Premorbid functioning versus duration of untreated psychosis in 1 year outcome in first-episode psychosis

OBJECTIVE: This study examines 1year outcome in patients having first-episode non-affective psychosis, with emphasis on Duration of Untreated Psychosis (DUP) and premorbid functioning, in order to clarify how these factors interact. METHOD: Forty-three consecutively admitted patients were all rated on the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning Scale (GAF), both upon hospitalization and at 1year follow-up. In addition, premorbid functioning, DUP, duration of hospitalization, and social functioning were rated. RESULTS: Fifty-six per cent were in remission, 18% suffered multiple relapses and 26% were continuously psychotic at 1 year follow-up. Both poor premorbid functioning and long DUP are significantly correlated with more negative symptoms and poorer global functioning at follow-up. Long DUP is also significantly correlated with more positive symptoms. Even when we control for other factors, including premorbid functioning and gender, DUP is a strong predictor of outcome. To a limited degree premorbid functioning and DUP interact, but DUP has an independent influence on outcome. CONCLUSIONS: these findings strengthen the rationale for establishing health service programs for early detection and treatment of first-onset psychosis     

Association between duration of untreated psychosis, premorbid functioning, and cognitive performance and the outcome of first-episode schizophrenia in Japanese patients: prospective study

OBJECTIVE: The aim of the present study was to identify the relationship between duration of untreated psychosis (DUP), premorbid functioning, and cognitive dysfunction and the outcome of first-episode schizophrenia. METHOD: Thirty-four neuroleptic-na?ve patients who consulted hospitals in Tokyo and who were treated by psychiatrists for the first time were evaluated with regard to DUP, premorbid functioning, psychiatric symptoms, and global functioning. The neuropsychological test battery consisted of the Letter Cancellation Test, Trail-Making Test, Digit Span and Verbal Fluency Test. One year later, 24 of the subjects were reassessed for psychiatric symptoms, global functioning, and social functioning, and the relationships between DUP, premorbid functioning, and cognitive performance and the outcome was investigated. RESULTS: Short DUP, good premorbid functioning, and good Letter Cancellation Test, Digit Span and Verbal Fluency Test scores were significantly associated with good outcome. CONCLUSIONS: The present results in a Japanese sample are consistent with previous international evidence that delay of initial treatment, premorbid functioning, and cognitive deficits are associated with outcome. A major limitation of the present study was the small size of the subject group. But because the subjects were relatively homogeneous and not influenced by psychoactive substances, the results reflect the essence of the disorder.     

Premorbid adjustment, symptom development and quality of life in first episode psychosis: a systematic review and critical reappraisal

Objective: To systematically review the relationship of premorbid adjustment to symptomatology in first episode psychosis (FEP), taking into account the influence of duration of untreated psychosis (DUP). Method: Electronic databases were searched to identify relevant studies. Results: A variety of approaches to the reporting of premorbid adjustment were identified. There was no significant association between premorbid adjustment and DUP, supporting the proposition that they are independent constructs. The effect of premorbid adjustment upon positive symptomatology was negligible. Premorbid adjustment had a modest effect upon negative symptoms and quality of life, increasing over duration of follow‐up. Conclusion: Premorbid adjustment remains a valid construct in the study of FEP. Both premorbid adjustment and DUP confer independent effects on aspects of symptomatology in FEP. Results for premorbid adjustment are similar to previous findings in more chronic samples. The potential for conceptualizing premorbid functioning by developmental, academic/social and typological approaches is currently underexploited.     

Clinical epidemiologic first-episode psychosis: 1-year outcome and predictors

OBJECTIVE: To describe 1-year outcome in a large clinical epidemiologic sample of first-episode psychosis and its predictors. METHOD: A total of 301 patients with first-episode psychosis from four healthcare sectors in Norway and Denmark receiving common assessments and standardized treatment were evaluated at baseline, at 3 months, and at 1 year. RESULTS: Substantial clinical and social improvements occurred within the first 3 months. At 1-year 66% were in remission, 11% in relapse, and 23% continuously psychotic. Female gender and better premorbid functioning were predictive of less severe negative symptoms. Shorter DUP was predictive for shorter time to remission, stable remission, less severe positive symptoms, and better social functioning. Female gender, better premorbid social functioning and more education also contributed to a better social functioning. CONCLUSION: This first-episode sample, being well treated, may be typical of the early course of schizophrenia in contemporary centers.     

The relevance of cognitive,clinical and premorbid variables in predicting functional outcome for individuals with first-episode psychosis: A 3 year longitudinal study

Real-world functional deficits are common and persistent in individuals with psychosis. Cognitive deficits have been shown to compromise functioning. We aimed to study the predictive values of premorbid, sociodemographic, and baseline clinical and neurocognitive factors on long-term functional outcome for individuals with first episode non-affective psychosis. We failed to demonstrate a significant relationship between cognitive deficits at baseline and functional disability at 3 year follow-up. Diagnosis of schizophrenia (OR=2.457, p=0.011), shorter education (OR=1.177, p=0.005) and poor premorbid social adjustment (OR=1.628, p=0.013) emerged as the strongest predictors for the 114 subjects (56%) that exhibited functional disability at 3-year follow-up. A considerable proportion of the variance in functioning (74% at 1 year and 77% at 3 year) remained unexplained by baseline variables. The set of variables that predicted functional outcome at medium- (1 year) and long-term (3 years) differed. In conclusion, the length of follow-up influenced the relationship between baseline variables and functional outcome. A substantial proportion of the variance in function was not explained by these variables and therefore the influence of other factors warrants further investigation. The data support the notion that premorbid social adjustment is an important aspect in functional outcome over the course of the illness.     

Early identification of non‐remission in first‐episode psychosis in a two‐year outcome study

Simonsen E, Friis S, Opjordsmoen S, Mortensen EL, Haahr U, Melle I, Joa I, Johannessen JO, Larsen TK, Røssberg JI, Rund BR, Vaglum P, McGlashan TH. Early identification of non‐remission in first‐episode psychosis in a two‐year outcome study. Objective: To identify predictors of non‐remission in first‐episode, non‐affective psychosis. Method: During 4 years, we recruited 301 patients consecutively. Information about first remission at 3 months was available for 299 and at 2 years for 293 cases. Symptomatic and social outcomes were assessed at 3 months, 1 and 2 years. Results: One hundred and twenty‐nine patients (43%) remained psychotic at 3 months and 48 patients (16.4%) remained psychotic over 2 years. When we compared premorbid and baseline data for the three groups, the non‐remitted (n = 48), remitted for <6 months (n = 38) and for more than 6 months (n = 207), duration of untreated psychosis (DUP) was the only variable that significantly differentiated the groups (median DUP: 25.5, 14.4 and 6.0 weeks, respectively). Three months univariate predictors of non‐remission were being single, longer DUP, core schizophrenia, and less excitative and more negative symptoms at baseline. Two‐year predictors were younger age, being single and male, deteriorating premorbid social functioning, longer DUP and core schizophrenia. In multivariate analyses DUP, negative and excitative symptoms predicted non‐remission at 3 months, but only DUP predicted at 2 years. Conclusion: Long DUP predicted both 3 month and 2‐year non‐remission rates in first‐episode psychosis.     

Impact of duration of untreated psychosis on pre-treatment, baseline, and outcome characteristics in an epidemiological first-episode psychosis cohort

INTRODUCTION: To assess the impact of duration of untreated psychosis (DUP) on baseline and 18-month follow-up characteristics controlling for relevant confounders in an epidemiological first-episode psychosis (FEP) cohort. METHOD: The Early Psychosis Prevention and Intervention Centre (EPPIC) in Australia admitted 786 FEP patients from January 1998 to December 2000. Data were collected from medical files using a standardized questionnaire. Data from 636 patients were analyzed. RESULTS: Median DUP was 8.7 weeks. Longer DUP was associated with worse premorbid functioning (p<0.001), higher rate of schizophrenia-spectrum disorders (p<0.001), and younger age at onset of psychosis (p=0.004). Longer DUP was not associated with baseline variables but with a lower rate of remission of positive symptoms (p<0.001) and employment/occupation (p<0.001), a higher rate of persistent substance use (p=0.015), worse illness severity (p<0.001) and global functioning (p<0.001) at follow-up after controlling for relevant confounders, explaining approximately 5% of variance of remission of positive symptoms (p<0.001) in the total sample and 3% in schizophrenia-spectrum disorders excluding bipolar I disorder (p=0.002). Outcome was significantly worse when DUP exceeded 1-3 months. CONCLUSION: Avoiding pitfalls of non-epidemiological studies, DUP appears to be a modest independent predictor of prognosis in the medium-term. Results support the need for assertive early detection strategies.     

Is the association between duration of untreated psychosis and outcome confounded? A two year follow-up study of first-admitted patients

OBJECTIVE: To assess whether a long duration of untreated psychosis (DUP) before first admission predicts poor clinical and social outcome, and whether this association, if any, is confounded by premorbid and clinical characteristics. METHOD: A population-based sample of first-admitted subjects with psychosis (n = 65) was assessed at six monthly intervals over a two year follow-up using multiple sources of information. RESULTS: Most subjects (87%) with a life-chart 'continuous' course of psychotic symptoms had a history of a 'long' delay between onset of psychotic symptoms and first admission (> or = 3 months, median split), compared with 55% of subjects with a course of 'neither episodic nor continuous', 42% of subjects with an 'episodic' course, and 33% of subjects with 'no psychotic symptoms' during the follow-up period (RR = 9; 95%CI 1.5-54.8, P = 0.02). The strength of association between DUP and continuous course of psychosis was strongly reduced (63%) after adjustment for premorbid functioning, and to a lesser extent for the severity of illness and for the intensity of negative symptoms at first admission. CONCLUSIONS: The association between DUP and poor outcome may be spurious, confounded by the fact that poor premorbid functioning is independently associated with both DUP and poor outcome, with no direct causal link between these two latter variables. DUP may also be on the causal pathway between poor premorbid functioning and poor outcome, poor adjustment delaying access to care, and subsequently increasing the risk of presenting with a non-remitting course of illness. The links between premorbid functioning, DUP and outcome have to be further explored to clarify the directions of the associations between these variables.     

Early premorbid adjustment as a moderator of the impact of duration of untreated psychosis

OBJECTIVES: Shorter duration of untreated psychosis (DUP) is often correlated with a poorer response to treatment. In this paper we test the hypothesis that the importance of DUP is moderated by early premorbid adjustment. METHOD: Three year prospective data were collected for 154 first episode patients. DUP, premorbid adjustment and symptoms were assessed at time of presentation for treatment and symptoms were reassessed after three years of treatment. RESULTS: DUP was correlated with level of symptoms at three years only for patients with better premorbid adjustment in childhood and early adolescence. CONCLUSIONS: These results suggest that DUP may have more of an impact on treatment response for those with a less pernicious, more reversible form of illness.     

Neurocognitive dysfunction in first-episode psychosis: correlates with symptoms, premorbid adjustment, and duration of untreated psychosis

OBJECTIVE: The authors examined the relationship of neurocognitive function with duration of untreated psychosis, premorbid illness factors, and clinical symptoms to determine whether long duration of untreated psychosis independently compromises cognitive function. METHOD: Patients recruited to a study of the effect of an early detection program on the duration of untreated first-episode psychosis in two catchment areas were compared to patients in a similar treatment program in two other catchment areas without an early detection program. The median duration of untreated psychosis was 10.5 weeks for all patients. A total of 301 patients entered the study, and 207 completed a comprehensive neuropsychological test battery that assessed working memory/fluency, executive function, verbal learning, impulsivity, and motor speed. The median time from start of treatment to neuropsychological testing was 108 days; all patients were tested within 9 months. RESULTS: No significant association was found between duration of untreated psychosis and any of the cognitive measures. Strong associations were demonstrated between poorer premorbid school functioning and neurocognitive deficits, especially in verbal learning and working memory. No relationship was found between neurocognitive functions and clinical measures, except for an inverse correlation of Positive and Negative Syndrome Scale negative symptoms and working memory and a positive correlation between positive symptoms and motor speed. CONCLUSIONS: The data contribute to a disconfirmation of the hypothesis of an association between duration of untreated psychosis and neurocognitive performance at baseline.     

Duration of untreated psychosis: a proposition regarding treatment definition

Aim: Duration of untreated psychosis (DUP) refers to the time elapsing between psychosis onset and treatment initiation. Despite a certain degree of consensus regarding the definition of psychosis onset, the definition of treatment commencement varies greatly between studies and DUP may be underestimated due to lack of agreement. In the present study, three sets of criteria to define the end of the untreated period were applied in a first‐episode psychosis cohort to assess the impact of the choice of definition on DUP estimation. Methods: The DUP of 117 patients admitted in the Treatment and Early Intervention in Psychosis Program Psychosis in Lausanne was measured using the following sets of criteria to define treatment onset: (i) initiation of antipsychotic medication; (ii) entry into a specialized programme; and (iii) entry into a specialized programme and adequate medication with a good compliance. Results: DUP varied greatly according to definitions, the most restrictive criteria leading to the longest DUP (median DUP1 = 2.2 months, DUP2 = 7.4 months and DUP3 = 13.6 months). A percentage of 19.7 of the patients who did not meet these restrictive criteria had poorer premorbid functioning and were more likely to use cannabis. Longer DUP3 was associated with poorer premorbid functioning and with younger age at onset of psychosis. Conclusion: These results underline the need for a unique and standardized definition of the end of DUP. We suggest that the most restrictive definition of treatment should be used when using the DUP concept in future research.     

Differential associations of cognitive insight components with pretreatment characteristics in first-episode psychosis

An increasing number of studies have focused on cognitive insight (i.e. awareness of one's own thinking) in psychotic disorders. However, little is known about the premorbid and pretreatment correlates of cognitive insight in the early course of psychosis. One hundred and three patients experiencing first-episode psychosis (FEP) were assessed shortly after treatment initiation for cognitive insight. Pretreatment and baseline clinical, functional and neurocognitive characteristics were examined. The self-reflectiveness dimension of cognitive insight was independently associated with clinical insight and executive functioning, whereas self-certainty was associated with premorbid IQ, premorbid academic adjustment and clinical insight. The amount of variance explained by the independent variables was small to moderate. Self-reflectiveness and self-certainty have differential pretreatment correlates in FEP and may reflect separate cognitive processes which require targeted interventions.     

One year outcome in first episode schizophrenia

The aim of this study was to identify the predictors of outcome at one year follow-up after the first psychotic episode of schizophrenia. Seventy-nine first-episode schizophrenia patients were assessed monthly with the Brief Psychiatric Rating Scale (BPRS), Scale for Assessment of Positive Symptoms (SAPS), and Scale for Assessment of Negative Symptoms (SANS) after discharge from their first hospitalization. Outcome measures were presence of relapse and rehospitalization, level of global functioning, employment status and severity of symptoms at one year. A total of 33% of the patients had a relapse, and 12.1% were rehospitalized during one year follow-up. Premorbid childhood functionality was worse in patients who had relapse, but there was no correlation between premorbid adjustment scores and BPRS, SANS and SAPS scores at one year. There was no difference in duration of untreated psychosis (DUP) between patients who had relapse and not; however, the patients who had double relapse, had longer DUP than those without relapse. The time period between discharge and rehospitalization was shorter in patients with longer DUP. Functionality in childhood and noncompliance to the treatment independently contributed to the relapse rate. Functionality in late adolescence independently contributed to the Global Assessment of Functioning (GAF) scale score at one year and the GAF score at discharge appeared as a predictor of employment. The results of the present study suggest that treatment compliance and early premorbid adjustment level seem to be important predictors of relapse rate in first episode schizophrenia.     

Duration of untreated psychosis and neuropsychological function in first episode psychosis

PURPOSE: We investigated whether duration of untreated psychosis (DUP) prior to first presentation was associated with cognitive function in first episode psychosis (FEP) subjects. We predicted that longer DUP would be associated with greater neurocognitive impairment. METHOD: 180 subjects with schizophrenia (and 93 subjects with Other Psychoses) performed a neurocognitive battery assessing IQ, verbal learning, working memory, visual learning and speed of processing. DUP was defined as the number of days between first onset of psychotic symptoms and first contact with psychiatric services. RESULTS: Longer DUP was associated with impaired performance in verbal IQ (p=0.04), verbal learning (p=0.02), and verbal working memory (p=0.04) in FEP subjects with schizophrenia. These associations remained significant for verbal IQ when scores were corrected for age, gender, educational level and ethnicity. CONCLUSIONS: Longer DUP is associated with poorer neurocognitive ability in schizophrenia subjects at time of first presentation. Since this was a cross-sectional study we can not tell whether longer DUP was a cause or a consequence of the poorer performance.     

Executive functioning correctly classified diagnoses in patients with first-episode psychosis: evidence from a 2-year longitudinal study

Few studies have analysed factors that predict the ultimate clinical diagnosis in first-episode psychosis (FEP), and none has included cognitive factors. Eighty-six FEP patients and 34 healthy controls were recruited and followed up for two years. Positive and negative symptoms, depression, mania, duration of untreated psychosis (DUP), premorbid functioning, functional outcome and neurocognition were assessed over 2 years. Logistic regression models revealed that Wisconsin Card Sorting Test correctly distinguished the patients ultimately diagnosed with schizophrenia (87%) from those with bipolar disorder (80%) and those with other psychoses (85%), for an overall correct-diagnosis rate of 84.4%. The prediction was stable despite the inclusion of clinical and affective symptoms, DUP, clinical impression, and functional outcome scores. Results highlight the importance of reconsidering neurocognition as a diagnostic criterion for psychosis and schizophrenia.     

Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review

CONTEXT: Duration of untreated psychosis (DUP) is the time from manifestation of the first psychotic symptom to initiation of adequate treatment. It has been postulated that a longer DUP leads to a poorer prognosis. If so, outcome might be improved through earlier detection and treatment. OBJECTIVES: To establish whether DUP is associated with prognosis and to determine whether any association is explained by confounding with premorbid adjustment. DATA SOURCES: The CINAHL (Cumulative Index to Nursing and Allied Health), EMBASE, MEDLINE, and PsychLIT databases were searched from their inception dates to May 2004. STUDY SELECTION: Eligible studies reported the relationship between DUP and outcome in prospective cohorts recruited during their first episode of psychosis. Twenty-six eligible studies involving 4490 participants were identified from 11 458 abstracts, each screened by 2 reviewers. DATA EXTRACTION: Data were extracted independently and were checked by double entry. Sensitivity analyses were conducted excluding studies that had follow-up rates of less than 80%, included affective psychoses, or did not use a standardized assessment of DUP. DATA SYNTHESIS: Independent meta-analyses were conducted of correlational data and of data derived from comparisons of long and short DUP groups. Most data were correlational, and these showed a significant association between DUP and several outcomes at 6 and 12 months (including total symptoms, depression/anxiety, negative symptoms, overall functioning, positive symptoms, and social functioning). Long vs short DUP data showed an association between longer DUP and worse outcome at 6 months in terms of total symptoms, overall functioning, positive symptoms, and quality of life. Patients with a long DUP were significantly less likely to achieve remission. The observed association between DUP and outcome was not explained by premorbid adjustment. CONCLUSIONS: There is convincing evidence of a modest association between DUP and outcome, which supports the case for clinical trials that examine the effect of reducing DUP.     

Substance abuse in first-episode non-affective psychosis

Abuse of alcohol and drugs is an important and clinically challenging aspect of first-episode psychosis. Only a few studies have been carried out on large-sized and reliably characterized samples. These are reviewed, and the results are compared with a sample of 300 first-episode psychosis patients recruited for the TIPS (Early Treatment and Identification of Psychosis) study from Norway and Denmark. Prevalence rates from the literature vary from 6% to 44% for drugs and 3% to 35% for alcohol. In our sample, 23% abused drugs and 15% abused alcohol during the last 6 months. When compared to non-abusers, the drug-abusing group is characterized by the following: male gender, younger age, better premorbid social, poor premorbid academic functioning, and more contact with friends in the last year before onset. Alcohol abusers were the oldest group and they had the least contact with friends. A group of patients abusing both drugs and alcohol had poor premorbid academic functioning from early childhood. Overall, drug and alcohol abuse are highly prevalent in contemporary first-episode psychosis samples. In our study, substance abuse comorbidity did not generate differences on diagnosis, duration of untreated psychosis, psychiatric symptoms, or global functioning at onset/baseline. The premorbid profiles of the substance abusers were clearly different from the non-abusers. Drug abusers, in particular, were more socially active both premorbidly and during the year preceding the start of treatment.     

Substance abuse in first-episode non-affective psychosis

Abuse of alcohol and drugs is an important and clinically challenging aspect of first-episode psychosis. Only a few studies have been carried out on large-sized and reliably characterized samples. These are reviewed, and the results are compared with a sample of 300 first-episode psychosis patients recruited for the TIPS (Early Treatment and Identification of Psychosis) study from Norway and Denmark. Prevalence rates from the literature vary from 6% to 44% for drugs and 3% to 35% for alcohol. In our sample, 23% abused drugs and 15% abused alcohol during the last 6 months. When compared to non-abusers, the drug-abusing group is characterized by the following: male gender, younger age, better premorbid social, poor premorbid academic functioning, and more contact with friends in the last year before onset. Alcohol abusers were the oldest group and they had the least contact with friends. A group of patients abusing both drugs and alcohol had poor premorbid academic functioning from early childhood. Overall, drug and alcohol abuse are highly prevalent in contemporary first-episode psychosis samples. In our study, substance abuse comorbidity did not generate differences on diagnosis, duration of untreated psychosis, psychiatric symptoms, or global functioning at onset/baseline. The premorbid profiles of the substance abusers were clearly different from the non-abusers. Drug abusers, in particular, were more socially active both premorbidly and during the year preceding the start of treatment.     

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.