Healthy adolescent performance on the MATRICS Consensus Cognitive Battery (MCCB): Developmental data from two samples of volunteers

Abstract

The MATRICS Consensus Cognitive Battery (MCCB) fills a significant need for a standardized battery of cognitive tests to use in clinical trials for schizophrenia in adults aged 20–59. A need remains, however, to develop norms for younger individuals, who also show elevated risks for schizophrenia. Toward this end, we assessed performance in healthy adolescents. Baseline MCCB, reading and IQ data were obtained from healthy controls (ages 12–19) participating in two concurrent NIMH-funded studies: North American Prodromal Longitudinal Study phase 2 (NAPLS-2; n = 126) and Boston Center for Intervention Development and Applied Research (CIDAR; n = 13). All MCCB tests were administered except the Managing Emotions subtest from the Mayer–Salovey–Caruso Emotional Intelligence Test. Data were collected from 8 sites across North America. MCCB scores were presented in four 2-year age cohorts as T-scores for each test and cognitive domain, and analyzed for effects of age and sex. Due to IQ differences between age-grouped subsamples, IQ served as a covariate in analyses. Overall and sex-based raw scores for individual MCCB tests are presented for each age-based cohort. Adolescents generally showed improvement with age in most MCCB cognitive domains, with the clearest linear trends in Attention/Vigilance and Working Memory. These control data show that healthy adolescence is a dynamic period for cognitive development that is marked by substantial improvement in MCCB performance through the 12–19 age range. They also provide healthy comparison raw scores to facilitate clinical evaluations of adolescents, including those at risk for developing psychiatric disorders such as schizophrenia-related conditions.

Introduction

Neurocognitive impairments are a central problem for individuals with schizophrenia, beginning in childhood during the premorbid period and continuing throughout life. The development of a pathway for regulatory approval for new treatment strategies to reduce cognitive deficits in schizophrenia created the need for a standardized battery of neuropsychological tests to assess the effectiveness of proposed treatments. A National Institute of Mental Health (NIMH) initiative to encourage the development of novel interventions to attenuate cognitive deficits in schizophrenia, called Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS), addressed this need. This led to the development of a reliable, valid “MATRICS Consensus Cognitive Battery” (MCCB) for use in clinical trials and for other purposes (Kern et al., 2008, Nuechterlein et al., 2008). The MCCB is comprised of 9 tests that reflect six distinct, replicated dimensions of neurocognitive dysfunction in schizophrenia, including: Speed of Processing, Attention/Vigilance, Working Memory, Verbal Learning, Visual Learning, and Reasoning and Problem Solving (Nuechterlein et al., 2004). A 10th test, the Managing Emotions Branch of the Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT), and the additional dimension, Social Cognition, was added because of growing interest in this component of function, and because of its relevance to real world function (Nuechterlein and Green, 2006).

Thus far, investigations into the psychometric properties of the MCCB have been positive. The MCCB demonstrates excellent reliability, minimal practice effects, a low rate of missing data and significant correlations with functional capacity measures (Green et al., 2011, Nuechterlein et al., 2008). Subsequent large, industry-sponsored, multi-site clinical trial studies have affirmed these positive psychometric characteristics (Buchanan et al., 2011, Keefe et al., 2011). The MCCB has also shown strong sensitivity to change in adults with schizophrenia who participated in an intensive cognitive remediation program (Fisher et al., 2009).

Validation studies involving the MCCB have also been encouraging. Progress has been made in demonstrating that improvement on neuropsychological tests such as those in the MCCB is related to improvement in ‘real-world’ tasks (Buchanan et al., 2005, Buchanan et al., 2011). Methods for evaluating performance-based and interview-based measures were developed as part of the MATRICS Psychometric and Standardization Study (PASS) (Green et al., 2008), and supported by the Validation of Intermediate Measures study (VIM) (Green et al., 2011). The success of the MCCB has also been facilitated by its translation into many languages for use in international trials. Indeed, the MATRICS website (http://www.matricsinc.org) listed 21 languages by 2015.

The initial success of the MCCB reliability and validity studies has spurred efforts to characterize the battery further and expand its utility. Recent investigations focused on efforts to refine its factor structure (Burton et al., 2013, McCleery et al., 2015), assess its performance in other psychiatric conditions such as bipolar disorder (Burdick et al., 2011, Sperry et al., 2015), and evaluate its performance in older individuals (Rajji et al., 2013). One area in particular need of further study is the performance of psychiatrically healthy adolescents on the MCCB. While the MCCB norms are stratified for age and sex, and cover the adult age ranges of 20–59 in five year intervals, a substantial proportion of people with schizophrenia experience the onset of their illness (Cannon et al., 1999, Juuhl-Langseth et al., 2014, Thomsen, 1996) or associated, prodromal symptoms of their illness before age 20. The interpretation of the MCCB scores is thus limited in pharmacological and/or psychosocial clinical trials involving youth. Individuals with early-onset schizophrenia (EOS; onset before age 18), including childhood onset (COS; onset by age 13) and adolescent-onset schizophrenia (AOS; onset between ages 13–18), constitute an important clinical population, particularly for early intervention.

There are additional reasons to study cognitive functions in this younger age group. First, the identification of cognitive problems is significant in its own right, regardless of etiology. Second, it is often prognostic, especially in clinical high risk (CHR) adolescent samples (Fusar-Poli et al., 2012a, Fusar-Poli et al., 2012b, Giuliano et al., 2012, Seidman et al., 2010, Woodberry et al., 2008). Moreover, cognitive weaknesses often predict current function in high risk youth (Lin et al., 2011), rates of premorbid abnormalities, familial schizophrenia-spectrum disorders (Nicolson et al., 2003), subsequent exacerbations of cognitive problems (Rajji et al., 2009), greater social disability (Eggers and Bunk, 1997) and functional outcomes over time (Amminger et al., 2011, Ballageer et al., 2005, Hollis, 2000, Insel, 2007, Insel, 2010).

It is thus important to clearly interpret MCCB performance in healthy individuals younger than 20, and particularly in adolescents. Among the few published studies using the MCCB in patients with schizophrenia-spectrum disorders and healthy control subjects below the age of 18, adolescents aged 11–13 years old who showed symptoms of psychosis performed more poorly on several MCCB tasks than adolescents who did not show psychotic symptoms (Kelleher et al., 2013). Similarly, adolescents 12 to 18 years old with schizophrenia-spectrum disorders (mean = 15.8 years) showed stable performance deficits compared to age-matched healthy controls on all MCCB domains except social cognition (Holmen et al., 2010, Juuhl-Langseth et al., 2014).

Still needed, however, are studies of MCCB performance across normal development, both to identify developmental trajectories, and to establish useful comparison data for researchers and clinicians. A Norwegian standardization project reported progress toward this goal by measuring MCCB performance for 5 groups ranging from 12 to 59 years of age, including a 12 to 19 year-old group (n = 50) (Mohn et al., 2012). Similarly, a recent study assessed MCCB performance in 5 groups ranging from 8 to 23 years of age and narrowed the age bands to 4-year bins (e.g. 8 to 11 years; n's = 21 to 54 for the 3 adolescent bins) (Nitzburg et al., 2014). This study provided raw scores and T-scores, the latter of which were derived across all age groups. While both of these studies assessed adolescents, they covered this dynamically complex and heterogeneous stage of development as either a single eight-year period (Mohn et al., 2012), or as 3 four-year periods that also included younger children in the earlier period and adults older than 19 in the later period (Nitzburg et al., 2014). The current study extends the analysis of normal MCCB performance by focusing solely on a teenage sample to assess age-related differences within adolescence, with data presented in 4 two-year age periods that range from ages 12 to 19, further refining healthy comparison data for this period.

We present adolescent control data and examine the influence of age and sex on test performance, comparing our findings with those described in the original adult (aged 20–59) version. Our goal is to expand the utility of the MCCB as a standard battery for adolescents by providing both developmental trajectories for each of its cognitive domains (except social cognition), and control comparison data as raw scores to facilitate clinical evaluations of adolescents who may be at risk for developing psychiatric disorders.