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

• Published in: Psychological medicine Vol. 50; no. 13; pp. 2182 - 2193
• Main Authors: Bojesen, Kirsten B., Ebdrup, Bjørn H., Jessen, Kasper, Sigvard, Anne, Tangmose, Karen, Edden, Richard A.E., Larsson, Henrik B.W., Rostrup, Egill, Broberg, Brian V., Glenthøj, Birte Y.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.10.2020
• Subjects: Adolescent; Adult; Antipsychotic Agents - therapeutic use; Antipsychotics; Aripiprazole; Case-Control Studies; Cortex; Cortex (cingulate); Creatine; Dopamine; Dopamine receptors; Female; First time; Gamma-aminobutyric acid; gamma-Aminobutyric Acid - analysis; gamma-Aminobutyric Acid - drug effects; gamma-Aminobutyric Acid - metabolism; Glutamatergic transmission; Glutamic Acid - analysis; Glutamic Acid - drug effects; Glutamic Acid - metabolism; Gyrus Cinguli - drug effects; Gyrus Cinguli - metabolism; Humans; Logistic Models; Magnetic resonance imaging; Magnetic resonance spectroscopy; Magnetic Resonance Spectroscopy - methods; Male; Medical prognosis; Neurotransmitters; Original; Original Articles; Patients; Psychiatric Status Rating Scales; Psychosis; Psychotic Disorders - drug therapy; Psychotropic drugs; Schizophrenia; Socioeconomic factors; Thalamus; Thalamus - drug effects; Thalamus - metabolism; Time Factors; Young Adult; γ-Aminobutyric acid; Anterior cingulate cortex; first-episode psychosis; GABA; magnetic resonance spectroscopy; antipsychotic-naïve; treatment outcome; glutamate; thalamus
• ISSN: 0033-2917; 1469-8978; 1469-8978
• DOI: 10.1017/S0033291719002277

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). 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. 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. 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.