Isabel Andia

Expression in normals and in subjects with schizophrenia of a novel gene fragment originally isolated from monozygotic twins discordant for schizophrenia

Differentially expressed clones from subtracted cDNA libraries of a pair of monozygotic twins discordant for schizophrenia have been reported in the literature. The clones were expressed in lymphocytes from the healthy twin, but not from the schizophrenic twin. In the current study, we assessed the expression of one of these clones, oksc12b, in 10 normal controls and in 10 patients who met DSM-IV criteria for schizophrenia and had never received neuroleptic medication. We hypothesized that this clone would be differentially expressed in normal controls and in the schizophrenic patients, and that its expression could be a peripheral marker of the disease. Lymphocytes were isolated and total RNA was purified, reverse-transcribed, and quantified by two PCR methods. In the first PCR assay, oksc12b expression was measured relative to beta-actin gene expression. The second PCR assay consisted of a competitive procedure using a heterologous DNA internal standard. Neither method confirmed any difference in oksc12b expression between schizophrenic patients and normal controls. Subtypes of schizophrenia or the general heterogeneity of this syndrome may explain the discrepancy found. It is also possible that the differentially expressed clones are present in discordant monozygotic twins, but not in other patients.

Morning variations of plasma homovanillic acid in untreated schizophrenic patients.

Plasma concentrations of homovanillic acid were determined in samples obtained at 8.30 a.m. and 12.30 p.m. from 29 untreated schizophrenic patients, 14 males and 15 females. When the earlier samples were compared with the later, a significant decrease in mean plasma homovanillic acid level was observed, but only in the male patients. The morning fall was observed in 10 of 14 male patients and 6 of the 15 female patients. This morning rhythm in plasma homovanillic acid concentration may mask the putative rises in plasma homovanillic acid provoked by neuroleptic administration and may explain some of the observed differences between findings in studies involving the assessment of this metabolite.

Differential Effect of Haloperidol and Clozapine on Plasma Homovanillic Acid in Elderly Schizophrenic Patients with or without Tardive Dyskinesia

BACKGROUND Plasma homovanillic acid (HVA) changes in response to a challenge of several days with haloperidol have been found to be predictive of the therapeutic response to haloperidol over a longer period of treatment. METHODS Twenty-six elderly women who gave informed consent were divided into two groups, with or without tardive dyskinesia, and subjected to an 80-day washout, after which both the dyskinetic and nondyskinetic group was divided, and half of each group given haloperidol or clozapine. CONCLUSIONS The nondyskinetic group had a brief rise in plasma HVA, then a decline. The dyskinetic group had no change in plasma HVA. Neither group challenged with clozapine had any change in plasma HVA.

Chronic neuroleptic treatment does not suppress the dynamic characteristics of the dopaminergic receptor D2 system

1. Rats were treated with either haloperidol (0.5 mg/kg) or haloperidol plus an anticholinergic drug (0.5 and 0.15 mg/kg/day respectively) for 3 days, 7 days and 16 months. 2. Estimates made twenty hours after the last doses showed that haloperidol reduced the concentrations of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum and the olfactory tubercle. 3. A challenge dose of either haloperidol or haloperidol plus an anticholinergic drug was administered to rats pretreated with haloperidol or haloperidol plus an anticholinergic drug; this challenge dose reversed the reduction in dopamine metabolites caused by neuroleptic administration. 4. After sixteen months of haloperidol administration dopamine levels were reduced, but adding an anticholinergic drug to haloperidol treatment prevented this reduction in dopamine concentration.

Quantitative determination of gene expression in human lymphocytes assessed by reverse transcription–polymerase chain reaction coupled to high-performance liquid chromatography

Gene expression in human lymphocytes was assessed using reverse transcription and polymerase chain reaction amplification followed by ion-pair reversed-phase chromatography analysis. Competitive PCR was used to quantitate the desired cDNAs with a polivalent competitor adaptable to multiple novel mRNAs estimations with minor changes. Accuracy was 11.27+/- 11.87% (n = 7), as determined using standards. The coefficients of variation of the assessment of human OK12b were 7% (n = 6), 7.68 attmol/microg of total RNA, and 21% (n = 6), 0.93 attmol/microg of total RNA. Sample-to-sample variation in the reverse transcription and in the quantity and quality of RNA was attenuated by normalising results to beta-actin mRNA expression. The correlation between the OK12b/beta-actin ratio and competitive assessments of OK12b was 0.984, n = 6. The correlation between HPLC results and an independent method based on radionuclide uptake by the product, detected by electrophoretic separation, was 0.848, n = 10.