Caravaggio Fernando, Borlido Carol, Wilson Alan, Graff-Guerrero Ariel
Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada; Institute of Medical Science, University of Toronto, 2374 Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada.
Clin Chim Acta. 2015 Sep 20;449:60-2. doi: 10.1016/j.cca.2015.03.020. Epub 2015 Mar 23.
Using positron emission tomography (PET) it is possible to estimate endogenous dopamine (DA) occupying D2/3 receptors (D2/3R) in the living human brain. Persons with schizophrenia (SZ) (previously medicated and naïve) have increased endogenous DA occupying D2/3R in the caudate. It is unknown whether currently medicated patients demonstrate increased DA levels at D2/3R. Moreover, DA levels have not been estimated in SZ using agonist radiotracers, which may offer a more sensitive quantification over antagonists.
Using the agonist radiotracer [(11)C]-(+)-PHNO, DA levels were estimated at D2/3R (ΔBP(ND)) in three patients with SZ (male, mean age=30±16). Patients were currently being treated long-term with Olanzapine (147±88 nmol/L). Results were compared to ten healthy controls (HCs).
Medicated persons with SZ had greater ΔBP(ND) in the left caudate (U=2, Z=-2.20, p=.03) and right putamen (U=2, Z=-2.20, p=.03). No differences were observed in the ventral striatum or globus pallidus.
It is possible to estimate endogenous DA at D2/3R in SZ patients currently taking antipsychotics. Despite medication, patients continue to have increased endogenous DA at D2/3R. This lends more biological support to the clinical observation that relapses in symptoms can occur in the face of complete antipsychotic discontinuation. Future studies with larger samples are warranted.
利用正电子发射断层扫描(PET)技术能够估计活体人类大脑中内源性多巴胺(DA)占据D2/3受体(D2/3R)的情况。精神分裂症(SZ)患者(既往用药和未用药者)尾状核中内源性DA占据D2/3R的比例增加。目前正在服药的患者D2/3R处的DA水平是否升高尚不清楚。此外,尚未使用激动剂放射性示踪剂对SZ患者的DA水平进行估计,而激动剂放射性示踪剂可能比拮抗剂提供更敏感的定量分析。
使用激动剂放射性示踪剂[(11)C]-(+)-PHNO,对3例SZ患者(男性,平均年龄 = 30±16岁)D2/3R处的DA水平(ΔBP(ND))进行估计。患者目前正在接受奥氮平长期治疗(147±88 nmol/L)。将结果与10名健康对照者(HCs)进行比较。
正在服药的SZ患者左尾状核(U = 2,Z = -2.20,p = 0.03)和右壳核(U = 2,Z = -2.20,p = 0.03)的ΔBP(ND)更高。腹侧纹状体或苍白球未观察到差异。
对于目前正在服用抗精神病药物的SZ患者,可以估计其D2/3R处的内源性DA。尽管服用了药物,但患者D2/3R处的内源性DA仍然升高。这为临床观察到的在完全停用抗精神病药物时症状可能复发提供了更多生物学支持。有必要进行更大样本量的未来研究。