Resting vagal activity in schizophrenia: Meta-analysis of heart rate variability as a potential endophenotype
Open accessAbstract
Background: Cardiac vagal tone, indexed by heart rate variability (HRV), is a proxy for the functional integrity of feedback mechanisms integrating central and peripheral physiology. Aims: To quantify differences in HRV in individuals with schizophrenia compared with healthy controls. Method: Databases were systematically searched for studies eligible for inclusion. Random effect meta-analyses of standardised mean differences were calculated for vagal activity indicated by high-frequency HRV and the root mean square of successive R–R interval differences (RMSSD). Results: Thirty-four studies were included. Significant main effects were found for high-frequency HRV (P = 0.0008; Hedges' g =–0.98, 95% CI −1.56 to −0.41, k = 29) and RMSSD (P<0.0001; g =–0.91, 95% CI −1.19 to −0.62, k = 24), indicating lower vagal activity in individuals with schizophrenia than in healthy controls. Considerable heterogeneity was evident but effects were robust in subsequent sensitivity analyses. Conclusions: Given the association between low HRV, threat processing, emotion regulation and executive functioning, reduced vagal tone may be an endophenotype for the development of psychotic symptoms.
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The meta-analysis did not find any difference in heart rate variability markers of parasympathetic functioning between antipsychotic-naïve and medicated patients with schizophrenia.
“As mentioned earlier, the meta-analysis did not find any difference in HRV markers of parasympathetic functioning between AP-naïve and medicated patients with SCZ.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [27]
The Meta-regressions and subgroup analyses section reports no significant effect of medication status on high-frequency HRV or RMSSD findings, and the Discussion says reduced vagal activity was found in both medicated and unmedicated groups. But the claim specifies antipsychotic-naïve patients: the Discussion cautions that, except in two first-episode studies, some participants in the unmedicated studies had previously received antipsychotics. The analysis also compared medication-status effects on patient-versus-control differences, not HRV directly between the two patient groups. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSubgroup analyses did not reveal differences in heart rate variability outcomes between inpatients and outpatients with schizophrenia.
“Similarly, subgroup analyses did not reveal any differences in HRV outcomes between inpatients and outpatients.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [27]
Compared with non-psychiatric healthy controls, patients with schizophrenia exhibit reduced heart rate variability and vagal cardiac control, including lower HF-HRV and RMSSD.
“In comparison to non-psychiatric HCs, patients with SCZ exhibit reduced HRV and vagal cardiac control26.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [27]
Meta-regressions did not show significant effects of age, illness duration, or medication status on heart rate variability differences between schizophrenia patients and healthy controls.
“Subsequent meta-regressions did not show any significant effects as a function of age, illness duration, or medication status (medicated vs. unmedicated).”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [27]
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Self-citation
- Authors
- Clamor, A., Lincoln, T. M., Thayer, J. F., & Koenig, J.
- Affiliations
- Universität Hamburg (DE)
- Corresponding author
- Clamor, Annika
- Venue
- British Journal of Psychiatry
- Publisher
- Royal College of Psychiatrists
- Published
- 2016-01
- Volume
- 208
- Issue
- 1
- Pages
- 9-16
- ISSN
- 0007-1250 (ISSN-L)
- 1472-1465
- OpenAlex
- W2236535974
- Cited by
- 167
- References
- 65
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 22 · 2023: 18 · 2022: 16 · 2021: 17 · 2020: 20 · 2019: 11 · 2018: 16 · 2017: 9 · 2016: 11 · 2015: 4
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The British Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ohio State University
- Deutscher Akademischer Austauschdienst
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Keywords
- schizophrenia, heart rate variability, vagal tone, endophenotypes, high-frequency HRV, RMSSD, cardiac autonomic function, threat processing, emotion regulation, executive function, psychotic symptoms
- MeSH terms
- Brain, Emotions, Heart Rate, Humans, Schizophrenia, Vagus Nerve, Executive Function, Endophenotypes
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