Department of Psychiatry, The University of Iowa, United States; Iowa Neuroscience Institute, The University of Iowa, United States; Department of Radiology, The University of Iowa, United States.
Department of Psychiatry, The University of Iowa, United States; Department of Epidemiology, The University of Iowa, United States.
J Affect Disord. 2023 Nov 1;340:269-279. doi: 10.1016/j.jad.2023.08.018. Epub 2023 Aug 8.
The neural underpinnings of bipolar disorder (BD) remain poorly understood. The cerebellum is ideally positioned to modulate emotional regulation circuitry yet has been understudied in BD. Literature suggests differences in cerebellar activity and metabolism in BD, however findings on structural differences remain contradictory. Potential reasons include combining BD subtypes, small sample sizes, and potential moderators such as genetics, adverse childhood experiences (ACEs), and pharmacotherapy.
We collected 3 T MRI scans from participants with (N = 131) and without (N = 81) BD type I, as well as blood and questionnaires. We assessed differences in cerebellar volumes and explored potentially influential factors.
The cerebellar cortex was smaller bilaterally in participants with BD. Polygenic propensity score did not predict any cerebellar volumes, suggesting that non-genetic factors may have greater influence on the cerebellar volume difference we observed in BD. Proportionate cerebellar white matter volumes appeared larger with more ACEs, but this may result from reduced ICV. Time from onset and symptom burden were not associated with cerebellar volumes. Finally, taking sedatives was associated with larger cerebellar white matter and non-significantly larger cortical volume.
This study was cross-sectional, limiting interpretation of possible mechanisms. Most of our participants were White, which could limit the generalizability. Additionally, we did not account for potential polypharmacy interactions.
These findings suggest that external factors, such as sedatives and childhood experiences, may influence cerebellum structure in BD and may mask underlying differences. Accounting for such variables may be critical for consistent findings in future studies.
双相情感障碍（BD）的神经基础仍知之甚少。小脑的位置非常适合调节情绪调节回路，但在 BD 中研究较少。文献表明 BD 中存在小脑活动和代谢的差异，但结构差异的发现仍然存在矛盾。潜在的原因包括合并 BD 亚型、样本量小以及潜在的调节剂，如遗传、不良童年经历（ACEs）和药物治疗。
我们从患有（N=131）和不患有（N=81）BD 型 I 的参与者中收集了 3T MRI 扫描，以及血液和问卷。我们评估了小脑体积的差异，并探讨了潜在的影响因素。
BD 患者的小脑皮层双侧均较小。多基因倾向评分不能预测任何小脑体积，这表明非遗传因素可能对我们在 BD 中观察到的小脑体积差异有更大的影响。随着 ACE 数量的增加，比例性小脑白质体积似乎更大，但这可能是由于 ICV 减少所致。发病时间和症状负担与小脑体积无关。最后，服用镇静剂与较大的小脑白质和非显著较大的皮质体积有关。
本研究为横断面研究，限制了对可能机制的解释。我们的大多数参与者都是白人，这可能会限制其普遍性。此外，我们没有考虑潜在的多药相互作用。
这些发现表明，外部因素，如镇静剂和童年经历，可能会影响 BD 中的小脑结构，并可能掩盖潜在的差异。在未来的研究中，考虑这些变量可能是至关重要的。
