University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands; Radiology Morphological Solutions, Berkel en Rodenrijs, The Netherlands.
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of General Practice, Groningen, The Netherlands.
Brain Behav Immun. 2016 Aug;56:21-33. doi: 10.1016/j.bbi.2015.09.004. Epub 2015 Sep 5.
The hippocampus is one of the brain regions that is involved in several pathophysiological theories about bipolar disorder (BD), such as the neuroinflammation theory and the corticolimbic metabolic dysregulation theory. We compared hippocampal volume and hippocampal metabolites in bipolar I disorder (BD-I) patients versus healthy controls (HCs) with magnetic resonance imaging (MRI) and spectroscopy (MRS). We post hoc investigated whether hippocampal volume and hippocampal metabolites were associated with microglial activation and explored if potential illness modifying factors affected these hippocampal measurements and whether these were associated with experienced mood and functioning.
Twenty-two BD-I patients and twenty-four HCs were included in the analyses. All subjects underwent psychiatric interviews as well as an MRI scan, including a T1 scan and PRESS magnetic resonance spectroscopy (MRS). Volumetric analysis was performed with Freesurfer. MRS quantification was performed with LC Model. A subgroup of 14 patients and 11 HCs also underwent a successful [(11)C]-(R)-PK11195 neuroinflammation positron emission tomography scan.
In contrast to our hypothesis, hippocampal volumes were not decreased in patients compared to HC after correcting for individual whole-brain volume variations. We demonstrated decreased N-acetylaspartate (NAA)+N-acetyl-aspartyl-glutamate (NAAG) and creatine (Cr)+phosphocreatine (PCr) concentrations in the left hippocampus. In the explorative analyses in the left hippocampus we identified positive associations between microglial activation and the NAA+NAAG concentration, between alcohol use and NAA+NAAG concentration, between microglial activation and the depression score and a negative relation between Cr+PCr concentration and experienced occupational disability. Duration of illness associated positively with volume bilaterally.
Compared to HCs, the decreased NAA+NAAG concentration in the left hippocampus of BD-I patients suggests a decreased neuronal integrity in this region. In addition we found a positive relation between microglial activation and neuronal integrity in vivo, corresponding to a differentiated microglial function where some microglia induce apoptosis while others stimulate neurogenesis.
海马体是参与几种双相障碍（BD）病理生理学理论的脑区之一，如神经炎症理论和皮质边缘代谢失调理论。我们使用磁共振成像（MRI）和光谱（MRS）比较了双相 I 型障碍（BD-I）患者与健康对照（HC）的海马体体积和海马体代谢物。我们随后调查了海马体体积和海马体代谢物是否与小胶质细胞激活有关，并探讨了潜在的疾病修饰因素是否影响这些海马体测量值，以及这些因素是否与经历的情绪和功能有关。
22 名 BD-I 患者和 24 名 HC 纳入分析。所有受试者均接受了精神病学访谈以及 MRI 扫描，包括 T1 扫描和 PRESS 磁共振波谱（MRS）。容积分析使用 Freesurfer 进行。MRS 定量使用 LC Model 进行。14 名患者和 11 名 HC 的亚组还进行了成功的 [(11)C]-(R)-PK11195 神经炎症正电子发射断层扫描。
与我们的假设相反，在对个体全脑体积变化进行校正后，患者的海马体体积与 HC 相比并未减少。我们发现在左侧海马体中，N-乙酰天冬氨酸（NAA）+N-乙酰天冬氨酸谷氨酸（NAAG）和肌酸（Cr）+磷酸肌酸（PCr）浓度降低。在左侧海马体的探索性分析中，我们发现小胶质细胞激活与 NAA+NAAG 浓度之间存在正相关，酒精使用与 NAA+NAAG 浓度之间存在正相关，小胶质细胞激活与抑郁评分之间存在负相关，Cr+PCr 浓度与经历职业障碍之间存在负相关。病程与双侧体积呈正相关。
与 HC 相比，BD-I 患者左侧海马体中 NAA+NAAG 浓度降低表明该区域神经元完整性降低。此外，我们发现体内小胶质细胞激活与神经元完整性之间存在正相关，这对应于一种分化的小胶质细胞功能，其中一些小胶质细胞诱导细胞凋亡，而另一些则刺激神经发生。
