Recherche de convergence diagnostique croisée: mécanismes neuronaux régissant l'équilibre entre l'excitation et inhibition dans la schizophrénie et les troubles du spectre de l'autisme

Aperçu: G.M.

Des rapports théoriques récents ont proposé le déséquilibre d'excitation et d'inhibition (E / I) comme une hypothèse mécaniste, au niveau du réseau, sous-jacente au dysfonctionnement neuronal et comportemental et commun aux troubles du développement neurologique, en particulier le trouble du spectre de l'autisme (TSA) et la schizophrénie (SCZ). 

Ces deux troubles partagent un certain chevauchement dans leur présentation clinique ainsi que leur convergence dans leurs gènes sous-jacents et leur neurobiologie. Cependant, il existe également des points clairs de dissociation en termes de phénotypes et de circuits neuronaux putativement affectés.

L'étude porte sur les travaux qui émergent de la littérature sur les neurosciences cliniques examinant les corrélats neuronaux du déséquilibre E / I chez les enfants et les adultes avec un diagnostic de TSA et d'adultes avec une SCZ chronique et débutant. Tout au long de cette revue, les auteurs discutent des points de convergence et de divergence dans la littérature TSAet SCZ, en mettant l'accent sur les perturbations dans l'équilibre E / I des neurones.

Biol Psychiatry. 2017 May 15;81(10):848-861. doi: 10.1016/j.biopsych.2017.03.005. Epub 2017 Mar 14.

Searching for Cross-Diagnostic Convergence: Neural Mechanisms Governing Excitation and Inhibition Balance in Schizophrenia and Autism Spectrum Disorders

Foss-Feig JH¹, Adkinson BD², Ji JL³, Yang G³, Srihari VH², McPartland JC⁴, Krystal JH⁵, Murray JD⁶, Anticevic A⁷.

Author information

1

Department of Psychiatry, Icahn School of Medicine at Mount Sinai Hospital, New York, New York; Seaver Autism Center, Icahn School of Medicine at Mount Sinai Hospital, New York, New York; Child Study Center, Yale University School of Medicine, New Haven, Connecticut; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut. Electronic address: jennifer.foss-feig@mssm.edu.

2

Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.

3

Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut.

4

Child Study Center, Yale University School of Medicine, New Haven, Connecticut; Department of Psychology, Yale University, New Haven, Connecticut.

5

Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Division of Neurocognition, Neurocomputation, & Neurogenetics (N3), Yale University School of Medicine, New Haven, Connecticut; Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut; Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut; Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, Connecticut.

6

Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Division of Neurocognition, Neurocomputation, & Neurogenetics (N3), Yale University School of Medicine, New Haven, Connecticut; Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut.

7

Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Division of Neurocognition, Neurocomputation, & Neurogenetics (N3), Yale University School of Medicine, New Haven, Connecticut; Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut; Department of Psychology, Yale University, New Haven, Connecticut.

Abstract

Recent theoretical accounts have proposed excitation and inhibition (E/I) imbalance as a possible mechanistic, network-level hypothesis underlying neural and behavioral dysfunction across neurodevelopmental disorders, particularly autism spectrum disorder (ASD) and schizophrenia (SCZ). These two disorders share some overlap in their clinical presentation as well as convergence in their underlying genes and neurobiology. However, there are also clear points of dissociation in terms of phenotypes and putatively affected neural circuitry. We highlight emerging work from the clinical neuroscience literature examining neural correlates of E/I imbalance across children and adults with ASD and adults with both chronic and early-course SCZ. We discuss findings from diverse neuroimaging studies across distinct modalities, conducted with electroencephalography, magnetoencephalography, proton magnetic resonance spectroscopy, and functional magnetic resonance imaging, including effects observed both during task and at rest. Throughout this review, we discuss points of convergence and divergence in the ASD and SCZ literature, with a focus on disruptions in neural E/I balance. We also consider these findings in relation to predictions generated by theoretical neuroscience, particularly computational models predicting E/I imbalance across disorders. Finally, we discuss how human noninvasive neuroimaging can benefit from pharmacological challenge studies to reveal mechanisms in ASD and SCZ. Collectively, we attempt to shed light on shared and divergent neuroimaging effects across disorders with the goal of informing future research examining the mechanisms underlying the E/I imbalance hypothesis across neurodevelopmental disorders. We posit that such translational efforts are vital to facilitate development of neurobiologically informed treatment strategies across neuropsychiatric conditions.

Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

PMID: 28434615

DOI: 10.1016/j.biopsych.2017.03.005