phosphorus-radioisotopes and Schizophrenia

Magnetic resonance spectroscopy is a noninvasive investigative technique for in vivo detection of biochemical changes in neuropsychiatric disorders for which especially proton (1H-MRS) and phosphorus (31P-MRS) magnetic resonance spectroscopy have been used. In this review we explain the principles of MRS and summarize the studies in schizophrenia. A systematic literature review was carried out for 1H-MRS studies investigating schizophrenic patients compared to controls. The inconsistent results in the cited studies may be due to different study population, specific neuroimaging technique, and selected brain regions. Frequent findings are decreased PME and increased PDE concentrations (31P-MRS) linked to altered metabolism of membrane phospholipids and decreased N-acetylaspartate (NAA) or NAA/choline ratio (1H-MRS) linked to neuronal damage in frontal (DLPFC) or temporal regions in patients with schizophrenia. These results contribute to the disturbed frontotemporal-thalamic network assumed in schizophrenia and are supported by additional functional neuroimaging, MRI morphometry, and neuropsychological evaluation. The combination of the described investigative techniques with MRS in follow-up studies may provide more specific clues for understanding the pathogenesis and disease course in schizophrenia.

Topics: Brain; Clinical Trials as Topic; Humans; Magnetic Resonance Spectroscopy; Nerve Tissue Proteins; Neurotransmitter Agents; Phospholipids; Phosphorus Radioisotopes; Protons; Schizophrenia

31Phosphorus nuclear magnetic resonance spectroscopy (31P-MRS) has gained much interest in schizophrenia research in the last years, since it allows noninvasive measurement of high energy phosphates and phospholipids of the human brain in vivo. Thus, several studies have reported cerebral metabolic differences between patients and healthy controls as well as on lateralization effects and influences of epidemiological and psychopathological factors. This review gives a survey of the potential of 31P-MRS in schizophrenia research and summarizes and comments on the results of preceding studies. The discussion covers the reduction of phospholipids in patients in the context of the membrane phospholipid hypotheses, the question of an energetic hypometabolism in schizophrenics, and the influence of neuroleptic medication.

Topics: Adenosine Triphosphate; Age Factors; Brain; Brain Chemistry; Controlled Clinical Trials as Topic; Dominance, Cerebral; Humans; Magnetic Resonance Spectroscopy; Phosphates; Phosphocreatine; Phospholipids; Phosphorus Radioisotopes; Schizophrenia; Sex Factors

Alterations in the phosphoinositide signalling system have been proposed as a possible biological marker of schizophrenia. We studied the levels of inositol 1,4,5-trisphosphate (IP3), cytosolic Ca2+ concentrations ([Ca2+]i), and the incorporation of [32P]-orthophosphate into inositol phospholipids and phosphatidic acid (PA) in blood platelets of neuroleptic-treated schizophrenics in comparison with controls. The [Ca2+]i was significantly higher in platelets of one month neuroleptic-treated patients (155+/-5.8 nM) in comparison with controls (95+/-5.4 nM). Neuroleptic therapy decreased the [Ca2+]i, but even after long-term therapy it remained significantly higher (114+/-5.7 nM) than in controls. Differences were also found in the level of IP3 between controls (30+/-4.0 pmol/10(9) platelets), drug-free schizophrenics (52+/-9.0 pmol/10(9) platelets) and treated patients (50+/-6.0 pmol/10(9) platelets). The increased turnover of PA was observed in platelets of neuroleptic-treated schizophrenic patients. The study suggests that the regulation of calcium homeostasis and pathways involved in the phosphoinositide signalling system are altered in the platelets of schizophrenics. Neuroleptic therapy did not remove the observed changes in [Ca2+]i and IP3 levels.

Topics: Adolescent; Adult; Antipsychotic Agents; Blood Platelets; Calcium; Female; Humans; Inositol 1,4,5-Trisphosphate; Male; Middle Aged; Phosphatidic Acids; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositol Phosphates; Phosphatidylinositols; Phosphorus Radioisotopes; Schizophrenia; Signal Transduction; Time Factors

This study directly assessed, for the first time, whether there was a change in brain cell motion-restricted membrane phospholipids in vivo in patients with schizophrenia with mild to moderate negative symptoms, by quantification of the underlying broad resonance signal of cerebral 31-phosphorus magnetic resonance scans. Cerebral 31-phosphorus magnetic resonance spectroscopy was carried out in 16 schizophrenia patients and 16 age- and gender-matched normal controls. Spectra were obtained from 70x70x70 mm3 voxels using an image-selected in vivo spectroscopy pulse sequence. There was no significant difference in the broad resonances between the two groups, with the mean (S.E.) percentage signal being 59.4 (5.6) for the patients and 53.5 (5.9) for the controls. The phosphomonoesters and phosphodiesters narrow signals also did not differ significantly, their ratio being 0.26 (0.01) in the patients and 0.25 (0.01) in the controls. These results appear to be at variance with the changes expected under the membrane phospholipid hypothesis of schizophrenia.

Topics: Brain; Humans; Magnetic Resonance Spectroscopy; Membrane Lipids; Phospholipids; Phosphorus Radioisotopes; Schizophrenia

Topics: Adenosine Triphosphate; Biomedical Research; History, 20th Century; Human Experimentation; Humans; Norway; Phosphorus Radioisotopes; Radioisotopes; Radionuclide Imaging; Schizophrenia

Topics: Adult; Brain; Humans; Huntington Disease; Magnetic Resonance Spectroscopy; Male; Phosphorus Radioisotopes; Schizophrenia

The cellular expression of the mRNAs encoding the dopamine D1 receptor, dopamine D2 receptor and the neuropeptides enkephalin and substance P was determined in fresh frozen sections of human post-mortem caudate nucleus from control and schizophrenic brains using the technique of radioactive in situ hybridisation coupled with computer-assisted image analysis. Measurements of silver grain densities and mean cross-sectional somatic areas revealed no significant differences in the expression of any of these four gene transcripts. Further, cell count estimates revealed that each of these four mRNAs was expressed by approximately 20% of caudate cells (neurones and glia) in both control and schizophrenic tissue. These data demonstrate that the cellular expression of the dopamine D1 and D2 receptors and the neuropeptides enkephalin and substance P mRNAs are stable post mortem and that the relative cellular abundance of these mRNAs is not altered in the caudate nucleus of schizophrenic brains when compared to controls. These findings draw into focus the possible sites of action of clinically prescribed neuroleptics and suggest that chronic neuroleptic treatment of patients displaying negative schizophrenic symptoms may 're-set' an underlying neurochemical imbalance within the caudate nucleus.

Topics: Aged; Autoradiography; Caudate Nucleus; Enkephalins; Female; Gene Expression; Humans; In Situ Hybridization; Male; Middle Aged; Oligonucleotide Probes; Organ Specificity; Phosphorus Radioisotopes; Protein Precursors; Putamen; Receptors, Dopamine D1; Receptors, Dopamine D2; Reference Values; Schizophrenia; Substance P

Using a complex of physiological methods developed by the author the initial state of bilateral permeability of the capillaries, the supply of tissues with blood through the capillaries, and the character of changes of those parameters in the conditions of the adaptational activity of microcirculation in schizophrenic patients were studied. It has been found that three types of microcirculation disturbances leading to tissue hypoxia can be distinguished in schizophrenia depending on the process type and stage. The types of the capillary permeability disturbances in various forms of the schizophrenic process are described.

Topics: Adult; Capillary Permeability; Diphenhydramine; Ethinyl Estradiol; Female; Haloperidol; Histamine H1 Antagonists; Humans; Male; Methyltestosterone; Microcirculation; Parasympatholytics; Phosphorus Radioisotopes; Schizophrenia; Trihexyphenidyl

Topics: Adult; Amitriptyline; Capillary Permeability; Chronic Disease; Drug Therapy, Combination; Female; Humans; Insulin; Male; Mental Disorders; Microcirculation; Phosphorus; Phosphorus Radioisotopes; Psychotropic Drugs; Remission, Spontaneous; Schizophrenia; Schizophrenia, Catatonic; Schizophrenia, Paranoid

Cerebrospinal fluid (CSF) contains two groups of proteins that bind tightly to DNA and to polyriboguanylic acid, respectively. In certain diseases the amounts of a given nucleic acid bound by a constant volume of CSF may increase, while in others the amount of such proteins may be reduced. Binding of polyriboguanylic acid increased in CSF samples from patients with brain tumors, stroke, multiple sclerosis, and communicating hydrocephalus, but it significantly decreased in CSF samples from patients with obstructive hydrocephalus. These increases may or may not be proportional to the rise in total CSF proteins characteristic for these diseases. Elevated binding of DNA was observed in samples from patients with hydrocephalus, epilepsy, and cortical atrophy. The technique described may be applicable to the diagnosis of a variety of diseases of the central nervous system.

Topics: Alcoholism; Astrocytoma; Brain Diseases; Brain Injuries; Brain Neoplasms; Carcinoma; Cerebrospinal Fluid Proteins; Cerebrovascular Disorders; Child, Preschool; DNA; Epilepsy; Female; Guanine Nucleotides; Headache; Humans; Hydrocephalus; Meningioma; Middle Aged; Multiple Sclerosis; Neurilemmoma; Phosphorus Radioisotopes; Polynucleotides; Protein Binding; Schizophrenia; Tritium