Discussion
The main findings of this study were that 1) there were no significant
differences in neurometabolites in SZ compared to healthy controls, 2)
the MAP group had lower NAA+NAAG/Cr+PCr than healthy controls in the
left DLPFC and left FWM, 3) There were significant positive associations
between glutamatergic neurometabolites and neuronal integrity markers in
the ACC in the SZ group, and 4) there were significant positive
associations between mI in the left thalamus and mI in bilateral ACC in
the MAP group.
The lack of a significant differences between 1H-MRS
neurometabolite findings in SZ group and healthy controls could be
attributed to the chronic use of antipsychotic medicine in these
patients. Antipsychotic medicine has been shown to normalize
neurometabolites over time and thus increase metabolic activity in the
thalamus, reduce neuroinflammation and partially reverse NMDAR
dysfunction in patients with SZ .
The finding of altered lower NAA+NAAG in left DLPFC and left FWM in MAP
is consistent with previous studies of MA abuse and one study of MAP and
could indicate compromised neuronal health, density and metabolism .
Previous studies found lower NAA and NAA+NAAG in frontal brain areas in
MA abuse , and the present work extends this finding by showing lower
NAA+NAAG/Cr+PCr in the left DLPFC and left FWM in the MAP group,
suggesting that neuronal integrity remains compromised over time.
The associations between glutamatergic neurometabolites and neuronal
integrity markers in the ACC in SZ, but not in healthy controls, may
suggest disruptions in the glutamate-glutamine cycle. Few studies on
these associations have been done and much further work is needed to
understand the relevant underlying causal mechanisms. The brain areas
investigated in the present study form part of the thalamo-cortical
circuitry and previous studies, limited to post-mortem , structural
magnetic resonance imaging and imaging techniques to assess
neurocognitive functioning (PET/SPECT) and fMRI, did not specifically
investigate the thalamo-cortical circuit) . Two previous studies report
positive relationships between NAA and Glu concentrations in healthy
controls, but not in SZ patients . Considering that no individual
neurometabolite differences for the SZ were found, it could be
considered that the mechanism of dysfunction in SZ lies within
associations between neurometabolites and not changes in specific
standalone neurometabolites.
Stronger associations of mI between the left thalamus and bilateral ACC
were also found in the MAP group, compared to healthy controls. Higher
thalamic mI was positively associated with higher mI in the left and
right ACC, suggesting neuroinflammation in the thalamus-ACC circuit in
chronic MAP. MA has been shown to disrupt the thalamo-cortical circuit
at the ventral striatum, within the ACC-thalamus circuit . This is
supported by previous studies in MA abstinence where higher
concentrations of mI have been reported . These are the first data on
higher mI concentrations, suggestive of neuroinflammation, within the
thalamus-ACC circuit in chronic MAP.
Several limitations deserve emphasis. First, use of antipsychotic
medication use was obtained through retrospective self-report and may
not be accurate. Second, studies of substance abuse are almost
invariably confounded by selective disclosure and polysubstance use.
Third, the effect of alcohol and nicotine could potentially have
influenced neurometabolite concentrations, as participants did not cease
their alcohol or nicotine use during the study.