Depression, GABA and age correlate with the plasma levels of inflammatory markers

Bhandage, Amol K.; Cunningham, Janet L.; Jin, Zhe; Shen, Qiujin; Bongiovanni, Santiago; Korol, Sergiy V.; Syk, Mikaela; Kamali‐Moghaddam, Masood; Ekselius, Lisa; Birnir, Bryndis

doi:10.1101/689984

Cited by 5 publications

(2 citation statements)

References 74 publications

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“…It is indicated that thyroid hormones influence multiple aspects of the GABA system, including the synthesis and degradation of GABA, the expression and function of GABA-A receptor, as well as GABA release and reuptake (Karakatsoulis et al, 2021). Moreover, studies have demonstrated that the GABA system could participate in the pathogenesis of major depressive disorder by possible interactions with different processes involved in this disorder, including monoamine neurotransmission, hypothalamuspituitary-adrenal axis, immune response, and neurotrophic factors (Bhandage et al, 2019;Della Vecchia et al, 2022;Slattery et al, 2005;Suzdak & Gianutsos, 1985). Thyroid abnormalities have been suggested to be associated with the occurrence of stroke and adverse functional outcomes (Squizzato et al, 2005;Wollenweber et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Association between thyroid hormone levels in the acute stage of stroke and risk of poststroke depression: A meta‐analysis

Fu,

Zhao,

et al. 2023

Brain and Behavior

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BackgroundThyroid hormones have been indicated to be associated with depression, but their relationship with poststroke depression (PSD) remains controversial. Therefore, we performed a meta‐analysis to explore the correlation between thyroid hormone levels in acute stroke and PSD.MethodsWe searched databases for eligible studies. Standard mean differences (SMD) and 95% confidence intervals (CI) were applied to evaluate the association among levels of thyroid hormones, including thyroid‐stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), in acute stroke patients and the risk of PSD.ResultsA total of 13 studies were included in the analysis. Compared to non‐PSD patients, PSD patients had remarkably lower serum TSH and FT3 levels (TSH: SMD = −0.59, 95%CI = −1.04 to −.15, p = .009; FT3: SMD = −0.40, 95%CI = −.51 to −.30, p = .000) and higher serum FT4 levels (SMD = 0.33, 95%CI = .07–.59, p = .013). Subgroup analysis showed that there may be a more statistically significant association between FT3 and the risk of PSD compared to TSH and FT4.ConclusionsOur results suggested that patients with lower serum TSH and FT3 levels as well as higher serum FT4 levels in the acute stage of stroke may be more susceptible to PSD.

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Section: Discussionmentioning

confidence: 99%

Association between thyroid hormone levels in the acute stage of stroke and risk of poststroke depression: A meta‐analysis

Fu,

Zhao,

et al. 2023

Brain and Behavior

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“…autism spectrum disorder (Marotta et al ., 2020). Evidence for altered GABA function comes through multiple lines of enquiry including animal models (Enna and McCarson, 2006; Sun et al ., 2018), genetics (Baulac et al ., 2001; Coghlan et al ., 2012), post-mortem studies (de Jonge et al ., 2017), blood plasma (Petty, 1994; Bhandage et al ., 2019) and in-vivo Magnetic Resonance Spectroscopy (MRS) (Schur et al ., 2016; Peek et al ., 2020). Given the wealth of evidence, targeting the GABAergic system with therapeutic interventions may therefore prove fundamental to improving patient outcomes in these conditions.…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Guide to MEGA-PRESS for GABA Measurement

Peek

Rebbeck

Leaver

et al. 2021

Preprint

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BackgroundThe aim of this guideline is to provide a series of evidence-based recommendations that allow those new to the field of MEGA-PRESS to produce high-quality data for the measurement of GABA levels using edited magnetic resonance spectroscopy with the MEGA-PRESS sequence at 3T. GABA is the main inhibitory neurotransmitter of the central nervous system and has been increasingly studied due to its relevance in many clinical disorders of the central nervous system. MEGA-PRESS is the most widely used method for quantification of GABA at 3T, but is technically challenging and operates at a low signal-to-noise ratio. Therefore, the acquisition of high-quality MRS data relies on avoiding numerous pitfalls and observing important caveats.MethodsThe guideline was developed by a working party that consisted of experts in MRS and experts in guideline development and implementation, together with key stakeholders. Strictly following a translational framework, we first identified evidence using a systematically conducted scoping literature review, then synthesised and graded the quality of evidence that formed recommendations. These recommendations were then sent to a panel of 21 world leaders in MRS for feedback and approval using a modified-Delphi process across two rounds.ResultsThe final guideline consists of 23 recommendations across six domains essential for GABA MRS acquisition (Parameters, Practicalities, Data acquisition, Confounders, Quality/reporting, Post-processing). Overall, 78% of recommendations were formed from high-quality evidence, and 91% received agreement from over 80% of the expert panel.ConclusionThese 23 expert-reviewed recommendations and accompanying extended documentation form a readily usable guideline to allow those new to the field of MEGA-PRESS to design appropriate MEGA-PRESS study protocols and generate high-quality data.

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The GABA and GABA-Receptor System in Inflammation, Anti-Tumor Immune Responses, and COVID-19

Tian

Kaufman

2023

Biomedicines

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GABA and GABAA-receptors (GABAA-Rs) play major roles in neurodevelopment and neurotransmission in the central nervous system (CNS). There has been a growing appreciation that GABAA-Rs are also present on most immune cells. Studies in the fields of autoimmune disease, cancer, parasitology, and virology have observed that GABA-R ligands have anti-inflammatory actions on T cells and antigen-presenting cells (APCs), while also enhancing regulatory T cell (Treg) responses and shifting APCs toward anti-inflammatory phenotypes. These actions have enabled GABAA-R ligands to ameliorate autoimmune diseases, such as type 1 diabetes (T1D), multiple sclerosis (MS), and rheumatoid arthritis, as well as type 2 diabetes (T2D)-associated inflammation in preclinical models. Conversely, antagonism of GABAA-R activity promotes the pro-inflammatory responses of T cells and APCs, enhancing anti-tumor responses and reducing tumor burden in models of solid tumors. Lung epithelial cells also express GABA-Rs, whose activation helps maintain fluid homeostasis and promote recovery from injury. The ability of GABAA-R agonists to limit both excessive immune responses and lung epithelial cell injury may underlie recent findings that GABAA-R agonists reduce the severity of disease in mice infected with highly lethal coronaviruses (SARS-CoV-2 and MHV-1). These observations suggest that GABAA-R agonists may provide off-the-shelf therapies for COVID-19 caused by new SARS-CoV-2 variants, as well as novel beta-coronaviruses, which evade vaccine-induced immune responses and antiviral medications. We review these findings and further advance the notions that (1) immune cells possess GABAA-Rs to limit inflammation in the CNS, and (2) this natural “braking system” on inflammatory responses may be pharmacologically engaged to slow the progression of autoimmune diseases, reduce the severity of COVID-19, and perhaps limit neuroinflammation associated with long COVID.

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Depression, GABA and age correlate with the plasma levels of inflammatory markers

Cited by 5 publications

References 74 publications

Association between thyroid hormone levels in the acute stage of stroke and risk of poststroke depression: A meta‐analysis

Association between thyroid hormone levels in the acute stage of stroke and risk of poststroke depression: A meta‐analysis

A Comprehensive Guide to MEGA-PRESS for GABA Measurement

The GABA and GABA-Receptor System in Inflammation, Anti-Tumor Immune Responses, and COVID-19

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