Ashok Malla

Duration of untreated psychosis: a critical examination of the concept and its importance.

BACKGROUND The concept of duration of untreated psychosis (DUP) has recently attracted much interest because of its possible relationship to treatment outcome and implications for preventive efforts with reference to psychotic disorders, especially schizophrenia. In this paper we review critically the literature concerning the concept and its importance. METHODS Articles concerned with measuring DUP and those that have been suggested to provide indirect or direct evidence of the effect of DUP on treatment outcome are reviewed. RESULTS Evidence thus far suggests that DUP may be related to ease of reducing psychotic symptoms once treatment begins for first episode patients, but there is no evidence of a relationship to likelihood of relapse. There has been little investigation of the relationship of DUP to other long-term outcomes such as negative symptoms and cognitive functioning neither have the possible confounds of DUP been widely investigated or controlled. CONCLUSIONS It is important that there should be more thorough investigations of DUP, its correlates, and the extent to which it does mediate any advantages of earlier intervention.

A meta-analysis of the risk for psychotic disorders among first- and second-generation immigrants

BACKGROUND There is increasing acceptance of migration as a risk factor for schizophrenia and related disorders; however, the magnitude of the risk among second-generation immigrants (SGIs) remains unclear. Generational differences in the incidence of psychotic disorders among migrants might improve our understanding of the relationship between migration, ethnicity and psychotic disorders. This meta-analysis aimed at determining the risk of psychotic disorders among SGIs in comparison with non-migrants and first-generation immigrants (FGIs). METHOD Medline, EMBASE and PsycINFO databases were searched systematically for population-based studies on migration and psychotic disorders published between 1977 and 2008. We also contacted experts, tracked citations and screened bibliographies. All potential publications were screened by two independent reviewers in a threefold process. Studies were included in the meta-analysis if they reported incidence data, differentiated FGIs from SGIs and provided age-adjusted data. Data extraction and quality assessment were conducted for each study. RESULTS Twenty-one studies met all inclusion criteria. A meta-analysis of 61 effect sizes for FGIs and 28 for SGIs yielded mean-weighted incidence rate ratios (IRRs) of 2.3 [95% confidence interval (CI) 2.0-2.7] for FGIs and 2.1 (95% CI 1.8-2.5) for SGIs. There was no significant risk difference between generations, but there were significant differences according to ethno-racial status and host country. CONCLUSIONS The increased risk of schizophrenia and related disorders among immigrants clearly persists into the second generation, suggesting that post-migration factors play a more important role than pre-migration factors or migration per se. The observed variability suggests that the risk is mediated by the social context.

One year outcome in first episode psychosis: influence of DUP and other predictors

BACKGROUND A number of studies have reported evidence of a relationship between longer duration of untreated psychosis (DUP) and poorer outcome at 1 year while others have failed to find such evidence. It is possible that several other predictors may confound this relationship and there may be different predictors for different dimensions of outcome. In the current study we examined relationship between DUP and several other predictors, and 1 year outcome on rate and level of remission as well as level of positive, negative, depressive and anxiety symptoms in a community cohort of first episode psychosis patients. METHOD All potential cases of a first episode of non-affective psychosis were assessed and offered treatment in a comprehensive treatment program. Data were collected on all patients who completed 1 year of treatment on a number of predictor variables (DUP, length of the prodromal period, age of onset, gender, pre-morbid adjustment during childhood and adolescence, diagnosis) and outcome variables (level of remission, positive, negative, depression and anxiety symptoms based on ratings on SAPS, SANS, CDS and HAS, respectively). Data were analysed using an analysis of variance, bivariate correlations and hierarchical regression analysis. RESULTS Of a total of 130 patients were offered treatment, 106 completed 1 year of treatment and complete data were available on 88 subjects, 80% of whom met criteria for schizophrenia spectrum psychosis. The rate and level of remission were significantly higher for patients with shorter DUP (<22 weeks). DUP was the only independent predictor of the level of remission as well as reality distortion at 1 year; for disorganization syndrome and negative symptoms it was the age of onset and level of premorbid adjustment in adolescence, respectively; while the level of anxiety was predicted by the length of the prodrome. Additional predictors increased the variance explained by each model. CONCLUSION Our results confirmed the independent role of DUP in remission and positive symptom outcome at 1 year, thus providing support for the enthusiasm for early intervention. However, the model including DUP and premorbid adjustment in early adolescence explained a greater amount of variance in outcome on positive symptoms than DUP alone. On the other hand, outcome on negative symptoms, disorganization and anxiety are more likely to be influenced by longer term characteristics such as premorbid adjustment, earlier age of onset, gender and the length of the prodromal period, and therefore may not be as responsive to effects of early intervention.

Predictors of rate and time to remission in first-episode psychosis : a two-year outcome study

BACKGROUND The evidence regarding the independent influence of duration of untreated psychosis (DUP) on rate and time to remission is far from unequivocal. The goal of the current study was to examine the role of predictors for rate and time to remission in first-episode psychosis (FEP). METHOD The differential effect of age, gender, age of onset, duration of untreated psychosis (DUP), duration of untreated illness (DUI), pre-morbid adjustment, co-morbid diagnosis of substance abuse and adherence to medication on the rate of and time to remission were estimated using a logistic and Poisson regression, and survival analysis respectively, in FEP patients. RESULTS In a sample of 107 FEP patients 82.2% achieved remission over a period of 2 years after a mean of 10.3 weeks (range 1-72). Regression analysis, based on complete data on all variables of interest (n=80), showed status of remission to be positively influenced by better pre-morbid adjustment (RR 0.57, 95% CI 0.34-0.95, p<0.05), later age of onset (RR 1.09, 95% CI 1.05-1.13, p<0.0001), higher level of adherence to medication (RR 1.96, 95% CI 1.38-2.76, p<0.001) and shorter DUI (RR 0.99, 95% CI 0.997-0.999, p<0.005). Time to remission was influenced by age of onset (HR 1.04, 95% CI 1.00-1.08, p<0.04) and adherence to medication (HR 1.58, 95% CI 1.11-2.23, p<0.01). CONCLUSIONS Improving adherence to medication early in the course of treatment may be an important intervention to improve short-term outcome.

The relationship of symptoms and level of functioning in schizophrenia to general wellbeing and the Quality of Life Scale

Objective: Reports suggesting that quality of life in schizophrenia is more highly related to negative rather than positive symptoms are largely based on use of the Quality of Life Scale which was devised to assess deficit symptoms and does not include an assessment of subjective general wellbeing. In the current paper we examined symptoms, level of community functioning as well as living circumstances as correlates of Quality of Life Scale scores and scores on the General Well‐Being Scale.

Understanding delay in treatment for first-episode psychosis

BACKGROUND A lengthy delay often occurs between the onset of symptoms of psychotic disorders and initiation of adequate treatment. In this paper we examine the extent to which this represents a delay in individuals contacting health professionals or a delay in receiving treatment once such contact is made. METHOD Pathways to care were examined in 110 patients of the Prevention and Early Intervention Program for Psychosis in London, Canada. Data were collected using structured interviews with patients, family members, consultation with clinicians and review of case records. RESULTS Family physicians and hospital emergency rooms were prominent components of pathways to care. Both delay to contact with a helping professional and delay from such contact to initiation of adequate treatment appear to be about equally important for the sample as a whole, but some individuals appear to be at risk for particularly lengthy delay in the second component. Individuals with younger age of onset, or who had initial contact with professional helpers before the onset of psychosis and were being seen on an ongoing basis at the time of onset of psychosis, had longer delays from first service contact after onset to initiation of adequate treatment. The greater delay to treatment for those being seen at the onset of psychosis does not appear to reflect differences in age, gender, symptoms, drug use or willingness to take medication. CONCLUSIONS Interventions to reduce treatment delay should increase the publics awareness of the symptoms of psychotic illness and the need to seek treatment, but of equal importance is the education of service providers to recognize such illness and the potential benefits of earlier intervention.

Symptoms, cognition, treatment adherence and functional outcome in first-episode psychosis.

BACKGROUND The differential strength of correlation between symptoms, cognition and other patient characteristics with community functioning in first-episode psychosis has not been fully investigated. METHOD In a sample of 66 first-episode psychosis patients demographic variables, ratings of pre-morbid adjustment, positive and negative symptoms, duration of untreated psychosis (DUP) and assessment of cognitive functions at baseline, and symptoms, cognitive functions and adherence to medication 1 year, were correlated with scores on social relations and activities of daily living (ADL) (outcome) at 1 year. Hierarchical regression analysis was used to confirm the independent contribution of baseline and concurrent variables to functional outcome at 1 year. RESULTS Scores on functioning related to social relations and ADL were both significantly correlated with pre-morbid adjustment, all dimensions of residual positive and negative symptoms and adherence to medication at 1 year. Scores on social relations were also modestly correlated with DUP and several cognitive measures at baseline and 1 year (verbal IQ, attention, visual memory, word fluency and working memory). Hierarchical regression confirmed independent contribution of pre-morbid adjustment, total residual symptoms and adherence to medication at 1 year for both dimensions of outcome, and psychomotor poverty and working memory for social relations. CONCLUSIONS In addition to pre-morbid adjustment potentially malleable variables such as level of residual (but not acute) symptoms, adherence to medication and cognitive deficits are likely to influence outcome on aspects of community functioning in individuals treated for first episode of psychosis.

A Canadian programme for early intervention in non-affective psychotic disorders.

Objectives: To provide a brief overview of the development of clinical services and research for early intervention in psychotic disorders in Canada; to describe components of a comprehensive clinical/research programme for nonaffective psychotic disorders; and to present a summary of results of clinical and social outcomes achieved. Method: This is a descriptive paper providing some details of how clinical services are being developed in Canada and concentrating on one particular early intervention programme, Prevention and Early intervention Programme for Psychoses (PEPP) London, Ontario, which is using a historical control design to evaluate the impact of an assertive approach to community case detection. Components of a phase-specific treatment programme and early case detection are described followed by results based on clinical and psychosocial data collected according to a defined protocol. Results: One year outcome for patients treated in PEPP shows use of low dose, predominantly novel antipsychotics and high (81.5%) retention and remission (75%) rates. Highly significant improvements were also reported for self-rated quality of life and cognition. Duration of untreated psychosis (DUP) and premorbid adjustment were associated with improvement in positive and negative symptoms, respectively. Systemic changes to improve access to the service resulted in substantial increases in number of cases treated and a < 50% decline in DUP. Conclusions: Phase-specific treatment approach and case identification strategies to reduce delay in treatment are likely to substantially improve outcome in nonaffective psychotic disorders compared with what has been reported with traditional approaches.

Three syndrome concept of schizophrenia: A factor analytic study

One hundred and fifty-five DSM-IIIR schizophrenic patients were assessed for positive and negative symptoms using Andreasens Scale for Assessment of Positive Symptoms (SAPS) and the Scale for Assessment of Negative Symptoms (SANS). Interrelationships of individual positive and negative symptoms were examined using a factor analysis. Results of the factor analysis are consistent with Liddles proposition that there are three syndromes underlying symptomatology in schizophrenia: disorganization; psychomotor poverty and reality distortion.

A 4.0-T fMRI study of brain connectivity during word fluency in first-episode schizophrenia

OBJECTIVE To use functional magnetic resonance imaging (fMRI) to investigate functional connectivity, and hence, underlying neural networks, in never-treated, first-episode patients with schizophrenia using a word fluency paradigm known to activate prefrontal, anterior cingulate, and thalamic regions. Abnormal connectivity between the prefrontal cortex (PFC) and other brain regions has been demonstrated in chronic, medicated patients in previous positron emission tomography (PET) studies, but has not to our knowledge, previously been demonstrated using both first-episode, drug-naïve patients and fMRI technology. METHODS A 4.0-Tesla (T) fMRI was used to examine activation and functional connectivity [psychophysiological interactions (PPIs)] during a word fluency task compared to silent reading in 10 never-treated, first-episode patients with schizophrenia and 10 healthy volunteers of comparable age, sex, handedness, and parental education. RESULTS Compared to healthy volunteers, the schizophrenia patient group exhibited less activation during the word fluency task, mostly in the right anterior cingulate and prefrontal regions. Psychophysiological interactions between right anterior cingulate and other parts of the brain revealed a localized interaction with the left temporal lobe in healthy volunteers during the task and a widespread unfocussed interaction in patients. CONCLUSION These findings suggest anterior cingulate involvement in the neuronal circuitry underlying schizophrenia.