Elsevier

Biological Psychiatry

Volume 93, Issue 2, 15 January 2023, Pages 167-177
Biological Psychiatry

Archival Report
Are Brain Responses to Emotion a Reliable Endophenotype of Schizophrenia? An Image-Based Functional Magnetic Resonance Imaging Meta-analysis

https://doi.org/10.1016/j.biopsych.2022.06.013Get rights and content

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.

Section snippets

Inclusion of Studies

The meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines (39) (see Table S1 for the checklist). The protocol for this meta-analysis was not preregistered. We performed a comprehensive literature search using PubMed and Web of Science. The search (which identified records published until April 15, 2020) used a combination of terms constructed according to 4 stems relating to 1) schizophrenia (schizophren∗,

Results

Whole-brain maps of within- and between-group meta-analyses are available on NeuroVault (52) for both frequentist and Bayesian analyses (https://neurovault.org/collections/CRLVVOUU/).

Discussion

Our meta-analysis aimed to investigate whether brain activation in response to negative emotional stimuli could be considered as an endophenotype of schizophrenia. Results showed that healthy control subjects and individuals at risk of schizophrenia present a remarkably similar pattern of brain activation in response to processing negative emotional stimuli. These similarities were observed in salient regions of the emotion processing network including the amygdala, thalamus, and inferior

Acknowledgments and Disclosures

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

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