A double-blind, randomized comparison study of efficacy and safety of intramuscular olanzapine and intramuscular haloperidol in patients with schizophrenia and acute agitated behavior.

Studies of intramuscular (IM) olanzapine in Asian and Taiwanese populations are limited. This study examined the efficacy and safety of IM olanzapine in Taiwanese patients with schizophrenia and acute agitated behavior.This was a multicenter, double-blind, randomized, parallel study comparing the efficacy and safety of 10 mg/d IM olanzapine (n = 25) against 7.5 mg/d haloperidol (n = 24). The primary objective was to assess the change of agitation from baseline to 2 hours after the first IM injection on the Positive and Negative Symptom Scale-Excited Component Scale.The changes of Positive and Negative Symptom Scale-Excited Component Scale score from baseline to 2 hours after the first IM injection did not show statistically significant difference between study groups (olanzapine -9.0 ± 5.7, haloperidol -7.9 ± 4.0, P = 0.254). Both groups reported insomnia as the most common treatment-emergent adverse event, and no serious adverse event was reported.Intramuscular olanzapine and IM haloperidol are similarly effective antipsychotic agents in treating agitated symptoms in Taiwanese patients with schizophrenia. Both IM olanzapine and IM haloperidol were proven to be safe and well tolerated, which also provided alternative options in the treatment of patients with schizophrenia with agitation.

Genetic variants of IL-6 and its receptor are not associated with schizophrenia in Taiwan.

The pathophysiological process of schizophrenia is still unclear. The levels of interleukine-6 (IL-6) and its receptor, soluble IL-6R, have been reported to be elevated in the plasma and cerebrospinal fluid of schizophrenic patients. In this study, we tested the association of genetic variants of IL-6 and IL-6R with schizophrenia. Genotyping of three single nucleotide polymorphisms (SNP) for each IL-6 (IL-6-1, IL-6-2, and IL-6-3) and IL-6R (rs4845617=IL-6R1, rs4553185=IL-6R2, and rs4379670=IL-6R3) gene was performed in 100 patients with schizophrenia and 113 normal controls. The polymorphisms of IL-6R2 were genotyped using Tetra-primer ARMS PCR. IL-6R3 polymorphisms were genotyped using restriction fragment length polymorphism (RFLP) with Apo I enzyme as the restriction enzyme. All other polymorphisms were genotyped using the direct sequencing method. We found a di-nucleotide haplotype block and a tri-nucleotide haplotype block in the genes of IL-6 and IL-6R, respectively. All six SNPs and their haplotypes failed to show a significant association with schizophrenia. The IL-6-2 SNP showed a nominally significant association with the positive symptoms of schizophrenia (p=0.0472). We conclude that the genetic variants of IL-6 and IL-6R are not associated with schizophrenia. In order to verify this result, further study using a larger sample size and exploring the association between the genotype of IL-6-2 and plasma level of IL-6 is recommended.

A single nucleotide polymorphism fine mapping study of chromosome 1q42.1 reveals the vulnerability genes for schizophrenia, GNPAT and DISC1: Association with impairment of sustained attention.

BACKGROUND: The marker D1S251 of chromosome 1q42.1 showed significant association with schizophrenia in a Taiwanese sample. We used single nucleotide polymorphism (SNP) fine mapping to search for the vulnerability genes of schizophrenia. METHODS: We selected 120 SNPs covering 1 Mb around D1S251 from the public database. These selected SNPs were initially validated if allele frequency was >10%. Forty-seven validated SNPs were genotyped in 102 families with at least 2 siblings affected with schizophrenia. RESULTS: Two SNP blocks showed significant association with schizophrenia. Block 1 (five-SNP), located between intron 2 and intron 13 of the glyceronephosphate O-acyltransferase (GNPAT) gene, showed the most significant associations using single-locus TDT (z = -2.07, p = .038, df = 1) and haplotype association analyses (z = -1.99, p = .046, df = 1). Block 2 (two-SNP), located between intron 4 and intron 5 of the disrupted-in-schizophrenia 1 (DISC1) gene, also showed the most significant results in both the single-locus (z = -3.22, p = .0013, df = 1) and haplotype association analyses (z = 3.35, p = .0008, df = 1). The association of the DISC1 gene with schizophrenia was mainly in the patient group with sustained attention deficits as assessed by the Continuous Performance Test. CONCLUSIONS: Chromosome 1q42.1 harbors GNPAT and DISC1 as candidate genes for schizophrenia, and DISC1 is associated with sustained attention deficits.