High plasma nesfatin-1 level in Chinese adolescents with depression.

Depression is a common psychiatric disorder with high prevalence and mortality rates as well as high risk of serious harm in adolescents that have significant negative impact on families and society. The feeding inhibitor Nesfatin-1 contributes to the regulation of stress and emotion. The purpose of this project was to compare the differences in the levels of Nesfatin-1 between adolescents with depression and healthy adolescents, and verify the association between the levels of Nesfatin-1 and severity of depression in adolescents. Adolescents with depression (n = 61) and healthy adolescents (n = 30) were evaluated. The Hamilton Depression Rating Scale (HAMD-17) was used to classify the adolescents with depression. Thirty-one and thirty-two was assigned to the mild-to-moderate (HAMD-17 ≤ 24) depression group and severe group (HAMD-17 > 24). Plasma Levels of Nesfatin-1 were measured by human ELISA Kit and differences among groups evaluated. Data were analyzed using the statistical software SPSS 23. HAMD-17 score was significantly higher in adolescents with depression than that in the healthy adolescents (P < 0.001). Median plasma Nesfatin-1 levels in adolescents with depression and healthy adolescents differed significantly at 37.3 pg/ml (22.1 pg/ml, 63.6 pg/ml) and 18.1 pg/ml (10.0 pg/ml, 25.7 pg/ml) (p < 0.001). A multivariate logistic regression analysis showed high plasma Nesfatin-1 concentrations were associated with increased risk of depression (OR = 0.914, 95% CI 0.87-0.96, P < 0.001). The receiver operating characteristic curve showed that the area under curve were 0.808 (95% CI 0.722-0.894, P < 0.001). Plasma Nesfatin-1 cut-off point of 32.45 pg/mL showed 59% sensitivity and 100% specificity. Median plasma Nesfatin-1 levels in the severe depression group (n = 30), mild-to-moderate depression group (n = 31), and control group (n = 30) were 53.4 pg/ml (28.2 pg/ml, 149.1 pg/ml), 29.9 pg/ml (14.5 pg/ml, 48.5 pg/ml) and 18.1 pg/ml (10.0 pg/ml, 25.7 pg/ml), and differed significantly among the three groups (P < 0.001). Median plasma level of Nesfatin-1 in males (n = 20) was 38.6 pg/ml (23.5 pg/ml, 70.1 pg/ml), while that in females (n = 41) was 37.3 pg/ml (22.0 pg/ml, 63.6 pg/ml), which was not a significant difference (P > 0.05). Plasma levels of Nesfatin-1 increased with severity of depression in adolescents and may be useful as a biomarker of depression severity. Further studies are needed in future projects.

Chemokine (C-C motif) ligand 5 (RANTES) concentrations in the peripheral blood of patients with a depressive disorder.

BACKGROUND: Inflammation plays a role in the pathomechanism of depressive disorder. Cytokines interact with iodothyronine deiodinases (DIOs) that are involved in thyroid hormone (TH) metabolism. DIOs are known as modifiers of the inflammatory response. RANTES is a chemokine that has been detected in a wide range of inflammatory disorders, but is less studied in depression. We aimed to investigate the concentration of RANTES in patients with recurrent depressive disorder (rDD) and examine any potential correlation with other molecules, such as interleukins (ILs) and DIOs. METHODS: The levels of RANTES and other molecules associated with depressive disorder, including deiodinase type 1 (DIO1), interleukin (IL)1ß, and IL-6, were measured by enzymatic immune assay (ELISA) in the serum of 43 patients with depressive disorder and 36 controls. RESULTS: RANTES levels were higher in depressed patients than in controls. The level of RANTES was negatively correlated with the deiodinase type 1 (DIO1) level in women diagnosed with rDD. IL-1ß and IL-6 levels were significantly higher in depressed patients than in controls. IL-1ß was positively correlated with deiodinase type 3 (DIO3). A negative correlation between DIO1 and the number of depressive episodes in women with rDD was observed. CONCLUSION: With the observed elevated RANTES levels, increases in ILs concentrations, and a possible link between immune aspects and DIOa in patients with rDD, our study contributes to the current pool of knowledge about the complex aetiology of depression and suggests future studies focus on precision mechanisms that explain the link between TH-related molecules and immune molecules.

The role of selenium in depression: a systematic review and meta-analysis of human observational and interventional studies.

The results of human studies are inconsistent regarding selenium and depressive disorders. Therefore, we aimed to conduct a systematic review and meta-analysis of observational and interventional studies and provided an overview of the role of selenium in depression. Three databases including Medline, Scopus, and Web of Science were searched on June 30, 2020 and updated on April 12, 2021. Also, we searched in electronical databases of WHO Global Index Medicus and ClinicalTrials.gov. No time or language restrictions were used for the search. A random effects model was used to pool effect sizes. In total, 20 studies were included in the systematic review, and 15 studies were included in the meta-analysis. There were no significant differences in serum selenium levels between patients with depression and healthy subjects (WMD: 2.12 mg/L; 95% CI: - 0.11, 4.36; I2 = 98.0%, P < 0.001). Also, no significant correlation was found between serum levels of selenium and depression scores (r: - 0.12; 95% CI: - 0.33, 0.08; I2 = 73.5%, P = 0.010). Nevertheless, there was a significant negative association between high selenium intake and the risk of postpartum depression (OR: 0.97; 95% CI: 0.95, 0.99; I2 = 0.0%, P = 0.507). In addition, selenium supplementation significantly reduced depressive symptoms (WMD: - 0.37; 95% CI: - 0.56, - 0.18; I2 = 0.0%, P = 0.959). Taken these results together, selenium seems to have a protective role against postpartum depression and can be considered as a beneficial adjuvant therapy in patients with depression. Further studies are necessary to draw definitive conclusions.

Comparison of thyroid-stimulating hormone levels in adolescents with schizophrenia, bipolar disorder, unipolar depression, conduct disorders, and hyperkinetic disorders.

ABSTRACT: The aim of this study was to retrospectively compare values of thyroid-stimulating hormone (TSH) in adolescent patients diagnosed with schizophrenia, bipolar disorder, unipolar depression (UNI-DEP), conduct disorders (CD), and hyperkinetic disorders.The research involved 1122 patients (718 women, 64%); aged 12 to 18 hospitalized in the Department of Adolescent Psychiatry, Medical University of Lodz. We analyzed TSH levels in the whole study population and compared it between the above-mentioned subgroups of diagnoses.Mean serum TSH concentration in the studied population (n = 1122) was 2.06 µIU/mL. The values of percentiles were as follows: 2.5th - 0.53 µIU/mL, 10th - 0.89 µIU/mL, 25th - 1.31 µIU/mL, 50th - 1.9 µIU/mL, 75th - 2.6 µIU/mL, 90th - 3.43 µIU/mL, 97.5th - 4.72 µIU/mL. TSH values were negatively correlated with patients' age (P = .00001). Patients with bipolar depression had higher TSH levels than patients with CD (P = .002). Also, when male and female groups were examined separately we found that female patients with UNI-DEP and bipolar disorder had higher TSH levels than female patients with CD (P = .001; P = .001).Our results confirm that there may be a higher prevalence of thyroid dysfunctions in bipolar and UNI-DEP subgroups among adolescents and that it is worthy to consider some kind of interventions regarding thyroid function in depressed individuals.

Correlation of Antibodies to Neurotransmitters in the Sera of Women with Alcohol Dependence and Depressive Disorders.

Comparative analysis of blood sera from women with alcohol dependence and depressive disorders or from conditionally healthy women revealed reduced level of antibodies to dopamine, norepinephrine, serotonin, glutamate, and GABA in blood serum in women with dysthymic disorder and a depressive episode and their increased content in women with alcohol dependence in combination with depressive disorders.

Use of the PsycheMERGE Network to Investigate the Association Between Depression Polygenic Scores and White Blood Cell Count.

Importance: Although depression is a common psychiatric disorder, its underlying biological basis remains poorly understood. Pairing depression polygenic scores with the results of clinical laboratory tests can reveal biological processes involved in depression etiology and in the physiological changes resulting from depression. Objective: To characterize the association between depression polygenic scores and an inflammatory biomarker, ie, white blood cell count. Design, Setting, and Participants: This genetic association study was conducted from May 19, 2019, to June 5, 2021, using electronic health record data from 382 452 patients across 4 health care systems. Analyses were conducted separately in each health care system and meta-analyzed across all systems. Primary analyses were conducted in Vanderbilt University Medical Center's biobank. Replication analyses were conducted across 3 other PsycheMERGE sites: Icahn School of Medicine at Mount Sinai, Mass General Brigham, and the Million Veteran Program. All patients with available genetic data and recorded white blood cell count measurements were included in the analyses. Primary analyses were conducted in individuals of European descent and then repeated in a population of individuals of African descent. Exposures: Depression polygenic scores. Main Outcomes and Measures: White blood cell count. Results: Across the 4 PsycheMERGE sites, there were 382 452 total participants of European ancestry (18.7% female; median age, 57.9 years) and 12 383 participants of African ancestry (61.1% female; median age, 39.0 [range, birth-90.0 years]). A laboratory-wide association scan revealed a robust association between depression polygenic scores and white blood cell count (ß, 0.03; SE, 0.004; P = 1.07 × 10-17), which was replicated in a meta-analysis across the 4 health care systems (ß, 0.03; SE, 0.002; P = 1.03 × 10-136). Mediation analyses suggested a bidirectional association, with white blood cell count accounting for 2.5% of the association of depression polygenic score with depression diagnosis (95% CI, 2.2%-20.8%; P = 2.84 × 10-70) and depression diagnosis accounting for 9.8% of the association of depression polygenic score with white blood cell count (95% CI, 8.4%-11.1%; P = 1.78 × 10-44). Mendelian randomization provided additional support for an association between increased white blood count and depression risk, but depression modeled as the exposure showed no evidence of an influence on white blood cell counts. Conclusions and Relevance: This genetic association study found that increased depression polygenic scores were associated with increased white blood cell count, and suggests that this association may be bidirectional. These findings highlight the potential importance of the immune system in the etiology of depression and may motivate future development of clinical biomarkers and targeted treatment options for depression.

Serum Proteomic Analysis of Cannabis Use Disorder in Male Patients.

Cannabis use has been growing recently and it is legally consumed in many countries. Cannabis has a variety of phytochemicals including cannabinoids, which might impair the peripheral systems responses affecting inflammatory and immunological pathways. However, the exact signaling pathways that induce these effects need further understanding. The objective of this study is to investigate the serum proteomic profiling in patients diagnosed with cannabis use disorder (CUD) as compared with healthy control subjects. The novelty of our study is to highlight the differentially changes proteins in the serum of CUD patients. Certain proteins can be targeted in the future to attenuate the toxicological effects of cannabis. Blood samples were collected from 20 male individuals: 10 healthy controls and 10 CUD patients. An untargeted proteomic technique employing two-dimensional difference in gel electrophoresis coupled with mass spectrometry was employed in this study to assess the differentially expressed proteins. The proteomic analysis identified a total of 121 proteins that showed significant changes in protein expression between CUD patients (experimental group) and healthy individuals (control group). For instance, the serum expression of inactive tyrosine protein kinase PEAK1 and tumor necrosis factor alpha-induced protein 3 were increased in CUD group. In contrast, the serum expression of transthyretin and serotransferrin were reduced in CUD group. Among these proteins, 55 proteins were significantly upregulated and 66 proteins significantly downregulated in CUD patients as compared with healthy control group. Ingenuity pathway analysis (IPA) found that these differentially expressed proteins are linked to p38MAPK, interleukin 12 complex, nuclear factor-κB, and other signaling pathways. Our work indicates that the differentially expressed serum proteins between CUD and control groups are correlated to liver X receptor/retinoid X receptor (RXR), farnesoid X receptor/RXR activation, and acute phase response signaling.

Monoamine Oxidase as a Potential Biomarker of the Efficacy of Treatment of Mental Disorders.

The review summarizes the results of our own studies and published data on the biological markers of psychiatric disorders, with special emphasis on the activity of platelet monoamine oxidase. Pharmacotherapy studies in patients with the mixed anxiety-depressive disorder and first episode of schizophrenia have shown that the activity of platelet monoamine oxidase could serve as a potential biomarker of the efficacy of therapeutic interventions in these diseases.

Association of depressive disorder with biochemical and anthropometric indices in adult men and women.

Depression is a common psychiatric disorder. Although many risk factors for depression have been reported, the associations of biochemical and anthropometric indices with depressive disorder remain unclear. The objective of this study was to assess whether there are significant associations of depressive disorder with biochemical and obesity indices. This study was based on data from the Korea National Health and Nutrition Examination Survey from 2007 to 2018, and logistic regression was performed to examine the association of depression with biochemical and obesity indices. A total of 33,993 subjects were included in the analyses. Study subjects consisted of 13,178 men in the control group (mean age of 51.12 years), 509 men in the depression group (53.67), 18,279 women in the control group (50.5), and 2027 women in the depression group (55.39). Among men, the depression group was significantly more likely to have a lower height and weight than the control group. Compared to the control group, the depression group was more likely to have higher triglyceride levels and tended to have lower hematocrit and blood urea nitrogen (BUN) levels. Among women, the depression group was more likely to have higher triglyceride, aspartate aminotransferase (AST), BUN, and creatinine levels and lower high-density lipoprotein cholesterol (HDL-C), hematocrit, and red blood cell counts. Several biochemical and anthropometric indices used in this study were associated with depressive disorder, but these associations may differ according to sex.

Assessing the links between childhood trauma, C-reactive protein and response to antidepressant treatment in patients with affective disorders.

Adverse Childhood Experiences (ACE) are a well-known risk-factor for depression. Additionally, (high-sensitive) C-reactive Protein (hsCRP) is elevated in subgroups of depressed patients and high following ACE. In this context the literature considers hsCRP and ACE to be associated with treatment resistant depression. With the data being heterogenous, this study aimed to explore the associations of ACE, hsCRP levels and response to antidepressant treatment in uni- and bipolar depression. N = 76 patients diagnosed with uni- or bipolar depression and N = 53 healthy controls were included. Treatment was over 6 weeks in an inpatient psychiatric setting within an observatory study design. Depressive symptoms were assessed by the Montgomery-Asberg Depression Rating Scale (MADRS), ACE were assessed by the Childhood Trauma Questionnaire (CTQ); the body-mass-index (BMI) and hsCRP were measured. HsCRP levels did not differ between the study population and the healthy controls. While the depressive symptoms decreased, the hsCRP levels increased. Sexual abuse was associated with significant higher and emotional abuse with lower levels of hsCRP after 6 weeks. The baseline hsCRP levels and the ACE subgroups did not show significant associations with the treatment response in unipolar depressed patients. The long-lasting effects of specific forms of ACE may have relevant impact on inflammation, supporting hsCRP to be a suitable biomarker. With ACE and hsCRP not showing any significant associations with treatment response in the unipolar depressed subgroup, a more differentiate research concerning biomarkers and treatment regimens is needed when talking about treatment response.

CYP2D6*10 polymorphism and the enantioselective O-desmethylation of S-(+)- and R-(-)-venlafaxine in Japanese psychiatric patients.

According to previous studies, R-(-)-venlafaxine (VEN) has higher enantioselectivity than S-(+)-VEN, and the plasma concentration of R-(-)-VEN varies depending on CYP2D6 activity. Therefore, we examined the pharmacokinetic effects of CYP2D6*10 genotypes on the steady-state concentrations of the enantiomers of VEN. The individuals were 71 Japanese depressed patients treated with racemic VEN. The concentrations of the enantiomers of VEN and O-desmethylvenlafaxine (ODV) were measured. Polymerase chain reaction (PCR) was used to determine the CYP2D6*10 genotypes. The plasma concentrations of S-(+)-VEN were approximately 1.9-fold higher than those of R-(-)-VEN. The plasma concentrations of S-(+)-VEN and R-(-)-VEN seemed to be higher in individuals with two mutant alleles of CYP2D6*10, although no significant differences were found in the plasma levels of S-(+)-VEN and R-(-)-VEN between CYP2D6*10 genotypes. The number of mutant alleles of CYP2D6*10 was a significant factor associated with the R-(-)-ODV/R-(-)-VEN ratio (P = .004) in multiple regression analysis. This suggests that CYP2D6*10 mutations affect the metabolism of R-(-)-VEN and S-(+)-VEN. Further studies are needed to examine how these findings affect clinical practice.

The association between serum homocysteine and depression: A systematic review and meta-analysis of observational studies.

BACKGROUND: Hyperhomocysteinaemia is known to interfere with neurological functions; however, there is a controversy regarding the relationship between homocysteine and depression. MATERIALS AND METHODS: Science Direct, MEDLINE and ISI Web of Science were searched to find relevant articles, published up to August 2020. Studies were included if they compared homocysteine levels in healthy subjects with subjects with depression. Also, articles that reported the association between hyperhomocysteinaemia and risk of depression were included. Odds ratios of depression and means of homocysteine were used to ascertain the overall effect size. RESULTS: Homocysteine level was higher in subjects with depression in comparison with healthy controls (weight mean difference = 2.53 µmol/L, 95% confidence interval: 1.77, 3.30), and the depression diagnostic tool was a source of heterogeneity. Homocysteine level was significantly higher in subjects with depression in studies that used Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV), Geriatric Depression Scale (GDS), Zung Self-Rating Depression Scale (ZDRS) and Beck Depression Index II (BDI-II) as depression diagnostic tools. Also, participants with hyperhomocysteinaemia had a higher chance of depression (Pooled risk = 1.34, 95% confidence interval: 1.19, 1.52), where the depression diagnostic tool was a source of heterogeneity. In contrast to ZDRS and Patient Health Questionnaire (PHQ) subgroups, hyperhomocysteinaemia yielded a significantly higher risk of depression in DSM-IV, GDS and 'other' subgroups. CONCLUSION: Homocysteinemia level is higher in individuals with depression. However, the depression diagnostic tool used is instrumental in influencing their association, and thus, future studies should focus on the tools for depression assessment.

A peripheral inflammatory signature discriminates bipolar from unipolar depression: A machine learning approach.

BACKGROUND: Mood disorders (major depressive disorder, MDD, and bipolar disorder, BD) are considered leading causes of life-long disability worldwide, where high rates of no response to treatment or relapse and delays in receiving a proper diagnosis (~60% of depressed BD patients are initially misdiagnosed as MDD) contribute to a growing personal and socio-economic burden. The immune system may represent a new target to develop novel diagnostic and therapeutic procedures but reliable biomarkers still need to be found. METHODS: In our study we predicted the differential diagnosis of mood disorders by considering the plasma levels of 54 cytokines, chemokines and growth factors of 81 BD and 127 MDD depressed patients. Clinical diagnoses were predicted also against 32 healthy controls. Elastic net models, including 5000 non-parametric bootstrapping procedure and inner and outer 10-fold nested cross-validation were performed in order to identify the signatures for the disorders. RESULTS: Results showed that the immune-inflammatory signature classifies the two disorders with a high accuracy (AUC = 97%), specifically 92% and 86% respectively for MDD and BD. MDD diagnosis was predicted by high levels of markers related to both pro-inflammatory (i.e. IL-1ß, IL-6, IL-7, IL-16) and regulatory responses (IL-2, IL-4, and IL-10), whereas BD by high levels of inflammatory markers (CCL3, CCL4, CCL5, CCL11, CCL25, CCL27, CXCL11, IL-9 and TNF-α). CONCLUSIONS: Our findings provide novel tools for early diagnosis of BD, strengthening the impact of biomarkers research into clinical practice, and new insights for the development of innovative therapeutic strategies for depressive disorders.

Depression: Biological markers and treatment.

Nowadays depression is considered as a systemic illness with different biological mechanisms involved in its etiology, including inflammatory response, hypothalamic-pituitary-adrenal (HPA) axis dysregulation and neurotransmitter and neurotrophic systems imbalance. Novel "omics" approaches, such as metabolomics and glycomics provide information about altered metabolic pathways and metabolites, as well as disturbances in glycosylation processes affected by or causing the development of depression. The clinical diagnosis of depression continues to be established based on the presence of the specific symptoms, but due to its heterogeneous underlying biological background, that differs according to the disease stage, there is an unmet need for treatment response biomarkers which would facilitate the process of appropriate treatment selection. This paper provides an overview of the role of major stress response system, the HPA axis, and its dysregulation in depression, possible involvement of neurotrophins, especially brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and insulin-like growth factor-1, in the development of depression. Article discusses how activated inflammation processes and increased cytokine levels, as well as disturbed neurotransmitter systems can contribute to different stages of depression and could specific metabolomic and glycomic species be considered as potential biomarkers of depression. The second part of the paper includes the most recent findings about available medical treatment of depression. The described biological factors impose an optimistic conclusion that they could represent easy obtainable biomarkers potentially predicting more personalized treatment and diagnostic options.

The relationship between oxytocin blood concentrations and antidepressants over pregnancy and the postpartum.

Antidepressant treatment of perinatal depression is increasingly common and accepted in clinical guidelines. It has been suggested that serotonergic antidepressants may effect changes in the oxytocinergic system, including oxytocin levels, and that this may be one of the beneficial mechanisms of action for these drugs. Furthermore, oxytocin has been associated with the quality of the parent-child relationship, which may be important in treatment of perinatal depression. This study will explore if there is a relationship between antidepressant use over the perinatal period and oxytocin levels. Data from a pregnancy cohort study are used from 279 women across three groups: women taking antidepressants in pregnancy (n = 48), women with untreated depression (n = 31) and healthy control women (n = 200). Data included antidepressant use, maternal depression and oxytocin plasma concentrations in pregnancy and up to 12 months postpartum. We found that concurrent oxytocin blood concentrations were not associated with perinatal antidepressant use. However, oxytocin blood concentrations increased more steeply in those on antidepressants across the perinatal period compared to control women. A steeper increase for Selective Serotonergic Reuptake Inhibitors was observed, however, this effect was on the boarder of statistical significance. In conclusion, although antidepressant use and oxytocin was not associated at any time point, women taking antidepressants during pregnancy had larger increases in oxytocin over the perinatal period. Future research could examine specific agents and class of antidepressant and the relationship to parenting.

Sex difference in cerebrospinal fluid/blood albumin quotients in patients with schizophreniform and affective psychosis.

BACKGROUND: The importance of cerebrospinal fluid (CSF) diagnostics for psychiatry is growing. The CSF/blood albumin quotient (QAlb) is considered to be a measure of the blood-CSF barrier function. Recently, systematically higher QAlb in males than in females was described in neurological patients. The aim of this study was to investigate whether a sex difference could also be detected in a well-characterized psychiatric cohort. METHODS: The patient cohort comprised 989 patients, including 545 females and 444 males with schizophreniform and affective syndromes who underwent CSF diagnostics, including QAlb measurement. The basic CSF findings and antineuronal autoantibody data of this cohort have already been published. This re-analysis employed analysis of covariance with age correction for QAlb mean values and chi2-testing for the number of increased age-corrected QAlb levels to investigate sex differences in QAlb. RESULTS: The QAlb levels were elevated above reference levels by 18% across all patients, and a comparison between male and female patients revealed a statistically significant sex difference, with increased values in 26% of male patients and a corresponding rate of only 10% in female patients (chi2 = 42.625, p < 0.001). The mean QAlb values were also significantly higher in males (6.52 ± 3.69 × 10-3) than in females (5.23 ± 2.56 × 10-3; F = 52.837, p < 0.001). DISCUSSION: The main finding of this study was a significantly higher QAlb level in male compared to female patients with psychiatric disorders, complementing previously described sex differences in neurological patient cohorts. This result indicates bias from some general factors associated with sex and could be partly explained by sex differences in body height, which is associated with spine length and thus a longer distance for CSF flow within the subarachnoid space down the spine from the occipital area to the lumbar puncture site in males compared to females. Hormonal influences caused by different estrogen levels and other sex-specific factors could also play a relevant role. The significance of the study is limited by its retrospective design, absence of a healthy control group, and unavailability of exact measures of spine length.

Iron Status is Associated with Mood, Cognition, and Functional Ability in Older Adults: A Cross-Sectional Study.

Several conditions are risk factors for iron deficiency (ID), some of which are highly prevalent in older individuals. Despite the amount of evidence pointing for a role of ID in cognition, mood and physical functional ability, the research addressing these associations in older individuals is still scarce. In the present study, 162 older community-dwelling individuals (29.53% classified as ID) were enrolled in a cross-sectional analysis and characterized regarding cognition, mood, functional ability, general nutritional intake and iron status. Assessment of iron status was performed using several blood biomarkers. Storage and erythropoiesis dimensions were positively associated with memory, along with an interaction (moderator effect) between iron storage and nutritional status. A more depressed mood was negatively associated with (iron) transport, transport saturation and erythropoiesis dimensions, and functional tiredness was positively associated with the erythropoiesis dimension. These observations indicate that lower iron status is associated with depressive mood, functional tiredness and poorer memory ability, with the latter moderated by nutritional status. These findings suggest that using iron as a continuous variable may be useful in finding associations with iron homeostasis, eventually missed when iron levels are considered within the usual classification groups.

Lipid Profile, Lipoprotein Subfractions, and Fluidity of Membranes in Children and Adolescents with Depressive Disorder: Effect of Omega-3 Fatty Acids in a Double-Blind Randomized Controlled Study.

Depressive disorder (DD) is a psychiatric disorder whose molecular basis is not fully understood. It is assumed that reduced consumption of fish and omega-3 fatty acids (FA) is associated with DD. Other lipids such as total cholesterol (TCH), LDL-, and HDL-cholesterols (LDL-CH, HDL-CH) also play a role in depression. The primary endpoint of the study was the effect of omega-3 FA on the severity of depression in children and adolescents. This study aimed to investigate the secondary endpoint, relationship between depressive disorder symptoms and lipid profile, LDL- and HDL-cholesterol subfractions, Paraoxonase 1 (PON1) activities, and erythrocyte membrane fluidity in 58 depressed children and adolescents (calculated by the statistical program on the effect size), as well as the effect of omega-3 FA on the monitored parameters. Depressive symptoms were assessed by the Children's Depression Inventory (CDI), lipid profile by standard biochemical procedures, and LDL- and HDL-subfractions by the Lipoprint system. Basic biochemical parameters including lipid profile were compared with levels in 20 healthy children and were in the physiological range. Improvement of symptoms in the group supplemented with a fish oil emulsion rich in omega-3 FA in contrast to omega-6 FA (emulsion of sunflower oil) has been observed. We are the first to report that omega-3 FAs, but not omega-6 FA, increase large HDL subfractions (anti-atherogenic) after 12 weeks of supplementation and decrease small HDL subfractions (proatherogenic) in depressed children. We found a negative correlation between CDI score and HDL-CH and the large HDL subfraction, but not LDL-CH subfractions. CDI score was not associated with erythrocyte membrane fluidity. Our results suggest that HDL-CH and its subfractions, but not LDL-CH may play a role in the pathophysiology of depressive disorder. The study was registered under ISRCTN81655012.

Effects of Early Life Stress on Bone Homeostasis in Mice and Humans.

Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (µCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.