Department of Nuclear Medicine, University of Leipzig, Germany.
Int J Neuropsychopharmacol. 2011 Jun;14(5):606-17. doi: 10.1017/S1461145710001604. Epub 2011 Jan 14.
The pathogenetic role of central serotonin transporters (SERT) in obsessive-compulsive disorder (OCD) has been investigated in vivo by positron emission tomography (PET) or single-photon emission computed tomography (SPECT) studies with inconsistent results. This might reflect methodological differences but possibly also the pathophysiological heterogeneity of the disorder, i.e. the age at onset of OCD. The aim of our study was to compare SERT availability in patients with OCD to healthy controls (HC) taking into account the onset type, other factors and covariates (e.g. SERT genotype, age, depression level, gender). We studied 19 drug-naive OCD patients (36±13 yr, eight females) with early onset (EO-OCD, n=6) or with late onset (LO-OCD, n=13), and 21 HC (38±8 yr, nine females) with PET and the SERT-selective radiotracer [11C]DASB. Statistical models indicated that a variety of covariates and their interaction influenced SERT availability measured by distribution volume ratios (DVR). These models revealed significant effects of onset type on DVR with lower values in LO-OCD (starting at age 18 yr) compared to EO-OCD and HC in limbic (e.g. the amygdala), paralimbic brain areas (the anterior cingulate cortex), the nucleus accumbens and striatal regions, as well as borderline significance in the thalamus and the hypothalamus. The putamen, nucleus accumbens and hypothalamus were found with significant interaction between two SERT gene polymorphisms (SERT-LPR and VNTR). These findings suggest that late but not early onset of OCD is associated with abnormally low SERT availability. In part, functional polymorphisms of the SERT gene might determine the differences.
中枢 5-羟色胺转运体（SERT）在强迫症（OCD）中的致病作用已经通过正电子发射断层扫描（PET）或单光子发射计算机断层扫描（SPECT）研究进行了体内研究，但结果不一致。这可能反映了方法学上的差异，但也可能反映了该疾病的病理生理异质性，即 OCD 的发病年龄。我们的研究目的是比较 OCD 患者和健康对照者（HC）的 SERT 可用性，同时考虑发病类型、其他因素和协变量（例如 SERT 基因型、年龄、抑郁水平、性别）。我们研究了 19 名未经药物治疗的 OCD 患者（36±13 岁，8 名女性），其中 6 名患者为早发性（EO-OCD），13 名患者为晚发性（LO-OCD），并对 21 名 HC（38±8 岁，9 名女性）进行了 PET 和 SERT 选择性放射性示踪剂 [11C]DASB 研究。统计模型表明，多种协变量及其相互作用影响了通过分布容积比（DVR）测量的 SERT 可用性。这些模型显示，发病类型对 DVR 有显著影响，LO-OCD（发病年龄为 18 岁）的 DVR 值低于 EO-OCD 和 HC，在边缘（如杏仁核）、边缘旁脑区（前扣带皮层）、伏隔核和纹状体区域，以及丘脑和下丘脑的结果接近显著。纹状体、伏隔核和下丘脑的结果与 SERT 基因两个多态性（SERT-LPR 和 VNTR）之间存在显著的相互作用。这些发现表明，迟发性但不是早发性 OCD 与 SERT 可用性异常降低有关。部分原因可能是 SERT 基因的功能多态性决定了这些差异。
