Wulff Sanne, Pinborg Lars Hageman, Svarer Claus, Jensen Lars Thorbjørn, Nielsen Mette Ødegaard, Allerup Peter, Bak Nikolaj, Rasmussen Hans, Frandsen Erik, Rostrup Egill, Glenthøj Birte Yding
Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Psychiatric Center Glostrup, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen, Denmark;
Neurobiology Research Unit (NRU), Rigshospitalet, University of Copenhagen, Denmark;
Schizophr Bull. 2015 Sep;41(5):1143-52. doi: 10.1093/schbul/sbu220. Epub 2015 Feb 18.
One of best validated findings in schizophrenia research is the association between blockade of dopamine D2 receptors and the effects of antipsychotics on positive psychotic symptoms. The aim of the present study was to examine correlations between baseline striatal D(2/3) receptor binding potential (BP(p)) values and treatment outcome in a cohort of antipsychotic-naïve first-episode schizophrenia patients. Additionally, we wished to investigate associations between striatal dopamine D(2/3) receptor blockade and alterations of negative symptoms as well as functioning and subjective well-being. Twenty-eight antipsychotic-naïve schizophrenia patients and 26 controls were included in the study. Single-photon emission computed tomography (SPECT) with [(123)I]iodobenzamide ([(123)I]-IBZM) was used to examine striatal D(2/3) receptor BP(p). Patients were examined before and after 6 weeks of treatment with the D(2/3) receptor antagonist amisulpride. There was a significant negative correlation between striatal D(2/3) receptor BP(p) at baseline and improvement of positive symptoms in the total group of patients. Comparing patients responding to treatment to nonresponders further showed significantly lower baseline BP(p) in the responders. At follow-up, the patients demonstrated a negative correlation between the blockade and functioning, whereas no associations between blockade and negative symptoms or subjective well-being were observed. The results show an association between striatal BP(p) of dopamine D(2/3) receptors in antipsychotic-naïve first-episode patients with schizophrenia and treatment response. Patients with a low BP(p) have a better treatment response than patients with a high BP(p). The results further suggest that functioning may decline at high levels of dopamine receptor blockade.
精神分裂症研究中得到最佳验证的发现之一是多巴胺D2受体阻断与抗精神病药物对阳性精神病性症状的作用之间的关联。本研究的目的是在一组未使用过抗精神病药物的首发精神分裂症患者中,检查基线纹状体D(2/3)受体结合潜能(BP(p))值与治疗结果之间的相关性。此外,我们希望研究纹状体多巴胺D(2/3)受体阻断与阴性症状的改变以及功能和主观幸福感之间的关联。28名未使用过抗精神病药物的精神分裂症患者和26名对照者被纳入研究。使用[(123)I]碘苄胺([(123)I]-IBZM)单光子发射计算机断层扫描(SPECT)来检查纹状体D(2/3)受体BP(p)。患者在使用D(2/3)受体拮抗剂氨磺必利治疗6周前后接受检查。在患者总组中,基线时纹状体D(2/3)受体BP(p)与阳性症状的改善之间存在显著负相关。将治疗有反应的患者与无反应的患者进行比较,进一步显示有反应者的基线BP(p)显著更低。在随访时,患者表现出阻断与功能之间的负相关,而未观察到阻断与阴性症状或主观幸福感之间的关联。结果显示,在未使用过抗精神病药物的首发精神分裂症患者中,纹状体多巴胺D(2/3)受体的BP(p)与治疗反应之间存在关联。BP(p)低的患者比BP(p)高的患者有更好的治疗反应。结果进一步表明,在多巴胺受体阻断水平较高时,功能可能会下降。