31P-spectroscopy of frontal lobe in schizophrenia: alterations in phospholipid and high-energy phosphate metabolism

Abstract

Studies using 31P-magnetic resonance spectroscopy (MRS) reported on abnormalities in frontal lobe metabolism in schizophrenia. The most consistent findings were a reduction in the resonances of phosphomonoesters (PME) and/or increased phosphodiesters (PDE), which are, respectively, the precursors and the metabolites of membrane phospholipids, thus suggesting an accelerated phospholipid metabolism in the disease. Other studies reported increased high-energy phosphates (ATP—adenosine triphosphate and PCr—phosphocreatine) in schizophrenia, reflecting decreased use of energy in the frontal lobe. We investigated 53 schizophrenic patients (DSM-IV) and 35 healthy controls. Eighteen from these patients were drug naı̈ve and the remaining 35 were drug-free for an average of 6 months. Phospholipid metabolism and high-energy phosphates were assessed in the left frontal lobe using 31P-MRS. Psychopathological evaluation was done with the Brief Psychiatric Rating Scale (BPRS) and the Negative Symptoms Rating Scale (NSRS). Neuropsychological evaluation was performed with the Wisconsin Card Sorting Test (WCST), Stroop Test and Wechsler Adult Intelligence Scale. Drug-naı̈ve patients showed reduced PDE in the left frontal lobe compared to controls and to previously medicated patients ( p<0.05). No differences among the three groups were found regarding the other spectroscopy parameters. In healthy controls, but not in schizophrenics, a negative (and probably physiological) correlation was found between PME and PDE ( p<0.01). In schizophrenic patients, ATP was correlated with negative symptoms and with neuropsychological impairment ( p<0.01). The lack of a correlation between PME and PDE, as well as the reduction of PDE in schizophrenia, suggest a disrupted phospholipid metabolism in the disease, albeit on a contrary direction of that reported in literature. The relationships of ATP with negative symptoms and neuropsychological deficit suggest an alteration of energetic demand in the frontal lobe of schizophrenic patients, which is in line with the hypofrontality hypothesis of the disease.