Duration of untreated psychosis and outcome in first-episode psychosis. Perspective from a developing country.

OBJECTIVE: To investigate the association between duration of untreated psychosis (DUP) and treatment outcome in a sample of subjects from a developing country. METHOD: Forty-eight subjects with a first episode of psychosis were evaluated prior to treatment and at 3-month intervals over a period of 24 months. We first examined correlations between DUP and symptom improvement as measured on the Positive and Negative Symptom Scale (PANSS), and then performed multivariate analysis to determine the validity of DUP as a predictor of outcome. RESULTS: DUP was significantly correlated with improvement in PANSS total and negative subscale scores as well as the PANSS depression factor at 21 and 24 months. Multivariate analysis found DUP to be the only significant predictor of improvement in negative symptoms at 24 months. CONCLUSION: DUP was a significant predictor of outcome in a cohort form a developing country. This study provides support for early detection and intervention strategies.

Suicide attempts in an African schizophrenia population: an assessment of demographic risk factors.

This study investigated demographic variables, including affected sibling pair status, as risk factors for suicidal behavior in schizophrenia patients of African (Xhosa) descent. Xhosa subjects with schizophrenia were interviewed with the Diagnostic Interview for Genetic Studies (DIGS) and then stratified into two groups: those with ( n = 90) and those without ( n = 364) a history of previous suicide attempts. Demographic parameters (including gender, age, and social circumstances, sib ship) were then compared across these groups. Demographic predictors of suicide included sib ship status ( p = 0.038; OR = 1.7) and age of onset of illness ( p = 0.008; OR = 2.5). On further analysis of suicide in siblings, only a minority of sib pairs was found to be concordant for a lifetime history of suicide attempts (3%). These findings raise the possibility that affected sib pair status may be protective in nature. Given the counter-intuitive nature of this finding, further work is needed to replicate it, and to explore possible underlying mechanisms.

A culture-bound syndrome 'amafufunyana' and a culture-specific event 'ukuthwasa': differentiated by a family history of schizophrenia and other psychiatric disorders.

BACKGROUND: 'Amafufunyana' and 'ukuthwasa' are two culture-specific descriptive terms used by Xhosa traditional healers to explain aberrant behavioral and psychological phenomena. Some overlap between these conditions and schizophrenia (DSM-IV) is apparent. The aim of this study was to determine the extent to which amafufunyana and ukuthwasa were used as cultural explanatory models by traditional healers for DSM-IV-defined schizophrenia and whether there were significant phenomenological differences in schizophrenia symptoms in patients with the diagnosis of amafufunyana rather than ukuthwasa. SAMPLING AND METHODS: Xhosa patients with schizophrenia underwent a structured clinical diagnostic interview (Diagnostic Interview for Genetic Studies). The use of traditional diagnostic and treatment methods was assessed by structured open-ended interviewer-rated questions. The sample was then stratified for the presence/absence of a past/current diagnosis of amafufunyana and/or ukuthwasa. The clinical parameters were compared across groups by means of the chi2 or Student t tests. RESULTS: 247 adult subjects participated in the study. 106 (53%) patients reported a previous diagnosis of amafufunyana, and 9 (4.5%) reported a diagnosis of ukuthwasa. A family history of schizophrenia (p = 0.004) or any psychiatric disorder (p = 0.008) was more common in the ukuthwasa group. Subjects with a primary diagnosis other than amafufunyana or ukuthwasa were more likely to be married (p = 0.004), to have a history of stressor(s) prior to illness onset (p = 0.026), to be from a rural environment (p = 0.007) or to have a history of cannabis abuse/dependency (p = 0.015). CONCLUSION: The culture-bound syndrome amafufunyana and the culture-specific phenomenon of ukuthwasa are both used to explain symptoms in patients with schizophrenia (DSM-IV). Identification of cases as amafufunyana and ukuthwasa may correlate with a distinction between familial and sporadic cases of schizophrenia. Whether the positive connotations associated with ukuthwasa, as opposed to the more negative connotations associated with amafufunyana, hold any implications for the treatment or prognosis of schizophrenia remains to be clarified.

Violence in male patients with schizophrenia: risk markers in a South African population.

OBJECTIVE: We investigate the role of functional variants in the catecholamine-O-methyl transferase gene (COMT) and the monoamine oxidase-A gene (MOA-A), as well as previously identified non-genetic risk factors in the manifestation of violent behaviour in South African male schizophrenia patients. METHOD: A cohort of 70 acutely relapsed male schizophrenia patients was stratified into violent and non-violent subsets, based on the presence or absence of previous or current violent behaviour. Standardized violence rating scales were also applied and the COMT/NlaIII and MAO-A promoter region variable number of tandem repeats (VNTR) polymorphisms were genotyped. RESULTS: A multiple logistic regression model based on the clinical, genetic and socio-demographic variables indicated that delusions of control (OR = 3.7, 95% CI = 1.21-11.61) and the combined use of cannabis and alcohol (OR = 6.89, 95% CI = 1.28-37.05) were two significant predictors of violent behaviour in this schizophrenia population. No association was found between the tested polymorphisms and violent behaviour. CONCLUSIONS: Although the sample size may have limited power to exclude a minor role for these specific gene variants, such a small contribution would have limited clinical relevance given the strong significance of the non-genetic markers. These findings suggest that currently proactive management of violent behaviour in this schizophrenia population should continue to be based on clinical predictors of violence.

Incidence of tardive dyskinesia in first-episode psychosis patients treated with low-dose haloperidol.

BACKGROUND: Previous studies suggest that the risk of tardive dyskinesia is increased with higher doses of conventional antipsychotics. This study evaluates the 12-month incidence of tardive dyskinesia in subjects with first-episode psychosis who were treated with very low doses of haloperidol. METHOD: Fifty-seven subjects with first-episode psychosis and a DSM-IV diagnosis of schizophreniform disorder, schizophrenia, or schizoaffective disorder were treated according to a fixed protocol with a mean dose of haloperidol of 1.68 mg/day and prospectively studied for 12 months. Subjects were assessed for extrapyramidal symptoms and psychiatric symptoms at 3-month intervals. Data were gathered from 1999 to 2001. RESULTS: Twelve-month incidence of probable or persistent tardive dyskinesia according to Schooler and Kane criteria was 12.3% (N = 7). Subjects with tardive dyskinesia did not differ from the rest of the sample regarding gender, race, duration of untreated psychosis, or baseline clinical characteristics. Subjects with tardive dyskinesia were older compared with subjects without tardive dyskinesia (37.14 +/- 9.23 vs. 27.30 +/- 8.09 years, respectively; t = -2.77, df = 30, p = .01) and received higher mean doses of haloperidol at 12 months (2.80 +/- 1.64 vs. 1.39 +/- 0.69 mg/day, respectively; t = -3.13, df = 25, p = .004). Cox regression analysis revealed that age at inclusion (p = .031), percentage change in negative symptoms (p = .028), and dose of haloperidol at 12 months (p = .016) were significant predictors of risk for tardive dyskinesia. CONCLUSION: Incidence of tardive dyskinesia was at least as high as in other samples treated with standard doses of conventional antipsychotics. Subjects at risk for tardive dyskinesia could not be identified on the basis of initial clinical features or acute treatment response. Risk of tardive dyskinesia was related to age, antipsychotic dose, and worsening of negative, depressive, and parkinsonian symptoms.

Determining the optimal dose of haloperidol in first-episode psychosis.

Uncertainty exists as to the most appropriate dose of haloperidol in first-episode psychosis. This study set out to determine whether ultra-low doses of haloperidol could successfully treat patients with first-episode psychosis. Thirty-five patients with a first episode of psychosis were treated with haloperidol in an open label, fixed protocol over a 12-week period with doses restricted to 1 mg per day for the first 4 weeks. Twenty-nine (83%) remained on haloperidol after 12 weeks at a mean dose of 1.78 mg per day, 16 (55%) had stabilized on 1 mg/day or less. The mean percentage reduction in Positive and Negative Symptom Scale score between baseline and 6 and 12 weeks was 30.3% (SD 20.9%) and 41.4% (SD 16.6%), respectively. There were no significant differences in mean extrapyramidal symptom ratings between baseline and 12 weeks. Ultra-low doses of haloperidol are effective and well tolerated in first-episode psychosis. Initial doses should be maintained for a sufficient period of time to allow for the medication to take full effect.