Investigation of the Relationship between Inflammatory Factors CRP, IL-6 and IL-1â and Major Depressive Disorder: A Hospital Based, Case-Control Study

The mediating role of family functioning between childhood trauma and depression severity in major depressive disorder and bipolar disorder

BackgroundEven with continuous antidepressant treatment, residual symptoms and the risk of relapse can persist in remitted major depressive disorder (MDD) patients. Hence, having a clear recognition of the persistent abnormalities of the underlying neural substrate in MDD through a longitudinal investigation is of great importance.MethodsA total of 127 adult medication-free MDD patients with an acute depressive episode and 118 matched healthy controls (HCs) underwent diffusion tensor imaging. Over a 6-month treatment course, 62 remitted patients underwent a second scan. Remission was defined as a 24-item Hamilton Depression Rating Scale (HAMD24) score ≤7 for at least two weeks. Diffusion tensor imaging was performed with a 3.0 T scanner. Differences in whole-brain fractional anisotropy (FA) between MDD patients and HCs were assessed by an independent t-test using gender, age, and education as covariates.ResultsSignificant FA reductions in the left insula, left middle occipital gyrus, right thalamus, left pallidum and left precuneus were observed in current MDD (cMDD) patients compared with HCs. Moreover, significant FA reductions in the left insula were observed in remitted (rMDD) patients compared to HCs. However, no significant differences in FA values were found when comparing cMDD and rMDD patients.ConclusionsThe abnormalities in the insula showed state-independent characteristics, while the abnormalities in the middle occipital gyrus, thalamus, pallidum and precuneus seemed to be state-dependent impairments in MDD patients.

Recently, scientists have focused on pro-inflammatory cytokines and immunological dysregulation in major depressive disorder (MDD). Some research suggests pro-inflammatory cytokines' role in MDD development, whereas anti-inflammatory studies are sparse. There is no systematic investigation of Bangladeshi MDD patients' pro- and anti-inflammatory cytokines. This study examines the blood levels of IL-12 and IL-4 in Bangladeshi patients and healthy controls (HCs) to determine the diagnostic accuracy of these cytokines to identify MDD patients from those without MDD. A total of 110 people with MDD from the department of psychiatry of a teaching hospital in Dhaka and 107 HCs from Dhaka participated in this case–control study. Depression and illness severity were gauged using DSM-5 criteria and Ham-D scores. Commercially marketed ELISA kits were used in accordance with manufacturer guidelines to measure the levels of IL-12 and IL-4 in peripheral blood, allowing a comparison of the patient and control groups. In comparison to HCs, MDD patients (5333.00 ± 307.40 pg/ml) showed noticeably higher levels of IL-12 than in HCs (2331.00 ± 207.40 pg/ml). The increased levels were positively correlated with Ham-D scores (male: r = 0.351, p < 0.050; female: r = 0.389, p < 0.050), suggesting a possible relationship to disease progression. Additionally, compared to HCs (272.81 ± 23.94 pg/ml), MDD patients had significantly higher peripheral blood levels of IL-4 (876.35 ± 66.73 pg/ml) (p < 0.001). Also, there was a positive correlation between IL-4 serum levels and Ham-D scores (male: r = 0.361, p < 0.050; female: r = 0.398, p < 0.050). Therefore, we observed increased levels of these serum cytokines and their association with the severity of depression. The results of this study demonstrate the possibility of IL-12 and IL-4 blood levels as distinct markers capable of differentiating between MDD patients and HCs, possibly acting as markers of MDD susceptibility. To ascertain the diagnostic effectiveness of these two cytokines, more research is necessary.

Major depressive disorder (MDD) is a heterogeneous mental disorder having a very diverse course and causing a significant changes in daily life. Though the exact pathophysiology of depression is still not known, an alteration in the serum levels of cytokines and neurotrophic factors was seen in MDD subjects. In this study, we compared the serum levels of 'pro-inflammatory cytokine leptin and neurotrophic factor EGF' in healthy controls (HCs) and MDD patients. To make the findings more accurate, we eventually looked for a correlation between altered serum leptin and EGF levels and the severity of the disease condition. For this case-control study, about 205 MDD patients were enrolled from the Department of Psychiatry, Bangabandhu Sheikh Mujib Medical University, Dhaka, and about 195 HCs were enrolled from various parts of Dhaka. The DSM-5 was utilized to evaluate and diagnose the participants. The HAM-D 17 scale was used to measure the severity of depression. After collecting blood samples, they were centrifuged to produce clear serum samples. These serum samples were analyzed using enzyme-linked immunosorbent assay (ELISA) kits to measure serum leptin and EGF levels. We observed lowered serum EGF levels in MDD patients compared to HCs (524.70 ± 27.25 pg/ml vs. 672.52 ± 49.64 pg/ml, p = 0.009), and HAM-D score was elevated in MDD patients compared to HCs (17.17 ± 0.56 vs. 2.49 ± 0.43, p<0.001). But no correlation was established between serum EGF levels and the severity of depression. However, no significant differences were observed between MDD patients and HCs in the case of serum leptin levels (p = 0.231). Our study findings suggest that reduced serum EGF levels have an impact on the pathogenesis of depression. But as per our investigation, the severity of depression is not correlated with altered EGF levels. Our findings regarding the association of EGF with MDD would help to use EGF as a risk indicator of depression. We suggest further clinical investigations to determine the precise function of leptin and EGF in depression.

Insomnia is a common comorbidity symptom in major depressive disorder (MDD) patients. Abnormal brain activities have been observed in both MDD and insomnia patients, however, the central pathological mechanisms underlying the co-occurrence of insomnia in MDD patients are still unclear. This study aimed to explore the differences of spontaneous brain activity between MDD patients with and without insomnia, as well as patients with different level of insomnia. A total of 88 first-episode drug-naïve MDD patients including 44 with insomnia (22 with high insomnia and 22 with low insomnia) and 44 without insomnia, as well as 44 healthy controls (HC), were enrolled in this study. The level of depression and insomnia were evaluated by HAMD-17, adjusted HAMD-17 and its sleep disturbance subscale in all subjects. Resting-state functional and structural magnetic resonance imaging data were acquired from all participants and then were preprocessed by the software of DPASF. Regional homogeneity (ReHo) values of brain regions were calculated by the software of REST and were compared. Finally, receiver operating characteristic (ROC) curves were conducted to determine the values of abnormal brain regions for identifying MDD patients with insomnia and evaluating the severity of insomnia. Analysis of variance showed that there were significant differences in ReHo values in the left middle frontal gyrus, left pallidum, right superior frontal gyrus, right medial superior frontal gyrus and right rectus gyrus among three groups. Compared with HC, MDD patients with insomnia showed increased ReHo values in the medial superior frontal gyrus, middle frontal gyrus, triangular inferior frontal gyrus, calcarine fissure and right medial superior frontal gyrus, medial orbital superior frontal gyrus, as well as decreased ReHo values in the left middle occipital gyrus, pallidum and right superior temporal gyrus, inferior temporal gyrus, middle cingulate gyrus, hippocampus, putamen. MDD patients without insomnia demonstrated increased ReHo values in the left middle frontal gyrus, orbital middle frontal gyrus, anterior cingulate gyrus and right triangular inferior frontal gyrus, as well as decreased ReHo values in the left rectus gyrus, postcentral gyrus and right rectus gyrus, fusiform gyrus, pallidum. In addition, MDD patients with insomnia had decreased ReHo values in the left insula when compared to those without insomnia. Moreover, MDD patients with high insomnia exhibited increased ReHo values in the right middle temporal gyrus, and decreased ReHo values in the left orbital superior frontal gyrus, lingual gyrus, right inferior parietal gyrus and postcentral gyrus compared to those with low insomnia. ROC analysis demonstrated that impaired brain region might be helpful for identifying MDD patients with insomnia and evaluating the severity of insomnia. These findings suggested that MDD patients with insomnia had wider abnormalities of brain activities in the prefrontal-limbic circuits including increased activities in the prefrontal cortex, which might be the compensatory mechanism underlying insomnia in MDD. In addition, decreased activity of left insula might be associated with the occurrence of insomnia in MDD patients and decreased activities of the frontal-parietal network might cause more serious insomnia related to MDD.

Background: Deficits in reward processing, such as approaching motivation, reward learning and effort-based decision-making, have been observed in patients with schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). However, little is known about the nature of reward-processing deficits in these 3 diagnostic groups. The present study aimed to compare and contrast amotivation in these 3 diagnostic groups using an effort-based decision-making task. Methods: Sixty patients (19 SCZ patients, 18 BD patients and 23 MDD patients) and 27 healthy controls (HC) were recruited for the present study. The Effort Expenditure for Reward Task (EEfRT) was administered to evaluate their effort allocation pattern. This task required participants to choose easy or hard tasks in response to different levels of reward magnitude and reward probability. Results: Results showed that SCZ, BD, and MDD patients chose fewer hard tasks compared to HC. As reward magnitude increased, MDD patients made the least effort to gain reward compared to the other groups. When reward probability was intermediate, MDD patients chose fewer hard tasks than SCZ patients, whereas BD patients and HC chose more hard tasks than MDD and SCZ patients. When the reward probability was high, all 3 groups of patients tried fewer hard tasks than HC. Moreover, SCZ and MDD patients were less likely to choose hard tasks than BD patients and HC in the intermediate estimated value conditions. However, in the highest estimated value condition, there was no group difference in hard task choices between these 3 clinical groups, and they were all less motivated than HC. Conclusion: SCZ, BD, and MDD patients shared common deficits in gaining reward if the reward probability and estimated value were high. SCZ and MDD patients showed less motivation than BD patients in gaining reward when the reward probability and estimated value was intermediate.

Introduction: Major depressive disorder (MDD) patients experience a systemic inflammatory stage. Monocytes play an important role in innate inflammatory responses and may be modulated by bacterial translocation. Our aim was to investigate the subset distribution and function of circulating monocytes, levels of proinflammatory cytokines, gut barrier damage, and bacterial translocation in MDD patients.Methods: Twenty-two MDD patients without concomitant diseases and 14 sex- and age-matched healthy controls were studied. The levels of circulating CD14++CD16- (classical), CD14++CD16++ (intermediate) and CD14-CD16++ (nonclassical) monocytes and the intracytoplasmic tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 expression in the presence or absence of lipopolysaccharide (LPS) stimulation were analyzed by polychromatic flow cytometry. The serum TNF-α, IL-1β, IL-6, and IL-10 levels were measured by Luminex. LPS-binding protein (LBP), intestinal fatty acid-binding protein (I-FABP), and zonulin were measured by enzyme-linked immunosorbent assay (ELISA).Results: MDD patients had a significant increase in the frequency of intermediate monocytes and a significant decrease in the frequency of classical monocytes compared to those in the healthy controls. MDD patients had a significantly increased percentage of classical monocytes that expressed IL-1β, intermediate monocytes that expressed IL-1β and IL6 and nonclassical monocytes that expressed IL-1β, and decreased levels of nonclassical monocytes that expressed IL6 compared to those in the healthy controls. MDD patients had significantly increased levels of circulating TNF-α, IL-1β, LBP, and I-FABP compared to those in the healthy controls. MDD patients with high LBP levels had a significant reduction in the number of circulating monocytes compared to that in the normal-LBP MDD patients, which can be mainly ascribed to a decrease in the number of intermediate and nonclassical monocytes.Conclusions: We have demonstrated that compared to the healthy controls, MDD patients show a marked alteration in circulating monocytes, with an expansion of the intermediate subset with increased frequency of IL-1β and IL-6 producing cells. These patients also exhibited a systemic proinflammatory state, which was characterized by the enhanced serum TNF-α and IL-1β levels compared to those in the healthy controls. Furthermore, MDD patients showed increased LBP and I-FABP levels compared to those in healthy controls, indicating increased bacterial translocation and gut barrier damage.

BackgroundPrevious studies have noticed that systemic inflammation may alter the integrity of white matter. However, how the levels of serum cytokine affect the integrity of white matter in major depressive disorder (MDD) patients are unclear. Our study aimed to investigate the association between the inflammatory cytokine levels and white matter microstructure in drug-naïve patients with MDD pre- and post-treatment.MethodIn total, 29 MDD patients and 25 healthy controls (HC) were included in this study. Diffusion tensor imaging (DTI) was conducted in all subjects at baseline, and the MDD patients were reassessed after venlafaxine treatment, using a tract-based spatial statistics (TBSS) analysis. Morning serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) concentrations in MDD patients were also measured pre- and post-treatment.ResultsSignificantly reduced fractional anisotropy (FA) values were found in the bilateral superior fronto-occipital fasciculus (SFO), posterior limb of the internal capsule (IC-PL), and fornix compared with the HC, and FA values in these regions in MDD patients have risen to normal levels except the bilateral SFO after treatment. The FA value of the left IC-PL was inversely correlated with the peripheral hs-CRP levels in both pre- and post-treatment MDD patients.ConclusionOur results suggested that the white matter integrity in the left IC-PL was significantly inversely correlated with the peripheral hs-CRP levels in both pre- and post-treatment MDD patients.

Background:Abnormal expression of inflammatory cytokines in major depressive disorder (MDD) suggests the activation of an inflammatory process. The pattern of alterations in cytokine levels is still ambiguous. The present study aimed to evaluate interleukin-7 (IL-7) and interleukin-10 (IL-10) for their involvement in the pathophysiology of MDD and determine their relationships with depression risk.Methods:The study included 166 medication-free subjects: 84 MDD patients and 82 sex- and age-matched healthy controls (HCs). A qualified psychiatrist diagnosed patients and evaluated controls based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). Hamilton depression rating scale (Ham-D) was used to measure the severity of depression in MDD patients. Serum IL-7 and IL-10 levels were measured using enzyme-linked immunosorbent assay (ELISA) kits.Results:Compared with HCs, the serum levels of IL-7 were significantly decreased, whereas that of IL-10 increased in MDD patients. Moreover, the severity of depression is correlated with the altered levels of IL-7 and IL-10 in MDD patients. We found a negative correlation between IL-7 and Hamilton depression rating (Ham-D) scores (r = –0.580, p < 0.05), whereas there was a positive correlation between IL-10 and Ham-D scores (r = 0.555, p < 0.05).Conclusions:The altered levels of serum IL-7 and IL-10 in MDD patients may represent a homeostatic mechanism that enhances the inflammatory process during depression. The alterations of these cytokine levels in MDD and their association with the severity of depression support them as promising, but there may still be controversial factors for understanding the pathophysiology of depression.

Altered tryptophan catabolite concentrations in major depressive disorder and associated changes in hippocampal subfield volumes

Disrupted reward circuits is associated with cognitive deficits and depression severity in major depressive disorder

Major Depressive Disorder (MDD) patients exhibit difficulty in forgetting negative material, which may result from specific impairments in memory and attention. However, the underlying neural correlates of the corresponding cognitive deficit have not been elucidated. The present study investigated the electrophysiological characteristics and differences, using event-related potentials (ERPs), between MDD patients and healthy controls (HCs) in an emotional directed forgetting task (EDF) with negative and neutral images. A total of 26 MDD patients and 28 HCs were recruited for the current study, all of whom were clinically evaluated using the Hamilton Depression Scale. All participants were subjected to ERP measurements during the EDF task, and behavioral data and ERP components were analyzed. HCs had higher hit rates than did MDD patients; more false alarms occurred in MDD patients than in HCs, and higher false alarm rates occurred with negative images than with neutral images. The reaction times were also longer for MDD patients than for HCs. Larger image-evoked P2 amplitudes and smaller image-evoked N2 amplitudes occurred in MDD patients, whereas they had higher image-evoked late positive potential (LPP) amplitudes both in negative and neutral emotional conditions than the HCs. MDD patients had higher cue-evoked N2 amplitudes and lower cue-evoked P3 amplitudes, elicited by the Remember cue, than the HCs. The Hamilton Depression Rating Scale (24-item edition) scores were positively correlated with the LPP amplitudes that were evoked by negative images in a central location. Based on these results, we concluded that poor attentional recruiting and allocation, memory inhibitory deficits, and difficulties in memory retention may contribute to the poor performance in the EDF task in MDD patients. The observed ERP patterns provide valuable insights into the neural mechanisms underlying the EDF task in MDD and underscore the potential of EDF as an assessment tool for cognitive and emotional dysregulation in MDD.

Abnormalities in emotion recognition (ER) are frequently reported in depression, with lower recognition accuracy in patients with major depressive disorder (MDD) when compared to healthy individuals. Mindfulness was found to directly impact the severity of depressive symptoms, by recognizing negative cognitions and dysfunctional reactions. The aims of this study were to compare ER and mindfulness levels between MDD patients and healthy controls (HCs), as well as to examine whether ER and mindfulness are related to symptom severity in MDD patients. Sixty-eight patients with MDD and 93 HCs participated in the study. A sociodemographic form, reading the mind in the eyes test (RMET), five facet mindfulness questionnaire-short form (FFMQ-S) and the Montgomery-Asberg depression scale (MADRS) were administered. Group comparison in ER and mindfulness was performed using the multivariate analysis of covariance (MANCOVA). Bivariate correlations and hierarchical linear regression analyses were performed to assess the associations between depression severity, ER and mindfulness in the patient group. Higher level of mindfulness was found in HCs relative to MDD group, however, no ER difference was present between the groups. A positive association between depression severity and the non-reactivity facet of mindfulness was found. On the other hand, ER was not significantly associated with symptom severity among individuals with MDD. Non-reactivity, unlike other dimensions of mindfulness, seems to increase with the severity of depressive symptoms among MDD patients. A particular focus on this subdimension in mindfulness techniques may yield better outcomes in alleviation of depressive symptoms.

IntroductionAbnormalities in emotion recognition (ER) are frequently reported in depression, with lowered recognition accuracy in patients with major depressive disorder (MDD) when compared to healthy individuals. Mindfulness was found to directly impact the severity of depressive symptoms, by negative cognition and dysfunctional reaction recognition.ObjectivesThe aims of this study were to compare ER and mindfulness levels between MDD patients and healthy controls (HC), as well as to examine whether ER and mindfulness are related to symptom severity in MDD patients.Methods68 patients with MDD and 93 HC participated in the study. A sociodemographic form, Reading the Mind in the Eyes Test (RMET), Five Facet Mindfulness Questionnaire-Short Form (FFMQ-S) and the Montgomery Asperg Depression Scale (MADRS) were administered. Group comparison in ER and mindfulness was assessed using the Multivariate analysis of covariance (MANCOVA). Bivariate correlations and multiple linear regression analyses were performed to assess the associations between depression severity, ER and mindfulness in the patient group.ResultsBetter ER and higher levels of mindfulness were found in HCs relative to the MDD group. A positive association between depression severity and the non-reactivity facet of mindfulness was found, indicating that in the MDD group non-reactivity was a significant predictor for depression severity. On the other hand, ER was not significant in predicting symptom severity.ConclusionsNon-reactivity, unlike other dimensions of mindfulness, seems to increase with the severity of depressive symptoms among MDD patients. To particularly focus on this subdimension in mindfulness techniques may yield better outcomes in alleviation of depressive symptoms.DisclosureNo significant relationships.

A cross-sectional survey to investigate the prevalence of pain in Japanese patients with major depressive disorder and schizophrenia