Robin G. McCreadie

Diet, smoking and cardiovascular risk in people with schizophrenia: descriptive study.

BACKGROUND Physical health of people with schizophrenia is poor and they die early from cardiovascular disease. AIMS To describe the lifestyle of people with schizophrenia through diet, smoking habits, weight and exercise, and to report risk of coronary heart disease (CHD). METHOD Dietary habits of 102 community-dwelling people with schizophrenia were assessed by the Scottish Health Survey Questionnaire. Also assessed were smoking habits, physical activity, biochemical indices of nutrition and future risk of CHD. RESULTS Fewer males, compared with the general population, reached acceptable levels for consumption of fruit, vegetables, milk, potatoes and pulses. Fewer females reached the levels for consumption of milk and potatoes. Mean number of fruit and vegetable portions consumed per week was 16 (s.d.=14); 71 (70%) were smokers; 25 (86%) females and 50 (70%) males were over weight or obese; 59 (59%) considered themselves physically active; 46 (53%) had a raised cholesterol: high-density lipoprotein ratio, and 64 (74%) a low alpha-tocopherol: cholesterol ratio. Mean 10-year risk of CHD in males was 10.5% (s.d.=8) and in females 7% (s.d.=6). CONCLUSIONS The lifestyle of people with schizophrenia must give cause for concern in relation to CHD. Care from concern in relation to secondary care services must address physical as well as mental health.

Pharmacogenetics of Tardive Dyskinesia: Combined Analysis of 780 Patients Supports Association with Dopamine D3 Receptor Gene Ser9Gly Polymorphism

Variability among individuals in their therapeutic response to psychotropic drugs and in susceptibility to adverse effects is considerable. Pharmacogenetics addresses the contribution of genetic factors to this variability. An important focus of interest in pharmacogenetics has been on candidate genes that play a role in susceptibility to the antipsychotic drug-induced adverse effect, tardive dyskinesia (TD). Four published studies have reported an association between a serine (ser) to glycine (gly) polymorphism in exon 1 of the dopamine D3 receptor gene (DRD3) and TD; three failed to replicate this finding and one found an insignificant trend. We examined the association in a pooled sample of 780 patients (317 with TD and 463 without TD) drawn from 6 research centers, who were divided into 8 groups based on their population origin. The analysis employed stepwise logistic regression so as to allow confounding effects of group, age, and gender to be taken into account. TD was significantly associated with DRD3 gly allele carrier status (x2=4.46, df 1, p = .04) and with DRD3 genotype (x2=6.62, df 2, p = .04) over and above the effect of group. Similar positive effects were observed when controlling for age and gender (x2=5.02, df 1, p = .02 for gly allele carrier status; x2 = 7.51, df 2, p = .002 for genotype). Examining abnormal involuntary movement scores as a continuous variable, we found that patients homozygous for the gly allele had significantly higher scores than ser-gly heterozygotes (p = .006) or ser-ser homozygotes (p < .0001). We also performed a meta-analysis that included, besides the groups in the combined analysis, three other published studies on DRD3 and TD. The Mantel-Haenszel pooled odds ratio for DRD3 gly allele carrier status increasing susceptibility to TD was 1.33 (95% CI 1.04–1.70, p = .02); the cumulative pooled estimate showed an odds ratio of 1.52 (95% CI 1.08–1.68, p < .0001). These findings support a small but significant contribution of the DRD3 ser9gly polymorphism to TD susceptibility that is demonstrable over and above population effects and the effect of age and gender on the phenotype.

Dopamine D3-receptor gene variant and susceptibility to tardive dyskinesia in schizophrenic patients.

Schizophrenia is a serious psychiatric illness with a life-time risk of approximately one percent. Many of the patients, but not all, benefit from treatment with anti-psychotic drugs known to block dopamine D2-like receptors. The use of conventional neuroleptics is, however, hampered by the risk of extrapyramidal side-effects. Tardive dyskinesia (TD) is usually regarded as the most serious of these drug-induced movement disorders due to its high prevalence and potentially irreversible nature. In this study, we have investigated the genetic variation of the dopamine D3 receptor gene (DRD3) as a putative risk factor for TD in schizophrenic patients receiving long-term anti-psychotic drug therapy. We found a high frequency (22–24%) of homozygosity for the Ser9Gly variant (allele 2) of the DRD3 gene among subjects with TD in both a cross-sectional and a longitudinal evaluation, as compared with the relative under-representation (4–6%) of this genotype in patients with no or fluctuating TD. This result indicates that autosomal inheritance of two polymorphic Ser9Gly alleles (2-2 genotype), but not homozygosity for the wild-type allele (1-1 genotype), is a susceptibility factor for the development of TD, an observation which may improve the understanding of the pathophysiological mechanisms of TD and influence the design and choice of future anti-psychotic drugs. The correlation between a serious motor side-effect and a genetic marker could lead to selection bias in the sampling of schizophrenic patients for genetic studies, and may therefore explain the apparent association reported between susceptibility for schizophrenia per se and homozygosity for the DRD3 gene.

Support for RGS4 as a susceptibility gene for schizophrenia

BACKGROUND The gene encoding the regulator of G-protein signaling 4 has recently been associated with susceptibility to schizophrenia. This finding is particularly interesting, because it was replicated within the same study and also because there are functional, positional, and expression data to support the regulator of G-protein signaling 4 as a schizophrenia candidate gene. Although the original report was highly suggestive, a limitation was that the study was conducted on rather small samples. METHODS We have examined a large case (n = 709) control (n = 710) sample for association between schizophrenia using four markers investigated in the earlier study, denoted single nucleotide polymorphisms 1, 4, 7, and 18. RESULTS We were able to replicate the associations with single nucleotide polymorphisms 4 and 18 that had previously been reported individually and have also identified significant association with haplotypes constructed from single nucleotide polymorphisms 1 and 4. CONCLUSIONS Our data give modest support for the hypothesis that the regulator of G-protein signaling 4 is a susceptibility gene for schizophrenia.

The Nithsdale schizophrenia surveys : an overview

SummaryThe Nithsdale surveys over a ten year period have examined a community of schizophrenic patients. Although almost three-quarters of patients were living outside hospital, social and psychiatric disability was considerable, with flattening of affect and social withdrawal most prominent. The majority probably cause little disturbance to most people in the community. Only 13% of the total Nithsdale schizophrenic population were living in a high contact/high Expressed Emotion family, the family structure believed to be most conducive to schizophrenic relapse. An attempt at family intervention found it difficult to engage relatives in treatment; however, where such intervention did take place, there was a fall in the total number of relapses. Reassesment found that the levels of EE was stable in most relatives over a five year period. Patients who lived in a high or fluctuating EE home, and who relapsed, did so more often than those who lived in a low EE home. Assessment of the prevalence of motor disorders secondary to antipsychotic medication found a point prevalence of parkinsonism of 27%, of tardive dyskinesia (TD) 29%, and of akathisia or pseudoakathisa 23%. Only 44% had no movement disorder. Eight percent had persistent TD. Parkinsonism was associated with a history of obstetric complications and TD with left-handedness. An obstetric history obtained from mothers of schizophrenic patients found there was no difference in the proportion of schizophrenic patients and their sibs who had at least one definite obstetric complication.

The Scottish first episode schizophrenia study. VII: Two-year follow-up

ABSTRACT— Of 49 schizophrenic patients followed up 2 years after their first admission to hospital, 37% were well, 47% had been readmitted to hospital at some time over the 2 years, and 18mo showed schizophrenic symptoms at follow‐up. A poor outcome at 2 years was associated with male sex, poor outcome after the first 5 weeks of the first admission, negative schizophrenic symptoms on first admission, and a diagnosis of definite or probable schizophrenia using the Feighner criteria. Only 23% were in employment. A small double‐blind discontinuation study of maintenance antipsychotic medication during the second year found more relapses in those switched to placebo medication. Repeat psychometric assessment at 2 years confirmed modest improvements found at 12 months; that is, there was no evidence of intellectual decline. Relatives showed no more psychosocial distress than that found in a normal community sample; what distress there was correlated with patients’ schizophrenic symptoms.

The dental health of people with schizophrenia

Objective:  To examine the dental health of community dwelling people with schizophrenia and to compare results with those in the general population.

Non-functional CYP2D6 alleles and risk for neuroleptic-induced movement disorders in schizophrenic patients.

Abstract The use of classic anti-psychotic drugs in the long-term treatment of schizophrenia is associated with risk for extrapyramidal side-effects, such as akathisia, parkinsonism and tardive dyskinesia (TD). Approximately 5–10% of European Caucasians lack the cytochrome P450 enzyme CYP2D6 (so-called poor metabolizers; PM), which normally metabolizes several drugs including many neuroleptics. PM subjects may achieve high or toxic plasma levels upon standard drug therapy. In this study we have examined 100 subjects from the Nithsdale cohort of schizophrenic patients in South-west Scotland receiving long-term neuroleptic medication, which enabled us to perform both a cross-sectional and longitudinal evaluation of extrapyramidal side-effects in relation to the genetically impaired CYP2D6 metabolism. We identified ten (10%) schizophrenic subjects with the PM genotype. In the cross-sectional study, the prevalence of TD, parkinsonism and akathisia was 51%, 38% and 15%, respectively. Patients with TD or parkinsonism were significantly older than patients without these side-effects. In contrast, patients with akathisia were significantly younger than patients without akathisia. There was a non-significant tendency for PM subjects to have more severe ratings for TD and parkinsonism. In the long-term evaluation based on repeated ratings since 1981, there was a non-significant 3-fold higher frequency of PM subjects among schizophrenic patients with longitudinal TD, as compared with the group of patients with fluctuating or no TD. These results indicate that genetically impaired CYP2D6 metabolism may be a contributing factor for the development of persistent TD.

Low prevalence of obesity and metabolic syndrome in never-treated chronic schizophrenia

INTRODUCTION Antipsychotic medication and lifestyle factors are implicated in the high rates of obesity and metabolic syndrome in schizophrenia. While the two Consensus Statements made in 2004 concluded they were unclear whether psychiatric disorders per se accounted for increased prevalence of metabolic disorders several later studies have presented the case for an association between schizophrenia and metabolic disorders, especially impaired glucose metabolism and Type 2 diabetes mellitus, independent of antipsychotic drug treatment. METHODS This is a comparative study of 51 patients with chronic schizophrenia who never received antipsychotic drug treatment and 51 healthy controls. Physical and laboratory assessments were made to measure body-mass index and diagnose metabolic syndrome using the International Diabetes Federation (2006) criteria. RESULTS The study observed a significantly lower mean body-mass index in patients (19.4) than controls (22.7) and very low and comparable rates of metabolic syndrome (3.9% in patients, 7.8% in controls). DISCUSSION Economic affordability and lifestyles modified by living conditions were discussed as factors underlying the high rates of underweight in the patient population and low rates of metabolic disorders in all the study subjects. The study concluded that schizophrenia in the absence of antipsychotic drug treatment is not a factor contributing to high prevalence of metabolic abnormalities. Lifestyle factors and the social and economic circumstances that drive them should be considered for better understanding and management of excess weight gain and metabolic abnormalities in people with schizophrenia.

A double‐blind comparative study of remoxipride and thioridazine in the acute phase of schizophrenia

This is the first comparative double blind study of remoxipride. Sixty‐one patients with acute schizophrenia received either remoxipride (75–375 mg daily) or thioridazine (150‐750 mg daily) for 6 weeks. There was no statistically significant between‐drug difference in improvement in mental state, as measured by the Brief Psychiatric Rating Scale, although the trend favoured thioridazine; global assessment of illness severity at the last rating also, favoured thioridazine. Sedation, anti‐cholinergic effects, autonomic dysfunction and weight gain were significantly more common in patients receiving thioridazine. Both drugs produced few extrapyramidal effects, but both produced cardiovascular changes in two patients; neither drug produced significant abnormalities in laboratory tests.