Neuroprotection after a first episode of mania: a randomized controlled maintenance trial comparing the effects of lithium and quetiapine on grey and white matter volume.
Neuroprotection after a first episode of mania: a randomized controlled maintenance trial comparing the effects of lithium and quetiapine on grey and white matter volume.
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DOI：
10.1038/tp.2016.281
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发表时间：
2017-01-24
影响因子：
6.8
通讯作者：
Yücel M
中科院分区：
文献类型：
--
作者：
Berk M;Dandash O;Daglas R;Cotton SM;Allott K;Fornito A;Suo C;Klauser P;Liberg B;Henry L;Macneil C;Hasty M;McGorry P;Pantelis C;Yücel M
锂和喹硫平是双相情感障碍的有效治疗方法，但它们对人类潜在的神经保护作用仍不清楚。在首发躁狂 (FEM) 患者 (n=26) 前瞻性队列中进行了一项单盲等效随机对照维持试验，纵向比较锂和喹他平对灰质和白质体积的假定保护作用。还收集了健康对照样本（n=20）。使用结构 MRI 扫描，研究了基线时的体素灰质和白质体积以及治疗反应随时间的变化。患者在三个时间点（基线、3 个月和 12 个月随访）进行评估，而健康对照在两个时间点（基线和 12 个月随访）进行评估。患者被随机分配接受锂（血清水平 0.6mmoll−1，n=20）或喹硫平（灵活剂量高达每天 800mg，n=19）单药治疗。在基线时，与健康对照受试者相比，FEM 患者的眶额皮层、前扣带回、额下回和小脑的灰质减少。此外，患者双侧内囊白质体积减少（t1,66>3.20，P<0.01）。纵向上，仅左侧内囊白质存在显着的治疗×时间效应（F2,112=8.54，P<0.01）。事后测试表明，与基线相比，12 个月后锂剂比喹硫平更能有效减缓白质体积减少的进展（t1,24=3.76，P<0.01）。我们的数据支持锂而非喹硫平疗法在限制 FEM 后病程早期白质减少方面的作用。
Lithium and quetiapine are effective treatments for bipolar disorder, but their potential neuroprotective effects in humans remain unclear. A single blinded equivalence randomized controlled maintenance trial was conducted in a prospective cohort of first-episode mania (FEM) patients (n=26) to longitudinally compare the putative protective effects of lithium and quetapine on grey and white matter volume. A healthy control sample was also collected (n=20). Using structural MRI scans, voxel-wise grey and white matter volumes at baseline and changes over time in response to treatment were investigated. Patients were assessed at three time points (baseline, 3 and 12-month follow-up), whereas healthy controls were assessed at two time points (baseline and 12-month follow-up). Patients were randomized to lithium (serum level 0.6 mmol l−1, n=20) or quetiapine (flexibly dosed up to 800 mg per day, n=19) monotherapy. At baseline, compared with healthy control subjects, patients with FEM showed reduced grey matter in the orbitofrontal cortex, anterior cingulate, inferior frontal gyrus and cerebellum. In addition, patients had reduced internal capsule white matter volume bilaterally (t1,66>3.20, P<0.01). Longitudinally, there was a significant treatment × time effect only in the white matter of the left internal capsule (F2,112=8.54, P<0.01). Post hoc testing showed that, compared with baseline, lithium was more effective than quetiapine in slowing the progression of white matter volume reduction after 12 months (t1,24=3.76, P<0.01). Our data support the role of lithium but not quetiapine therapy in limiting white matter reduction early in the illness course after FEM.
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