Cerebral benzodiazepine receptors in depressed patients measured with [123i]iomazenil SPECT

Kugaya, Akira; Sanacora, Gerard; Verhoeff, Nicolaas Paul L.G.; Fujita, Masahiro; Mason, Graeme F.; Seneca, Nicholas; Bozkurt, Ali; Khan, Shaukat; Anand, Amit; Degen, Kathleen; Charney, Dennis S.; Zoghbi, Sami S.; Baldwin, Ronald M.; Seibyl, John; Innis, Robert B.

doi:10.1016/s0006-3223(02)01788-2

Cited by 55 publications

(35 citation statements)

References 42 publications

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“…To increase statistical power, data from depressive subjects and controls were pooled. This is justified, as no significant differences between depressive patients and healthy controls were observed for any of the ROIs investigated, in line with findings reported by Kugaya et al (2003). In addition, within the group of depressed patients, no relationship between severity of depression and either V T or BP ND was found (data not shown).…”

Section: Discussionsupporting

confidence: 87%

Comparison of Plasma Input and Reference Tissue Models for Analysing [¹¹C]flumazenil Studies

Klumpers

Veltman

Boellaard

et al. 2007

J Cereb Blood Flow Metab

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A single-tissue compartment model with plasma input is the established method for analysing [ 11 C]flumazenil ([ 11 C]FMZ) studies. However, arterial cannulation and measurement of metabolites are time-consuming. Therefore, a reference tissue approach is appealing, but this approach has not been fully validated for [11 C]FMZ. Dynamic [ 11 C]FMZ positron emission tomography scans with arterial blood sampling were performed in nine drug-free depressive patients and eight healthy subjects. Regions of interest were defined on co-registered magnetic resonance imaging scans and projected onto dynamic [11 C]FMZ images. Using a Hill-type metabolite function, single (1T) and reversible two-tissue (2T) compartmental models were compared. Simplified reference tissue model (SRTM) and full reference tissue model (FRTM) were investigated using both pons and (centrum semiovale) white matter as reference tissue. The 2T model provided the best fit in 59% of cases. Two-tissue V T values were on average 1.6% higher than 1T V T values. Owing to the higher rejection rate of 2T fits (7.3%), the 1T model was selected as plasma input method of choice. SRTM was superior to FRTM, irrespective whether pons or white matter was used as reference tissue. BP ND values obtained with SRTM correlated strongly with 1T V T (r = 0.998 and 0.995 for pons and white matter, respectively). Use of white matter as reference tissue resulted in 5.5% rejected fits, primarily in areas with intermediate receptor density. No fits were rejected using pons as reference tissue. Pons produced 23% higher BP ND values than white matter. In conclusion, for most clinical studies, SRTM with pons as reference tissue can be used for quantifying [ 11 C]FMZ binding.

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Section: Discussionsupporting

confidence: 87%

Comparison of Plasma Input and Reference Tissue Models for Analysing [¹¹C]flumazenil Studies

Klumpers

Veltman

Boellaard

et al. 2007

J Cereb Blood Flow Metab

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“…Our search identified 45 studies: 26 studies for the comparison of patients with current MDE versus healthy controls, [8][9][10][11][12][13][14][15][16][17][18]30,[33][34][35][36][37][38][39][40][41][42][43][44][45][46] 12 studies for the comparison of patients with current MDE before treatment versus after treatment, 12,20,23,25,26,28,36,43,[47][48][49][50] and 11 for the comparison of euthymic patients and controls. 18,[21][22][23]27,29,38,[51][52][53][54] Figure 1 depicts the study selection proce...…”

Section: Resultsmentioning

confidence: 99%

“…For MRS studies, we calculated SMDs for the following regions of interest (ROIs) independently: the occipital cortex, [8][9][10][11][12]14,15,[20][21][22][23][24][25][26][27][28] the anterior cingulate cortex (ACC), 13,15,16,18,22 the dorsolateral prefrontal cortex (dlPFC), 29,30 the ventromedial prefrontal cortex (vmPFC) 29,30 and the left inferior frontal gyrus. 27 We estimated study heterogeneity using the Q statistic when SMDs were significant.…”

Section: Discussionmentioning

confidence: 99%

“…Results of studies assessing GABA levels in individuals with depression appear highly variable according to the type of measure (plasma, CSF, or MRS) or to clinical characteristics of the included depressed samples. For example, MRS studies have reported GABA diminution, [8][9][10] no GABA change, [11][12][13] or GABA increase in participants with depression compared with healthy participants. 14 Furthermore, many authors have described specific implications of GABA neurotransmission according to different clinical characteristics of depression, such as pharmacological resistance, 15 anhedonia, 16 melancholia 9,11 or unipolar or bipolar depression.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Meta-analysis of central and peripheral γ-aminobutyric acid levels in patients with unipolar and bipolar depression

Roméo

Choucha

Fossati

et al. 2018

jpn

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“…However, Stocks and coworkers [60] reported that the density and affinity of benzodiazepine binding sites did not differ significantly in the hippocampus and amygdala between depressed suicide victims and controls. Similarly, Kugaya et al [22] also reported no differences between patients with major depression and healthy control subjects in GABA A receptor binding measured in vivo with a benzodiazepine radioligand. In addition, Merali and coworkers [31] reported low levels of mRNAs encoding several alpha subunits of the GABA A receptor in the frontal cortex of suicide victims.…”

Section: Discussionmentioning

confidence: 93%

Normal [3H]flunitrazepam binding to GABAA receptors in the locus coeruleus in major depression and suicide

Zhu¹,

Karolewicz²,

Nail³

et al. 2006

Brain Research

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Major depression and suicide are associated with altered concentrations of specific noradrenergic proteins in the human locus coeruleus (LC). Based on experimental studies that can reproduce these LC abnormalities in laboratory animals, we hypothesized that noradrenergic pathobiology in depression is a result of over-activity of the LC. LC activity is under the control of both excitatory and inhibitory inputs. A major inhibitory input to the LC is GABAergic, arising from the nucleus prepositus hypoglossi. Numerous studies demonstrating low levels of GABA in the CSF and plasma of subjects with major depressive disorder (MDD) raise the possibility that LC over-activity in depression may be secondary to reduced GABAergic input to the LC. Here, GABAergic input to the LC in depression was evaluated by studying the binding of [ 3 H]flunitrazepam to GABA A receptors at three anatomically-defined levels of the human postmortem LC. LC tissues were collected from subjects with MDD, subjects with depressive disorders including MDD that died as a result of suicide, and psychiatrically normal control subjects. A modest rostral-caudal gradient of GABA A receptor binding density was observed amongst all subjects. No significant differences in the amount of binding to GABA A receptors were observed between control subjects (n=21) and MDD subjects (n=9) or depressed suicide victims (n=17). These results demonstrate that GABA A receptor binding in the LC measured with [ 3 H]flunitrazepam is not altered in subjects with depressive illnesses.

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Cerebral benzodiazepine receptors in depressed patients measured with [123i]iomazenil SPECT

Cited by 55 publications

References 42 publications

Comparison of Plasma Input and Reference Tissue Models for Analysing [¹¹C]flumazenil Studies

Comparison of Plasma Input and Reference Tissue Models for Analysing [¹¹C]flumazenil Studies

Meta-analysis of central and peripheral γ-aminobutyric acid levels in patients with unipolar and bipolar depression

Normal [3H]flunitrazepam binding to GABAA receptors in the locus coeruleus in major depression and suicide

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Cerebral benzodiazepine receptors in depressed patients measured with [123i]iomazenil SPECT

Cited by 55 publications

References 42 publications

Comparison of Plasma Input and Reference Tissue Models for Analysing [11C]flumazenil Studies

Comparison of Plasma Input and Reference Tissue Models for Analysing [11C]flumazenil Studies

Meta-analysis of central and peripheral γ-aminobutyric acid levels in patients with unipolar and bipolar depression

Normal [3H]flunitrazepam binding to GABAA receptors in the locus coeruleus in major depression and suicide

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Comparison of Plasma Input and Reference Tissue Models for Analysing [¹¹C]flumazenil Studies

Comparison of Plasma Input and Reference Tissue Models for Analysing [¹¹C]flumazenil Studies