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.

Peripheral Inflammatory Markers in Autism Spectrum Disorder and Attention Deficit/Hyperactivity Disorder at Adolescent Age.

Autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are associated with immune dysregulation. We aimed to estimate the pro- and anti-inflammatory activity/balance in ASD and ADHD patients at a little-studied adolescent age with respect to sex. We evaluated 20 ASD patients (5 girls, average age: 12.4 ± 1.9 y), 20 ADHD patients (5 girls, average age: 13.4 ± 1.8 y), and 20 age- and gender-matched controls (average age: 13.2 ± 1.9 y). The evaluated parameters included (1) white blood cells (WBCs), neutrophils, monocytes, lymphocytes, platelets, platelet distribution width (PDW), mean platelet volume, and derived ratios, as well as (2) cytokines-interferon-gamma, interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, and IL-10, tumor necrosis factor-alpha (TNF-α), and derived profiles and ratios. ASD adolescents showed higher levels of WBC, monocytes, IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, and IL-10, macrophages (M)1 profile, and anti-inflammatory profile than the controls, with ASD males showing higher monocytes, IL-6 and IL-10, anti-inflammatory profile, and a lower T-helper (Th)1/Th2+T-regulatory cell ratio than control males. The ADHD adolescents showed higher levels of PDW, IL-1ß and IL-6, TNF-α, M1 profile, proinflammatory profile, and pro-/anti-inflammatory ratio than the controls, with ADHD females showing a higher TNF-α and pro-/anti-inflammatory ratio than the control females and ADHD males showing higher levels of IL-1ß and IL-6, TNF-α, and M1 profile than the control males. Immune dysregulation appeared to be different for both neurodevelopmental disorders in adolescence.

Electrodermal activity spectral and nonlinear analysis - potential biomarkers for sympathetic dysregulation in autism.

Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by emotional and social deficits, which can be associated with sympathetic dysregulation. Thus, we aimed to analyze the electrodermal activity (EDA) using time, and novel spectral and nonlinear indices in ASD. The cohort consisted of 45 ASD boys and 45 age-matched controls. EDA was continuously recorded at rest. The EDA indices were evaluated by time-, spectral-, and nonlinear-domain analysis. Our results revealed increased non-specific skin conductance responses, spectral parameters in high and very-high frequency bands, approximate and symbolic information entropy indicating sympathetic overactivity in ASD vs. controls (p < 0.05, for all). Surprisingly, the nonlinear index from detrended fluctuation analysis α1 was lower in ASD vs. controls (p = 0.024) providing thus distinct information about qualitative features of complex sympathetic regulation. Concluding, the complex time, spectral, and nonlinear EDA indices revealed discrete abnormalities in sympathetic cholinergic regulation as one of the potential pathomechanisms contributing to cardiovascular complications in ASD.

Association of Sleep Architecture and Physiology with Depressive Disorder and Antidepressants Treatment.

Sleep problems are frequently associated with the principal diagnostic criteria for many mental disorders. Alterations in the sleep of depressive patients are of high clinical significance because continuous sleep problems raise the chance of relapse, recurrence, or suicide, as well as the need for augmenting medications. Most antidepressants have been proven to influence the sleep architecture. While some classes of antidepressants improve sleep, others may cause sleep impairment. The successful treatment of depressive disorder also requires an understanding of the effects of antidepressants on sleep. This article briefly reviews the physiology of sleep and the typical alterations in the sleep architecture in depressive patients and updates the different effects of the majority of antidepressants including novel drugs in clinical practice on sleep. The summary of the updated scientific findings of the relationship between depression and sleep disturbances could be clinically beneficial in choosing the best medication for depressive patients with concurrent sleep disorders.

Role of Neuroendocrine, Immune, and Autonomic Nervous System in Anorexia Nervosa-Linked Cardiovascular Diseases.

Anorexia nervosa represents a severe mental disorder associated with food avoidance and malnutrition. In patients suffering from anorexia nervosa, cardiovascular complications are the main reason leading to morbidity and mortality. However, the origin and pathological mechanisms leading to higher cardiovascular risk in anorexia nervosa are still unclear. In this aspect, the issue of exact pathological mechanisms as well as sensitive biomarkers for detection of anorexia nervosa-linked cardiovascular risk are discussed. Therefore, this review synthesised recent evidence of dysfunction in multiple neuroendocrine axes and alterations in the immune system that may represent anorexia nervosa-linked pathological mechanisms contributing to complex cardiovascular dysregulation. Further, this review is focused on identification of non-invasive biomarkers for the assessment of increased cardiovascular risk in anorexia nervosa that can be linked to a clinical application. Complex non-invasive assessment of cardiovascular autonomic regulation-cardiac vagal control (heart rate variability), sympathetic vascular activity (blood pressure variability), and cardiovascular reflex control (baroreflex sensitivity)-could represent a promising tool for early diagnosis, personalized therapy, and monitoring of therapeutic interventions in anorexia nervosa particularly at a vulnerable adolescent age.

Anxiolytic effects of venlafaxine/olanzapine combination in treatment of anxious depression.

OBJECTIVE: Both venlafaxine and olanzapine have been previously found to have anxiolytic properties, however no study examined the effect of their combination on anxiety in anxious MDD. The aim of this study was to reveal if and when venlafaxine/olanzapine combination (VOC) can reduce the anxiety and depressive symptoms in patients with severe MDD at the level of patients with moderate-severe depression treated with venlafaxine monotherapy. METHODS: Fifty seven patients were included into the study. Symptoms of depression were objectively assessed by Montgomery-Asberg Depression Rating Scale and subjectively scored by BECK Depression scale, symptoms of anxiety were objectively assessed by Hamilton Anxiety scale and subjectively evluated by ZUNG Self-Rating Anxiety scale before treatment and after each following week untill the fourth week of treatment. RESULTS: VOC eliminated the pre-treatment score differences in all the scales within the first week of treatment. At the third week, VOC group had significantly lower level of anxiety symptoms and the effect maintained through the fourth week of medication. CONCLUSION: Our results indicate that VOC could replace another anxiolytic medication in managing the symptoms of anxiety in patients with severe anxious MDD already within the first week of treatment.

QTc prolongation after ADHD medication.

OBJECTIVE: Multicenter studies have shown that cardiovascular risks of ADHD medication are extremely low. However, QTc length has been shown to be increased in smaller samples of patients or case reports after stimulant and atomoxetine medication. Based on recent studies of genetic polymorphisms associated with drug-induced QTc prolongation and polymorphisms linkage to regional populations, we hypothesized that the drug-induced QTc prolongation could be a factor of particular polymorphisms linked to specific regional populations undistinguished in multicenter studies. METHODS: We included 69 patients from a region of central Slovakia, 36 patients were taking atomoxetine and 33 patients methylphenidate. QTc, heart rate, potassium levels and BMI were examined before and after 8 weeks of treatment. Therapeutic effect was measured by ADHD-RS-IV. RESULTS: We found QTc prolongation after 8 weeks of treatment both with atomoxetine and methylphenidate that was neither followed by the significant changes in BMI and potassium levels nor the significant increase of heart rate. CONCLUSION: This is the first study revealing QTc prolongation in the group of ADHD children from the same region after 8-week treatment with atomoxetine and methylphenidate, indicating the potential discrete abnormalities in cardiac functioning associated with polymorphisms in genes of dopaminergic and noradrenergic system.

Symbolic dynamics of heart rate variability - a promising tool to investigate cardiac sympathovagal control in attention deficit/hyperactivity disorder (ADHD)?

We aimed to evaluate complex cardiac sympathovagal control in attention deficit/hyperactivity disorder (ADHD) by using heart rate variability (HRV) nonlinear analysis - symbolic dynamics. We examined 29 boys with untreated ADHD and 25 healthy boys (age 8-13 years). ADHD symptoms were evaluated by ADHD-RS-IV scale. ECG was recorded in 3 positions: baseline supine position, orthostasis, and clinostasis. Symbolic dynamics indices were used for the assessment of complex cardiac sympathovagal regulation: normalised complexity index (NCI), normalised unpredictability index (NUPI), and pattern classification measures (0V%, 1V%, 2LV%, 2UV%). The results showed that HRV complexity was significantly reduced at rest (NUPI) and during standing position (NCI, NUPI) in ADHD group compared to controls. Cardiac-linked sympathetic index 0V% was significantly higher during all posture positions and cardiovagal index 2LV% was significantly lower to standing in boys suffering from ADHD. Importantly, ADHD symptom inattention positively correlated with 0V%, and negatively correlated with NCI, NUPI. Concluding, symbolic dynamics revealed impaired complex neurocardiac control characterised by potential cardiac beta-adrenergic overactivity and vagal deficiency at rest and to posture changes in boys suffering from ADHD that is correlated with inattention. We suggest that symbolic dynamics indices could represent promising cardiac biomarkers in ADHD.

Anxiety reduction on atomoxetine and methylphenidate medication in children with ADHD.

BACKGROUND: Atomoxetine and methylphenidate are widely used to treat attention-deficit-hyperactivity disorder (ADHD) with similar effectiveness after 8 weeks of treatment, when atomoxetine has reached its a full effect. Both drugs have also been shown to have an effect on comorbid anxiety. To the best of our knowledge, no study has compared their effect on the dynamics of anxiety symptom reduction. The aim of this study was to compare the medication effect on core and comorbid anxiety symptom dynamics in children with ADHD. METHODS: Sixty-nine patients participated in the study: 36 patients were taking atomoxetine and 33 patients, methylphenidate. Therapeutic effect on core symptoms of ADHD was measured on the ADHD-rating scale IV, and symptoms of anxiety were measured using the Conners Parent Rating Scale (CPRS). Symptoms were measured prior to and every 2 weeks during 8 weeks of treatment. RESULTS: There was a significant decrease in CPRS anxiety subscale score in both medication groups. Anxiety subscale score was significantly lower in the atomoxetine group in the fourth week, and lasted through to 8 weeks of medication. CONCLUSION: Both atomoxetine and methylphenidate reduced the symptoms of ADHD and anxiety. Atomoxetine was more effective in anxiety symptom reduction from the fourth week of treatment.

Association of EGF, IGFBP-3 and TP53 Gene Polymorphisms with Major Depressive Disorder in Slovak Population.

BACKGROUND: Major depressive disorder (MDD) is a main public health concern worldwide. Despite extensive investigations, the exact mechanisms responsible for MDD have not been identified. Epidermal growth factor (EGF) and insulin growth factor binding protein-3 (IGFBP-3) are involved in brain function. Tumour suppressor protein p53 is widely involved in neuronal death in response to different forms of acute insults and neurological disorders. The present study focuses on the possible associations of the single-nucleotide polymorphisms (SNP) of EGF A61G (rs4444903), IGFBP-3 C32G (rs2854746) and TP53 G72C (rs1042522) genes with MDD risk in the Slovak population. METHODS: The present case-control association study was carried out in 111 confirmed MDD patients and 207 healthy subjects. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: Logistic regression analysis showed no association between SNPs of selected genes and MDD risk in the Slovak population. However, the stratification of individuals by gender revealed that males carrying IGFBP-3 G alleles (G32G or GG) had marginally increased risk for developing MDD as compared to CC homozygous males (p=0.09). In women, inverse association was observed between SNP rs1042522 and MDD risk (p=0.04 for recessive model). CONCLUSION: Our results suggest the protective effect of minor allele 72C of TP53 gene towards MDD. The disruption of mechanisms involved in cell survival and death regulation may be involved in pathophysiology of MDD.

Antitussive activity of Withania somnifera and opioid receptors.

Arabinogalactan is a polysaccharide isolated from the roots of the medicinal plant Withania somnifera L. It contains 65% arabinose and 18% galactose. The aim of the present study was to evaluate the antitussive activity of arabinogalactan in conscious, healthy adult guinea pigs and the role of the opioid pathway in the antitussive action. A polysaccharide extract was given orally in a dose of 50 mg/kg. Cough was induced by an aerosol of citric acid in a concentration 0.3 mol/L, generated by a jet nebulizer into a plethysmographic chamber. The intensity of cough response was defined as the number of cough efforts counted during a 3-min exposure to the aerosol. The major finding was that arabinogalactan clearly suppressed the cough reflex; the suppression was comparable with that of codeine that was taken as a reference drug. The involvement of the opioid system was tested with the use of a blood-brain barrier penetrable, naloxone hydrochloride, and non-penetrable, naloxone methiodide, to distinguish between the central and peripheral mu-opioid receptor pathways. Both opioid antagonists acted to reverse the arabinogalactan-induced cough suppression; the reversion was total over time with the latter antagonist. We failed to confirm the presence of a bronchodilating effect of the polysaccharide, which could be involved in its antitussive action. We conclude that the polysaccharide arabinogalactan from Withania somnifera has a distinct antitussive activity consisting of cough suppression and that this action involves the mu-opioid receptor pathways.

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.

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.

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.

Effects of Vortioxetine on Sleep Architecture of Adolescents with Major Depressive Disorder.

The relationship between depression and insomnia is bidirectional and both conditions need to be treated adequately, especially in a vulnerable neurodevelopmental stage of adolescence. This study aimed to evaluate the effects of antidepressant treatment using vortioxetine (VOR) on the sleep architecture of depressed adolescents by using video-polysomnography (v-PSG), which has not been researched before. The v-PSG was performed on 30 adolescent in-patients (mean age of 15.0 years ± 1.5 SD, 21 girls) treated with VOR (dosage of 10/15/20 mg/day) administered orally once a day, before and after VOR treatment. The evaluated parameters were conventional sleep parameters, sleep fragmentation parameters, and selected spectral power indices. Symptoms of depression and insomnia before and after the treatment period were evaluated using valid and reliable questionnaires (the Children´s Depression Inventory and the Athens Insomnia Scale). Depressed adolescents showed higher REM latency and decreased REM sleep percentage after treatment than before the treatment period (p = 0.005, p = 0.009, respectively). Our study revealed REM suppression (increased REM latency and reduced REM sleep percentage), indicating altered sleep architecture as a potential result of VOR treatment, which seems to be dose-dependent.

Hippocampal neurometabolite changes in depression treatment: a (1)H magnetic resonance spectroscopy study.

Previous studies using magnetic resonance spectroscopy have related abnormalities in hippocampal metabolism to depression. Current evidence is consistent with the conclusion that the hippocampal formation plays an important role in the presentation of depressive symptoms. Eighteen adult patients with major depressive disorder, aged 20 to 60 years, underwent magnetic resonance spectroscopy of the hippocampus during a period of depressive symptomatology and after 7-11 weeks of antidepressant medication with at least 50% reduction in the Montgomery-Åsberg Depression Rating Scale ()MADRS score. During therapy, we found a significantly decreased Lac/Cr ratio in the left hippocampus. The Ins/Cr ratio showed a significant negative correlation with the severity of depression as assessed by the MADRS at baseline. Moreover, we found a negative association of NAA/Cho with age and a positive association of Cho/Cr with age, both on the left and right sides at baseline. In light of our findings and previous studies results we hypothesize that mitochondrial dysfunction leading to predominantly anaerobic glycolysis in connection with the intracellular signaling pathways disturbances and decreased astrocytic function/number might subsequently lead to decreased brain neuroplasticity in depression. These mechanisms could be positively influenced by antidepressant treatment with selective serotonin or norepineprine reuptake inhibitors, with potential effects on untimely neuronal aging in depression.

Analysis of genetic polymorphisms of brain-derived neurotrophic factor and methylenetetrahydrofolate reductase in depressed patients in a Slovak (Caucasian) population.

Major depressive disorder (MDD) is a complex neuropsychiatric disorder where both gene-gene and gene-environment interactions play an important role, but the clues are still not fully understood. One carbon metabolism in the CNS plays a critical role in the synthesis and release of neurotransmitters which are relevant to depressive disorder. We studied genetic polymorphisms of the brain derived neurotrophic factor (BDNF) and the methylenetetrahydrofolate reductase (MTHFR) in association with major depressive disorder. We genotyped the BDNF G196A, the MTHFR C677T, and A1298C polymorphisms in 134 patients diagnosed with major depression and 143 control subjects in Slovak (Caucasian) cohort of patients and probands. We found no significant association of either the BDNF G196A or MTHFR C677T polymorphisms with major depressive disorder neither in female nor male group of patients. However, the MTHFR A1298C genotype distribution was 36.6% (for AA genotype), 48.5% (AC) and 14.9% (CC) for the depressed patients, and 48.9% (AA), 42.7% (AC) and 8.4% (CC), respectively, for the control subjects. Patients with MDD had a higher prevalence of the CC genotype (OR = 2.38; 95% CI = 1.07-5.32; p = 0.032) and the AC + CC genotype (OR = 1.67; 95% CI = 1.03-2.69; p = 0.037) in comparison with the control subjects. This study shows that CC genotype of the MTHFR A1298C is associated with higher risk of MDD in Slovak population.

Evaluation of Inflammatory Response System (IRS) and Compensatory Immune Response System (CIRS) in Adolescent Major Depression.

Purpose: Nowadays, the role of two tightly interconnected systems, the inflammatory response system (IRS) and the compensatory immune response system (CIRS) in depression, is increasingly discussed. Various studies indicate pro-inflammatory activity in adolescent depression; however, there is an almost complete lack of findings about IRS and CIRS balance. Thus, we aimed to assess different IRS and CIRS indices, profiles, and IRS/CIRS ratios in drug-naïve MDD patients at adolescent age, with respect to sex. Patients and Methods: One hundred MDD adolescents (40 boys, average age: 15.4±1.2 yrs.) and 60 controls (28 boys, average age: 15.3±1.5 yrs.) were examined. Evaluated parameters were 1. plasma levels of interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, interferon gamma, tumor necrosis factor alpha (TNF-α), soluble receptor of IL-6 (sIL-6R), soluble receptors of TNF-α (sTNF-R1, sTNF-R2); 2. profiles: IL-6 trans-signaling, M1 macrophage signaling, helper T lymphocytes (Th) 1 profile, regulatory T lymphocytes (Treg)+Th2, allIRS, and allCIRS; 3. IRS vs CIRS activity ratios: TNF-α/TNF-R1, TNF-α/TNF-R2, TNF-α/sTNF-Rs (ie sTNF-R1+sTNF-R2), Th1/Th2, Th1/Treg, Th1/Th2+Treg, M1/Th2, M1/Treg, M1/Treg+Th2, allIRS/allCIRS. Results: MDD patients showed increased IL-4, IL-10, TNF-α, sIL-6R, Treg+Th2, allIRS, allCIRS, and TNF-α/sTNF-Rs, and decreased Th1/Th2+Treg. MDD females showed increased IL-10 and TNF-α compared to control females. MDD males showed increased IL-4, IL-10, sIL-6R, Treg+Th2, and TNF-α/TNF-R1 compared to control males. Increased sTNF-R1 was found in MDD males compared to MDD females. Positive correlations were found between CDI score and sIL-6R and IL-10 in the total group and between CDI score and IL-10 in adolescent males. Conclusion: Our study for the first time extensively evaluated IRS and CIRS interactions revealing enhanced pro-inflammatory TNF-α signaling and IL-6 trans-signaling in association with increased IL-10- and IL-4-mediated anti-inflammatory activity in first-episode depression at the adolescent age. Moreover, results reflect the sex-specific simultaneous activation of IRS and CIRS pathways in adolescent depression.

Major depressive disorder at adolescent age is associated with impaired cardiovascular autonomic regulation and vasculature functioning.

Cardiovascular adverse complications represent a risk factor for increased cardiovascular morbidity and mortality in patients with major depressive disorder (MDD). However, there is little knowledge of adolescent MDD. We aimed to study complex cardiovascular autonomic regulation and early atherosclerotic damage with a focus on an analysis of heart rate variability (HRV), blood pressure variability (BPV), systolic time intervals, and measures of early atherosclerotic changes in adolescent MDD. Ninety depressive adolescents (34 boys, age 15.8 ± 1.3 yrs.) and 90 age-/gender-matched controls were examined. Evaluated parameters: HRV - time and spectral parameters, BPV - mean, systolic, and diastolic blood pressure, spectral systolic parameters; haemodynamic indices - stroke volume, cardiac output, total peripheral resistance, systolic time intervals - left ventricular ejection time, pre-ejection period; atherosclerotic indices - ankle-brachial index (ABI), pulse wave velocity, brachial-ankle pulse wave velocity, cardio-ankle vascular index; growth factors - epidermal growth factor (EGF), vascular endothelial growth factor associated with monocyte chemoattractant protein-1. Our results showed that the MDD group had significantly reduced HRV and higher BPV measures, shortened systolic time intervals, lower ABI, and higher EGF compared to controls. Concluding, our study revealed that adolescent MDD is associated with cardiovascular dysregulation and early vasculature dysfunction as preclinical markers of higher risk for cardiovascular morbidity, thus adolescence seems to represent an important age period for early diagnosis and prevention of later MDD-linked cardiovascular diseases manifesting in adulthood.

The Plasma Levels of 3-Hydroxybutyrate, Dityrosine, and Other Markers of Oxidative Stress and Energy Metabolism in Major Depressive Disorder.

Major depressive disorder (MDD) is a serious mental disease with a pathophysiology that is not yet fully clarified. An increasing number of studies show an association of MDD with energy metabolism alteration and the presence of oxidative stress. We aimed to evaluate plasma levels of 3-hydroxybutyrate (3HB), NADH, myeloperoxidase, and dityrosine (di-Tyr) in adolescent and adult patients with MDD, compare them with healthy age-matched controls, and assess the effect of antidepressant treatment during hospitalisation on these levels. In our study, plasmatic levels of 3HB were elevated in both adolescents (by 55%; p = 0.0004) and adults (by 88%; p < 0.0001) with MDD compared to controls. Levels of dityrosine were increased in MDD adults (by 19%; p = 0.0092) but not adolescents. We have not found any significant effect of antidepressants on the selected parameters during the short observation period. Our study supports the findings suggesting altered energy metabolism in MDD and demonstrates its presence independently of the age of the patients.