Assessment of Relationship of Ketamine Dose With Magnetic Resonance Spectroscopy of Glx and GABA Responses in Adults With Major Depression

Milak, Matthew S.; Rashid, Rain; Dong, Zhengchao; Kegeles, Lawrence S.; Grunebaum, Michael F.; Ogden, R. Todd; Lin, Xuejing; Mulhern, Stephanie T.; Suckow, Raymond F.; Cooper, Thomas B.; Keilp, John G.; Mao, Xiangling; Shungu, Dikoma C.; Mann, J. John

doi:10.1001/jamanetworkopen.2020.13211

Cited by 40 publications

(27 citation statements)

References 73 publications

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“…While our small sample size limited the ability to assess between group differences in the Glu response between scan days, we replicate our previous findings with ketamine (21), finding that DCS combined with lurasidone, appears to diminish the Glx or glutamate response and this effect correlates with degree of antidepressant effect. A reduced stress response is consistent with preclinical studies, indicating that NMDAR antagonist related antidepressant response may produce a resilience effect (49).…”

Section: Discussionsupporting

confidence: 85%

“…For this reason, we did not focus on Glx, nor report Gln. This limits the direct comparison to our Glx results in prior studies (21,27). Better spectral fitting methods need to be developed to improve the fitting of Glu, Gln, and Glx.…”

Section: Discussionmentioning

confidence: 93%

“…Glx was analyzed as a secondary measure. Based on pharmacokinetics ( 39 – 41 ) of DCS, our prior finding of the 1 H MRS peak at ~35 min DCS post-dose ( 27 ) and our prior ketamine study using peak level ( 21 ), Glu 1 H MRS peak level was used, defined as a mean from 30 to 46 min post drug. We used Cr as a reference for the relative quantification of Glu and expressed the outcome measure from 1 H MRS as Glu/Cr.…”

Section: Methodsmentioning

confidence: 99%

“…In our recently published, placebo-controlled, dose-finding, randomized clinical trial of ketamine ( 21 ), we found that improvement in MDD had a positive linear relationship with ketamine dose and blood level, and a negative correlation with Glx response. Reduction of Glx mediated the relationship of ketamine dose and level with antidepressant response.…”

Section: Introductionmentioning

confidence: 92%

“…In previous studies, we used proton magnetic resonance spectroscopy ( 1 H MRS) to quantify ketamine effects on Glx (a combination of glutamate (Glu) and glutamine resonance signals: Glu+glutamine) in the ventromedial prefrontal cortex, along with the adjacent anterior cingulate cortex (vmPFC/ACC) in both healthy (19) and depressed (20,21) individuals. Our focus on the vmPFC and the ACC stems from extensive research implicating these regions in the pathogenesis of mood disorders (22)(23)(24) and microdialysis rodent (25,26) studies suggesting that the glutamatergic surge in response to NMDAR antagonists is maximal in the vmPFC.…”

Section: Introductionmentioning

confidence: 99%

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Relationship of Brain Glutamate Response to D-Cycloserine and Lurasidone to Antidepressant Response in Bipolar Depression: A Pilot Study

et al. 2021

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N-methyl-D-aspartate glutamate-receptor (NMDAR) antagonists such as ketamine have demonstrated efficacy in both major depressive disorder (MDD) and bipolar disorder depression (BP-D). We have previously reported that reduction in Glx (glutamate + glutamine) in the ventromedial prefrontal cortex/anterior cingulate cortex (vmPFC/ACC), measured by proton magnetic resonance spectroscopy (1H MRS) at 3T during a ketamine infusion, mediates the relationship of ketamine dose and blood level to improvement in depression. In the present study, we assessed the impact of D-cycloserine (DCS), an oral NMDAR antagonist combined with lurasidone in BP-D on both glutamate and Glx. Subjects with DSM-V BP-D-I/II and a Montgomery-Asberg Depression Rating Scale (MADRS) score>17, underwent up to three 1H MRS scans. During Scan 1, subjects were randomized to receive double-blind lurasidone 66 mg or placebo. During Scan 2, all subjects received single-blind DCS 950 mg + lurasidone 66 mg, followed by 4 weeks of open label phase of DCS+lurasidone and an optional Scan 3. Five subjects received lurasidone alone and three subjects received placebo for Scan 1. Six subjects received DCS+lurasidone during Scan 2. There was no significant baseline or between treatment-group differences in acute depression improvement or glutamate response. In Scan 2, after a dose of DCS+lurasidone, peak change in glutamate correlated negatively with improvement from baseline MADRS (r = −0.83, p = 0.04). There were no unexpected adverse events. These preliminary pilot results require replication but provide further support for a link between antidepressant effect and a decrease in glutamate by the NMDAR antagonist class of antidepressants.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Relationship of Brain Glutamate Response to D-Cycloserine and Lurasidone to Antidepressant Response in Bipolar Depression: A Pilot Study

et al. 2021

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Proton magnetic resonance spectroscopy thermometry: Impact of separately acquired full water or partially suppressed water data on quantification and measurement error

2022

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In proton magnetic resonance spectroscopy (1H MRS) thermometry, separately acquired full water and partially suppressed water are commonly used for measuring temperature. This paper compares these two approaches. Single‐voxel 1H MRS data were collected on a 3‐T GE scanner from 26 human subjects. Every subject underwent five continuous MRS sessions, each separated by a 2‐min phase. Each MRS session lasted 13 min and consisted of two free induction decays (FIDs) without water suppression (with full water [FW or w]) and 64 FIDs with partial water suppression (with partially suppressed water [PW or w’]). Frequency differences between the two FWs, the first two PWs, the second FW and the first PW (FW2, PW1), or between averaged water ( wav′) and N‐acetylaspartate (NAA), were measured. Intrasubject and intersubject variations of the frequency differences were used as a metric for the error in temperature measurement. The intrasubject variations of frequency differences between FW2 and PW1 ()fw2−fw1′, calculated from the five MRS sessions for each subject, were larger than those between the two FWs or between the first two PWs (p = 1.54 x 10−4 and p = 1.72 x 10−4, respectively). The mean values of intrasubject variations of ()fw2−fw1′ for all subjects were 4.7 and 4.5 times those of ()fw2−fw1 and ()fw2′−fw1′, respectively. The intrasubject variations of the temperatures based on frequency differences, ()fw2−fNAA or ( fw1′−fNAA), were about 2.5 times greater than those based on averaged water and NAA frequencies true(fwitalicav′−fNAA). The mean temperature measured from true(fwitalicav′−fNAA) (n = 26) was 0.29°C lower than that measured from ()fw2−fNAA and was 0.83°C higher than that from ( fw1′−fNAA). It was concluded that the use of separately acquired unsuppressed or partially suppressed water signals may result in large errors in frequency and, consequently, temperature measurement.

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Ketamine and Other Glutamate Receptor Antagonists As Fast-Actin

Chen

Tsai

2022

Neuromethods

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Assessment of Relationship of Ketamine Dose With Magnetic Resonance Spectroscopy of Glx and GABA Responses in Adults With Major Depression

Cited by 40 publications

References 73 publications

Relationship of Brain Glutamate Response to D-Cycloserine and Lurasidone to Antidepressant Response in Bipolar Depression: A Pilot Study

Relationship of Brain Glutamate Response to D-Cycloserine and Lurasidone to Antidepressant Response in Bipolar Depression: A Pilot Study

Proton magnetic resonance spectroscopy thermometry: Impact of separately acquired full water or partially suppressed water data on quantification and measurement error

Ketamine and Other Glutamate Receptor Antagonists As Fast-Actin

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