Rahul Manchanda

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.

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.

Social support and three-year symptom and admission outcomes for first episode psychosis

This paper presents the first published findings examining the relationship of social support to three-year symptom outcome and hospitalizations for a group of first episode patients with psychotic disorders. Social support was measured using items from the provider version of the Wisconsin Quality of Life Scale as assessed at the time of initiation of treatment for 113 patients. Outcome was assessed by level of positive and negative symptoms at three-year follow-up and number of psychiatric admissions during those three years. Higher levels of social support were found to correlate with lower levels of positive symptoms and few hospitalizations at follow-up. The relationship of social support to follow-up symptoms and hospitalization was independent of other potential predictors such as gender, age, premorbid adjustment and duration of untreated illness.

Can patients at risk for persistent negative symptoms be identified during their first episode of psychosis

Patients with schizophrenia who show persistent negative symptoms are an important subgroup, but they are difficult to identify early in the course of illness. The objective of this study was to examine characteristics that discriminate between first-episode psychosis (FEP) patients in whom primary negative symptoms did or did not persist after 1 year of treatment. Patients with a DSM-IV diagnosis of FEP whose primary negative symptoms did (N = 36) or did not (N = 35) persist at 1 year were contrasted on their baseline and 1-year characteristics. Results showed that patients with persistent primary negative symptoms (N = 36) had a significantly longer duration of untreated psychosis (p < .005), worse premorbid adjustment during early (p < .001) and late adolescence (p < .01), and a higher level of affective flattening (p < .01) at initial presentation compared with patients with transitory primary negative symptoms. The former group also showed significantly lower remission rates at 1 year (p < .001). Multiple regression analysis confirmed the independent contribution of duration of untreated psychosis, premorbid adjustment, and affective flattening at baseline to the patients’ likelihood of developing persistent negative symptoms. It may therefore be possible to distinguish a subgroup of FEP patients whose primary negative symptoms are likely to persist on the basis of characteristics shown at initial presentation for treatment.

Negative symptoms in first episode non-affective psychosis

Objective: To determine the prevalence of negative symptoms and to examine secondary sources of influence on negative symptoms and the role of specific negative symptoms in delay associated with seeking treatment in first episode non‐affective psychosis.

Symptom and functional outcomes for a 5 year early intervention program for psychoses

There continues to be controversy concerning the long term benefits of specialized early intervention programs (SEI) for psychotic disorders. Recent reports of five year outcomes for SEI programs indicate that benefits of early intervention programs at two year follow-up have disappeared at five years. The Prevention and Early Intervention Program for Psychoses (PEPP) in London, Ontario offers continuity of care for five years, with a lower intensity level of specialized intervention after the initial two years. In this paper we examine whether the outcomes observed at two years were maintained at five year follow-up. In addition, it was possible to compare PEPP outcomes with those of the OPUS project at two and five years. Results indicate that improvement of symptoms between entry into PEPP and two year follow-up were maintained at five years. In addition, there was further improvement in global functioning between two and five year follow-up. Comparison of PEPP outcomes at two and five year follow-up to those of OPUS suggest that longer term continuity of care within SEI is associated with continuing benefits at least with respect to level of positive symptoms and functioning.

Testing Definitions of Symptom Remission in First-Episode Psychosis for Prediction of Functional Outcome at 2 Years

BACKGROUND To determine the clinical relevance of different definitions of symptom remission for prediction of functional outcome in first-episode psychosis (FEP). METHODS One hundred forty-one individuals receiving treatment for an FEP at a specialized early intervention service had positive and negative symptoms and functional status rated every month over the first 2 years of treatment using the Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, and Social and Occupational Functioning Assessment Scale. Subjects were classified according to 4 definitions of remission varying the criteria for severity (negative symptom inclusion/exclusion) and duration (3/6 mo sustained). RESULTS Positive symptom remission was achieved by 94% and 84% of subjects for 3 and 6 months, respectively, compared with 70% and 56% for positive and negative symptom remission, respectively. Linear regression analyses showed that only definitions of remission containing both positive and negative symptoms independently predicted functional outcome. This was confirmed by receiver operating characteristic analyses where remission based on positive and negative symptoms was marginally better than positive symptoms alone (difference in area under the curve; z = 1.94, P = .052). There was little difference between a time criterion of remission of positive and negative symptoms of 3 (sensitivity = 100%, specificity = 42%) or 6 (sensitivity = 90%, specificity = 57%) months. DISCUSSION Consistent with the consensus definition of remission in schizophrenia, severity of both positive and negative symptoms in defining remission in FEP is necessary although a 3-month criterion had equal predictive validity to the 6-month criterion.

Relationship of neuromotor disturbances to psychosis symptoms in first-episode neuroleptic-naïve schizophrenia patients

From the very inception of the modern diagnostic scheme for psychotic disorders, abnormalities in motor function have been observed in these conditions. Despite convergence from multiple areas of research supporting the notion that multiple frontal-subcortical circuits regulate motor and limbic behavior, the precise relationship between motor abnormalities and psychopathology has not been elucidated. The goals of this study were to examine the prevalence of extrapyramidal signs (EPS) in first-episode schizophrenia patients and their relationships to three psychopathological dimensions (positive psychosis syndrome, negative syndrome, and disorganization). We assessed EPS using traditional observer-based as well as quantitative instrumental measures in 39 neuroleptic-naive first-episode schizophrenia subjects. Subjects were followed for 6 months after initiating antipsychotic treatment to examine the stability of motor-limbic relationships. Four main findings emerged from this study. First, depending on the measure used the prevalence of dyskinesia prior to treatment ranged from 13% to 20%. The prevalence of parkinsonism ranged from 18% to 28%. Second, severity of dyskinesia was associated with the positive psychotic syndrome; whereas parkinsonism was associated with the positive psychosis, negative syndrome and disorganization. Third, psychopathology improved significantly across all symptom dimensions following antipsychotic treatment, while EPS remained stable. This suggests that some motor abnormalities in schizophrenia may reflect trait characteristics. Fourth, abnormalities on the pre-treatment instrumental measure of parkinsonism predicted greater improvement on positive psychosis symptoms following treatment (p=0.008). Our findings support the notion that neuromotor disturbances may be a core feature of schizophrenia in a substantial proportion of patients and implicate multiple fronto-striatal circuits regulating limbic and neuromotor behavior in schizophrenia.

Grey matter and social functioning correlates of glutamatergic metabolite loss in schizophrenia

BACKGROUND Thalamic glutamine loss and grey matter reduction suggest neurodegeneration in first-episode schizophrenia, but the duration is unknown. AIMS To observe glutamine and glutamate levels, grey matter volumes and social functioning in patients with schizophrenia followed to 80 months after diagnosis. METHOD Grey matter volumes and proton magnetic resonance spectroscopy metabolites in left anterior cingulate and left thalamus were measured in 17 patients with schizophrenia before medication and 10 and 80 months after diagnosis. Social functioning was assessed with the Life Skills Profile Rating Scale (LSPRS) at 80 months. RESULTS The sum of thalamic glutamate and glutamine levels decreased over 80 months, and correlated inversely with the LSPRS. Thalamic glutamine and grey matter loss were significantly correlated in frontal, parietal, temporal and limbic regions. CONCLUSIONS Brain metabolite loss is correlated with deteriorated social functioning and grey matter losses in schizophrenia, consistent with neurodegeneration.