@article{1a5e016fffad41729e48fd5f0669d44c,
title = "Are Brain Responses to Emotion a Reliable Endophenotype of Schizophrenia?: An Image-Based Functional Magnetic Resonance Imaging Meta-analysis",
abstract = "Background: Impaired emotion processing constitutes a key dimension of schizophrenia and a possible endophenotype of this illness. Empirical studies consistently report poorer emotion recognition performance in patients with schizophrenia as well as in individuals at enhanced risk of schizophrenia. Functional magnetic resonance imaging studies also report consistent patterns of abnormal brain activation in response to emotional stimuli in patients, in particular, decreased amygdala activation. In contrast, brain-level abnormalities in at-risk individuals are more elusive. We address this gap using an image-based meta-analysis of the functional magnetic resonance imaging literature.Methods: Functional magnetic resonance imaging studies investigating brain responses to negative emotional stimuli and reporting a comparison between at-risk individuals and healthy control subjects were identified. Frequentist and Bayesian voxelwise meta-analyses were performed separately, by implementing a random-effect model with unthresholded group-level T-maps from individual studies as input.Results: In total, 17 studies with a cumulative total of 677 at-risk individuals and 805 healthy control subjects were included. Frequentist analyses did not reveal significant differences between at-risk individuals and healthy control subjects. Similar results were observed with Bayesian analyses, which provided strong evidence for the absence of meaningful brain activation differences across the entire brain. Region of interest analyses specifically focusing on the amygdala confirmed the lack of group differences in this region.Conclusions: These results suggest that brain activation patterns in response to emotional stimuli are unlikely to constitute a reliable endophenotype of schizophrenia. We suggest that future studies instead focus on impaired functional connectivity as an alternative and promising endophenotype.",
keywords = "Amygdala, Emotions, Endophenotype, Functional MRI, Meta-analysis, Schizophrenia",
author = "Fiorito, {Anna M.} and Andr{\'e} Aleman and Giuseppe Blasi and Josiane Bourque and Hengyi Cao and Chan, {Raymond C.K.} and Asadur Chowdury and Patricia Conrod and Diwadkar, {Vaibhav A.} and Goghari, {Vina M.} and Salvador Guinjoan and Gur, {Raquel E.} and Gur, {Ruben C.} and Kwon, {Jun Soo} and Johannes Lieslehto and Lukow, {Paulina B.} and Andreas Meyer-Lindenberg and Gemma Modinos and Tiziana Quarto and Spilka, {Michael J.} and Venkataram Shivakumar and Ganesan Venkatasubramanian and Mirta Villarreal and Yi Wang and Wolf, {Daniel H.} and Yun, {Je Yeon} and Eric Fakra and Guillaume Sescousse",
note = "Funding Information: GB has received lecture fees from Lundbeck. EF has received consultancy fees from Bristol Myers Squibb, Janssen-Cilag, Lilly, Lundbeck, Otsuka Pharmaceutical Co., Ltd., Recordatti, and Sanofi and has lectured for AbbVie, AstraZeneca, Bristol Myers Squibb, Janssen-Cilag, Lundbeck, Otsuka, MSD, and Sanofi. AM-L has received grants from the Federal Ministry of Education and Research; the German Research Foundation; the Seventh Framework Programme of the European Union and the Ministry of Science, Research, Australia; and the Arts of the State of Baden-W{\"u}rttemberg. All other authors report no biomedical financial interest or potential conflicts of interest. Funding Information: AMF was supported by the Fondation Pierre Deniker. EF was supported by the Fondation de France. GS was supported by the Agence Nationale de la Recherche (Grant No. ANR-19-CE37-0012-01) and the Fondation NRJ-Institut de France. The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. AMF and GS have full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: AMF, GS, and EF. Acquisition (sharing data and/or performing additional analyses): all authors but AMF, GS, and EF. Analyses and interpretation of data: AMF, GS, and EF. Statistical analyses: AMF, GS, and EF. Drafting of the manuscript: AMF, GS, and EF. Critical revision of the manuscript for important intellectual content: all authors. Obtained funding: EF. Authors who were exclusively involved in data acquisition and critical revision of the manuscript are listed following alphabetical order in the authorship list. We thank Hyemin Han, Educational Psychology Program, University of Alabama, Tuscaloosa, AL, for his help with the BayesFactorFMRI toolbox. A previous version of this article was published as a preprint on bioRxiv: https://doi.org/10.1101/2022.05.31.22275506. GB has received lecture fees from Lundbeck. EF has received consultancy fees from Bristol Myers Squibb, Janssen-Cilag, Lilly, Lundbeck, Otsuka Pharmaceutical Co. Ltd. Recordatti, and Sanofi and has lectured for AbbVie, AstraZeneca, Bristol Myers Squibb, Janssen-Cilag, Lundbeck, Otsuka, MSD, and Sanofi. AM-L has received grants from the Federal Ministry of Education and Research; the German Research Foundation; the Seventh Framework Programme of the European Union and the Ministry of Science, Research, Australia; and the Arts of the State of Baden-W{\"u}rttemberg. All other authors report no biomedical financial interest or potential conflicts of interest. Funding Information: AMF was supported by the Fondation Pierre Deniker . EF was supported by the Fondation de France . GS was supported by the Agence Nationale de la Recherche (Grant No. ANR-19-CE37-0012-01) and the Fondation NRJ-Institut de France. Publisher Copyright: {\textcopyright} 2022 Society of Biological Psychiatry",
year = "2023",
month = jan,
day = "15",
doi = "10.1016/j.biopsych.2022.06.013",
language = "English",
volume = "93",
pages = "167--177",
journal = "Biological Psychiatry",
issn = "1873-2402",
publisher = "ELSEVIER SCIENCE INC",
number = "2",
}