Association of Molecular Senescence Markers in Late-Life Depression With Clinical Characteristics and Treatment Outcome.
Association of Molecular Senescence Markers in Late-Life Depression With Clinical Characteristics and Treatment Outcome.
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DOI：
10.1001/jamanetworkopen.2022.19678
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发表时间：
2022-06-01
影响因子：
13.8
通讯作者：
Lenze, Eric J.
中科院分区：
文献类型：
--
作者：
Diniz, Breno S.;Mulsant, Benoit H.;Reynolds, Charles F., III;Blumberger, Daniel M.;Karp, Jordan F.;Butters, Meryl A.;Mendes-Silva, Ana Paula;Vieira, Erica L.;Tseng, George;Lenze, Eric J.
这项非随机临床试验评估了老年抑郁症患者分子衰老标志物与治疗缓解之间的关系。与衰老相关分泌表型（SASP）相关的标志物是否与老年人重度抑郁发作的治疗缓解相关？在这项416名参与者的非随机临床试验中，较高的SASP指数（与SASP相关的22个生物标志物的综合评分）与抗抑郁治疗缓解的可能性较低显著相关。这些发现表明，分子和细胞衰老异常可能是导致老年人重度抑郁发作治疗结果恶化的一个假定机制。许多老年抑郁症患者在接受抗抑郁药物治疗后并没有得到缓解，而且晚年抑郁症（LLD）的细胞衰老标志与更严重的抑郁症、更严重的执行功能障碍和更高的医疗疾病负担相关。由于这些临床特征与LLD的缓解有关，因此分子和细胞衰老异常可能是该人群治疗反应不良的可能生物学机制。研究衰老相关分泌表型（SASP）指数是否与老年人抑郁发作缓解的可能性相关。2009年8月至2014年8月在宾夕法尼亚州匹兹堡进行了一项非随机、开放标签的临床试验；密苏里州的圣路易斯；根据精神障碍诊断和统计手册（第四版，文本修订）的诊断标准，加拿大安大略省多伦多的老年人目前患有重度抑郁症。根据2021年3月进行的临床试验存档血浆样本，报告了生物标志物分析数据。数据分析时间为2021年6月至11月。文拉法辛缓释（剂量范围从37.5毫克至300毫克每日）长达12周。使用临床数据和血液样本测量了基于复合生物标志物的指数（SASP指数）与老年抑郁症患者治疗缓解之间的关系。416名参与者平均（SD）年龄为60.02（7.13）岁；64%（265名参与者）是自我报告的女性，Montgomery-Asberg抑郁评定量表的平均（SD）得分为26.6（5.7）。较高的SASP指数评分与较高的不缓解率独立相关，SASP指数评分每增加1个单位，不缓解的几率增加19%（校正优势比为1.19;95% CI, 1.05-1.35; P = 0.006）。相反，没有单独的SASP因素与LLD的缓解相关。使用临床数据和来自一项非随机临床试验的血液样本，本研究的结果表明，用SASP指数测量的分子和细胞衰老与LLD较差的治疗结果相关。将反映相关生物学过程的指数得分与其他分子、临床和神经影像学标记相结合，可能有助于评估抗抑郁药治疗结果。这些发现为以衰老为目标，以提高LLD缓解率的老年科学指导干预措施指明了前进的道路。ClinicalTrials.gov标识符：NCT00892047
This nonrandomized clinical trial evaluates the association between molecular senescence markers and treatment remission in older adults with depression. Are markers associated with the senescence-associated secretory phenotype (SASP) associated with treatment remission in older adults with major depressive episode? In this nonrandomized clinical trial of 416 participants, higher SASP index, a composite score of 22 biomarkers associated with the SASP, was significantly associated with lower likelihood of remission to antidepressant treatment. These findings suggest that molecular and cellular senescence abnormalities could be a putative mechanism associated with worse treatment outcomes in older adults with a major depressive episode. Many older adults with depression do not experience remission with antidepressant treatment, and markers of cellular senescence in late-life depression (LLD) are associated with greater severity of depression, greater executive dysfunction, and higher medical illness burden. Since these clinical characteristics are associated with remission in LLD, molecular and cellular senescence abnormalities could be a possible biological mechanism underlying poor treatment response in this population. To examine whether the senescence-associated secretory phenotype (SASP) index was associated with the likelihood of remission from a depressive episode in older adults. A nonrandomized, open-label clinical trial was conducted between August 2009 and August 2014 in Pittsburgh, Pennsylvania; St Louis, Missouri; and Toronto, Ontario, Canada, with older adults in a current major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) diagnostic criteria. Data from biomarker analyses were reported according to the clinical trial archived plasma samples run in March 2021. Data were analyzed from June to November 2021. Venlafaxine extended release (dose ranging from 37.5 mg to 300 mg daily) for up to 12 weeks. The association between a composite biomarker-based index (SASP index) and treatment remission in older adults with major depression was measured using clinical data and blood samples. There were 416 participants with a mean (SD) age of 60.02 (7.13) years; 64% (265 participants) were self-reported female, and the mean (SD) Montgomery-Asberg Depression Rating Scale score was 26.6 (5.7). Higher SASP index scores were independently associated with higher rates of nonremission, with an increase of 1 unit in the SASP index score increasing the odds of nonremission by 19% (adjusted odds ratio, 1.19; 95% CI, 1.05-1.35; P = .006). In contrast, no individual SASP factors were associated with remission in LLD. Using clinical data and blood samples from a nonrandomized clinical trial, the results of this study suggest that molecular and cellular senescence, as measured with the SASP index, is associated with worse treatment outcomes in LLD. Combining this index score reflecting interrelated biological processes with other molecular, clinical, and neuroimaging markers may be useful in evaluating antidepressant treatment outcomes. These findings inform a path forward for geroscience-guided interventions targeting senescence to improve remission rates in LLD. ClinicalTrials.gov Identifier: NCT00892047
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影响因子：
4
作者：
Diniz BS;Fisher-Hoch S;McCormick J
通讯作者：
McCormick J
影响因子：
64.5
作者：
de Cabo R;Carmona-Gutierrez D;Bernier M;Hall MN;Madeo F
通讯作者：
Madeo F
影响因子：
3.7
作者：
de la Torre-Luque, Alejandro;Luis Ayuso-Mateos, Jose;Lopez-Garcia, Pilar
通讯作者：
Lopez-Garcia, Pilar
影响因子：
4.8
作者：
Diniz, Breno Satler;Lin, Chien-Wei;Butters, Meryl A.
通讯作者：
Butters, Meryl A.
DOI：
10.1038/s41569-018-0064-2
发表时间：
2018-09
期刊：
Nature reviews. Cardiology
影响因子：
--
作者：
Ferrucci L;Fabbri E
通讯作者：
Fabbri E