Reduced phosphodiesters and high-energy phosphates in the frontal lobe of schizophrenic patients: a (31)P chemical shift spectroscopic-imaging study.

BACKGROUND: (31)Phosphorous magnetic resonance spectroscopy has been widely used to evaluate schizophrenic patients in comparison to control subjects, because it allows the investigation of both phospholipid and energy metabolism in vivo; however, the results achieved so far are inconsistent. Chemical shift imaging (CSI) has the advantage that instead of only one or a few preselected voxels the tissue of a whole brain slice can be examined. The aim of the present investigation was to determine whether the results of previous studies of our group, showing that phosphodiesters (PDE) are decreased in the frontal lobe of schizophrenic patients as compared to control subjects, might be confirmed in an independent unmedicated patient sample using the CSI technique. METHODS: A carefully selected new cohort including 11 neuroleptic-free schizophrenic patients and 11 age- and gender-matched healthy control subjects was recruited. CSI was applied and an innovative analysis method for CSI data based on a general linear model was used. RESULTS: PDE, phosphocreatine, and adenosine triphosphate (ATP) were found to be significantly decreased in the frontal lobe of patients with schizophrenia. CONCLUSIONS: Because PDE was decreased in schizophrenic patients, the membrane phospholipid hypothesis of schizophrenia could not be corroborated. Further results indicate decreased ATP production in the frontal lobe of patients with schizophrenia.

Multilead quantitative electroencephalogram profile and cognitive evoked potentials (P300) in healthy subjects after a single dose of olanzapine.

RATIONALE: Olanzapine is an atypical antipsychotic drug with a more favourable safety profile than typical antipsychotics with a hitherto unknown topographic quantitative electroencephalogram (QEEG) profile. OBJECTIVES: We investigated electrical brain activity (QEEG and cognitive event related potentials, ERPs) in healthy subjects who received olanzapine. METHODS: Vigilance-controlled, 19-channel EEG and ERP in an auditory odd-ball paradigm were recorded before and 3 h, 6 h and 9 h after administration of either a single dose of placebo or olanzapine (2.5 mg and 5 mg) in ten healthy subjects. QEEG was analysed by spectral analysis and evaluated in nine frequency bands. For the P300 component in the odd-ball ERP, the amplitude and latency was analysed. Statistical effects were tested using a repeated-measurement analysis of variance. RESULTS: For the interaction between time and treatment, significant effects were observed for theta, alpha-2, beta-2 and beta-4 frequency bands. The amplitude of the activity in the theta band increased most significantly 6 h after the 5-mg administration of olanzapine. A pronounced decrease of the alpha-2 activity especially 9 h after 5 mg olanzapine administration could be observed. In most beta frequency bands, and most significantly in the beta-4 band, a dose-dependent decrease of the activity beginning 6 h after drug administration was demonstrated. Topographic effects could be observed for the beta-2 band (occipital decrease) and a tendency for the alpha-2 band (frontal increase and occipital decrease), both indicating a frontal shift of brain electrical activity. There were no significant changes in P300 amplitude or latency after drug administration. CONCLUSION: QEEG alterations after olanzapine administration were similar to EEG effects gained by other atypical antipsychotic drugs, such as clozapine. The increase of theta activity is comparable to the frequency distribution observed for thymoleptics or antipsychotics for which treatment-emergent somnolence is commonly observed, whereas the decrease of beta activity observed after olanzapine administration is not characteristic for these drugs. There were no clear signs for an increased cerebral excitability after a single-dose administration of 2.5 mg and 5 mg olanzapine in healthy controls.