Neurocognitive deficit changes in relation to the course of schizophrenia and schizophrenia spectrum disorders: 5-year follow-up study

Cognitive deficit is present in most of schizophrenia cases and even better explains functional outcomes then positive and negative symptoms. There have been less consensus regarding the long-term course of cognitive functioning after onset of the illness. In our study we used a neuropsychological test battery based on Luria`s systematic approach in testing of patients at their first episode of schizophrenia and schizophrenia spectrum disorders and during 5-year follow-up. The results indicated that patients with various types of course of schizophrenia and schizophrenia spectrum disorders and hence, good and poor outcomes demonstrated different patterns of dynamic of cognitive decline during the follow-up.     

Long-term diagnostic stability and outcome in recent first-episode cohort studies of schizophrenia

Knowing the long-term outcomes of schizophrenia and stability of a schizophrenia diagnosis are important from a clinical standpoint as well as essential to future research on diagnostic classifications and outcome. As in prior research on schizophrenia, prospectively designed long-term studies over the past 30 years find that the predominant course of illness includes chronically poor functioning, with little evidence of long-term improvement. Mortality due to suicide is significant at about 10% over 10-year periods of follow-up. Within studies, outcome domains are interrelated, and the relatively consistent predictors of poorer outcome include family history of schizophrenia, insidious onset, poor premorbid functioning, severity of negative symptoms, and severity and duration of untreated psychosis. Residing in a developed rather than a developing country is also associated with a poorer long-term course. The diagnostic stability of schizophrenia is less well studied. The positive predictive value exceeds 90%, and preliminary findings from the 10-year follow-up of the Suffolk County Mental Health Project cohort have found that the agreement across time increased from k = .52 (baseline to 10 years) to k = .76 (6 or 24 months to 10 years). After discussing several limitations of the existing body of research, we suggest that future studies incorporate more "modifiable" risk factors into the assessment battery that could potentially be used as building blocks in experimental intervention designs.     

Identification of psychopathological course trajectories in schizophrenia

Course trajectory analyses have been performed primarily for treatment response in acute episodes of schizophrenic disorders. As yet, corresponding data for the long-term course are lacking. Within a multicenter prospective observational study, 268 patients with schizophrenia were assessed at discharge from hospital and followed up after 6, 12, 18, and 24 months. A latent class growth analysis was performed on the scores from the Positive and Negative Syndrome Scale (PANSS). A two-class conditional latent class model showed the best data fit (Entropy: 0.924). The model divided the sample into a group with amelioration in all PANSS subscales (60%) and a group with stable positive/negative and deteriorating general psychopathology symptoms (40%). Global functioning (GAF score), gender, age, living situation and involuntary admission predicted course trajectory class membership. The model was predictive of significant differences between the two groups in health care service costs and quality of life. The results underline the heterogeneous course of the illness, which ranged from amelioration to deterioration over a 2-year period. Statistical models such as trajectory analysis could help to identify more homogenous subtypes in schizophrenia.     

Depression during the longitudinal course of schizophrenia

This prospective research investigated the occurrence and persistence of depression during the longitudinal course of schizophrenia. The research goals were to (1) compare depression in schizophrenia with that in schizoaffective and major depressive disorders, (2) assess whether some schizophrenia patients are vulnerable to depression, and (3) assess the relationship of depression to posthospital adjustment in schizophrenia. A total of 70 schizophrenia, 31 schizoaffective depressed, 17 psychotic unipolar major depressed, and 69 nonpsychotic unipolar major depressed patients were assessed during hospitalization and prospectively assessed for depression, psychosis, and posthospital functioning at 4.5- and 7.5-year followups. A large number (30% to 40%) of schizophrenia patients evidenced full depressive syndromes at each followup, including a subgroup of patients who evidenced repeated depression. Even when considering the influence of psychosis on outcome, depression in schizophrenia was associated with poor overall outcome, work impairment, lower activity, dissatisfaction, and suicidal tendencies. During the post-acute phase assessed, neither the rates nor the severity of depressive syndromes differentiated depression in schizophrenia from schizodepressive or major depressive disorders. However, the depressed schizophrenia patients showed poorer posthospital adjustment in terms of less employment, more rehospitalizations, and more psychosis than the patients with primary major depression. The high prevalence of depression in schizophrenia warrants its incorporation into theory about the disorder. A continuum of vulnerability to depression contributes to the heterogeneity of schizophrenia, with some schizophrenia patients being prone to depression even years after the acute phase. Depression in schizophrenia is one factor, in addition to psychosis, associated with poor outcome and requires specific attention to the treatment strategies by psychiatrists.     

Expressed-emotion development and course of schizophrenic illness: considerations based on results of a CFI replication

This study examines the correlation between development of expressed emotion (EE) in relatives and course of illness of 99 DSM-III schizophrenic patients. Patients whose relatives were high EE at baseline and at the 2nd CFI approximately 20 months later had a poor prognosis at the very outset of the study and an unfavourable course of illness. They had a higher rehospitalisation rate, more symptoms, lower psychosocial assessment, and a poorer 2-year and even 8-year outcome. Patients from families with a fluctuating EE or a consistently low EE had better courses. Expessed emotion is therefore a valid predictor not only of symptomatic relapses, but also of other important aspects of schizophrenia. The connection between EE index and course of illness seerns not to be simply reactive or causal, but complex and non-uniform.     

The effect of gender on the long-term course and outcome of schizophrenia in rural Ethiopia: a population-based cohort

Background

Although some studies have suggested that women with schizophrenia are more likely to achieve positive outcomes, the evidence-base is fraught with inconsistencies. In this study we compare the long-term course and outcomes for men and women living with schizophrenia in rural Ethiopia.

Methods

The Butajira course and outcome study for severe mental disorders is a population-based cohort study. Community ascertainment of cases was undertaken between 1998 and 2001, with diagnostic confirmation by clinicians using the Schedules for Clinical Assessment in Neuropsychiatry. Findings from annual outcome assessments were combined with clinical records, patient and caregiver report, and psychiatric assessments at 10–13 years using the Longitudinal Interval Follow-up Evaluation- LIFE chart. For the sub-group of people with schizophrenia (n = 358), we compared course of illness and treatment, co-morbidity, recovery, social outcomes and mortality between men and women. Multivariable analyses were conducted for modelling associations identified in bivariate analyses according to blocks shaped by our a priori conceptual framework of the biological and social pathways through which gender might influence the course and outcome of schizophrenia.

Results

Looking into over 10–13 years of follow-up data, there was no difference in the functioning or recovery in women compared to men (AOR = 1.79, 95% CI = 0.91, 3.57). Women were less likely to report overall life satisfaction (AOR = 0.22, 95% CI = 0.09, 0.53) or good quality of spousal relationships (AOR = 0.09, 95% CI = 0.01–1.04). Men were more likely to have co-morbid substance use and there was a trend towards women being more likely to be prescribed an antidepressant (AOR = 2.38, 95% CI = 0.94, 5.88). There were no gender differences in the course of illness, number of psychotic episodes or adherence to medications.

Conclusion

In this rural African setting, we found little evidence to support the global evidence indicating better course and outcome of schizophrenia in women. Our findings are suggestive of a gendered experience of schizophrenia which varies across contexts. Further investigation is needed due to the important implications for the development of new mental health services in low and middle-income country settings.

     

The natural course of schizophrenia and psychopathological predictors of outcome. A community-based cohort study

The natural course of schizophrenia is extremely heterogeneous and generally considered unpredictable. This prospective research investigated the natural course of schizophrenia in a community-based population linked to an Italian Mental Health Center, looking for the identification of psychopathological predictors of outcome. Forty schizophrenic patients were assessed at baseline in a stabilized phase of illness with clinical scales of psychopathology and social functioning and afterwards were followed up for 36 months. All of them were treated with antipsychotic drugs. According to their symptoms and function scores patients were empirically classified into three groups with a cluster analysis: a group characterized by low symptoms and good functioning, a group with high symptoms and poor functioning and an intermediate group. A crosstabs analysis revealed that the empirical classification correctly predicted long-term outcome. A survival analysis with comparison of distributions (Wilcoxon Gehan test) also revealed significant differences in terms of hospital admission and occurrence of alcohol-related diagnosis across groups. This study suggests that the long-term outcome in schizophrenic patients followed by a community-based mental health service is generally poor and multifaceted. However, outcome may be predicted on the basis of the psychopathological and social functioning profile assessed in a stabilized phase of illness defined with operational criteria.     

Early course of schizophrenia in a representative Dutch incidence cohort

PURPOSE: To describe the early course of psychotic disorders in general and to examine whether certain variables can predict the early course of schizophrenic disorders (DSM-IV: schizophrenia, schizophreniform or schizoaffective disorder). SUBJECTS AND METHOD: Follow-up and re-diagnosis of a highly representative Dutch incidence cohort (N=181), thirty months after first contact with a physician for a psychotic disorder. Poor course was defined as a continuous psychotic illness or a score of less than 39 on the Global Assessment of Functioning scale. RESULTS: The follow-up rate was 92%. 125 Subjects were diagnosed with a schizophrenic disorder. Poor course was present in 70 of these subjects (56%). Univariable analysis showed that male sex, heavy cannabis use during the follow-up period (sometimes or often more than one joint a day) and long duration of dysfunctioning before psychosis onset (>1 month) were predictors of poor course, while age at onset, ethnicity, socioeconomic status and duration of untreated psychosis (trend, p=0.08) were not. The effect of cannabis was confounded by sex. Multivariable analysis showed that male sex was the sole significant and independent predictor of poor course and explained 13% of the variation. The odds ratio for males, adjusted for duration of pre-psychotic dysfunctioning and cannabis use during the follow-up period, was 3.0 (95% CI, 1.0-8.9). STRENGTHS AND LIMITATIONS: This is the first study to examine the influence of cannabis in an epidemiological, highly representative sample. A limitation was the sample size. CONCLUSION: Male sex is an independent risk factor for an unfavorable early course in schizophrenia.     

Long-term course of schizophrenic illness: Bleuler's study reconsidered

OBJECTIVE: The influential 1972 study by Manfred Bleuler on the long-term course of schizophrenic illness has been reconsidered. The authors tested the diagnosis of schizophrenia in all patients and investigated how the distribution of the types of illness course and outcome would change after exclusion of patients whose diagnosis of schizophrenia could not be confirmed by modern diagnostic standards. METHOD: Clinical charts and Bleuler's research notes on the original sample were assessed, and all patients were rediagnosed with the help of DSM-IV, DSM-III-R, ICD-10, the Research Diagnostic Criteria (RDC), Schneider's criteria, and an operationalized version of the criteria of Eugen Bleuler. RESULTS: The diagnosis of schizophrenia was not confirmed in about 30% of the sample; the majority of these patients were rediagnosed with schizoaffective disorder. High diagnostic agreement was found between DSM-IV, DSM-III-R, ICD-10, and RDC; there was much less agreement with Bleuler's and Schneider's criteria. After exclusion of patients whose schizophrenia diagnosis was not confirmed, the proportion of patients with undulating course and recovery slightly decreased, and the proportion of patients with severe end state slightly increased. Nevertheless, the distribution of the types of long-term course did not significantly change, and even among patients with strictly defined schizophrenia, half had an undulating course with remissions and 12%-15% recovered. CONCLUSIONS: Schizophrenic illness remains heterogeneous with regard to illness course and outcome even when narrowly diagnosed with the help of modern operationalized diagnostic criteria. Contemporary differentiation between schizophrenic and schizoaffective disorders is prognostically valid.     

Prediction of clinical course and outcome in delusional psychoses. A multivariate analysis of a 4-year re-follow-up

The purpose of the study was to examine the predictive value of clinical and socio-vocational variables of first-admitted patients with delusional psychoses as regards clinical course and outcome, which was illustrated by the dimensions: psychotic symptoms, impairment, remission, and relapse at a 4-year re-follow-up. An excess of patients had poor course and outcome. In the multivariate logistic analysis an independent statistically significant effect was assigned to male sex, low social group, few social contacts, no work, and long duration of psychosis. The most informative clinical and social predictors yielded a maximal information of 19-50% for the different dimensions of course and outcome. One-fifth of the patients had good outcome. Living with others and at the same time having frequent social contacts was a variable with an independent statistically significant effect. The most informative predictors of good outcome yielded a maximal information of 34%. Differences between predictors of 2-year and 4-year course and outcome are discussed. It is concluded that good prognosis is exceptional in patients with delusional psychoses and from a nosological approach attached to patients with reactive psychosis. However, socio-vocational variables at index admission are predictors of higher statistical information than any clinical variable.     

Is the outcome of schizophrenia really better in developing countries?

That schizophrenia has a better prognosis in non-industrialized societies has become an axiom in international psychiatry; the evidence most often cited comes from three World Health Organization (WHO) cross-national studies. Although a host of socio-cultural factors have been considered as contributing to variation in the course of schizophrenia in different settings, we have little evidence from low-income countries that clearly demonstrates the beneficial influence of these variables. In this article, we suggest that the finding of better outcomes in developing countries needs re-examination for five reasons: methodological limitations of the World Health Organization studies; the lack of evidence on the specific socio-cultural factors which apparently contribute to the better outcomes; increasing anecdotal evidence describing the abuse of basic human rights of people with schizophrenia in developing countries; new evidence from cohorts in developing countries depicting a much gloomier picture than originally believed; and, rapid social and economic changes are undermining family care systems for people with schizophrenia in developing countries. We argue that the study of the long-term course of this mental disorder in developing countries is a major research question and believe it is time to thoroughly and systematically explore cross-cultural variation in the course and outcome of schizophrenia.     

Care strategies for schizophrenic patients in a transcultural comparison

This study was conducted in order to test the hypothesis derived from the International Pilot Study of Schizophrenia (IPSS) that the existence of extended families in developing countries contributes to the more favorable course and outcome of schizophrenia in these countries in comparison with industrial countries. For this purpose, we compared data from the 5- and 10-year follow-up obtained within the IPSS at Cali, Colombia with data from two 5- to 8-year follow-up studies of former schizophrenic inpatients of the Max Planck Institute of Psychiatry (MPIP) in Munich, FRG. Although, in Cali, schizophrenics are hospitalized and treated with drugs only during acute episodes of the psychosis and no facilities exist for long-term treatment, the psychopathological outcome was, on the whole, not worse than in Munich. Furthermore, the duration of hospitalization during the follow-up period was much lower at Cali and a significantly lower number of Colombian than of German patients was not separated from their families. However, contrary to the hypothesis, family size did not predict course and outcome at both centers.     

Prevalence and course of schizophrenia in a Chinese rural area

OBJECTIVE: To assess the characteristics and factors affecting course of schizophrenia in a Chinese rural area. METHOD: An epidemiological investigation was conducted to identify all the patients with schizophrenia among 149 231 people in Xinjin County, Chengdu. RESULTS: The total prevalence of schizophrenia was 4.13 per 1000 population. Males had an earlier mean age of onset (29.6 years) than females (32.3 years). Duration of illness before treatment and the total duration of illness were found to be significantly associated with level of remission. The status of treatment, family economy, housing, and families' care of patients had a significant effect on the clinical course of the illness. CONCLUSIONS: Duration of illness before treatment may be an important predictor of course in schizophrenia. Early treatment for the patients may produce higher level of improvement in prognosis. Education intervention and community-based service are urgent priorities for these patients.     

Outcome on quality of life in a Canadian national sample of patients with schizophrenia and related psychotic disorders

OBJECTIVE: To examine changes in subjective and objective dimensions of quality of life (QoL) in a large Canadian sample of patients with diagnosis of schizophrenia or schizoaffective disorder treated in academic and non-academic settings over a 2-year period. METHOD: Patients recruited in the study across the country were assessed for QoL and functioning using the Client and Provider versions of the Wisconsin Quality of Life Questionnaire (WQoL) and the Short Form-36 (SF-36) at baseline (n = 448), 1 year (n = 308-353) and 2 years (188-297). Data were analyzed to examine change across time using multivariate analyses controlling for potential influence of variables such as age, regional variation, gender, duration of illness, type of treatment taken and baseline measures of symptoms and QoL. RESULTS: The weighted quality of life index (W-QoL-I) showed a significant change on both the client and the provider versions of the WQoL while the physical and mental composites of the SF-36 showed change only at 2 years. These changes were influenced significantly by baseline scores on W-QoL-I and in the case of provider version of the WQoL by baseline Brief Psychiatric Rating Scale (BPRS) scores. Regional variation or type of medication had no impact on improvement in QoL. CONCLUSION: Within a naturalistic sample of schizophrenia patients treated and followed in routine care the overall QoL showed an improvement over time but this improvement was not influenced by the type of medication prescribed.     

Twenty-year course of schizophrenia: the Madras Longitudinal Study.

OBJECTIVE: To follow up 90 first-episode schizophrenia patients after 20 years and to study the course of symptomatology, work, social functioning, and pattern of illness during this period. METHODS: The Present State Examination and the Psychiatric and Personal History Schedule were administered at fixed points during follow-up. The measures adopted to ensure a good follow-up rate (67%) after 20 years under adverse conditions are described. RESULTS: Complete data were obtained from 61 subjects; 16 had died, and 13 could not be traced. After 20 years, 5 patients had recovered completely, and another 5 were continuously ill. Most of the cohort had multiple relapses with or without complete remission between them. The Global Assessment of Functioning Scale showed that symptoms and social functioning in this sample approximated results from developing countries and were much better than those of developed nations. There were not many sex differences. Marriage and occupational rates were higher than those observed in many published reports. CONCLUSIONS: This is one of the few long-term follow-up studies from the developing world. It reveals a pattern of course and functioning distinctly better than that found in many such studies from the developed nations.     

The impact of the duration of untreated psychosis prior to first psychiatric admission on the 15-year outcome in schizophrenia

OBJECTIVE: There is a large amount of evidence to support the hypothesis that the duration of untreated psychosis (DUP) prior to first psychiatric admission adversely affects acute treatment response and short-term outcome in schizophrenia. However, only few prospective studies have attempted to address a possible association between DUP and long-term outcome. METHOD: Fifty-eight DSM-III-R schizophrenic patients were assessed at their first psychiatric admission and after a 15-year course of the illness. The 15-year outcome in different domains was compared between patients with different DUPs prior to the first psychiatric admission. RESULTS: A longer DUP was associated with more pronounced negative, positive and general psychopathological symptoms as well as a lower global functioning 15 years after the first psychiatric admission, even after effects of other factors, possibly related to the long-term outcome, were controlled for. CONCLUSIONS: The DUP prior to first psychiatric admission adversely affects the long-term outcome in schizophrenia. The findings underline the importance of establishing health service programs for early detection and treatment of schizophrenic patients with the aim to shorten the DUP and to consequently improve the course and outcome of schizophrenic patients.     

Predictors of antipsychotic medication adherence in patients recovering from a first psychotic episode

BACKGROUND: Many patients recovering from a first psychotic episode will discontinue medication against medical advice, even before a 1-year treatment course is completed. Factors associated with treatment adherence in patients with chronic schizophrenia include beliefs about severity of illness and need for treatment, treatment with typical versus atypical antipsychotic and medication side effects. METHOD: In this 2-year prospective study of 254 patients recovering from a first episode of schizophrenia, schizophreniform, or schizoaffective disorder we examined the relationship between antipsychotic medication non-adherence and patient beliefs about: need for treatment, antipsychotic medication benefits, and negative aspects of antipsychotic medication treatment. We also examined the relationship between medication non-adherence and treatment with either haloperidol or olanzapine, and objective measures of symptom response and side effects. RESULTS: The likelihood of becoming medication non-adherent for 1 week or longer was greater in subjects whose belief in need for treatment was less (HR=1.75, 95% CI 1.16, 2.65, p=0.0077) or who believed medications were of low benefit (HR=2.88, 95 CI 1.79-4.65, p<0.0001). Subjects randomized to haloperidol were more likely to become medication non-adherent for >or=1 week than subjects randomized to olanzapine (HR-1.51, 95% CI 1.01, 2.27, p=0.045). CONCLUSION: Beliefs about need for treatment and the benefits of antipsychotic medication may be intervention targets to improve likelihood of long-term medication adherence in patients recovering from a first episode of schizophrenia, schizoaffective, or schizophreniform disorder.     

Posthospital course and outcome in schizophrenia.

To study the early course of schizophrenia, we assessed 79 early phase, young, DSM-III schizophrenic patients at two successive posthospital follow-ups, 2.5 and 5.0 years after index hospitalization. More than 50% of the sample had poor overall outcome, with either severe impairment in functioning and symptoms, or suicide, in the follow-up period. Rehospitalization rates decreased significantly during the course of the two posthospital assessments, despite the sample showing persisting psychosis. Only a small group of schizophrenic patients showed complete remission: 10% at the first follow-up and 17% at the second follow-up, when patients who suicided are excluded from consideration. While progressive deterioration is not common in schizophrenia, our relatively negative findings challenge the conclusions of some other longitudinal studies. Implications of our data on schizophrenic course are discussed.     

Long-term course of adolescent schizophrenia

Our study investigated premorbid functioning, course, and outcome in early-onset schizophrenia. All inpatients with DSM-III-R diagnoses of schizophrenia (n = 101) consecutively admitted between 1983 and 1988 to the Department of Child and Adolescent Psychiatry at the University of Marburg in Germany were included. To assess premorbid adaptation and precursor symptoms, we administered the Instrument for the Retrospective Assessment of the Onset of Schizophrenia, which we modified to assess children and adolescents. Symptomatology was measured by the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, and the Brief Psychiatric Rating Scale. In addition, the Global Assessment of Functioning was applied. Followup data for 81 patients (80.2%) were available. The mean duration of schizophrenia at followup was 9.5 +/- 2.2 years. Assessment of the highest level of adaptive functioning revealed very good or good outcome in 19.8 percent of the patients, fair or poor outcome in 38.2 percent, and very poor outcome and gross impairment in 42.0 percent. Premorbid adjustment was the best predictor of outcome in our schizophrenia sample. A poor prognosis was found in patients with premorbid developmental delays and those who were introverted and withdrawn before their psychotic state.