Hajek T, Bauer M, Simhandl C, Rybakowski J, O'Donovan C, Pfennig A, König B, Suwalska A, Yucel K, Uher R, Young L T, MacQueen G, Alda M
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
Psychol Med. 2014 Feb;44(3):507-17. doi: 10.1017/S0033291713001165. Epub 2013 May 31.
Neuroimaging studies have demonstrated an association between lithium (Li) treatment and brain structure in human subjects. A crucial unresolved question is whether this association reflects direct neurochemical effects of Li or indirect effects secondary to treatment or prevention of episodes of bipolar disorder (BD).
To address this knowledge gap, we compared manually traced hippocampal volumes in 37 BD patients with at least 2 years of Li treatment (Li group), 19 BD patients with <3 months of lifetime Li exposure over 2 years ago (non-Li group) and 50 healthy controls. All BD participants were followed prospectively and had at least 10 years of illness and a minimum of five episodes. We established illness course and long-term treatment response to Li using National Institute of Mental Health (NIMH) life charts.
The non-Li group had smaller hippocampal volumes than the controls or the Li group (F 2,102 = 4.97, p = 0.009). However, the time spent in a mood episode on the current mood stabilizer was more than three times longer in the Li than in the non-Li group (t(51) = 2.00, p = 0.05). Even Li-treated patients with BD episodes while on Li had hippocampal volumes comparable to healthy controls and significantly larger than non-Li patients (t(43) = 2.62, corrected p = 0.02).
Our findings support the neuroprotective effects of Li. The association between Li treatment and hippocampal volume seems to be independent of long-term treatment response and occurred even in subjects with episodes of BD while on Li. Consequently, these effects of Li on brain structure may generalize to patients with neuropsychiatric illnesses other than BD.
神经影像学研究已证实在人类受试者中锂（Li）治疗与脑结构之间存在关联。一个关键的未解决问题是这种关联反映的是锂的直接神经化学作用，还是双相情感障碍（BD）发作的治疗或预防所继发的间接作用。
为填补这一知识空白，我们比较了37例接受锂治疗至少2年的BD患者（锂组）、19例在2年多前有过不到3个月终生锂暴露的BD患者（非锂组）和50名健康对照者手动追踪的海马体积。所有BD参与者均进行前瞻性随访，患病至少10年且至少有5次发作。我们使用美国国立精神卫生研究所（NIMH）的生命图表确定疾病病程和对锂的长期治疗反应。
非锂组的海马体积小于对照组或锂组（F 2,102 = 4.97，p = 0.009）。然而，锂组在当前情绪稳定剂作用下处于情绪发作的时间是非锂组的三倍多（t(51) = 2.00，p = 0.05）。即使在服用锂期间有BD发作的锂治疗患者，其海马体积与健康对照者相当，且显著大于非锂治疗患者（t(43) = 2.62，校正p = 0.02）。
我们的研究结果支持锂的神经保护作用。锂治疗与海马体积之间的关联似乎独立于长期治疗反应，甚至在服用锂期间有BD发作的受试者中也存在。因此，锂对脑结构的这些作用可能适用于BD以外的神经精神疾病患者。
