Tumor necrosis factor haplotype analysis amongst schizophrenia probands from four distinct populations in the Asia-Pacific region.

A single nucleotide polymorphism (TNF(-308A)) within the promoter region of the gene encoding tumor necrosis factor (TNF), has been significantly associated with schizophrenia in a study of Italian patients and control subjects Boin et al. [2001: Mol Psychiatry 6:79-82]. We have applied case-control analyses to examine TNF promoter haplotypes (containing TNF(-308) and two additional promoter variants: TNF(-376) and TNF(-238)) in four schizophrenia cohorts drawn from Australian, Indian Fijian, Indigenous Fijian, and Brahmin populations. In addition, we have applied the sibling transmission disequilibrium (STD) test to promoter haplotypes within 81 trios drawn from Australian Caucasian pedigrees with multiple schizophrenia cases, and 86 trios drawn from the Brahmin population of Tamil Nadu province in Southern India. Within each of these cohorts, we found no evidence of recombination between these tightly linked promoter variants, supporting previous studies which demonstrated that only a subset of the eight possible haplotypes exist. Of the four observed haplotypes, we and others have observed only one carries the TNF(-308A) variant allele. We report no significant differences in TNF promoter haplotype frequencies between the patient and control groups within each population, although the Indian Fijian cohort showed a trend towards reduced TNF(-308A) alleles amongst schizophrenia cases (P = 0.07). We found no evidence of bias in TNF promoter haplotype transmission to schizophrenia probands. Very similar results were obtained when only the TNF(-308) polymorphism was considered. Taken together, these data provide no support for the involvement of TNF promoter variants TNF(-308), TNF(-376), and TNF(-238) in schizophrenia susceptibility within four ethnically distinct cohorts.

Spontaneous dyskinesia and parkinsonism in never-medicated, chronically ill patients with schizophrenia: 18-month follow-up.

BACKGROUND: Spontaneous dyskinesia and parkinsonism have been reported in never-medicated patients with schizophrenia but there has been no previous study of the natural history of these conditions. AIMS: To determine the prevalence of spontaneous dyskinesia and parkinsonism in a group of never-medicated, chronically ill patients with schizophrenia on two occasions separated by an 18-month interval. METHOD: Dyskinesia was assessed by the Abnormal Involuntary Movements Scale using Schooler and Kane criteria for its presence; parkinsonism by the Simpson and Angus scale; and mental state by the Positive and Negative Syndrome Scale for schizophrenia. RESULTS: Thirty-seven patients were examined on two occasions. Nine (24%) had dyskinesia on both occasions, 12 (33%) on one occasion and 16 (43%) on neither occasion. Twenty-one (57%) had dyskinesia on at least one occasion. Thirteen patients (35%) had parkinsonism on at least one occasion. CONCLUSIONS: Spontaneous dyskinesia and parkinsonism fluctuate over time. The former was found on at least one occasion in the majority of patients. It is an integral part of the schizophrenic disease process.

Smoking in schizophrenia -- all is not biological.

High rate of tobacco smoking reported in schizophrenia has been related to the effect of nicotine on the neurobiology of schizophrenia. Nicotine is said to alleviate psychotic symptoms in some patients. The relationship between smoking and psychiatric status may not be simply a biological one as several sociocultural and economic factors could influence smoking behaviour. In this study in India on 286 urban male outpatients with schizophrenia, only 38% were found to be current smokers. This was significantly more than in other psychiatric patients studied (major affective disorders and non-psychotic disorders) but not medically ill controls and not higher than the rates for the general male population in India. Smokeless use of tobacco was infrequent in the study population. More than half of the patients did not experience any positive effects due to smoking. Lack of economic independence and restrictions imposed by the family appeared to be crucial factors that controlled the prevalence of smoking among schizophrenia patients. As smoking is a leading cause of preventable morbidity and mortality, there is a serious need to review the neurobiological issue of smoking in schizophrenia considering the influence culture and social practices could have upon the behaviour.

Initiating care for untreated schizophrenia patients and results of one year follow-up.

A number of schizophrenia patients live untreated in the community in the developing countries. There is little recorded experience of how such patients would respond to treatment after years of untreated illness. A cohort of 72 never-treated chronic schizophrenia patents in Chennai, India were directed to attend a health facility. A substantial proportion of them (68%) came for treatment. Unemployed status of male patients, living in a joint family setting and families initially unaware of the psychiatric nature of the problem were the factors that related to failure to seek treatment. Patient's sex, age, education, marital status, economic status, age at onset and duration of illness, degree of disability and clinical symptoms (except self-neglect) were not related to taking treatment. Those who attended were treated with typical antipsychotic drugs and followed up for one year. Evaluation was done using the Present State Examination and Psychiatric History and Sociodemographic Schedule and Disability Assessment Schedule. The clinical outcome was good (Best Remission) in 29%. There was no impairment in social functioning in 35% and 51% has no impairment in occupational functioning at the end of one year.

Beliefs about causation of schizophrenia: do Indian families believe in supernatural causes?

BACKGROUND: Beliefs about the causation of schizophrenia could influence the attitudes patients' families adopt towards the patient and may also influence their help-seeking behaviour. Indian families have been typically described as often believing in causes like supernatural forces and therefore seeking help from magico-religious healers. In the changing mental health scenario in India, this impression needs verification. METHOD: Key relatives living with 254 chronic schizophrenia patients were interviewed and asked to name the causes they believed were behind the illness. A list of possible causes was provided for the families to select from, and relatives were also encouraged to mention other possible causes, not featured in the list. The possible causes identified and the factors related to attributions made were analysed. RESULTS: A supernatural cause was named by only 12% of the families and as the only cause by 5%. Psychosocial stress was most commonly cited cause, followed by personality defect and heredity. A small number of families (14%) could not name any cause and 39% named more than one cause. Patient gender and education, duration of illness and the key relative's education and the nature of relationship were related to the type of causal attributions made. CONCLUSION: Families living with patients suffering chronic schizophrenia receiving treatment in urban India rarely subscribe to the idea of supernatural causation of the illness. The causal attributions made by them are fairly rational and understandable, given the relative lack of exposure to proper information about the illness.

Relationship of extrapyramidal symptoms to age at onset and drug treatment in middle-aged and elderly schizophrenic patients.

The relationship between antipsychotic drugs and dyskinesias and other extrapyramidal symptoms (EPS) in schizophrenia is not simple. There is a need to study variables that may influence the occurrence of EPS in schizophrenic patients receiving drugs. The present study examined the relationship of age at onset of illness and treatment to the development of EPS in 122 middle-aged and elderly schizophrenic patients, 84 treated and 38 who had never received antipsychotic drugs. The illness had an early onset (before 45years, EOS) in 68 patients and a late onset (after 45years, LOS) in 54 patients. The patients were evaluated for dyskinesia and parkinsonism using abnormal involuntary movements scale (AIMS) and Simpson-Angus scale. The prevalence of dyskinesia and parkinsonism was similar in all the patient groups. The scores on limb-axial and severity subscales of AIMS were significantly higher in the treated than the untreated patients of the early onset group. This was not so with the late onset patients. The total parkinsonism score was higher among the treated, notably the LOS patients. The development of dyskinesia and parkinsonism in schizophrenia is possibly related to the age at onset of the illness. In late onset forms the ageing of the patient and a possible neurological abnormality related to schizophrenia might enhance the EPS-inducing effect of drugs.

How stigmatising is schizophrenia in India?

Stigma is a social devaluation of a person because of personal attribute leading to an experience of sense of shame, disgrace and social isolation. The nature of stigma in schizophrenia and its relationship to attribution was studied in one hundred and fifty-nine urban patients of Madras, India who fulfilled DSM-IV criteria for schizophrenia. The response of the primary care givers to fourteen questions on stigma and 14 on what they thought attributed to the illness was elicited. Based on the mean stigma score, the entire sample was divided into two groups- those with high and low stigma. Marriage, fear of rejection by neighbour, and the need to hide the fact from others were some of the more stigmatising aspects. Many care givers reported feelings of depression and sorrow. Discriminant function analysis showed that female sex of the patient and a younger age of both patient and caregiver were related to higher stigma. Among attribution items, having no explanation to offer, and attributions to faulty biological functioning, character of life style, substance abuse and intimate interpersonal relationship discriminated between the two groups. The relevance of stigma in the cultural context is described.

Issues related to disability in India: a focus group study.

BACKGROUND: Systematic research into disability has been scarce, especially from India, even though an estimated 5% of the population may have significant disability due to physical disorders. Depression as a common psychiatric disorder affects about 3%-5% of the population. Thus, the impact of disability related to physical, mental and substance use disorders is enormous and it influences resource allocation and policy planning. METHODS: The issues relating to disability were addressed through a qualitative multicentered study. Focus groups were conducted at three sites in Chennai, Bangalore and Delhi on three themes: (i) parity, stigmatization and social participation; (ii) current practices and needs; and (iii) the General Disability Model as proposed by the World Health Organization. The focus groups were homogeneous and included members from six categories of participants: individuals with physical disability, individuals with mental disability, individuals with alcohol/drug-related disability, family members of mentally disabled persons, family members of physically disabled persons and health professionals. In all, 118 groups were conducted with a mean (SD) group size of 8.6 (1.6). RESULTS: Patients with mental and alcohol/drug-related disability were more discriminated against than those with physical disability. Awareness regarding the existing laws and social programmes was uniformly poor across the three centres. Stigmatization was a major reason for under-utilization of the meagre resources available. There was poor awareness of the Disability Act, 1996. The consumers felt more comfortable with the earlier terms of 'handicap' and 'impairment'. CONCLUSIONS: The study has implications for policy planning, clinical decision-making and social behaviour. Awareness of the laws, facilities and programmes needs to be increased, especially regarding the Disability Act, 1996 among consumers as well as health professionals. More disability-friendly facilities are required.

Schizophrenic patients who were never treated--a study in an Indian urban community.

BACKGROUND: A significant number of patients with severe psychiatric disorders remain untreated in the community although health services are available. The factors related to non-treatment are not well understood. METHOD: A door-to-door survey was conducted on an Indian urban population of 100,000 using standardized screening and clinical instruments as a part of a larger epidemiological study. Treatment status was determined from multiple sources of information. RESULTS: Nearly one-third of 261 schizophrenia patients were found never to have received treatment. They were older in age and ill for a longer duration than those who had been treated and were more symptomatic and severely disabled. They were more often uneducated and divorced and lived with larger extended/joint families. This last factor was considered as being the important factor in determining whether the patient received treatment. CONCLUSION: The larger extended/joint family, which was able to compensate and cope with the dysfunctional member, seemed to be the crucial factor related to non-treatment of the schizophrenic patient.

Clozapine-induced agranulocytosis and use of g-csf.

Use of clozapine is attended with the serious though rare risk of agranulocytosis. Clozapineinduced agranulocytosis is reversible with the use of cytokines like granulocyte-colony stimulating factor (G-CSF). Reports of the haematological complication of clozapine have not been forthcoming from India though it has been in use for nearly three years. This report is on an young patient who developed total absence of granulocytes during the 4th month of treatment who was successfully treated with G-CSF.

Fertility and schizophrenia: evidence for increased fertility in the relatives of schizophrenic patients.

Fertility has been observed to be reduced in patients with schizophrenia, although the disorder was seen to occur at a steady rate in the general population. The hypothesis of increased fertility in the healthy relatives of the patients, which maintained the genetic contribution to the disorder has been proposed but has not received much support. The present study reports the fertility rate in 100 schizophrenic patients and their relatives (grandparents, parents, uncles, aunts and siblings). The fertility of the different family members was compared, taking into account the completion of age of maximum reproductivity, i.e. up to 50 years of age. The trends in fertility rates over three generations of patients' families were compared with those in the general population of India over a corresponding period from 1950 to 2000 AD. The patients were observed to be hypofertile, but their parents showed a higher fertility than all other relatives, as well as the general population. The siblings of the patients also tended to have higher fertility rates than the general population. This increased fertility in parents and sibs, who are the probable carriers of the abnormal gene, could compensate for the reduction in genetic contribution to morbid risk for schizophrenia due to reduced reproductivity of the patients themselves.

How do men with schizophrenia fare at work? A follow-up study from India.

Occupational activity, an indicator of the functional status of an individual, is a major component in the long-term management of schizophrenia. The work functioning of 40 first-episode male schizophrenic patients was assessed prospectively every year over a period of 10 years. The comprehensive evaluation of occupational outcome measured in terms of duration of employment, quality of work done, and level of earned income was good in 53% of the patients, comparable to figures from developed countries. This outcome was not related to many of the socio-demographic and clinical variables but was strongly associated with overall clinical, social and marital outcome. The educational and economic status of the study group, the type of work available to them, and the compelling need for men to be the wage-earners in the Indian situation are discussed as influencing the findings of the study.

Outcome of marriage in schizophrenia.

Marriage is a social process requiring certain social abilities for it to be successful. Schizophrenia, which can lead to a reduction of such abilities, has been associated with a low marital rate, especially in men. Data on long-term marital outcome are, however, sparse. This paper deals with changing marital status in a cohort of 76 first-onset schizophrenic patients followed-up for 10 years. A fairly high marital rate of 70% was observed in this sample, with more men remaining single and more women facing broken marriages. It was observed that good marital outcome, in terms of getting married and keeping the marriage intact, was associated with a number of clinical and sociodemographic variables. Duration of illness, type of onset, auditory hallucinations and simple depression at intake, unemployment and economic slide during the course of illness and a relapsing course of illness were all related to marital outcome. Outcome in other areas such as clinical, social and occupational functioning discriminated between the groups of good and poor marital functioning.

Marriage and gender in schizophrenia.

This paper reports a study of marital rates in a group of the first-break schizophrenia patient followed up over II) wars and examines the various factors related to marriage. A high rate, 70% of the patients married and 80% of the marriages were intact at follow up. Less men got married and more women had broken marriages especially if they were childless. A relapsing course of illness was associated with a 'never married' stale, and occupational stability in men seemed to determine their getting married after the onset of illness.

Use of clozapine in childhood schizophrenia.

Childhood onset schizophrenia is a rare disorder whose prognosis is generally worse than that in the adult onset type of schizophrenia. Conventional neuroleptics have yielded inconsistent results with the risk of exposing the child to extrapyramidal and cognitive adverse effects which could interfere with proper development of the child. Effective and safe use of clozapine in children with schizophrenia has been reported. This drug is recently introduced in India and reports of its use in children are yet to come from this part of the world. This case report is on the effective and safe use of clozapine in a girl child with schizophrenia who became ill at 9 years of age.

Adverse effects of disulfiram and patient compliance.

Use of Disulfiram under supervision in well-motivated alcoholics is effective in reducing relapse rates. Several adverse effects, some of them life-threatening, have been reported due to the drug. An awareness of the adverse effects is useful to keep a follow up and sustain patient compliance with the drug. This study of 158 out patients on daily oral disulfiram revealed that though many patients report unpleasant effects most of them could not be distinguished from symptoms of alcoholism present before taking disulfiram and hence cannot be considered as adverse effects of the drug. The actual adverse symptoms were also mild and could be easily managed and were infrequent and not the common cause for poor patient compliance. The study suggests that Disulfiram with its low toxicity can be offered to patients without too much reservation.