The trajectory of putative astroglial dysfunction in first episode schizophrenia: a longitudinal 7-Tesla MRS study

Abstract

Myo-inositol is mainly found in astroglia and its levels has been shown to be reduced in the anterior cingulate cortex (ACC) of patients with schizophrenia. We investigate the status of astroglial integrity indexed by ACC myo-inositol at the onset and over the first 6 months of treatment of first episode schizophrenia. We employed 7 T magnetic resonance spectroscopy (1H-MRS) and quantified myo-inositol spectra at the dorsal ACC in 31 participants; 21 patients with schizophrenia with median lifetime antipsychotic exposure of less than 3 days, followed up after 6 months of treatment, and 10 healthy subjects scanned twice over the same period. We studied the time by group interaction for myo-inositol after adjusting for gender and age. We report significant reduction in myo-inositol concentration in the ACC in schizophrenia at an early, untreated state of acute illness that becomes insignificant over time, after instituting early intervention. This trajectory indicates that dynamic astroglial changes are likely to operate in the early stages of schizophrenia. MRS myo-inositol may be a critical marker of amelioration of active psychosis in early stages of schizophrenia.

Redefining the Cut-Off Ranges for TSH Based on the Clinical Picture, Results of Neuroimaging and Laboratory Tests in Unsupervised Cluster Analysis as Individualized Diagnosis of Early Schizophrenia

“…The dependencies between TSH and myoinositol in ACC shown by us, according to the literature data, indicate astroglial dysfunction in this brain area, which is mainly responsible for the pathogenesis of the disease according to one of the theories [122]. According to the literature on the subject, damage to astrocytic cells leads to a disturbance of the redox balance, a reduction in the functioning of the immune system by the use of glial cells [123], a reduction in the secretion of synaptogenic factors involved in the formation of synapses [124] and a reduction in synthesis L-serine, which is a substrate for D-serine building NMDA receptors [125]. Thus, damage to astrocytes also leads to glutamatergic dysregulation, which was proved crucial in endophenotypes of schizophrenia [30].…”

Basal glutamate in the hippocampus and the dorsolateral prefrontal cortex in schizophrenia: Relationships to cognitive proficiency investigated with structural equation modelling

“…The other significant finding is the reduced hippocampal myo-inositol level in SCZ, which has been previously reported in SCZ but mainly in the mPFC [55,56]. Myo-Inositol, which is generally viewed as a cerebral osmolyte, is an intermediate of several important pathways involving inositol-polyphosphate second messengers [57,58].…”

Thalamic neurometabolite alterations in chronic low back pain: a common phenomenon across musculoskeletal pain conditions?

“…65 Myo-inositol is primarily found in glial cells 10 and has been proposed as a marker of glial activation. 5 An increase in mIns levels in MRS studies may be explained by a microglial or astrocyte proliferation 4,14,31,45 , and might therefore suggest the presence of neuroinflammation. As such, these results are in line with our previous PET imaging work, which has documented elevated thalamic levels of the 18-kDa TSPO, another putative marker of glial activation, in multiple, independent cohorts of patients with cLBP compared with controls.…”