Article

The course of schizophrenia: Progressive deterioration, amelioration or both?

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Abstract

Schizophrenia may follow a course of amelioration, deterioration or stability. It is possible that deterioration at the aggregate level may be due to a sub-group of patients with a tendency to deteriorate. To examine the course of schizophrenia in a national population-based cohort. All first admissions for schizophrenia in Israel 1978-1986 were followed for readmissions in the Israeli psychiatric hospitalization registry for 10 years (n=6865). Readmission rates were examined using cluster analysis. This was followed by an examination of changes in readmission patterns. Cluster analysis identified a small cluster of patients who spent more days in the hospital over time and two clusters that improved. A priori classification of the patients into deteriorating, improving and stable (based on days hospitalized per year) revealed that approximately 75% of patients improved over time. Over time a majority of patients appear to improve and a minority appear to deteriorate.

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... Contrary to these notions, others have suggested that the course of schizophrenia improves with time, and is thus described as following a course of 'progressive amelioration' (Eaton et al., 1992a(Eaton et al., ,b, 1998Hopper et al., 2007;Mortensen and Eaton, 1994;Munk-Jörgensen et al., 1991). These divergent views of the long-term course of schizophrenia have been reevaluated with national population-based psychiatric hospitalization registries, with longer psychiatric admissions being a proxy for symptomatic exacerbation (e.g., Rabinowitz et al., 2007). Research in Denmark, based on up to 18 years of follow-up, has shown that deterioration is observed in a small group of patients (Olesen and Mortensen, 2002). ...
... These two national population-based registry studies and other reports based on different outcomes and methods (e.g., Hopper et al., 2007;Modestin et al., 2003) lead to the conclusion that heterogeneity characterizes the course of schizophrenia (Tandon et al., 2008). Existing registry-based epidemiological research of the long-term course (i.e., Olesen and Mortensen, 2002;Rabinowitz et al., 2007): (a) used under 20 years of follow-up; (b) studied people with first and subsequent re-hospitalizations during a given period (e.g., 1978 to 1992), thereby increasing the extent of variability at onset, and not people born in sequential birth cohorts; and (c) do not provide information on the extent of heterogeneity, amelioration and deterioration that may characterize the course of schizophrenia at different ages. ...
... Validation studies have shown that the last clinical diagnosis of schizophrenia in the registry has acceptable sensitivity and specificity, when assessed against research diagnosis (Weiser et al., 2005), and acceptable reliability, as indicated by their stability over time (Rabinowitz et al., 1994). Since past research indicates that diagnostic agreement increases over the course of time in the registry (Rabinowitz et al., 1994), the current study includes only persons with a final discharge diagnosis of schizophrenia (see also: Davidson et al., 1999;Levav et al., 2007;Rabinowitz et al., 2007;Reichenberg et al., 2006). ...
Article
The extent of heterogeneity in the long-term course of schizophrenia is unclear. To examine the course of schizophrenia in a population-based cohort. This study included all Israeli individuals born in 1970-1988, of North African or European origin (N=2290), entered in the National Psychiatric Hospitalization Case Registry with a last discharge diagnosis of schizophrenia (1978-2004) and followed to 2009. Linked socio-demographic information was extracted from the Population Registry. Based on the number of hospitalized days at each age, trajectory groups were empirically derived, plotted and compared on psychiatric hospitalization measures of the course of illness, social factors and family stressors. Trajectory analysis identified four course groups. Group I (57%) assumed a prototypical course, had an average first hospitalization age of 20, deteriorated until 23 and then ameliorated. Group II (15.5%) assumed an early-onset protracted course, had an average first hospitalization age of 17.1, and deteriorated until 21. Group III (15%) assumed a late-onset with longest deterioration period course, had an average first hospitalization age of 22.7, and deteriorated until 29. Group IV (12%) assumed an early-onset refractory illness course, had an average first hospitalization age of 18, and had the longest hospitalization period. Groups significantly differed on hospitalization (i.e., onset), social (i.e., socioeconomic and ethnic status) and familial factors (i.e., parental death). Despite group differences all deteriorated and then ameliorated on average by the age of 23. The course of schizophrenia was heterogeneous, yet evolved from deterioration to assume a course consistent with amelioration.
... The personalization of treatment is essential for the provision of effective treatments and the reduction of illness-related economic burden (Alda 2013). Surprisingly, few studies have focused on patterns or predictors of outcome of psychotic disorders (Rabinowitz et al. 2007;Levine and Rabinowitz 2010;Case et al. 2011;Levine et al. 2011;Schennach et al. 2012;Green et al. 2013;Austin et al. 2015;Hodgekins et al. 2015); among them, only two have examined the course of patients over a medium-term period (Rabinowitz et al. 2007;Austin et al. 2015) and just three of them have involved FEP patients (Levine et al. 2011;Austin et al. 2015;Hodgekins et al. 2015). Thus, to our knowledge, this is the first study on the impact of gender on clinical and social course of FEP patients over the medium-run. ...
... The personalization of treatment is essential for the provision of effective treatments and the reduction of illness-related economic burden (Alda 2013). Surprisingly, few studies have focused on patterns or predictors of outcome of psychotic disorders (Rabinowitz et al. 2007;Levine and Rabinowitz 2010;Case et al. 2011;Levine et al. 2011;Schennach et al. 2012;Green et al. 2013;Austin et al. 2015;Hodgekins et al. 2015); among them, only two have examined the course of patients over a medium-term period (Rabinowitz et al. 2007;Austin et al. 2015) and just three of them have involved FEP patients (Levine et al. 2011;Austin et al. 2015;Hodgekins et al. 2015). Thus, to our knowledge, this is the first study on the impact of gender on clinical and social course of FEP patients over the medium-run. ...
Article
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Most studies on gender and psychosis have focused on gender differences at illness onset or on the long-term outcome, whereas little is known about the impact of gender on the first years after psychosis onset. A total of 185 first episode psychosis (FEP) patients were followed for 5 years after psychosis onset, and gender differences were explored in psychopathology (PANSS), needs for care (CAN), and insight (SAI-E). Male patients showed more negative symptoms than females over time, whereas female patients showed higher levels of depressive symptoms than males throughout the study period. In addition, female patients presented more functioning unmet needs for care, but higher levels of insight into illness than males. Therapy and rehabilitative programs for FEP patients should be gender-targeted, as gender has proved to impact on psychopathology, needs for care, and insight in the very first years following psychosis onset.
... Rabinowitz and colleagues identified three response trajectories within a cohort of people with schizophrenia over a period of ten years. A significant majority showed improvement and stabilization in positive symptoms (Rabinowitz et al., 2007). Levine et al. (2011) identified five distinct illness trajectories, where the typical course was one of initial deterioration followed by progressive amelioration (Levine et al., 2011). ...
... Similar studies examining positive symptom response within schizophrenia have found a comparable number of trajectories, usually characterized by amelioration of positive symptoms over time with the process taking up to 10 years (Levine et al., 2011). Furthermore, a small but significant group also showed a deteriorating course (Rabinowitz et al., 2007). While there appears to some convergence in results across studies, the OPUS cohort had fewer people that achieved sustained symptom remission and a greater variation in the trajectories displayed compared to the previous studies. ...
... The registry has been used in various studies. [19][20][21] Quality of life Quality of life was measured using a translated version of the Manchester Short Assessment of Quality of Life, an abbreviation of the Lancashire Quality of Life Profile. 22 Eight items measured satisfaction with physical and mental health, work or volunteering projects, social status, financial situation, family ties, leisure activities and residential status. ...
Article
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Background Evidence from various sources suggests that females with schizophrenia tend to report lower quality of life than males with schizophrenia despite having a less severe course of the disorder. However, studies have not examined this directly. Aims To examine gender differences in the association between quality of life and the risk of subsequent psychiatric hospital admissions in a national sample with schizophrenia. Method The sample consisted of 989 (60.90%) males and 635 (39.10%) females with an ICD-10 diagnosis of schizophrenia. Quality of life was assessed and scored using the Manchester Short Assessment of Quality of Life. The course of schizophrenia was assessed from the number of psychiatric hospital admissions. Participants completed the quality of life assessment and were then followed up for 18-months for subsequent psychiatric admissions. Hazard ratios (HR) from Cox proportional hazards regression models were estimated unadjusted and adjusted for covariates (age at schizophrenia onset and birth year). Analyses were computed for males and females separately, as well as for the entire cohort. Results A subsample of 93 males and 55 females was admitted to a psychiatric hospital during follow-up. Higher quality of life scores were significantly ( P < 0.05) associated with a reduced risk of subsequent admissions among males (unadjusted: HR = 0.96, 95% CI 0.93–0.99; adjusted HR = 0.96, 95% CI 0.93–0.99) but not among females (unadjusted: HR = 0.97, 95% CI 0.93–1.02; adjusted HR = 0.97, 95% CI 0.93–1.02). Conclusions Quality of life in schizophrenia is a gender-specific construct and should be considered as such in clinical practice and future research.
... The median number of admissions in the total sample was four. Thus, the majority of our sample consisted of the schizophrenia subgroup of patients with incomplete symptom control and multiple relapses [22]. ...
Article
Evidence based treatment of schizophrenia as well as antipsychotic drug utility patterns have changed considerably in recent years and the present study aims to investigate the current level of unplanned hospital readmissions in a cohort of patients with schizophrenia, and to determine the risk-reducing effects of current antipsychotic drug treatment. An open cohort study included all consecutively discharged patients with schizophrenia in a 3-year period (n=277). The treatment-dependent variables were entered in a multivariate Cox survival analyses with time to unplanned readmission as the dependent variable. 11.2% of patients were readmitted within 30days of discharge, and 44.8% were readmitted within 12months. Antipsychotic monotherapy reduced the risk of readmission by 74.9%. Treatment in CMHC also had a risk-reducing effect. The prescription rate of clozapine in this sample was 10.1%. The over-all level of unplanned readmissions was in correspondence with the findings of others. Current antipsychotic drug treatment independently offers strong protection against unplanned readmissions. There may be a potential for further optimalizing antipsychotic drug treatment according to treatment guidelines. Unplanned readmissions are very common for patients with schizophrenia but antipsychotic drug treatment is associated with a strong risk-reducing effect in this regard.
... The next set of drugs that were developed (e.g., risperidone, olanzapine, quetiapine, and aripiprazole) demonstrated at least equal efficacy and better tolerability than typical antipsychotics and improved safety compared with clozapine [34,[42][43][44][45][46][47][48][49][50][51][52][53][54][55][56]. Nevertheless, heterogeneity in the individual response to treatments is still the rule in schizophrenia patients [57][58][59][60][61][62][63][64][65][66], and discontinuation of treatment is a very frequent occurrence [64,67]. Recently, Cuyún Carter et al. [68], analyzing the data from the United States Schizophrenia Care and Assessment Program, reported that only 10% of the sample had a positive outcome after two years. ...
Article
Full-text available
Objectives. The aim of this naturalistic study was to investigate whether treatment with clozapine and other atypical antipsychotics for at least 2 years was associated with a reduction in psychotic and depressive symptoms and an improvement in chronic schizophrenia patients' awareness of their illness. Methods. Twenty-three adult outpatients (15 men and 8 women) treated with clozapine and 23 patients (16 men and 7 women) treated with other atypical antipsychotics were included in the study. Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS), depressive symptoms were assessed with the Calgary Depression Scale for Schizophrenia (CDSS), and insight was assessed with the Scale to Assess Unawareness of Mental Disorder (SUMD). Results. The sample as a whole had a significant reduction in positive, negative, and general symptoms, whereas the reduction in depression was significant only for patients with CDSS scores of 5 and higher at the baseline. At the follow-up, patients treated with other atypical antipsychotics reported a greater reduction in depression than patients treated with clozapine, but not when limiting the analyses to those with clinically relevant depression. Conclusions. Atypical antipsychotics may be effective in reducing psychotic and depressive symptoms and in improving insight in patients with chronic schizophrenia, with no differences in the profiles of efficacy between compounds.
... O comprometimento funcional decorrente da evolução da esquizofrenia representa um imenso desafio para o paciente, seus familiares e cuidadores. A esquizofrenia é tida como um transtorno caracterizado por promover grave deterioração funcional em várias esferas da vida e tem mobilizado inúmeros recursos com a meta de minimizar esses danos (Wallace e Liberman, 1985;Rabinowitz et al., 2007). ...
Article
Full-text available
CONTEXTO: A necessidade de avaliar o comprometimento de aspectos funcionais em transtornos psiquiátricos tem assumido crescente importância, particularmente no que se refere ao estudo da esquizofrenia. O funcionamento social deficiente é considerado na atualidade um importante sintoma da esquizofrenia. Vários instrumentos de mensuração para o acompanhamento da reabilitação desses pacientes foram desenvolvidos até o momento. OBJETIVO: Este artigo discute a avaliação do comprometimento do funcionamento social na esquizofrenia. MÉTODO: Resultados de recentes revisões da literatura são resumidos e discutidos. RESULTADOS: Vários estudos têm abordado a importância da análise da performance social e pessoal na esquizofrenia. Essa avaliação tem se mostrado uma medida de desfecho confiável em estudos clínicos e programas de reabilitação. CONCLUSÃO: O DSM-III apresentou uma proposta inovadora com a divisão diagnóstica multiaxial, onde foi incluído o eixo V com o objetivo de avaliar o funcionamento global de pacientes com transtorno mental. Atualmente, encontramos esse eixo atualizado no DSM IV com a proposta do uso de escalas mais precisas para a prática clínica. A escala de Performance Social e Pessoal (PSP) desenvolvida por Morosini et al. (2000) é considerada útil e prática e tem servido como instrumento de mensuração no processo de reabilitação e os resultados das intervenções farmacológicas de pacientes com esquizofrenia.
... Des é tudes ré centes attestent d'une é volution favorable et significative pour un nombre croissant de patients atteints de schizophré nie [7,15]. Cette progression passe par une adhé sion correcte au traitement pharmacologique prescrit, qui, à son tour, traduit le cheminement inté rieur effectué par le patient pour assumer un rôle actif dans la prise en charge de son traitement [16]. ...
Article
The aim of this qualitative study is to investigate the psychological path and the defence mechanisms that contribute to achieve and maintain a satisfactory compliance to treatment, in schizophrenia. Eleven outpatients, with a diagnosis of psychosis, mean age = 48.54 years, mean illness duration 20 years, responded to a questionnaire and participated to a focus group. Data were processed by content analysis and descriptive statistics. Results show the existence of cognitive schemes and defence mechanisms (such as denial and splitting), which appear to reinforce together a positive attitude towards the therapeutic regimen.
... O comprometimento funcional decorrente da evolução da esquizofrenia representa um imenso desafio para o paciente, seus familiares e cuidadores. A esquizofrenia é tida como um transtorno caracterizado por promover grave deterioração funcional em várias esferas da vida e tem mobilizado inúmeros recursos com a meta de minimizar esses danos (Wallace e Liberman, 1985;Rabinowitz et al., 2007). ...
Article
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BACKGROUND: The assessment of functioning disability in patients with mental disorders and mainly in schizophrenia has increased in the last years. The social function impairment is nowadays recognized as an important symptom of schizophrenia. Many tools to measure social function impairment have been developed. OBJECTIVE: This article discusses the assessment of functioning disability in schizophrenic patients. METHOD: The results of recently reported reviews of the literature are summarized and commented. RESULTS: Several studies have evaluated the importance of Personal and Social Performance assessments in schizophrenia. These assessments have been shown as a reliable outcome measure in clinical trials and rehabilitation programs. CONCLUSION: Axis V has been inserted to the multiaxial system in DSM-III for assessing global function in mental disorders. DSM-IV has brought axis V up to date with improvements of accurate scales for clinical practice. Personal and Social Performance scale (PSP) was developed by Morosini et al. (2000). PSP is a useful and practical scale for assessing rehabilitation and pharmacology interventions in schizophrenic patients.
... The observation of age-related improvement in positive symptoms is used to argue that schizophrenia does not follow a debilitating course, as in Alzheimer's disease or other dementias, with clinical deterioration usually limited to the first 5 years after onset (Lieberman, 1999;Levine et al., 2011). There exists, however, heterogeneity among different illness course trajectories, with a minority of patients deteriorating over time (Harding, 1988;Olesen and Mortensen, 2002;Rabinowitz et al., 2007). ...
Article
Objectives Impaired insight into illness is a prevalent feature of schizophrenia, which negatively influences treatment adherence and clinical outcomes. Little is known about the effects of aging on insight impairment. We aimed to review the available research literature on the effects of aging on insight into illness in schizophrenia, in relation to positive, negative, and cognitive symptoms. Ultimately, we propose a trajectory of insight in schizophrenia across the lifespan. MethodA systematic Medline (R) literature search was conducted, searching for English language studies describing the relationship of insight into illness in schizophrenia with aging. ResultsWe identified 62 studies. Insight impairment is associated with illness severity, premorbid intellectual function (i.e. IQ), executive function, and memory. Insight impairment improves modestly during midlife, worsening again in late life. It tends to fluctuate with each episode of psychosis, likely in relation to worsening positive symptoms that improve with antipsychotic treatment. The relationship between insight impairment and cognitive dysfunction appears to attenuate with age, while the relationship with lower premorbid intellectual function is preserved. The association between impaired insight and negative symptoms is unclear. Conclusions The available literature suggests that the course of insight impairment follows a U-shaped curve, where insight impairment is severe during the first episode of psychosis, modestly improves over midlife, and declines again in late life. Future studies are required to investigate the trajectory of insight into illness and its core domains across the lifespan from prodromal phase to late life. Copyright (c) 2014 John Wiley & Sons, Ltd.
... Schizophrenia is a severe mental disorder characterized by hallucinations, delusions, cognitive deficits, and a heterogeneous clinical course 1,2 . Brain imaging studies of this disorder have revealed a disturbance of brain function and a progressive decline in brain volume 3,4 . ...
Preprint
Schizophrenia is a brain disorder of unknown etiology. Brain imaging studies have revealed evidence for hypoperfusion of the frontal cortex (hypofrontality) and progressive brain volume reduction in schizophrenic patients. Mild cerebral ischemia (oligemia) has been postulated as a cause of the disorder. If the ischemia hypothesis for the adult brain is correct, genes induced by cerebral ischemia should be increased in the frontal cortex of schizophrenic patients during acute psychosis. Here, we show for the first time through a combined analysis of gene expression data from all the studies of the Stanley Brain Collection covering the Brodmann area 46 of the frontal cortex and employing the well-established Affymetrix HGU133a microarray platform that genes upregulated by cerebral ischemia are significantly overexpressed (4.5-fold) in the frontal cortex of acute schizophrenic patients (representation factor (RF) 4.5, p < 0.0002) and to a lesser degree in chronic patients (RF 3.9, p < 0.008) in comparison to normal controls. Neurodevelopmental-, repair-, inflammation- and synapse-related genes showed no significant change. The difference between acute and chronic schizophrenic patients regarding cerebral ischemia-induced genes was highly significant (RF 2.8, p < 0.00007). The results reported here are in line with evidence from biochemical, cellular, electroencephalographic, brain imaging, cerebral near-infrared spectroscopy, vascular, and genetic association studies. In summary, our genomic analysis revealed a clear ischemic signature in the frontal cortex of schizophrenia patients, confirming the prediction of the adult ischemia hypothesis for this disorder. This finding suggests new possibilities for the treatment and prevention of schizophrenia.
... Dans le champ de la recherche sur l'évolution de la maladie schizophrénique, il est désormais établi que la majorité des patients connaissent une évolution favorable de leur trouble [18]. Levine et al. [11] établissent, au sein d'une cohorte de 2 300 patients, plusieurs profils évolutifs sur cette trajectoire d'amélioration progressive. ...
Article
Full-text available
The recovery of the self in schizophrenia The question of the course of schizophrenia disease, especially recovery, is of considerable interest in different clinical and social areas. We propose a qualitative study of the narratives told by patients relating their recovery process. The recovery of the self, all along the stages of the recovery conceptualized in the existing models, is also highlighted. Some of the psychological mechanisms are described in relation to the insights of the disorder and the insight of the self. These mechanisms lead to an integration of schizophrenic experiences into the identity. Our study involves clinical applications. For example, we emphasize the need to support the narrative consciousness as developed in some recent psychotherapeutic models.
... In some studies even an evolution of progressive amelioration was observed [5]. Based on the few long-term national follow-up studies about one [6] or two decades [7], the majority of schizophrenia patients seem to improve, while only few deteriorate. In order to reconcile opinions and research with real life and multiple interfering factors, the course of schizophrenia is currently accepted as heterogeneous [8] [9]. ...
Article
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The objectives of e-STAR Romania (NCT00283517) were to collect clinical outcome data of Romania schizophrenia or schizo-affective disorder patients; prospectively to assess the reasons of treatment initiation, medication usage patterns; to document (long-term) clinical efficacy; and to collect safety data, as well as recording 2-year corresponding retrospective data. In total, 378 eligible subjects were enrolled who were initiated either on risperidone long-acting injectable (RLAI) (290) or on an oral antipsychotic (OA) (88) at baseline as required by the local Summary of the Product Characteristics. Data were collected from per patient both retrospectively and prospectively over a 24-month period at 3-month intervals after starting treatment. The results indicated that subjects suffering from schizophrenia or schizo-affective disorder initiated on RLAI were less likely to be hospitalized within the first 24 months after the initiation of treatment. Moreover, subjects treated with RLAI experienced significant improvements in their illness severity and functioning. Discontinuation rates for RLAI were low and doses were stable throughout the 24 months following the initiation of treatment. In addition, the necessity for supplementary concomitant medication was reduced. Adverse events were reported in 20.3% (RLAI) and 11.4% (OA) of the subjects. In general, patients initiated on RLAI and OA at baseline both clinically improved on all assessed parameters but a larger improvement was observed for patients on RLAI. Incidences of reported AEs during the use of RLAI in a naturalistic setting are comparable with those described in clinical studies; however, the incidence of extrapyramidal signs and weight gain was lower than expected.
... La nécessité scientifique de définir le rétablissement provient de la prise en compte des nombreuses études longitudinales de longue durée qui ont montré qu'un taux non négligeable de personnes atteintes de schizophrénie s'améliorent sur le plan fonctionnel et symptomatique au fil du temps [12], [13], [14], [15], [16], [38], [39], [40]. ...
... Schizophrenia is characterized by cognitive deficits, hallucinations, delusions and a heterogeneous, sometimes deteriorating clinical course. 1 Brain imaging studies show neuronal processing abnormalities 2 and a progressive decline of brain volume affecting both white and gray matter. 3,4 Although it has a strong genetic component heritability estimates (64-90%), [5][6][7] onset and relapse are associated with environmental factors. ...
Article
Full-text available
In search for the elusive schizophrenia pathway, candidate genes for the disorder from a discovery sample were localized within the energy-delivering and ischemia protection pathway. To test the adult vascular-ischemic (AVIH) and the competing neurodevelopmental hypothesis (NDH), functional genomic analyses of practically all available schizophrenia-associated genes from candidate gene, genome-wide association and postmortem expression studies were performed. Our results indicate a significant overrepresentation of genes involved in vascular function (P<0.001), vasoregulation (that is, perivascular (P<0.001) and shear stress (P<0.01), cerebral ischemia (P<0.001), neurodevelopment (P<0.001) and postischemic repair (P<0.001) among schizophrenia-associated genes from genetic association studies. These findings support both the NDH and the AVIH. The genes from postmortem studies showed an upregulation of vascular-ischemic genes (P=0.020) combined with downregulated synaptic (P=0.005) genes, and ND/repair (P=0.003) genes. Evidence for the AVIH and the NDH is critically discussed. We conclude that schizophrenia is probably a mild adult vascular-ischemic and postischemic repair disorder. Adult postischemic repair involves ND genes for adult neurogenesis, synaptic plasticity, glutamate and increased long-term potentiation of excitatory neurotransmission (i-LTP). Schizophrenia might be caused by the cerebral analog of microvascular angina.
... A recent study exploring treatment response trajectories in schizophrenia using data from clinical trials found that 77% of patients were classified as moderate responders, 8% as poor responders, and 15% as rapid responders [11]. A study that used hospitalization as a proxy measure for psychotic symptom exacerbation over a 10-year period found schizophrenia amelioration in approximately 75% of patients, deterioration in approximately 25% of patients, and stability in less than 1% of patients [12] . These results underscore the need to better understand patients' heterogeneity to help improve patient long-term outcomes. ...
Article
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This study of chronically ill patients with schizophrenia aimed to identify patients who achieve sustained favorable long-term outcome - when the outcome incorporates severity of symptoms, level of functioning, and use of acute care services - and to identify the best baseline predictors of achieving this sustained favorable long-term outcome. Using data from the United States Schizophrenia Care and Assessment Program (US-SCAP) (N = 2327), a large 3-year prospective, multisite, observational study of individuals treated for schizophrenia in the US, a hierarchical cluster analysis was performed to group patients based upon baseline symptom severity. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS) scores, level of functioning, and use of acute care services. Level of functioning reflected patient-reported productivity and clinician-rated occupational role functioning. Use of acute care services reflected self-reported psychiatric hospitalization and emergency service use. Change of health state was determined over the 3-year period. A patient was classified as having a sustained favorable long-term outcome if their health state values had the closest distance to the defined "best baseline cluster" at each point over the length of the study. Stepwise logistic regression was used to determine baseline predictors of sustained favorable long-term outcome. At baseline, 5 distinct health state clusters were identified, ranging from "best" to "worst." Of 1635 patients with sufficient data, only 157 (10%) experienced sustained favorable long-term outcome during the 2-years postbaseline. The baseline predictors associated with sustained favorable long-term outcome included better quality of life, more daily activities, patient-reported clearer thinking from medication, better global functioning, being employed, not being a victim of a crime, not having received individual therapy, and not having received help with shopping and leisure activities. Only a small percentage of patients achieved sustained favorable long-term outcome in this study, suggesting there continues to be a great need for improvement in the treatment of schizophrenia. Findings suggest that clinicians could make early projections of health states and identify those patients more likely to achieve favorable long-term outcomes enabling early therapeutic interventions to enhance benefits for patients.
... O comprometimento funcional decorrente da evolução da esquizofrenia representa um imenso desafio para o pacientes, seus familiares e cuidadores. A esquizofrenia é tida como um transtorno caracterizado por promover grave deterioração funcional em varias esferas da vida e tem mobilizado inúmeros recursos com a meta de minimizar esses danos(WALLACE & LIBERMAN, 1985;RABINOWITZ et al., 2007). ...
... During the prodromal phase of schizophrenia development, individuals may manifest cognitive dysfunction, affective disturbance, and behavioural changes (e.g., social withdrawal), as well as decline in the ability to sustain role functioning such as performance at school or work (Hafner & Maurer, 2006;Rabinowitz, Levine, Haim, & Hafner, 2007). Furthermore, negative symptoms such as depression, anxiety, restless, irritability are common experiences in this stage. ...
Thesis
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The aim of this study was to explore mental health clinicians’ perspectives on the working alliance in the treatment of psychosis. Six clinicians (2 males and 4 females) volunteered to have a one hour semi-structured interview session. Two were mental health practitioners, two clinical psychologists and two psychoanalysts. Open-ended questions were used as a guide to encourage the clinicians to describe their experiences and perspectives on the working alliance in the treatment of psychosis. The thematic analysis of the qualitative data revealed two major themes (a) clinicians’ perspectives of clients’ expectations in a therapeutic relationship and (b) clinicians’ reflections upon their clinical experience in relation to the working alliance in the treatment of psychosis. These two major themes were further subdivided into six and three sub-themes respectively. It was concluded that without compromising the necessary limits or boundaries of the working alliance, mental health clinicians, irrespective of theoretical orientation need to be sensitive to both the general and idiosyncratic expectations of their clients.
... As an alternative to using pre-specified cut-offs to define remission or recovery, one can employ a data-driven approach to identify groups or clusters of patients with differing treatment outcomes. Cluster analysis has been used to assess a variety of outcomes in schizophrenia including course of schizophrenia (Rabinowitz et al., 2007), outcomes for psychiatric symptoms and functioning (Di Michele and Bolino, 2004), alignment of resources with patients' clinical and psychosocial needs (Lora et al., 2001), and symptom subtypes (Dollfus et al., 1996). Cluster analysis is well suited to explore multivariate data that may facilitate identifying subpopulations of patients with distinct profiles in terms of different treatment outcomes (i.e., best vs. worst outcomes). ...
Article
The study's goal was to characterize the typology of patient outcomes based on social and occupational functioning and psychiatric symptoms following antipsychotic drug treatment, and to explore predictors of group membership representing the best/worst outcomes. A hierarchical cluster analysis was used to define groups of patients (n=1449) based on endpoint values for psychiatric symptoms, social functioning, and useful work measured up to 30 weeks of treatment. Stepwise logistic regression was used to construct predictive models of cluster membership for baseline predictors, and with 2/4/8 weeks of treatment. Five distinct clusters of patients were identified at endpoint (Clusters A-E). Patients in Cluster A (25.6%, best outcome) had minimal psychiatric symptoms and mild functional impairment, while patients in Cluster D (14.3%) and E (14.8%) (worst outcome) had moderate-to-severe symptoms and severe functional impairment. Occupational functioning, disorganized thinking, and positive symptoms were sufficient to describe the clusters. Membership in the best/worst clusters was predicted by baseline scores for functioning and symptom severity, and by early changes in symptoms with treatment. Psychiatric symptoms and functioning provided complementary information to describe treatment outcomes. Early symptom response significantly improved the prediction of outcome, suggesting that early monitoring of treatment response may be useful in clinical practice.
... Schizophrenia is often a chronic, life-long condition with an early onset (Rabinowitz et al. 2007;Andreasen et al. 2011). It accounts for 1.1% of the total disability-adjusted life years (DALYs) and 2.8% of years lived with disability (Levav & Rutz, 2002) and is the eighth leading cause of DALYs worldwide in the 15-44 years age group. ...
Article
Background: Early diagnosis of schizophrenia could improve the outcomes and limit the negative effects of untreated illness. Although participants with schizophrenia show aberrant functional connectivity in brain networks, these between-group differences have a limited diagnostic utility. Novel methods of magnetic resonance imaging (MRI) analyses, such as machine learning (ML), may help bring neuroimaging from the bench to the bedside. Here, we used ML to differentiate participants with a first episode of schizophrenia-spectrum disorder (FES) from healthy controls based on resting-state functional connectivity (rsFC). Method: We acquired resting-state functional MRI data from 63 patients with FES who were individually matched by age and sex to 63 healthy controls. We applied linear kernel support vector machines (SVM) to rsFC within the default mode network, the salience network and the central executive network. Results: The SVM applied to the rsFC within the salience network distinguished the FES from the control participants with an accuracy of 73.0% (p = 0.001), specificity of 71.4% and sensitivity of 74.6%. The classification accuracy was not significantly affected by medication dose, or by the presence of psychotic symptoms. The functional connectivity within the default mode or the central executive networks did not yield classification accuracies above chance level. Conclusions: Seed-based functional connectivity maps can be utilized for diagnostic classification, even early in the course of schizophrenia. The classification was probably based on trait rather than state markers, as symptoms or medications were not significantly associated with classification accuracy. Our results support the role of the anterior insula/salience network in the pathophysiology of FES.
... Every person with schizophrenia has their own individual pathway of problems, challenges, abilities and experiences, and their own risk and protective resources arising from their own unique situation (Lambert et al. 2008;Levine et al. 2011;Rabinowitz et al. 2007;Strauss et al. 2010). Individuals will use different coping strategies, skills, strengths, and systems in the face of challenges. ...
Article
The aim of this study was to understand the meaning of resilience as described by people who experience schizophrenia. Building resilience is a component of recovery-oriented mental health care and yet almost no research has been conducted into the resilience of people who live with schizophrenia and who are routinely considered vulnerable. Establishing the meaning of resilience in the context of schizophrenia is an important first step in building understanding. Van Kaam’s Psychophenomenological Method was used to interpret 14 interviews with people with schizophrenia who are currently well and living in the community. Resilience is invoked in the tension between opposing forces of challenge and support and in the act of striving to take control of schizophrenia. Striving includes repeated, seemingly backwards steps and during this, the person takes risks and seeks out and uses supportive people and resources. Those same supportive people and resources can also be challenging. Resilience is an energy embedded in the process of recovery from schizophrenia and is manifest in an attitude of striving. Taking on challenges and engaging in risk is important within treatment and recovery from schizophrenia.
... Earlier studies have suggested that a low level of substance abuse in schizophrenia patients is associated with less frequent relapse and good treatment response. However, a sub-group of patients showed less than optimal treatment response as indicated by early response and relapse, slower response and no response, and delayed response trajectories in positive, negative and general psychopathology symptoms similar to the study by Rabinowitz et al who identified a deteriorating course of symptom severity in a small group of patients [27]. Our four distinct trajectories identified from negative symptoms appear to be comparable to the four trajectories found in the OPUS cohort study [9]. ...
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Background Few studies have examined the trajectories of symptom severity in first episode psychosis (FEP) and their impact on functioning. This study aimed to identify discrete trajectories of positive, negative and general psychopathological symptoms and functioning, determine predictors of the identified symptom trajectories and subsequently investigate the relationship between symptom and functioning trajectories over the 2-year follow-up period. Methods Data were extracted from the Singapore Early Psychosis Intervention Programme clinical database. Trajectories of the Positive and Negative Syndrome Scale and Global Assessment of Functioning (GAF) scale over the two-year follow up were modelled using latent class growth curve modelling. Results Two distinct trajectories (early response and stable trajectory and delayed response trajectory) for positive symptoms, four distinct trajectories (early response and stable trajectory, early response and relapse trajectory, slower response and no response trajectory and delayed response trajectory) for negative and general psychopathology symptoms and three distinct trajectories for functioning (high functioning trajectory, moderately stable functioning trajectory and deterioration in functioning trajectory) were identified in our sample. Compared to individuals in the early response and stable trajectory, those in the delayed response trajectory for positive and negative symptoms, early response and relapse for negative and general psychopathology symptoms and slower response and no response trajectories for general psychopathology symptoms were significantly associated with higher odds of having deterioration in functioning over time. Poor symptom trajectories were also significantly predicted by younger age, male gender, unemployed and economically inactive status, lower education, longer duration of untreated psychosis and diagnosis of schizophrenia spectrum and delusional disorders. Conclusions The results confirm that the symptoms trajectories among patients with FEP are heterogeneous and suggest that a small group of patients may be at higher risk of deterioration in symptom severity and functioning over the 2-year follow-up.
... Schizophrenia is a complex psychiatric disorder with a variable trajectory of symptomatic status that may include stabilization, remission, relapse, deterioration, or total incapacitation. 1,2 Clinical studies evaluating antipsychotics for schizophrenia are replete with data; however, discerning the data in a clinically useful way is often difficult. 3 Assessment of antipsychotics using valid indicators of treatment effects would assist clinicians and psychiatrists with robust, reliable, and comparative data for making treatment decisions. ...
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Antipsychotics are the mainstay in schizophrenia management, and long-acting injectable (LAI) antipsychotics contribute to the successful maintenance of treatment by improving non-adherence and preventing relapses. Paliperidone palmitate 3-monthly (PP3M) formulation is the only available LAI antipsychotic that offers an extended 3-month window of stable plasma drug concentration, enabling only four injections per year. This paper summarizes clinically relevant endpoints from available evidence for PP3M to bridge translational research gaps and provide measurable outcomes that can be interpreted in clinical practice. Low number-needed-to-treat (NNT) for relapse prevention (NNT [95% CI] 6-month estimate: 4.8 [3.2; 10.0]; 12-month estimate: 3.4 [2.2; 7.0]), and high number-needed-to-harm (NNH [95% CI] akathisia, 27.1 [12.3; -667.1]; tremor, 80.0 [22.5; 67.3]; dyskinesia, -132.6 [44.5; -23.2]; parkinsonism, 160.0 [28.9; -49.8]) quantify the relative benefits and low propensity for adverse events with PP3M. Symptom remission and reductions in positive and negative symptoms indicate treatment stability. Additionally, meaningful functional remission, reduced dosing frequency, and freedom from daily negotiations favorably impact patient preference and attenuate burdensome aspects of caregiving, representing important healthcare determinants that enhance prospects of treatment continuity in schizophrenia. This information can potentially improve clinicians' judgment of treatment choices, clinical response, and patient selection in routine care. Taken together, PP3M is a valuable antipsychotic treatment option, meriting consideration for a broader role in the long-term management of schizophrenia; its utility should not be limited to patients with poor adherence or when oral antipsychotics have failed.
... The disorder typically occurs in late teens to early adulthood. An earlier age of onset is associated with higher incidence of re-admission ( Rabinowitz et al., 2007), greater resistance to antipsychotic treatment ( Meltzer et al., 1997), augmented developmental deviance, more severe general psychopathology (Frazier et al., 2007;Vyas et al., 2010aVyas et al., , 2011a) and worse outcome ( Vyas et al., 2007). Epidemiological studies have reported gender differences in schizophrenia with evidence that the male-female rate ratio is 1.4:1 ( Aleman et al., 2003;McGrath, 2007). ...
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There is no doubt that schizophrenia has a significant genetic component and a number of candidate genes have been identified for this debilitating disorder. Of note, several of these are implicated in cognition. Cognitive deficits constitute core symptoms of schizophrenia, and while current antipsychotic treatment strategies aim to help psychosis-related symptomatology, the cognitive symptom domain is largely inadequately treated. A number of other pharmacological approaches (e.g. using drugs that target specific neurotransmitter systems) have also been attempted for the amelioration of cognitive deficits in this population; however, these too have had limited success so far. Psychological interventions appear promising, though there has been speculation regarding whether or not these produce long-term functional improvements. Pharmacogenetic studies of the cognitive effects of currently available antipsychotics, although in relatively early stages, suggest that the treatment of cognitive deficits in schizophrenia may be advanced by focusing on genetic variants associated with specific cognitive dysfunctions in the general population and using this to match the most relevant pharmacological and/or psychological interventions with the genetic and cognitive profiles of the target population. Such a strategy would encourage bottom-up advances in drug development and provide a platform for individualised treatment of cognitive deficits in schizophrenia.
Article
This article examined suicide attempt rates at first psychiatric hospitalization and risk factors for subsequent suicide attempts over the early course of schizophrenia in national population-based data. Data were extracted from the National Psychiatric Hospitalization Case Registry of the State of Israel that contains all first psychiatric admissions with schizophrenia 1989-1992 and were followed up to 1996 (N=2293). Attempted suicide rates were: 8.5% (n=196) at the time of first psychiatric hospitalization and 6.6% (n=151) over the follow-up period of 4 to 7 years. Of those with a suicide attempt at first admission, 31.6% (n=62) made a subsequent suicide attempt during the follow-up period (OR=10.44, 95% CIs=7.22 to 15.09). Risk profiles were derived using recursive partitioning to predict sub-groups at risk of a subsequent suicide attempt. Those characterized by an attempt at the time of first admission were college educated, female and not married (45.9% (17/37), OR=13.46, 95% CIs=6.89 to 26.3). The risk profiles together correctly classified 90.7% (137/151) of subsequent suicide attempts. Suicide attempts at first admission and premorbid years of education have long-term prognostic utility and risk profiles are available.
Article
An association has previously been demonstrated between prefrontal cortex (PFC) volume decreases and illness progression in schizophrenia. The impact of illness duration on the fronto-parietal working memory neural network, however, remains unexplored. We investigated the effect of ageing and duration of illness, and explored possible sex-specific effects of duration of illness, in working memory-related brain activity in schizophrenia. Fifty individuals (25 stable schizophrenia outpatients, 25 healthy controls) underwent functional magnetic resonance imaging during performance of an 'n-back' task. Patients performed significantly worse than controls. Duration of illness correlated with reduced dorsolateral prefrontal cortex activity in males and reduced cerebellum activity in females, regardless of performance and age. Sex-specific effects of illness duration were also evident in the inferior frontal and superior temporal gyri (females) and the inferior parietal cortex (males) which generally show sexually dimorphic activation in healthy people. We detected no significant effect of ageing on neural activation of the working memory network in patients though such an effect was present in healthy controls. In conclusion, our findings demonstrate that a longer duration of schizophrenic illness has sex-specific associations within the working memory neural network, with expected association between illness duration and impaired PFC activation apparent in male, but not in female patients. Additionally, brain regions that exhibit sexually dimorphic activation in healthy people may become compromised in the corresponding sex with illness progression.
Article
Generally, immigrant status and male sex are separately documented to increase the risk of schizophrenia; although population-based risk trends by sex and immigration over time have not been examined. This study aims to examine the extent to which immigration acts as a risk factor for schizophrenia, delineated by origin, sex and year, using national population-based data over 15 years. Data on all first psychiatric admissions from 1978 to 1992 (n = 10,892) from the National Psychiatric Hospitalization Case Registry of the State of Israel were merged with aggregate national data from the Israeli Central Bureau of Statistics. Compared to native-born Israelis, people who migrated prior to the age of 15 (n = 2,335) were at a greater risk of schizophrenia (n = 8,557; RR = 1.6, 95% CI = 1.53; 1.68), particularly those from Far Eastern (RR = 2.43, 95% CI = 1.91; 3.1) and Caribbean and South American (RR = 1.94, 95% CI = 1.51; 2.51) countries. Aggregate risk was higher among female than male immigrants and over the 15-year study immigration-related risk declined across the sexes. The current findings replicate past research showing that immigrants, particularly from a social minority, as suggested by the social defeat-hypothesis, are at an increased risk of schizophrenia, and extend past findings to show that risk at least in Israel has decreased with time irrespective of sex.
Article
Few studies have compared long-acting injectable second-generation antipsychotics with oral antipsychotics. Long-acting injectable antipsychotics-developed specifically to address the problem of adherence-might have an important role to play in treating early psychosis. The effects of oral antipsychotics versus risperidone long-acting injection (RLAI) were compared between 2 similar studies lasting 2 years each that were conducted at our site in South Africa. Results of an open-label study in which patients were treated with flexible doses of RLAI were compared with the results of a randomized controlled trial of flexible doses of oral risperidone or haloperidol. Inclusion criteria for both studies were age 16 to 45 years; confirmed diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder; <or=2 hospitalizations for psychosis; and lifetime exposure to <or=12 weeks of antipsychotic medication. The dose of RLAI was 25 mg every 2 weeks, which could be increased to 50 mg. Doses of oral risperidone or haloperidol began at 1 mg/d and were increased if necessary up to a maximum dose of 4 mg/d (8 mg/d in exceptional cases). Study assessments included the Positive and Negative Syndrome Scale (PANSS), the Extrapyramidal Symptom Rating Scale (ESRS), and body mass index (BMI). The RLAI group included 50 patients (32 men and 18 women; mean [SD] age, 25.4 [7.4] years; BMI, 20.6 [4.6] kg/m(2)). The oral risperidone or haloperidol group included 47 patients (27 men and 20 women; mean [SD] age, 25.9 [5.8] years; BMI, 20.1 [3.4] kg/m(2)). Compared with patients treated with oral risperidone or haloperidol, RLAI-treated patients had significantly fewer all-cause discontinuations (26.0% [13/50] vs 70.2% [33/47] at 24 months; P < 0.005), greater reduction on the PANSS total score (-39.7 vs -25.7; P = 0.009), higher remission rate (64.0% [32/50] vs 40.4% [19/47]; P = 0.028), and lower relapse rate (9.3% [4/43] vs 42.1% [16/38]; P = 0.001) among the responders. Extrapyramidal symptoms were significantly lower in the RLAI group than in patients treated with oral risperidone or haloperidol, as measured by the maximum change in the mean [SD] ESRS total score (1.40 [2.60] vs 5.61 [5.21] vs 9.04 [6.21], respectively; P <or= 0.001). The increase in BMI after 6 months was significantly greater in the RLAI group than in oral haloperidol-treated patients (mean [SD], 3.9 [1.9] vs 2.2 [1.3] kg/m(2); P = 0.001) but not significantly different from oral risperidone (3.4 [2.0] kg/m(2); P = NS). Four patients in the RLAI group had adverse events that were possibly related to prolactin, compared with 1 each in the oral risperidone and haloperidol groups. The findings of this post hoc analysis suggest that there were advantages in terms of efficacy, fewer extrapyramidal symptoms, and more weight gain with long-acting injectable second-generation antipsychotics as compared with oral antipsychotic treatment in early-episode psychosis.
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Growth mixture modeling (GMM) identified latent groups based on treatment outcome trajectories of headache disability measures in patients in headache subspecialty treatment clinics. Using a longitudinal design, 219 patients in headache subspecialty clinics in 4 large cities throughout Ohio provided data on their headache disability at pretreatment and 3 follow-up assessments. GMM identified 3 treatment outcome trajectory groups: (1) patients who initiated treatment with elevated disability levels and who reported statistically significant reductions in headache disability (high-disability improvers; 11%); (2) patients who initiated treatment with elevated disability but who reported no reductions in disability (high-disability nonimprovers; 34%); and (3) patients who initiated treatment with moderate disability and who reported statistically significant reductions in headache disability (moderate-disability improvers; 55%). Based on the final multinomial logistic regression model, a dichotomized treatment appointment attendance variable was a statistically significant predictor for differentiating high-disability improvers from high-disability nonimprovers. Three-fourths of patients who initiated treatment with elevated disability levels did not report reductions in disability after 5 months of treatment with new preventive pharmacotherapies. Preventive headache agents may be most efficacious for patients with moderate levels of disability and for patients with high disability levels who attend all treatment appointments.
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Little is known about the extent of heterogeneity of symptomatology in treated early-onset psychosis. The current study aims to quantify the extent of heterogeneity in trajectories of treated symptom severity in early-episode psychosis and their antecedents. Data were from 491 persons with early-episode psychosis from a clinical trial of haloperidol and risperidone. Positive and Negative Syndrome Scale (PANSS) administrations were used to measure symptom severity trajectories for (a) rapid treatment response scores over 4 weeks and (b) medium-term course over 24 weeks. Baseline antecedents included sex, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis, age of onset, the Premorbid Adjustment Scale, and a cognitive test battery. Symptom severity trajectories were calculated with mixed mode latent class regression modeling from which groups were derived. Five groups based on PANSS scores over time were identified. Over 4 weeks, 3 groups with varied baseline PANSS scores (54-105) did not surpass 30% PANSS improvement. Another group improved and then was stable (n = 76,15.3%), and another showed marked improvement (n = 94,18.9%). Logistic regression showed that membership in the best response trajectory was associated with not having a diagnosis of schizophrenia, good premorbid functioning, and higher cognitive functioning, whereas membership in the poor response trajectory was associated with earlier age of onset and poorer cognitive functioning. Amelioration generally characterizes treated symptom severity. Age of onset, diagnosis, cognitive functioning, and premorbid functioning have prognostic value in predicting treatment response trajectories.
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More than half a century after the introduction of effective pharmacotherapy for the illness, in most patients schizophrenia remains a chronic, relapsing condition with poor long-term outcomes. We examine the pharmacological treatment of schizophrenia from different perspectives to understand why there have not been significant advances, and to consider what the future might hold in store. We argue that the treatment of schizophrenia addresses the phenotype and not the cause; that the causes may not be treatable even if identifiable; that secondary prevention approaches involving treating the phenotype before full-fledged illness develops have, so far, not yielded promising results; and that shifting the focus of treatment from dopamine to other neurotransmitter systems is merely a tertiary prevention approach which will not reverse the extensive structural and functional pathology of schizophrenia. We believe that, given the current state of our knowledge of the illness, the future of the pharmacotherapy of schizophrenia looks bleak.
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The present study compared 21 high functioning individuals with autism, 21 individuals with schizophrenia and 21 healthy individuals in self-reported features of autism, as measured by the Autism-spectrum Quotient (AQ). The individuals with autism reported impairment on all AQ subscales, compared to the neurotypical group. The schizophrenia group reported deficits on all subscales except Attention to Detail, compared to the neurotypical group.The autism group reported more impairment than the individuals with schizophrenia in Social skill, Communication and Attention switching.
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The concepts of remission and recovery applied to schizophrenia refer to different processes of the positive evolution of the trouble: A psychiatric one and the other one more psychological. In this paper, we aim to better understand and characterize the links between these two continuums of evolution. Our qualitative study is based on the narratives of two subjects suffering from schizophrenia, presenting different clinical profiles according to the criteria of the symptomatic and functional remission. We recorded with the consent of both subjects a semi-structured interview built around three topics: The history of the disease, the lived-experience of the disease and the projection onto the future. Considering the recovery process, our results highlight a different attitude toward the disease between the two patients. The psychological evolution appears relatively independent of the psychiatric criterion of the symptomatic remission. Taking into consideration our qualitative analysis, the recognition of the disease and the integration of its lived-experience to the personality can be conceived as stages of the process of the “recovery of the self” (Davidson, 2008).
Article
There have been several recent advances in the ability to identify people at high risk of developing psychosis. This development has spawned efforts at preventing progression to psychosis in individuals with prodromal symptoms of schizophrenia with different approaches including cognitive-behavioral therapy, family psychoeducation, and low-dose antipsychotic medication (e.g., risperidone [Risperdal], olanzapine).30 Although data emerging from some of these trials have been promising, a recent review concluded that there was insufficient evidence to draw any definitive conclusions about the effectiveness of any of these therapeutic approaches at present due to small sample sizes.30 Larger, well-designed studies are now required to replicate these preliminary observations. Ultimately, greater success in preventing the onset of psychosis in patients may depend upon developing a better understanding of the underlying pathophysiology of schizophrenia. Several lines of evidence suggest that anatomic pathology is present at the first episode of schizophrenia. While schizophrenia is widely believed to be a neurodevelopmental disorder, it also seems to encompass limited neurodegenerative features in the early phase of illness. Some data suggest that progression of these anatomic deficits in both the prodromal phase and during the first episode of illness may predict longitudinal course. Strategies aimed at reducing gray matter loss in the early phase of illness potentially hold promise for improving functional outcomes. The observation that gray matter loss may be ameliorated with some second-generation antipsychotics suggests that these drugs may offer some degree of neuroprotection. It is possible that the improved clinical outcomes associated with clozapine and olanzapine treatment may in part be mediated by the neuroprotective properties of these agents.
Chapter
Ursprünglich wurde die Gruppe der Schizophrenien als eine chronische Erkrankung betrachtet, die einen unaufhaltsam progressiven Verlauf nimmt (Kraepelin 1913). Die Recovery-Bewegung und empirische Ergebnisse wirken jedoch diesem Stigma der Unheilbarkeit entgegen. So wird zum Beispiel bei der Recovery-Bewegung durch eine ganzheitliche Betrachtungsweise des Menschen die Möglichkeit betont, krankheitsbedingte Beeinträchtigungen zu überwinden und trotz der Diagnose einer Schizophrenie ein selbstbestimmtes und sinnerfülltes Leben zu führen (Amering u. Schmolke 2009). Recovery ist heute in vielen Ländern gesundheitspolitische Vorgabe für den Bereich der Gesundheitsförderung und der psychiatrischen Versorgung. Unterstützt wird dies durch die Ergebnisse mehrerer Langzeitverlaufsstudien, in denen sich unerwartet hohe Recovery-Raten zwischen 25 % und 65 % ergaben (Rabinowitz et al. 2007; Davidson et al. 2008). Für den Begriff „Recovery“, der übersetzt Gesundung bedeutet, existiert bislang jedoch noch keine einheitliche Definition. Das Recovery-Konzept wurde von verschiedenen Richtungen geprägt und unterschiedlich konzeptualisiert.
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In origine, la schizofrenia è stata considerata una patologia con un andamento cronico progressivamente ingravescente (Kraepelin, 1913). Tale stigma di inguaribilità è stato messo fortemente in discussione dal movimento del recovery (letteralmente “recupero”) e dai risultati provenienti dalle ricerche empiriche. Il movimento del recovery, improntato a una visione olistica dell’uomo, sottolinea la possibilità di superare i limiti connessi alla malattia e, nonostante la diagnosi di schizofrenia, di condurre una vita autodeterminata e piena di significato (Amering e Schmolke, 2009). Oggi, in molti paesi, il concetto di recovery è alla base della politica sanitaria nell’ambito della promozione della salute mentale e dell’assistenza psichiatrica ed è sostenuto dai risultati di studi a lungo termine molto favorevoli che dimostrano tassi di recovery compresi tra il 25% e il 65% (Rabinowitz et al., 2007; Davidson et al., 2008). Ad oggi, non esiste una definizione unitaria del termine “recovery”. Il concetto di recovery è stato inoltre definito in vari modi ed influenzato da diverse correnti culturali.
Article
Objectives: To identify the psychopathological, cognitive, functional, physical health and inflammatory markers that differentiate between early-stage schizophrenia (ESSCH) and late-stage schizophrenia (LSSCH). Methods: Cross-sectional, naturalistic study of 104 patients with SCH. The sample was divided in two groups: 35 ESSCH (≤7 years' duration of illness) and 69 LSSCH (>10 years' duration of illness). Statistical analysis: chi-square test and Student's t-test and ANCOVA (or Quade test) controlling for age, sex, BMI and number of cigarettes/day. Finally, a binomial logistic regression was made. Results: ESSCH show greater negative symptom severity (t = 2.465, p = 0.015), lower levels of IκBα (F = 7.644, p = 0.007), were more frequently classified as normal weight (40% vs 18.8%, p = 0.032) compared with LSSCH. The binomial logistic regression model included age (B = 0.127, p = 0.001) and IκBα (B = 0.025, p = 0.002) and accounted for 38.9% of the variance (model df =7, chi-square =41.841, p < 0.0001). Conclusions: Age and IκBα are the unique markers that differentiate between ESSCH patients whose duration of illness is less than 7 years and LSSCH patients. These results support the hypothesis of toxicity of episodes and highlight the importance of preventing new episodes.
Chapter
The degree of gender equality in a country has been found to be proportional to gender differences in mental health [1, 2], and this has led to great efforts to include gender sensitivity in policy making with a specific focus on mental healthcare delivery and research [3]. Despite this, implementation of gender-specific interventions is slow [4] and research limited.
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Background: Schizophrenia with an onset in adolescence is known to be associated with a poorer outcome and cognitive difficulties. These impairments have an impact on quality of life and represent treatment targets. Cognitive remediation therapy (CRT) attempts to improve cognitive deficits by teaching information processing strategies through guided mental exercises. The objective of this study is to evaluate the efficacy of CRT in alleviating cognitive deficits compared to treatment as usual and explore the mediating and moderating effects of cognitive improvement. Method: Single-blind randomized controlled trial with two groups, one receiving CRT (N21) and the other standard care (N19) assessed at baseline, 3 months (post therapy) and follow-up (3 months post therapy). Participants were recruited from specialist inpatient and community mental health services and were young patients with recent onset schizophrenia (average age of 18) and evidence of cognitive and social behavioural difficulties. The intervention was individual cognitive remediation therapy delivered over a period of 3 months with at least three sessions per week. The main outcome measures were cognition (memory, cognitive flexibility and planning) and secondary outcomes (symptoms, social contacts and self-esteem). Results: Compared to standard care, CRT produced significant additional improvements in cognitive flexibility as measured by the Wisconsin Card Sort Test (WCST). Therapy moderated the effects of improved planning ability on symptoms such that improvements only had a beneficial effect when they were achieved in the context of CRT. Improvements in cognition in all domains had a direct effect on social functioning and improvements in WCST had a direct effect on overall symptom improvement. Conclusions: Cognitive remediation therapy can contribute to the improvement in WCST even in adolescents. The changes in cognitive outcomes also contributed to improvements in functioning either directly or solely in the context of CRT. Evidence of the mediator and moderator effects of cognitive changes should lead to more effective therapy development.
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This analysis examines the notion of progressive deterioration in schizophrenia, using long-term followup data on hospital episodes in defined cohorts from psychiatric case registers in Victoria, Australia; Denmark; and Salford, England. The analyses differentiate heterogeneity existing at the first hospitalization for schizophrenia, which produces a widely varying natural course, from heterogeneity that develops over time, as episodes of hospitalization occur. Episodes of hospitalization for schizophrenia tend to cluster earlier rather than later in the treatment career, suggesting a progressive amelioration rather than deterioration. When overall chronicity is adjusted, each additional episode of hospitalization lowers the risk for a further hospitalization by about 10 percent.
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The probability of rehospitalization following the initial discharge on which a diagnosis of schizophrenia was made is described using data from psychiatric case registers in Victoria, Australia; Maryland, U.S.A.; Denmark; and Salford, England. The percentage eventually rehospitalized, after followup intervals as long as two decades, varies from about 50 to 80 percent in the four service systems. Survival curves for duration in the community without rehospitalization bend sharply in the period between 2 and 3 years following discharge in all four cohorts and are almost flat after 20 years. Early age of onset predicts higher risk for rehospitalization in multivariate proportional hazards models in each cohort. When age of onset is included as a covariate, neither gender nor marital status has consistent or statistically significant effects on risk for rehospitalization.
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All first admitted patients in 1972 from a catchment area of 582,000 inhabitants aged 15 years or more who were diagnosed as schizophrenic at least once from 1972 until September 1983 (n = 53) were followed-up on average 13 years after first admission. About 20% of the cohort was hospitalized on any given day throughout the length of the follow-up period. The duration of hospitalization decreased from a mean of 8.2 months for the first admission to 1.7 months for the tenth or later admission. The readmission risk increased as a function of the number of previous admissions. Patients with income from occupation or from grants for education had shorter duration of first in-patient period. If the patients were diagnosed as schizophrenics already during the first hospitalization the risk for prolonged duration of the first in-patient period was increased but the readmission risk diminished. Furthermore, readmission risk after the first discharge was diminished by own income and by out-patient treatment and increased by low social status. High proportion of follow-up time in hospital (greater than or equal to 30%) was correlated to affective flattening present at first admission. Of the cohorts' total number of admissions (n = 493) 12% were involuntary. Involuntary admissions were more frequent in the first half of the follow-up period and were correlated to a previous involuntary admission.
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While previous studies have found an increased incidence of schizophrenia in some immigrant groups, differences in age of onset in these groups has not been examined. The purpose of this study was to compare age of first hospitalization of (1) native-born people versus immigrants, (2) immigrants from different countries of origin, and (3) first generation immigrants versus second generation immigrants; and to reexamine gender differences in age of first hospitalization. Data were extracted on all first hospital admissions nationally for the years 1978–1992 (n = 10,902) from the National Psychiatric Hospitalization Case Registry of the State of Israel Ministry of Health. Immigrants were older at time of first hospitalization than nonimmigrants, with considerable variations between different countries of origin. Second generation immigrants (i.e., born in Israel to immigrant parents) had ages of first hospitalization similar to people with native-born parents. Males had earlier ages at first hospitalization than females. The results suggest that immigration may have a delaying effect on age of first admission and support previous findings regarding gender difference in age of onset.
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Decades of research on schizophrenia have not produced major breakthroughs, but gradual progress has been made in identifying risk factors and clarifying the nature of the etiologic process. This article provides an overview of trends in research findings as well as current assumptions about the interplay between environmental and genetic factors in the etiology of schizophrenia. Based on the cumulative findings, it appears that both genetic and prenatal factors can give rise to constitutional vulnerability. Subsequent neuromaturational processes, especially those that occur during adolescence, and exposure to stressful events can trigger the behavioral expression of this vulnerability.
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The Israeli National Psychiatric Hospitalization Registry is a nationwide list of all psychiatric hospitalizations in the country and has been widely used as a source of data for psychiatric research. This study assessed the sensitivity of the diagnosis of psychotic disorders ( International Statistical Classification of Diseases, 10th Revision [ ICD-10 ] F20.0-F29.9) and schizophrenia ( ICD-10 F20.0-F20.9) in the Registry. Registry discharge diagnoses of psychotic disorders ( ICD-10 F20.0-F29.9) and schizophrenia ( ICD-10 F20.0-F20.9) were compared with research diagnoses derived from best-estimate procedures based on Research Diagnostic Criteria (RDC) using structured clinical research interviews, hospital records, and family information. Out of 169 patients meeting RDC for psychotic disorder, 150 also had a diagnosis of psychotic disorders in the Registry, yielding a sensitivity of 0.89. Re-running this analysis for the narrow definition of schizophrenia identified 94 patients who were diagnosed with schizophrenia using RDC; 82 of those patients also had a diagnosis of schizophrenia in the Registry, yielding a sensitivity of 0.87. In 87% to 89% of cases with psychotic disorders or with schizophrenia, Registry diagnoses agreed with RDC diagnoses, a rate of agreement comparable with those of other, similar registries. Because a large number of analyses derived from this and similar national registries will be published in the coming years, this constitutes relevant information.
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IntroductionMethodological aspects of course and outcome researchComorbidity with alcohol and drug abuseLong-term course of schizophreniaQuality of life
Article
Studied are changes in diagnosis in a random sample of 10% of all first admissions to psychiatric hospitals and psychiatric wards of general hospitals in Israel from 1983 to 1990 with follow-up evaluation to 1991. This included 4,570 hospitalizations of 2,220 patients. Data were extracted from the National Psychiatric Case Registry of the Ministry of Health. Almost 59% of the sample had one admission, 18% had two, 9% had three, and 14% had four or more. From the first admission to the last discharge (a mean of 2.15 years), 59.2% of the patients' diagnoses did not change. In 89.46% of the cases in which the diagnosis changed, the changes took place during the first admission. Diagnostic change differed between diagnostic groups. In descending order of stability in diagnosis from the first admission to the last discharge were neurotic and personality disorder (73.6%), mental retardation (73.5%), schizophrenia (73.0%), organic conditions (70.6%), affective disorders (66.2%), substance abuse (65.6%), childhood disorders (60%), paranoid disorder (43.6%), other nonorganic psychosis (30.3%), and V-codes (25.0%). The average level of diagnostic agreement between the first admission and the last discharge was a kappa of .52. The average length of stay for patients whose diagnosis became more severe was considerably longer than for patients whose diagnosis became less severe or did not change in level of severity. Older age was related to less change in diagnosis. For patients aged less than 18 years, diagnosis changed in 46.7% of the cases, for patients aged 19 to 44, 31.2%, and for patients older than 45, 27.8%.
Article
Schizophrenia follows a relapsing course for life in most sufferers. In one study almost 80% of patients relapsed repeatedly, and at five years half showed persistent handicap.1 Relapse takes a toll on patients and their families and imposes a financial burden on hospital and community services.2 Some patients relapse while taking maintenance medication,3,4 and this stimulated a search for other contributory factors which has now led to an emerging consensus.*RF 5-10* What are the psychosocial factors, how do they operate, and what interventions are effective? The chance of relapse in patients with schizophrenia living at home depends heavily on the emotional environment provided by the family.11 The concept of expressed emotion has evolved as an index of the quality of this environment.*RF 11-13* Expressed emotion covers many of the emotional responses by a key relative, usually the spouse or parent, towards the patient. The key relative's level of expressed emotion is classed as high or low on the basis of the frequency of critical comments and the intensity of hostility and emotional overinvolvement elicited during a structured interview …
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Synopsis Readmission risk was assessed at the first and subsequent discharges in a total Danish national sample consisting of 8705 first admitted patients who had been discharged alive at least once with a diagnosis of schizophrenia. Predictors for readmission risk were identified using the Cox proportional hazards model. Following the first discharge, 19% of the surviving patients had not been readmitted after 10 years of follow-up. Readmission risk increased with the number of previous admissions. At the first discharge readmission risk decreased with increasing age and was significantly predicted by clinical subtype and gender. At later discharges (5th, 10th, and 15th) the effect of these variables gradually disappeared. At the 15th discharge readmissions were mainly predicted by the duration of the latest admission and discharge periods. Both the increase in readmission risk with the number of previous admissions and the evolving pattern of predictors for readmission risk are interpreted as supporting the existence of a smaller subpopulation among schizophrenic patients with frequent relapses.
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This paper describes the basis for the reform in mental health care system in Israel as presented in the report of the Netanyahu Commission (State Commission for Investigation of Functioning and Efficiency of the Health Care System in Israel, 1990) and the report of the State Comptroller's office (State Comptroller, 1991). These reports pointed to seven major problem areas in the mental health care system: (1) segregation of mental health and general health care systems, (2) variations in availability of services across the country, (3) conflict of interests within Ministry of Health which provides services and oversight, (4) overuse of hospital based care and under use of community based care, (5) reliance on hospitals for custodial care, (6) lack of appreciation of mental health service needs of non-severely mentally ill, and (7) lack of regional service planning. The article describes these problems and the proposed solutions.
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This paper uses monthly symptom data on 90 first-onset schizophrenics in Madras, India, to characterize, in a continuous manner, the course of remission and relapse. Remission from the first episode occurs in about 6 months and in about 3 months for later episodes. Syndromes from the Present State Exam, assessed at the first episode, predict differentially to early and later parts of the course. Hypomania and simple depression predict early remission from the first episode; flat affect and grandiose delusions predict longer episodes and shorter remissions later in the course.
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Several studies have investigated the issue of the natural course of schizophrenia. Our study addressed whether there is evidence for progression, potentially deteriorating, over the long-term course of the disorder. Modern survival analysis techniques were applied to case-register data on the pattern of readmission to in-patient psychiatric facilities. The sample consisted of a total of 8953 persons with schizophrenia. No evidence of a progressive course of schizophrenia was found in the present study. The accelerating pattern of the course of schizophrenia described by some authors, including a previous analysis of an almost identical dataset, can be explained by selection. Heterogeneity reflecting the various levels of individual vulnerability may govern the overall individual course of schizophrenia. We hypothesize that the persistent deficit syndrome and negative symptoms are influential determinants of this heterogeneity.
Article
Schizophrenia is a mental illness that is among the world's top ten causes of long-term disability. The symptoms of schizophrenia include psychosis, apathy and withdrawal, and cognitive impairment, which lead to problems in social and occupational functioning, and self-care. About 1% of the population is affected by schizophrenia, with similar rates across different countries, cultural groups, and sexes. The illness tends to develop between the ages of 16 and 30 years, and mostly persists throughout the patient's lifetime. The cause of schizophrenia is unknown, but evidence suggests that genetic factors, early environmental influences (eg, obstetric complications), and social factors (eg, poverty) contribute. No biological alterations are pathognomonic of schizophrenia, although several pathophysiological differences exist in a wide range of brain structures. Antipsychotic medications are the mainstay for managing schizophrenia. A range of psychosocial treatments are also helpful, including family intervention, supported employment, cognitive-behaviour therapy for psychosis, social skills training, teaching illness self-management skills, assertive community treatment, and integrated treatment for co-occurring substance misuse.
Article
The loss of a child is considered one of the most stressful events in the life of a parent. We hypothesized that parental bereavement increases the risk of hospital admission for a psychiatric disorder, especially for affective disorders. We studied a cohort of 1,082,503 persons identified from national registers in Denmark who were born between 1952 and 1999 and had at least one child under 18 years of age during the follow-up period, from 1970 to 1999. Parents who lost a child during follow-up were categorized as "bereaved" from the date of death of the child. As compared with parents who did not lose a child, parents who lost a child had an overall relative risk of a first psychiatric hospitalization for any disorder of 1.67 (95 percent confidence interval, 1.53 to 1.83). Bereaved mothers had a higher relative risk of being hospitalized for any psychiatric disorder than bereaved fathers (relative risks, 1.78 [95 percent confidence interval, 1.60 to 1.98] and 1.38 [95 percent confidence interval, 1.17 to 1.63], respectively; P value for interaction, 0.01). The relative risks of hospitalization specifically for affective disorders were 1.91 (95 percent confidence interval, 1.59 to 2.30) and 1.61 (95 percent confidence interval, 1.15 to 2.27) for bereaved mothers and fathers, respectively. Among mothers, the relative risk of being hospitalized for any psychiatric disorder was highest during the first year after the death of the child but remained significantly elevated five years or more after the death. The risk of psychiatric hospitalization was increased among parents, especially mothers, who lost a child.
Article
Chronic diseases are roughly speaking lifelong transitions between the states: relapse and recovery. The long-term pattern of recurrent times-to-relapse can be investigated with routine register data on hospital admissions. The relapses become readmissions to hospital, and the time spent in hospital are gaps between subsequent times-at-risk. However, problems of selection and dependent censoring arise because the calendar period of observation is limited and the study population likely to be heterogeneous. We will theoretically verify that an assumption of conditional independence of all times-at-risk and gaps, given the latent individual frailty level, allows for consistent inference in the shared frailty model. Using simulation studies, we also investigate cases where gaps (and/or staggered entry) are informative for the individual frailty. We found that the use of the shared frailty model can be extended to situations, where gaps are dependent on the frailty, but short compared to the distribution of the times-to-relapse. Our motivating example deals with the course of schizophrenia. We analysed routine register data on readmissions in almost 9000 persons with the disorder. Marginal survival curves of time-to-first-readmission, time-to-second-readmission, etc. were estimated in the shared frailty model. Based on the schizophrenia literature, the conclusion of our analysis was rather surprising: one of a stable course of disorder.
Article
Despite suggestions that an earlier age of onset and being male confer to a poorer course of schizophrenia, evidence regarding when these effects are most salient appears to be ambiguous. To examine the relationship of age of first hospitalization and sex with the course of hospitalization in a population based cohort. All first admissions for schizophrenia in a national population based cohort in Israel from 1978 to 1992 were followed through 1996 (n=12,071) using data from the National Psychiatric Hospitalization Case Registry of the State of Israel, a complete national registry of psychiatric admissions. Recursive partitioning was conducted to empirically determine cut-off points for age groups showing the greatest difference on the variables of interest. A younger age of first hospital admission was associated with a greater likelihood of having more than one hospital admission, longer first admissions, more hospital admissions and more inpatient days per year. Of patients with age of first admission below 17, 82.5% had more than one admission which decreased for subsequent age groups to 73.54% (18-28), 69.36% (29-31), 62.88% (32-45), and 50.77% (over 45). Men had an earlier first admission than women, and had slightly more cut-off values. Irrespective of sex, the relationship between age at first admission and later hospitalization conformed to a linear trend. An earlier onset corresponds linearly with the severity of the course of illness and appears to have prognostic value.
Cluster Analysis Psychosocial factors and relapse of schizophrenia
  • M S Aldenderfer
  • R K Blashfield
Aldenderfer, M.S., Blashfield, R.K., 1984. Cluster Analysis. Sage, London. Davies, T., 1994. Psychosocial factors and relapse of schizophrenia. BMJ 309, 353–354.