Thiel Katharina, Flinkenflügel Kira, Grotegerd Dominik, Jurischka Christoph, Hubbert Julia, Hahn Tim, Leehr Elisabeth J, Meinert Hannah, Schrammen Elisabeth, Thomas-Odenthal Florian, Usemann Paula, Teutenberg Lea, Straube Benjamin, Alexander Nina, Jamalabadi Hamidreza, Jansen Andreas, Stein Frederike, Bauer Michael, Pfennig Andrea, Mennigen Eva, Kanske Philipp, Förster Katharina, Nenadić Igor, Kircher Tilo, Meinert Susanne, Dannlowski Udo
Institute for Translational Psychiatry, University of Münster, Münster, German.
Department of Clinical Psychology and Psychotherapy, University of Göttingen, Göttingen, Germany.
Eur Psychiatry. 2025 Sep 15;68(1):e148. doi: 10.1192/j.eurpsy.2025.10105.
Bipolar disorder (BD) is assumed to follow a progressive course, conceptualized through staging models. It is unclear whether white matter (WM) microstructure abnormalities, central to BD pathophysiology, parallel this development throughout disease progression. This study explored the link between WM and disease progression in BD, using a comprehensive approach based on clinical staging models.
This cross-sectional diffusion tensor-imaging study included 153 BD patients and 153 healthy controls (HCs) matched for age, sex, and study site. Using tract-based spatial statistics (TBSS), we examined associations between WM integrity and three criteria: (1) number of manic episodes, (2) remission quality between episodes, and (3) inter-episode global functioning.
Analyses revealed significant fractional anisotropy (FA) differences between early and late stages of BD based on the number of manic episodes ( = 0.003), but not on remission quality ( = 0.075). However, compared to HC, BD patients with persistent symptoms between episodes showed more widespread FA differences ( < 0.001) than those with stable remission ( = 0.031). Regression analyses indicated a positive association between global functioning and FA in euthymic BD patients ( < 0.001).
Results indicated more severe WM disruptions in patients at advanced stages compared to earlier stages of the disease. While these findings may imply changes occurring with disease progression, the cross-sectional design cannot rule out that they instead reflect stable clinical subtypes of varying severity. The results highlight the clinical relevance of WM alterations and the need for longitudinal studies to better understand the neurobiology and complexity of BD.
双相情感障碍（BD）被认为遵循一种渐进性病程，可通过分期模型来概念化。目前尚不清楚作为BD病理生理学核心的白质（WM）微观结构异常是否在疾病进展过程中与这种发展并行。本研究采用基于临床分期模型的综合方法，探讨了BD中WM与疾病进展之间的联系。
这项横断面扩散张量成像研究纳入了153例BD患者和153名年龄、性别及研究地点相匹配的健康对照（HC）。使用基于纤维束的空间统计学（TBSS），我们检查了WM完整性与三个标准之间的关联：（1）躁狂发作次数；（2）发作间的缓解质量；（3）发作间的整体功能。
分析显示，基于躁狂发作次数，BD早期和晚期之间存在显著的各向异性分数（FA）差异（P = 0.003），但在缓解质量方面无差异（P = 0.075）。然而，与HC相比，发作间有持续症状的BD患者比缓解稳定的患者表现出更广泛的FA差异（P < 0.001）。回归分析表明，心境正常的BD患者的整体功能与FA呈正相关（P < 0.001）。
结果表明，与疾病早期相比，晚期患者的WM破坏更严重。虽然这些发现可能意味着随疾病进展发生的变化，但横断面设计不能排除它们反而反映了不同严重程度的稳定临床亚型。这些结果突出了WM改变的临床相关性以及进行纵向研究以更好地理解BD的神经生物学和复杂性的必要性。
