Metabolite differences in the medial prefrontal cortex in schizophrenia patients with and without persistent auditory verbal hallucinations: a (1)H MRS study

Studies of schizophrenia (SCZ) have associated auditory verbal hallucinations (AVH) with structural and functional abnormalities in frontal cortex, especially medial prefrontal cortex (mPFC). Although abnormal prefrontal network connectivity associated with language production has been studied extensively, the relationship between mPFC dysfunction (highly relevant to the pathophysiology of SCZ) and AVH has been rarely investigated. In this study, proton magnetic resonance spectroscopy was used to measure metabolite levels in the mPFC in 61 SCZ patients with persistent AVH (pAVH), 53 SCZ patients without AVH (non-AVH), and 59 healthy controls (HC). The pAVH group showed significantly lower levels of N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (tNAA) and glutamate + glutamine (Glx), compared with the non-AVH (tNAA: p = 0.022, Glx: p = 0.012) and HC (tNAA: p = 0.001, Glx: p = 0.001) groups. No difference was found in the levels of tNAA and Glx between non-AVH and HC. The levels of tNAA and Glx in the mPFC was negatively correlated with the severity of pAVH (tNAA: r = −0.24, p = 0.014; Glx: r = −0.30, p = 0.002). In conclusion, pAVH in SCZ patients might be related to decreased levels of tNAA and Glx in the mPFC, indicating that tNAA or Glx might play a key role in the pathogenesis of pAVH.