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BACKGROUND: The predictors of functional capacity in first episode schizophrenia among seven separable cognitive domains and clinical variables are unknown. AIM: To investigate predictors of functional capacity in first episode schizophrenia and the associations between functional capacity and measures of real-world functioning. METHODS: Socio-demographic, clinical, and cognitive measures from a sample of patients with first episode schizophrenia spectrum disorders aged 18-34years (N=117) were examined at baseline, 4-month follow-up, and 10-month follow-up and used to predict concurrent and longitudinal functional capacity. Symptoms were assessed with the Positive and Negative Syndrome Scale, cognitive functioning with the MATRICS Cognitive Consensus Battery, and functional capacity with the brief version of the University of California San Diego Performance-based Skills Assessment. Linear and logistic regression analyses were adjusted for age, gender, and site. RESULTS: Working memory, negative symptoms, and social cognition accounted for 41% of the variance in functional capacity at baseline. Longitudinally, verbal learning, working memory, and negative symptoms predicted 4-month functional capacity. Working memory and visual learning predicted 10-month functional capacity. Functional capacity was associated to global functioning in the univariate analysis, but in multivariable analyses global functioning, financial independence, and independent living were predicted by negative symptoms or general symptoms explaining 15-23% of the variance. CONCLUSIONS: The strongest single predictor of functional capacity is working memory, followed by negative symptoms. Clinical symptoms, but not functional capacity, predicted real-world functioning. The usability of the UPSA-B in first episode schizophrenia is discussed. Neurocom, ClinicalTrials.gov Identifier: NCT00472862, http://clinicaltrials.gov/ct2/show/NCT00472862?term=neurocom&rank=1.

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BACKGROUND: The Danish OPUS I trial randomized 547 patients with first-episode psychosis to a two-year early-specialised assertive treatment programme (OPUS) versus standard treatment. The two years OPUS treatment had significant positive effects on psychotic and negative symptoms, secondary substance abuse, treatment adherence, lower dosage of antipsychotic medication, and a higher treatment satisfaction. However, three years after end of the OPUS treatment, the positive clinical effects were not sustained, except that OPUS-treated patients were significantly less likely to be institutionalised compared with standard-treated patients. The major objective of the OPUS II trial is to evaluate the effects of five years of OPUS treatment versus two years of OPUS treatment. METHODS: The OPUS II trial is designed as a randomized, open label, parallel group trial with blinded outcome assessment. Based on our sample size estimation, 400 patients treated in OPUS for two years will be randomized to further three years of OPUS treatment versus standard treatment. The specialized assertive OPUS treatment consists of three core elements: assertive community treatment, psycho-educational family treatment, and social skills training. DISCUSSION: It has been hypothesized that there is a critical period from onset up to five years, which represents a window of opportunity where a long-term course can be influenced. Extending the specialized assertive OPUS treatment up to five years may allow the beneficial effects to continue beyond the high-risk period, through consolidation of improved social and functional outcome. TRIAL REGISTRATION: Clinical Trial.gov NCT00914238.

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BACKGROUND: Up to 85% of patients with schizophrenia demonstrate cognitive dysfunction in at least one domain. Cognitive dysfunction plays a major role in functional outcome. It is hypothesized that addition of cognitive training to a comprehensive psychosocial programme (OPUS) enhances both cognitive and everyday functional capacity of patients more than the comprehensive psychosocial programme alone. METHODS: The NEUROCOM trial examines the effect on cognitive functioning and everyday functional capacity of patients with schizophrenia of a 16-week manualised programme of individual cognitive training integrated in a comprehensive psychosocial programme versus the comprehensive psychosocial programme alone. The cognitive training consists of four modules focusing on attention, executive functioning, learning, and memory. Cognitive training involves computer-assisted training tasks as well as practical everyday tasks and calendar training. It takes place twice a week, and every other week the patient and trainer engage in a dialogue on the patient's cognitive difficulties, motivational goals, and progress in competence level. Cognitive training relies on errorless learning principles, scaffolding, and verbalisation in its effort to improve cognitive abilities and teach patients how to apply compensation strategies as well as structured problem solving techniques. At 16-week post-training and at ten-months follow-up, assessments are conducted to investigate immediate outcome and possible long-term effects of cognitive training. We conduct blinded assessments of cognition, everyday functional capacity and associations with the labour market, symptom severity, and self-esteem. DISCUSSION: Results from four-month and ten-month follow-ups have the potential of reliably providing documentation of the long-term effect of CT for patients with schizophrenia. TRIAL REGISTRATION: Clinicaltrials.gov NCT00472862.

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INTRODUCTION: This paper aims to investigate the predictors of good outcome after first-episode non-affective psychosis and the clinical and social trajectories of those that recover. METHODS: A cohort of 255 patients with first-episode non-affective psychosis was interviewed 5 years after first diagnosis and treatment. Recovery was defined as working or studying, having a GAF-function score of 60 or above, having remission of negative and psychotic symptoms, and not living in a supported housing facility or being hospitalized during the last 2 years before the five-year follow-up interview. RESULTS: A total of 40 (15.7%) were found to be recovered, and 76 (29.8%) had a job or were studying after 5 years. Of those working, as many as 20 still had psychotic symptoms. Also notable is that out of the 40 recovered, less than half were recovered after 2 years. Recovery after 5 years was predicted by female sex (OR 2.4, 95% CI 1.0-5.8), higher age (OR 0.91, 95% CI 0.83-0.99), pre-morbid social adaptation (OR 0.72, 95% CI 0.56-0.93), growing up with both parents (OR 2.6, 95% CI 1.0-6.8) and low level of negative symptoms (OR 0.51, 95% CI 0.33 to 0.77) at baseline. DISCUSSION: Our findings suggest that a stable social life with normal social functioning has a predictive value for good outcome. These measures might be influenced by negative symptoms, but in the multivariate analysis with negative symptoms included they have an independent effect. Also our findings suggest that, after first-episode psychosis, some patients can still experience psychotic symptoms, but have a job and a fairly stable life.

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A total of 547 patients with a first episode of psychosis were randomised to two years of intensive early intervention programme (OPUS) versus standard treatment. OPUS treatment consisted of Assertive Community Treatment (ACT) with manuals for family involvement and social skills training. Standard treatment comprised contact with a community mental health centre. OPUS treatment improved the clinical outcome after two years of treatment, but the effects were not sustainable up to five years after. The secondary outcome measures showed a difference on supported housing and use of bed-days at the five-year follow-up in favour of OPUS treatment.

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AIM: This study sought to identify predictors for poor adherence to medication among patients with first-episode schizophrenia-spectrum disorder. METHODS: Medication adherence was measured 1 and 2 years after initiation of antipsychotic medication in a follow-up study of 547 patients. Relevant variables were systematically assessed at baseline, 1- and 2-year follow up. RESULTS: Most patients have difficulties with medication adherence over time. Negative attitudes towards medication and lack of consistent family support are the strongest predictors for poor adherence to medication for first-episode psychotic patients in the first 2 years. After 1 year of treatment, unawareness of the effect of medication, lack of positive attitudes towards medication, substance abuse, young age and high global functioning also predict poor adherence to medication. CONCLUSIONS: A number of variables were independently associated with poor adherence. Rating of insight and attitudes towards medication makes it possible to predict poor adherence in incident cases with schizophrenia.

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There is an ongoing debate as to whether psychosis is a progressively deteriorating illness or one of progressive amelioration. This paper aims at investigating the rate of recovery and institutionalization and predicting a continuous illness course in a descriptive prospective study of a sub-sample of the OPUS trial of 265 first-episode psychotic patients after five years. Recovery, defined as no psychotic or negative symptoms, living independently, GAF (f)>59, working or studying, was reached for 18% after five years, whereas 13% were institutionalized either at hospital or supported housing after five years. Male gender (OR 1.9, 95% CI 1.06 to 3.23), premorbid social functioning (OR 1.2, 95% CI 1.01 to 1.33), psychotic symptoms (OR 1.3, 95% CI 1.07 to 1.66), and negative symptoms (OR 1.3, 95% CI 1.01 to 1.67) were found to predict a continuous illness course at five-year follow-up. Rates of recovery and institutionalization contradict the assumption that the illness deteriorates progressively, since no changes in the rates are seen from two to five years.

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The article describes psychotherapy for schizophrenia. There is evidence for the effect of cognitive behavioural therapy in reducing persistent positive symptoms, improving social function, improving insight and reducing the time to remission. Personal therapy is a relatively new kind of psychotherapeutic intervention. There is lack of evidence for any effect on relapse rates from psychodynamic therapy, but the model is helpful for therapists in obtaining an empathic understanding of patients.

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OBJECTIVE: To examine the frequency and predictors of good outcome for patients with first-episode schizophrenia spectrum disorder (SSD). METHOD: We conducted a 2-year follow-up of a cohort of patients (n = 547) with first-episode SSD. We evaluated the patients on demographic variables, diagnosis, duration of untreated psychosis (DUP), premorbid functioning, psychotic and negative symptoms, substance abuse, adherence to medication, and service use. ORs were calculated with logistic regression analyses. RESULTS: A total of 369 patients (67%) participated in the follow-up interview. After 2 years, 36% remitted and 17% were considered fully recovered. Full recovery was associated with shorter DUP, better premorbid adjustment, fewer negative symptoms at baseline, no substance abuse at baseline, and adherence to medication and OPUS treatment. CONCLUSIONS: Several predictive factors were identified, and focus should be on potentially malleable predictors of outcome, for example, reducing DUP and paying special attention to patients who are unlikely to achieve good outcome, for example, patients with a substance abuse problem and poor premorbid adjustment.

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CONTEXT: Intensive early treatment for first-episode psychosis has been shown to be effective. It is unknown if the positive effects are sustained for 5 years. OBJECTIVE: To determine the long-term effects of an intensive early-intervention program (OPUS) for first-episode psychotic patients. DESIGN: Single-blinded, randomized, controlled clinical trial of 2 years of an intensive early-intervention program vs standard treatment. Follow-up periods were 2 and 5 years. SETTING: Copenhagen Hospital Corporation and Psychiatric Hospital, Aarhus, Denmark. Patients A total of 547 patients with a first episode of psychosis. Of these, 369 patients were participating in a 2-year follow-up, and 301 were participating in a 5-year follow-up. A total of 547 patients were followed for 5 years. INTERVENTIONS: Two years of an intensive early-intervention program vs standard treatment. The intensive early-intervention treatment consisted of assertive community treatment, family involvement, and social skills training. Standard treatment offered contact with a community mental health center. MAIN OUTCOME MEASURES: Psychotic and negative symptoms were recorded. Secondary outcome measures were use of services and social functioning. RESULTS: Analysis was based on the principles of intention-to-treat. Assessment was blinded for previous treatment allocation. At the 5-year follow-up, the effect of treatment seen after 2 years (psychotic dimension odds ratio [OR], -0.32; 95% confidence interval [CI], -0.58 to -0.06; P = .02; negative dimension OR, -0.45; 95% CI, -0.67 to -0.22; P = .001) had equalized between the treatment groups. A significantly smaller percentage of patients from the experimental group were living in supported housing (4% vs 10%, respectively; OR, 2.3; 95% CI, 1.1-4.8; P = .02) and were hospitalized fewer days (mean, 149 vs 193 days; mean difference, 44 days; 95% CI, 0.15-88.12; P = .05) during the 5-year period. CONCLUSIONS: The intensive early-intervention program improved clinical outcome after 2 years, but the effects were not sustainable up to 5 years later. Secondary outcome measures showed differences in the proportion of patients living in supported housing and days in hospital at the 5-year follow-up in favor of the intensive early-intervention program.

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The effect of integrated treatment on the use of coercive measures in first-episode schizophrenia-spectrum disorder in Denmark is not known. A total of 328 patients were randomly assigned to integrated treatment (167 patients) or standard treatment (161 patients). Integrated treatment consisted of assertive community treatment, psycho-educational multi-family groups, and social skills training. Data on coercion were extracted from the register from the National Board of Health, and data on continuity from medical records. Even though the level of continuity seemed higher in integrated treatment, this did not reduce the use of coercive measures compared to the use in standard treatment.

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INTRODUCTION: Duration of untreated psychosis (DUP) is shown to be associated with poor outcome in many domains. It has been shown that it is possible to shorten DUP when combining a detection team and an information campaign. The aim of this study was to evaluate whether DUP was shortened during the first 3 years after establishing detection teams without a concomitant information campaign. METHODS: All patients included in the OPUS trial were examined with the Instrument for Retrospective Assessment of Onset of Psychosis to determine DUP. A total of 552 patients with first episode psychotic disorder (n=470) or schizotypal disorder (n=82) were included in the study. The 3-year inclusion period was divided into six consecutive periods of 6 months each. RESULTS: The median DUP was 52 weeks. DUP was not significantly reduced during the 3-year inclusion period, but a larger proportion of patients with symptoms below the threshold for frank psychosis were included compared with the beginning of the trial. The proportion referred from primary care remained small (8-10%) and unchanged during the inclusion period. DISCUSSION: The availability of a detection team increased the referral of patients with schizotypal disorder, but the DUP among psychotic patients remained almost unaltered throughout the period. It seems that an information campaign and possibilities for direct access and self-referral are necessary in order to shorten DUP.

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Gender differences in age at first onset, duration of untreated psychosis, psychopathology, social functioning, and self-esteem were investigated in a group of 578 young adults with a first-episode schizophrenia spectrum disorder. The mean age at first-onset of symptoms, age at first contact, and duration of untreated psychosis were similar for men and women. Men had more severe negative symptoms, poorer premorbid functioning, and poorer social networks, whereas women had more severe hallucinations. More men than women were substance abusers, were unemployed, and lived alone. Women had poorer self-esteem than men, in spite of better scores in functioning. Premorbid social adjustment was significantly related to the level of negative symptoms and number of friends. Conclusion is that men and women with first-episode psychosis showed different psychopathological characteristics and different social functioning, which cannot be explained by older age of onset for women. Women make more suicide attempts and experience lower self-esteem in spite of better social functioning.

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BACKGROUND: Those with first-episode psychosis are at high-risk of suicide. AIMS: To identify predictive factors for suicidal thoughts, plans and attempts, and to investigate the rate of suicides and other deaths during the 5 years after first diagnosis and initiation of treatment. METHOD: A longitudinal, prospective, 5-year follow-up study of 547 individuals with first-episode schizophrenia spectrum psychosis. Individuals presenting for their first treatment in mental health services in two circumscribed urban areas in Denmark were included in a randomised controlled trial of integrated v. standard treatment. All participants were followed in the Danish Cause of Death Register for 5 years. Suicidal behaviour and clinical and social status were assessed using validated interviews and rating scales at entry, and at 1- and 2-year follow-ups. RESULTS: Sixteen participants died during the follow-up. We found a strong association between suicidal thoughts, plans and previous attempts, depressive and psychotic symptoms and young age, and with suicidal plans and attempts at 1- and 2-year follow-up. CONCLUSIONS: In this first-episode cohort depressive and psychotic symptoms, especially hallucinations, predicted suicidal plans and attempts, and persistent suicidal behaviour and ideation were associated with high risk of attempted suicide.

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AIM: To evaluate whether integrated treatment (given by OPUS), in comparison with standard treatment, significantly reduced the number of patients with substance abuse and improved clinical and social outcome in the group of substance abusers after 2 years. METHODS: A total of 547 patients with first-episode schizophrenia-spectrum disorders were included in the study, 275 randomly assigned to OPUS treatment and 272 to standard treatment. OPUS treatment consisted of assertive community treatment with family involvement and social skills training. Standard treatment offered contact with a community mental health centre. Main outcome measure was reduction in comorbid substance abuse. RESULTS: At 2-year follow up, 42 (17.3%) patients from OPUS and 40 (20.7%) patients from standard treatment met criteria for substance abuse (odds ratio=0.5, 95% confidence interval 0.3-1.0). OPUS treatment compared with standard treatment significantly reduced negative and disorganized symptoms in the substance abuser group. Patients with substance abuse in the OPUS treatment spent significantly fewer days in hospital during the 2-year period than patients given standard treatment (109 days vs. 167 days) and adhered to treatment significantly more often. CONCLUSIONS: Results from this trial indicate that integrated treatment given by OPUS reduced substance abuse and improved clinical outcome in the substance abuser group. Supplementing the OPUS treatment with therapeutic programmes for patients with a comorbid substance abuse would probably further improve outcome.

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BACKGROUND: Social network has considerable impact on physical and mental health. Patients experiencing first-episode psychosis early in adult life may experience severe problems concerning development and maintenance of their social network. METHODS: A total of 547 first-episode psychotic patients (18-45) were randomised to standard or integrated treatment, (ACT, social skills training and family intervention), and followed up at 2 years. RESULTS: Service use or psychotic symptom score did not influence the social network size, measured after the first 2 years of treatment. Small network size was associated with long duration of untreated psychosis (DUP), poor premorbid adjustment, male gender and severe negative symptoms. The number of friends at 2-year follow-up was predicted by age, A-level status, negative symptoms and number of friends at entry, while the determinants for number of family contacts were age, gender, disorganised dimension and family contacts at entry. CONCLUSIONS: Premorbid functioning, network size at entry and DUP is closely related to small social network size. The integrated psychosocial treatment programme was not sufficient to address this problem.

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BACKGROUND: Only a few randomized clinical trials have tested the effect on transition rates of intervention programs for patients with sub-threshold psychosis-like symptoms. AIM: To examine whether integrated treatment reduced transition to psychosis for first-contact patients diagnosed with schizotypal disorder. METHODS: Seventy-nine patients were randomized to integrated treatment or standard treatment. Survival analysis with multivariate Cox-regression was used to identify factors determinant for transition to psychotic disorder. RESULTS: In the multivariate model, male gender increased risk for transition to psychotic disorder (relative risk=4.47, (confidence interval 1.30-15.33)), while integrated treatment reduced the risk (relative risk=0.36 (confidence interval 0.16-0.85)). At two-year follow-up, the proportion diagnosed with a psychotic disorder was 25.0% for patients randomized to integrated treatment compared to 48.3% for patients randomized to standard treatment. CONCLUSION: Integrated treatment postponed or inhibited onset of psychosis in significantly more cases than standard treatment.

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A total of 547 patients with first-episode psychosis were included in a randomised clinical trial comparing integrated treatment with standard treatment. The integrated treatment consisted of assertive community treatment with programmes for family involvement and social skills training. Patients in integrated treatment had significantly fewer psychotic and negative symptoms, less comorbid substance abuse, better adherence to treatment and more satisfaction with treatment at one-year and two-year follow-ups.

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OBJECTIVES: To evaluate the effects of integrated treatment for patients with a first episode of psychotic illness. DESIGN: Randomised clinical trial. SETTING: Copenhagen Hospital Corporation and Psychiatric Hospital Aarhus, Denmark. PARTICIPANTS: 547 patients with first episode of schizophrenia spectrum disorder. INTERVENTIONS: Integrated treatment and standard treatment. The integrated treatment lasted for two years and consisted of assertive community treatment with programmes for family involvement and social skills training. Standard treatment offered contact with a community mental health centre. MAIN OUTCOME MEASURES: Psychotic and negative symptoms (each scored from 0 to a maximum of 5) at one and two years' follow-up. RESULTS: At one year's follow-up, psychotic symptoms changed favourably to a mean of 1.09 (standard deviation 1.27) with an estimated mean difference between groups of -0.31 (95% confidence interval -0.55 to -0.07, P = 0.02) in favour of integrated treatment. Negative symptoms changed favourably with an estimated difference between groups of -0.36 (-0.54 to -0.17, P < 0.001) in favour of integrated treatment. At two years' follow-up the estimated mean difference between groups in psychotic symptoms was -0.32 (-0.58 to -0.06, P = 0.02) and in negative symptoms was -0.45 (-0.67 to -0.22, P < 0.001), both in favour of integrated treatment. Patients who received integrated treatment had significantly less comorbid substance misuse, better adherence to treatment, and more satisfaction with treatment. CONCLUSION: Integrated treatment improved clinical outcome and adherence to treatment. The improvement in clinical outcome was consistent at one year and two year follow-ups.

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