Department of Psychiatry, University of Oxford, Oxford, UK.
Oxford Health NHS Foundation Trust, Oxford, UK.
Psychopharmacology (Berl). 2023 Aug;240(8):1719-1734. doi: 10.1007/s00213-023-06395-7. Epub 2023 Jun 20.
Emotion regulation (ER) difficulties have been previously described in bipolar disorder (BD). Whilst lithium has been shown to be effective in the treatment of BD, the mechanisms underlying lithium's effect on mood stabilisation remain unclear.
Unravelling lithium's effect on psychological processes impaired in BD, such as ER, could address this translational gap and inform the development of new treatments.
This study investigated the neural effects of lithium (800mg) on ER in 33 healthy volunteers in a double-blind between-groups design, randomised to lithium (n=17) or placebo (n=16) for 11 days. At treatment completion, participants underwent 3-Tesla fMRI scan whilst performing an ER task.
Reappraisal reduced negative affect across groups and led to the expected increase in frontal brain activity. Participants receiving lithium showed (1) decreased activation in prefrontal and posterior parietal cortices and connectivity between the fronto-limbic network (Z>2.3, p<0.05 corrected); and (2) increased activity in the right superior temporal gyrus (Z>3.1, p<0.05 corrected) and connectivity between the right medial temporal gyrus (MTG) and left middle frontal gyrus (Z>2.3, p<0.05 corrected) during reappraisal. Further effects of lithium were found in response to negative picture presentation, whereby an anticorrelation was found between the left amygdala and the frontal cortex, and greater connectivity between the right MTG and the bilateral medial prefrontal cortex extending into the paracingulate gyrus, compared to placebo (Z>2.3, p < 0.05 corrected).
These results show a potential effect of lithium on ER through its effects on activity and connectivity, and further elaborate the neural underpinnings of cognitive reappraisal. Future work should investigate longer term effects of lithium on ER in BD, ultimately benefitting the development of novel and more effective treatments.
情绪调节（ER）困难已在双相情感障碍（BD）中被描述。虽然锂已被证明对 BD 的治疗有效，但锂对情绪稳定的作用机制仍不清楚。
阐明锂对 BD 中受损的心理过程（如 ER）的影响，可以解决这一转化差距，并为新的治疗方法的发展提供信息。
本研究采用双盲分组设计，将 33 名健康志愿者随机分为锂（n=17）或安慰剂（n=16）治疗组，为期 11 天，研究锂对 ER 的神经影响。治疗结束时，参与者接受 3T 磁共振成像（fMRI）扫描，同时执行 ER 任务。
再评价在各组中均减少了负性情绪，并导致额叶脑活动的预期增加。服用锂的参与者表现出（1）前额叶和后顶叶皮质的激活减少，以及额-边缘网络之间的连接减少（Z>2.3，p<0.05 校正）；（2）右侧上颞回（Z>3.1，p<0.05 校正）和右侧颞中回（MTG）与左侧额中回（Z>2.3，p<0.05 校正）之间的连接增加，在再评价期间。在对负性图片呈现的反应中，还发现了锂的进一步作用，即左杏仁核与额叶之间存在反相关，并且与安慰剂相比，右侧 MTG 与双侧前额叶皮层之间的连接更强，延伸到旁中央回（Z>2.3，p<0.05 校正）。
这些结果表明，锂通过对活动和连接的影响对 ER 产生潜在影响，进一步阐述了认知再评价的神经基础。未来的工作应该研究锂对 BD 中 ER 的长期影响，最终有益于开发新的、更有效的治疗方法。
