In vivo 31P NMR spectroscopy shows an increase in glycerophosphorylcholine concentration without alterations in mitochondrial function in the prefrontal cortex of medicated schizophrenic patients at rest.
The (31)P NMR localised method was used to study the metabolism of phospholipid and high energy phosphate in the prefrontal cortex. The spectra were taken from patients with schizophrenia (11 males) receiving neuroleptic medication, and were compared to normal controls (15 males). Their spectral intensities were analysed using a non-linear least-squares method with a prior knowledge of the fixed chemical shifts and linewidths, leading to further resolution into resonances of glycerophosphorylethanolamine (GPE), glycerophosphorylcholine (GPC), phosphorylethanolamine (PE) and phosphorylcholine (PC). The metabolite concentrations were calculated referring to the spectral intensities of phosphate phantoms with known concentrations. T1 values of phantom and cerebrum were estimated from a series of localised inversion recovery spectra to correct for the signal saturation effects. The schizophrenic patients showed an increased concentration of GPC but not GPE, PE or PC. Furthermore, no difference was observed regarding the concentration of high-energy phosphates such as phosphocreatine, inorganic phosphate and ATP. The patients did not show any differences in mitochondrial function such as phosphorylation potential and the ratio of the rate of ATP synthesis. Thus, an increase in GPC concentration in the prefrontal cortex could be characteristic of the pathophysiology of schizophrenia with mild negative symptoms.
Shirayama
Yukihiko
Y
Department of Psychiatry, National Center Hospital for Mental, Nervous and Muscular Disorders, and Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan. shirayama@rapid.ocn.ne.jp
Yano
Toshio
T
Takahashi
Kiyohisa
K
Takahashi
Seizo
S
Ogino
Takashi
T
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001923:Brain Chemistry; D016022:Case-Control Studies; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D004734:Energy Metabolism; D005997:Glycerylphosphorylcholine / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008928:Mitochondria / Q000502:physiology*; D010710:Phosphates / Q000378:metabolism; D010759:Phosphorus Isotopes; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*
D014150:Antipsychotic Agents; D010710:Phosphates; D010759:Phosphorus Isotopes; D005997:Glycerylphosphorylcholine