Department of Psychiatry,New York University School of Medicine,New York, NY,USA.
Department of Psychiatry,Hofstra Northwell School of Medicine,Hempstead, NY,USA.
Psychol Med. 2017 Jul;47(10):1706-1718. doi: 10.1017/S0033291717000137. Epub 2017 Feb 14.
Hippocampal dysfunction is considered central to many neurobiological models of schizophrenia, yet there are few longitudinal in vivo neuroimaging studies that have investigated the relationship between antipsychotic treatment and morphologic changes within specific hippocampal subregions among patients with psychosis.
A total of 29 patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure received structural neuroimaging examinations at illness onset and then following 12 weeks of treatment with either risperidone or aripiprazole in a double-blind randomized clinical trial. In addition, 29 healthy volunteers received structural neuroimaging examinations at baseline and 12-week time points. We manually delineated six hippocampal subregions [i.e. anterior cornu ammonis (CA) 1-3, posterior CA1-3, subiculum, dentate gyrus/CA4, entorhinal cortex, and fimbria] from 3T magnetic resonance images using an established method with high inter- and intra-rater reliability.
Following antipsychotic treatment patients demonstrated significant reductions in dentate gyrus/CA4 volume and increases in subiculum volume. Healthy volunteers demonstrated non-significant volumetric changes in these subregions across the two time points. We observed a significant quadratic (i.e. inverted U) association between changes in dentate gyrus/CA4 volume and cumulative antipsychotic dosage between the scans.
This study provides the first evidence to our knowledge regarding longitudinal in vivo volumetric changes within specific hippocampal subregions in patients with psychosis following antipsychotic treatment. The finding of a non-linear relationship between changes in dentate gyrus/CA4 subregion volume and antipsychotic exposure may provide new avenues into understanding dosing strategies for therapeutic interventions relevant to neurobiological models of hippocampal dysfunction in psychosis.
海马功能障碍被认为是许多精神分裂症神经生物学模型的核心，然而，很少有纵向的体内神经影像学研究调查抗精神病药物治疗与精神病患者特定海马亚区形态变化之间的关系。
总共 29 名首次发作精神分裂症且以前很少或没有接受过抗精神病药物暴露的患者，在疾病发作时和接受利培酮或阿立哌唑双盲随机临床试验治疗 12 周后接受结构神经影像学检查。此外，29 名健康志愿者在基线和 12 周时间点接受了结构神经影像学检查。我们使用一种具有高度内部和内部可靠性的既定方法，从 3T 磁共振图像手动描绘六个海马亚区[即前角 CA1-3、后角 CA1-3、下托、齿状回/CA4、内嗅皮质和穹窿]。
抗精神病药物治疗后，患者的齿状回/CA4 体积减少，下托体积增加。健康志愿者在这两个时间点的这些亚区没有观察到体积变化。我们观察到在扫描之间，齿状回/CA4 体积的变化与累积抗精神病药物剂量之间存在显著的二次（即倒 U）关联。
本研究首次提供了关于抗精神病药物治疗后精神病患者特定海马亚区体积纵向变化的证据。在齿状回/CA4 亚区体积变化与抗精神病药物暴露之间发现的非线性关系，可能为理解与精神分裂症中海马功能障碍神经生物学模型相关的治疗干预的剂量策略提供了新途径。
