Brain metabolite levels in remitted psychotic depression with consideration of effects of antipsychotic medication.

Hideaki Tani, Iska Moxon-Emre, Natalie J Forde, Nicholas H Neufeld, Kathleen S Bingham, Ellen M Whyte, Barnett S Meyers, George S Alexopoulos, Matthew J Hoptman, Anthony J Rothschild, Hiroyuki Uchida, Alastair J Flint, Benoit H Mulsant, Aristotle N Voineskos

Journal: Brain imaging and behavior 2024;18(1):117-129

PMID: 37917311

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Abstract

BACKGROUND

The neurobiology of psychotic depression is not well understood and can be confounded by antipsychotics. Magnetic resonance spectroscopy (MRS) is an ideal tool to measure brain metabolites non-invasively. We cross-sectionally assessed brain metabolites in patients with remitted psychotic depression and controls. We also longitudinally assessed the effects of olanzapine versus placebo on brain metabolites.

METHODS

Following remission, patients with psychotic depression were randomized to continue sertraline + olanzapine (n = 15) or switched to sertraline + placebo (n = 18), at which point they completed an MRS scan. Patients completed a second scan either 36 weeks later, relapse, or discontinuation. Where water-scaled metabolite levels were obtained and a Point-RESolved Spectroscopy sequence was utilized, choline, myo-inositol, glutamate + glutamine (Glx), N-acetylaspartate, and creatine were measured in the left dorsolateral prefrontal cortex (L-DLPFC) and dorsal anterior cingulate cortex (dACC). An ANCOVA was used to compare metabolites between patients (n = 40) and controls (n = 46). A linear mixed-model was used to compare olanzapine versus placebo groups.

RESULTS

Cross-sectionally, patients (compared to controls) had higher myo-inositol (standardized mean difference [SMD] = 0.84; 95%CI = 0.25-1.44; p = 0.005) in the dACC but not different Glx, choline, N-acetylaspartate, and creatine. Longitudinally, patients randomized to placebo (compared to olanzapine) showed a significantly greater change with a reduction of creatine (SMD = 1.51; 95%CI = 0.71-2.31; p = 0.0002) in the dACC but not glutamate + glutamine, choline, myo-inositol, and N-acetylaspartate.

CONCLUSIONS

Patients with remitted psychotic depression have higher myo-inositol than controls. Olanzapine may maintain creatine levels. Future studies are needed to further disentangle the mechanisms of action of olanzapine.

Address: Centre for Addiction and Mental Health and Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada.; Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.; University Health Network and Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada.; Department of Psychiatry, University of Pittsburgh School of Medicine and UPMC Western Psychiatric Hospital, Pittsburgh, PA, USA.; Department of Psychiatry, Weill Medical College of Cornell University and New York Presbyterian Hospital, White Plains, NY, USA.; Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.; Department of Psychiatry, New York University School of Medicine, New York, NY, USA.; University of Massachusetts Medical School and UMass Memorial Health Care, Worcester, MA, USA.; Centre for Addiction and Mental Health and Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada. [email protected].

DOI: 10.1007/s11682-023-00807-0

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MeSH Terms: Humans, Antipsychotic Agents, Aspartic Acid, Brain, Choline, Creatine, Depression, Glutamine, Inositol, Magnetic Resonance Imaging, Olanzapine, Sertraline