Generalized Anxiety Disorder, Comorbid Major Depression and Heart Rate Variability: A Case-Control Study in Taiwan

Abstract

ObjectiveDecreased heart rate variability (HRV) has been reported in generalized anxiety disorder (GAD), but the results are mixed. Little is known about the impact of comorbid major depression (MD) on HRV in GAD patients. Both issues necessitate further investigation.MethodsTwenty unmedicated, physically healthy GAD patients, 20 GAD patients with a secondary diagnosis of MD, 40 MD patients and 60 matched controls were recruited. We used the Hamilton Anxiety Rating Scale and the Hamilton Depression Rating Scale to assess anxiety and depression severity, respectively. Cardiac autonomic function was evaluated by measuring HRV parameters. Frequency-domain indices of HRV were obtained.ResultsThree patient groups had more anxiety and depression symptoms than control subjects, but heart rates (HRs) were significantly elevated only in GAD patients with comorbid depression. Relative to controls, GAD patients had reduced HRV while GAD patients with comorbid depression displayed the greatest reductions in HRV among three patients groups. Correlation analyses revealed anxiety/depression severity significantly associated with HRs, variance, LF-HRV and HF-HRV. However, separately analyzing among individual groups and adjusting for HRV-associated covariables rendered the correlations non-significant.ConclusionOur results suggest that reduction in HRV is a psychophysiological marker of GAD and individuals with comorbid GAD and MD may be distinguished based on psychophysiological correlates (for example, HF-HRV) from non-comorbid GAD patients. Taken into account that comorbid depression may confer increased risks for cardiovascular events in GAD patients, this subgroup of GAD patients may benefit better from cardiovascular risk reduction strategies.

Impact of Comorbid Depressive Disorders on Subjective and Physiological Responses to Emotion in Generalized Anxiety Disorder

“…Although these findings results should be regarded as preliminary pending independent replication with a UDD-only group and a stronger emotion elicitation procedure, the lack of baseline differences in HRV here, in contrast to some previous work (e.g., Chang et al 2013), supports previous findings that suggest that examining change across various contexts (e.g., Hofmann et al 2010) should better allow dysregulated processes that may not be evident at the tonic level to emerge. For instance, the GAD + UDD group reported elevated depressive symptoms and negative affect at the time of the experiment, which may suggest that their observed lack of physiological response to the film clips might be more related to broader deficits in emotion-related phenomena (e.g., amotivation, anhedonia, and emotion context insensitivity) which can limit individuals from fully engaging with their environment.…”

“…Kemp and colleagues (2012) found decreased HRV in patients with MDD, compared to individuals with no psychiatric diagnosis; further, the comorbid MDD + GAD group exhibited the lowest HRV relative to MDD-only and control groups. Likewise, in a sample of Taiwanese patients, individuals with GAD and comorbid MDD showed the lowest levels of HRV relative to individuals with GAD alone, though HRV was reduced in both groups relative to controls (Chang et al 2013). However, both studies focused solely on tonic HRV.…”

Diminished autonomic neurocardiac function in patients with generalized anxiety disorder

“…Previous studies18,19 have reported that GAD has a high rate of comorbidity with other psychiatric disorders, such as major depression, bipolar disorder, and other anxiety disorders. A recent study showed that patients with GAD and comorbid depression had the greatest reductions in HRV among the three groups of GAD without comorbidity, GAD with comorbid major depression, and healthy controls, suggesting a possible cumulative effect 18. In this study, patients were excluded if they met diagnostic criteria for a psychiatric diagnosis other than GAD.…”

“…Previous studies have also shown that benzodiazepines can influence autonomic neurocardiac regulation, reducing central vagal tone, possibly through their interaction with the gamma-aminobutyric acid-A receptor chloride ion channel complex 59. However, there have been other studies reporting that medication-free patients with GAD show significantly reduced HRV measures and that GAD is associated with reduced HRV regardless of the effects of antidepressants 16,18,19. Although, in this study, patients were all medication-free for at least 7 days at the time of HRV assessment, the after-effects of previous pharmacotherapy might have affected the values of the HRV parameters.…”

Genetic influences on heart rate variability

“…Reduced time and frequency domain resting HRV presumably indicating lower vagal tone has been associated with anxiety disorders and related trait measures such as deficits in social approach behavior, impaired stress regulation, and behavioral inhibition (Alvares et al, 2013; Bleil et al, 2008; Chang et al, 2013; Scott and Weems, 2014). A recent meta-analysis of HRV studies in anxiety disorders showed significant HRV reductions in patients relative to controls with a small-to-moderate effect size (Chalmers et al, 2014).…”