Cytokine profile in first-episode drug-naïve major depressive disorder patients with or without anxiety.

OBJECTIVE: It is known that cytokines play a role in both depression and anxiety. This study aimed to compare the levels of multiple cytokines in patients with first-episode drug-naive major depressive disorder (MDD) with or without anxiety and analyze the correlation between the level of depression or anxiety and the serum cytokine levels. METHODS: The study involved 55 patients with first-episode drug-naive MDD. To assess anxiety symptoms, the 14-item HAMA was used. MDD patients were divided into two groups: 23 MDD patients without anxiety and 32 MDD patients with anxiety. The measurement of 37 cytokines was conducted. Serum cytokine levels between patients with MDD without anxiety and anxiety were compared. In multiple linear regression models, the relationship between the group and abnormal cytokines was explored. The receiver operating characteristic (ROC) curve analysis was performed to estimate diagnostic performance of serum cytokines in discriminating MDD patients with anxiety from MDD patients without anxiety. A correlation was evaluated between the scores of HAMD or HAMA and the serum cytokine levels. RESULTS: In MDD patients with anxiety, IL-17 C and CCL17 levels were significantly lower than in MDD patients without anxiety (all P < 0.05). Multiple measurements were corrected with Benjamini-Hochberger corrections, but none of these differences persisted (all P > 0.05). The results of multiple linear regression models revealed that after controlling for other independent variables, group was not a significant independent predictor of serum IL-17 C or CCL17 (all P > 0.05). The AUC values of IL-17 C and CCL17 were 0.643 and 0.637, respectively, in discriminating MDD patients with anxiety from MDD patients without anxiety. The results of partial correlation analyses showed the scores of HAMD were negatively correlated with the IL-17 C (r = -0.314, P = 0.021) levels with sex as a covariate. CONCLUSIONS: The findings suggest that there is a potential absence of disparity in the levels of circulating cytokines among individuals diagnosed with first-episode drug-naïve MDD, regardless of the presence or absence of comorbid anxiety.

Serum TSH Levels are Associated with Hyperactivity Behaviors in Children with Attention Deficit/Hyperactivity Disorder.

Objective: Previous studies indicated that maternal thyroid dysfunction increase the offspring's risk for attention deficit/hyperactivity disorder (ADHD). However, the relationship between thyroid function and symptoms in children with ADHD remains unclear. Methods: A total of 49 children with ADHD were enrolled. The Conners 3 scale was used to estimate the symptoms associated with ADHD. Correlation between thyroid hormones and the scores of the Conners 3 scale was evaluated by Pearson correlation analysis. Then, ADHD children were divided into two groups according to the hyperactivity index (HI) of the Conners 3 scale: ADHD children with hyperactivity behaviors (HB) (HI > 1.5) and ADHD children without HB (HI < 1.5). The demographic characteristics, thyroid hormones, and routine laboratory parameters between the two groups were collected. To distinguish HI-related factors, a univariate analysis and a binary logistic regression predictive model were used. The discriminative ability of thyroid stimulating hormone (TSH) in predicting ADHD children with HB from ADHD children without HB was investigated using the receiver operating characteristic (ROC) curve method. Results: The levels of TSH were positively correlated to the scores of the Conners 3 scale (r = 0.338, P = 0.033) and HI (r = 0.371, P = 0.019). Moreover, the levels of TSH, serum ferritin, and lactic acid were significantly increased in ADHD children with HB compared to ADHD children without HB (all P < 0.05). Furthermore, the results of binary logistic regression found that TSH (OR 2.243 (CL 1.052-4.783)) and lactic acid (OR 1.018 (CI 1.003-1.032)) were independently associated with HI. Additionally, ROC analysis indicated the potential diagnostic value of TSH in discriminating ADHD children with HB from ADHD children without HB with an AUC of 0.684. Conclusion: These results suggested that the serum TSH levels may be related to the HB in children with ADHD.

Peripheral blood cytokines as potential diagnostic biomarkers of suicidal ideation in patients with first-episode drug-naïve major depressive disorder.

Objective: Major Depressive Disorder (MDD) is a leading cause of disability, with a high risk of suicidal ideation (SI). Few studies have evaluated the potential of multiple cytokines as biomarkers for SI in patients with MDD. In the present study, we examined the serum levels of multiple cytokines in patients with first-episode drug-naïve MDD, with the aim to discover and identify serum cytokines-based biomarkers for identification of SI in MDD. Methods: A total of 55 patients with first-episode drug-naïve MDD were enrolled and divided into two groups: 26 MDD patients without SI and 29 MDD patients with SI. Beck Scale for Suicide Ideation was used to estimate SI. A total of 37 cytokines were measured using Multiplex Luminex Assays. The levels of serum cytokines between MDD patients without SI and MDD patients with SI were compared and diagnostic values of different cytokines were evaluated using the receiver operating characteristic (ROC) curve method for discriminating MDD patients with SI from MDD patients without SI. The relationship between the group and the abnormal cytokines were investigated in multiple linear regression models, with adjustments for age, gender, BMI, smoking, and Hamilton Depression Rating Scale-24 (HAMD-24) scores. Results: The levels of CCL26 and VEGF in MDD patients with SI were significantly lower than those in MDD patients without SI (all P < 0.05). On the contrary, the levels of IL-17C, CXCL10, and TNF-ß in MDD patients with SI were significantly higher than those in MDD patients without SI (all P < 0.05). Moreover, the results of multiple linear regression revealed that group was a significant independent predictor of serum IL-17C, CCL-26, VEGF, and TNF-ß levels (all P < 0.05). In terms of CXC10, group was also likely to be a significant independent predictor (ß = 0.257, P = 0.063). Furthermore, the AUC values of IL-17C and TNF-ß were 0.728 and 0.732, respectively. Additionally, a combined panel of IL-17C and TNF-ß achieved a high accuracy in discriminating MDD patients with SI from MDD patients without SI (AUC = 0.848, sensitivity = 75.9%, specificity = 72.7%). Conclusions: These results suggested that circulating IL-17C and TNF-ß may hold promise in the discovery of biomarkers for identification of SI in MDD.

Comparison of serum cytokines levels in normal-weight and overweight patients with first-episode drug-naïve major depressive disorder.

Objective: Abnormal levels of blood cytokines have been demonstrated to be associated with both excess weight and major depressive disorder (MDD). However, few studies have addressed the direct effect of body mass index (BMI) on basal serum cytokines in individuals with first-episode drug-naïve MDD. Methods: A total of 49 patients with first-episode drug-naïve MDD were categorized into normal weight (18.5 ≤ BMI < 25 kg/m2) and overweight (25 ≤ BMI < 30 kg/m2) groups according to WHO-criteria. The severity of depressive symptoms was assessed using the 24-items Hamilton Depression Scale (HAMD-24). A total of 37 cytokines were measured using Multiplex Luminex Assays. The scores of HAMD-24 and the levels of serum cytokines between normal weight group and overweight group were compared. Multiple linear regression analysis was performed to evaluate the association between abnormal serum cytokines levels and group after adjusting for HAMD-24 scores. The correlation between BMI and the scores of HAMD-24 and the levels of serum cytokines was evaluated using Pearson correlation analysis. Results: The scores of HAMD-24 in overweight group were significantly higher than normal weight group (t = -2.930, P = 0.005). Moreover, the levels of IL-1α, IL-1RA, IL-3, CXCL10, TNF-α, and ICAM-1 in overweight patients with MDD were significantly higher than those in normal-weight patients with MDD (all P < 0.05). Furthermore, after adjustment for HAMD-24 scores, there was a significant correlation between abnormal serum cytokines levels (IL-1α, IL-1RA, IL-3, CXCL10, TNF-α, and ICAM-1) and group (all P < 0.05). Additionally, BMI was positively correlated to the serum levels of IL-1α (r = 0.428, P = 0.002), IL-3 (r = 0.529, P < 0.001), IL-6 (r = 0.285, P = 0.050), IL-10 (r = 0.423, P = 0.003), IL-12 (r = 0.367, P = 0.010), IL-15 (r = 0.300, P = 0.036), CXCL10 (r = 0.316, P = 0.030), TNF-α (r = 0.338, P = 0.021), and ICAM-1 (r = 0.440, P = 0.002) in MDD patients. Conclusions: These results provide direct evidence, probably for the first time, that overweight may be associated with several serum cytokines in patients with first-episode drug-naïve MDD. The underlying mechanisms are unclear and require further investigation.

Serum CC Chemokines as Potential Biomarkers for the Diagnosis of Major Depressive Disorder.

Objective: Evidence indicates a potential role of chemokines in depression-like behavior and depression-related pathophysiological processes. In the present study, we examined the serum levels of multiple chemokines, focusing on CC chemokines, in patients with major depressive disorder (MDD), with the aim to discover and identify serum chemokines-based biomarkers for MDD diagnosis. Methods: Participants included 24 patients with MDD and 24 healthy controls. The 24-item Hamilton Depression Rating Scale (HAMD-24) was administered to assess the disease severity of patients with MDD. A total of 9 serum CC chemokines including MCP-1 (CCL-2), MIP-1α (CCL-3), MIP-1ß (CCL-4), eotaxin-1 (CCL-11), MCP-4 (CCL-13), TARC (CCL-17), MIP-3α (CCL-20), MDC (CCL-22), and Eotaxin-3 (CCL-26) were measured using electrochemiluminescence immunoassays. The levels of serum CC chemokines between MDD group and control group were compared, and diagnostic values of different CC chemokines were evaluated using the receiver operating characteristic (ROC) curve method for discriminating MDD patients from healthy controls. Correlations between the levels of serum CC chemokines and depression severity (HAMD-24 scores) were evaluated using Pearson's correlation test. Results: Patients with MDD had higher levels of serum MIP-1α and MIP-1ß and lower levels of serum MCP-1, MCP-4, TARC, MDC, and Eotaxin-3 compared to controls (all P < 0.05). Moreover, ROC curve analysis showed that the Area Under Curve (AUC) values of MIP-1α, MCP-4, TARC, and Eotaxin-3 were > 0.7 in discriminating patients with MDD from healthy controls. Furthermore, no significant relationship was found between the levels of serum CC chemokines and HAMD-24 scores in MDD group. Conclusion: These results suggested that circulating CC chemokines may hold promise in the discovery of biomarkers for diagnosing MDD.

Evidence of a Relationship Between Plasma Leptin, Not Nesfatin-1, and Craving in Male Alcohol-Dependent Patients After Abstinence.

The goal of this study was to determine whether the plasma leptin, nesfatin-1, cortisol, brain-derived neurotrophic factor (BDNF), and inflammatory cytokines could be used as potential biomarkers for the degree of craving in the alcohol-dependent patients after 1 month of abstinence. A total of 83 patients with alcohol use disorder (AUD) and 61 healthy subjects were assessed. Patients with AUD were selected from Department of Material Dependence, Anhui Mental Health Center, and subjects in the control group were selected from healthy volunteers. The Alcohol Urge questionnaire Scale (AUQ) was used to evaluate the extent of craving for alcohol, and the Michigan Alcoholism Screening Test (MAST), the Fagerstrom Test for Nicotine Dependence (FTND), the Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS) were also assessed in patients with AUD. Enzyme-Linked Immunosorbent Assay (ELISA) was used for the measurement of plasma leptin, nesfatin-1, cortisol, BDNF, Interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) levels. Compare with healthy controls, the average leptin, leptin/BMI, IL-6, CRP, and TNF-α levels in patients with AUD were significantly increased, while the BDNF levels were significantly decreased. Moreover, the partial correlational analysis showed that the AUQ scores of the alcohol-dependent patients were positively correlated with the plasma leptin levels (r = 0.613, P < 0.001), rather than nesfatin-1 (r = 0.066, P = 0.569) after controlling for age as covariate. Furthermore, plasma nesfatin-1 levels were found to be correlated with the SDS scores (r = 0.366, P = 0.001) in the AUD group. In addition, plasma leptin levels were positively associated with the plasma IL-6 (r = 0.257, P = 0.033), CRP (r = 0.305, P = 0.011), and TNF-α (r = 0.311, P = 0.009) levels, and negatively associated with the BDNF levels (r = -0.245, P = 0.042) in patients with AUD. These results suggest that plasma leptin, but not nesfatin-1, might be a potential biomarker for the degree of craving in alcohol-dependent patients after 1 month of abstinence, the mechanism of which might be related to the dysfunction of the inflammatory cytokines and BDNF levels.

Inhibition of acid­sensing ion channel 1a attenuates acid­induced activation of autophagy via a calcium signaling pathway in articular chondrocytes.

Acid­sensing ion channel 1a (ASIC1a), member of the degenerin/epithelial sodium channel protein superfamily, serves a critical role in various physiological and pathological processes. The aim of the present study was to examine the role of ASIC1a in the autophagy of rat articular chondrocytes. Autophagy was induced by acidic stimulation in rat articular chondrocytes and the extent of autophagy was evaluated via the expression levels of microtubule­associated protein 1 light chain 3II, Beclin1 and uncoordinated­51 like kinase1. Suppression of ASIC1a was achieved using small interfering RNA technology and/or inhibitor psalmotoxin­1. The expression levels of autophagy markers were measured by western blot analysis and reverse transcription­quantitative polymerase chain reaction methods. Intracellular calcium ([Ca2+]i) was analyzed using a Ca2+­imaging method. Additionally, protein expression levels of the Ca2+/calmodulin­dependent protein kinase kinase ß (CaMKKß)/5'­monophosphate­activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway were measured by western blot analysis. The results showed that autophagy was increased in a pH­ and time­dependent manner with exposure to an acidic environment. In addition, silencing ASIC1a significantly decreased the expression levels of autophagy makers, accompanied by abrogation of the acid­induced [Ca2+]i increase. Furthermore, silencing of ASIC1a downregulated the levels of CaMKKß/ß­actin and phosphorylated (p­) AMPK/AMPK, and upregulated the levels of p­mTOR/mTOR. These results indicated that ASIC1a is a potent regulator of autophagy in chondrocytes, which may be associated with decreased Ca2+ influx and the CaMKKß/AMPK/mTOR pathway.

Inhibition of ASICs reduces rat hepatic stellate cells activity and liver fibrosis: an in vitro and in vivo study.

Hepatic fibrosis is a chronic inflammation-associated disease, which is involved in the infiltration of inflammatory cells and releasing of proinflammatory cytokines. In the pathological process, protons are released by damaged cells and acidosis is considered to play a critical role in cell injury. Although the underlying mechanism (s) remain ill-defined, ASICs (acid-sensing ion channels) are assumed to be involved in this process. The diuretic, amiloride, is neuroprotective in models of cerebral ischemia, a property attributable to the inhibition of central ASICs by the drug. However, the effect of inhibition of ASICs by amiloride in the liver fibrotic process remains unclear. We found that amiloride (25, 50, or 100 µM) could restrain acid-induced HSCs at pH6 in vitro. In vivo experiments showed that amiloride could significantly alleviate liver injury, decreasing levels of profibrogenic cytokines, collagen deposition, and reducing pathological tissue damage. In summary, amiloride inhibits hepatic fibrosis in vivo and in vitro, which is probably associated with the downregulation of ASICs.