Cooper Elena C, Schindler Matthew K, Bar-Or Amit, Brandstadter Rachel B, Calkins Monica E, Gur Ruben, Jacobs Dina A, Markowitz Clyde, Moore Tyler, Naydovich Laura R, Perrone Christopher M, Ruparel Kosha, Spangler Bailey C, Troyan Scott, Shinohara Russell T, Satterthwaite Theodore D, Baller Erica Berlin
Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
BMJ Open. 2025 May 30;15(5):e094733. doi: 10.1136/bmjopen-2024-094733.
Multiple sclerosis (MS) is an immune-mediated neurological disorder that affects one million people in the USA. Up to 50% of patients with MS experience depression, yet the mechanisms of depression in MS remain underinvestigated. MS is characterised by white matter lesions, suggesting that brain network disruption may underlie depression symptoms. Studies of medically healthy participants with depression have described associations between white matter variability and depressive symptoms, but frequently exclude participants with medical comorbidities and thus cannot be extrapolated to people with intracranial diseases. The purpose of this current study is to investigate how brain network disruption underlies depression by learning from the example of MS.
We will obtain structured clinical and cognitive assessments from 250 participants with MS and prospectively evaluate white matter disease burden as a predictor of depressive symptoms. White matter lesion burden will be quantified by identifying streamlines within white matter fascicles that intersect lesions along any portion of their trajectory, classifying these streamlines as injured, and calculating the total volume of injured streamlines to serve as the metric of disease burden.
Ethics approval was obtained from The University of Pennsylvania Institutional Review Board (protocol #853883). The results of this study will be presented at scientific meetings and conferences and published in peer-reviewed journals.
多发性硬化症（MS）是一种免疫介导的神经系统疾病，在美国影响着100万人。高达50%的MS患者会出现抑郁症状，然而MS中抑郁的机制仍未得到充分研究。MS的特征是白质病变，这表明脑网络破坏可能是抑郁症状的基础。对患有抑郁症的健康参与者的研究描述了白质变异性与抑郁症状之间的关联，但这些研究通常排除了患有其他疾病的参与者，因此不能外推到患有颅内疾病的人群。本研究的目的是通过以MS为例，探讨脑网络破坏如何导致抑郁。
我们将对250名MS患者进行结构化临床和认知评估，并前瞻性地评估白质疾病负担作为抑郁症状的预测指标。白质病变负担将通过识别白质束内与病变轨迹任何部分相交的纤维束来量化，将这些纤维束分类为受损纤维束，并计算受损纤维束的总体积作为疾病负担的指标。
本研究已获得宾夕法尼亚大学机构审查委员会的伦理批准（协议编号#853883）。本研究结果将在科学会议上展示，并发表在同行评审期刊上。
