Baller Erica B, Sweeney Elizabeth M, Cieslak Matthew C, Robert-Fitzgerald Timothy, Covitz Sydney C, Martin Melissa L, Schindler Matthew K, Bar-Or Amit, Elahi Ameena, Larsen Bart S, Manning Abigail R, Markowitz Clyde E, Perrone Christopher M, Rautman Victoria, Seitz Madeleine M, Detre John A, Fox Michael D, Shinohara Russell T, Satterthwaite Theodore D
Penn Lifespan Informatics and Neuroimaging Center (PennLINC), Philadelphia, PA USA.
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA USA.
medRxiv. 2023 Jun 12:2023.06.09.23291080. doi: 10.1101/2023.06.09.23291080.
Multiple sclerosis (MS) is an immune-mediated neurological disorder that affects nearly one million people in the United States. Up to 50% of patients with MS experience depression.
To investigate how white matter network disruption is related to depression in MS.
Retrospective case-control study of participants who received research-quality 3-tesla neuroimaging as part of MS clinical care from 2010-2018. Analyses were performed from May 1 to September 30, 2022.
Single-center academic medical specialty MS clinic.
Participants with MS were identified via the electronic health record (EHR). All participants were diagnosed by an MS specialist and completed research-quality MRI at 3T. After excluding participants with poor image quality, 783 were included. Inclusion in the depression group () required either: 1) ICD-10 depression diagnosis (F32-F34.*); 2) prescription of antidepressant medication; or 3) screening positive via Patient Health Questionnaire-2 (PHQ-2) or -9 (PHQ-9). Age- and sex-matched nondepressed comparators (-) included persons with no depression diagnosis, no psychiatric medications, and were asymptomatic on PHQ-2/9.
Depression diagnosis.
We first evaluated if lesions were preferentially located within the depression network compared to other brain regions. Next, we examined if MS+Depression patients had greater lesion burden, and if this was driven by lesions specifically in the depression network. Outcome measures were the burden of lesions (e.g., impacted fascicles) within a network and across the brain. Secondary measures included between-diagnosis lesion burden, stratified by brain network. Linear mixed-effects models were employed.
Three hundred-eighty participants met inclusion criteria, (232 MS+Depression: age[SD]=49[12], %females=86; 148 MS-Depression: age[SD]=47[13], %females=79). MS lesions preferentially affected fascicles within versus outside the depression network (β=0.09, 95% CI=0.08-0.10, P<0.001). MS+Depression had more white matter lesion burden (β=0.06, 95% CI=0.01-0.10, P=0.015); this was driven by lesions within the depression network (β=0.02, 95% CI 0.003-0.040, P=0.020).
We provide new evidence supporting a relationship between white matter lesions and depression in MS. MS lesions disproportionately impacted fascicles in the depression network. MS+Depression had more disease than MS-Depression, which was driven by disease within the depression network. Future studies relating lesion location to personalized depression interventions are warranted.
多发性硬化症（MS）是一种免疫介导的神经疾病，在美国影响着近100万人。高达50%的MS患者会出现抑郁。
研究白质网络破坏与MS患者抑郁之间的关系。
对2010年至2018年作为MS临床护理一部分接受研究级3特斯拉神经成像的参与者进行回顾性病例对照研究。分析于2022年5月1日至9月30日进行。
单中心学术医学专科MS诊所。
通过电子健康记录（EHR）识别MS参与者。所有参与者均由MS专科医生诊断，并在3T下完成研究级MRI检查。排除图像质量差的参与者后，纳入783人。纳入抑郁组（）需要满足以下任一条件：1）ICD-10抑郁诊断（F32-F34.*）；2）抗抑郁药物处方；或3）通过患者健康问卷-2（PHQ-2）或-9（PHQ-9）筛查呈阳性。年龄和性别匹配的非抑郁对照者（-）包括无抑郁诊断、无精神科药物且PHQ-2/9无症状的人。
抑郁诊断。
我们首先评估与其他脑区相比，病变是否优先位于抑郁网络内。接下来，我们检查MS+抑郁患者是否有更大的病变负担，以及这是否由抑郁网络中的特定病变驱动。结局指标是网络内和全脑的病变负担（例如，受影响的束）。次要指标包括诊断间病变负担，按脑网络分层。采用线性混合效应模型。
380名参与者符合纳入标准，（232名MS+抑郁：年龄[标准差]=49[12]，女性比例=86%；148名MS-抑郁：年龄[标准差]=47[13]，女性比例=79%）。MS病变优先影响抑郁网络内而非网络外的束（β=0.09，95%置信区间=0.08-0.10，P<0.001）。MS+抑郁患者有更多的白质病变负担（β=0.06，95%置信区间=0.01-0.10，P=0.015）；这是由抑郁网络内的病变驱动的（β=0.02，95%置信区间0.003-0.040，P=0.020）。
我们提供了新的证据支持MS中白质病变与抑郁之间的关系。MS病变对抑郁网络中的束影响不成比例。MS+抑郁患者比MS-抑郁患者病情更严重，这是由抑郁网络内的疾病驱动的。未来有必要开展将病变位置与个性化抑郁干预相关联 的研究。
