Juliana Yacubian

Increased phospholipase A2 activity in schizophrenia with absent response to niacin

An absent response to the niacin skin test has been reported to occur in about 80% of schizophrenic patients, as compared to 20% of healthy individuals. Niacin provokes redness in skin caused by a capillary vasodilatation mediated by prostaglandins. The metabolism of prostaglandins is regulated by the enzyme phospholipase A2 (PLA2). Several studies have reported increased PLA2 activity in schizophrenia. In this study we investigated the relationship between niacin response and PLA2 activity in 38 drug-free schizophrenic patients and in 28 healthy controls. Twenty-two of these patients were reevaluated after 8 weeks under treatment with new generation antipsychotic drugs. Niacin response was absent in 23% of the schizophrenic patients and in 14% in controls (n.s.). PLA2 activity was higher in schizophrenics than in controls (344+/-115 vs. 290+/-71 pmol/ml/min; p=0.03). Patients with absent response to niacin had the highest PLA2 activity as compared to those with positive response (426+/-155 vs. 319+/-111; p=0.02). After 8 weeks on antipsychotic treatment, PLA2 activity was reduced (355+/-115 before, 267+/-39 after, p=0.001) and 4 out of 13 patients with absent response to niacin converted to positive. The reduction of PLA2 activity in these patients was higher than in patients who remained with absent response (36% vs. 23%). Our data support the findings that absent response to niacin is more frequent in schizophrenic than in healthy individuals although the magnitude of the difference was smaller than that reported in the literature. The relationship between absent response to niacin in schizophrenia and increased PLA2 activity suggests further that the skin test may be useful to easily identify a subgroup of patients with a disordered phospholipid metabolism.

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

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 nai;ve 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-nai;ve 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.

Nogo CAA 3'UTR insertion polymorphism is not associated with schizophrenia nor with bipolar disorder

The Nogo gene maps to 2p14-p13, a region consistently associated with schizophrenia and bipolar disorder. The association of a polymorphism in Nogo was previously investigated by two groups, with divergent results. In this report, using an alternative approach, we evaluated this same polymorphism in 725 individuals, including patients with schizophrenia, bipolar disorder, normal controls and non-human primate samples. Our results indicate that the polymorphism is not associated with any of these diseases, but has a remarkably biased distribution in ethnic groups. Genotyping of primate samples, suggest that this polymorphism is a recent event in human speciation.

Topographic abnormality of slow cortical potentials in schizophrenia

A recent study from our laboratory has provided evidence for the generation of slow potentials occurring in anticipation to task-performance feedback stimuli, in multiple association cortical areas, consistently including two prefrontal areas. In the present study, we intended to determine whether these slow potentials would indicate some abnormality (topographic) in schizophrenic patients, and thus serve as an indication of abnormal association cortex activity. We recorded slow potentials while subjects performed a paired-associates memory task. A 123-channel EEG montage and common average reference were used for 20 unmedicated schizophrenic (mean duration of illness: 11.3 +/- 9.2 years; mean number of previous hospitalizations: 1.2 +/- 1.9) and 22 healthy control subjects during a visual paired-associates matching task. For the topographic analysis, we used a simple index of individual topographic deviation from normality, corrected for absolute potential intensities. Slow potentials were observed in all subjects. Control subjects showed a simple spatial pattern of voltage extrema (left central positive and right prefrontal negative), whereas schizophrenic patients presented a more complex, fragmented pattern. Topographic deviation was significantly different between groups (P<0.001). The increased topographic complexity in schizophrenics could be visualized in grand averages computed across subjects. Increased topographic complexity could also be seen when grand averages were computed for subgroups of patients assembled either according to task-performance (high versus low) or by their scores on psychopathological scales. There was no significant correlation between topographic deviation and psychopathology scores. We conclude that the slow potential topographic abnormalities of schizophrenia indicate an abnormality in the configuration of large-scale electrical activity in association cortices.