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We investigated stability and change of plasma and urinary oxytocin as well as OXTR DNA methylation patterns through psychotherapy. Furthermore, we explored the potential impact of inpatient psychotherapy on oxytocin-related biomarkers and vice versa by differentiating patients who remitted from depression versus non-remitters. Blood and urine samples were taken from 85 premenopausal women (aged 19-52), 43 clinically depressed patients from a psychosomatic inpatient unit, and 42 healthy control subjects matched for age and education at two points of time. Serum and urine oxytocin were measured using standard ELISA, and DNA methylation of the OXTR gene was assessed using bisulfite sequencing at the time of admission (baseline) and at discharge and from controls at matched time points. Oxytocin plasma levels were not associated with depression and were influenced by neither time in healthy controls nor psychotherapy in patients. Non-remitting depressed patients had significantly lower oxytocin urine levels before and after psychotherapy treatment. We found significantly lower exon 1 OTXR methylation in depressed patients over time and these differences were driven by patients remitting due to psychotherapy. A reverse pattern - higher levels of methylation in remitters - was found for exon 2 OXTR DNA methylation. Plasma oxytocin, urinary oxytocin, and OXTR DNA methylation patterns were intrapersonally relatively stable. OXTR-related factors were seemingly unaffected by inpatient psychotherapeutic treatment, but we found significant differences between remitting and non-remitting patients in urinary oxytocin and OXTR DNA methylation. If replicated, this suggests that OXTR-related markers may predict inpatient treatment outcomes of clinically depressed patients., (© 2021. The Author(s).)

Background: The model of neuroinflammation has been proposed as a possible explanation of depression. Investigations of serum levels of tumor necrosis factor- α (TNF- α ) in depressed patients have previously shown contradictory results of increased and decreased levels of TNF- α during the treatment of depression., Methods: We compared the serum levels of TNF- α in two cohorts of patients suffering from depression (ICD-10 criteria): one cohort from a psychotherapeutic unit ( n = 18), where patients were treated with Cognitive Behavioral Analysis System of Psychotherapy (CBASP), and the other cohort from a psychiatric day care unit ( n = 16). Both cohorts were investigated at the beginning and at the end of treatment. The intensity of depression was measured by means of the Beck Depression Inventory, 2 nd edition (BDI-II) at both time points., Results: We observed a statistically significant increase of TNF- α in the psychotherapeutic unit at time point 2 compared to time point 1 ( T = -14.71, p < 0.001), but not in the psychiatric day care unit. In both cohorts, BDI-II scores at time point 2 were significantly decreased compared to time point 1 (psychiatric day care unit: T = 3.32, p = 0.005; psychotherapeutic unit: T = 6.22, p < 0.001). There was a significant correlation in the psychotherapeutic unit at time point 2 ( r = -0.682, p = 0.02)., Conclusion: As TNF- α was increased at time point 2 in the psychotherapeutic unit but not in patients of the psychiatric day care unit, we propose the different durations of pretreatments in both cohorts and the associated processes of neuroinflammation as a possible explanation for our results. The lack of information about the time course of TNF- α in depression could in general explain the huge variety of TNF- α levels in different cohorts of depressed patients reported in the literature., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Adrian Groh et al.)

Introduction: Depression and alcohol dependence are frequently co-morbid and among the most prevalent mental disorders. They are a serious global health problem with social, interpersonal, and legal interpolations. Among pharmacological alternatives, anti-craving compounds as well as antidepressants, antipsychotics, anticonvulsants, benzodiazepines, and beta-blockers have shown efficacy for depression as well as alcohol consumption. The pharmacological treatment of both complex interwoven mental diseases is still challenging given the inconsistent results of open and double-blind randomized placebo-controlled studies with approved and open label medications., Areas Covered: The authors provide a systematic review of the literature with PubMed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to obtain an overview of the pharmacotherapeutic options for co-morbid depression and alcohol dependence., Expert Opinion: The effect of treating only depressive or alcohol-related symptoms appears limited. Therapies directly targeting the addiction are warranted among such dually diagnosed patients. Despite limited data, the reviewed pharmacotherapeutic treatments demonstrated efficacy in most but not in all relevant parameters of alcohol dependence and depression.

Alpha-synuclein (SNCA) is associated with a range of psychiatric diseases including neurodegeneration, alcohol craving, and depression. It regulates cellular homeostasis by virtue of its ability to interfere in dopaminergic, serotonergic, and noradrenergic pathways. To date, it is unclear whether the previously described association between SNCA and depressive symptomatology is limited to females with eating disorders or whether it could be extended to include healthy individuals. We included 105 women and 108 men. Genetic data and mRNA expression analyses were drawn from peripheral blood and the severity of depressive symptoms was quantified by the Beck's Depression Inventory (BDI). We found a significant association between the NACP-Rep1 length polymorphism and the BDI score (p = 0.004). Moreover, there was a significant gender dimorphism regarding mRNA expression of SNCA (p = 0.011). Our analysis revealed no further association between the In4 polymorphism or between the mRNA expression of SNCA and the BDI score. Since this investigation was limited to healthy individuals, conclusions concerning depression according to ICD-10 or DSM-IV cannot be drawn. The reported results may contribute to a better understanding of the molecular mechanisms linked to depressive symptoms.

Elevated plasma homocysteine levels have been found in different psychiatric disorders, including major depression and eating disorders. The aim of the present study was to evaluate whether presence of depression or depressive symptoms is associated with elevated homocysteine levels in patients with eating disorders. Total plasma homocysteine levels were assessed in 44 females with anorexia nervosa (n = 21) or bulimia nervosa (n = 23). Comorbid major depressive disorder (MDD) was diagnosed according to DSM-IV criteria using a semi-structured interview (SCID-I). Furthermore, depressive symptoms were assessed using Beck's depression inventory (BDI). Presence of MDD was not associated with elevated homocysteine levels (t-test: T = 0.42; df = 42; P = 0.68). However, self-rated presence of clinically relevant depressive symptoms (BDI score18) was associated with elevated homocysteine (T = -2.8; df = 42; P = 0.008). Presence of depressive symptoms may explain elevated homocysteine levels previously reported in patients with eating disorders or vice versa. Longitudinal studies are needed to unravel this hen or egg problem.

Alpha-synuclein (alpha-Syn) is a neuronal protein involved in the regulation of brain serotonin and dopamine levels. We analyzed the peripheral expression of alpha-Syn mRNA and Beck Depression Inventory scores in female patients suffering from anorexia nervosa (n = 18) or bulimia nervosa (n = 24). We found a significant positive association between alpha-Syn mRNA expression and the total scores of the Beck Depression Inventory (linear regression; R(2) = 0.20; p = 0.003). alpha-Syn may play a pathophysiological role in depressive symptoms associated with eating disorders. Further investigations in patients with depression as a sole diagnosis are needed to support its role in the pathogenesis of major depression., (Copyright 2008 S. Karger AG, Basel.)

Background: Major depressive disorder (MDD) represents a tremendous health threat to the world's population. Electroconvulsive therapy (ECT) is the most effective treatment option for refractory MDD patients. Ample evidence suggests brain-derived neurotrophic factor (BDNF) to play a crucial role in ECT's mode of action. Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) are involved in BDNF production. Hypothesis: The DNA methylation of gene regions encoding for t-PA and PAI-1 might be a suitable biomarker for ECT response prediction. Methods: We withdrew blood from two cohorts of treatment-resistant MDD patients receiving ECT. In the first cohort (n = 59), blood was collected at baseline only. To evaluate DNA methylation changes throughout the treatment course, we acquired a second group (n = 28) and took blood samples at multiple time points. DNA isolated from whole blood and defined immune cell subtypes (B cells, monocytes, natural killer cells, and T cells) served for epigenetic analyses. Results: Mixed linear models (corrected for multiple testing by Sidak's post-hoc test) revealed (1) no detectable baseline blood DNA methylation differences between ECT remitters (n = 33) and non-remitters (n = 53) in the regions analyzed, but (2) a significant difference in t-PA's DNA methylation between the investigated immune cell subtypes instead (p < 0.00001). This difference remained stable throughout the treatment course, showed no acute changes after ECT, and was independent of clinical remission. Conclusion: DNA methylation of both proteins seems to play a minor role in ECT's mechanisms. Generally, we recommend using defined immune cell subtypes (instead of whole blood only) for DNA methylation analyses. [ABSTRACT FROM AUTHOR]

The irreversible inhibitor of monoamine oxidase, tranylcypromine, is a potent antidepressant, but its use is limited to special indications due to side effects and dietary restrictions. The antidepressant action of tranylcypromine is not completely explainable by its effects on monoamine oxidase. Tranylcypromine also leads to an increase in brain trace amines, which are believed to play a key role in the pathophysiology of depression. It also affects other pathophysiological pathways associated with depression. Tranylcypromine treatment leads to an up-regulation of GABAB-receptors and modulates the phospholipid metabolism, which is essential for normal brain function. These findings implicate that the efficacy of tranylcypromine as an antidepressant may be due to its multiple actions within the human brain. [ABSTRACT FROM AUTHOR]

• ECT remitters and non-remitters differ in their immune profile at baseline. • After a single ECT session, the relative proportion of cytotoxic NK cells increases. • The rise in cytotoxic NK cells correlates with seizure quality. • ECT-induced NK cell increases were independent of treatment remission. Major Depressive Disorder (MDD) is a major contributor to the global burden of disease. Approximately 30–50% of depressed patients fail to reach remission with standard treatment approaches. Electroconvulsive therapy (ECT) is one of the most effective options for these patients. Its exact therapeutic mechanism remains elusive, and reliable predictors of response are absent in the routine clinical practice. To characterize its mode of action and to facilitate treatment decision-making, we analyzed ECT's acute and chronic effects on various immune cell subsets. For this purpose, blood was withdrawn from depressed patients (n =21) directly before and 15 min after the first and last ECT session, respectively. After isolating peripheral blood mononuclear cells, we investigated defined populations of immune cells and their proportional changes upon ECT treatment using flow cytometry. By these means, we found ECT remitters (R; n =10) and non-remitters (NR; n =11) to differ in their relative proportion of putative immunoregulatory CD56highCD16 –/dim and cytotoxic CD56dimCD16 + natural killer (NK) cells (CD56highCD16 –/dim/CD56dimCD16 + : R =0.064(±0.005), NR=0.047(±0.005), p <0.05; linear mixed models) and thus in their NK cell cytotoxicity. NK cell cytotoxicity was further increased after a single ECT session (before=0.066(±0.005), after=0.045(±0.005), p <0.001) and was associated with ECT quality parameters (maximum sustained coherence: r 2=0.389, β =−0.656, p <0.001) and long-term BDI-II rating changes (r 2=0.459, β =−0.726, p <0.05; both linear regression analysis). To conclude, particular NK cell subsets seem to be involved in ECT's acute effect and its clinical outcome. Due to the limited number of patients participating in our pilot study, future approaches are required to replicate our findings. [ABSTRACT FROM AUTHOR]

Objective Reduced muscle mass is a characteristic finding in sarcopenia, the central element of physical frailty syndrome, and a major cause of physical function decay, morbidity and mortality in the elderly. Studies so far demonstrated reduced muscle mass in depressed patients with an average age over 60 years. An open question is whether muscle mass reduction is already observed earlier. Therefore, muscle mass was assessed in middle-aged male and female depressive patients, and the findings were related to indicators of hypothalamus-pituitary adrenal axis activation, lifestyle factors, endocrine and immune measures. Methods Sixty-seven depressed patients (mean age 38.6y; 58.2% female) and 26 healthy volunteers (mean age 40.5y; 61.5% female) were included. Muscle mass, adrenal gland volume, and intra-abdominal adipose tissue were assessed by magnetic resonance tomography. Laboratory parameters included fasting cortisol, pro-inflammatory cytokines, factors constituting the metabolic syndrome, and relative insulin resistance according to the homeostasis model assessment (HOMA-IR). Results We found significant effects of depression (F = 4.2; P = 0.043) and gender (F = 182; P < 0.001) on muscle mass. Muscle mass was reduced in depressed men compared to healthy men (F = 3.4; P = 0.044), particularly in those with chronic depression. In contrast, no such association was observed in depressed females. Adrenal gland volume and intra-abdominal fat was increased in depressed men and women, although not significantly. Correlations were observed for muscle mass with the amount of self-reported exercise and depression severity, and for depression severity with self-reported exercise. Further findings comprised lower self-reported activity and higher cortisol concentrations in depressed male and female compared to healthy probands. Conclusions Muscle mass is reduced in middle-aged depressed men, particularly those with chronic disease course. This association is not observed in depressed females, possibly pointing to the role of female sex steroids in maintaining muscle mass. The increase of adrenal gland volume in depressed patients may point to the role of a dysregulated hypothalamus-pituitary-adrenal system. The inverse association of exercise with muscle mass demonstrates the importance of physical activity. Looking at the long term consequences of reduced muscle mass, interventions to preserve and rebuild muscle mass in depression – such as structured exercise interventions – should be recommended. Significant outcomes Muscle mass is decreased in male patients with major depressive disorder, particular those with chronic disease course. This difference was not observed in female depressed patients. The extent of muscle mass reduction is correlated to depression severity and inversely to physical activity, pointing to the role of depression associated inactivity. Low muscle mass is a risk factor for physical frailty, therefore interventions aiming at improving physical fitness may be recommended. Limitations Sex steroids were not assessed in the study groups. [ABSTRACT FROM AUTHOR]

Outbred rat lines such as Wistar rats are commonly used for models of depressive disorders. Such rats arise from random mating schedules. Hence, genetic drift occurs in outbred populations which could lead to genotypic and phenotypic heterogeneity between rats from different vendors. Additionally, vendor specific rearing conditions could contribute to intrastrain variability. In the present study differences in behavioral responses to the chronic mild stress (CMS) model of depression within Wistar rat strains from different vendors are described. DNA methylation studies and mRNA expression analysis of p11 revealed that the behavioral differences between the substrains are reflected at the epigenetic and genetic level. The results suggest that there are breeder-dependent differences in vulnerability to stress in the CMS model of depression, which might bear on the validity of the model and contribute to contradictory findings and difficulties of replication between laboratories. P11 mRNA expression seems to be differently regulated depending on the quality of the stress response evoked by CMS exposure. [ABSTRACT FROM AUTHOR]

Objective Major depressive disorder (MDD) is associated with decreased physical activity and increased rates of the metabolic syndrome (MetS), a risk factor for the development of type 2 diabetes and cardiovascular disorders. Exercise training has been shown to improve cardiorespiratory fitness and metabolic syndrome factors. Therefore, our study aimed at examining whether patients receiving an exercise program as an adjunct to inpatient treatment will benefit in terms of physiological and psychological factors. Method Fourty-two inpatients with moderate to severe depression were included. Twenty-two patients were randomized to additional 3x weekly exercise training (EXERCISE) and compared to treatment as usual (TAU). Exercise capacity was assessed as peak oxygen uptake (VO2peak), ventilatory anaerobic threshold (VAT) and workload expressed as Watts (W). Metabolic syndrome was defined according to NCEP ATPIII panel criteria. Results After 6 weeks of treatment, cardiorespiratory fitness (VO2peak, VAT, Watt), waist circumference and HDL cholesterol were significantly improved in EXERCISE participants. Treatment response expressed as ≥50% MADRS reduction was more frequent in the EXERCISE group. Conclusions Adjunctive exercise training in depressed inpatients improves physical fitness, MetS factors, and psychological outcome. Given the association of depression with cardiometablic disorders, exercise training is recommended as an adjunct to standard antidepressant treatment. [ABSTRACT FROM AUTHOR]

Abstract: Semicarbazide sensitive aminooxidase (SSAO) is known to interplay with monoamine oxidases (MAO) and several antidepressants. Taking into account the monoamine hypothesis concerning the pathophysiology of depression, the aim of the present pilot study was to evaluate serum SSAO activity in depressed patients. A total of 21 inpatients with major depression and 41 healthy controls were studied. Serum SSAO activity was determined by HPLC on days 1, 5 and 10 of inpatient treatment. At baseline without medication including antidepressants, highly depressed patients (MADRS score ≥30) had significantly decreased serum SSAO activity (mean 385±161mU/l) when compared to healthy controls (mean 526±141mU/l; p =0.003). This SSAO decrease was less pronounced at day 5 and day 10 under an antidepressive drug regime. Decreased serum SSAO activity was observed in patients with major depression, especially in those with high MADRS scores. The present results support the hypothesis of dysfunctional monoaminergic metabolism in the pathogenesis of depressive disorders. The disputable association between depression and monoamine metabolism requires further investigation, particularly with regard to SSAO activity and medication status. [Copyright &y& Elsevier]