Chuan Chia Chang

Distinguishing bipolar II depression from unipolar major depressive disorder: Differences in heart rate variability

Abstract Objectives. Bipolar II (BPII) depression is commonly misdiagnosed as unipolar depression (UD); however, an objective and reliable tool to differentiate between these disorders is lacking. Whether cardiac autonomic function can be used as a biomarker to distinguish BPII from UD is unknown. Methods. We recruited 116 and 591 physically healthy patients with BPII depression and UD, respectively, and 421 healthy volunteers aged 20–65 years. Interviewer and self-reported measures of depression/anxiety severity were obtained. Cardiac autonomic function was evaluated by heart rate variability (HRV) and frequency-domain indices of HRV. Results. Patients with BPII depression exhibited significantly lower mean R–R intervals, variance (total HRV), low frequency (LF)-HRV, and high frequency (HF)-HRV but higher LF/HF ratio compared to those with UD. The significant differences remained after adjusting for age. Compared to the controls, the patients with BPII depression showed cardiac sympathetic excitation with reciprocal vagal impairment, whereas the UD patients showed only vagal impairment. Depression severity independently contributed to decreased HRV and vagal tone in both the patients with BPII depression and UD, but increased sympathetic tone only in those with BPII depression. Conclusions. HRV may aid in the differential diagnosis of BPII depression and UD as an adjunct to diagnostic interviews.

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

Objective Decreased 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. Methods Twenty 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. Results Three 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. Conclusion Our 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.

Heart rate variability in unmedicated patients with bipolar disorder in the manic phase

Decreased heart rate variability (HRV) has been proposed in bipolar disorder. To date, there has been no adequate study that has investigated resting HRV in unmedicated patients with bipolar disorder in the manic state.

Decreased Cardiac Vagal Control in Drug-Naïve Patients with Posttraumatic Stress Disorder

Objective Decreased cardiac vagal control (CVC) has been proposed in posttraumatic stress disorder (PTSD), but the results are mixed. Analyses with larger sample sizes and better methodology are needed. Methods Thirty-two drug-naïve survivors with current PTSD, 32 survivors without PTSD and 192 matched controls were recruited for a case-control analysis. We used the PTSD checklist-civilian version (PCL-C) to assess posttraumatic symptoms severity. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV) parameters. Frequency-domain indices of HRV were obtained. The obtained results were evaluated in association with personality traits assessed by the Tridimensional Personality Questionnaire (TPQ). Results PTSD patients exhibited decreased LF-HRV and HF-HRV as compared to survivors without PTSD and to matched controls. The PTSD symptoms severity was associated with reduced mean RR intervals, Var-HRV, LF-HRV and HF-HRV. The harm avoidance score (which has been suggested to be associated with serotonergic activity) was negatively correlated with Var-HRV, LF-HRV and HF-HRV. Conclusion These data suggest that PTSD is accompanied by decreased CVC, highlighting the importance of assessing HRV in PTSD patients. In view of the increased risk for cardiovascular diseases in these vulnerable individuals, one might consider the treatment to restore their autonomic function while reducing PTSD symptoms.

Heart rate variability in major depressive disorder and after antidepressant treatment with agomelatine and paroxetine: Findings from the Taiwan Study of Depression and Anxiety (TAISDA)

Evidence from previous studies suggests that heart rate variability (HRV) is reduced in major depressive disorder (MDD). However, whether this reduction is attributable to the disorder per se or to medication, since antidepressants may also affect HRV, is still debated. There is a dearth of information regarding the effects of agomelatine, a novel antidepressant, on HRV. Here, we investigated whether HRV is reduced in MDD and compared the effects of agomelatine and paroxetine on HRV. We recruited 618 physically healthy unmedicated patients with MDD and 506 healthy volunteers aged 20-65 years. Frequency-domain measures of resting HRV were obtained at the time of enrollment for all participants. For patients with MDD, these measures were obtained again after 6 weeks of either agomelatine or paroxetine monotherapy. Compared with healthy subjects, unmedicated patients with MDD exhibited significantly lower variance (total HRV), low frequency (LF), and high frequency (HF) HRV, and a higher LF/HF ratio. Depression severity independently contributed to decreased HRV and vagal tone. Fifty-six patients completed the open-label trial (n=29 for agomelatine, n=27 for paroxetine). Between-group analyses showed a significant group-by-time interaction for LF-HRV and HF-HRV, driven by increases in LF-HRV and HF-HRV only after agomelatine treatment. Within the paroxetine-treated group, there were no significant changes in mean R-R intervals or any HRV indices. We therefore concluded that MDD is associated with reduced HRV, which is inversely related to depression severity. Compared with paroxetine, agomelatine has a more vagotonic effect, suggesting greater cardiovascular safety. Clinicians should consider HRV effects while selecting antidepressants especially for depressed patients who already have decreased cardiac vagal tone.

Cardiac autonomic dysregulation in acute schizophrenia

Objective Altered cardiac autonomic function has been proposed in schizophrenia, but the results are mixed. Therefore, analyses with larger sample sizes and better methodology are needed. Methods To examine whether acute schizophrenia is associated with cardiac autonomic dysfunction, 314 unmedicated patients with acute schizophrenia and 409 healthy volunteers, aged 18–65 years, were recruited for a case–control analysis. The severity of schizophrenia symptoms was assessed with the Positive and Negative Syndrome Scale. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV) parameters during the supine–standing–supine test. Frequency-domain indices of HRV were obtained. Results Unmedicated patients with acute schizophrenia consistently exhibited reduced mean RR interval and HRV levels in a supine rest and standing position compared with healthy volunteers. The severity of psychopathology, in particular positive symptoms, was negatively correlated with cardiac vagal control. Conclusion These data suggest that acute schizophrenia is accompanied by cardiac autonomic dysregulation. In view of the higher risk for cardiac complications in these patients, one might also consider the antipsychotic treatment in favour of improving cardiac autonomic modulation. Further studies using larger patient groups and controlled therapeutics may better understand the influence of antipsychotic treatment on cardiac autonomic regulation in schizophrenia.

Decreased cardiac vagal control in drug-naive patients with panic disorder: a case-control study in Taiwan.

Cardiac autonomic dysregulation has been proposed in panic disorder (PD), but the results are mixed. Analyses with larger sample sizes and better methodology are needed.

Effects of depression and melatonergic antidepressant treatment alone and in combination with sedative–hypnotics on heart rate variability: Implications for cardiovascular risk

Abstract Objectives: To examine heart rate variability (HRV) in unmedicated patients with major depressive disorder (MDD) and its changes after treatment with agomelatine alone and in combination with sedative–hypnotics. Methods: We recruited 152 physically healthy, unmedicated patients with MDD and 472 age- and sex-matched healthy volunteers. Frequency-domain measures of HRV were obtained during enrolment for all participants and again for MDD patients after 6 weeks of treatment with agomelatine alone and combining sedative–hypnotics. Results: Compared to the controls, unmedicated patients exhibited significantly lower mean R-R intervals, low-frequency (LF) HRV, and high-frequency (HF) HRV, but higher LF/HF ratios. Fifty-six and 49 patients successfully completed agomelatine monotherapy and the combination therapy of agomelatine and sedative–hypnotics, respectively. Between-group analyses showed significant treatment-by-group interactions for LF-HRV, HF-HRV and LF/HF ratio. The results showed a significant increase in HF-HRV after agomelatine monotherapy, a significant decrease in LF-HRV and HF-HRV, and a increase in the LF/HF ratio after combination therapy. Conclusions: MDD patients had reduced HRV, and the patterns of HRV changes differed between patients treated with agomelatine alone and in combination with sedative–hypnotics. Clinicians should consider HRV effects when adding sedative–hypnotics to agomelatine, which is important for depressed patients who already have decreased cardiac vagal tone.

Reduced cardiac autonomic response to deep breathing: A heritable vulnerability trait in patients with schizophrenia and their healthy first-degree relatives

Reduced resting heart rate variability (HRV) has been observed in patients with schizophrenia and their relatives, suggesting genetic predispositions. However, findings have not been consistent. We assessed cardiac autonomic response to deep breathing in first-degree relatives of patients with schizophrenia (n=45; 26 female; aged 39.69±14.82 years). Data were compared to healthy controls (n=45; 26 female; aged 38.27±9.79 years) matched for age, gender, body mass index and physical activity as well as to unmedicated patients with acute schizophrenia (n=45; 25 female; aged 37.31±12.65 years). Electrocardiograms were recorded under supine resting and deep-breathing conditions (10-12breaths/min). We measured HRV components including variance, low-frequency (LF) power, which may reflect baroreflex function, high-frequency (HF) power, which reflects cardiac parasympathetic activity, and LF/HF ratio, which may reflect sympatho-vagal balance. Patients rather than relatives exhibited lower resting-state HRV (variance, LF, and HF) than controls. As expected, deep breathing induced an increase in variance and HF-HRV in controls. However, such a response was significantly reduced in both patients and their relatives. In conclusion, the diminished cardiac autonomic reactivity to deep breathing seen in patients and their unaffected relatives indicates that this pattern of cardiac autonomic dysregulation may be regarded as a genetic trait marker for schizophrenia.

Risk of psychiatric disorders in Guillain-Barre syndrome: A nationwide, population-based, cohort study

BACKGROUND Guillain-Barre syndrome (GBS) is a rare immune-related neurological disorder with high mortality and morbidity, but the comorbid psychiatric disorders garnered little attention in the GBS patients. This study aimed to investigate the association between GBS and the risk of developing psychiatric disorders. METHODS A total of 18,192 enrolled patients, with 4548 study subjects who had suffered GBS, and 13,644 controls matched for gender and age, from the Inpatient Dataset of 2000-2013 in Taiwan, and selected from the National Health Insurance Research Database (NHIRD). After adjusting for confounding factors, Cox proportional hazards analysis was used to compare the risk of developing psychiatric disorders during the 13years of follow-up. RESULTS Of the study subjects, 471 (10.35%) developed psychiatric disorders when compared to 1023 (7.50%) in the control group. Fine and Grays competing risk model analysis revealed that the study subjects were more likely to develop psychiatric disorders (crude hazard ratio [HR]: 4.281 (95% CI=3.819-4.798, p<0.001). After adjusting for gender, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted HR was 4.320 (95% CI=3.852-4.842, p<0.001). Dementia, depressive disorders, sleep disorders, and psychotic disorders predominate in these psychiatric disorders. Mechanical ventilation and hemodialysis are associated with a lower risk of dementia when compared to the control groups. CONCLUSIONS Patients who suffered from GBS had a higher risk of developing psychiatric disorders, and this finding should act as a reminder to the clinicians that a regular psychiatric follow-up might well be needed for those patients.