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Developmental trajectories of premorbid functioning predict cognitive remediation treatment response in first-episode schizophrenia

Published online by Cambridge University Press:  09 November 2022

Susan S. Kuo*
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA
Joseph Ventura
Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, USA
Jennifer K. Forsyth
Department of Psychology, University of Washington, Seattle, USA
Kenneth L. Subotnik
Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, USA
Luana R. Turner
Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, USA
Keith H. Nuechterlein
Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, USA Department of Psychology, UCLA, Los Angeles, USA
Author for correspondence: Susan S. Kuo, E-mail:



Cognitive development after schizophrenia onset can be shaped by interventions such as cognitive remediation, yet no study to date has investigated whether patterns of early behavioral development may predict later cognitive changes following intervention. We therefore investigated the extent to which premorbid adjustment trajectories predict cognitive remediation gains in schizophrenia.


In a total sample of 215 participants (170 first-episode schizophrenia participants and 45 controls), we classified premorbid functioning trajectories from childhood through late adolescence using the Cannon-Spoor Premorbid Adjustment Scale. For the 62 schizophrenia participants who underwent 6 months of computer-assisted, bottom-up cognitive remediation interventions, we identified MATRICS Consensus Cognitive Battery scores for which participants demonstrated mean changes after intervention, then evaluated whether developmental trajectories predicted these changes.


Growth mixture models supported three premorbid functioning trajectories: stable-good, deteriorating, and stable-poor adjustment. Schizophrenia participants demonstrated significant cognitive remediation gains in processing speed, verbal learning, and overall cognition. Notably, participants with stable-poor trajectories demonstrated significantly greater improvements in processing speed compared to participants with deteriorating trajectories.


This is the first study to our knowledge to characterize the associations between premorbid functioning trajectories and cognitive remediation gains after schizophrenia onset, indicating that 6 months of bottom-up cognitive remediation appears to be sufficient to yield a full standard deviation gain in processing speed for individuals with early, enduring functioning difficulties. Our findings highlight the connection between trajectories of premorbid and postmorbid functioning in schizophrenia and emphasize the utility of considering the lifespan developmental course in personalizing therapeutic interventions.

Original Article
Copyright © The Author(s), 2022. Published by Cambridge University Press

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