Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
J Psychiatry Neurosci. 2012 Sep;37(5):333-43. doi: 10.1503/jpn.110143.
Smaller hippocampal volumes relative to controls are among the most replicated neuroimaging findings in individuals with unipolar but not bipolar depression. Preserved hippocampal volumes in most studies of participants with bipolar disorder may reflect potential neuroprotective effects of lithium (Li).
To investigate hippocampal volumes in patients with bipolar disorder while controlling for Li exposure, we performed a meta-analysis of neuroimaging studies that subdivided patients based on the presence or absence of current Li treatment. To achieve the best coverage of literature, we categorized studies based on whether all or a majority, or whether no or a minority of patients were treated with Li. Hippocampal volumes were compared by combining standardized differences between means (Cohen d) from individual studies using random-effects models.
Overall, we analyzed data from 101 patients with bipolar disorder in the Li group, 245 patients in the non-Li group and 456 control participants from 16 studies. Both the left and right hippocampal volumes were significantly larger in the Li group than in controls (Cohen d = 0.53, 95% confidence interval [CI] 0.18 to 0.88; Cohen d = 0.51, 95% CI 0.21 to 0.81, respectively) or the non-Li group (Cohen d = 0.93, 95% CI 0.56 to 1.31; Cohen d = 1.07, 95% CI 0.70 to 1.45, respectively), which had smaller left and right hippocampal volumes than the control group (Cohen d = -0.36, 95% CI -0.55 to -0.17; Cohen d = -0.38, 95% CI -0.63 to -0.13, respectively). There was no evidence of publication bias.
Missing information about the illness burden or lifetime exposure to Li and polypharmacy in some studies may have contributed to statistical heterogeneity in some analyses.
When exposure to Li was minimized, patients with bipolar disorder showed smaller hippocampal volumes than controls or Li-treated patients. Our findings provide indirect support for the negative effects of bipolar disorder on hippocampal volumes and are consistent with the putative neuroprotective effects of Li. The preserved hippocampal volumes among patients with bipolar disorder in most individual studies and all previous meta-analyses may have been related to the inclusion of Li-treated participants.
与单相抑郁患者相比，双相抑郁患者的海马体体积较小，这是神经影像学研究中最具重复性的发现之一。在大多数双相障碍患者的研究中，海马体体积保持不变，这可能反映了锂（Li）的潜在神经保护作用。
为了在控制 Li 暴露的情况下研究双相障碍患者的海马体体积，我们对根据当前 Li 治疗情况对患者进行细分的神经影像学研究进行了荟萃分析。为了最好地涵盖文献，我们根据所有或大多数患者是否接受 Li 治疗或是否只有少数或没有患者接受 Li 治疗对研究进行了分类。通过使用随机效应模型合并来自个体研究的均值之间标准化差异（Cohen d），对海马体体积进行比较。
总体而言，我们分析了来自 16 项研究的 101 名 Li 组双相障碍患者、245 名非 Li 组患者和 456 名对照参与者的数据。Li 组的左、右海马体体积均明显大于对照组（Cohen d = 0.53，95%置信区间 [CI] 0.18 至 0.88；Cohen d = 0.51，95% CI 0.21 至 0.81）或非 Li 组（Cohen d = 0.93，95% CI 0.56 至 1.31；Cohen d = 1.07，95% CI 0.70 至 1.45），而对照组的左、右海马体体积较小（Cohen d = -0.36，95% CI -0.55 至 -0.17；Cohen d = -0.38，95% CI -0.63 至 -0.13）。没有证据表明存在发表偏倚。
一些研究中缺少关于疾病负担或终生 Li 暴露和多药治疗的信息，这可能导致一些分析中的统计异质性。
当最小化 Li 暴露时，双相障碍患者的海马体体积小于对照组或 Li 治疗患者。我们的发现间接支持了双相障碍对海马体体积的负面影响，并且与 Li 的潜在神经保护作用一致。大多数单独研究和所有先前荟萃分析中双相障碍患者的海马体体积保持不变，这可能与纳入 Li 治疗参与者有关。
