Translational Developmental Neuroscience Section, Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, TU Dresden, Dresden, Germany.
Department of Internal Medicine III, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany; Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
Metabolism. 2024 Oct;159:155983. doi: 10.1016/j.metabol.2024.155983. Epub 2024 Jul 30.
Steatotic liver disease (SLD) is characterized by excessive accumulation of lipids in the liver. It is associated with elevated risk of hepatic and cardiometabolic diseases, as well as mental disorders such as depression. Previous studies revealed global gray matter reduction in SLD. To investigate a possible shared neurobiology with depression, we examined liver fat-related regional gray matter alterations in SLD and its most significant clinical subgroup metabolic dysfunction-associated steatotic liver disease (MASLD).
We analyzed regional cortical thickness and area obtained from brain MRI in 29,051 participants in UK Biobank. Liver fat amount was computed as proton density fat fraction (PDFF) from liver MRI scans. We examined the relationship between brain structure and PDFF, adjusting for sociodemographic, physical, lifestyle, and environmental factors, as well as alcohol intake and a spectrum of cardiometabolic covariates. Finally, we compared patterns of brain alterations in SLD/MASLD and major depressive disorder (MDD) using previously published results.
PDFF-related gray matter alterations were region-specific, involving both increases and decreases in cortical thickness, and increased cortical area. In several regions, PDFF effects on gray matter could also be attributed to cardiometabolic covariates. However, PDFF was consistently associated with lower cortical thickness in middle and superior temporal regions and higher cortical thickness in pericalcarine and right frontal pole regions. PDFF-related alterations for the SLD and the MASLD group correlated with those observed in MDD (Pearson r = 0.45-0.54, p < 0.01).
These findings suggest the presence of shared biological mechanisms linking MDD to SLD and MASLD. They might explain the well-known elevated risk of depression in these groups and support early lifestyle interventions and treatment of metabolic risk factors for the successful management of the interconnected diseases depression and SLD/MASLD.
脂肪性肝病（SLD）的特征是肝脏内脂质过度积累。它与肝和心脏代谢疾病以及精神障碍（如抑郁症）的风险升高有关。先前的研究表明 SLD 存在全脑灰质减少。为了研究与抑郁症可能存在的共同神经生物学机制，我们检查了 SLD 及其最显著的临床亚组代谢功能障碍相关脂肪性肝病（MASLD）中与肝脂肪相关的区域性灰质改变。
我们分析了英国生物银行 29051 名参与者的大脑 MRI 获得的皮质厚度和区域。肝脏脂肪量是从肝脏 MRI 扫描中质子密度脂肪分数（PDFF）计算得出的。我们在调整了社会人口学、身体、生活方式和环境因素以及酒精摄入量和一系列心脏代谢因素后，检查了大脑结构与 PDFF 之间的关系。最后，我们使用先前发表的结果比较了 SLD/MASLD 和重度抑郁症（MDD）之间的大脑改变模式。
PDFF 相关的灰质改变具有区域特异性，涉及皮质厚度的增加和减少以及皮质面积的增加。在几个区域，PDFF 对灰质的影响也可以归因于心脏代谢因素。然而，PDFF 与中颞叶和上颞叶区域的皮质厚度降低以及中央旁回和右侧额极区域的皮质厚度增加始终相关。SLD 和 MASLD 组的 PDFF 相关改变与 MDD 中观察到的改变相关（Pearson r=0.45-0.54，p<0.01）。
这些发现表明，将 MDD 与 SLD 和 MASLD 联系起来的存在共同的生物学机制。它们可能解释了这些人群中众所周知的抑郁风险升高，并支持早期生活方式干预和代谢危险因素的治疗，以成功管理相互关联的疾病抑郁和 SLD/MASLD。
