The association between circulating Hcy and Lp-PLA2 levels and poststroke depression: A meta-analysis.

OBJECTIVE: To analyze the correlation between circulating homocysteine (Hcy) and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and poststroke depression (PSD). MATERIALS AND METHODS: Chinese (Chinese National Knowledge Infrastructure, Wanfang, and VIP) and English (PubMed, EMBASE, MEDLINE, and Cochrane Library) databases on the correlation between circulating Hcy and Lp-PLA2 and PSD were collected. Meta-analysis was performed to compare the distinctions in circulating Hcy and Lp-PLA2 levels between PSD and non-PSD groups. Meta-analysis was conducted by using STATA 15.0 software. RESULTS: A total of 20 literatures were included in this study. The level of circulating Lp-PLA2 in the PSD group was obviously higher than that in the non-PSD group (weighted mean differences: 2.75, 95%CI: 0.10-5.39, P = .002), which was an independent predictor of PSD (effect size = 0.05, 95%CI: 0.03, 0.07, P < .001). The level of circulating Hcy in the PSD group was obviously higher than that in the non-PSD group (weighted mean differences = 1.41, 95%CI: 1.01, 1.81, P < .001), which was an independent influencing factor for the occurrence of PSD (effect size = 0.07, 95%CI: 0.04, 0.09, P = .011). CONCLUSION: Circulating Hcy and Lp-PLA2 levels are linked to the development of PSD, and can be applied as predictive or diagnostic indicators.

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.

Sex- and age-specific prevalence and risk factors of depressive symptoms in Parkinson's disease.

Although depressive symptoms are common in PD, few studies investigated sex and age differences in depressive symptoms. Our study aimed to explore the sex and age differences in the clinical correlates of depressive symptoms in patients with PD. 210 PD patients aged 50-80 were recruited. Levels of glucose and lipid profiles were measured. The Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA) and the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) assessed depressive symptom, cognition and motor function, respectively. Male depressive PD participants had higher fasting plasma glucose (FPG) levels. Regarding the 50-59 years group, depressive patients had higher TG levels. Moreover, there were sex and age differences in the factors associated with severity of depressive symptoms. In male PD patients, FPG was an independent contributor to HAMD-17 (Beta = 0.412, t = 4.118, p < 0.001), and UPDRS-III score was still associated with HAMD-17 in female patients after controlling for confounding factors (Beta = 0.304, t = 2.961, p = 0.004). Regarding the different age groups, UPDRS-III (Beta = 0.426, t = 2.986, p = 0.005) and TG (Beta = 0.366, t = 2.561, p = 0.015) were independent contributors to HAMD-17 in PD patients aged 50-59. Furthermore, non-depressive PD patients demonstrated better performance with respect to visuospatial/executive function among the 70-80 years group. These findings suggest that sex and age are crucial non-specific factors to consider when assessing the relationship between glycolipid metabolism, PD-specific factors and depression.

Association of remnant cholesterol with depression among US adults.

BACKGROUND: Remnant cholesterol is receiving increasing attention because of its association with various diseases. However, there have been no studies on remnant cholesterol levels and depression. METHODS: A cross-sectional analysis was performed based on the National Health and Nutrition Examination Survey (NHANES) 2005-2016. Depression was assessed using a Patient Health Questionnaire (PHQ-9). Fasting remnant cholesterol was calculated as the total cholesterol minus high-density lipoprotein cholesterol (HDL-C) minus low-density lipoprotein cholesterol (LDL-C). Logistic regression analysis with sampling weights was used to examine the association between remnant cholesterol concentration and depression. RESULTS: Among 8,263 adults enrolled in this study (weighted mean age, 45.65 years), 5.88% (weighted percentage) had depression. Compared to the participants without depression, those with depression had higher concentration of remnant cholesterol (weighted mean, 26.13 vs. 23.05, P < 0.001). There was a significant positive relationship between remnant cholesterol concentration and depression and multivariable-adjusted OR with 95% CI was 1.49 (1.02-2.17). Among the subgroup analyses, remnant cholesterol concentration was positively associated with depression among participants less than 60 years (OR, 1.62; 95% CI, 1.09-2.42), male (OR, 2.02; 95% CI, 1.01-4.05), BMI under 30 (OR, 1.83; 95% CI, 1.14-2.96), and those with diabetes (OR, 3.88; 95% CI, 1.43-10.49). CONCLUSIONS: Remnant cholesterol concentration positively correlated with depression, suggesting that a focus on remnant cholesterol may be useful in the study of depression.

Association of Interleukin-6 Polymorphisms with Schizophrenia and Depression: A Case-Control Study.

OBJECTIVE: Growing evidence suggests a crossover in genetic susceptibility to schizophrenia and depression. We aimed to investigate the association of the rs1800795 and rs1800796 polymorphisms of the IL-6 gene with schizophrenia and depression in the Han Chinese population, combined with IL-6 serum levels. METHODS: Gene sequencing and enzyme-linked immunosorbent assay were performed on 113 subjects with schizophrenia, 114 subjects with depression, and 110 healthy controls. RESULTS: Our findings showed that IL-6 concentrations in schizophrenia and depression groups were significantly higher than in the control group. The rs1800796 CC genotype and C allele were significantly associated with depression (P = .012 and P < .05, respectively). The rs1800796 CC and CG genotype was significantly associated with chronic schizophrenia (P = .020 and P = .009, respectively). Regarding the rs1800795 polymorphism, only one case of CG genotype was detected. The remainder were of the GG genotype. CONCLUSION: The IL-6 rs1800796 might serve as a protective factor for depression and schizophrenia in the Han Chinese population.

Correlation of Serum IL-18, BDNF, and IL-1ß with Depression and Prognosis after Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Objective: To explore the correlation of serum IL-18, BDNF, and IL-1ß with depression and prognosis after acute exacerbation of chronic obstructive pulmonary disease (COPD). Methods: By means of retrospective analysis, the data of 240 patients at the acute exacerbation of COPD treated in our hospital (February 2018-February 2021) were analyzed. All patients received conventional treatment 1 d after admission, patients' serological indicators were measured before treatment, and after 30 d of follow-up, the patients were divided into the survival group (SG) and death group (DG) according to their clinical outcomes, the Beck's Depression Inventory (BDI) scores of the surviving patients were investigated, the correlation of IL-18, BDNF, and IL-1ß levels with depression was analyzed by R analytics, and the correlation of IL-18, BDNF, and IL-1ß levels with prognosis was analyzed by ROC curve analysis. Results: The results of 30 d follow-up showed that 220 patients survived (91.7%) and 20 patients died (8.3%). Among the surviving patients, 95 patients had depression and 125 patients did not have depression; the BDI scores of the depressed subjects and the nondepressed subjects were 10.35 ± 1.25 points and 2.06 ± 0.76 points, respectively; significant differences in IL-18, BDNF, and IL-1ß levels between SG and DG were observed (P < 0.05); significant differences in IL-18, BDNF, and IL-1ß levels between the depressed subjects and the nondepressed subjects were observed (538.43 ± 19.02 vs. 515.32 ± 9.65, 7.54 ± 0.56 vs. 12.11 ± 2.41, and 8.70 ± 0.98 vs. 8.12 ± 0.87; P < 0.001); among the depressed patients, the IL-18 and IL-1ß levels were positively correlative with the BDI scores (r = 0.781, r = 0.2583, P < 0.001, P = 0.012), and the BDNF level was negatively correlative with the BDI scores (r = -0.3277, P = 0.001) before treatment; according to the ROC analysis, the AUC (95% CI) of IL-18, BDNF, and IL-1ß in predicting prognosis was 0.8770 (0.8281-0.9260), 0.7723 (0.6879-0.8567), and 0.7165 (0.6080-0.8250) (P < 0.05), respectively. Conclusion: In regard to the depression in COPD patients after acute exacerbation, IL18 and IL-1ß show positive correlation, and BDNF presents negative correlation. All three indicators have predictive value for patient outcome.

Effect of Ramadan intermittent fasting on inflammatory markers, disease severity, depression, and quality of life in patients with inflammatory bowel diseases: A prospective cohort study.

BACKGROUND: Intermittent fasting (IF) during the month of Ramadan is part of the religious rituals of Muslims. The effect of intermittent fasting on disease activity in inflammatory bowel diseases (IBD) is still unknown. This is the first study to assess the effect of IF during Ramadan on inflammatory markers in patients diagnosed with IBD. The effects on clinical disease activity, quality of life, and levels of depression were also assessed. METHODS: Patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) who intended to observe Ramadan fasting were recruited. The following were assessed immediately before and at the end of Ramadan: Serum CRP and stool calprotectin, partial Mayo score, Harvey Bradshaw index (HBI), Simple IBD questionnaire (SIBDQ), and Hamilton depression scale questionnaire. RESULTS: 80 patients diagnosed with IBD were recruited (60 UC, 20 CD). Serum CRP and stool calprotectin did not show a significant change before vs after fasting (median CRP 0.53 vs 0.50, P value = 0.27, Calprotectin 163 vs 218 respectively, P value = 0.62). The partial Mayo score showed a significant rise after fasting (median 1 before vs 1 after fasting, mean: 1.79 vs 2.33 respectively, P value = 0.02). Harvey-Bradshaw index did not show a significant change after fasting (median 4 vs 5, P value = 0.4). Multiple linear regression revealed that older age and a higher baseline calprotectin were associated with a higher change in Mayo score after fasting (P value = 0.02 and P value = 0.01, respectively). No significant change was detected in SIBDQ or Hamilton depression scale scores. CONCLUSIONS: In patients diagnosed with UC, IF during Ramadan was associated with worsening of clinical parameters, the effect was more pronounced in older patients and those with higher baseline calprotectin levels. However, IF during Ramadan was not associated with an adverse effect on objective inflammatory markers (CRP and calprotectin).

Changes of Mental State and Serum Prolactin Levels in Patients with Schizophrenia and Depression after Receiving the Combination Therapy of Amisulpride and Chloroprothixol Tablets.

OBJECTIVE: To investigate the changes in mental state and serum prolactin levels in patients with schizophrenia and depression after receiving the combination therapy of amisulpride and chloroprothixol tablets. METHODS: A total of 148 schizophrenic patients with depression were randomly divided into control group (N = 73) and study group (N = 75). The control group was treated with clopidothiol, and the study group was treated with amisulpride. Symptom scores, sleep quality, adverse reactions, therapeutic effects, prolactin, and progesterone levels, HAMD, PANSS, and PSP scores were compared between the two groups. RESULTS: The symptom scores of both groups were significantly reduced, but when compared to the control group, the symptom scores of the research group were significantly reduced more significantly (P < 0.05); serum GDNF levels of both groups were significantly increased, while serum NSE, IL-1, and MBP levels were significantly reduced (P < 0.05). However, the research group altered more substantially (P < 0.05) than the control group; the overall PSQI score of the research group was lower (P < 0.05) than the control group; and the incidence of adverse responses in the control and study groups was 12.3 percent and 4.0 percent. The research group had a lower rate of adverse responses (P < 0.05) than the control group, and the effective treatment of the control and research groups was 82.2 percent and 98.7%, respectively. The research group had a lower rate of adverse reactions (P < 0.05) than the control group, while the control and research groups' successful treatment rates were 82.2 percent and 98.7%, respectively. When compared to the control group, the research group had a greater treatment efficiency (P < 0.05); blood prolactin and progesterone levels were considerably lowered in both groups, but the reductions in the research group were more evident (P < 0.05). Both groups had considerably lower HAMD and PANSS scores, and both had significantly higher PSP scores, although the difference in the research group was more evident (P < 0.05). CONCLUSION: For people with schizophrenia and depression, a combination of amisulpride and chloroprothixol pills has a considerable effect. It can help patients with their clinical symptoms and sleep quality while also lowering their serum prolactin levels, which is favorable to their illness recovery. As a result, the combined treatment of amisulpride and chloroprothixol pills deserves to be promoted and used.

Body self-esteem is related to subjective well-being, severity of depressive symptoms, BMI, glycated hemoglobin levels, and diabetes-related distress in type 2 diabetes.

BACKGROUND: There are limited data on the role of body image in patients with type 2 diabetes. The purpose of this study was to compare body self-esteem in this group with norms for the general Polish population and to investigate the relationship between body self-esteem and the psychological and clinical characteristics of the course of diabetes. METHODS: A group of 100 consecutive adult patients with type 2 diabetes (49 women and 51 men) aged 35 to 66 years were assessed using the Body Esteem Scale (BES), World Health Organization-Five Well-Being Index (WHO-5), Problem Areas in Diabetes Scale (PAID), and Hamilton Rating Scale for Depression (HAM-D). RESULTS: In comparison to norms for the general population, women with type 2 diabetes had lower body self-esteem only in the dimension of Physical Condition (M = 30.71; SD = 7.11 versus M = 32.96; SD = 5.69; P = 0.003), whereas men in the dimensions of Physical Condition (M = 42.43; SD = 9.43 versus M = 48.30; SD = 8.42; P <0.001) and Upper Body Strength (M = 32.16; SD = 6.60 versus M = 33.97; SD = 5.86; P = 0.015). There were moderate or weak positive correlations between the overall BES score and/or its dimensions and subjective well-being, and negative correlations between the overall BES score and/or its dimension and the severity of depression symptoms, level of glycated hemoglobin (HbA1c), body mass index (BMI), and diabetes-related distress among women. Among men, BES scores were positively correlated with well-being, and negatively, with BMI and diabetes-related distress. A correlation of r = 0.39 between BES scores and HbA1c levels was relatively high compared with values for other psychosocial factors. Both in women and men, a high Physical Condition score was a significant predictor of better well-being, less severe depression, and milder diabetes-related distress. Among men, it was also a significant predictor of lower BMI, whereas among women, BMI was predicted by Weight Concern. CONCLUSIONS: Persons with diabetes seem to have lower body self-esteem than the general population, which is significantly associated with clinical and psychological characteristics of the diabetes course. The observed differences and relationships are gender-specific.

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.

Metabolite trajectories across the perinatal period and mental health: A preliminary study of tryptophan-related metabolites, bile acids and microbial composition.

Depression and anxiety during pregnancy and postpartum are common, but affected women differ in timing, trajectories, and extent of symptoms. The objective of this pilot, feasibility study is to analyze trajectories of serotonin and tryptophan-related metabolites, bile acid metabolites, and microbial composition, in relation to psychiatric history and current symptoms across the perinatal period. Serum and fecal samples were collected from 30 women at three times points in the perinatal period and assayed with LC-MS/MS and 16S sequencing respectively. We defined mean trajectories for each metabolite, clustered individuals by metabolite trajectories, tested associations between metabolites, and examined metabolite levels in relation to microbial composition. Findings of note include: (1) changes in kynurenine and the ratio of kynurenic acid to kynurenine from second trimester to third trimester were strongly associated with baseline primary and secondary bile acids. (2) Secondary bile acid UDCA and its conjugated forms were associated with lower bacterial diversity and levels of Lachnospiraceae, a taxa known to produce Short Chain Fatty Acids. (3) History of anxiety was associated with UDCA levels, but history of major depression was not associated with any of the bile acids. (4) There was a trend towards lower dietary fiber for those with history of anxiety or depression. Overall, our results reveal substantial temporal variation in tryptophan-related metabolites and in bile acid metabolites over the perinatal period, with marked inter-individual variability. Trajectories of TRP -related metabolites, primary and secondary bile acids, and the absence or presence of microbes that produce Short Chain Fatty Acids (SCFAs) considered in concert have the potential to differentiate individuals based on perinatal adaptations that may impact mental and overall health.

Analysis of serum levels of organochlorine pesticides and related factors in Parkinson's disease.

BACKGROUND: There is evidence that environmental factors contribute to the onset and progression of Parkinson's disease (PD). Pesticides are a class of environmental toxins that are linked to increased risk of developing PD. However, few studies have investigated the association between specific pesticides and PD, especially in China, which was one of the first countries to adopt the use of pesticides. METHODS: In this study, serum levels of 19 pesticides were measured in 90 patients with PD and 90 healthy spouse controls. We also analyzed the interaction between specific pesticides and PD. In addition, the association between pesticides and clinical features of PD was also investigated. Finally, we investigated the underlying mechanism of the association between pesticides and PD. RESULTS: Serum levels of organochlorine pesticides, which included α-hexachlorocyclohexane (HCH), ß-HCH, γ-HCH, δ-HCH, propanil, heptachlor, dieldrin, hexachlorobenzene, p,p'-dichlorodiphenyltrichloroethane and o,p'-dichloro-diphenyl-trichloroethane were higher in PD patients than controls. Moreover, α-HCH and propanil levels were associated with PD. Serum levels of dieldrin were associated with Hamilton Depression Scale and Montreal Cognitive Assessment scores in PD patients. In SH-SY5Y cells, α-HCH and propanil increased level of reactive oxygen species and decreased mitochondrial membrane potential. Furthermore, propanil, but not α-HCH, induced the aggregation of α-synuclein. CONCLUSIONS: This study revealed that elevated serum levels of α-HCH and propanil were associated with PD. Serum levels of dieldrin were associated with depression and cognitive function in PD patients. Moreover, propanil, but not α-HCH, induced the aggregation of α-synuclein. Further research is needed to fully elucidate the effects of pesticides on PD.

Pigment epithelium-derived factor may induce antidepressant phenotypes in mice by the prefrontal cortex.

Pigment epithelium-derived factor (PEDF) is a multifunctional glycoprotein encoded by SERPINF1 and our previous study reported that PEDF may have antidepressant effects. As a key brain region regulating cognition, memory and emotion, the prefrontal cortex (PFC) has been studied extensively in major depressive disorder (MDD), but there are few reports on the relationship between PEDF and the PFC. In this study, enzyme-linked immunosorbent assay showed that the PEDF level was decreased in the plasma of MDD patients compared with that of healthy controls. Western blotting validated that the PEDF expression in the PFC was downregulated in the mouse chronic social defeat stress and rat chronic unpredictable mild stress models of depression. Correspondingly, normal mice overexpressing PEDF in the PFC showed depression-resistant phenotypes. We detected PFC metabolite levels by liquid chromatography-tandem mass spectrometry and found significant upregulation of 5-hydroxyindoleacetic acid, kynurenine, 5-hydroxytryptamine, ornithine and glutamine, and downregulation of 5-hydroxytryptophan, glutamic acid and aspartic acid in PEDF-overexpressing mice compared with control mice, in which no such changes were detected. Combined with the above findings, this provides an insight into a potential mechanism of the antidepressant effects of PEDF via the PFC, which may help to improve understanding of depression pathophysiology.

The bidirectional longitudinal association between depressive symptoms and HbA1c : A systematic review and meta-analysis.

AIM: To investigate whether there is a bidirectional longitudinal association of depression with HbA1c . METHODS: We conducted a systematic literature search in PubMed, PsycINFO, CINAHL and EMBASE for observational, longitudinal studies published from January 2000 to September 2020, assessing the association between depression and HbA1c in adults. We assessed study quality with the Newcastle-Ottawa-Scale. Pooled effect estimates were reported as partial correlation coefficients (rp ) or odds ratios (OR). RESULTS: We retrieved 1642 studies; 26 studies were included in the systematic review and eleven in the meta-analysis. Most studies (16/26) focused on type 2 diabetes. Study quality was rated as good (n = 19), fair (n = 2) and poor (n = 5). Of the meta-analysed studies, six investigated the longitudinal association between self-reported depressive symptoms and HbA1c and five the reverse longitudinal association, with a combined sample size of n = 48,793 and a mean follow-up of 2 years. Higher levels of baseline depressive symptoms were associated with subsequent higher levels of HbA1c (partial r = 0.07; [95% CI 0.03, 0.12]; I2 38%). Higher baseline HbA1c values were also associated with 18% increased risk of (probable) depression (OR = 1.18; [95% CI 1.12,1.25]; I2 0.0%). CONCLUSIONS: Our findings support a bidirectional longitudinal association between depressive symptoms and HbA1c . However, the observed effect sizes were small and future research in large-scale longitudinal studies is needed to confirm this association. Future studies should investigate the role of type of diabetes and depression, diabetes distress and diabetes self-management behaviours. Our results may have clinical implications, as depressive symptoms and HbA1c levels could be targeted concurrently in the prevention and treatment of diabetes and depression. REGISTRATION: PROSPERO ID CRD42019147551.

Links Between Inflammation, Mood, and Physical Function Among Older Adults With HIV.

OBJECTIVES: People living with human immunodeficiency virus (PLWH) treated with antiretrovirals have life spans similar to their HIV-negative peers. Yet, they experience elevated inflammation-related multimorbidity. Drawing on biopsychosocial determinants of health may inform interventions, but these links are understudied in older PLWH. We investigated cross-sectional relationships between psychosocial factors (mood, loneliness, and stigma), inflammatory markers, and age-related health outcomes among 143 PLWH aged 54-78 years. METHOD: Participants provided blood samples for serum cytokine and C-reactive protein (CRP) analyses, completed surveys assessing psychosocial factors and health, and completed frailty assessments. Regression models tested relationships between key psychosocial-, inflammation, and age-related health variables, adjusting for relevant sociodemographic and clinical factors. RESULTS: Participants with more depressive symptoms had higher composite cytokine levels than those with fewer depressive symptoms (ß = 0.22, t(126) = 2.71, p = .008). Those with higher cytokine levels were more likely to be prefrail or frail (adjusted odds ratio = 1.72, 95% confidence interval = 1.01-2.93) and reported worse physical function (ß = -0.23, t(129) = -2.64, p = .009) and more cognitive complaints (ß = -0.20, t(129) = -2.16, p = .03) than those with lower cytokine levels. CRP was not significantly related to these outcomes; 6-month fall history was not significantly related to inflammatory markers. DISCUSSION: Novel approaches are needed to manage comorbidities and maximize quality of life among older PLWH. Illustrating key expected biopsychosocial links, our findings highlight several factors (e.g., depressive symptoms, poorer physical function) that may share bidirectional relationships with chronic inflammation, a key factor driving morbidity. These links may be leveraged to modify factors that drive excessive health risk among older PLWH.

Circulating microRNAs and Molecular Oxidative Stress in Older Adults with Neuroprogression Disorders.

BACKGROUND: circulating microRNAs are potential blood biomarkers differentially expressed in many diseases including neuro depression disorders. It controls the expression of human genes and associated cellular and physiological processes in normal and diseased cells. We aimed to evaluate the potential role of circulating miRNAs and their association with both stress hormones and cellular oxidative stress in neuro depression disorders occurred among older adults. METHODS: a total of 70 healthy subjects were included in this study. Based upon the profile of mood states (POMS-32 score), the participants classified into two groups; healthy subjects (n =30) and depression (n =40). The expression of microRNAs; miR-124, miR-34a-5p, miR-135, and miR-451-a and their correlation with cellular oxidative stress parameters; cellular NO, genes of SOD2, CAT and iNOS, and hormones; cortisol and serotonin were estimated by a quantitative real-time RT-PCR, high-performance liquid chromatography, and ELISA Immunoassay techniques, respectively. RESULTS: depression was reported in 57.14% of the participants. The results showed a significant increase (p =0.01) in the total mood scores, and relative depression domains in older adults with depression compared to healthy controls. The relative expression levels of miR-124, miR-34a-5p significantly increased and the expression levels of miR-135, and miR-451-a significantly decreased in older adults with depression compared to healthy controls. In addition, the levels of cortisol significantly increased and serotonin (5HT) significantly reduced in all participants with depression. Cellular oxidative stress analysis for depressed subjects showed that serum NO levels and the expression of iNO gene significantly increased conversely with a decline in the molecular expression antioxidative genes; SOD2, CAT, respectively. The results showed that cellular oxidative stress parameters correlated positively with depression scores, cortisol, and negatively with cellular serotonin levels. In depressed subjects, the relative expression of microRNAs correlated positively with depression score, NO, iNOS, cortisol, and negatively associated with SOD2, CAT, and serotonin. CONCLUSION: The combination of cellular oxidative stress and hormonal levels strongly supports a role for circulating miRNAs; miR-124, miR-34a-5p, miR-135, and miR-451-a in the regulation of depression and mood disorders among older adults. The expressed microRNAs with their related association to cellular oxidative stress and adrenal hormones are a step towards understanding the role of these small RNA molecules in the progression of depression among older adults. Thus, cellular miRNAs might have a prognostic role in the diagnosis and as a target for treatment strategies in depressed subjects.

Serum metabolomics of end-stage renal disease patients with depression: potential biomarkers for diagnosis.

BACKGROUND: End-stage renal disease (ESRD) is the final stage during the development of renal failure. Depression is the most common psychiatric disorder in patients with ESRD, which in turn aggravates the progression of renal failure, however, its underlying mechanism remains unclear. This study aimed to reveal the pathogenesis and to discover novel peripheral biomarkers for ESRD patients with depression through metabolomic analysis. METHODS: Ultra-high-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) was used to explore changes of serum metabolites among healthy controls, ESRD patients with or without depression. The differential metabolites between groups were subjected to clustering analysis, pathway analysis, receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 57 significant serum differential metabolites were identified between ESRD patients with or without depression, which were involved in 19 metabolic pathways, such as energy metabolism, glycerolipid metabolism, and glutamate-centered metabolism. Moreover, the area under the ROC curve of gentisic acid, uric acid, 5-hydroxytryptamine, 2-phosphoglyceric acid, leucyl-phenylalanine, propenyl carnitine, naloxone, pregnenolone, 6-thioxanthene 5'-monophosphate, hydroxyl ansoprazole, zileuton O-glucuronide, cabergoline, PA(34:2), PG(36:1), probucol and their combination was greater than 0.90. CONCLUSIONS: Inflammation, oxidative stress and energy metabolism abnormalities, glycerolipid metabolism, and glutamate-centered metabolism are associated with the pathogenesis of ESRD with depression, which may be promising targets for therapy. Furthermore, the identified differential metabolites may serve as biomarkers for the diagnosis of ESRD patients with depression.

Disturbances in branched-chain amino acid profile and poor daily functioning in mildly depressed chronic obstructive pulmonary disease patients.

BACKGROUND: Depression is one of the most common and untreated comorbidities in chronic obstructive pulmonary disease (COPD), and is associated with poor health outcomes (e.g. increased hospitalization/exacerbation rates). Although metabolic disturbances have been suggested in depressed non-diseased conditions, comprehensive metabolic phenotyping has never been conducted in those with COPD. We examined whether depressed COPD patients have certain clinical/functional features and exhibit a specific amino acid phenotype which may guide the development of targeted (nutritional) therapies. METHODS: Seventy-eight outpatients with moderate to severe COPD (GOLD II-IV) were stratified based on presence of depression using a validated questionnaire. Lung function, disease history, habitual physical activity and protein intake, body composition, cognitive and physical performance, and quality of life were measured. Comprehensive metabolic flux analysis was conducted by pulse stable amino acid isotope administration. We obtained blood samples to measure postabsorptive kinetics (production and clearance rates) and plasma concentrations of amino acids by LC-MS/MS. Data are expressed as mean [95% CI]. Stats were done by graphpad Prism 9.1.0. ɑ < 0.05. RESULTS: The COPD depressed (CD, n = 27) patients on average had mild depression, were obese (BMI: 31.7 [28.4, 34.9] kg/m2), and were characterized by shorter 6-min walk distance (P = 0.055), physical inactivity (P = 0.03), and poor quality of life (P = 0.01) compared to the non-depressed COPD (CN, n = 51) group. Lung function, disease history, body composition, cognitive performance, and daily protein intake were not different between the groups. In the CD group, plasma branched chain amino acid concentration (BCAA) was lower (P = 0.02), whereas leucine (P = 0.01) and phenylalanine (P = 0.003) clearance rates were higher. Reduced values were found for tyrosine plasma concentration (P = 0.005) even after adjustment for the large neutral amino acid concentration (= sum BCAA, tyrosine, phenylalanine and tryptophan) as a marker of dopamine synthesis (P = 0.048). CONCLUSION: Mild depression in COPD is associated with poor daily performance and quality of life, and a set of metabolic changes in depressed COPD that include perturbation of large neutral amino acids, specifically the BCAAs. Trial registration clinicaltrials.gov: NCT01787682, 11 February 2013-Retrospectively registered; NCT02770092, 12 May 2016-Retrospectively registered; NCT02780219, 23 May 2016-Retrospectively registered; NCT03796455, 8 January 2019-Retrospectively registered.

Effects of Importin α1/KPNA1 deletion and adolescent social isolation stress on psychiatric disorder-associated behaviors in mice.

Importin α1/KPNA1 is a member of the Importin α family widely present in the mammalian brain and has been characterized as a regulator of neuronal differentiation, synaptic functionality, and anxiety-like behavior. In humans, a de novo mutation of the KPNA1 (human Importin α5) gene has been linked with schizophrenia; however, the precise roles of KPNA1 in disorder-related behaviors are still unknown. Moreover, as recent studies have highlighted the importance of gene-environment interactions in the development of psychiatric disorders, we investigated the effects of Kpna1 deletion and social isolation stress, a paradigm that models social stress factors found in human patients, on psychiatric disorder-related behaviors in mice. Through assessment in a behavioral battery, we found that Kpna1 knockout resulted in the following behavioral phenotype: (1) decreased anxiety-like behavior in an elevated plus maze test, (2) short term memory deficits in novel object recognition test (3) impaired sensorimotor gating in a prepulse inhibition test. Importantly, exposure to social isolation stress resulted in additional behavioral abnormalities where isolated Kpna1 knockout mice exhibited: (1) impaired aversive learning and/or memory in the inhibitory avoidance test, as well as (2) increased depression-like behavior in the forced swim test. Furthermore, we investigated whether mice showed alterations in plasma levels of stress-associated signal molecules (corticosterone, cytokines, hormones, receptors), and found that Kpna1 knockout significantly altered levels of corticosterone and LIX (CXCL5). Moreover, significant decreases in the level of prolactin were found in all groups except for group-housed wild type mice. Our findings demonstrate that Kpna1 deletion can trigger widespread behavioral abnormalities associated with psychiatric disorders, some of which were further exacerbated by exposure to adolescent social isolation. The use of Kpna1 knockout mice as a model for psychiatric disorders may show promise for further investigation of gene-environment interactions involved in the pathogenesis of psychiatric disorders.