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. 2019 May 30;19(1):164.
doi: 10.1186/s12888-019-2160-1.

Investigation of anterior cingulate cortex gamma-aminobutyric acid and glutamate-glutamine levels in obsessive-compulsive disorder using magnetic resonance spectroscopy

Affiliations

Investigation of anterior cingulate cortex gamma-aminobutyric acid and glutamate-glutamine levels in obsessive-compulsive disorder using magnetic resonance spectroscopy

Yan Li et al. BMC Psychiatry. .

Abstract

Background: Obsessive-compulsive disorder (OCD) is a relatively common and disabling psychiatric disorder whose pathophysiology is incompletely understood. In this study, we utilized magnetic resonance spectroscopy (MRS) in an effort to provide a better understanding of the role of brain gamma-aminobutyric acid (GABA) and glutamate in the pathophysiology of OCD. We hypothesized that beyond the separate effects of these neurotransmitter systems, a disruption in the balance between GABA and glutamate could be particularly relevant to OCD.

Methods: We obtained MRS measures of GABA and glutamate concentrations in the anterior cingulate cortex from 23 adult patients with OCD and 20 sex- and age-matched healthy community volunteers. Established clinical rating scales were used to assess the severities of OCD, anxiety, and depression symptoms. Statistical analysis involved the assessment of patient-control group differences in the individual measures of GABA and glutamate, as well as in the ratio of the GABA to glutamate measures. Additionally, we explored whether differences in the MRS measures existed between two subgroups of patients formed according to the severity of their OCD symptoms. Finally, we assessed the relations of demographic and clinical variables to the MRS measures.

Results: Patients with OCD displayed a higher estimated GABA level and a higher GABA to glutamate ratio than healthy participants, but no significant group differences were observed in the measure of glutamate. The MRS measures did not vary by subgroup and showed no correlations with demographic and clinical variables.

Conclusions: These results indicate that GABA abnormalities within the anterior cingulate cortex contribute to the pathophysiology of OCD. The results fail to provide evidence that glutamate abnormalities alone are involved in adult OCD. Yet, it seems that a disruption in the balance between glutamate and GABA neurotransmission may have a particularly important role to play in OCD pathophysiology.

Keywords: GABA; Glutamate-glutamine; H-MR spectroscopy; Obsessive-compulsive disorder; Pathophysiology.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Position of MRS region of interest. A region of interest (ROI) with a size of 30 × 30 × 30 mm3 was created over the anterior cingulate cortex according to a high-resolution anatomic 3D T1WI MRI scan. The ROI is shown in (a) sagittal, (b) coronal, and (c) transversal orientations
Fig. 2
Fig. 2
Flowchart of the MEGA-PRESS MRS data processing procedure and representative results of each step. (a). Schematic picture of the MEGA-PRESS MRS data processing procedure. (b) The processed GABA-edited difference spectrum (EDIT-OFF − EDIT-ON = DIFF) is the key output of the GannetLoad module. This plot shows the spectrum before frequency and phase correction (above in green) and the spectrum after frequency and phase correction (below in blue). (c) The Cr signal over the duration of the acquisition. The y-axis represents the frequency in ppm of the Cr signal. The spectra at each time point are presented as a vertical stripe in the image (color-coded according to signal intensity), so the Cr signal appears as a ‘hot’ stripe running through the image. In the lower half (POST), the result of frequency and phase correction is shown. (d) Model fitting of GABA+ and Glx spectrum peaks, representing the GABA+ signal modeling (GannetFit output). The blue line represents the actual edited spectrum while the overlaid red line is the model of best fit (using a simple Gaussian model by default). The residual is represented by the black curve below the modeling plot. (e) The modeling of the signal against which GABA is quantified, using the same color scheme as in (d). In our experiment, the unsuppressed water data were incorporated, so that the main spectrum is the water signal; the Cr signal is shown in an inset. The water signal was modeled as a mixed Gaussian-Lorentzian and served as the reference for GABA quantification
Fig. 3
Fig. 3
Comparison between OCD and HC groups in a GABA+, b Glx and c GABA+/ Glx values. Significant differences between the OCD and HC groups were observed in the level of GABA+ and the GABA+/Glx ratio. The OCD group showed a higher level of GABA+ and a higher GABA+/Glx ratio than the control group. By contrast, no significant differences between the OCD and HC groups were observed in the level of Glx

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