Greater Choline-Containing Compounds and Myo-inositol in Treatment-Resistant vs. Responsive Schizophrenia: A 1 H-Magnetic Resonance Spectroscopy Meta-Analysis.

BACKGROUND: The neurobiology of treatment-resistant schizophrenia (TRS) is poorly understood, and meta-analytic consensus regarding magnetic resonance spectroscopic profiles of glutamate, choline-containing compounds, myo-inositol, and other metabolites in the condition is lacking.

METHODS: In this meta-analysis, we examined published findings for N-acetyl aspartate, choline-containing compounds (phosphocholine+glycerophosphocholine (PCho+GPCho)), myo-inositol, creatine+phosphocreatine, glutamate, and glutamate+glutamine in the anterior cingulate cortex (ACC) and dorsal striatum in people with TRS vs. non-TRS (nTRS) as well as TRS vs. healthy controls (HCs) and TRS vs. ultra TRS (i.e., TRS with clozapine resistance). A MEDLINE search revealed 9 articles including 239 people with TRS-All (pooled TRS and ultra TRS), 59 with ultra TRS, 175 with nTRS, and 153 HCs that met meta-analytic criteria.

RESULTS: Significant effects included higher ACC PCho+GPCho and myo-inositol in TRS-All compared to both nTRS and to HCs, but no differences in other regional metabolites.

CONCLUSIONS: The observed metabolite profile in TRS (higher PCho+GPCho and myo-inositol signal) is consistent with the hypothesis that TRS has a neuroinflammatory component, although it is not a critical test of that hypothesis. A similar profile is seen in healthy aging, which is known to involve increased neuroinflammation and glial activation. As the overall number of datasets was low, however, results should be considered preliminary and highlight the need for additional studies of brain metabolites in TRS and their possible association with inflammatory processes.