Nicotine dependence and illness severity in schizophrenia.

BACKGROUND: Reasons for the increased prevalence of cigarette smoking in schizophrenia are unclear. Studies assessing clinical symptoms have sampled heterogeneous populations, with discrepant findings. AIMS: To examine the relationship between clinical features, social adjustment and nicotine dependence in a geographically defined population of people with schizophrenia. METHOD: Cross-sectional clinical study of 131 people with schizophrenia in Nithsdale, Scotland. RESULTS: Smokers were younger, mostly males and three times more likely to be unemployed. Those with severe nicotine dependence had greater scores on the positive subscale of the Positive and Negative Syndrome Scale (PANSS), and were prescribed higher doses of antipsychotic. Those with mild-moderate dependence had greater scores on the PANSS negative subscale. Greater symptom severity was associated with poorer social adjustment. Psychopathology and social adjustment were similar in quitters and never-smokers. CONCLUSIONS: Our findings indicate an association between nicotine dependence, clinical symptoms and social adjustment in schizophrenia. Although causal links cannot be inferred, identifying the relationship between nicotine dependence and psychopathology may have some value in the management of smoking in schizophrenia. Further longitudinal studies are required to explore this relationship.

Extrapyramidal symptoms in unmedicated schizophrenia.

Studies of spontaneous extrapyramidal symptoms, dyskinesia and parkinsonism, in unmedicated schizophrenia are of importance in understanding their underlying pathology and relation to the psychosis. This is a study of extrapyramidal symptoms using Abnormal Involuntary Movements Scale for dyskinesia and Simpson-Angus Scale for parkinsonism in 143 schizophrenia patients who never received antipsychotic medication. Psychopathology was measured using the Positive and Negative Syndrome Scale. Dyskinesia was present in 35% of patients and parkinsonism in 15%. The two disorders coexisted in 11 subjects. Orofacial dyskinesia, rigidity and tremor were common symptoms noted. There was no significant change in the rates and total scores of dyskinesia and parkinsonism with gender, age, duration of illness or age at onset of psychosis. Dyskinesia was unrelated to psychopathology. Parkinsonism score correlated positively with the motor symptom cluster of psychopathology. Dyskinesia and parkinsonism scores correlated positively with each other and parkinsonism score discriminated presence of dyskinesia. The associations between the spontaneous abnormal movements and other aspects of schizophrenia differed from those described in treated patients. Dyskinesia and parkinsonism are an integral part of the schizophrenia disease process whose relationship with other factors could be influenced by antipsychotic drug treatment.

Structural brain differences between never-treated patients with schizophrenia, with and without dyskinesia, and normal control subjects: a magnetic resonance imaging study.

BACKGROUND: In south India, abnormal movements indistinguishable from tardive dyskinesia have been observed in chronically ill patients with schizophrenia who have never received antipsychotic medication. The present study, using magnetic resonance imaging, examines brain structure in such patients, in those without dyskinesia, and in normal control subjects. METHODS: Chronically ill patients with schizophrenia with and without dyskinesia and controls were identified in villages south of Chennai, India (each group, n = 31). Patients' mental state was assessed by the Positive and Negative Syndrome Scale for schizophrenia, dyskinesia by the Abnormal Involuntary Movements Scale, and parkinsonism by the Simpson and Angus scale. In patients and controls, magnetic resonance imaging measured the volume of the caudate and lentiform nuclei and the lateral ventricle-hemisphere ratio. RESULTS: The left lentiform nucleus was significantly (11%) larger in patients with dyskinesia compared with controls, and the right lateral ventricle-hemisphere ratio was significantly (33%) larger in patients without dyskinesia compared with controls. In all 3 groups, there were significant positive correlations between age and ventricle-hemisphere ratio. In controls, but not in patients, there were significant negative correlations between age and the volume of the caudate and lentiform nuclei. CONCLUSIONS: Never-treated patients with dyskinesia may have striatal pathologic conditions and may represent a subgroup of patients with schizophrenia; in those without abnormal movements, cortical atrophy is more apparent. The schizophrenic process may interfere with normal age-related anatomical changes in the basal ganglia.

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.

Summer birth and deficit schizophrenia in Dumfries and Galloway, southwestern Scotland.

OBJECTIVE: An association between deficit schizophrenia and summer birth has previously been reported. Confirmation of a separate risk factor for this group of patients is potentially important, but the number of subjects with deficit schizophrenia in previous reports has been small. This analysis used data from an epidemiological study of incident cases of psychosis to test the hypothesis that deficit schizophrenia is associated with summer birth. METHOD: Data were drawn from records for the first year of clinical contact for all new patients coming into treatment for psychosis in the region of Dumfries and Galloway, Scotland, from 1979 to 1998. Patients with schizophrenia were classified as having deficit (N=65) or nondeficit (N=277) schizophrenia. Time of birth in the deficit and nondeficit groups was compared, and time of birth in the deficit group was compared with that for all births in Dumfries and Galloway during the study period. RESULTS: The deficit schizophrenia group had an excess of summer births, compared to both the nondeficit schizophrenia group and all births in Dumfries and Galloway. The difference between the deficit and nondeficit schizophrenia groups remained significant after accounting for demographic characteristics and symptoms of disorganization and hallucinations plus delusions. A measure of negative symptoms (as opposed to deficit schizophrenia) was a weaker predictor of summer birth. CONCLUSIONS: This study confirmed an association between deficit schizophrenia and summer birth in the nontropical regions of the Northern Hemisphere. The existence of a risk factor for deficit but not nondeficit schizophrenia is also consistent with other evidence that the pathophysiology of deficit schizophrenia differs from that for other types of the disorder.

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 (x(2)=4.46, df 1, p =.04) and with DRD3 genotype (x(2)=6.62, df 2, p =.04) over and above the effect of group. Similar positive effects were observed when controlling for age and gender (x(2)=5.02, df 1, p =.02 for gly allele carrier status; x(2) = 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.

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.

Do symptom dimensions or categorical diagnoses best discriminate between known risk factors for psychosis?

OBJECTIVE: To describe symptom dimensions of psychosis using detailed psychopathological information from epidemiologically defined incident cases which include the full spectrum of functional psychosis across all age ranges. Then, assess the comparative usefulness of the dimensional and categorical representations of psychosis in discriminating between demographic and pre-morbid risk factors. METHOD: A total of 464 incident cases of psychosis assessed with OPCRIT (Operational Checklist for Psychotic Symptoms) were included in an exploratory factor analysis. Using Regression analyses we modelled the associations of the dimensional and categorical representations of psychosis with antecedent validating variables and compared the subsequent models using the likelihood ratio test. RESULTS: Factor analysis produced five-symptom dimensions, manic, disorganisation, depressive, delusional and auditory hallucinatory symptoms, explaining 58% of the total variance. Different dimensions were differentially associated with the pre-morbid risk factors. Neither the dimensional nor the categorical representations on their own were sufficient to explain associations with the antecedent validating variables. CONCLUSION: Neither the dimensional or the diagnostic representation of psychosis was superior in discriminating between known risk factors, combining dimensional measures with categorical diagnoses will probably be more informative in determining the causes and correlates of psychosis.

Insight and psychopathology in never-treated schizophrenia.

Insight is a feature of schizophrenia related to psychopathology, which could be modified by treatment. The real relationship will be more evident in the never-treated state. This study compared insight and its relationship to psychopathology in 143 never-treated patients with chronic schizophrenia with 183 treated patients. The treated patients had not received any structured intervention for improvement of insight. The item on insight and judgment from the Positive and Negative Syndrome Scale for schizophrenia was used as a measure of insight. Never-treated patients were more ill and poorer in insight than the TT group. Sex, age, duration of illness, negative symptoms related to insight only in the TT group. Positive symptoms score correlated with insight in both the groups, but negative symptoms correlated with insight only among the treated patients. Delusions, uncooperativeness, and poor attention predicted 27% of variation in the level of insight in the never-treated, whereas age; duration of illness; and symptoms of emotional withdrawal, difficulty in abstract thinking, and uncooperativeness predicted 30.3% of variation in insight of the TT group. The observed differences between the never-treated and treated subjects were due to influence of treatment on the association between insight and psychopathology. A subgroup of patients with a treatment-resistant trait of negative symptoms associated with poor insight was hypothesized.

Psychopathology in never-treated schizophrenia.

The effect of drug treatment and its adverse effects confound studies on symptoms and associated factors in schizophrenia. Knowledge of psychopathology in the untreated state would identify the natural state of the illness and is relevant to understand pathology underlying the illness. We report here symptoms of schizophrenia as measured by Positive and Negative Syndrome Scale in 143 patients with schizophrenia living in the community never treated with antipsychotic drugs. Positive symptoms were more frequent than negative ones. Negative subscale scores correlated negatively with positive subscale scores and positively with general psychopathology subscale scores. Age correlated negatively with negative and general psychopathology subscale scores independent of duration of illness. Duration of illness and the proportion of life spent in psychosis did not correlate with any Positive and Negative Syndrome Scale scores. The factors (negative, positive, anxiety-depression, motor, and excitement) extracted by a forced 5-factor analysis explained 56% of variance. This factor structure resembled that of treated patients reported in most studies except for the identification of a motor symptom cluster. Psychopathology in the never-treated schizophrenia varied in some aspects from descriptions in the treated state. The differences can be said to demarcate the natural features of the illness from medication effects on the relationship of symptoms with one another and to sex, age, duration of illness, and age at onset.

Dietary improvement in people with schizophrenia: randomised controlled trial.

BACKGROUND: People with schizophrenia make poor dietary choices. AIMS: To measure the impact of giving free fruit and vegetables for 6 months on eating habits in schizophrenia. METHOD: We randomly allocated 102 people with schizophrenia in two areas of Scotland to receive free fruit and vegetables for 6 months, supported by instruction in meal planning and food preparation; free fruit and vegetables alone; or to continue as before. Diet was assessed using the Scottish Health Survey questionnaire. Blood samples to measure micronutrients were taken and mental state, body mass index, level of physical activity and future risk of coronary heart disease (CHD) were assessed. RESULTS: After the intervention, those who received free fruit and vegetables, or free fruit and vegetables and associated instruction, were consuming significantly more fruit and vegetables than those in the treatment as usual group. Consumption fell to pre-intervention levels 12 months after the intervention stopped. There was no between-group difference at any time in blood micronutrients, body mass index, physical activity or risk of CHD. CONCLUSIONS: The diet of people with schizophrenia improved when they were given free fruit and vegetables but this was given free fruit and vegetables but this was not sustained after withdrawal of the intervention. A support programme added no benefit.

Use of drugs, alcohol and tobacco by people with schizophrenia: case-control study.

BACKGROUND: Specialised services should be developed to help people with schizophrenia and associated substance misuse. The extent of the problem therefore needs to be known. AIMS: To determine the use of drugs, alcohol and tobacco by people with schizophrenia drawn from rural, suburban and urban settings, and to compare use by general population control subjects. METHOD: People with schizophrenia (n=316) and general population controls of similar gender distribution, age and postcode area of residence (n=250) were identified in rural, urban and suburban areas of Scotland. Use of drugs and alcohol was assessed by the Schedules for Clinical Assessment in Neuropsychiatry, and use of tobacco by a questionnaire. RESULTS: More patients than controls reported problem use of drugs in the past year (22 (7%) v. 5 (2%)) and at some time before then (50 (20%) v. 15 (6%)) and problem use of alcohol in the past year (42 (17%) v. 25 (10%)) but not at some time previously (99 (40%) v. 84 (34%)). More patients were current smokers (162 (65%) v. 99 (40%)). CONCLUSIONS: Problem use of drugs and alcohol by people with schizophrenia is greater than in the general population, but absolute numbers are small. Tobacco use is the greatest problem.

Spontaneous dyskinesia in first-degree relatives of chronically ill, never-treated people with schizophrenia.

BACKGROUND: We have suggested recently that there may be a subgroup of schizophrenia, namely schizophrenia with dyskinesia and striatal pathology. Might movement disorders be more common in relatives of those with schizophrenia and dyskinesia than in relatives of those without dyskinesia? Aims To determine the prevalence of abnormal movements in first-degree relatives of people with schizophrenia who themselves do or do not have abnormal movements. METHOD: Chronically ill, never-treated people with schizophrenia in south India (n=70) and their first-degree relatives (n=181) were examined for dyskinesia using the Abnormal Involuntary Movements Scale (AIMS) and for parkinsonism by the Simpson and Angus scale. RESULTS: Of all relatives, 25 (14%) had dyskinetic movements in at least one body area and 6 (3%) had parkinsonism. Siblings of people with schizophrenia and dyskinesia, compared with siblings of people without dyskinesia, had a higher total AIMS score and more had mild dyskinetic movements in at least one area (5/15 v. 3/34, P=0.04). There were no between-group differences in parkinsonism. CONCLUSIONS: Dyskinesia but not parkinsonism is more common in siblings of people with schizophrenia who have the corresponding movement disorder.