Connecting Neurobiological Features with Interregional Dysconnectivity in Social-Cognitive Impairments of Schizophrenia

Author:

Adraoui Florian W.1ORCID,Douw Linda2ORCID,Martens Gerard J. M.34ORCID,Maas Dorien A.2ORCID

Affiliation:

1. Biotrial, Preclinical Pharmacology Department, 7-9 rue Jean-Louis Bertrand, 35000 Rennes, France

2. Anatomy and Neurosciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, Boelelaan, 1081 HZ Amsterdam, The Netherlands

3. Donders Centre for Neuroscience (DCN), Department of Molecular Animal Physiology, Faculty of Science, Donders Institute for Brain, Cognition and Behavior, Radboud University, 6525 GA Nijmegen, The Netherlands

4. NeuroDrug Research Ltd., 6525 ED Nijmegen, The Netherlands

Abstract

Schizophrenia (SZ) is a devastating psychiatric disorder affecting about 1% of the world’s population. Social-cognitive impairments in SZ prevent positive social interactions and lead to progressive social withdrawal. The neurobiological underpinnings of social-cognitive symptoms remain poorly understood, which hinders the development of novel treatments. At the whole-brain level, an abnormal activation of social brain regions and interregional dysconnectivity within social-cognitive brain networks have been identified as major contributors to these symptoms. At the cellular and subcellular levels, an interplay between oxidative stress, neuroinflammation and N-methyl-D-aspartate receptor hypofunction is thought to underly SZ pathology. However, it is not clear how these molecular processes are linked with interregional dysconnectivity in the genesis of social-cognitive symptoms. Here, we aim to bridge the gap between macroscale (connectivity analyses) and microscale (molecular and cellular mechanistic) knowledge by proposing impaired myelination and the disinhibition of local microcircuits as possible causative biological pathways leading to dysconnectivity and abnormal activity of the social brain. Furthermore, we recommend electroencephalography as a promising translational technique that can foster pre-clinical drug development and discuss attractive drug targets for the treatment of social-cognitive symptoms in SZ.

Funder

Amsterdam UMC

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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