Vortioxetine's impact on the autonomic nervous system in depressed children and adolescents: analysis of the heart rate variability.

Relationship between depressive disorder and autonomic nervous system has been already discussed. Reduced emotional regulation is supposed to be associated with prefrontal hypofunction and subcortical hyperactivity. The aim of this study was to determine the effect of vortioxetine on heart rate variability (HRV), a parameter of cardiac autonomic regulation, in depressed hospitalized paediatric patients and assess the clinical effectiveness of the drug in this population. We performed repeated polysomnography analyses at admission and after a short treatment in hospital (15.2 days on average) and measured various HRV parameters (RRi, pNN50, RMSSD, LF-HRV, HF-HRV) during wakefulness, N3 and REM sleep stages. Out of 27 study subjects, 67% have improved depression symptoms as well as anxiety and subjective sleep quality after short vortioxetine treatment. We have found a significant decrease in parasympathetic parameters pNN50, RMSSD and HF-HRV during N3 sleep phase, though not exclusively among vortioxetine responders. The anticipated increase in cardiovagal regulation after vortioxetine treatment was not demonstrated in this pilot study, possibly due to the drug's multimodal mechanism and impact on the nucleus tractus solitarii, particularly its antagonism on 5HT-3 receptors. Application of selective drugs could further explain the effect of vortioxetine on HRV in depressed patients.

Mechanisms Involved in the Link between Depression, Antidepressant Treatment, and Associated Weight Change.

Major depressive disorder is a severe mood disorder associated with a marked decrease in quality of life and social functioning, accompanied by a risk of suicidal behavior. Therefore, seeking out and adhering to effective treatment is of great personal and society-wide importance. Weight changes associated with antidepressant therapy are often cited as the reason for treatment withdrawal and thus are an important topic of interest. There indeed exists a significant mechanistic overlap between depression, antidepressant treatment, and the regulation of appetite and body weight. The suggested pathomechanisms include the abnormal functioning of the homeostatic (mostly humoral) and hedonic (mostly dopaminergic) circuits of appetite regulation, as well as causing neuromorphological and neurophysiological changes underlying the development of depressive disorder. However, this issue is still extensively discussed. This review aims to summarize mechanisms linked to depression and antidepressant therapy in the context of weight change.

Effect of Acute Ketamine Treatment on Sympathetic Regulation Indexed by Electrodermal Activity in Adolescent Major Depression.

Ketamine is a potential rapid-onset antidepressant characterized by sympathomimetic effects. However, the question of ketamine's use in treating adolescents' major depressive disorder (MDD) is still discussed. Thus, we aimed to study the acute effect of ketamine infusion treatment on sympathetic regulation using electrodermal activity (EDA) in addition to an assessment of depressive symptomatology in MDD adolescents. Twenty hospitalized adolescent girls with MDD (average age: 15.0 ± 1.46 yrs.) were examined before and two hours after a single intravenous infusion of ketamine. EDA was continuously recorded for 6 min, and depressive symptoms were assessed before and two hours after ketamine administration. The evaluated parameters included skin conductance level (SCL), nonspecific electrodermal responses (NS-SCRs), MADRS (questions no. 1-10, total score), and CDI (items A-E, total score). EDA parameters showed no significant changes after the ketamine treatment, and depressive symptoms were significantly reduced after the ketamine infusion. The analysis revealed a significant negative correlation between index SCL and CDI-A, CDI-E, and the total CDI score and between index NS-SCRs and MADRS no. 4 before the ketamine treatment. In conclusion, ketamine improved depressive symptomatology without a significant effect on EDA, indicating its potential safety and efficiency as an acute antidepressant intervention in adolescent MDD.

Cardiac Autonomic Balance Is Altered during the Acute Stress Response in Adolescent Major Depression-Effect of Sex.

Autonomic nervous system (ANS) abnormalities are associated with major depressive disorder (MDD) already at adolescent age. The majority of studies so far evaluated parasympathetic and sympathetic branches of ANS individually, although composite indices including cardiac autonomic balance (CAB) and cardiac autonomic regulation (CAR) seem to measure ANS functioning more comprehensively and thus could provide better psychopathologies' predictors. We aimed to study CAB and CAR derived from high-frequency bands of heart rate variability and left ventricular ejection time during complex stress response (rest-Go/NoGo task-recovery) in MDD adolescents with respect to sex. We examined 85 MDD adolescents (52 girls, age: 15.7 ± 0.14 yrs.) and 80 age- and sex-matched controls. The MDD group showed significantly reduced CAB compared to controls at rest, in response to the Go/NoGo task, and in the recovery phase. Moreover, while depressed boys showed significantly lower CAB at rest and in response to the Go/NoGo task compared to control boys, depressed girls showed no significant differences in evaluated parameters compared to control girls. This study for the first time evaluated CAB and CAR indices in drug-naïve first-episode diagnosed MDD adolescents during complex stress responses, indicating an altered cardiac autonomic pattern (i.e., reciprocal sympathetic dominance associated with parasympathetic underactivity), which was predominant for depressed boys.