Phospholipid abnormalities in postmortem schizophrenic brains detected by 31P nuclear magnetic resonance spectroscopy: a preliminary study.

It has been hypothesized that schizophrenia arises from cell membrane abnormalities due to changes in phospholipid (PL) composition and metabolism. We have used high resolution, in vitro 31P nuclear magnetic resonance (NMR) to characterize the PLs in left frontal cortex (gray matter) of postmortem brain from four schizophrenics and five controls. High resolution 31P NMR spectra were obtained in an organic-solvent system to resolve PL classes (headgroups) and in a sodium-cholate, aqueous dispersion system to resolve phosphatidylcholine (PC) molecular species. Multivariate analysis which included the major PC molecular species and phosphatidylinositol (PI) showed a significant difference between schizophrenics and controls. Analysis of specific interactions showed that the PI was significantly higher in the schizophrenic group than in the control group. There were no differences between the two groups for other individual PL classes, or for individual PL subclasses determined by the linkage type at the sn-1 position on glycerol. There was a trend for total PL content to be higher in schizophrenics than in controls. There was no evidence for elevated lysophosphatidylcholine or lysophosphatidylethanolamine in schizophrenia. The intensity of the PC peak representing molecular species with one saturated and one unsaturated (one or two double bonds) acyl chain was higher for the schizophrenic group than for the control group. Although these results are not in complete agreement with previous studies, they support the idea that PL abnormalities occur in the brain in schizophrenia and that fatty acid metabolism may be abnormal.

In vitro 1H-magnetic resonance spectroscopy of postmortem brains with schizophrenia.

Some evidence suggests that thalamic dysfunction could explain some of the signs and symptoms of schizophrenia. We measured the absolute concentrations of amino acid metabolites in thalamus, frontal pole, and cerebellar vermis in extracts of postmortem brains from 8 schizophrenics and 10 controls using high-resolution 1H-magnetic resonance spectroscopy. The concentrations of N-acetyl aspartate, glutamate, and valine tended to be reduced in the thalamus of the schizophrenic group. Although it is difficult to ascribe significance to the "tendencies," these data may tend to support other data suggesting decreased thalamic volume or neuronal number in schizophrenia.

Choline acetyltransferase in schizophrenia.

OBJECTIVE: To test the hypothesis that schizophrenia involves altered cholinergic tone in the pons, the authors studied post-mortem brain tissue from subjects with schizophrenia. METHOD: The authors used Western immunoblot to measure the concentration of choline acetyltransferase, an acetylcholine synthesizing enzyme, in the post-mortem brain tissue of 25 schizophrenic subjects and 28 nonschizophrenic comparison subjects. They also measured the concentration of glial fibrillary acidic protein, a protein from astrocytes, to examine the question of neurodegeneration. RESULTS: The pontine choline acetyltransferase concentrations of the schizophrenic subjects were 46% lower than those of comparison subjects, a significant difference. Glial fibrillary acidic protein concentrations did not differ between the two groups. CONCLUSIONS: The lower concentration of choline acetyltransferase in the pontine tegmentum of schizophrenic subjects compared with comparison subjects suggests involvement of pontine cholinergic neurons in schizophrenia.

Age-dependent extinction of thyrotropin-releasing hormone in the human cerebellum.

Immunoreactive TRH was quantified in eight regions of the cerebellum as well as in the medulla, pons, and hypothalamus of the fetal and adult human brain. High levels of TRH were detected in the fetal cerebellum, ranging from 216 +/- 103 pg/mg protein (mean +/- SD) in the deep cerebellar nuclei to 591 +/- 153 pg/mg protein in the anterior vermis. The concentrations of TRH were significantly greater (P less than 0.001) in each of the eight regions of the cerebellum of the fetal brain than in the corresponding regions of the adult brain. The magnitude of the difference between adult and fetal cerebellar levels ranged from an 18-fold difference in the deep cerebellar nuclei to more than a 100-fold difference in the anterior hemisphere. However, the TRH levels in pons and medulla were similar among fetuses and adults, and the TRH concentration in the adult hypothalamus was significantly higher (P less than 0.01) than that in the fetal hypothalamus. The TRH levels in adult rat hypothalami were extremely stable for several hours post mortem. We, therefore, conclude that the differences in cerebellar TRH concentrations of the fetal compared to those of the adult human are not related to a difference in the extent of postmortem degradation of TRH. Rather, we postulate that the decline in cerebellar TRH during maturation is a normal developmental process, and speculate that TRH, which has been found to have diverse effects on the central nervous system, may also influence the development of the human cerebellum.