Psychiatric disability as mediator of the neurocognition-functioning link in schizophrenia spectrum disorders: SEM analysis using the Evaluation of Cognitive Processes involved in Disability in Schizophrenia (ECPDS) scale

Abstract

The functional outcome in schizophrenia spectrum disorders is affected by multiple factors such as cognitive performance and clinical symptoms. Psychiatric disability may be another important determinant of functional outcome. The purpose of this study was to test whether schizophrenia symptoms and psychiatric disability mediated the association between cognition and functioning.

Between April 2013 and July 2017, we included 108 community-dwelling adults with stable schizophrenia spectrum disorder in a multicenter study. Psychiatric disability was assessed with the Evaluation of Cognitive Processes involved in Disability in Schizophrenia (ECPDS) scale by relatives of patients. ECPDS focused on the broad array of motivational, neurocognitive, sociocognitive, and metacognitive impairments that result in activity restrictions. We used a battery of tests to assess seven cognition domains (processing speed, attention/vigilance, working, verbal and visual memory, reasoning and problem solving, and executive functioning) and cross-sectional structural equation modeling (SEM) for the mediation analyses. We estimated the one-year temporal stability of ECPDS scores in 45 participants.

The model provided showed good fit and explained 43.9% of the variance in functioning. The effect of neurocognition on functioning was fully mediated by symptoms (proportion mediated: 36.5%) and psychiatric disability (proportion mediated: 31.3%). The ECPDS score had acceptable one-year temporal stability.

The ECPDS scale has satisfactory psychometric properties, and shows significant convergence with neurocognition and functioning, suggesting a role for this tool in the routine evaluation of cognitive remediation needs. Our model validates psychiatric disability as a crucial step from cognitive impairment to restricted participation in life situations.

Introduction

Schizophrenia spectrum disorders are among the most disabling psychiatric conditions worldwide. Psychiatric disability can be defined as a restriction in activities related to clinical symptoms and cognitive impairments due to a psychiatric disorder. This restriction leads to a handicap, i.e., limits participation in life situations. According to the International Classification of Functioning, Disability, and Health (ICF) – a conceptualization developed by the World Health Organization (WHO) – disability and functional outcome impairment result from complex interactions between the health condition of the individual and contextual factors (World Health Organization, 2001). Nevertheless, having a simple and reliable measurement of schizophrenia-induced disability may provide valuable insight into the gap between measurable cognitive function and real-life functioning.

Several approaches have been used to estimate the extent to which cognitive impairments lead to a restriction in daily life activities of individuals with schizophrenia. One approach uses self-ratings of cognitive complaints, but these are only weakly correlated with objective cognition (Prouteau et al., 2004). Another relies on semi-structured, interview-based measures of cognitive-related disability in schizophrenia, which requires the intervention of a trained clinician (Keefe et al., 2006b). Although free of bias related to insight deficits, this approach ignores social cognitive and metacognitive skills and motivation levels. Functional outcome is strongly associated with social cognition (Galderisi et al., 2016), metacognition (Arnon-Ribenfeld et al., 2017) and motivation (Nakagami et al., 2008) in schizophrenia. This limitation may explain why previous interview-based screening for cognitive-related disability show only moderate correlations with functional outcome. To address these limitations, we recently developed the Evaluation of Cognitive Processes involved in Disability in Schizophrenia (ECPDS) (Passerieux et al., 2017). The relatives or friends of the patient can complete this instrument in about 15 min, without receiving specific training. The ECPDS scale provides an original focus on the broad array of motivational, neurocognitive, sociocognitive, and metacognitive impairments that result in schizophrenia-related disability and activity restrictions. Recent work demonstrated both excellent concurrent validity of this scale against independent living outcomes and good convergent validity with the proxy-completed WHO Disability Assessment Schedule (Passerieux et al., 2017). However, no previous studies assessed convergent validity of the ECPDS scale against objective cognitive performance and functioning evaluated by a trained clinician.

The identification of factors contributing to functional outcome and participation in life situations is now among the critical issues for psychiatric rehabilitation planning. Neurocognitive deficits are widely accepted as a core feature of schizophrenia spectrum disorders (Gold, 2004), and several studies demonstrated significant associations of neurocognition with functional deficiency (Bowie et al., 2010; Harvey et al., 2006a). For instance, functioning measured with the Personal and Social Performance Scale (PSP) correlated positively with cognition, mainly memory and attention (Hsieh et al., 2011). A longitudinal study found that neurocognition caused significant changes in psychosocial functioning, whereas the reverse was not true, suggesting a causality vector from neurocognition to functioning (Nakagami et al., 2010). Symptomatology is another crucial determinant of functioning impairment in schizophrenia. Among schizophrenia symptoms, negative symptoms are particularly linked to functional outcome (Milev et al., 2005) and, more specifically, to avolition (Galderisi et al., 2016) and inexpressivity (Velthorst et al., 2017). Other psychotic symptoms may have a direct negative impact on functioning in schizophrenia, such as disorganization (Galderisi et al., 2014), positive symptoms (Alessandrini et al., 2016; Craig et al., 1999; Galderisi et al., 2014, Galderisi et al., 2016; Lin et al., 2013) and depressive symptoms (Alessandrini et al., 2016; Lin et al., 2013). Therefore, for the present work, we assumed that a global measure of schizophrenia symptoms would be negatively associated with functional outcome.

A substantial body of literature supports significant associations with neurocognition of several schizophrenia symptoms, chiefly negative symptoms (Lin et al., 2013; Milev et al., 2005; Ventura et al., 2009) and disorganization (Brazo et al., 2002; Galderisi et al., 2014, Galderisi et al., 2016). This line of research raises the issue of whether schizophrenia symptoms mediate the relationship between neurocognition and functioning. Several studies show that schizophrenia symptoms – mainly the negative symptoms – fully (Lin et al., 2013) or partially (Chan and Yeung, 2008; Ventura et al., 2009) mediate the decrease in functioning associated with impaired cognition. Psychiatric disability measured with the ECPDS scale may be another candidate for mediation between neurocognition and functioning in schizophrenia, according to the ICF model (World Health Organization, 2001). This model is built around the following three broad components: body structures and functions (including psychological functions), activities (related to tasks and actions done by an individual), and participation (involvement in a life situation), with additional information about disorder severity and environmental factors. The ICF defines impairments as “problems in body function or structure such as a significant deviation or loss”. According to this definition, neurocognitive deficits should be classified as impairments. The ECPDS scale measures activity limitations, according to the definition given by the ICF. At one end of the spectrum, functioning measured with the PSP assesses restricted participation, defined by the ICF as “problems an individual may experience in involvement in life situations”. According to the ICF, impairments, activity limitations, and restricted participation interact with one another, with the contextual factors of the environment and with personal factors.

The primary objective of this study was to investigate whether the relationship between neurocognition and functioning was mediated by a global measure of schizophrenia symptoms and psychiatric disability, using Structural Equation Modeling (SEM) and controlling for the premorbid intelligence quotient. The secondary objective was to evaluate the ECPDS scale regarding internal consistency, one-year temporal stability, and convergent validity against neuropsychological performance and daily functioning.