Healthy adolescent performance on the MATRICS Consensus Cognitive Battery (MCCB): Developmental data from two samples of volunteers
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.
Section snippets
Participants
Participants included 139 adolescents and young adults between the ages of 12–19 who were recruited as healthy control (HC) volunteers from two concurrent NIMH-funded studies: the second phase of the multi-site North American Prodromal Longitudinal Study (NAPLS-2; n = 126; 91% of the overall sample, which included eight sites from four geographic regions), and the single-site Boston Center for Intervention Development and Applied Research (CIDAR) study, “Vulnerability to Progression in
Results
Several distributions of the nine MCCB tasks were skewed and thus transformed as described above. Logarithmically transformed variables included Trail Making Test Part A (following which the direction of the log scores was reversed before T-score conversion), HVLT-R, BVMT-R, and NAB Mazes. Sociodemographic and other characteristics of the overall sample and age cohorts are provided in Table 3. The age range from 12 to 19 provides coverage of the adolescent period of development up to the lower
Discussion
These findings show that performance in MCCB cognitive domains follows a dynamic trajectory of improvement in adolescent NAPLS and CIDAR control subjects that is at least partially independent of overall cognitive ability (i.e. IQ). They also show means and standard deviations for individual test scores throughout adolescence. These data add to a small literature describing the performance of healthy individuals below the age of 20 on the MCCB. It is the first study to focus on adolescents
Role of funding source
This project was a cooperative agreement between the investigator sites and the National Institutes of Health.
Funding
National Institute of Mental Health grants (U01MH0818902 to T.D.C., U01MH081984 to J.M.A., P50MH066286 to C.E.B., U01MH082022 to K.S.C., U01MH081857 to B.A.C., U01MH082004 to D.O.P., U01MH081928 to L.J.S., U01MH081988 to E.F.W., U01MH066160 to S.W.W., P50MH080272 to R.W. M.) and the Commonwealth Research Center of the Massachusetts Department of Mental Health (SCDMH82101008006 to
Contributors
All data was collected by the Principal Investigators of the NAPLS Study (JA, CEB, KSC, TDH, BAC, DHM, THM, DOP, MTT, EFW, SWW, LJS) and the Boston Cidar Study (RWM). WSS, RMG, AJG, and LJS conceptualized the paper and analyses. WSS, RMG, and AJG wrote the first draft of the paper. RMG, AJG, and KAW performed the statistical analyses. WSS, RMG, AJG, KAW, and LJS provided the clinical and neuropsychological training and supervision of staff. LJS provided scientific oversight and reviewed all
Conflict of interest
Dr. Green has been a consultant to AbbVie, Biogen, DSP, EnVivo/Forum and Roche, and he is on the scientific advisory board of Mnemosyne. Dr. Nuechterlein has received unrelated research support from Janssen Scientific Affairs, Genentech, and Brain Plasticity, Inc., and has consulted to Genentech, Otsuka, Janssen, and Brain Plasticity, Inc. All other authors declare that they have no actual or potential conflict of interest including any financial, personal or other relationships with other
Acknowledgments
We acknowledge and thank the study participants and their family members. We also thank the clinical, research assistant, and data management staff from the Boston CIDAR and NAPLS-2 studies, including Caitlin Bryant, Ann Cousins, Grace Francis, Molly Franz, Michelle Friedman-Yakoobian, Lauren Gibson, Andréa Gnong-Granato, Maria Hiraldo, Sarah Hornbach, Matcheri Keshavan, Kristy Klein, Grace Min, Elena Molokotos, Keira O′Donovan, Corin Pilo, Janine Rodenhiser-Hill, Julia Schutt, Rachael Serur,
References (60)
- et al.
Outcome in early-onset schizophrenia revisited: findings from the Early Psychosis Prevention and Intervention Centre long-term follow-up study
Schizophr. Res.
(2011) - et al.
Is adolescent-onset first-episode psychosis different from adult onset?
J. Am. Acad. Child Adolesc. Psychiatry
(2005) - et al.
Factor structure of the MATRICS Consensus Cognitive Battery in schizophrenia
Schizophr. Res.
(2013) - et al.
The Continuous Performance Test, Identical Pairs verstion (CPT-IP): I. New findings about sustained attention in normal families
Psychiatry Research
(1988) - et al.
Relative stability of neurocognitive deficits in early onset schizophrenia spectrum patients
Schizophr. Res.
(2014) - et al.
Characteristics of the MATRICS Consensus Cognitive Battery in a 29-site antipsychotic schizophrenia clinical trial
Schizophr. Res.
(2011) - et al.
The brief assessment of cognition in schizophrenia: reliability, sensitivity, and and comparison with a standard neurocognitive battery
Schizophrenia Research
(2004) - et al.
Neurocognitive predictors of functional outcome two to 13 years after identification as ultra high risk for psychosis
Schizophr. Res.
(2011) - et al.
MATRICS Cognitive Consensus Battery (MCCB) performance in children, adolescents and young adults
Schizophr. Res.
(2014) - et al.
Identification of separable cognitive factors in schizophrenia
Schizophr. Res.
(2004)
Cognitive performance of individuals with schizophrenia across seven decades: a study using the MATRICS Consensus Cognitive Battery
Am. J. Geriatr. Psychiatr.
Brief Visuospatial Memory Test - Revised
Predicting premorbid IQ: A revision of the National Adult Reading Test
Clinical Neuropsychology
The Hopkins Verbal Learning Test - Revised
A summary of the FDA-NIMH-MATRICS workshop on clinical trial design for neurocognitive drugs for schizophrenia
Schizophr. Bull.
The FDA-NIMH-MATRICS guidelines for clinical trial design of cognitive-enhancing drugs: what do we know 5 years later?
Schizophr. Bull.
The MATRICS Consensus Cognitive Battery in patients with bipolar I disorder
Neuropsychopharmacology
School performance in Finnish children and later development of schizophrenia: a population-based longitudinal study
Arch. Gen. Psychiatry
The long-term course of childhood-onset schizophrenia: a 42-year follow-up
Schizophr. Bull.
Using neuroplasticity-based auditory training to improve verbal memory in schizophrenia
Am. J. Psychiatry
Structured clinical interview for DSM-IV-TR axis I disorders, research version, non-patient edition (SCID-I/NP)
The psychosis high risk state: a comprehensive state-of-the-art review
JAMA Psychiatry
Cognitive functioning in prodromal psychosis: a meta-analysis
Arch. Gen. Psychiatry
Neurocognition in psychosis risk syndrome: a quantitative and qualitative review
Curr. Pharm. Des.
Auditory working memory and Wisconsin card sorting test performance in schizophrenia
Arch. Gen. Psychiatry
Functional co-primary measures for clinical trials in schizophrenia: results from the MATRICS psychometric and standardization study
Am. J. Psychiatry
Evaluation of co-primary measures for clinical trials of cognition enhancement in schizophrenia
Am. J. Psychiatry
Intraindividual neuropsychological test variability in healthy individuals with high average intelligence and educational attainment
Int. J. Neurosci.
Structured clinical interview for DSM-IV-child edition (version 1.0)
Adolescent schizophrenia
Adv. Psychiatr. Treat.
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