Increase of phosphodiesters during neuroleptic treatment of schizophrenics: a longitudinal 31P-magnetic resonance spectroscopic study.

BACKGROUND: Increased levels of phosphodiesters (PDE%) and reduced relative concentrations of phosphomonoesters (PME%) have been reported in unmedicated schizophrenics, whereas findings in brain of medicated patients were not consistent. METHODS: We determined in vivo the metabolism of phospholipids and high-energy phosphates in the left and right frontal lobes of 8 patients with schizophrenia using 31P-magnetic resonance spectroscopy (31P-MRS). Serial investigations were performed first after a neuroleptic-free period (mean 7.5 +/- 1.9 days) and second, after neuroleptic treatment (mean 20.6 +/- 11.1 days). RESULTS: PDE% increased significantly in the left frontal lobe (32.0 +/- 5.9% versus 36.9 +/- 5.6%, p = .009) after medication. All other parameters showed no significant differences. CONCLUSIONS: Our study suggests that neuroleptics do not decrease phospholipase A2 activity in schizophrenia. Individual neuroleptics may have different effects on phospholipase A2 activity as indicated by animal studies. An influence of neuroleptics on high-energy phosphates cannot be confirmed by our data.

31Phosphorus magnetic resonance spectroscopy of the dorsolateral prefrontal region in schizophrenics--a study including 50 patients and 36 controls.

BACKGROUND: In a preliminary study we found decreased phosphodiester (PDE)% values and an increased phosphomonoester (PME)/phosphodiester ratio in the dorsolateral prefrontal region (DLPFR) of 13 chronic schizophrenics vs. 14 controls using 31phosphorus magnetic resonance spectroscopy (31P-MRS). Since these results are in contrast to the findings of other groups, we increased our study group to a total of 50 chronic schizophrenics on stable neuroleptic medication and 36 controls to minimize the possibility of a chance result due to small sample size. METHODS: An image-selected in vivo 31P-MRS method on a Philips Gyroscan ACS II scanner working at 1.5 T was used. RESULTS: We could confirm our earlier findings of decreased PDE% levels in schizophrenics. Additionally, we found phosphocreatine (PCr)% and PCr/adenosine triphosphate (ATP) to be increased in the schizophrenics. While no association between PME% and PDE% with neuroleptic medication was found, ATP% correlated positively and PCr/ATP negatively with the chlorpromazine equivalent dose. CONCLUSIONS: The decreased PDE% levels might be characteristic only for chronic, neuroleptic-treated patients. The finding of altered high-energy phosphate levels can be interpreted as an indication of decreased energy-demanding processes in the DLPFR of the investigated patients compared to controls.

High-energy phosphates in the frontal lobe correlate with Wisconsin Card Sort Test performance in controls, not in schizophrenics: a 31phosphorus magnetic resonance spectroscopic and neuropsychological investigation.

In recent years, a number of 31phosphorus magnetic resonance spectroscopy (P-MRS) studies on the frontal lobe of schizophrenics have been performed, reporting alterations of phospholipids and high-energy phosphates. Deicken et al. (1994b) recently found positive correlations between left frontal phosphomonoester% (PME%) levels and the performance of a specific frontal lobe task, the Wisconsin Card Sorting Test (WCST), in schizophrenics. In the present paper, the correlations between phospholipids and high-energy phosphates in the frontal lobe of 26 schizophrenics and 23 controls measured with a volume-selective P-MRS method were investigated. Overall, we could not find any correlations between WCST results and phospholipid levels, but in controls phosphocreatine% (PCr%) and PCr/adenenosine triphosphate (ATP) ratios were negatively correlated with test performance. Since PCr behaves as a buffer of ATP, in the sense that when ATP is consumed by neuronal activity PCr is catalysed rapidly to ATP, increased PCr% values and, moreover, increased PCr/ATP ratios point to a decreased ATP consumption. Thus, the correlations found between PCr% and PCr/ATP and test performance in controls point to an association between reduced performance in a specific frontal lobe task and decreased energy demanding processes at rest. This association was not found in schizophrenics, possibly due to the influence of neuroleptic medication or the disease process per se.

Decreased energy demanding processes in the frontal lobes of schizophrenics due to neuroleptics? A 31P-magneto-resonance spectroscopic study.

In the present investigation on 31P-magneto-resonance spectroscopic parameters in the frontal lobe, we found phosphocreatine levels and the ratio phosphocreatine/adenosine triphosphate to be increased (12.62 +/- 1.98% resp. 0.31 +/- 0.06) in 50 neuroleptic-treated schizophrenics, whereas no differences were detected in 10 neuroleptic-free patients (11.66 +/- 2.57% resp. 0.29 +/- 0.08) compared to 36 controls (11.37 +/- 1.45 resp. 0.29 +/- 0.04). This result points to a major role of neuroleptics in the metabolism of high-energy phosphates.

[Electrophysiologic and histomorphological studies on the nervus ischiadicus of rats. I. The uninjured nerves]. / Elektrophysiologische und histomorphologische Untersuchungen am Nervus ischiadicus der Ratte. I. Untersuchungen des ungeschädigten Nerven.

We report in the model described above on measurements of striking features of the normal sciatic nerve of adult male Wistarrats (250-300 g). Electrophysiological parameters were measured by means of an Electromyoneurograph (needle stimulation). The calculation of the maximum motor nerve conduction velocity results in a mean value of 59.6 ms-1. The mean compound action potentials of the foot muscle are 9.2 mV (proximal stimulated) and 10.1 mV (distal stimulated). Counting out 10011 nerve fibres in Light Microscoping Findings for histological studies we got a nearly Normal distribution of the fibre diameters with a mean fibre diameter of 7.09 microns. The corresponding density of nerve fibres is 8700.4 mm-2. The calculated percentage of neural tissue, related to the surrounding connective tissue is about 36.32%.

[Coronary heart diseases and associated risk factors in newly manifested type II diabetic patients over the course of 5 years]. / Koronare Herzkrankheit und assoziierte Risikofaktoren bei frisch manifestierten Typ-II-Diabetikern im 5-Jahres-Ablauf.

Using the baseline data of the diabetes intervention study (DIS) from 1126 newly manifested type II-diabetics our analysis demonstrates higher mean-values of some components of the so-called metabolic syndrome in patients with ECG-abnormalities indicating coronary heart disease (CHD) in diagnosis of diabetes compared with subjects without ECG-findings. The impact of general risk factors for the prevalence of CHD in diagnosis and after a 5-year follow-up is obviously different in both sexes. In multivariate analysis only systolic blood pressure was persistently a significant predictor in both sex groups. With increasing age life-duration gets as time-related factor importance for the development of CHD. The mathematically demonstrated association of triglyceride levels to the presence of ECG-abnormalities agrees with the results of WHO multinational study of vascular disease in diabetes mellitus. In the interventions as well as in the control-groups diabetic subjects with CHD after 5 year follow-up showed in comparison to diabetics without CHD higher levels of investigated risk factors which develop their pathogenetic effect probably by their clustering impact, because the differences of their mean-values are only in some cases significant. The common lower level of the most risk factors at the intervention group compared with the conventionally treated group is the result of the intervention measures.

[Intensive basic therapy decreases the need for drug treatment and improves glucose control: an important result of the diabetes intervention study]. / Intensivierte Basistherapie verringert die Notwendigkeit medikamentöser Behandlung und verbessert die Glukosekontrolle: ein wichtiges Ergebnis der Diabetesinterventionsstudie (DIS).

In a period of five years in the diabetes intervention study (DIS), 1,139 diabetics aged 30-55 years, who in a 6-week screening phase had been classified as dietetically manageable, were treated in a controlled randomized study with intensified non-medicamentous basic therapy and--in a double blind trial--with 1,6 g clofibric acid. The essential components of the basic therapy were a fat-modified diet (so-called prudent diet) and recommendations for endurance training. Thus in comparison to the control group we succeeded in performing a ca. 40% decrease of the application of oral antidiabetic drugs. The fasting blood values were, nevertheless, with 155 mg% significantly lower than in the control group (169 mg%). Clofibric acid had no influence neither on the necessity to use insulin or oral antidiabetic drugs nor to the control of glycaemia.

[Phosphorus 31 magnetic resonance spectroscopy in schizophrenia research. Pathophysiology of cerebral metabolism of high-energy phosphate and membrane phospholipids]. / 31Phosphor-Magnetresonanzspektroskopie in der Schizophrenieforschung. Zur Pathophysiologie des zerebralen Stoffwechsels energiereicher Phosphate und Membranphospholipide.

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.

Frontal lobe in vivo (31)P-MRS reveals gender differences in healthy controls, not in schizophrenics.

Phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) has gained much interest in schizophrenia research in recent years since it allows the non-invasive measurement of high-energy phosphates and phospholipids in vivo. However, until now only differences in metabolite concentrations between certain brain areas of schizophrenic patients and healthy controls have been examined. We investigated the influence of gender on the concentrations of different phosphorus compounds. For this purpose, well-defined volumes in the frontal lobe of 32 healthy controls and 51 schizophrenic in-patients were examined with an image selected in vivo spectroscopy (ISIS) sequence on a whole-body scanner at 1.5 T. Healthy females exhibited increased values of inorganic phosphate (P(i)) and decreased values of phosphocreatine (PCr) in comparison to their male counterparts. In schizophrenic patients such gender differences were not present. Thus, the results can be interpreted in the sense that frontal energy demanding processes are enhanced in female compared to male healthy volunteers; schizophrenia seems to reduce these gender differences.

[Early diagnosis of diabetes mellitus--studies on the effectiveness and value of diabetes screening actions]. / Frühdiagnostische Erfassung des Diabetes mellitus -- Untersuchungen zur Effektivität und Aussagefähigkeit der Diabetessuchaktionen.

Actions to found out cases of diabetes, which exclusively worked with a proof of glucosuria using the biophan-test stripe, were always loaded by a high percentage of falsely pathologic, but also by a not insignificant number of falsely negative investigation results. -- Therefore a multiphasic screening was carried out in 5,424 persons at the age of 20 and more years, which tested the problems mentioned and judged the possibilities of an improved diagnosis.