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We found elevated ventricular lactate and decreased GSH in patients with CFS and MDD relative to HVs. GSH did not differ significantly between the two patient groups. In addition, we found lower rCBF in the left anterior cingulate cortex and the right lingual gyrus in patients with CFS relative to HVs, but rCBF did not differ between those with CFS and MDD. We found no differences between the three groups in terms of any high-energy phosphate metabolites.
Are you familiar with the lactate shuttle hypothesis? As I understand it (probably poorly), lactate produced from anaerobic glycolysis in astrocytes is then released from astrocytes and provides the primary metabolic fuel for neurons. When oxidative phosphorylation is activated in neurons (dendrites), it causes a decrease in mitochondrial NADH content. Recovery of the mitochondrial NADH in dendrites is accomplished by stimulation of the TCA cycle, fueled by lactate from the extracellular pool. This part of the cycle apparently needs a constant supply of NAD+. I had been thinking a while back that an error in this cycle is revealed as elevated lactate in the ventricles and CSF.
I wonder if there are any established links between GSH status and this supply...
Yes, I just did. Well worth a read. It's a more thoughtful paper than the abstract suggests - they don't give up on the other theories and even point out why there could have been problems with their study which might put some theories back in the frame.Has anyone read the full text?
For all participants, general eligibility requirements included age
between 18 and 45 years, negative urine toxicology at screening
and on the day of scan and, for females of reproductive age, the
use of an effective birth control method and negative day-ofscan
pregnancy test. In addition, all participants were instructed
to refrain from the consumption of alcohol for at least 48 h prior
to the neuroimaging scans, as the measured lactate CH3 group
has nearly the same MR frequency as the ethanol CH3 group at
1.3 ppm. Exclusion criteria consisted of any unstable medical or
neurological illness or any condition precluding MRI exposure
(e.g. pacemaker, metallic prosthesis). All participants were
assessed for psychiatric disorders using the Structured Clinical
Interview for the Diagnostic and Statistical Manual of Mental
Disorders, 4th edn. (14).
All participants had been psychotropic medication
free for 2 weeks or more (? 4 weeks for fluoxetine) prior to the
scans, had been free of substance abuse/dependence for
6 months or more, had no lifetime history of psychotic disorder,
mania or hypomania, had no pervasive developmental disorder
or mental retardation, and had no current eating disorder.
Brain GSH measurement by 1H MRS and assessment of voxel
brain matter content
It should be noted
that, because of its low brain concentration (0.51.5 mmol/L) and
overlap by a total creatine (tCr) resonance at 3.0 ppm, which is
up to 10-fold stronger (Fig. 3B, spectrum a), in vivo brain GSH is
technically challenging to detect by 1H MRS. However, using
the J-edited spin echo difference technique (23,24), we reliably
achieved unobstructed detection of the GSH b-cysteinyl resonance
at 2.98ppm in this study (Fig. 3B, C).
The subtraction of the two subspectra
acquired yields the desired GSH resonance at 2.98ppm
Prior to the analyses, the normality of all data was assessed using
the ShapiroWilks test. The Type I error rate (i.e. chance findings)
was protected against by limiting the statistical tests only to our
specified hypotheses. Differences in the means of the primary
outcome measures (GSH and CSF lactate) between the three
groups were assessed using one-way analysis of variance
(ANOVA), with Bonferroni correction for multiple comparisons.
Exploratory associations between MRS measures and
With a sample size of, at most, 15 subjects per group, this study
did not have sufficient statistical power to enable the assessment
of within-group correlations, which we estimate would require
40 or more subjects per group to be meaningful.