Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-naïve patients with psychosis

Kirsten B. Bojesen, Bjorn H. Ebdrup, Kasper Jessen, Anne Sigvard, Karen Tangmose, Richard A.E. Edden, Henrik B.W. Larsson, Egill Rostrup, Brian V. Broberg, Birte Y. Glenthoj

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Background Poor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and γ-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs). Methods Thirty-nine antipsychotic-naïve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response. Results Before treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ. Conclusion Glutamatergic and GABAergic abnormalities in antipsychotic-naïve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.

Original languageEnglish (US)
Pages (from-to)2182-2193
Number of pages12
JournalPsychological medicine
Issue number13
StatePublished - Oct 1 2020


  • Anterior cingulate cortex
  • GABA
  • antipsychotic-naïve
  • first-episode psychosis
  • glutamate
  • magnetic resonance spectroscopy
  • thalamus
  • treatment outcome

ASJC Scopus subject areas

  • Applied Psychology
  • Psychiatry and Mental health


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