The relationship between negative symptoms and MATRICS neurocognitive domains: A meta-analysis and systematic review

Negative symptoms (NS) are a core symptom domain in schizophrenia spectrum disorders and are associated with poorer social and vocational functioning, and with increased likelihood and durations of hospital admission. NS are not well understood, limiting available interventions. However, numerous studies have reported associations between neurocognitive domains and NS severity. Thus, one promising area in understanding NS is in relation to neurocognition. Currently, the specificity of the relationship between NS and neurocognition is unknown, meaning that there is no consensus regarding which neurocognitive domain is most strongly associated with NS. There is a need to systematically examine the relationship between NS and various neurocognitive domains within study samples.

A systematic search of Ovid PsycINFO, Ovid MEDLINE and Web of Science was performed for articles published since 2004 (year of MATRICS Consensus publication). Inclusion criteria were: 1) individuals with schizophrenia spectrum disorders, first episode psychosis or clinical high risk 2) assessed all six MATRICS neurocognitive domains (processing speed, attention, working memory, verbal learning & memory, visual learning & memory, reasoning & problem solving), 3) reported correlations between all six MATRICS neurocognitive domains and global NS. A three-level random effects hierarchical meta-analysis was performed to assess the relationship between NS (global, expressive, and experiential dimensions) and the six MATRICS neurocognitive domains.

21 studies were included in the review (n = 3619). All MATRICS neurocognitive domains had small significant correlations with global NS (r = -0.16 to -0.20, p < 0.0001). This relationship was significantly moderated by diagnosis and the moderating effect of sex/ gender trended on significance. Analysis of a subset of the studies revealed that MATRICS neurocognitive domains also had small significant correlations with the two NS dimensions, expressive and experiential. Correlations were stronger with the expressive NS dimension.

This review is novel in assessing the relationship between multiple neurocognitive domains and NS within the same sample, by synthesizing close to two decades of research. Our results suggest that there is a non-specific relationship between neurocognition and NS, and that expressive NS may have a stronger relationship with neurocognitive functioning-based on the MATRICS classification of neurocognition and the neurocognitive assessments used in the included studies. This has implications on our understanding of NS and neurocognition, as well as their treatments. As we gain better understanding of the directionality of the NS-cognition relationship, it could suggest that NS, particularly in the expressive domain, could be improved by targeting cognition globally or that neurocognitive treatments could be more effective if NS are addressed first. Further implications of these results are discussed.