Cardiac Phenotypes and Endophenotypes in Schizophrenia : A systematic Review

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Published Nov 9, 2025
https://doi.org/10.62438/tunismed.v103i9.6395
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Vol. 103 No. 9 (2025): Tunis Med sept 2025

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Amine Larnaout
Department of Psychiatry D, Research Laboratory LR18SP03 : Maladies Neurodégénératives et Troubles Psychiatriques, 2010, Manouba, Razi Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, 1002, Tunisia
Zeynab Jebberi
Cardiology Department,La Rabta University Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar,1002, Tunis, Tunisia
Mohamed Salah Hamdi
Internal Medicine Department , Charles Nicolle University Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, 1002, Tunis, Tunisia
Rania Lansari
Department of Psychiatry D, Research Laboratory LR18SP03 : Maladies Neurodégénératives et Troubles Psychiatriques, 2010, Manouba, Razi Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, 1002, Tunisia
Mohamed Sami Mourali
Cardiology Department,La Rabta University Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar,1002, Tunis, Tunisia
Wahid Melki
Department of Psychiatry D, Research Laboratory LR18SP03 : Maladies Neurodégénératives et Troubles Psychiatriques, 2010, Manouba, Razi Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, 1002, Tunisia

Abstract

Background: Schizophrenia is increasingly recognized as a multisystemic disorder. Cardiac anomalies, including autonomic, electrophysiological, and structural heart abnormalities, are frequently reported in patients with schizophrenia. However, the distinction between phenotypes and endophenotypes remains unclear.


Methods: In this review, we synthesized clinical, neurobiological, and genetic evidence to assess cardiac alterations in schizophrenia and evaluate their potential as endophenotypes.


Results: Autonomic dysfunction, especially reduced heart rate variability (HRV) and impaired parasympathetic regulation, emerged as the most consistent cardiac phenotype, and the only one that fulfills the criteria for an endophenotype. In contrast, electrophysiological anomalies such as QT/QTc prolongation, T-wave changes, and some structural heart anomalies show genetic associations with schizophrenia but lack sufficient heritability and longitudinal data to be classified as endophenotypes.


Conclusion: Among all cardiac anomalies reported in schizophrenia, autonomic dysfunction, particularly HRV impairment, was the only one that fulfilled the endophenotype criteria. However, most of the reviewed studies were observational, which limits the robustness of our conclusions. Future heritability and multi-omic studies are needed to understand the complex pathogenomic interlink between mental and heart diseases.

Keywords:

Schizophrenia, heart, anomalies, phenotypes, endophenotypes

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