The course of negative symptom in first episode psychosis and the relationship with social recovery

doi:10.1016/j.schres.2016.04.017

Schizophrenia Research

Volume 174, Issues 1–3, July 2016, Pages 165-171

https://doi.org/10.1016/j.schres.2016.04.017 Get rights and content

Abstract

Aims

To investigate trajectories of negative symptoms during the first 12 months of treatment for first episode psychosis (FEP), their predictors and relationship to social recovery.

Method

1006 participants were followed up for 12 months following acceptance into Early Intervention in Psychosis services. Negative symptom trajectories were modelled using latent class growth analysis (LCGA) and predictors of trajectories examined using multinomial regression. Social recovery trajectories – also modelled using LCGA – of members of each negative symptom trajectory were ascertained and the relationship between negative symptom and social recovery trajectories examined.

Results

Four negative symptom trajectories were identified: Minimal Decreasing (63.9%), Mild Stable (13.5%), High Decreasing (17.1%) and High Stable (5.4%). Male gender and family history of non-affective psychosis predicted stably high negative symptoms. Poor premorbid adolescent adjustment, family history of non-affective psychosis and baseline depression predicted initially high but decreasing negative symptoms. Members of the Mild Stable, High Stable and High Decreasing classes were more likely to experience stably low functioning than the Minimal Decreasing class.

Conclusions

Distinct negative symptom trajectories are evident in FEP. Only a small subgroup present with persistently high levels of negative symptoms. A substantial proportion of FEP patients with elevated negative symptoms at baseline will achieve remission of these symptoms within 12 months. However, elevated negative symptoms at baseline, whether or not they remit, are associated with poor social recovery, suggesting targeted interventions for service users with elevated baseline negative symptoms may help improve functional outcomes.

Introduction

Negative symptoms represent a significant unmet clinical need and the search for effective treatments has received renewed interest in recent years (Kirkpatrick et al., 2006). However, the mechanisms that underpin negative symptoms remain poorly understood. Negative symptoms can be subject to significant fluctuations over time, particularly in the early course of psychosis (Edwards et al., 1999, Ventura et al., 2004). Individuals vary in the stability of their negative symptoms (Kelley et al., 2008) and those with persistently elevated negative symptoms are at highest risk of poor outcome (Husted et al., 1992, Mäkinen et al., 2008). Increased understanding of variation in negative symptom course might help illuminate the mechanisms which underlie negative symptoms.

The prevalence of persistent negative symptoms in first episode psychosis (FEP) remains unclear due to the use of inconsistent criteria for persistence. Moreover, grouping individuals into those with persistent negative symptoms and those without might mask the true complexity of individual variation in negative symptom course. Chen et al. (2013) found that variation in negative symptom course in a cohort of schizophrenia patients was best modelled by four distinct trajectory classes, characterised by differing levels of negative symptoms at baseline and a distinctive pattern of longitudinal change. It is not yet known whether multiple negative symptoms trajectories are similarly evident in FEP. This study examines negative symptom trajectories in a large FEP sample using latent class growth analysis (LCGA), a data-driven approach to identifying patterns of longitudinal change within a heterogeneous population. Predictors of the identified trajectories are then investigated.

This study also explores the relationship between negative symptom course and social recovery. Although the association between negative symptoms during FEP and poor functional outcomes is well established (Evensen et al., 2012, Galderisi et al., 2013), the relationship between the trajectory of an individual's negative symptoms and concurrent change in their functioning has yet to be investigated. Understanding the relationship between negative symptom course and contemporaneous changes in functioning might inform the development of targeted interventions to improve functional outcomes following FEP.

Section snippets

Participants

The sample comprises participants in the National EDEN study: a national evaluation of the impact and cost-effectiveness of Early Intervention in Psychosis (EIP) services in the UK (Birchwood et al., 2014). All individuals accepted into EIP services in Birmingham, Bristol, Cambridge, Cornwall, Lancashire and Norfolk between August 2005 and April 2009 were invited to take part. The Policy Implementation Guide (Department of Health, 2001) provides details of the acceptance criteria for these

Exploratory structural equation modelling

A five-factor model which fit the data adequately (RMSEA = 0.054; CFI = 0.914; TLI = 0.874) resulted in a negative symptoms factor including the items ‘Blunted affect’, ‘Lack of spontaneity’, ‘Emotional withdrawal’, ‘Passive social withdrawal’, ‘Poor rapport’, ‘Motor retardation’ and ‘Active social avoidance’. The mean rating of these items was used to measure negative symptom severity. The identified factor structure was similar to that found in van der Gaag et al.'s (2006) study employing similar

General discussion

This study identified four distinct negative symptom trajectories in a large sample of individuals receiving treatment for FEP. Only a small proportion of the sample (5.4%) had persistently high levels of negative symptoms. A further 13.5% of the sample presented with consistently elevated negative symptoms of lesser severity. The mean intercept of both these trajectories was sufficiently high to indicate multiple clinically significant negative symptoms. Membership of the class with the

Role of funding source

This article presents independent research funded by the National Institute for Health Research (NIHR) under the Programme Grants for Applied Research programme (RP-PG-0109-10074). Professor Max Birchwood, Chief Investigator of National EDEN and Super EDEN, is part-funded by NIHR CLAHRC West Midlands; Professor Singh is part funded by the NIHR through the Collaborations for Leadership in Applied Health Research and Care for the West Midlands; and Professor Jones is part funded by the NIHR

Contributors

BG was involved in designing the study, analysed the data and wrote the first draft of the manuscript. JH and DF were involved in designing the study and supervised the data analysis and interpretation. MB, MM, LE, HL, PJ, TA, SS, VS, NF and DF were key investigators on the National EDEN study and contributed to the analysis and interpretation of this data.

All authors contributed to and have approved the final manuscript.

Conflict of interest

The authors declare that they have no conflicts of interest concerning this article.

Acknowledgments

We thank all National EDEN participants and the EIP teams who supported this research. Helen Lester, our great friend and colleague, who was a co-CI on National EDEN sadly died during the production of this paper. We thank the UK Mental Health Research Network for their support in case finding and follow-up.

References (39)

D. Addington et al.
Specificity of the Calgary depression scale for schizophrenics
Schizophr. Res.
(1994)
N. Boonstra et al.
Duration of untreated psychosis and negative symptoms—a systematic review and meta-analysis of individual patient data
Schizophr. Res.
(2012)
J. Edwards et al.
Enduring negative symptoms in first-episode psychosis: comparison of six methods using follow-up data
Schizophr. Res.
(1999)
J. Evensen et al.
Flat affect and social functioning: a 10 year follow-up study of first episode psychosis patients
Schizophr. Res.
(2012)
S. Galderisi et al.
Persistent negative symptoms in first episode patients with schizophrenia: results from the European first episode schizophrenia trial
Eur. Neuropsychopharmacol.
(2013)
J. Hodgekins et al.
Comparing time use in individuals at different stages of psychosis and a non-clinical comparison group
Schizophr. Res.
(2015)
J.A. Husted et al.
Negative symptoms and the early course of schizophrenia
Psychiatry Res.
(1992)
M.E. Kelley et al.
Longitudinal progression of negative symptoms in schizophrenia: a new look at an old problem
Schizophr. Res.
(2008)
E. Liemburg et al.
Two subdomains of negative symptoms in psychotic disorders: established and confirmed in two large cohorts
J. Psychiatr. Res.
(2013)
E.J.C.G. Van den Oord et al.
Factor structure and external validity of the PANSS revisited
Schizophr. Res.
(2006)

M. Van der Gaag et al.

The five-factor model of the positive and negative syndrome scale II: a ten-fold cross-validation of a revised model

Schizophr. Res.

(2006)

J. Ventura et al.

The timing of negative symptom exacerbations in relationship to positive symptom exacerbations in the early course of schizophrenia

Schizophr. Res.

(2004)

H. Andruff et al.

Latent class growth modelling: a tutorial

Tutor. Quant. Methods Psychol.

(2009)

T. Asparouhov et al.

Exploratory structural equation modeling

Struct. Equ. Model.

(2009)

M. Birchwood et al.

The UK national evaluation of the development and impact of early intervention services (the national EDEN studies): study rationale, design and baseline characteristics

Early Interv. Psychiatry

(2014)

J.J. Blanchard et al.

Toward the next generation of negative symptom assessments: the collaboration to advance negative symptom assessment in schizophrenia

Schizophr. Bull.

(2011)

H.E. Cannon-Spoor et al.

Measurement of premorbid adjustment in chronic schizophrenia

Schizophr. Bull.

(1982)

L. Chen et al.

The longitudinal interplay between negative and positive symptom trajectories in patients under antipsychotic treatment: a post hoc analysis of data from a randomized, 1-year pragmatic trial

BMC Psychiatry

(2013)

Department of Health

The Mental Health Policy Implementation Guide

(2001)

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The findings highlight the importance of conducting a multidimensional assessment not only at FEP but also during follow-up to customize the effectiveness of interventions. Furthermore, the results emphasize the relevance of assessing premorbid predictors from the onset of illness. This may enable the identification of FEP patients at high-risk of poor long-term outcomes who would benefit from targeted prevention programs on specific psychopathological dimensions.
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Given the strong prognostic value of early negative symptoms (NS), understanding their associations with long-term outcomes of schizophrenia is essential. The study examined early NS patterns in trajectory, severity and variability and their association with 12-year outcomes. NS in the first 36 months after onset and the symptomatology, cognitive function, and functioning at 12 years were examined in 330 patients with first-episode schizophrenia spectrum disorders. The relationships and pathways between the outcomes at 12 years and the trajectory, severity, and variability of early NS were examined. We found that the prediction of trajectory of early NS to long-term outcomes was limited, whereas variability was negatively associated with the patient's long-term executive function, and severity was positively associated with long-term symptomatology and negatively associated with long-term functioning. Path modelling revealed that the severity and variability of early NS influenced patients’ long-term functioning via cognitive function and/or clinical symptom pathways. Our findings support the notion that severity of early NS influences the prognosis of schizophrenia and the closer examination revealed that the severity and variability of early NS are differentially associated with long-term clinical symptoms, executive function, and functional outcomes via distinct pathways.
The relationship between negative symptoms, social cognition, and social functioning in patients with first episode psychosis
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Following this premise, we would underline, on the one hand, the importance of the affectation of subdomains of social cognition, as well as the role of negative symptoms, specifically the experiential factor (Reddy et al., 2016), in the functioning of patients with FEP. This is the reason why some authors have shown that treatments aimed at improving social cognition will not improve functioning if they do not also address negative symptoms (Strassnig et al., 2015), currently considered as a therapeutic need unsatisfied for a large number of patients (Galderisi et al., 2018a; Gee et al., 2016; Hunter and Barry, 2012; Sarkar, 2015), partly due to the difficulty in treating these symptoms (Aleman et al., 2017) and the issues in designing clinical trials for their research (Marder and Kirkpatrick, 2014). The inclusion of specific components targeting negative symptoms in prevention and treatment programs could thus allow us to reduce the impact on the social functioning of these patients, carrying out an early and comprehensive approach in these cases (Arango et al., 2017, 2018).
Social functioning is severely affected in psychotic disorders. Negative symptoms and social cognition seem to play an important role in social functioning, although the preponderance and relationship between these three domains is not clear. In this study, we sought to assess the interrelation between social cognition, social functioning, and the expressiveness and experiential factors of negative symptoms in first-episode psychosis (FEP).
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Our findings suggest that there is a direct relationship between social cognition and social functioning (weight = -.077), but also an indirect connection between them, mediated by the experiential (but not the expressiveness) factor of negative symptoms (weight = 0.300).
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Unlike theory-driven approaches (e.g., PNS), which rely on a priori definitions of grouping variables, patient classification is informed by measures of between-subjects and within-subjects variability (van der Nest et al., 2020). Several studies (Abdin et al., 2017; Austin et al., 2015; Chan et al., 2020; Chang et al., 2019; Gee et al., 2016; Pelayo-Teran et al., 2014) have applied LGM to categorise patients based on negative symptom severity. Three such studies (Abdin et al., 2017; Austin et al., 2015; Chang et al., 2019) linked poorer functioning to latent classes with more severe negative symptoms.
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The course of negative symptom in first episode psychosis and the relationship with social recovery

Abstract

Aims

Method

Results

Conclusions

Introduction

Section snippets

Participants

Exploratory structural equation modelling

General discussion

Role of funding source

Contributors

Conflict of interest

Acknowledgments

Schizophr. Res.

Schizophr. Res.

Schizophr. Res.

Schizophr. Res.

Eur. Neuropsychopharmacol.

Schizophr. Res.

Psychiatry Res.

Schizophr. Res.

J. Psychiatr. Res.

Schizophr. Res.

Schizophr. Res.

Schizophr. Res.

Latent class growth modelling: a tutorial

Tutor. Quant. Methods Psychol.

Exploratory structural equation modeling

Struct. Equ. Model.

The UK national evaluation of the development and impact of early intervention services (the national EDEN studies): study rationale, design and baseline characteristics

Early Interv. Psychiatry

Toward the next generation of negative symptom assessments: the collaboration to advance negative symptom assessment in schizophrenia

Schizophr. Bull.

Measurement of premorbid adjustment in chronic schizophrenia

Schizophr. Bull.

The longitudinal interplay between negative and positive symptom trajectories in patients under antipsychotic treatment: a post hoc analysis of data from a randomized, 1-year pragmatic trial

BMC Psychiatry

The Mental Health Policy Implementation Guide