Exploratory genome-wide analyses of cortical inhibition, facilitation, and plasticity in late-life depression.
Exploratory genome-wide analyses of cortical inhibition, facilitation, and plasticity in late-life depression.
复制标题
DOI：
10.1038/s41398-023-02532-0
复制
发表时间：
2023-06-30
影响因子：
6.8
通讯作者：
Blumberger, Daniel M.
中科院分区：
文献类型：
--
作者：
Wathra, Rafae A.;Men, Xiaoyu;Elsheikh, Samar S. M.;Marshe, Victoria S.;Rajji, Tarek K.;Lissemore, Jennifer I.;Mulsant, Benoit H.;Karp, Jordan F.;Reynolds, Charles F.;Lenze, Eric J.;Daskalakis, Zafiris J.;Mueller, Daniel J.;Blumberger, Daniel M.
晚年抑郁症（LLD）是一种受遗传因素影响的异质性情绪障碍。皮质生理过程，如皮质抑制、促进和可塑性，可能是疾病的标志，与遗传因素的相关性比与临床表型的相关性更强。因此，探索遗传因素与这些生理过程之间的关系可能有助于表征 LLD 的生物学机制并改善诊断和治疗选择。采用经颅磁刺激 (TMS) 结合肌电图测量 79 名 LLD 参与者的短间隔皮质内抑制 (SICI)、皮质静默期 (CSP)、皮质内促进 (ICF) 和配对联想刺激 (PAS)。我们使用探索性全基因组关联和基于基因的分析来评估这些 TMS 测量的遗传相关性。 MARK4（编码微管亲和力调节激酶 4）和 PPP1R37（编码蛋白磷酸酶 1 调节亚基 37）显示出全基因组范围内与 SICI 的显着关联。 EGFLAM（编码 EGF 样纤连蛋白 III 型和层粘连蛋白 G 结构域）显示出与 CSP 在全基因组范围内的显着关联。没有基因与 ICF 或 PAS 在全基因组范围内显着相关。我们观察了遗传对 LLD 老年人皮质抑制的影响。为了更好地表征遗传对 LLD 皮质生理学的影响，需要进行更大样本量的重复、临床表型亚组的探索以及相关基因型的功能分析。需要开展这项工作来确定皮质抑制是否可以作为生物标志物来提高 LLD 的诊断精度并指导治疗选择。
Late-life depression (LLD) is a heterogenous mood disorder influenced by genetic factors. Cortical physiological processes such as cortical inhibition, facilitation, and plasticity may be markers of illness that are more strongly associated with genetic factors than the clinical phenotype. Thus, exploring the relationship between genetic factors and these physiological processes may help to characterize the biological mechanisms underlying LLD and improve diagnosis and treatment selection. Transcranial magnetic stimulation (TMS) combined with electromyography was used to measure short interval intracortical inhibition (SICI), cortical silent period (CSP), intracortical facilitation (ICF), and paired associative stimulation (PAS) in 79 participants with LLD. We used exploratory genome-wide association and gene-based analyses to assess for genetic correlations of these TMS measures. MARK4 (which encodes microtubule affinity-regulating kinase 4) and PPP1R37 (which encodes protein phosphatase 1 regulatory subunit 37) showed genome-wide significant association with SICI. EGFLAM (which encodes EGF-like fibronectin type III and laminin G domain) showed genome-wide significant association with CSP. No genes met genome-wide significant association with ICF or PAS. We observed genetic influences on cortical inhibition in older adults with LLD. Replication with larger sample sizes, exploration of clinical phenotype subgroups, and functional analysis of relevant genotypes is warranted to better characterize genetic influences on cortical physiology in LLD. This work is needed to determine whether cortical inhibition may serve as a biomarker to improve diagnostic precision and guide treatment selection in LLD.
登录
查看更多内容
影响因子：
3.4
作者：
Eichhammer, P;Langguth, B;Hajak, G
通讯作者：
Hajak, G
影响因子：
3.4
作者：
Cirillo, John;Hughes, James;Semmler, John G.
通讯作者：
Semmler, John G.
影响因子：
3.3
作者：
Di Lazzaro, V.;Manganelli, F.;Uncini, A.
通讯作者：
Uncini, A.
影响因子：
5.5
作者：
Cheeran, Binith;Talelli, Penelope;Rothwell, John C.
通讯作者：
Rothwell, John C.
DOI：
10.1016/j.neucli.2015.12.003
发表时间：
2016-02-01
影响因子：
3
作者：
Cueva, Ana Sofia;Galhardoni, Ricardo;de Andrade, Daniel Ciampi
通讯作者：
de Andrade, Daniel Ciampi