de Kwaasteniet Bart P, Pinto Chedwa, Ruhé Henricus G, van Wingen Guido A, Booij Jan, Denys Damiaan
Department of Psychiatry, Academic Medical Center, Amsterdam, the Netherlands; Brain Imaging Center, Academic Medical Center, Amsterdam, the Netherlands.
Department of Psychiatry, MC groep, Lelystad, the Netherlands.
PLoS One. 2014 Nov 20;9(11):e113612. doi: 10.1371/journal.pone.0113612. eCollection 2014.
Several studies demonstrated improvement of depressive symptoms in treatment resistant depression (TRD) after administering dopamine agonists which suggest abnormal dopaminergic neurotransmission in TRD. However, the role of dopaminergic signaling through measurement of striatal dopamine D(2/3) receptor (D2/3R) binding has not been investigated in TRD subjects. We used [(123)I]IBZM single photon emission computed tomography (SPECT) to investigate striatal D2/3R binding in TRD. We included 6 severe TRD patients, 11 severe TRD patients on antipsychotics (TRD AP group) and 15 matched healthy controls. Results showed no significant difference (p = 0.75) in striatal D2/3R availability was found between TRD patients and healthy controls. In the TRD AP group D2/3R availability was significantly decreased (reflecting occupancy of D2/3Rs by antipsychotics) relative to TRD patients and healthy controls (p<0.001) but there were no differences in clinical symptoms between TRD AP and TRD patients. This preliminary study therefore does not provide evidence for large differences in D2/3 availability in severe TRD patients and suggests this TRD subgroup is not characterized by altered dopaminergic transmission. Atypical antipsychotics appear to have no clinical benefit in severe TRD patients who remain depressed, despite their strong occupancy of D2/3Rs.
多项研究表明，在给予多巴胺激动剂后，难治性抑郁症（TRD）患者的抑郁症状有所改善，这表明TRD中存在异常的多巴胺能神经传递。然而，尚未在TRD患者中通过测量纹状体多巴胺D(2/3)受体（D2/3R）结合来研究多巴胺能信号传导的作用。我们使用[(123)I]IBZM单光子发射计算机断层扫描（SPECT）来研究TRD患者的纹状体D2/3R结合情况。我们纳入了6名重度TRD患者、11名正在服用抗精神病药物的重度TRD患者（TRD AP组）和15名匹配的健康对照者。结果显示，TRD患者与健康对照者之间纹状体D2/3R的可利用性无显著差异（p = 0.75）。与TRD患者和健康对照者相比，TRD AP组的D2/3R可利用性显著降低（反映抗精神病药物对D2/3R的占据）（p<0.001），但TRD AP组和TRD患者之间的临床症状没有差异。因此，这项初步研究没有提供证据表明重度TRD患者的D2/3可利用性存在巨大差异，并表明该TRD亚组的特征不是多巴胺能传递改变。非典型抗精神病药物似乎对尽管D2/3R被其强烈占据但仍处于抑郁状态的重度TRD患者没有临床益处。
