In vivo proton magnetic resonance spectroscopic examination of benzodiazepine action in humans

Yıldız, Ayşegül; Gökmen, Ali Necati; Küçükgüçlü, Semih; Yurt, Ayşegül; Olson, David P.; Rouse, Elizabeth D.; Moore, Constance M.; Dıcle, Oğuz; Renshaw, Perry F.

doi:10.1016/j.pscychresns.2010.07.004

Cited by 9 publications

(11 citation statements)

References 25 publications

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“…We believe manic symptom severity in the study population might have contributed the neurochemical signal related with the disease state as well as its treatment (41, 42). Optimization of the spectral data acquisition via restricted head motion might have further contributed to the detection of the anticipated spectral signal (28). …”

Section: Discussionmentioning

confidence: 99%

“…Following 3 weeks of a double-blind treatment period, 1 H MR spectra were obtained again (within 12 hours after the last dose of treatment with no concomitant psychotropic medication administered). For enabling reliable data acquisition in the manic state, all patients were sedated with midazolam (0.03 mg/kg) and fentanyl (2 µg/kg) administration just before both MR scans (28). As reported previously, the chemical sedation was found safe and did not cause any alterations in the measured metabolites of the brain (28).…”

Section: Methodsmentioning

confidence: 99%

“…For enabling reliable data acquisition in the manic state, all patients were sedated with midazolam (0.03 mg/kg) and fentanyl (2 µg/kg) administration just before both MR scans (28). As reported previously, the chemical sedation was found safe and did not cause any alterations in the measured metabolites of the brain (28). 1 H MRS measurements were made on a Philips System MR scanner with field strength of 1.5 Tesla.…”

Section: Methodsmentioning

confidence: 99%

“…The commercial spectral-fitting package LC Model (version 6.1-4E) was used to measure individual metabolite peak integrals (28, 33). To accept individual metabolite fitting, we set Cramer-Rao lower bounds (CRLB) threshold of less than 20% for NAA, Cho, and tCr.…”

Section: Methodsmentioning

confidence: 99%

“…MRS is a noninvasive neuroimaging tool enabling investigation of in vivo neurochemistry. Proton ( 1 H) MRS is most commonly used in clinical research settings and it can provide information on the levels of (i) NAA, a marker synthesized in the mitochondria and considered to reflect neuronal density, viability, and function; (ii) phosphorylcholine plus glycerophospocholine (Cho), which participate in membrane phospholipid turnover; and (iii) tCr, which is involved in brain energy metabolism and can be used to store high energy phosphate bonds used to generate adenosine triphosphate (ATP) (1, 28). …”

Section: Introductionmentioning

confidence: 99%

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Antimanic Treatment With Tamoxifen Affects Brain Chemistry: A Double-Blind, Placebo-Controlled Proton Magnetic Resonance Spectroscopy Study

Yıldız

Aydın

Gökmen

et al. 2016

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

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Background The antimanic efficacy of a protein kinase C (PKC) inhibitor, tamoxifen, has been tested in several clinical trials, all reporting positive results. However, mechanisms underlying the observed clinical effects requires further confirmation through studies of biological markers. Methods We investigated the effect of tamoxifen versus placebo on brain metabolites via a proton (1H) magnetic resonance spectroscopy (MRS) study. Forty-eight adult bipolar I manic patients (mean Young Mania Rating Scale (YMRS) score of 37.8±5.8) were scanned at baseline and following 3 weeks of double-blind treatment. We hypothesized that manic symptom alleviation would improve the levels of markers associated with brain energy metabolism (creatine plus phosphocreatine [total creatine; tCr]) and neuronal viability (N-acetylaspartate [NAA]). Results The YMRS scores decreased from 38.6±4.5 to 20.0±11.1 in the tamoxifen group and increased from 37.0±6.8 to 43.1±7.8 in the placebo group (p<0.001). 1H MRS measurements revealed a 5.5±13.8% increase in the dorsomedial prefrontal cortex (DMPFC) tCr levels in the tamoxifen group and a 5.3±13.1% decrease in tCr in the placebo group (p=0.027). A significant correlation between the YMRS score change and tCr percent change was observed in the whole group (Spearman ρ=0.341, p=0.029). Both tCr and NAA levels in the responder group were increased by 9.4±15.2% and 6.1±11.7%, whereas levels in the non-responder group were decreased by 2.1±13.2% and 6.5±10.5%, respectively (p<0.05). Conclusions Tamoxifen effectively treated mania while it also increased brain tCr levels, consistent with involvement of both excessive PKC activation and impaired brain energy metabolism in the development of bipolar mania. Clinical trial registration Registry name: ClinicalTrials.gov URL: https://clinicaltrials.gov/ct2/show/NCT00411203?term=NCT00411203&rank=1 Registration number: NCT00411203

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Antimanic Treatment With Tamoxifen Affects Brain Chemistry: A Double-Blind, Placebo-Controlled Proton Magnetic Resonance Spectroscopy Study

Yıldız

Aydın

Gökmen

et al. 2016

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

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No evidence of abnormal metabolic or inflammatory activity in the brains of patients with rheumatoid arthritis: results from a preliminary study using whole-brain magnetic resonance spectroscopic imaging (MRSI)

et al. 2020

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Introduction/objectives Many individuals with rheumatoid arthritis (RA) report persistent fatigue even after management of peripheral disease activity. This study used whole-brain magnetic resonance spectroscopic imaging (MRSI) to investigate whether abnormal inflammatory activity in the central nervous system may be associated with such symptoms. We hypothesized that RA patients would show higher brain choline (CHO), myo-inositol (MI), and lactate (LAC), and higher brain temperature than healthy controls. We further hypothesized that the metabolite levels would be positively correlated with self-reported fatigue. Method Thirteen women with RA provided fatigue severity ratings and underwent whole-brain MRSI and a joint examination. Thirteen healthy controls (HC) provided comparison imaging and fatigue data. CHO, MI, LAC, and brain temperature in 47 brain regions were contrasted between groups using independent-samples t tests. Significant differences were determined using a false discovery rate (FDR)-adjusted p value threshold of ≤ 0.0023. Secondary analyses obtained correlations between imaging and clinical outcomes in the RA group. Results No brain metabolic differences were identified between the groups. In the RA group, fatigue severity was positively correlated with CHO in several brain regions-most strongly the right frontal lobe (r s = 0.823, p < 0.001). MI was similarly correlated with fatigue, particularly in the right calcarine fissure (r s = 0.829, p < 0.001). CHO in several regions was positively correlated with joint swelling and tenderness. Conclusions We conclude that abnormal brain metabolites are not a common feature of RA, but may been seen in patients with persistent fatigue or disease activity after conventional treatment. Key Points • Whole-brain magnetic resonance spectroscopy revealed no metabolic abnormalities in the brain in patients with rheumatoid arthritis. • Brain choline levels were correlated with fatigue severity reported by RA patients and with peripheral joint swelling and tenderness. • Brain myo-inositol levels were similarly correlated with fatigue severity in RA patients.

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Trait-related alterations of N-acetylaspartate in euthymic bipolar patients: A longitudinal proton magnetic resonance spectroscopy study

Aydın

Yurt

Gökmen

et al. 2016

Journal of Affective Disorders

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Background Neurochemical changes are responsible for bipolar disorder (BD) pathophysiology. Despite current progress in BD research, mood- and trait-related alterations in BD continue to elicit further investigation. Methods In this study, we report a longitudinal proton magnetic resonance spectroscopy study evaluating dorsomedial prefrontal cortex (DMPFC) metabolites N-acetylaspartate (NAA), creatine plus phosphocreatine (total creatine [tCr]), phosphorylcholine plus glycerophosphocholine, myo-inositol, and glutamate plus glutamine levels of manic and euthymic adult BD type I patients (n=48) treated with standard antimanic medicines, compared to matching healthy controls (n=44). Results DMPFC NAA values and NAA/tCr ratio were significantly lower in euthymic BD patients when compared with healthy controls with similar levels of other metabolites in all groups, indicating a trait-related NAA abnormality in euthymic BD patients. Limitations Limitations of our study include a relatively low (1.5 tesla) magnetic resonance field strength and variable drugs administered to achieve euthymia despite the best efforts to standardize the open fashion treatment. Conclusions Our study contributes to the integrating models of trait-related metabolite alterations observed in euthymia since NAA is considered as a marker of neuronal viability and mitochondrial energy metabolism. In light of supporting and conflicting results reported previously, future studies with longitudinal designs and larger patient groups are warranted to better define both state- and trait-related cerebral metabolic alterations associated with BD pathophysiology.

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In vivo proton magnetic resonance spectroscopic examination of benzodiazepine action in humans

Cited by 9 publications

References 25 publications

Antimanic Treatment With Tamoxifen Affects Brain Chemistry: A Double-Blind, Placebo-Controlled Proton Magnetic Resonance Spectroscopy Study

Antimanic Treatment With Tamoxifen Affects Brain Chemistry: A Double-Blind, Placebo-Controlled Proton Magnetic Resonance Spectroscopy Study

No evidence of abnormal metabolic or inflammatory activity in the brains of patients with rheumatoid arthritis: results from a preliminary study using whole-brain magnetic resonance spectroscopic imaging (MRSI)

Trait-related alterations of N-acetylaspartate in euthymic bipolar patients: A longitudinal proton magnetic resonance spectroscopy study

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