Introduction
There are similarities in the phenomenology and psychobiology of
schizophrenia (SZ) and methamphetamine (MA)-induced psychosis (MAP) ,
with evidence of alterations in glutamatergic function in both
conditions , and of involvement of neuroinflammatory pathways in SZ and
MA abuse . In SZ, positron emission tomography (PET) and single-photon
emission computed tomography (SPECT) studies suggest hypofunction of
N-methyl-D-aspartate receptors (NMDAR) , while 1H-MRS
studies of myo-inositol (mI), which may indicate neuroinflammation , are
inconsistent . Studies of prefrontal glutamatergic function in MA abuse
and MAP are inconsistent, with some reporting higher glutamate (Glu) or
glutamate with glutamine (Glx) , others reporting lower Glx , and
several reporting no glutamatergic metabolite changes . In MAP, higher
concentration of prefrontal mI , suggestive of neuroinflammation have
been reported. Cytokines have been proposed to be involved during
psychotic states as IL-1β, TNF-α, IFN-γ, IL-8 and IL-10 are all reported
to be elevated during acute . IL-1β however is reported to return to
normal concentrations outside of psychotic state, whereas TNF-α, IFN-γ,
IL-8 remain elevated even in remission . It is proposed that IL-1β,
TNF-α, IFN-γ can therefore reflect neuroinflammation, and subsequent
disruption in thalamo-cortical circuitry. Pre-clinical studies and
animal models of MA abuse, and post-mortem studies of SZ have shown that
higher concentrations of IL-1β and IFN-γ have been associated with lower
concentrations of NAA , while higher concentration of IL-8 has been
associated with increased Glu .
Few studies have, however, directly compared glutamatergic (Glu, Gln and
Glx) and neuroinflammatory (mI) neurometabolites and neuronal integrity
markers (NAA and NAA+NAAG) in thalamo-cortical circuitry across SZ and
MA abuse and none have assessed the relationship between these
neurometabolites and peripheral inflammatory markers in either disorder
aside from preclinical and post-mortem studies and animal models. The
small literature on associations between neurometabolites and peripheral
inflammatory markers has found an association between higher
concentrations of TNF-α and IL-1β and lower NAA concentrations in active
psychosis in SZ as well as MA abuse . Increased IL-8 concentrations have
been associated with increased NMDAR in SZ and with withdrawal symptoms
in MA abuse . Lower concentrations of interferon gamma (IFN-γ) and IL-10
were associated with decreased neuronal integrity in the prefrontal
cortex and thalamus in SZ , and MA abuse . However, these associations
have not been explored using a combination of neuroimaging and
peripheral cytokine measures in living patients with SZ and MAP.
This study had two aims. First, to compare glutamatergic and
neuroinflammatory neurometabolites and neuronal integrity in
thalamo-cortical circuitry in SZ and MAP. It was hypothesized that
glutamatergic neurometabolites would be increased in SZ compared to
healthy controls, and that mI would be higher in SZ and MAP than in
healthy controls, consistent with neuroinflammation. It was also
hypothesized that NAA/NAA+NAAG concentrations would be lower in both SZ
and MAP groups. Second, this study aimed to investigate associations
between glutamatergic and neuroinflammatory neurometabolites, neuronal
integrity markers and peripheral cytokine levels in both disorders. It
was hypothesized that associations between neurometabolites, brain areas
and peripheral cytokines would differ in SZ compared with MAP.