Effect of Bilateral Prefrontal rTMS on Left Prefrontal NAA and Glx Levels in Schizophrenia Patients with Predominant Negative Symptoms: An Exploratory Study.
Prefrontal repetitive Transcranial Magnetic Stimulation (rTMS) may improve negative symptoms in patients with schizophrenia, but few studies have investigated the underlying neural mechanism.



This study aims to investigate changes in the levels of glutamate and glutamine (Glx, neurotransmitter and precursor) and N-Acetyl Aspartate (NAA) in the left dorsolateral prefrontal cortex of patients with schizophrenia treated with active bilateral prefrontal rTMS as compared to sham-rTMS, as measured with1H-Magnetic Resonance Spectroscopy (1H-MRS).



Patients were randomized to a 3-week course of active or sham high-frequency rTMS. Pre-treatment and post-treatment1H-MRS data were available for 24 patients with schizophrenia with moderate to severe negative symptoms (Positive and Negative Syndrome Scale (PANSS) negative subscale ≥ 15). Absolute metabolite concentrations were calculated using LCModel with the water peak as reference. To explore the association between treatment condition and changes in concentration of Glx and NAA, we applied a linear regression model.



We observed an increase of Glx concentration in the active treatment group and a decrease of Glx concentration in the group receiving sham treatment. The association between changes in Glx concentration and treatment condition was significant. No significant associations between changes in NAA and treatment condition were found.



Noninvasive neurostimulation with high-frequency bilateral prefrontal rTMS may influence Glx concentration in the prefrontal cortex of patients with schizophrenia. Larger studies are needed to confirm these findings and further elucidate the underlying neural working mechanism of rTMS.
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Rob Giel Research Centrum, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN Neuroimaging Center, Antonius Deusinglaan 2, 9713 AW Groningen, The Netherlands. Electronic address: j.j.l.a.s.n.dlabac@umcg.nl.
Jozarni J
JJ
Dlabac-de Lange
University of Groningen, University Medical Center Groningen, Rob Giel Research Centrum, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN Neuroimaging Center, Antonius Deusinglaan 2, 9713 AW Groningen, The Netherlands; Lentis Psychiatric Institute, Lentis Research, Hereweg 80, 9725 AG Groningen, The Netherlands.
Edith J
EJ
Liemburg
University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN Neuroimaging Center, Antonius Deusinglaan 2, 9713 AW Groningen, The Netherlands; Lentis Psychiatric Institute, Lentis Research, Hereweg 80, 9725 AG Groningen, The Netherlands.
Leonie
L
Bais
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Aida T
AT
van de Poel-Mustafayeva
VU University Medical Centre, Department of Epidemiology and Biostatistics, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Elly S M
ESM
de Lange-de Klerk
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Rob Giel Research Centrum, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN Neuroimaging Center, Antonius Deusinglaan 2, 9713 AW Groningen, The Netherlands; Lentis Psychiatric Institute, Lentis Research, Hereweg 80, 9725 AG Groningen, The Netherlands.
Henderikus
H
Knegtering
University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN Neuroimaging Center, Antonius Deusinglaan 2, 9713 AW Groningen, The Netherlands.
André
A
Aleman
D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D000067657:Pessimism; D017397:Prefrontal Cortex / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000628:therapy; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate
(1)H-Magnetic resonance spectroscopy; Dorsolateral prefrontal cortex; Glutamate; N-Acetyl aspartate; Negative symptoms; Randomized controlled trial; Schizophrenia; Transcranial magnetic stimulation