Tumor necrosis factor-alpha gene promoter polymorphisms in chronic schizophrenia.

BACKGROUND: Alterations in cytokine levels in patients with schizophrenia have been documented. Polymorphisms in these cytokine genes are thus potential genetic markers for schizophrenia. The aim of this study was to investigate four biallelic polymorphisms in the tumor necrosis factor-alpha (TNFalpha) gene promoter in relation to susceptibility to schizophrenia. METHODS: Three hundred two patients and 152 control subjects were genotyped and frequencies of genotypes and alleles were compared for the -1031T/C, -863C/A, -857C/T, and -308G/A polymorphisms. Genotype and allele frequencies were compared between controls and patients. RESULTS: There were statistically significant differences in genotype distribution and allele frequencies for the -308 polymorphism (p <.001). Genotype distribution and allele frequencies of the other three polymorphisms were not different between patients and reference controls. CONCLUSIONS:The -308 polymorphism or another genetic variant in linkage disequilibrium with it could be a susceptibility factor for chronic schizophrenia.     

HLA Bw57 and DR7 association with psoriasis vulgaris in south India

Eighty-three south Indian patients with psoriasis vulgaris were studied for HLA antigen frequencies and compared with 77 controls studied simultaneously. HLA Bw57, a split of B17 was found elevated in the patients. The two sexes differed in their age-at-onset curves: females had a preponderance to early onset of the disease, while the males had late onset. Among these patients, major group 3, a Western Brachycephal Armenoid group, revealed the highest risk for B17 & Bw57 but not major group 2, a Mediterranean one.     

An inter-ethnic comparison study of clozapine dosage, clinical response and plasma levels

The present study investigated clozapine dosage, plasma clozapine and metabolite levels, clinical and side-effect profiles in Asian versus Caucasian patients with chronic schizophrenia who were on stable maintenance treatment. Twenty Asian patients from Singapore and 20 Caucasian patients from Australia were systematically evaluated with the following rating scales: Positive and Negative Syndrome Scale for Schizophrenia, drug attitude scale (DAI-10), drug adverse reaction profile (Liverpool University Neuroleptic Side-effect Rating Scale), extrapyramidal side-effects scales (Abnormal Involuntary Movement Scale, Simpson and Angus Scale). Cigarette and caffeine consumption were recorded and steady-state plasma clozapine and metabolites levels were measured. Although Asian patients received a significantly lower mean clozapine dose (176 mg/day) than the Caucasian group (433 mg/day, P<0.001), plasma clozapine levels were similar between the groups. As a result, Asian patients had more than twice the effective clozapine concentration to dose ratio (P<0.001). The findings remained significant even after controlling for gender, body mass index, cigarette, alcohol and caffeine use. Conversely, the plasma metabolites (desmethylclozapine and clozapine N-oxide) to clozapine ratios were higher in the Caucasian patients (P<0.01). Compared to Caucasian patients, Asian patients appeared to have a lower dosage requirement for clinical efficacy. Hence, appropriate dose adjustment should be considered in Asian patients receiving maintenance clozapine therapy in clinical practice.     

Clinical practice guidelines for depression

The Ministry of Health Clinical Practice Guidelines for Depression were prepared and distributed to all doctors in Singapore in early 2004. This article highlights salient points and discusses pharmacotherapy, psychotherapy and psychoeducation in managing cases of depression. Assessment of suicide risk is elaborated upon, although this was not discussed in the guidelines. The learning points will be enhanced if this article is reviewed together with the Ministry of Health Clinical Practice Guidelines.