When Heart Beats Differently in Depression: Review of Nonlinear Heart Rate Variability Measures

Background: Disturbed heart dynamics in depression seriously increases mortality risk. Heart rate variability (HRV) is a rich source of information for studying this dynamics. This paper is a meta-analytic review with methodological commentary of the application of nonlinear analysis of HRV and its possibility to address cardiovascular diseases in depression. Objective: This paper aimed to appeal for the introduction of cardiological screening to patients with depression, because it is still far from established practice. The other (main) objective of the paper was to show that nonlinear methods in HRV analysis give better results than standard ones. Methods: We systematically searched on the web for papers on nonlinear analyses of HRV in depression, in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 framework recommendations. We scrutinized the chosen publications and performed random-effects meta-analysis, using the esci module in jamovi software where standardized effect sizes (ESs) are corrected to yield the proof of the practical utility of their results. Results: In all, 26 publications on the connection of nonlinear HRV measures and depression meeting our inclusion criteria were selected, examining a total of 1537 patients diagnosed with depression and 1041 healthy controls (N=2578). The overall ES (unbiased) was 1.03 (95% CI 0.703-1.35; diamond ratio 3.60). We performed 3 more meta-analytic comparisons, demonstrating the overall effectiveness of 3 groups of nonlinear analysis: detrended fluctuation analysis (overall ES 0.364, 95% CI 0.237-0.491), entropy-based measures (overall ES 1.05, 95% CI 0.572-1.52), and all other nonlinear measures (overall ES 0.702, 95% CI 0.422-0.982). The effectiveness of the applied methods of electrocardiogram analysis was compared and discussed in the light of detection and prevention of depression-related cardiovascular risk. Conclusions: We compared the ESs of nonlinear and conventional time and spectral methods (found in the literature) and demonstrated that those of the former are larger, which recommends their use for the early screening of cardiovascular abnormalities in patients with depression to prevent possible deleterious events. ©Milena Čukić, Danka Savić, Julia Sidorova

A theoretical study-of hypothalamo-pituitary adrenocortical axis dynamics

Does the hypothalamo-pituitary-adrenocortical (HPA) axis itself generate oscillations? The affirmative answer to this question is commonly assumed, because a regular daily rhythm of its hormones is observed. We offer another plausible explanation of the origin of this pattern: HPA just responds to an external pacemaker. A qualitative mathematical model is constructed wherein all the terms in the equations are physicochemically interpretable. Linear stability analysis shows that this system does not generate oscillations. Computer simulation yields oscillations that are the systems response to an external pulsing activator, implying that the observed pattern does not have to be an intrinsic property of this system.22nd International Biophysics Symposium, Oct 09-14, 2004, Belgrade, Serbi

A mathematical model of the hypothalamo-pituitary-adrenocortical system and its stability analysis

It is commonly assumed that the hypothalamo-pituitary-adrenocorticat (HPA) axis generates oscillations, because a regular daily rhythm of its component hormones is observed. We offer another plausible explanation of the origin of its circadian oscillations: HPA just responds to an independent external pacemaker (from the suprachiazmatic nucleus, SCN). Five versions (with and without time delay) of a qualitative non-phenomenological mathematical model of the HPA axis as a feedback mechanism are constructed wherein all the terms in the equations are introduced according to the rules of chemical kinetics, i.e. are physicochemically interpretable. The dynamics of the HPA axis model was examined using linear stability analysis. The results show stability of this system, meaning that it does not generate diurnal oscillations. Computer simulation based on this model shows oscillations that are systems response to an external pulsing activator (SCN) implying that the observed time-periodic pattern does not have to be an intrinsic property of the HPA axis. (c) 2005 Elsevier Ltd. All rights reserved

A mathematical model of stress reaction: Individual differences in threshold and duration

People differ in what they experience as stressful and to what extent. We define a variable-stress threshold (sigma)-that links the hypothalamo-pituitary-adrenocortical (HPA) axis and the memory system in a feedback mechanism. Current sigma dictates the intensity of a stimulus that turns the stress response on. On the other hand, each jump of the HPA axis helps long-term registration of the stressful event via concentration changes of some of its products, consequently changing the value of sigma for future stressors. After the action of a strong exterior stressor, the new stressful memory acts as an internal source of stress. We assume that its intensity decreases with the rate of processing the stressful information. This process is characterized by a time parameter tau. Both sigma and tau are individual: They depend on personality traits, genetic as well as acquired. The mathematical model presented here simulates the feedback mechanism between the HPA axis and the memory system involved in stress reaction

Stability of a general delay differential model of the hypothalamo-pituitary-adrenocortical system

Most of the systems in an organism (human included) function in a regular daily rhythm. Hypothalamo-pituitary-adrenocortical (HPA) axis, although mostly known for its role in stress response, probably has a role in conveying rhythmic signals from the major pacemaker, suprachiazmatic nucleus (SCN), to the periphery. A general qualitative nonphenomenological mathematical model of the HPA axis is constructed and its dynamics is examined using linear stability analysis and Roushes theorem. The results show that this system is asymptotically stable, i.e. it does not generate circadian oscillations, but only responds to the external pacemaker

From war-related trauma exposure to PTSD and depression: A personality perspective

The aim of the study is to test a model specifying the relations between personality traits, war-related traumas, PTSD and depression, as well as the measurement aspects of the model. This study was carried out in hospital on 400 male participants. Five-Factor Model of personality was complemented by a recently proposed trait Disintegration representing proneness to psychotic-like experiences/behaviors in the general population. The proposed model had excellent fit, despite its complexity. The results show that PTSD or depression symptoms after traumas are largely related to the number of traumas, Neuroticism, Extraversion, and Disintegration, and their different configurations and quantities. Disintegration turned out to be one of the most important dispositional correlates of depression and PTSD, but also of trauma exposure. © 202

Disintegration: A reconceptualization of psychosis proneness as a personality trait separate from the Big Five

A nine-facet hierarchical taxonomy of Disintegration, a trait-like disposition that causes variations in psychotic-like behavior, is proposed, along with the scales to assess it. Strong correlations were demonstrated in students (n = 466) between lower-level dimensions, independent of the assessment method. Disintegration lay beyond the Five-Factor Model (FFM) space. This finding was replicated across informant types (self, mother, and father), samples (students and a national representative sample, n = 1001), and units of analyses (facets and items). The most frequent approach to preserve the FFM taxonomy of both normal and non-normal personality variants - mapping psychotic-like phenomena onto the Openness domain - found little support in our data. Disintegration was normally distributed in the general population. (C) 2017 Elsevier Inc. All rights reserved

The role of personality and traumatic events in cortisol levels - Where does PTSD fit in?

Background: Studies of cortisol in post-traumatic stress disorder (PTSD) have yielded mixed results. We hypothesize that personality traits and traumatic experiences could be the confounders of cortisol measures and disease symptoms. Method: This study was a part of a broader project in which simultaneous psychological and biological investigations were carried out in hospital conditions on 400 male participants categorized by four groups: (A) 133 with current PTSD, (B) 66 with lifetime PTSD, (C) 102 trauma controls, and (D) 99 healthy controls (matched by age and education). Cortisol and ACTH were measured in blood samples taken hourly from 22:00 h to 09:00 h, with an additional sample at 07:30 h (resting state and morning rise). The next night, dexamethasone (0.5 mg) suppression test was performed. Results: No significant differences in basal cortisol and ACTH were found between study groups. The trait Conscientiousness, negatively modulated by Extraversion (assessed by NEO Personality Inventory-Revised) was found to correlate with cortisol (but not with ACTH). Group differences are found on suppression. Structural equation modeling shows excellent fit only when the paths (influences) from Conscientiousness to basal cortisol and from traumatic events to suppression are present. The paths connecting suppression and PTSD symptoms do not contribute. Conclusions: Two sources of differences of hypothalamo-pituitary-adrenocortical axis functioning are implied, both only indirectly connected to PTSD. It seems that basal cortisol secretion is associated more tightly with personality (introvertively modulated Conscientiousness), while the regulation by glucocorticoid receptor system is sensitized by repeated traumatic situations. (c) 2011 Elsevier Ltd. All rights reserved

Is there a biological difference between trauma-related depression and PTSD? DST says NO

The use of the low-dose dexamethasone suppression test (DST) as a potentially discriminative marker between post-traumatic stress disorder (PTSD) and depression is still under discussion. In order to compare the influence of these psychopathologies on the DST results, we examined suppression in war-traumatized subjects with one or both of these disorders, as well as in healthy controls. Based on our previous findings, we hypothesized that subjects with any disorder would exhibit higher dexamethasone suppression than healthy controls due to traumatic experiences. This study was a part of a broader project in which simultaneous psychological and biological investigations were carried out in hospital conditions on 399 mate participants: 57 with PTSD, 28 with depression, 76 with PTSD + depression, and 238 healthy controls. Cortisol was measured in blood samples taken at 0900 h before and after administering 0.5 mg of dexamethasone (at 2300 h). Group means standard deviation of cortisol suppression were: 79.4 +/- 18.5 in the PTSD group, 80.8 +/- 11.6 in the depression group, 77.5 +/- 24.6 in the group with PTSD+depression, and 66.8 +/- 34.6 in healthy controls. The first three groups suppressed significantly more than the fourth. When the number of traumas was introduced as a covariate, the differences disappeared. The hypothesis was confirmed: in respect to DST, the examined trauma-related psychopathologies showed the same pattern: hypersuppression, due to multiple traumatic experiences. (C) 2012 Elsevier Ltd. All rights reserved

The role of personality and traumatic events in cortisol levels - Where does PTSD fit in?

Background: Studies of cortisol in post-traumatic stress disorder (PTSD) have yielded mixed results. We hypothesize that personality traits and traumatic experiences could be the confounders of cortisol measures and disease symptoms. Method: This study was a part of a broader project in which simultaneous psychological and biological investigations were carried out in hospital conditions on 400 male participants categorized by four groups: (A) 133 with current PTSD, (B) 66 with lifetime PTSD, (C) 102 trauma controls, and (D) 99 healthy controls (matched by age and education). Cortisol and ACTH were measured in blood samples taken hourly from 22:00 h to 09:00 h, with an additional sample at 07:30 h (resting state and morning rise). The next night, dexamethasone (0.5 mg) suppression test was performed. Results: No significant differences in basal cortisol and ACTH were found between study groups. The trait Conscientiousness, negatively modulated by Extraversion (assessed by NEO Personality Inventory-Revised) was found to correlate with cortisol (but not with ACTH). Group differences are found on suppression. Structural equation modeling shows excellent fit only when the paths (influences) from Conscientiousness to basal cortisol and from traumatic events to suppression are present. The paths connecting suppression and PTSD symptoms do not contribute. Conclusions: Two sources of differences of hypothalamo-pituitary-adrenocortical axis functioning are implied, both only indirectly connected to PTSD. It seems that basal cortisol secretion is associated more tightly with personality (introvertively modulated Conscientiousness), while the regulation by glucocorticoid receptor system is sensitized by repeated traumatic situations. (c) 2011 Elsevier Ltd. All rights reserved