Presynaptic Dopamine Capacity in Patients with Treatment-Resistant Schizophrenia Taking Clozapine: An [18F]DOPA PET Study
Presynaptic Dopamine Capacity in Patients with Treatment-Resistant Schizophrenia Taking Clozapine: An [18F]DOPA PET Study
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DOI：
10.1038/npp.2016.258
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发表时间：
2017-03-01
影响因子：
7.6
通讯作者：
Kwon, Jun Soo
中科院分区：
文献类型：
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作者：
Kim, Euitae;Howes, Oliver D.;Kwon, Jun Soo
一些精神分裂症患者对一线抗精神病药物治疗的反应较差，这被称为难治性精神分裂症。对一线抗精神病药物的不同反应可能反映了不同的潜在神经生物学。事实上，先前的一项研究发现，难治性精神分裂症患者的多巴胺合成能力显着降低。然而，在这项研究中，难治性患者的症状非常明显，而有反应的患者则没有症状或症状很小。这项研究无法区分这是一种特质效应还是反映了症状水平的差异。因此，我们的目的是测试是否多巴胺能功能改变的患者治疗耐药的一线药物相对于治疗反应者的历史时，两组相匹配的症状严重程度水平招募治疗耐药患者目前表现出较低的症状严重程度与氯氮平治疗。健康对照组（n = 12），氯氮平治疗的患者（n = 12）谁没有响应的一线抗精神病药物，和患者谁响应的一线抗精神病药物（n = 12）被招募。参与者的年龄、性别和症状严重程度在患者组中相匹配。使用[F-18]DOPA PET测量参与者的多巴胺合成能力。我们发现，与对一线治疗有反应的患者相比，用氯氮平治疗的患者显示出较低的多巴胺合成能力（Cohen d=0.9191（全纹状体）、0.7781（联合纹状体）、1.0344（边缘纹状体）和1.0189（感觉运动纹状体），这与多巴胺能功能与治疗反应相关的假设一致。这表明，不同的神经生物学可能是治疗抵抗性精神分裂症的基础，多巴胺合成能力可能是预测治疗反应性的有用生物标志物。
Some patients with schizophrenia show poor response to first-line antipsychotic treatments and this is termed treatment-resistant schizophrenia The differential response to first-line antipsychotic drugs may reflect a different underlying neurobiology. Indeed, a previous study found dopamine synthesis capacity was significantly lower in patients with treatment-resistant schizophrenia However, in this study, the treatment-resistant patients were highly symptomatic, whereas the responsive patients showed no or minimal symptoms. The study could not distinguish whether this was a trait effect or reflected the difference in symptom levels. Thus, we aimed to test whether dopaminergic function is altered in patients with a history of treatment resistance to first-line drugs relative to treatment responders when both groups are matched for symptom severity levels by recruiting treatment-resistant patients currently showed low symptom severity with the clozapine treatment. Healthy controls (n = 12), patients treated with clozapine (n = 12) who had not responded to first-line antipsychotics, and patients who had responded to first-line antipsychotics (n = 12) were recruited. Participants were matched for age and sex and symptomatic severity level in patient groups. Participants' dopamine synthesis capacity was measured by using [F-18]DOPA PET. We found that patients treated with clozapine show lower dopamine synthesis capacity than patients who have responded to first-line treatment (Cohen's d=0.9191 (whole striatum), 0.7781 (associative striatum), 1.0344 (limbic striatum), and 1.0189 (sensorimotor striatum) in line with the hypothesis that the dopaminergic function is linked to treatment response. This suggests that a different neurobiology may underlie treatment-resistant schizophrenia and that dopamine synthesis capacity may be a useful biomarker to predict treatment responsiveness.