Nonlinear Complexity and Spectral Analyses of Heart Rate Variability in Medicated and Unmedicated Patients with Schizophrenia1
Open accessAbstract
Objective: Heart rate variability (HRV) reflects functioning of the autonomic nervous system and possibly also regulation by the neural limbic system, abnormalities of which have both figured prominently in various etiological models of schizophrenia, particularly those that address patients’ vulnerability to stress in connection to psychosis onset and exacerbation. This study provides data on cardiac functioning in a sample of schizophrenia patients that were either medication free or on atypical antipsychotics, as well as cardiac data on matched healthy controls. We included a medication-free group to investigate whether abnormalities in HRV previously reported in the literature and associated with atypical antipsychotics were solely the effect of medications or whether they might be a feature of the illness (or psychosis) itself. Method: We collected 24-hour ECGs on 19 patients and 24 controls. Of the patients, 9 were medication free and 10 were on atypical antipsychotics. All subject groups were matched for age and gender. Patient groups showed equivalent symptom severity and type, as well as duration of illness. We analyzed the data using nonlinear complexity (symbolic dynamic) HRV analyses as well as standard and relative spectral analyses. Results: For the medication-free patients as compared to the healthy controls, our data show decreased R–R intervals during sleep, and abnormal suppression of all frequency ranges, but particularly the low frequency range, which persisted even after adjusting the spectral data for the mean R–R interval. This effect was exacerbated for patients on atypical antipsychotics. Likewise, nonlinear complexity analysis showed significantly impaired HRV for medication-free patients that was exacerbated in the patients on atypical antipsychotics. Conclusions: Altogether, the data suggest a pattern of significantly decreased cardiac vagal function of patients with schizophrenia as compared to healthy controls, apart from and beyond any differences due to medication side effects. The data additionally confirm earlier reports of a deleterious effect of atypical antipsychotics on HRV, which may exacerbate an underlying vulnerability in patients. These results support previous evidence that autonomic abnormalities may be a core feature of the illness (or psychosis), and that an even more conservative approach to cardiac risk in schizophrenia than previously thought may therefore be clinically appropriate.
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Patients with schizophrenia have relatively preserved sympathetic functioning and do not differ significantly from healthy controls.
“Consistent with the findings of several previous studies31–34, these results imply that patients with SCZ have relatively preserved sympathetic functioning and do not differ significantly with HCs.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [31]
The Conclusions (page not available) report no significant between-group differences in LF/HF ratios, supporting a narrower claim about that measure. They also report reduced sympathetic inhibition during sleep in patients, while the Results find significant differences in nearly all cardiac variables. The paper therefore does not establish broadly preserved sympathetic functioning or an overall absence of differences from healthy controls. (LLM, conf=0.85)
Experimental — accuracy not yet measuredOne study found no association between HRV and any of the symptom domains of schizophrenia, as assessed by the PANSS.
“Only one study was identified that provided contradictory results, indicating no association between HRV and any of the symptom domains of SCZ, as assessed by the PANSS31.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [31]
The Results (page not provided) say cardiac variables were unrelated to several specific PANSS-described symptoms. But they also report a trend toward an association for suspiciousness and feelings of persecution, so the unqualified claim of no association with any symptom domain overstates the finding. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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271 – Schizophrenia – a parameters' game?
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- Authors
- Mujica-Parodi, L. R., Yeragani, V., & Malaspina, D.
- Affiliations
- Stony Brook University (US)
- Wayne State University (US)
- New York State Psychiatric Institute (US)
- Venue
- Neuropsychobiology
- Publisher
- S. Karger AG
- Published
- 2005
- Volume
- 51
- Issue
- 1
- Pages
- 10-15
- ISSN
- 0302-282X (ISSN-L)
- 1423-0224
- PMC
- PMC2983101
- OpenAlex
- W2096949188
- Cited by
- 107
- References
- 33
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 1 · 2017: 5 · 2016: 5 · 2015: 4 · 2014: 8 · 2013: 7 · 2012: 11
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuropsychobiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH01699 K24, K24MH001699)
- 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
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
- Keywords
- heart rate variability, schizophrenia, atypical antipsychotics, vagal function, autonomic nervous system, nonlinear complexity, symbolic dynamics, spectral analysis, heart disease risk, adverse drug reactions, sleep, psychosis
- MeSH terms
- Adult, Analysis of Variance, Demography, Electrocardiography, Female, Heart Rate, Humans, Male, Middle Aged, Schizophrenia, Spectrum Analysis, Antipsychotic Agents, Nonlinear Dynamics
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