GABA+ Levels in Postmenopausal Women with Mild-to-moderate Depression: A Preliminary Study

Overview

Journal Medicine (Baltimore)

Specialty General Medicine

Date 2016 Sep 30

PMID 27684829

Citations 11

Authors

Zhensong Wang

AiYing Zhang

Bin Zhao

Jie Gan

Guangbin Wang

Fei Gao

Bo Liu

Tao Gong

Wen Liu

Richard A E Edden

Affiliations

Soon will be listed here.

Abstract

Background: It is increasingly being recognized that alterations of the GABAergic system are implicated in the pathophysiology of depression. This study aimed to explore in vivo gamma-aminobutyric acid (GABA) levels in the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) and posterior-cingulate cortex (PCC) of postmenopausal women with depression using magnetic resonance spectroscopy (H-MRS).

Methods: Nineteen postmenopausal women with depression and thirteen healthy controls were enrolled in the study. All subjects underwent H-MRS of the ACC/mPFC and PCC using the "MEGA Point Resolved Spectroscopy Sequence" (MEGA-PRESS) technique. The severity of depression was assessed by 17-item Hamilton Depression Scale (HAMD). Quantification of MRS data was performed using Gannet program. Differences of GABA+ levels from patients and controls were tested using one-way analysis of variance. Spearman correlation coefficients were used to evaluate the linear associations between GABA+ levels and HAMD scores, as well as estrogen levels.

Results: Significantly lower GABA+ levels were detected in the ACC/mPFC of postmenopausal women with depression compared to healthy controls (P = 0.002). No significant correlations were found between 17-HAMD/14-HAMA and GABA+ levels, either in ACC/mPFC (P = 0.486; r = 0.170/P = 0.814; r = -0.058) or PCC (P = 0.887; r = 0.035/ P = 0.987; r = -0.004) in the patients; there is also no significant correlation between GABA+ levels and estrogen levels in patients group (ACC/mPFC: P = 0.629, r = -0.018; PCC: P = 0.861, r = 0.043).

Conclusion: Significantly lower GABA+ levels were found in the ACC/mPFC of postmenopausal women with depression, suggesting that the dysfunction of the GABAergic system may also be involved in the pathogenesis of depression in postmenopausal women.

Citing Articles

Charting brain GABA and glutamate levels across psychiatric disorders by quantitative analysis of 121 H-MRS studies.

Zhang J, Toulopoulou T, Li Q, Niu L, Peng L, Dai H Psychol Med. 2024; :1-12.

PMID: 39564744 PMC: 11650199. DOI: 10.1017/S0033291724001673.

Dorsal brain activity reflects the severity of menopausal symptoms.

Nakamura K, Hoshi H, Kobayashi M, Fukasawa K, Ichikawa S, Shigihara Y Menopause. 2024; 31(5):399-407.

PMID: 38626372 PMC: 11465762. DOI: 10.1097/GME.0000000000002347.

Relationships between GABA, glutamate, and GABA/glutamate and social and olfactory processing in children with autism spectrum disorder.

Johnson A, Shankland E, Richards T, Corrigan N, Shusterman D, Edden R Psychiatry Res Neuroimaging. 2023; 336:111745.

PMID: 37956467 PMC: 10841920. DOI: 10.1016/j.pscychresns.2023.111745.

Medial Frontal Cortex GABA Concentrations in Psychosis Spectrum and Mood Disorders: A Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies.

Simmonite M, Steeby C, Taylor S Biol Psychiatry. 2022; 93(2):125-136.

PMID: 36335069 PMC: 10184477. DOI: 10.1016/j.biopsych.2022.08.004.

Decreased GABA+ Levels in the Medial Prefrontal Cortex of Perimenopausal Women: A 3T 1H-MRS Study.

Tran K, Luki J, Hanstock S, Hanstock C, Seres P, Aitchison K Int J Neuropsychopharmacol. 2022; 26(1):32-41.

PMID: 36146906 PMC: 9850658. DOI: 10.1093/ijnp/pyac066.

References

Maciag D, Hughes J, ODwyer G, Pride Y, Stockmeier C, Sanacora G . Reduced density of calbindin immunoreactive GABAergic neurons in the occipital cortex in major depression: relevance to neuroimaging studies. Biol Psychiatry. 2009; 67(5):465-70. PMC: 2823848. DOI: 10.1016/j.biopsych.2009.10.027. View

Harlow S, Gass M, Hall J, Lobo R, Maki P, Rebar R . Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. Menopause. 2012; 19(4):387-95. PMC: 3340903. DOI: 10.1097/gme.0b013e31824d8f40. View

Morrison M, Kallan M, Ten Have T, Katz I, Tweedy K, Battistini M . Lack of efficacy of estradiol for depression in postmenopausal women: a randomized, controlled trial. Biol Psychiatry. 2004; 55(4):406-12. DOI: 10.1016/j.biopsych.2003.08.011. View

Weiland N . Glutamic acid decarboxylase messenger ribonucleic acid is regulated by estradiol and progesterone in the hippocampus. Endocrinology. 1992; 131(6):2697-702. DOI: 10.1210/endo.131.6.1446611. View

Sanacora G, Mason G, Rothman D, Hyder F, Ciarcia J, Ostroff R . Increased cortical GABA concentrations in depressed patients receiving ECT. Am J Psychiatry. 2003; 160(3):577-9. DOI: 10.1176/appi.ajp.160.3.577. View

Gjerris A, Bech P, Bojholm S, Bolwig T, Kramp P, Clemmesen L . The Hamilton Anxiety Scale. Evaluation of homogeneity and inter-observer reliability in patients with depressive disorders. J Affect Disord. 1983; 5(2):163-70. DOI: 10.1016/0165-0327(83)90009-5. View

Gao F, Edden R, Li M, Puts N, Wang G, Liu C . Edited magnetic resonance spectroscopy detects an age-related decline in brain GABA levels. Neuroimage. 2013; 78:75-82. PMC: 3716005. DOI: 10.1016/j.neuroimage.2013.04.012. View

Perez-Lopez F, Perez-Roncero G, Fernandez-Inarrea J, Fernandez-Alonso A, Chedraui P, Llaneza P . Resilience, depressed mood, and menopausal symptoms in postmenopausal women. Menopause. 2013; 21(2):159-64. DOI: 10.1097/GME.0b013e31829479bb. View

Altemus M, Fong J, Yang R, Damast S, Luine V, Ferguson D . Changes in cerebrospinal fluid neurochemistry during pregnancy. Biol Psychiatry. 2004; 56(6):386-92. DOI: 10.1016/j.biopsych.2004.06.002. View

10.

Woods N, Smith-DiJulio K, Percival D, Tao E, Mariella A, Mitchell S . Depressed mood during the menopausal transition and early postmenopause: observations from the Seattle Midlife Women's Health Study. Menopause. 2008; 15(2):223-232. DOI: 10.1097/gme.0b013e3181450fc2. View

11.

Hattemer K, Knake S, Reis J, Rochon J, Oertel W, Rosenow F . Excitability of the motor cortex during ovulatory and anovulatory cycles: a transcranial magnetic stimulation study. Clin Endocrinol (Oxf). 2007; 66(3):387-93. DOI: 10.1111/j.1365-2265.2007.02744.x. View

12.

Bustillo J, Lauriello J, Rowland L, Jung R, Petropoulos H, Hart B . Effects of chronic haloperidol and clozapine treatments on frontal and caudate neurochemistry in schizophrenia. Psychiatry Res. 2001; 107(3):135-49. DOI: 10.1016/s0925-4927(01)00102-0. View

13.

Clayton A, Guico-Pabia C . Recognition of depression among women presenting with menopausal symptoms. Menopause. 2008; 15(4 Pt 1):758-67. DOI: 10.1097/gme.0b013e31815dba9c. View

14.

Juang K, Wang S, Lu S, Lee S, Fuh J . Hot flashes are associated with psychological symptoms of anxiety and depression in peri- and post- but not premenopausal women. Maturitas. 2005; 52(2):119-26. DOI: 10.1016/j.maturitas.2005.01.005. View

15.

Bai X, Edden R, Gao F, Wang G, Wu L, Zhao B . Decreased γ-aminobutyric acid levels in the parietal region of patients with Alzheimer's disease. J Magn Reson Imaging. 2014; 41(5):1326-31. PMC: 5512098. DOI: 10.1002/jmri.24665. View

16.

Shumaker S, Legault C, Rapp S, Thal L, Wallace R, Ockene J . Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003; 289(20):2651-62. DOI: 10.1001/jama.289.20.2651. View

17.

Young E, Midgley A, Carlson N, Brown M . Alteration in the hypothalamic-pituitary-ovarian axis in depressed women. Arch Gen Psychiatry. 2000; 57(12):1157-62. DOI: 10.1001/archpsyc.57.12.1157. View

18.

Croarkin P, Levinson A, Daskalakis Z . Evidence for GABAergic inhibitory deficits in major depressive disorder. Neurosci Biobehav Rev. 2010; 35(3):818-25. DOI: 10.1016/j.neubiorev.2010.10.002. View

19.

Price R, Shungu D, Mao X, Nestadt P, Kelly C, Collins K . Amino acid neurotransmitters assessed by proton magnetic resonance spectroscopy: relationship to treatment resistance in major depressive disorder. Biol Psychiatry. 2008; 65(9):792-800. PMC: 2934870. DOI: 10.1016/j.biopsych.2008.10.025. View

20.

Amin Z, Mason G, Cavus I, Krystal J, Rothman D, Epperson C . The interaction of neuroactive steroids and GABA in the development of neuropsychiatric disorders in women. Pharmacol Biochem Behav. 2006; 84(4):635-43. DOI: 10.1016/j.pbb.2006.06.007. View