Brain entropy and neurotrophic molecular markers accompanying clinical improvement after ketamine: Preliminary evidence in adolescents with treatment-resistant depression.
Brain entropy and neurotrophic molecular markers accompanying clinical improvement after ketamine: Preliminary evidence in adolescents with treatment-resistant depression.
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脑熵和神经营养分子标记物伴随氯胺酮治疗后临床改善：青少年难治性抑郁症的初步证据。
DOI：
10.1177/0269881120928203
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Cullen KR
中科院分区：
文献类型：
--
作者：
Roy AV;Thai M;Klimes-Dougan B;Westlund Schreiner M;Mueller BA;Albott CS;Lim KO;Fiecas M;Tye SJ;Cullen KR
目前的理论表明，难治性抑郁症（TRD）涉及神经可塑性受损，导致认知和神经僵化，临床改善可能需要增加大脑的灵活性和适应性。在这项假设生成研究中，我们试图在 TRD 青少年的开放标签氯胺酮试验背景下确定大脑灵活性与临床变化相关的初步证据，重点关注神经灵活性的两个有希望的候选标志物：（a）静息态功能磁共振成像（fMRI）信号的熵； (b) 外周血单核细胞中胰岛素刺激的哺乳动物雷帕霉素靶点 (mTOR) 和糖原合酶 3-β (GSK3β) 的磷酸化。我们收集了 13 名 TRD 青少年在 2 周内注射 6 次氯胺酮前后的静息态功能磁共振成像数据和血液样本。可用的氯胺酮治疗前/治疗后数据来自 11 名青少年的成像数据和 10 名青少年的分子信号传导数据。我们检查了治疗反应与中枢和外周灵活性标记物变化之间的相关性。抑郁症的减轻与伏隔核熵的增加相关。后续分析表明生理变化与治疗反应相关。与治疗无反应者 (n=6) 相比，反应者 (n=5) 在氯胺酮治疗后伏核熵增加更大，治疗后胰岛素/mTOR/GSK3β 信号传导也更大。这些数据提供了初步证据，表明神经灵活性的变化可能是患有 TRD 的青少年服用氯胺酮后症状缓解的基础。未来需要使用足够动力的样本进行研究，以确认静息态熵和胰岛素刺激的 mTOR 和 GSK3β 作为大脑灵活性标记和未来临床试验的候选目标。氯胺酮治疗难治性抑郁症青少年 https://clinicaltrials.gov/ct2/show/NCT02078817 NCT02078817
Current theory suggests that treatment-resistant depression (TRD) involves impaired neuroplasticity resulting in cognitive and neural rigidity, and that clinical improvement may require increasing brain flexibility and adaptability. In this hypothesis-generating study, we sought to identify preliminary evidence of brain flexibility correlates of clinical change within the context of an open-label ketamine trial in adolescents with TRD, focusing on two promising candidate markers of neural flexibility: (a) entropy of resting-state functional magnetic resonance imaging (fMRI) signals; and (b) insulin-stimulated phosphorylation of mammalian target of rapamycin (mTOR) and glycogen synthase-3-beta (GSK3β) in peripheral blood mononuclear cells. We collected resting-state functional magnetic resonance imaging data and blood samples from 13 adolescents with TRD before and after a series of six ketamine infusions over 2 weeks. Usable pre/post ketamine data were available from 11 adolescents for imaging and from 10 adolescents for molecular signaling. We examined correlations between treatment response and changes in the central and peripheral flexibility markers. Depression reduction correlated with increased nucleus accumbens entropy. Follow-up analyses suggested that physiological changes were associated with treatment response. In contrast to treatment non-responders (n=6), responders (n=5) showed greater increase in nucleus accumbens entropy after ketamine, together with greater post-treatment insulin/mTOR/GSK3β signaling. These data provide preliminary evidence that changes in neural flexibility may underlie symptom relief in adolescents with TRD following ketamine. Future research with adequately powered samples is needed to confirm resting-state entropy and insulin-stimulated mTOR and GSK3β as brain flexibility markers and candidate targets for future clinical trials. Ketamine in adolescents with treatment-resistant depression https://clinicaltrials.gov/ct2/show/NCT02078817 NCT02078817
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影响因子：
15.9
作者：
Holtzheimer, Paul E.;Mayberg, Helen S.
通讯作者：
Mayberg, Helen S.
影响因子：
5.7
作者：
Bassett, Danielle S.;Nelson, Brent G.;Mueller, Bryon A.;Camchong, Jazmin;Lim, Kelvin O.
通讯作者：
Lim, Kelvin O.
影响因子：
11
作者：
Francis TC;Chandra R;Gaynor A;Konkalmatt P;Metzbower SR;Evans B;Engeln M;Blanpied TA;Lobo MK
通讯作者：
Lobo MK
影响因子：
11
作者：
Bessa, J. M.;Ferreira, D.;Sousa, N.
通讯作者：
Sousa, N.
DOI：
10.1001/jama.2017.3826
发表时间：
2017-04-18
期刊：
JAMA
影响因子：
--
作者：
Friedrich, M J
通讯作者：
Friedrich, M J