Relationship between 31P-NMR spectroscopy and neuropsychological performance in schizophrenia

Studies using 31P-Magnetic Resonance Spectroscopy (MRS) reported on abnormalities in frontal lobe metabolism in schizophrenia (1,2). 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, suggesting thus an accelerated phospholipid metabolism in the disease (1,3). Other studies reported increased high-energy phosphate (ATP – adenosine triphosphate and PCr – phosphocreatine) in schizophrenia, reflecting decreased use of energy in the frontal lobe (2,3). We investigated 53 schizophrenic patients (DSM-IV) and 35 healthy controls. Eighteen from these patients were drug-naïve, 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 and the Negative Symptoms Rating Scale. Neuropsychological evaluation was performed with the Wisconsin Card Sorting Test, Stroop Test, and Wechsler Adult Intelligence Scale. Drug-naïve patients showed reduced PDE in left frontal lobe compared to controls and to previously medicated patients (p<0.05). No differences among the 3 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 in the contrary direction of that reported in the 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.

Pettegrew, J.W.; Keshavan, M.S.; Minshew, N.J.; Mcclure, R.J. 31P MRS of metabolic alterations in schizophrenia and neurodevelopment. In: Nasrallah, H.A; Pettegrew, J.W. NMR spectroscopy in psychiatric brain disorders. Washington, American Psychiatric Press, 1995. p. 45–79.

Stanley, J.A.; Pettegrew, J.W.; Keshavan, M.S. Magnetic resonance spectroscopy in schizophrenia: Methodological issues and findings-Part I. Biological Psychiatry, v. 48, p. 357–368, 2000.

Volz, H.-P.; Hübner, G.; Rzanny, R.; Röbger, G.; Preubler, B.; Eichorn, M.; Kreitschmann-Andermahr, I.; Kaiser, W.A.; Sauer, H. High-energy phosphates in the frontal lobe correlate with Wisconsin Card Sort Test performance in controls, not in schizophrenics: a ³¹phosphorus magnetic resonance specroscopic and neuropsychological investigation. Schizophrenia Research, v. 31, p. 37–47, 1998.