Association of interleukin-2 and interleukin-10 with the pathophysiology and development of generalized anxiety disorder: a case-control study.

BACKGROUND: Generalized anxiety disorder (GAD) is a devastating mental health condition characterized by constant, uncontrolled worrying. Recent hypotheses indicate that pro-inflammatory cytokines and chemokines are potential contributors to the pathogenesis of GAD. Here, we aimed to assess the role of interleukin-2 (IL-2) and interleukin-10 (IL-10) in the pathophysiology and development of GAD. METHODS: This study recruited 50 GAD patients diagnosed according to the DSM-5 criteria and 38 age-sex-matched healthy controls (HCs). A qualified psychiatrist evaluated all study subjects. The socio-demographic and clinical characteristics of the study population were determined using pre-structured questionnaires or interviews, and cytokine serum levels were estimated using commercially available ELISA kits. RESULTS: We observed reduced serum IL-10 levels in GAD patients compared to HCs (33.69 ± 1.37 pg/ml vs. 44.12 ± 3.16 pg/ml). Also, we observed a significant negative correlation between altered IL-10 levels and GAD-7 scores (r=-0.315, p = 0.039). Moreover, IL-10 serum measurement exhibited good predictive value in receiver operating characteristics (ROC) analysis with an area under the curve (AUC) value of 0.793 (p < 0.001) with 80.65% sensitivity and 62.79% specificity at a cutoff value of 33.93 pg/ml. Conversely, we noticed elevated serum IL-2 levels in GAD patients than in HCs (14.81 ± 2.88 pg/ml vs. 8.08 ± 1.1 pg/ml); however, it failed to maintain any significant association with GAD-7 scores, implying that IL-2 might not be involved in GAD pathogenesis. The lower AUC value (0.640; p > 0.05) exhibited by IL-2 serum measurement in ROC analysis further supported that IL-2 might not be associated with GAD. CONCLUSION: This study provides new insights into the complex interplay between anti-inflammatory cytokines and GAD pathogenesis. Based on the present findings, we can assume that IL-10 but not IL-2 may be associated with the pathophysiology and development of GAD. However, further research with a larger population size and longitudinal design is required to confirm the potential diagnostic efficacy of IL-10.

Evaluation of serum interleukin-1 receptor antagonist levels in major depressive disorder: A case-control study.

Background and Aims: Major depressive disorder (MDD) is characterized by the occurrence of one or more depressive episodes lasting a minimum of 2 weeks and is marked by a persistently low mood and a lack of enjoyment in daily activities. The diagnosis of MDD is not possible by a well-established laboratory test or biomarker. A wide range of potential biomarkers for depression have been proposed by many studies, but none of them has adequately described the correlation between the biomarkers and depression. The purpose of this study was to evaluate serum interleukin-1 receptor antagonist (IL-1RA) levels as an early depression risk factor. Methods: The present case-control study included 88 participants. Among them, 44 MDD patients enrolled from the psychiatry department of a public hospital in Dhaka, Bangladesh, and 44 age- and sex-matched healthy controls (HCs) from various sites in Dhaka city. A qualified psychiatrist evaluated the cases and HCs based on the fifth edition of the diagnostic and statistical manual of mental disorders (DSM-5). The Hamilton depression (Ham-D) rating scale was employed to evaluate the intensity of depression. An enzyme-linked immunosorbent assay kit (Boster Bio, USA) was used to determine serum IL-1RA concentrations. Results: We observed no marked alteration in the serum concentration of IL-1RA in MDD patients in comparison to HCs (292.81 ± 24.81 and 288 ± 24.87 pg/mL; p > 0.05). Among MDD patients, we found no noteworthy association between the severity of depression and serum IL-1RA levels. Conclusion: The findings of the present study imply that IL-1RA may not be identified as a promising biomarker for risk assessment of depression. However, its neuroprotective role may be taken into consideration for the understanding of pathophysiology of MDD.

Higher serum interleukin-12 levels are associated with the pathophysiology of major depressive disorder: A case-control study results.

Background and Aims: Major depressive disorder (MDD) is the fourth biggest health-related concern that dramatically impacts individuals' mental and physical health. Alteration of serum proinflammatory cytokine levels may take part in the development and progression of MDD. We aimed to explore and compare the role of interleukin-12 (IL-12) in MDD patients and healthy controls (HCs) and its involvement with the disease severity. Methods: The present study included 85 patients and 87 age-sex matched HCs. A qualified psychiatrist utilized the diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) criteria to diagnose patients and evaluate HCs. We applied the Ham-D rating scale to measure the severity of depression. Serum IL-12 levels were measured using ELISA kits. Results: We observed a notable increase in the serum levels of IL-12 in MDD patients compared to HCs (164.27 ± 10.18 pg/ml and 82.55 ± 4.40 pg/ml; p < 0.001). Moreover, we noticed a positive correlation between serum IL-12 levels and Ham-D scores in MDD patients (r = 0.363; p = 0.001). Receiver operating characteristic analysis showed a good predictive performance (AUC = 0.871; p < 0.001) at the cut-off point of 53.46 pg/ml for serum IL-12. Conclusion: The current study findings support that IL-12 levels are involved with the pathogenesis and inflammatory process in MDD. At the same time, this involvement may make this cytokine eligible for the risk evaluation of MDD. However, we recommend further interventional studies to explore more accurate associations between IL-12 and depressive disorder.

Higher serum nerve growth factor levels are associated with major depressive disorder pathophysiology: a case-control study.

OBJECTIVE: There is a lack of established biological, psychological, social, and digital markers for the prediction, identification, and stratification of patients with major depressive disorder (MDD). We therefore aimed to evaluate serum nerve growth factor (NGF) in MDD patients. METHODS: In this case-control study, we recruited MDD patients and age- and sex-matched healthy controls (HCs). A qualified psychiatrist evaluated study participants according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Serum NGF levels were analyzed using a commercially available enzyme-linked immunosorbent assay kit. RESULTS: We analyzed data from 106 MDD patients and 88 HCs. Mean serum NGF concentrations were significantly higher in MDD patients (104.70 ± 6.43 pg/mL) than in HCs (72.09 ± 7.69 pg/mL). Receiver operating characteristic curve analysis revealed the good diagnostic performance of serum NGF in MDD. CONCLUSIONS: Higher serum NGF levels might be involved in MDD pathophysiology, and altered NGF levels may be an early warning sign of depression. The present findings will aid in the development of new and improved therapies for depressive patients. Further interventional studies are recommended to explore the underlying mechanisms, risk factors, disease course, and treatment responses of NGF in MDD.

Elevated Serum Macrophage Migration Inhibitory Factor Levels are Associated With Major Depressive Disorder.

Background: Previous studies have suggested the involvement of an activated inflammatory process in major depressive disorder (MDD), as altered expression of inflammatory cytokines is observed in depression. This alteration can be the cause or a consequence of MDD. However, acknowledging inflammatory cytokines as prospective biomarkers would aid in diagnosing or guiding better therapeutic options. Therefore, we designed this study to assess the macrophage migration inhibitory factor (MIF) in depression. Method: We collected blood samples from 115 MDD patients and 113 healthy controls (HCs) matched by age and sex. MDD patients were diagnosed by a qualified psychiatrist based on the symptoms mentioned in the diagnostic and statistical manual of mental disorders (DSM-5). We applied the Hamilton depression (Ham-D) rating scale to assess the severity of depression. We assessed serum levels of MIF using ELISA kit (Boster Bio, USA). Result: We detected increased serum MIF levels in MDD patients compared to HCs (6.15 ± 0.23 ng/mL vs 3.95 ± 0.21 ng/mL, P < 0.001). Moreover, this increase is more among female patients than female controls. Also, we noticed a positive correlation between altered MIF levels and the Ham-D scores (r = 0.233; P = 0.012), where we found that patients who scored higher on the Ham-D scale had higher MIF levels in serum. Moreover, the area under the curve (AUC) of receiver operating characteristic (ROC) curve represented the good diagnostic performance of altered serum MIF. Conclusion: Our study findings indicate the association of pro-inflammatory cytokine MIF in the pathophysiology of depression as we identified elevated serum MIF levels in depressive patients compared to HCs. However, more researches are required to confirm whether this alteration of cytokine is the causative factor or a consequence of depression. We recommend conducting further studies to understand the pattern of this alteration of MIF levels in MDD patients.

Increased serum resistin but not G-CSF levels are associated in the pathophysiology of major depressive disorder: Findings from a case-control study.

BACKGROUND: Many studies have predicted major depressive disorder (MDD) as the leading cause of global health by 2030 due to its high prevalence, disability, and illness. However, the actual pathophysiological mechanism behind depression is unknown. Scientists consider alterations in cytokines might be tools for understanding the pathogenesis and treatment of MDD. Several past studies on several inflammatory cytokine expressions in MDD reveal that an inflammatory process is activated, although the precise causes of that changes in cytokine levels are unclear. Therefore, we aimed to investigate resistin and G-CSF in MDD patients and controls to explore their role in the pathogenesis and development of depression. METHODS: We included 220 participants in this study. Among them, 108 MDD patients and 112 age-sex matched healthy control (HCs). We used DSM-5 to evaluate study participants. Also, we applied the Ham-D rating scale to assess the severity of patients. Serum resistin and G-CSF levels were measured using ELISA kits (BosterBio, USA). RESULTS: The present study observed increased serum resistin levels in MDD patients compared to HCs (13.82 ± 1.24ng/mL and 6.35 ± 0.51ng/mL, p <0.001). However, we did not find such changes for serum G-CSF levels between the groups. Ham-D scores showed a significant correlation with serum resistin levels but not G-CSF levels in the patient group. Furthermore, ROC analysis showed a fairly predictive performance of serum resistin levels in major depression (AUC = 0.746). CONCLUSION: The present study findings suggest higher serum resistin levels are associated with the pathophysiology of MDD. This elevated serum resistin level may serve as an early risk assessment indicator for MDD. However, the role of serum G-CSF in the development of MDD is still unclear despite its neuroprotective and anti-inflammatory effects.