Cognitive Enhancement Therapy Might Halt Progressive White Matter Microstructural Changes in Early Course Schizophrenia

Rachal Hegde, MS

Beth Israel Deaconess Medical Center
Cognitive Enhancement Therapy Might Halt Progressive White Matter Microstructural Changes in Early Course Schizophrenia

Scientific Abstract

Background: Cognitive enhancement therapy (CET) is an effective treatment intervention for improving cognitive impairments in schizophrenia. However, the neurobiological changes associated with CET- mediated cognitive improvements are limited. This study aims to investigate the effects of CET on white matter and cognitive changes in early course schizophrenia utilizing diffusion-weighted imaging.

Methods: Individuals with early course schizophrenia underwent CET (n=26) or enriched supportive therapy (EST) (n=20) for 18 months. Diffusion-weighted images were harmonized and processed using free water imaging, separately modeling tissue (FAt) and extracellular (FW) water diffusion. Tract-Based Spatial Statistics was performed using ENIGMA-DTI protocols. Annualized rate of change (ARCH) for average FAt/FW measures, as well as change for cognitive measures was calculated. ANCOVA was used to test for average FAt/FW differences. Fisher’s r-to-z transformation of relationships between average FAt or FW with cognitive measures was performed to test for potential significant differences between correlations.

Results: No significant average FAt/FW differences were found for baseline or ARCH measures. Significant group differences were detected for associations between baseline FW and attention/vigilance changes (CET, r=0.27, p=0.20; EST, r=-0.50, p=0.04; Z=2.44, p=0.02) and between longitudinal FAt and social cognitive changes (CET, r=-0.06, p=0.78; EST, r=0.54, p=0.02; Z=2.00, p=0.05).

Conclusions: For the EST group, FAt reductions correlated with decreased social cognitive performance over time and baseline FW elevations correlated with decreased attention/vigilance performance over time. We observed no significant effects for the CET group, suggesting that cognitive treatment may disrupt the progression of structural decline associated with poorer cognitive performance in early course schizophrenia.

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research Areas


Rachal Hegde, MS, Paulo Lizano, MD, PhD, Sinead Kelly, PhD, Olivia Lutz, BS, Suheyla Cetin Karayumak, PhD, Ofer Pasternak, PhD, Marek Kubicki, MD, PhD, Shaun Eack, PhD, Matcheri Keshavan, MD

Principal Investigator

Matcheri Keshavan, MD