Cortical GABA Levels Are Reduced in Post-Acute COVID-19 Syndrome, 2023, Marinkovic et al.

SNT Gatchaman · Dec 24, 2023

Cortical GABA Levels Are Reduced in Post-Acute COVID-19 Syndrome
Marinkovic, Ksenija; White, David R.; Alderson Myers, Austin; Parker, Katie S.; Arienzo, Donatello; Mason, Graeme F.

After recovering from the acute COVID-19 illness, a substantial proportion of people continue experiencing post-acute sequelae of COVID-19 (PASC), also termed “long COVID”. Their quality of life is adversely impacted by persistent cognitive dysfunction and affective distress, but the underlying neural mechanisms are poorly understood.

The present study recruited a group of mostly young, previously healthy adults (24.4 ± 5.2 years of age) who experienced PASC for almost 6 months following a mild acute COVID-19 illness. Confirming prior evidence, they reported noticeable memory and attention deficits, brain fog, depression/anxiety, fatigue, and other symptoms potentially suggestive of excitation/inhibition imbalance. Proton magnetic resonance spectroscopy (1H-MRS) was used to examine the neurochemical aspects of cell signaling with an emphasis on GABA levels in the occipital cortex. The PASC participants were compared to a control (CNT) group matched in demographics, intelligence, and an array of other variables.

Controlling for tissue composition, biological sex, and alcohol intake, the PASC group had lower GABA+/water than CNT, which correlated with depression and poor sleep quality. The mediation analysis revealed that the impact of PASC on depression was partly mediated by lower GABA+/water, indicative of cortical hyperexcitability as an underlying mechanism. In addition, N-acetylaspartate (NAA) tended to be lower in the PASC group, possibly suggesting compromised neuronal integrity.

Persistent neuroinflammation may contribute to the pathogenesis of PASC-related neurocognitive dysfunction.

Link | PDF (Brain Sciences)

Hutan · Dec 24, 2023

Sample size of 18, with their symptoms having reportedly relatively mild impacts. 20 controls

While experiencing the PASC symptoms, participants reported negligible functional limitations in their daily duties and activities, 0.83 ± 1.34, on the Post-COVID-19 Functional Status Scale ranging from 0 (no functional limitations) to 4 (severe functional limitation) [87]. Similarly, on a Likert scale from 0 (not at all) to 4 (very much), they reported that PASC “somewhat” impacted their daily life, 1.7 ± 1.2.
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The most noticeable deterioration was reflected in memory deficits, brain fog, attention deficits, depression/anxiety, fatigue, etc., which is broadly consistent with previously reported evidence [9,14,34,88,89,90].
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Hutan · Dec 24, 2023

1H-MRS spectra were acquired from a voxel located in the occipital lobe. Voxel placement was guided by each participant’s structural scan, with the voxel centered on the median and aligned with the tentorium in the sagittal plane (Figure 3a). Adjustments were made in the axial and coronal planes to ensure that the voxel volume did not include the skull.GABA-edited 1H-MRS data were obtained using the Siemens MEGA-PRESS sequence [62,111] from a 30 × 35 × 25 mm (26.3 mL) single voxel of interest (VOI)
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So the quantification of GABA+ is from one relatively small bit of brain.

One additional participant was scanned, but their GABA+/water value fell 6.6 standard deviations below the group mean, so this data set was excluded from the analysis.
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Just noting this. Abnormal results might be the result of some technical problem or some medical problem unique to the subjects, but might also be related to a transient impact of PASC. (It would be good to see this spectral scanning done before and during obvious PEM - I think I might have said that before.)

Figure 5. Group means ± standard errors of GABA+/water and NAA (N-acetylaspartate) for PASC and CNT groups. Controlling for the effect of tissue composition, biological sex, and drinking, the PASC group demonstrated lower values than CNT for both metabolites. * p < 0.05, # p < 0.14.
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The PASC sample had lower GABA+ and NAA (although the difference for NAA was not statistically significant)

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