Zhensong Wang1,2, Aiying Zhang3, Jie Gan2, Guangbin Wang1, Bin Zhao1, Huifang Qu4, Weibo Chen5, Bo Liu6, Fei Gao1, Tao Gong7, and Richard A.E. Edden8,9
1Shandong Medical Imaging Research Institute, Jinan, China, People's Republic of, 2Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China, People's Republic of, 3Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China, People's Republic of, 4Shandong Chest Hospital, Jinan, China, People's Republic of, 5Philips Healthcare, Shanghai, China, People's Republic of, 6QiLu Hospital of Shandong University, Jina, China, People's Republic of, 7Shandong Medical Imaging Research Institute, Shandong University, Jinan, China, People's Republic of, 8Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA, Baltimore, MD, United States, 9FM Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA, Baltimore, MD, United States
Synopsis
The
present study hypothesized that the GABA levels would be lower in
postmenopausal women with mild-to-moderate depression. We investigate the
cerebral GABA levels in postmenopausal women using the edited MRS technique
MEGA-PRESS. 18 postmenopausal women with mild-to-moderate depression and 11
healthy controls with the age- and body index-, educationally matched were
enrolled. GABA+ levels were
quantified in the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC)
and the posterior cingulated cortex (PCC). Water-scaled GABA+ levels were
significantly lower in the ACC/mPFC regions of patients group than in healthy
controls, which suggesting that dysfunctional GABAergic system may be involved in
depression in postmenopausal women.Purpose
In
postmenopausal women, depression is widespread and associated with functional
disability and decreased quality of life
[1, 2]. Studies indicated
alterations of the GABAergic system are implicated in the pathophysiology of
depression
[3, 4]. However, there is little information on cerebral
GABA levels in postmenopausal women with depression. Here, we explore
in vivo γ-aminobutyric acid (GABA)
levels in the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) and
posterior-cingulate cortex (PCC) of postmenopausal women with mild-to-moderate
depression.
Materials and Methods
Eighteen
postmenopausal women with depression and eleven healthy postmenopausal women
with the age- and body index-, educationally matched were enrolled in the
study. The severity of depression of patients was assessed by the 17-item
Hamilton Depression Scale (HAMD) and the 14-item Hamilton Anxiety Scale (HAMA).
All the subjects underwent 1H-MRS of the ACC/mPFC and PCC using the
“MEGA Point Resolved Spectroscopy Sequence” (MEGA-PRESS) technique on 3T MR
scanner (Achieva TX, Best, the Neatherland). The main
parameters as follows: TR = 2000 ms; TE = 68 ms; 320 signal averages;
acquisition bandwidth = 1000 Hz. Quantification of the MRS data was performed
using the ‘Gannet’
(GABA-MRS Analysis Tool) in Matlab2010b (Mathworks) with Gaussian curve-fitting
to the GABA+ peaks
[5]. To determine if tissue composition
differences, between subjects of patients group and controls group, could account for differences in GABA+ levels, each MRS
voxel was segmented as GM, WM, or CSF using the 3D T1-weighted brain images and
the automatic brain segmentation program (Fig. 1), FAST (FMRIB’s automated
segmentation tool) in the FSL package (Oxford University, Oxford, UK)
[6].
The VOIs were co-registered to the anatomical images using the “Re-creation of
VOI” Matlab tool
[7]. Differences of GABA+ levels between two
groups were analyzed using independent t-test analysis. Correlative
relationships between GABA+ levels and HAMD/HAMA scores were analyzed for the
two groups.
Results
Significantly lower GABA+
levels were found in the ACC/mPFC of postmenopausal women with depression
compared with that of healthy controls (
P=0.006),
while no significant differences in the PCC (
P =0.316) (Table 1; Fig. 2). There were no significant
differences in GM fraction in the VOIs between the two groups (ACC/mPFC,
P = 0.326; PCC,
P =
0.520) (Table 1). No significant correlations were found between 17-HAMD/14-HAMA and GABA+ levels, either in ACC/mPFC (
P= 0.397;
r= 0.213/
P=
0.077;
r= 0.428) or PCC (
P=
0.748;
r= 0.082/
P= 0.457;
r= 0.187) in patients group and healthy
controls (ACC/mPFC:
P=
0.213;
r= 0.408/
P= 0.998;
r= -0.001; PCC:
P=
0.181;
r= 0.435/
P= 0.817;
r= 0.079).
Discussion and Conclusion
The main result of this study is that
significantly decreased GABA+ levels are present
in the ACC/mPFC region of
postmenopausal women with mild-to-moderate depression, as compared to healthy
control subjects. The mean GABA+ levels in the PCC region shows no significant
difference. To our knowledge, there is little in vivo literature investigating GABA levels in postmenopausal
women with depression. Our findings are consistent with previous studies, which
detected reduced GABA levels in the anterior cingulate, the dorsomedial and
dorsal anterolateral prefrontal cortex in depressed patients [8, 9]. The reduced GABA+
levels may be due to the deficiency of GAD: Post-mortem studies suggest that
reduced protein and mRNA encoding GAD-67 (a key enzyme for the synthesis of
GABA) in prefrontal cortex and amygdale of patients and animal depression
models [10, 11]. On the other hand, studies suggested that the size or density of neurons
in MDD patients was reduced compared to the healthy controls in the
dorsolateral prefrontal cortex, occipital cortex and anterior cingulated cortex
[12, 13, 14]. However, the underlying mechanisms need to be
elucidated in future studies.
In conclusion, the GABA+ levels were
lower in the ACC/mPFC in postmenopausal women with depression, suggesting that
aberrant GABAergic system may be involved in depression in postmenopausal
women.
Acknowledgements
This study applies tools developed under NIH R01 EB016089 and P41
EB015909; RAEE also receives salary support from these grants.References
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