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

Fiorito, Anna M.; Alemán, André; Blasi, Giuseppe; Bourque, Josiane; Cao, Hengyi; Chan, Raymond C. K.; Chowdury, Asadur; Conrod, Patricia J.; Diwadkar, Vaibhav A.; Goghari, Vina M.; Guinjoan, Salvador M.; Gur, Raquel E.; Gur, Ruben C.; Kwon, Jun Soo; Lieslehto, Johannes; Lukow, Paulina; Meyer‐Lindenberg, Andreas; Modinos, Gemma; Quarto, Tiziana; Spilka, Michael J.; Shivakumar, Venkataram; Venkatasubramanian, Ganesan; Villarreal, Mirta F.; Wang, Yi; Wolf, Daniel H.; Yun, Je-Yeon; Fakra, Éric; Sescousse, Guillaume

doi:10.1016/j.biopsych.2022.06.013

Cited by 6 publications

(6 citation statements)

References 82 publications

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“…This meta-analysis was conducted following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA 20 ), using an approach similar to our recent work 17 . The protocol for this meta-analysis was not pre-registered.…”

Section: Methodsmentioning

confidence: 99%

“…However, these findings have not been replicated in more recent studies with larger sample sizes or confirmed by meta-analyses 13 – 16 . To date, neuroimaging studies have mainly focused on the general processing of emotional faces, with recent meta-analytical work showing that brain activity patterns in individuals at enhanced risk are similar to healthy controls 17 . Only a few studies have investigated the neural mechanisms associated with the processing of neutral faces in first-degree relatives.…”

Section: Introductionmentioning

confidence: 99%

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Blunted brain responses to neutral faces in healthy first-degree relatives of patients with schizophrenia: an image-based fMRI meta-analysis

Fiorito,

Blasi,

Brunelin

et al. 2024

Schizophr

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Schizophrenia is characterized by the misattribution of emotional significance to neutral faces, accompanied by overactivations of the limbic system. To understand the disorder’s genetic and environmental contributors, investigating healthy first-degree relatives is crucial. However, inconsistent findings exist regarding their ability to recognize neutral faces, with limited research exploring the cerebral correlates of neutral face processing in this population. Thus, we here investigated brain responses to neutral face processing in healthy first-degree relatives through an image-based meta-analysis of functional magnetic resonance imaging studies. We included unthresholded group-level T-maps from 5 studies comprising a total of 120 first-degree relatives and 150 healthy controls. In sensitivity analyses, we ran a combined image- and coordinate-based meta-analysis including 7 studies (157 first-degree relatives, 207 healthy controls) aiming at testing the robustness of the results in a larger sample of studies. Our findings revealed a pattern of decreased brain responses to neutral faces in relatives compared with healthy controls, particularly in limbic areas such as the bilateral amygdala, hippocampus, and insula. The same pattern was observed in sensitivity analyses. These results contrast with the overactivations observed in patients, potentially suggesting that this trait could serve as a protective factor in healthy relatives. However, further research is necessary to test this hypothesis.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Blunted brain responses to neutral faces in healthy first-degree relatives of patients with schizophrenia: an image-based fMRI meta-analysis

Fiorito,

Blasi,

Brunelin

et al. 2024

Schizophr

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“…Meta‐analyses of fMRI studies using emotion perception and theory of mind tasks in schizophrenia compared to healthy control groups have demonstrated altered brain activation in regions of the simulation and mentalizing networks 221‐225 . Decreased activation in regions of the mentalizing network have also been identified in a meta‐analysis of fMRI studies of theory of mind in individuals with CHR 226 , though no differences in brain activation were found between at‐risk and control groups in a recent meta‐analysis of fMRI studies examining negative emotion perception 227 .…”

Section: Diagnostic Markersmentioning

confidence: 99%

Functional magnetic resonance imaging in schizophrenia: current evidence, methodological advances, limitations and future directions

Voineskos,

Hawco,

Neufeld

et al. 2024

World Psychiatry

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Functional neuroimaging emerged with great promise and has provided fundamental insights into the neurobiology of schizophrenia. However, it has faced challenges and criticisms, most notably a lack of clinical translation. This paper provides a comprehensive review and critical summary of the literature on functional neuroimaging, in particular functional magnetic resonance imaging (fMRI), in schizophrenia. We begin by reviewing research on fMRI biomarkers in schizophrenia and the clinical high risk phase through a historical lens, moving from case‐control regional brain activation to global connectivity and advanced analytical approaches, and more recent machine learning algorithms to identify predictive neuroimaging features. Findings from fMRI studies of negative symptoms as well as of neurocognitive and social cognitive deficits are then reviewed. Functional neural markers of these symptoms and deficits may represent promising treatment targets in schizophrenia. Next, we summarize fMRI research related to antipsychotic medication, psychotherapy and psychosocial interventions, and neurostimulation, including treatment response and resistance, therapeutic mechanisms, and treatment targeting. We also review the utility of fMRI and data‐driven approaches to dissect the heterogeneity of schizophrenia, moving beyond case‐control comparisons, as well as methodological considerations and advances, including consortia and precision fMRI. Lastly, limitations and future directions of research in the field are discussed. Our comprehensive review suggests that, in order for fMRI to be clinically useful in the care of patients with schizophrenia, research should address potentially actionable clinical decisions that are routine in schizophrenia treatment, such as which antipsychotic should be prescribed or whether a given patient is likely to have persistent functional impairment. The potential clinical utility of fMRI is influenced by and must be weighed against cost and accessibility factors. Future evaluations of the utility of fMRI in prognostic and treatment response studies may consider including a health economics analysis.

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“…In addition, there are also significant knowledge gaps between each of these five major levels of analysis: (1) from molecular to cellular; (2) from cellular to neural networks; (3) from neural networks to brain systems; (4) from brain systems to neurocognitive functions; and (5) from neurocognitive functions to experiential phenomena. Empirical mapping between many of these levels remains limited to date [7,8].…”

Section: Recent Search For Psychosis Biomarkersmentioning

confidence: 99%

Unique Challenges in Biomarkers for Psychotic Disorders

Chen,

Wong

2024

Brain Sciences

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

Cited by 6 publications

References 82 publications

Blunted brain responses to neutral faces in healthy first-degree relatives of patients with schizophrenia: an image-based fMRI meta-analysis

Blunted brain responses to neutral faces in healthy first-degree relatives of patients with schizophrenia: an image-based fMRI meta-analysis

Functional magnetic resonance imaging in schizophrenia: current evidence, methodological advances, limitations and future directions

Unique Challenges in Biomarkers for Psychotic Disorders

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