PMID- 28939975
OWN - NLM
STAT- MEDLINE
DCOM- 20190913
LR  - 20191008
IS  - 0171-2004 (Print)
IS  - 0171-2004 (Linking)
VI  - 253
DP  - 2019
TI  - Ketamine-Induced Glutamatergic Mechanisms of Sleep and Wakefulness: Insights for 
      Developing Novel Treatments for Disturbed Sleep and Mood.
PG  - 337-358
LID - 10.1007/164_2017_51 [doi]
AB  - Ketamine, a drug with rapid antidepressant effects and well-described effects on 
      slow wave sleep (SWS), is a useful intervention for investigating sleep-wake 
      mechanisms involved in novel therapeutics. The drug rapidly (within minutes to 
      hours) reduces depressive symptoms in individuals with major depressive disorder 
      (MDD) or bipolar disorder (BD), including those with treatment-resistant 
      depression. Ketamine treatment elevates extracellular glutamate in the prefrontal 
      cortex. Glutamate, in turn, plays a critical role as a proximal element in a 
      ketamine-initiated molecular cascade that increases synaptic strength and 
      plasticity, which ultimately results in rapidly improved mood. In MDD, rapid 
      antidepressant response to ketamine is related to decreased waking as well as 
      increased total sleep, SWS, slow wave activity (SWA), and rapid eye movement 
      (REM) sleep. Ketamine also increases brain-derived neurotrophic factor (BDNF) 
      levels. In individuals with MDD, clinical response to ketamine is predicted by 
      low baseline delta sleep ratio, a measure of deficient early night production of 
      SWS. Notably, there are important differences between MDD and BD that may be 
      related to the effects of diagnosis or of mood stabilizers. Consistent with its 
      effects on clock-associated molecules, ketamine alters the timing and amplitude 
      of circadian activity patterns in rapid responders versus non-responders with 
      MDD, suggesting that it affects mood-dependent central neural circuits. Molecular 
      interactions between sleep homeostasis and clock genes may mediate the rapid and 
      durable elements of clinical response to ketamine and its active metabolite.
FAU - Duncan, Wallace C Jr
AU  - Duncan WC Jr
AD  - Experimental Therapeutics and Pathophysiology Branch, National Institute of 
      Mental Health, National Institute of Health, Bethesda, MD, 20892, USA. 
      wduncan@mail.nih.gov.
FAU - Ballard, Elizabeth D
AU  - Ballard ED
AD  - Experimental Therapeutics and Pathophysiology Branch, National Institute of 
      Mental Health, National Institute of Health, Bethesda, MD, 20892, USA.
FAU - Zarate, Carlos A
AU  - Zarate CA
AD  - Experimental Therapeutics and Pathophysiology Branch, National Institute of 
      Mental Health, National Institute of Health, Bethesda, MD, 20892, USA.
LA  - eng
GR  - ZIA MH002857-12/Intramural NIH HHS/United States
PT  - Journal Article
PL  - Germany
TA  - Handb Exp Pharmacol
JT  - Handbook of experimental pharmacology
JID - 7902231
RN  - 0 (Antidepressive Agents)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Antidepressive Agents/therapeutic use
MH  - *Depressive Disorder, Major/drug therapy
MH  - Humans
MH  - *Ketamine/therapeutic use
MH  - Sleep/drug effects
MH  - Wakefulness
PMC - PMC5866161
MID - NIHMS909905
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor (BDNF)
OT  - Circadian
OT  - Major depressive disorder
OT  - Neuroplasticity
OT  - Slow wave sleep
OT  - Suicidality
EDAT- 2017/09/25 06:00
MHDA- 2019/09/14 06:00
PMCR- 2019/03/23
CRDT- 2017/09/24 06:00
PHST- 2017/09/25 06:00 [pubmed]
PHST- 2019/09/14 06:00 [medline]
PHST- 2017/09/24 06:00 [entrez]
PHST- 2019/03/23 00:00 [pmc-release]
AID - 10.1007/164_2017_51 [doi]
PST - ppublish
SO  - Handb Exp Pharmacol. 2019;253:337-358. doi: 10.1007/164_2017_51.