Patients with chronic schizophrenia often display enlarged striatal volumes, and antipsychotic drugs may contribute via the dopamine D2/3 receptor (D2/3R) blockade. Separating the effects of disease from medication is challenging due to the lack of a proper placebo-group. To address this, we conducted a longitudinal study of antipsychotic-naïve, first-episode schizophrenia patients to test the hypothesis that selective blockade of D2/3R would induce a dose-dependent striatal volume increase. Twenty-one patients underwent structural magnetic resonance imaging (sMRI), single-photon emission computed tomography (SPECT), and symptom severity ratings before and after six weeks of amisulpride treatment. Twenty-three matched healthy controls underwent sMRI and baseline SPECT. Data were analyzed using repeated measures and multiple regression analyses. Correlations between symptom severity decrease, volume changes, dose and receptor occupancy were explored. Striatal volumes did not differ between patients and controls at baseline or follow-up, but a significant group-by-time interaction was found (p = 0.01). This interaction was explained by a significant striatal volume increase of 2.1% in patients (Cohens d = 0.45). Striatal increase was predicted by amisulpride dose, but not by either D2/3R occupancy or baseline symptom severity. A significant reduction in symptom severity was observed at a mean dose of 233.3 (SD = 109.9) mg, corresponding to D2/3R occupancy of 44.65%. Reduction in positive symptoms correlated significantly with striatal volume increase, driven by reductions in hallucinations. Our data demonstrate a clear link between antipsychotic treatment and striatal volume increase in antipsychotic-naïve schizophrenia patients. Moreover, the treatment-induced striatal volume increase appears clinically relevant by correlating to reductions in core symptoms of schizophrenia.

中文翻译：

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首发抗精神病药初治精神分裂症患者在选择性多巴胺 D2/3 受体阻断六周后纹状体体积增加

慢性精神分裂症患者经常表现出纹状体体积增大，抗精神病药物可能通过多巴胺 D2/3 受体 (D2/3R) 阻断起作用。由于缺乏适当的安慰剂组，将疾病的影响与药物分开是具有挑战性的。为了解决这个问题，我们对初次服用抗精神病药的首发精神分裂症患者进行了一项纵向研究，以检验选择性阻断 D2/3R 会诱导剂量依赖性纹状体体积增加的假设。21 名患者在氨磺必利治疗前后六周接受了结构磁共振成像 (sMRI)、单光子发射计算机断层扫描 (SPECT) 和症状严重程度评级。23 名匹配的健康对照接受了 sMRI 和基线 SPECT。使用重复测量和多元回归分析来分析数据。探讨了症状严重程度降低、体积变化、剂量和受体占有率之间的相关性。在基线或随访时，患者和对照之间的纹状体体积没有差异，但发现了显着的组间交互作用（p = 0.01）。这种相互作用可以通过患者纹状体体积显着增加 2.1% 来解释（Cohens d = 0.45）。纹状体增加是由氨磺必利剂量预测的，但不是由 D2/3R 占用率或基线症状严重程度预测的。在平均剂量为 233.3 (SD = 109.9) mg 时观察到症状严重程度的显着降低，对应于 44.65% 的 D2/3R 占用率。由于幻觉减少，阳性症状的减少与纹状体体积增加显着相关。我们的数据表明，抗精神病药物治疗与未使用抗精神病药物的精神分裂症患者纹状体体积增加之间存在明显联系。此外，通过与精神分裂症核心症状的减少相关联，治疗引起的纹状体体积增加似乎具有临床相关性。