Autonomic nervous system dysfunction in psychiatric disorders and the impact of psychotropic medications: a systematic review and meta-analysis

Alvares, Gail A.; Quintana, Daniel S.; Hickie, Ian B.; Guastella, Adam J.

doi:10.1503/jpn.140217

Cited by 503Heart Rate Variability and Autonomic ControlCardiac Health and Mental HealthVagus Nerve Stimulation Research

Autonomic nervous system dysfunction in psychiatric disorders and the impact of psychotropic medications: a systematic review and meta-analysis

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Alvares, Gail A., Quintana, Daniel S., Hickie, Ian B., Guastella, Adam J.·2016·Journal of Psychiatry and Neuroscience

DOI 10.1503/jpn.140217PMC PMC4764485

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Abstract

Background: Autonomic nervous system (ANS) dysfunction is a putative underlying mechanism for increased cardiovascular disease risk in individuals with psychiatric disorders. Previous studies suggest that this risk may be related to psychotropic medication use. In the present study we systematically reviewed and analyzed published studies of heart rate variability (HRV), measuring ANS output, to determine the effect of psychiatric illness and medication use. Methods: We searched for studies comparing HRV in physically healthy adults with a diagnosed psychiatric disorder to controls and comparing HRV pre- and post-treatment with a psychotropic medication. Results: In total, 140 case–control (mood, anxiety, psychosis, dependent disorders, k = 151) and 30 treatment (antidepressants, antipsychotics; k = 43) studies were included. We found that HRV was reduced in all patient groups compared to controls (Hedges g = −0.583) with a large effect for psychotic disorders (Hedges g = −0.948). Effect sizes remained highly significant for medication-free patients compared to controls across all disorders. Smaller and significant reductions in HRV were observed for specific antidepressants and antipsychotics. Limitations: Study quality significantly moderated effect sizes in case–control analyses, underscoring the importance of assessing methodological quality when interpreting HRV findings. Conclusion: Combined findings confirm substantial reductions in HRV across psychiatric disorders, and these effects remained significant even in medication-free individuals. Reductions in HRV may therefore represent a significant mechanism contributing to elevated cardiovascular risk in individuals with psychiatric disorders. The negative impact of specific medications on HRV suggest increased risk for cardiovascular disease in these groups, highlighting a need for treatment providers to consider modifiable cardiovascular risk factors to attenuate this risk.

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Low resting-state vagal modulation or parasympathetic activity is also observed in other psychiatric conditions such as mood disorders, anxiety disorders, and autism spectrum disorder.
“Low resting-state vagal modulation/parasympathetic activity is also observed in a variety of other psychiatric conditions, such as mood disorders, anxiety disorders and autism spectrum disorder30,45.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [30]
The Quantitative analyses section reports reduced heart-rate variability in mood and anxiety disorder groups compared with controls. The Description of included studies lists the diagnostic groups analyzed but does not include autism spectrum disorder, so this source does not support that part of the claim. The Outcome measures section also includes both resting-state and 24-hour recordings, rather than resting-state measurements alone. No page numbers are available in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measured
ANS function is purportedly modulated by the core-ICNs and one of the most robust ANS disturbances found in IDs is cardiac dysautonomia in the form of reduced HRV.
“ANS function is purportedly modulated by the core-ICNs and one of the most robust ANS disturbances found in IDs is cardiac dysautonomia in the form of reduced HRV [52, 96, 103, 280, 282–293].”
From Infraslow closed-loop brain training for anxiety and depression (ISAD): a protocol for a randomized, double-blind, sham-controlled pilot trial in adult females with internalizing disorders (2022) · cites this paper as [52]
The ‘ANS functioning in patients with psychiatric disorders’ section reports moderately reduced HRV versus controls, including in anxiety and mood disorders. The paper does not establish that core intrinsic connectivity networks modulate ANS function, so that part of the sentence is unsupported by this source. Page numbers were not supplied for these passages. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Autonomic dysfunction is a characteristic feature of other psychiatric illnesses such as anxiety and mood disorders, but it appears greatest in psychotic disorders.
“It is also noteworthy to add that autonomic dysfunction is a characteristic feature of other psychiatric illnesses, such as anxiety and mood disorders; however, it appears that autonomic dysfunction is greatest in psychotic disorders30.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [30]
Autonomic nervous system dysfunction is consistently reported across psychopathologies.
“possibly helping to explain the ANS dysfunction consistently reported across psychopathologies [51, 52].”
From Infraslow closed-loop brain training for anxiety and depression (ISAD): a protocol for a randomized, double-blind, sham-controlled pilot trial in adult females with internalizing disorders (2022) · cites this paper as [52]
Cardiovascular disease is the leading cause of mortality in people with mental illness.
“This has significant clinical implications considering that cardiovascular disease is the leading cause of mortality in people with mental illness [52, 294, 295].”
From Infraslow closed-loop brain training for anxiety and depression (ISAD): a protocol for a randomized, double-blind, sham-controlled pilot trial in adult females with internalizing disorders (2022) · cites this paper as [52]

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Authors: Alvares, G. A., Quintana, D. S., Hickie, I. B., & Guastella, A. J.
Affiliations: Oslo University Hospital (NO)
ORCID: Alvares, Gail A.
Quintana, Daniel S.
Hickie, Ian B.
Guastella, Adam J.
Venue: Journal of Psychiatry and Neuroscience
Publisher: Canadian Science Publishing
Published: 2016-03
Volume: 41
Issue: 2
Pages: 89-104
ISSN: 1180-4882 (ISSN-L)
1488-2434
DOI: 10.1503/jpn.140217
PMC: PMC4764485
OpenAlex: W2419517449
Cited by: 503
References: 257
Citations by year: 2026: 43 · 2025: 62 · 2024: 53 · 2023: 66 · 2022: 53 · 2021: 61 · 2020: 43 · 2019: 37 · 2018: 36 · 2017: 29 · 2016: 16 · 2015: 2
FWCI: 6.95
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.nrcresearchpress.com/page/about/CorporateTextAndDataMining (tdm)
Locations: Journal of Psychiatry and Neuroscience (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
UWA Profiles and Research Repository (UWA) (publishedVersion, other-oa)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Keywords: autonomic dysfunction, heart rate variability, mental illness, psychotropic drugs, cardiovascular risk, antidepressants, antipsychotic drugs, psychosis, mood disorders, anxiety disorders, substance use disorders
MeSH terms: Autonomic Nervous System Diseases, Mental Disorders, Humans, Psychotropic Drugs

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Autonomic nervous system dysfunction in psychiatric disorders and the impact of psychotropic medications: a systematic review and meta-analysis

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