Article Figures & Tables
Figures
- Fig. 1
Summary effect estimates comparing significant reductions in heart rate variability (HRV) in psychiatric disorder subgroups compared to healthy controls. Open diamonds depict summary effect sizes of each subgroup; filled diamond reflects the overall summary effect across groups. Diamond width indicates the 95% confidence interval (CI) for each summary effect size.
- Fig. 2
Results of meta-regression analyses in case–control studies examining effects of continuous moderators on the effect sizes of (A) mean patient age, (B) the proportion of men in the patient group, (C) independent study quality ratings and (D) year of publication. Studies are indicated by open circles, with size indicating relative weight.
- Fig. 3
Effects of antidepressant use on heart rate variability (HRV) in individuals with a mood or anxiety disorder. Removal of the outlier in the tricyclic antidepressant (TCA) group189 shifted the effect size of the TCA subgroup (Hedges g = −0.666, 95% confidence interval [CI] −0.900 to −0.432, p < 0.001) and the overall effect size (Hedges g = −0.231, 95% CI −0.364 to −0.097, p = 0.001). Point estimates are depicted by filled circles, with sizes indicating the relative weight of each study’s effect size estimate to the analysis. Open diamonds depict summary effects sizes of each subgroup; the filled diamond reflects the overall summary effect across groups. Line and diamond width indicate 95% CIs. SNRI = serotonin-norepinephrine reuptake inhibitor antidepressant; SSRI = selective serotonin reuptake inhibitor antidepressant.
- Fig. 4
Effects of antipsychotic use on heart rate variability (HRV) in individuals with schizophrenia. Point estimates are depicted by closed circles, with size indicating the relative weight of each study’s effect size estimate to the analysis. Open diamonds depict summary effect sizes of each subgroup; filled diamond reflects the overall summary effect across groups. Line and diamond width indicate 95% confidence intervals (CIs).
Tables
Comparator; mean ± SD Study type Included diagnoses No. of effect sizes* No. of patients No. of controls Men, % Age, yr Study quality Case–control studies Anxiety-related disorders47–58,60–92,240 Panic, generalized anxiety, social anxiety, posttraumatic stress, or obsessive–compulsive disorder, specific phobia 47 1365 1469 42.039 ± 22.244 35.752 ± 5.241 11.872 ± 1.907 Mood disorders50,68,73,90,93–137 Major depressive disorder, bipolar disorder 52 2838 2882 38.031 ± 18.543 38.706 ± 7.850 11.788 ± 1.775 Psychotic disorders73,107,113,138–175 Schizophrenia, schizoaffective disorder, schizophreniform disorder 41 1713 1660 57.493 ± 15.080 35.127 ± 6.332 11.756 ± 1.729 Substance dependence disorders159,176–186 Alcohol, methamphetamine, opioid dependence 11 310 415 84.836 ± 17.021 10.324 ± 5.958 11.364 ± 1.748 Total — 151 6226 6426 47.726 ± 22.637 36.933 ± 6.712 11.775 ± 1.789 Treatment studies Antidepressants†76,83,93,110,116,129,187–201 Major depressive disorder, panic disorder, generalized anxiety disorder 31 570 — 37.981 ± 12.797 42.412 ± 6.899 11.226 ± 1.892 Antipsychotics‡138,141,155,175,202–206 Schizophrenia 12 262 — 57.594 ± 14.892 34.668 ± 4.742 11.167 ± 1.586 Total — 43 832 — 44.342 ± 16.235 40.029 ± 7.224 11.209 ± 1.794 NASSA = noradrenergic and specific serotonergic antidepressant; SD = standard deviation; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant.
↵* Number of effect sizes differs from the number of studies included owing to some studies reporting multiple effect sizes for different disorders or subgroups. If studies reported a common control group, effect sizes were adjusted by dividing the number of controls by the number of comparisons made. Subgroups within disorders were pooled where sufficient information was provided for effect size estimates.
↵† Includes NASSA, SNRI, SSRI and TCA.
↵‡ Includes atypical and typical antipsychotics.
- Table 2
Meta-analytic results of HRV in patients compared to controls across psychiatric subgroups and current medication use
Category No. of effect sizes, k No. of patients No. of controls Hedges g (95% CI) Q Heterogeneity p value Egger regression p value* Fail-safe N* Sensitivity analysis, range† Overall 151 6226 6426 −0.582 (−0.663 to −0.501)§ 645.563 < 0.001 < 0.001 8069 −0.589 to −0.556 Disorder subgroups Anxiety 47 1365 1469 −0.360 (−0.505 to −0.215)§ 35.358 < 0.001 0.70 872 −0.379 to −0.331 Mood 52 2838 2882 −0.462 (−0.593 to −0.331)§ 0.020 2712 −0.471 to −0.439 Psychotic 41 1713 1660 −0.952 (−1.105 to −0.800)§ < 0.001 4978 −1.011 to −0.886 Substance dependence 11 310 415 −0.694 (−0.982 to −0.405)§ 0.011 193 −0.716 to −0.630 Medication use‡ 142 5994 6163 −0.581 (−0.662 to −0.500)§ < 0.001 5333 −0.590 to −0.555 Not medicated 82 3755 4343 −0.471 (−0.577 to −0.365)§ 9.893 0.002 0.009 5980 −0.479 to −0.440 Medicated 60 2239 1820 −0.734 (−0.859 to −0.609)§ 0.15 6624 −0.759 to −0.675 Anxiety disorders 44 1319 1439 −0.330 (−0.474 to −0.186)§ 0.37 678 −0.350 to −0.300 Not medicated 30 844 1035 −0.334 (−0.510 to −0.158)¶ 0.008 0.93 0.57 299 −0.363 to −0.288 Medicated 14 475 404 −0.321 (−0.571 to −0.071)** 0.38 63 −0.385 to −0.300 Mood disorders 49 2739 2784 −0.470 (−0.560 to −0.380)§ 0.014 2607 −0.488 to −0.454 Not medicated 29 2008 2182 −0.360 (−0.472 to −0.249)§ 10.332 0.001 0.41 628 −0.395 to −0.328 Medicated 20 731 602 −0.668 (−0.818 to −0.517)§ 0.31 651 −0.710 to −0.641 Psychotic disorders 40 1692 1639 −0.983 (−1.196 to −0.770)§ < 0.001 4765 −1.013 to −0.885 Not medicated 19 812 987 −0.901 (−1.210 to −0.592)§ 0.515 0.47 < 0.001 869 −0.939 to −0.735 Medicated 21 880 652 −1.058 (−1.353 to −0.763)§ 0.24 1541 −1.120 to −0.888 Substance dependence disorders 9 244 301 −0.694 (−0.897 to −0.491)§ 0.038 133 −0.744 to −0.649 Not medicated 4 91 139 −0.592 (−0.907 to −0.277)¶ 0.684 0.41 0.16 15 −0.731 to −0.465 Medicated 5 153 162 −0.766 (−1.032 to −0.501)§ 0.006 53 −0.906 to −0.686 CI = confidence interval; HRV = heart rate variability.
↵* Tests of publication bias conducted for the overall group of studies as well as for subgroups, p value 2-tailed.
↵† Sensitivity analyses conducted using 1 study removed.
↵‡ Current medication use not stated in 9 studies, which were thus were removed from medication subgroup analyses. “Not medicated” indicates patients who were either medication-free or medication-naive at time of physiological testing.
↵§ p < 0.0001, 2-tailed.
↵¶ p < 0.001, 2-tailed.
↵** p < 0.01, 2-tailed.
Category No. of effect sizes, k No. of patients Hedges g (95% CI) Q Heterogeneity p value Egger regression p value* Fail-safe N* Sensitivity analysis, range† Overall 43 832 −0.206 (−0.353 to −0.059)** 216.748 < 0.001 0.60 333 −0.246 to −0.188 Disorder subgroups‡ 42 814 −0.194 (−0.346 to −0.043)†† 0.62 272 −0.234 to −0.175 Anxiety 5 79 −0.133 (−0.570 to 0.303) 0.103 0.95 0.35 0 −0.287 to −0.032 Mood 25 473 −0.195 (−0.394 to 0.004) 0.24 63 −0.272 to −0.168 Psychotic 12 262 −0.218 (−0.498 to 0.062) 0.53 40 −0.270 to −0.172 Type of medication Antidepressant 31 570 −0.201 (−0.378 to −0.025)†† 0.004 0.95 0.18 119 −0.264 to −0.180 Antipsychotic 12 262 −0.218 (−0.496 to 0.059) 0.53 40 −0.270 to −0.172 Antidepressants§ 30 562 −0.183 (−0.374 to 0.007) 0.27 89 −0.245 to −0.157 SNRI 3 72 −0.181 (−0.752 to 0.390) 4.939 0.09 0.22 0 −0.338 to 0.028 SSRI 15 303 0.011 (−0.254 to 0.276) 0.99 0 −0.041 to 0.054 TCA 12 187 −0.454 (−0.766 to −0.141)** 0.79 89 −0.614 to −0.415 Antipsychotics¶ 9 209 −0.272 (−0.449 to −0.095)** 0.92 37 −0.328 to −0.225 Amisulpride 2 27 −0.322 (−0.731 to 0.088) 10.071 0.018 — — — Clozapine 3 63 −0.643 (−0.973 to −0.313)‡‡ 0.09 18 −0.900 to −0.520 Olanzapine 2 96 −0.191 (−0.502 to 0.120) — — — Sertindole 2 23 0.174 (−0.221 to 0.569) — — — CI = confidence interval; HRV = heart rate variability; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant.
↵* Tests of publication bias conducted for the overall group of studies as well as for subgroups where there were at least 3 studies per subgroup.
↵† Sensitivity analyses conducted using 1 study removed.
↵‡ One study removed199 owing to overlapping clinical diagnoses between the anxiety and mood disorder subgroups.
↵§ One study removed241 as it was the only study to examine the effects of a noradrenergic and specific serotonergic antidepressant.
↵¶ One study removed141 owing to inclusion of multiple antipsychotics, and 2 other studies removed as they were the only studies to examine a particular antipsychotic (haloperidol204 and risperidone155).
↵** p < 0.01, 2-tailed.
↵†† p < 0.05, 2-tailed.
↵‡‡ p < .001, 2-tailed.
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