Review
Cognition at illness onset as a predictor of later functional outcome in early psychosis: Systematic review and methodological critique

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Abstract

Background

Cognitive deficits occur early in the course of psychosis, are mostly stable, and have been identified as potential functional prognostic markers. Previous reviews of chronic schizophrenia have concluded that specific cognitive deficits are strongly associated with poorer functional outcomes. However, results of schizophrenia studies may be influenced by the effects of long-term illness or treatment or be biased toward individuals with poorer outcomes and may not be relevant to early psychosis (EP). This review aimed to systematically examine the evidence regarding general and social cognitive predictors of later functional outcome in EP and critique the methodology of the studies reviewed. A final aim was to conduct a meta-analysis of the studies reviewed, but methodological reasons precluded this.

Method

A comprehensive search of PsycINFO and MEDLINE databases identified 15 relevant articles and 7 further articles following a reference list search, totaling 22 included articles.

Results

Most studies found at least one cognitive domain predicted functional outcome, but examination of separate cognitive domains revealed there were more null than significant associations between cognition and functional outcome across every cognitive domain. No study examined social cognition as a predictor of outcome. The frequency with which different cognitive domains predicted outcome varied depending on study methodology and this was most noticeable when studies with short-term follow-up were compared with longer-term follow-up studies.

Conclusions

Due to the methodological variability and limitations of the studies reviewed, firm conclusions regarding the relationship between cognition and functional outcomes in EP cannot be made. Tentatively, cognition may be prognostic in EP, especially for longer-term outcomes. However, further research that addresses the methodological issues identified, including examination of social cognition and other non-cognitive predictors, is needed.

Introduction

Cognitive deficits, including impairments in social cognition, have been reliably identified early in the course of psychosis and appear to remain relatively stable at least over the first several years of the illness (Addington et al., 2005, Censits et al., 1997, Hill et al., 2004, Hoff et al., 1999, Inoue et al., 2006, Nopoulos et al., 1994, Saykin et al., 1994). It has been suggested that stable cognitive dysfunction early in the course of psychosis likely reflects a trait marker, rather than direct sequelae of illness (Nuechterlein et al., 1998), although recent research indicates that some neuroprogressive change occurs as the illness proceeds to more chronic forms (Sun et al., 2009).

Despite generally good symptomatic outcomes following the advent of antipsychotic medication, residual functional disabilities, particularly in vocational and social domains, are common and persistent in patients with psychosis (Gupta et al., 1997, Hegarty et al., 1994, Robinson et al., 2004, Tohen et al., 2000). Thus, for prognostic and treatment purposes it is highly important to find valid and reliable predictors of functional, as well as symptomatic outcomes.

Among other variables, such as long duration of untreated psychosis (DUP) and poor premorbid adjustment (Barnes et al., 2008, Harris et al., 2005, Jeppesen et al., 2008, Marshall et al., 2005, Perkins et al., 2005, Swanson et al., 1998), cognitive dysfunction, including impaired social cognition, has been identified as one of the primary factors that may contribute to residual poor functioning. Accordingly, over approximately the past 20 years there has been increased research into the relationship between cognitive function and a range of functional outcomes in psychosis, particularly in established or chronic schizophrenia (Bowie and Harvey, 2006, Christensen, 2007, Couture et al., 2006, Dickerson et al., 1999, Fett et al., 2011, Gold et al., 2002, Green, 1996, Green et al., 2000, Johnstone et al., 1990, McGurk and Mueser, 2004, Smith et al., 2002, Tsang et al., 2010, Velligan et al., 2000). Outcomes that have received the most attention include symptom-based functioning (e.g., relapse rates, hospital days, level of symptomatology), interpersonal or social functioning, vocational functioning (i.e., work or education), and independent living/residential status. This body of research has revealed that despite achievement of symptomatic remission, cognitive dysfunction in patients with schizophrenia frequently persists and may be more strongly predictive of functional outcome than symptomatology (Christensen, 2007, Green, 1996, Green et al., 2000, Velligan et al., 2000).

However, because a diagnosis of schizophrenia (by definition) represents the ‘end stage’ (i.e., Stages 3–4; McGorry et al., 2006) and arguably, the most severe form of psychotic disorder, results of these studies may be influenced by the effects of long-term illness (e.g., psychotic relapse, multiple episodes, persistent residual symptoms and social isolation) or treatment (e.g., medications and hospitalizations) and may not be relevant to individuals experiencing a first-episode or earlier stage of psychotic disorder (Green, 2007, Menezes et al., 2006, Robinson et al., 1999). Furthermore, participants in chronic schizophrenia studies may represent a subset of individuals who are biased toward poorer treatment responses and outcomes, as not all individuals with early psychosis (EP) or first-episode schizophrenia (FES) specifically, progress to more chronic stages, and therefore outcomes in the EP cohort may be more variable (Bilder et al., 2000, Carpenter and Strauss, 1991, Davidson and McGlashan, 1997, Harrison et al., 2001, Jarbin et al., 2003, Menezes et al., 2006). Additionally, psychosis onset peaks during adolescence and young adulthood (Jablensky et al., 1999), a dynamic period of the lifespan characterized by significant neurodevelopment coupled with the normal goals of attempting to initiate and achieve independence in vocational and social role functioning. Hence, stage of development may play a mediating role in the relationship between cognitive dysfunction and functional outcomes in psychosis (Pantelis et al., 2003, Pantelis et al., 2009).

The primary factors contributing to functional outcomes in individuals with EP are yet to be fully elucidated, although research into the role of cognition in the functioning of EP patients is fast gaining momentum. Data specific to the EP population are crucial for shaping appropriate and valid early intervention and prevention strategies that are likely to maximize the chances of optimal prognosis and outcomes (Birchwood et al., 1998, McGorry et al., 2006). If clinicians can identify those individuals at greatest risk of poorer functional outcomes via comprehensive assessments (that may include cognitive assessment) at an early stage of the illness, then they can plan and implement the most appropriate interventions by targeting the predictive factors, including cognitive domains, that are most related to functional outcome, with the ultimate goal being the prevention of illness progression and poor functional outcomes.

The principal aim of this review was to systematically examine the current evidence regarding general cognitive and social cognitive predictors of later functional outcome in EP. The review focused specifically on outcomes in community, vocational and social functioning (rather than symptomatic outcomes), given that these outcomes are predicted to be influenced by cognition based on results of schizophrenia studies. A secondary aim was to conduct a meta-analysis on the studies reviewed, but methodological reasons precluded this (see Method section). Finally, a critique of the methodology of the studies reviewed was also conducted.

Section snippets

Literature search and study inclusion

The PsycINFO and MEDLINE electronic databases were searched for English-language articles published before 31st July 2010 using the following search terms: ‘cognit*’, ‘neurocognit*’ or ‘neuropsych*,’ combined with ‘early psychosis’, ‘first-episode psychosis’, ‘first-episode schizophrenia’, ‘first-onset psychosis’ or ‘first-onset schizophrenia’, combined with ‘outcome’. For the purpose of this review, articles were required to report original empirical research (i.e., not reviews, meta-analyses,

Description of sample characteristics and methodology of included studies

Table 1 shows the 22 included studies and their corresponding sample and methodological characteristics, as well as the key findings. Most samples consisted of first-episode psychosis (FEP) patients inclusive of the full range of non-affective and affective psychosis diagnoses (e.g., Addington et al., 2005); however, some samples were restricted to pure schizophrenia or non-affective psychosis diagnoses (e.g., Gonzalez-Blanch et al., 2010). Half (11 out of 22) of the reviewed studies evaluated

Discussion

The aim of this review was to systematically examine the findings and methodology of studies that have investigated the relationship between cognition and later functional outcome in EP. Although there are cross-sectional studies that have examined this relationship in EP (e.g., Dickerson et al., 2007, Wegener et al., 2005, Williams et al., 2008), only studies that examined baseline cognitive function as a predictor of longitudinal functional outcome were included in this review. This was based

Role of funding source

This work was supported by a NHMRC Postdoctoral Clinical Research Fellowship [628884 to K.A.]; the Colonial Foundation [K.A., T.P., E.K.]; Australian Rotary Health [E.K.]; the Australian Research Council [LP0883237 to E.K.]; and a Ronald Phillip Griffith Fellowship [E.K.]. These funding sources had no role in the study design, data collection, analysis and interpretation of data, writing of the manuscript, or the decision to submit the paper for publication.

Contributors

All authors were involved in the design and conduct of the review. Dr. Allott managed the literature searches and wrote the first draft of the manuscript. Ms. Liu assisted with reviewing studies for the meta-analysis. All authors contributed to and have approved the final manuscript.

Conflict of interest

All authors declare that they have no conflicts of interest.

Acknowledgements

We thank Drs Sarah Hetrick and Mario Alvarez-Jimenez for their advice in preparing the manuscript.

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