Association of Cortical Glutamate and Working Memory Activation in Patients With Schizophrenia: A Multimodal Proton Magnetic Resonance Spectroscopy and Functional Magnetic Resonance Imaging Study

Jakob Kaminski; Tobias Gleich; Yu Fukuda; Teresa Katthagen; Jürgen Gallinat; Andreas Heinz; Florian Schlagenhauf

doi:10.1016/j.biopsych.2019.07.011

Association of Cortical Glutamate and Working Memory Activation in Patients With Schizophrenia: A Multimodal Proton Magnetic Resonance Spectroscopy and Functional Magnetic Resonance Imaging Study

Biol Psychiatry. 2020 Feb 1;87(3):225-233. doi: 10.1016/j.biopsych.2019.07.011. Epub 2019 Jul 26.

Authors

Jakob Kaminski¹, Tobias Gleich², Yu Fukuda², Teresa Katthagen², Jürgen Gallinat³, Andreas Heinz², Florian Schlagenhauf⁴

Affiliations

¹ Department of Psychiatry and Psychotherapy Charité Campus Mitte, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany. Electronic address: jakob.kaminski@charite.de.
² Department of Psychiatry and Psychotherapy Charité Campus Mitte, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
³ University Clinic Hamburg-Eppendorf, Clinic and Policlinic for Psychiatry and Psychotherapy, Hamburg, Germany.
⁴ Department of Psychiatry and Psychotherapy Charité Campus Mitte, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany; Bernstein Center for Computational Neuroscience, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

PMID: 31521336
DOI: 10.1016/j.biopsych.2019.07.011

Abstract

Background: Cognitive deficits such as working memory (WM) impairment are core features of schizophrenia. One candidate marker for the integrity of synaptic neurotransmission necessary for cognitive processes is glutamate. It is frequently postulated that antipsychotic medication possibly alters functional mechanisms in the living brain. We tested in vivo for group differences in activation of the dorsolateral prefrontal cortex (DLPFC) during WM performance and the association with glutamate concentration in DLPFC depending on medication status.

Methods: A total of 90 subjects (35 control subjects, 36 medicated patients, and 19 unmedicated patients) contributed magnetic resonance spectroscopy data. We estimated glutamate in left DLPFC. Subjects performed an n-back WM task (2-back vs. 0-back) during functional magnetic resonance imaging, and local activation in left DLPFC was measured. For analysis of association with medication status, we calculated linear regression models including an interaction effect with group.

Results: Medicated and unmedicated patients with schizophrenia showed impaired performance. We found significantly reduced WM activation in left DLPFC in medicated patients and a trendwise reduction in unmedicated patients as compared with control subjects. We found no group difference in local glutamate concentration. However, we found differential effects of medication status on the association between local glutamate concentration and WM activation in left DLPFC, with a positive association in unmedicated patients but not in medicated patients.

Conclusions: We provide evidence that WM-dependent activation is associated with glutamate concentration in unmedicated patients with schizophrenia. Our finding points to putative allostatic changes that affect the functioning of the brain and might be altered through medication.

Keywords: (1)H-MRS; Antipsychotic medication; Glutamate; Psychosis; Schizophrenia; Working memory.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Glutamic Acid
Humans
Magnetic Resonance Imaging
Memory, Short-Term
Prefrontal Cortex / diagnostic imaging
Proton Magnetic Resonance Spectroscopy
Schizophrenia* / diagnostic imaging
Schizophrenia* / drug therapy

Substances

Glutamic Acid