Plasticity of DNA methylation, functional brain connectivity and efficiency in cognitive remediation for schizophrenia

New Fei Ho; Jordon Xin Jie Tng; Mingyuan Wang; Guoyang Chen; Vigneshwaran Subbaraju; Suhailah Shukor; Desiree Si Xian Ng; Bhing-Leet Tan; Shu Juan Puang; Sok-Hong Kho; Rachel Wan En Siew; Gwen Li Sin; Pui Wai Eu; Juan Zhou; Judy Chia Ghee Sng; Kang Sim; Alice Medalia

doi:10.1016/j.jpsychires.2020.03.013

Plasticity of DNA methylation, functional brain connectivity and efficiency in cognitive remediation for schizophrenia

J Psychiatr Res. 2020 Jul:126:122-133. doi: 10.1016/j.jpsychires.2020.03.013. Epub 2020 Mar 28.

Authors

New Fei Ho¹, Jordon Xin Jie Tng², Mingyuan Wang², Guoyang Chen², Vigneshwaran Subbaraju³, Suhailah Shukor², Desiree Si Xian Ng², Bhing-Leet Tan⁴, Shu Juan Puang⁵, Sok-Hong Kho⁵, Rachel Wan En Siew⁵, Gwen Li Sin⁶, Pui Wai Eu², Juan Zhou⁷, Judy Chia Ghee Sng⁵, Kang Sim², Alice Medalia⁸

Affiliations

¹ Institute of Mental Health, Singapore; Duke-National University of Singapore Medical School, Singapore. Electronic address: newfei_ho@u.duke.nus.edu.
² Institute of Mental Health, Singapore.
³ A*STAR Human-Centric Artificial Intelligence Programme, Singapore.
⁴ Institute of Mental Health, Singapore; Singapore Institute of Technology, Singapore.
⁵ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
⁶ Singapore General Hospital, Singapore.
⁷ Duke-National University of Singapore Medical School, Singapore; Center for Sleep and Cognition, Cognitive Neuroscience, Yong Loo Lin School of Medicine, National University of Singapore, SIngapore.
⁸ Columbia University College of Physicians and Surgeons, New York, USA.

PMID: 32317108
DOI: 10.1016/j.jpsychires.2020.03.013

Abstract

Cognitive remediation (CR) is predicated on principles of neuroplasticity, but the actual molecular and neurocircuitry changes underlying cognitive change in individuals with impaired neuroplastic processes is poorly understood. The present study examined epigenetic-neurocircuitry-behavioral outcome measures in schizophrenia, before and after participating in a CR program that targeted higher-order cognitive functions. Outcome measures included DNA methylation of genes central to synaptic plasticity (CpG sites of Reelin promoter and BDNF promoter) from buccal swabs, resting-state functional brain connectivity and topological network efficiency, and global scores of a cognitive battery from 35 inpatients in a rehabilitative ward (18 CR, 17 non-CR) with similar premorbid IQ to 15 healthy controls. Baseline group differences between healthy controls and schizophrenia, group-by-time effects of CR in schizophrenia, and associations between the outcome measures were tested. Baseline functional connectivity abnormalities within the frontal, fronto-temporal and fronto-parietal regions, and trending decreases in global efficiency, but not DNA methylation, were found in schizophrenia; the frontal and fronto-temporal connectivity, and global efficiency correlated with global cognitive performance across all individuals. Notably, CR resulted in differential changes in Reelin promoter CpG methylation levels, altered within-frontal and fronto-temporal functional connectivity, increasing global efficiency and improving cognitive performance in schizophrenia, when compared to non-CR. In the CR inpatients, positive associations between the micro to macro measures: Reelin methylation changes, higher global efficiency and improving global cognitive performance were found. Present findings provide a neurobiological insight into potential CR-led epigenetics-neurocircuitry modifications driving cognitive plasticity.

Keywords: Brain efficiency; Cognitive remediation; DNA methylation; Functional connectivity; Neuroplasticity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain / diagnostic imaging
Brain Mapping
Cognitive Remediation*
DNA Methylation
Humans
Magnetic Resonance Imaging
Reelin Protein
Schizophrenia* / genetics