Abstract

Functional neuroimaging and schizophrenia: a view towards effective connectivity modeling and polygenic risk

Neuroimágenes funcionales y esquizofrenia: una mirada hacia el modelo de conectividad efectiva y el riesgo poligénico

Schizophrénie et neuroimagerie fonctionnelle: point de vue sur la modélisation de la connectivité effective et le risque polygénique

Rebecca Birnbaum, MD

Rebecca Birnbaum, Lieber Institute for Brain Development, Johns Hopkins Medical Campus (Rebecca Birnbaum, Daniel R. Weinberger); Johns Hopkins School of Medicine, Department of Psychiatry, Baltimore, Maryland, USA;

Daniel R. Weinberger, MD^*

Daniel R. Weinberger, Lieber Institute for Brain Development, Johns Hopkins Medical Campus; Johns Hopkins School of Medicine, Departments of Neurology, and Neuroscience, and The Institute of Genetic Medicine; Johns Hopkins School of Medicine, Department of Psychiatry, Baltimore, Maryland, USA;

^* E-mail: drweinberger/at/libd.org

Author information ► Copyright and License information ►

Copyright: © 2013 Institut la Conférence Hippocrate - Servier Research Group

This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Go to:

Abstract

We review critical trends in imaging genetics as applied to schizophrenia research, and then discuss some future directions of the field. A plethora of imaging genetics studies have investigated the impact of genetic variation on brain function, since the paradigm of a neuroimaging intermediate phenotype for schizophrenia first emerged. It was initially posited that the effects of schizophrenia susceptibility genes would be more penetrant at the level of biologically based neuroimaging intermediate phenotypes than at the level of a complex and phenotypically heterogeneous psychiatric syndrome. The results of many studies support this assumption, most of which show single genetic variants to be associated with changes in activity of localized brain regions, as determined by select cognitive controlled tasks. From these basic studies, functional neuroimaging analysis of intermediate phenotypes has progressed to more complex and realistic models of brain dysfunction, incorporating models of functional and effective connectivity, including the modalities of psycho-physiological interaction, dynamic causal modeling, and graph theory metrics. The genetic association approaches applied to imaging genetics have also progressed to more sophisticated multivariate effects, including incorporation of two-way and three-way epistatic interactions, and most recently polygenic risk models. Imaging genetics is a unique and powerful strategy for understanding the neural mechanisms of genetic risk for complex CNS disorders at the human brain level.

Keywords: schizophrenia, intermediate phenotype, functional neuroimaging, functional connectivity, effective connectivity, polygenic risk score

Go to: