Alterations of neurometabolism in the dorsolateral prefrontal cortex and thalamus in transition to psychosis patients change under treatment as usual – A two years follow-up 1H/31P-MR-spectroscopy study

Background The ultra-high risk (UHR) paradigm allows early contact with patients developing acute psychosis and the study of treatment effects on the underlying pathology. Methods 29 patients with first acute psychosis according to CAARMS criteria (transition patients, TP) (T0) and thereof 22 patients after two-year follow-up (mean 788 d) (T1) underwent 1H-/31P-MR spectroscopy of the prefrontal (DLPFC) and anterior midcingulate (aMCC) cortices and the thalamus. N-acetylaspartate (NAA), glutamate (Glu, Glx), energy (PCr, ATP) and phospholipid metabolites (PME, PDE) were compared to 27 healthy controls by ANCOVA and correlated with patients' symptom ratings (BPRS-E, SCL-90R). For longitudinal analysis, linear mixed model (LMM) and ANCOVA for repeated measures were used. Results DLPFC : In patients, NAA and PME were decreased bilaterally and Glu on the left side at T0. Left-sided Glu and NAA (trend) and bilateral Glx increased during follow-up. Thalamus : In TP, bilateral NAA, left-sided Glu and right-sided Glx were decreased at T0; bilateral NAA and left-sided Glx increased during follow-up. aMCC : In TP, bilateral NAA, right-sided Glu, and bilateral PME and PDE were decreased, while left-sided PCr was increased at T0. No changes were observed during follow-up. Conclusion Regardless of the long-term diagnosis, the psychotic state of illness includes disturbed neuronal function in the DLPFC, thalamus and aMCC. Treatment-as-usual (TAU), including antipsychotic/antidepressant medication and supportive psychotherapy, had an effect on the thalamo-frontal area but not or less pronounced on the neurometabolic deficits of the aMCC.