Heart Rate Variability a Biomarker of Bipolar Disorder Severity?

Liam Davenport

April 26, 2021

Reduced heart rate variability (HRV) is associated with severity in patients with bipolar disorder (BD), in terms of both individual and overall measures of disease severity, new research suggests.

In a study that included 53 adult patients with BD I or II, investigators used the Illness Burden Index (IBI) a novel measure developed by the research team to assess patients. Results showed that the higher the BD disease severity, the lower the HRV.

The new IBI is "an important component of this study, because by integrating several different indicators of illness burden in bipolar disorder...we were able to create a single measure that was associated with HRV," study investigator Abigail Ortiz, MD, Center for Addiction & Mental Health, Toronto, Canada, said during a presentation at the virtual European Psychiatric Association (EPA) 2021 Congress.

"We wanted to compress a lot of clinical information in a single number [in order to] make it very clinician-friendly," Ortiz told Medscape Medical News. "We are aware that this result needs to be replicated in a larger sample but the IBI could be a clinically useful index to assess clinical trajectories in bipolar disorder," she added.

The findings were also published online March 30 in the Journal of Psychosomatic Research.

HRV and Morbidity, Mortality

BD is associated with premature death, and ischemic heart disease is the main cause of excess mortality, Ortiz noted. HRV is an indicator of cardiac autonomic function and has been shown previously to be a predictor of morbidity and mortality in patients with, and without, cardiovascular disease.

Specifically, healthy individuals have a high degree of HRV, reflecting their ability to quickly adapt to the physical or psychological demands of their environment. On the other hand, reduced HRV, which is found in many illnesses, "is associated with fatal arrhythmias, myocardial infarction, and sudden death," said Ortiz.

The investigators examined the link between HRV and disease burden in patients with BD because previous studies examining this association have yielded conflicting results, she added.

The current study included 53 patients with bipolar I and II disorder. All were issued a wearable device — a sports t-shirt that incorporated an EKG monitor (Zephyr, Medtronic) — and wore it for 24 hours.

Researchers collected baseline clinical and demographic characteristics, and patients completed several scales to assess functional cardiovascular capacity and illness-burden factors including illness duration, number and type of previous episodes, and family history.

From this data, the investigators developed IBI. They integrated 10 disease factors using a weighted geometric mean that emphasized information such as number of previous episodes, a history of psychosis, past suicide attempts, and a family history of suicide.

The majority (66%) of the participants were women and the average age was 44 years. In addition, 90% were White and the average body mass index was 29.3 kg/m2.

Just over half (55%) of the patients had bipolar II disorder and 60% were euthymic at study entry. Average age of disease onset was 20.8 years, and the mean number of lifetime episodes was 11.6. A family history of bipolar disorder was reported by 36% of participants, 39% had a family history of major depressive disorder (MDD), and 36% had a family history of suicide.

Inverse Relationship

"There were four main clinical variables that were correlated with reduced HRV," said Ortiz. These included illness duration, lifetime number of depressive episodes, duration of the most severe manic or hypomanic episode, and family history of suicide.

Results showed that the greater the BD severity, the lower the HRV, which was significant for two measures of HRV, Oriz said.

The first measure was the root mean square of the successive differences (RMSSD), which estimates the short-term components of HRV. The second measure was the standard deviation of the normal-to-normal intervals (SNDD), which estimates overall HRV.

The RMSSD was also significantly associated with individual measures of disease burden, specifically age at onset (P = .009), comorbid anxiety (P = .006), and family history of suicide (P = .01).

The SNDD was significantly associated with lifetime number of depressive episodes (P = .02), lifetime number of depressive and manic/hypomanic episodes (P = .01), age at onset (P = .05), and family history of suicide (P = .02).

"Moreover, in participants who were experiencing a depressive episode, the score on the Montgomery–Åsberg Depression Rating Scale was negatively correlated with HRV," Ortiz told meeting attendees.

Ortiz told Medscape Medical News her team plans to use the IBI in future studies to assess, for example, the association between disease burden on the index and cognitive function.

They would also like to determine whether those with a very high score of 3.5 or 4 might be "better responders to lithium or to antipsychotics" or to combination therapy. They also plan to examine whether there is a relationship between IBI scores and common gene variants associated with BD.

Links Mental, Physical Health

Commenting on the findings for Medscape Medical News, Andrew Kemp, PhD, psychology professor at Swansea University, Swansea, United Kingdom, described the study as "important work that shows associations with a number of different clinical variables."

"I agree with the general conclusion that heart rate variability can be used as a clinical index to assess the trajectories of these patients," said Kemp, who was not involved in the study.

In fact, the findings fit with his previous research showing that mania is associated with increased heart rate and decreased HRV compared with euthymia. They also found that, compared with their healthy peers, patients with BD have high sympathetic heart modulation, reduced vagal modulation, and lower complexity of HRV.

One major question has been whether reductions in HRV are driven by the disorder or the treatment of the disorder," Kemp said. His research in MDD and generalized anxiety disorder has shown that "antidepressants have adverse effects but the disorder itself is also associated with reduced heart rate variability," he added.

BD is included in the list of mental health disorders associated with reduced HRV, suggesting that HRV is a "transdiagnostic marker of mental disorder" associated with emotion and its regulation, and an individual's sense of meaning, purpose in life, and longevity, said Kemp.

As such, HRV can be regarded as a structural link between mental and physical health, and provides a "psycho-physiological index of well-being [that supports our] capacity to connect with ourselves, others, and nature" — and to manage environmental stressors, Kemp concluded.

The study was funded by a grant from the University of Ottawa Department of Psychiatry Research Funds and was supported in part by Academic Scholars Awards from the Department of Psychia­try, University of Toronto and by the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto. The study authors and Kemp have disclosed no relevant financial relationships.

European Psychiatric Association (EPA) 2021 Congress: Abstract O006. Presented April 10, 2021.

J Psychosom Res. Published online March 30, 2021. Abstract

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