Ketamine has distinct electrophysiological and behavioral effects in depressed and healthy subjects.
Ketamine has distinct electrophysiological and behavioral effects in depressed and healthy subjects.
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DOI：
10.1038/s41380-018-0028-2
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发表时间：
2019-07
影响因子：
11
通讯作者：
Zarate CA Jr
中科院分区：
文献类型：
--
作者：
Nugent AC;Ballard ED;Gould TD;Park LT;Moaddel R;Brutsche NE;Zarate CA Jr
在一项0.5 mg/kg氯胺酮的双盲、安慰剂对照、随机交叉试验中，使用脑磁图（MEG）的伽马功率作为35例未用药的重度抑郁症（MDD）受试者和25例健康对照受试者体内平衡的替代指标，评估氯胺酮的作用机制。MDD受试者显示抑郁症状显著改善，健康对照受试者显示抑郁症状中度但显著增加，持续至氯胺酮给药后1天。氯胺酮给药后，两组均显示静息伽马功率增加。在MDD受试者中，伽马功率与抗抑郁作用的大小无关。然而，发现基线伽马功率可调节氯胺酮给药后伽马功率与抗抑郁药应答之间的关系;具体而言，在基线伽马较低的MDD受试者中，较高的氯胺酮给药后伽马功率与较好的应答相关，而在基线伽马较高的MDD受试者中，两者之间的关系相反。这种关系在参与网络的多个区域中观察到，这些网络假设参与MDD的病理生理学。这一发现表明生物亚型的基础上的方向稳态失调，并推断氯胺酮的作用机制，从健康对照的研究有重要意义。
Ketamine’s mechanism of action was assessed using gamma power from magnetoencephalography (MEG) as a proxy measure for homeostatic balance in 35 unmedicated subjects with major depressive disorder (MDD) and 25 healthy controls enrolled in a double-blind, placebo-controlled, randomized cross-over trial of 0.5 mg/kg ketamine. MDD subjects showed significant improvements in depressive symptoms, and healthy control subjects exhibited modest but significant increases in depressive symptoms for up to one day after ketamine administration. Both groups showed increased resting gamma power following ketamine. In MDD subjects, gamma power was not associated with the magnitude of the antidepressant effect. However, baseline gamma power was found to moderate the relationship between post-ketamine gamma power and antidepressant response; specifically, higher post-ketamine gamma power was associated with better response in MDD subjects with lower baseline gamma, with an inverted relationship in MDD subjects with higher baseline gamma. This relationship was observed in multiple regions involved in networks hypothesized to be involved in the pathophysiology of MDD. This finding suggests biological subtypes based on the direction of homeostatic dysregulation and has important implications for inferring ketamine’s mechanism of action from studies of healthy controls alone.
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影响因子：
82.9
作者：
Drysdale AT;Grosenick L;Downar J;Dunlop K;Mansouri F;Meng Y;Fetcho RN;Zebley B;Oathes DJ;Etkin A;Schatzberg AF;Sudheimer K;Keller J;Mayberg HS;Gunning FM;Alexopoulos GS;Fox MD;Pascual-Leone A;Voss HU;Casey BJ;Dubin MJ;Liston C
通讯作者：
Liston C
影响因子：
4.3
作者：
Gramfort A;Luessi M;Larson E;Engemann DA;Strohmeier D;Brodbeck C;Goj R;Jas M;Brooks T;Parkkonen L;Hämäläinen M
通讯作者：
Hämäläinen M
影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
DOI：
10.4088/jcp.09m05327blu
发表时间：
2010-12
期刊：
The Journal of clinical psychiatry
影响因子：
--
作者：
DiazGranados N;Ibrahim LA;Brutsche NE;Ameli R;Henter ID;Luckenbaugh DA;Machado-Vieira R;Zarate CA Jr
通讯作者：
Zarate CA Jr
DOI：
10.1017/s1461145714000959
发表时间：
2014-11-01
影响因子：
4.8
作者：
Anderson, Paul M.;Pinault, Didier;Jones, Nigel C.
通讯作者：
Jones, Nigel C.