Bellaagh Johansson Tobias, Klahn Anna Luisa, Göteson Andreas, Abé Christoph, Sellgren Carl M, Landén Mikael
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Neuropsychobiology. 2025;84(1):38-47. doi: 10.1159/000542888. Epub 2024 Dec 3.
Bipolar disorder has been associated with significant structural brain changes, potentially driven by central nervous system (CNS) inflammation. This study aimed to investigate the relationship between inflammation biomarkers in cerebrospinal fluid (CSF) and longitudinal structural brain changes.
We included 29 individuals with bipolar disorder and 34 healthy controls, analyzing three selected inflammation-related biomarkers - interleukin-6 (IL-6), interleukin-8 (IL-8), and chitinase-3-like protein 1 (YKL-40) - in both blood serum and CSF. Structural brain changes were assessed through magnetic resonance imaging at two timepoints, focusing on cortical thickness of the middle temporal cortex and inferior frontal gyrus, as well as ventricular volume.
In healthy controls, baseline CSF levels of YKL-40 predicted ventricular enlargement in both hemispheres. Among individuals with bipolar disorder, higher baseline levels of IL-8 were associated with a decline in cortical thickness in the right and left middle temporal cortex, as well as the right inferior frontal gyrus. No significant associations were observed with serum biomarkers.
These findings suggest that CSF IL-8 may contribute to cortical decline in bipolar disorder. The lack of association between serum biomarkers and brain changes highlights the specificity of CNS inflammation in these processes. Additionally, the observed link between CSF YKL-40 and ventricular enlargement in healthy controls may indicate a role of CNS inflammation processes in normal brain aging.
Bipolar disorder has been associated with significant structural brain changes, potentially driven by central nervous system (CNS) inflammation. This study aimed to investigate the relationship between inflammation biomarkers in cerebrospinal fluid (CSF) and longitudinal structural brain changes.
We included 29 individuals with bipolar disorder and 34 healthy controls, analyzing three selected inflammation-related biomarkers - interleukin-6 (IL-6), interleukin-8 (IL-8), and chitinase-3-like protein 1 (YKL-40) - in both blood serum and CSF. Structural brain changes were assessed through magnetic resonance imaging at two timepoints, focusing on cortical thickness of the middle temporal cortex and inferior frontal gyrus, as well as ventricular volume.
In healthy controls, baseline CSF levels of YKL-40 predicted ventricular enlargement in both hemispheres. Among individuals with bipolar disorder, higher baseline levels of IL-8 were associated with a decline in cortical thickness in the right and left middle temporal cortex, as well as the right inferior frontal gyrus. No significant associations were observed with serum biomarkers.
These findings suggest that CSF IL-8 may contribute to cortical decline in bipolar disorder. The lack of association between serum biomarkers and brain changes highlights the specificity of CNS inflammation in these processes. Additionally, the observed link between CSF YKL-40 and ventricular enlargement in healthy controls may indicate a role of CNS inflammation processes in normal brain aging.
双相情感障碍与显著的脑结构变化有关，这可能是由中枢神经系统（CNS）炎症驱动的。本研究旨在探讨脑脊液（CSF）中的炎症生物标志物与脑结构纵向变化之间的关系。
我们纳入了29名双相情感障碍患者和34名健康对照者，分析血清和脑脊液中三种选定的炎症相关生物标志物——白细胞介素-6（IL-6）、白细胞介素-8（IL-8）和几丁质酶-3样蛋白1（YKL-40）。通过在两个时间点进行磁共振成像来评估脑结构变化，重点关注颞中皮质和额下回的皮质厚度以及脑室容积。
在健康对照者中，YKL-40的基线脑脊液水平可预测双侧脑室扩大。在双相情感障碍患者中，较高的IL-8基线水平与右侧和左侧颞中皮质以及右侧额下回的皮质厚度下降有关。未观察到与血清生物标志物有显著关联。
这些发现表明脑脊液IL-8可能导致双相情感障碍患者的皮质萎缩。血清生物标志物与脑变化之间缺乏关联，突出了中枢神经系统炎症在这些过程中的特异性。此外，在健康对照者中观察到的脑脊液YKL-40与脑室扩大之间的联系，可能表明中枢神经系统炎症过程在正常脑老化中起作用。
双相情感障碍与显著的脑结构变化有关，这可能是由中枢神经系统（CNS）炎症驱动的。本研究旨在探讨脑脊液（CSF）中的炎症生物标志物与脑结构纵向变化之间的关系。
我们纳入了29名双相情感障碍患者和34名健康对照者，分析血清和脑脊液中三种选定的炎症相关生物标志物——白细胞介素-6（IL-6）、白细胞介素-8（IL-8）和几丁质酶-3样蛋白1（YKL-40）。通过在两个时间点进行磁共振成像来评估脑结构变化，重点关注颞中皮质和额下回的皮质厚度以及脑室容积。
在健康对照者中，YKL-40的基线脑脊液水平可预测双侧脑室扩大。在双相情感障碍患者中，较高的IL-8基线水平与右侧和左侧颞中皮质以及右侧额下回的皮质厚度下降有关。未观察到与血清生物标志物有显著关联。
这些发现表明脑脊液IL-8可能导致双相情感障碍患者的皮质萎缩。血清生物标志物与脑变化之间缺乏关联，突出了中枢神经系统炎症在这些过程中的特异性。此外，在健康对照者中观察到的值脑脊液YKL-40与脑室扩大之间的联系，可能表明中枢神经系统炎症过程在正常脑老化中起作用。
