Extending the ‘cross‐disorder’ relevance of executive functions to dimensional neuropsychiatric traits in youth

Abstract

Background Evidence that different neuropsychiatric conditions share genetic liability has increased interest in phenotypes with ‘cross-disorder’ relevance, as they may contribute to revised models of psychopathology. Cognition is a promising construct for study; yet, evidence that the same cognitive functions are impaired across different forms of psychopathology comes primarily from separate studies of individual categorical diagnoses versus controls. Given growing support for dimensional models that cut across traditional diagnostic boundaries, we aimed to determine, within a single cohort, whether performance on measures of executive functions (EFs) predicted dimensions of different psychopathological conditions known to share genetic liability. Methods Data are from 393 participants, ages 8 to 17, consecutively enrolled in the Longitudinal Study of Genetic Influences on Cognition (LOGIC). This project is conducting deep phenotyping and genomic analyses in youth referred for neuropsychiatric evaluation. Using structural equation modeling, we examined whether EFs predicted variation in core dimensions of autism spectrum disorder, bipolar illness and schizophrenia, including social responsiveness, mania/emotion regulation, and positive symptoms of psychosis, respectively. Results We modeled three cognitive factors (working memory, shifting, and executive processing speed) that loaded on a second-order EF factor. The EF factor predicted variation in our three target traits but not in a negative control (somatization). Moreover, this EF factor was primarily associated with the overlapping (rather than unique) variance across the three outcome measures, suggesting it related to a general increase in psychopathology symptoms across those dimensions. Conclusions Findings extend support for the relevance of cognition to neuropsychiatric conditions that share underlying genetic risk. They suggest that higher-order cognition, including EFs, relate to the dimensional spectrum of each of these disorders and not just the clinical diagnoses. Moreover, results have implications for bottom-up models linking genes, cognition, and a general psychopathology liability.

Disentangling unity from diversity in developmental psychopathology

“…The proposed model displayed differential validity in terms of executive function since we found a different profile for dimensions within the same broad spectrum. The proposed model confirmed previous findings of the association between worse executive function and the general psychopathology factor in youth [73], [55], [74], [75], [18] and the association between inattention-hyperactivity and worse executive function [11], [76], [77]. The bifactor model displayed an EF divergent profile for anxiety dimensions; worse performance related to fear and better performance related to distressful thoughts.…”

Specificity of executive functioning and processing speed problems in common psychopathology.

“…On the other hand, there also appears to be an underlying shared mechanism or ability that contributes to performance across different EF tasks lending support to the unity of the EF construct (Duncan et al, 1997; Hanes et al, 1996; Miyake et al, 2000; Salthouse et al, 2003) (McGrath et al, 2015). The unity and diversity of EF processes provides the opportunity to examine EF from a holistic perspective, with a focus on the combined measurement of EF, as well as from a component perspective.…”

Comorbid symptoms of inattention, autism, and executive cognition in youth with putative genetic risk

“…We found four latent factors: verbal memory, verbal fluency, visual-spatial processing, and common executive (CE). Similar to previous research (McGrath et al, 2016), CE was created as a broad factor reflecting inhibition, switching, and processing speed because we did not find support for distinction among these constructs in our analysis.…”

“…Previous research indicates that g and P are correlated (Caspi et al, 2014), and variance in P can be partially accounted for by cognitive skills. For example, McGrath and colleagues (2016) demonstrated that shared variance among psychosis, mania, and autistic traits was partially explained by a common executive cognition factor. This model is consistent with a cognitive endophenotype model and indicates that measures of cognition are more closely tied to brain functions that give rise to the abnormal psychiatric phenotype.…”