（4.0）%]（p = 0.009），皮质下灰质和白质体积变化在两组间无显著差异。在多元回归模型中，皮质体积变化的唯一显著预测因素是接受的抗精神病药物总剂量（p = 0.04）。皮质体积变化与精神病理学、功能、锥体外系症状、体重指数或年龄、性别以及未治疗精神病持续时间的变化均无显著关联。
与抗精神病药物治疗相关的脑容量减少并不局限于预后不良的患者，即使使用最低有效剂量抗精神病药物时也会发生。至少在短期内，缺乏与不良治疗反应或治疗相关不良反应的关联不利于将皮质体积减少视为神经毒性的反映。另一方面，体积减少与抗精神病药物的治疗益处无关。
