GABA and glutamate in schizophrenia: a 7 T ¹H-MRS study.
Schizophrenia is characterized by loss of brain volume, which may represent an ongoing pathophysiological process. This loss of brain volume may be explained by reduced neuropil rather than neuronal loss, suggesting abnormal synaptic plasticity and cortical microcircuitry. A possible mechanism is hypofunction of the NMDA-type of glutamate receptor, which reduces the excitation of inhibitory GABAergic interneurons, resulting in a disinhibition of glutamatergic pyramidal neurons. Disinhibition of pyramidal cells may result in excessive stimulation by glutamate, which in turn could cause neuronal damage or death through excitotoxicity. In this study, GABA/creatine ratios, and glutamate, NAA, creatine and choline concentrations in the prefrontal and parieto-occipital cortices were measured in 17 patients with schizophrenia and 23 healthy controls using proton magnetic resonance spectroscopy at an ultra-high magnetic field strength of 7 T. Significantly lower GABA/Cr ratios were found in patients with schizophrenia in the prefrontal cortex as compared to healthy controls, with GABA/Cr ratios inversely correlated with cognitive functioning in the patients. No significant change in the GABA/Cr ratio was found between patients and controls in the parieto-occipital cortex, nor were levels of glutamate, NAA, creatine, and choline differed in patients and controls in the prefrontal and parieto-occipital cortices. Our findings support a mechanism involving altered GABA levels distinguished from glutamate levels in the medial prefrontal cortex in schizophrenia, particularly in high functioning patients. A (compensatory) role for GABA through altered inhibitory neurotransmission in the prefrontal cortex may be ongoing in (higher functioning) patients with schizophrenia.
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands.
Anouk
A
Marsman
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands.
René C W
RC
Mandl
Department of Radiology, University Medical Center Utrecht, The Netherlands.
Dennis W J
DW
Klomp
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands.
Marc M
MM
Bohlken
Department of Radiology, University Medical Center Utrecht, The Netherlands.
Vincent O
VO
Boer
Department of Radiotherapy, University Medical Center Utrecht, The Netherlands.
Anna
A
Andreychenko
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands.
Wiepke
W
Cahn
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands.
René S
RS
Kahn
Department of Radiology, University Medical Center Utrecht, The Netherlands.
Peter R
PR
Luijten
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands.
Hilleke E
HE
Hulshoff Pol
D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D001923:Brain Chemistry; D002794:Choline / Q000032:analysis; D003401:Creatine / Q000032:analysis; D005260:Female; D018698:Glutamic Acid / Q000032:analysis*; D006801:Humans; D007360:Intelligence / Q000502:physiology; D008297:Male; D017397:Prefrontal Cortex / Q000737:chemistry; D066244:Proton Magnetic Resonance Spectroscopy; D012559:Schizophrenia / Q000378:metabolism*; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000032:analysis*
D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline
1H-MRS; 7 T; GABA; Glutamate; Schizophrenia