Molecular insights into schizophrenia

Abstract

A number of studies have demonstrated alterations in the structure and function of the frontal cortex in some schizophrenic patients. The possible etiology and pathogenesis of these abnormalities are unknown, but genetic and developmental causes are frequently mentioned. Recent in vivo 31P NMR studies of the dorsal prefrontal cortex have been conducted in eleven neuroleptic naive, first episode schizophrenic patients and compared with normal controls of comparable age, educational level and parental educational level. The findings in the schizophrenic patients are different from those of normal IQ adult autistic patients of comparable age and Alzheimer's patients but similar to normal elderly controls. These studies show decreased frontal lobe utilization of adenosine triphosphate in the schizophrenic patients which suggests a hypoactive dorsal prefrontal cortex. In addition, indices of membrane phospholipid metabolism are altered in the schizophrenic patients. However, the findings in the schizophrenic patients are quite similar to those observed in normal elderly controls and to those that normally occur to a lesser degree during adolescence. The phospholipid alterations observed in the schizophrenic patients are compatible with either premature aging or altered timing and exaggeration of the regressive events which occur during normal brain development. The changes in high-energy phosphate metabolism observed in the schizophrenic patients may prove to be state dependent, but the changes in membrane phospholipid metabolism could be related to molecular changes that precede the onset of clinical symptoms and brain structural changes in schizophrenia. These findings suggest new avenues of thinking about the pathogenesis and treatment of schizophrenia.