Search

Non-suicidal self-injury (NSSI) is an increasingly concerning issue that is linked to a range of mental health problems. However, little is known about the potential neurophysiological mechanisms underlying risk decision-making in Major depressive disorder (MDD) patients with NSSI—the present study aimed to fill this important literature gap. A total of 81 MDD patients (with NSSI: n = 40, without NSSI: n = 41) and 44 matched healthy controls (HC) underwent a modified version of the Iowa Gambling Task (IGT) while an electroencephalogram was recorded. Feedback-related negativity (FRN) and P300 were examined during the feedback stage of the risky decision-making process. Behavioural findings revealed that individuals diagnosed with MDD displayed a greater tendency to make risky decisions compared to the control group. Furthermore, MDD patients with NSSI demonstrated a significantly more negative ΔFN (i.e., the difference in neural response to losses compared to gains) than those without NSSI. Further, NSSI patients showed a larger difference ΔFN (loss minus gain), which was associated with enhanced impulsivity. Collectively, the findings suggest that there is an altered processing of risky decision-making in the electrophysiology of patients with MDD who engage in NSSI. The ΔFN may serve as a psychophysiological marker indicating risk for NSSI. • Major depressive disorder (MDD) patients had severe decision-making(DM) defects. • The MDD patients with NSSI showed more negative ΔFN during Iowa gambling task (IGT). • MDD-NSSI patients showed a larger difference ΔFN, which correlated enhanced impulsivity. [ABSTRACT FROM AUTHOR]

Low social support increases the risk of Major depressive disorder (MDD), yet its effects on brain function are unclear. Thirty-two MDD patients with low social support, 52 with high social support, and 54 healthy controls were recruited. We investigated regional brain activity in MDD patients with low social support using resting-state functional Magnetic Resonance Imaging, employing measures such as degree centrality (DC), regional homogeneity, amplitude of low-frequency fluctuations, and fractional amplitude of low-frequency fluctuations. Abnormal regions identified in these analyses were selected as regions of interest for functional connectivity (FC) analysis. We then explored relationships among social support, brain dysfunction, MDD severity, and insecurity using partial correlation and moderated mediation models. Our findings reveal that MDD patients with low social support show decreased DC in the right superior temporal pole and right medial geniculate nucleus, coupled with increased FC between the right superior temporal pole and right inferior temporal gyrus, and the right supramarginal gyrus compared to those with high social support. Furthermore, the DC of the right medial geniculate nucleus positively correlates with social support, while the FC between the right superior temporal pole and right supramarginal gyrus negatively correlates with both social support and subjective support. Additionally, a moderated mediation model demonstrates that the FC between the right superior temporal pole and right supramarginal gyrus mediates the relationship between social support and depression severity, with security moderating this mediation. These findings underscore the impact of low social support on brain function and depression severity in MDD patients. • In MDD patients, reduced social support was linked to decreased centrality in superior temporal pole (STP) and medial geniculate nucleus (MGN), yet increased connectivity with inferior temporal gyrus and supramarginal gyrus (SG). • MGN's centrality positively correlated with social support, while connectivity between STP and SG negatively correlated with social support. • Connectivity between STP and SG mediated the impact of social support on MDD severity, with security as a moderating factor. [ABSTRACT FROM AUTHOR]

Suicidal ideation (SI) is a common symptom of major depressive disorder (MDD), often accompanied by cognitive alterations and emotional dysregulation. However, it is unclear whether cognitive dysfunction in patients with MDD is related to the presence or absence of SI and impaired connectivity within or between large-scale neurocognitive networks. Previous studies have shown that the frontoparietal network (FPN) and default mode network (DMN) are critical for cognitive control and emotional regulation. Participants were 51 MDD patients with suicidal ideation (MDDSI), 52 MDD patients without suicidal ideation (MDDNSI), and 55 healthy controls (HC). Using areas located within FPN and DMN networks as regions of interest (ROIs), we compared the cognitive performance of the three groups and the strength of the resting state functional connections (RSFC) within and between the FPN and DMN networks. Additionally, we examined the correlation between the strength of FC within the FPN and cognitive function in the SI group. Furthermore, network-based statistics (NBS) were used to correct for the strength of FPN and DMN functional connections. The study identified significant cognitive deficits in MDD patients. Reduced strength of FC was observed within the FPN and DMN networks in the SI group compared to the NSI group. In the SI group, the strength of FC within the FPN network was positively correlated with attention/vigilance. These insights underscore the critical roles of the FPN and DMN in the suicidal ideation, shedding light on the cognitively relevant neurobiological characteristics of MDDSI, providing new insights into the neural mechanisms of MDDSI. URL: https://www.chictr.org.cn/bin/project/edit?pid=131537. Registration number: ChiCTR2100049646. • This study examines how suicidal ideation, cognitive function, and brain connectivity are related in depressed patients. • Distinct connectivity patterns linked to suicidal ideation were found in frontoparietal (FPN) and default mode networks (DMN). • These findings offer new insights into MDD-related suicidal ideation and may influence treatment strategies. [ABSTRACT FROM AUTHOR]

Non-suicidal self-injury (NSSI) may be related to serious cognitive impairment in patients with major depressive disorder (MDD), but the specific mechanism is still unclear. This study attempts to identify the neurobiological process alterations of cognitive impairment in MDD patients with NSSI by examining the functional connectivity of the frontotemporal cortex in MDD patients with or without NSSI. Thirty MDD patients with NSSI, 36 MDD patients without NSSI, and 35 healthy controls (HC) were included in the study. The MATRICS Consensus Cognitive Battery (MCCB) was used to comprehensively assess the cognitive function of the subjects and functional near-infrared spectroscopy (fNIRS) was used to detect the functional connectivity of the frontotemporal cortex and its brain regions of interest. MDD patients with or without NSSI had multi-domain cognitive impairments. MDD patients with NSSI showed the lowest score in performance of attention/alertness and the weakest functional connectivity of frontotemporal when compared with the MDD patients without NSSI and the HC. In addition, the functional connectivity of the bilateral frontotemporal cortex was positively correlated with verbal learning and working memory in MDD patients with NSSI. In MDD patients, the appearance of NSSI is often accompanied by further impairment of attention/alertness and a decline in functional connectivity of the frontotemporal cortex. The impairment of verbal learning and working memory was associated with decreased functional connectivity of the frontotemporal cortex in MDD patients with NSSI. [ABSTRACT FROM AUTHOR]

This study examines the effect of smoking on global and regional brain entropy in patients with Major Depressive Disorder (MDD), aiming to elucidate the relationship between smoking habits and brain network complexity in depression. The study enrolled 24 MDD patients, divided into smokers and non-smokers, from Alanya Alaaddin Keykubat University and Istanbul Medipol University. Resting-state fMRI data were acquired and processed. The complexity of neuronal activity was assessed using dispersion entropy, with statistical significance determined by a suite of tests including Kolmogorov–Smirnov, Student's t-test, and Mann–Whitney U test. The smoking cohort exhibited higher global brain entropy compared to the non-smoking group (p = 0.033), with significant differences in various brain networks, indicating that smoking may alter global brain activity and network dynamics in individuals with MDD. The study provides evidence that smoking is associated with increased brain entropy in MDD patients, suggesting that chronic smoking may influence cognitive and emotional networks. This underscores the importance of considering smoking history in the treatment and prognosis of MDD. The findings call for further research to understand the mechanistic links between smoking, brain entropy, and depression. • Smoking prevalence is notably higher among patients with mental disorders, especially depression. • Some studies suggest smoking might enhance cognition in mentally healthy individuals. • MDD patients who smoked exhibited increased brain network entropy compared to non-smokers. • Increased entropy is seen by some research as beneficial for MDD patients on antidepressants. • Our findings suggest smoking might increase brain entropy irrespective of depression's presence. [ABSTRACT FROM AUTHOR]

Electroconvulsive therapy (ECT) is a safe and effective treatment for major depressive disorder (MDD). After receiving ECT for MDD there is a large risk of relapse within the first year. Patient attitudes towards renewed treatment could impact their decisions regarding future therapy. We conducted a nationwide cohort study, using data from Swedish registers. Patients with MDD who received ECT were followed up to six months after the initial ECT-series. We investigated if certain patient and treatment characteristics during the initial treatment were correlated to their attitude towards renewed ECT at the six-month follow-up. Logistic regression models were used to calculate adjusted odds ratios for predictors. The Bonferroni method was used to adjust significance levels for multiple testing. The study included 1917 patients. 51.1% of patients were positive, 27.6% were undecided and 21.3% were negative towards renewed treatment. Patients with response to treatment were less likely to have a negative attitude towards renewed ECT (odds ratio 0.32, 95% CI 0.25–0.41, P < 0.001). Moreover, patients with experience of ECT prior to the index series were less likely to have a negative attitude towards renewed ECT (odds ratio 0.44, 95% CI 0.34–0.58, P < 0.001). In order to minimize the risk of negative attitudes towards renewed ECT for MDD, treatment should primarily be reserved for patients that are likely to respond to ECT. • When followed up six months later, the majority of patients who received ECT for MDD would accept future treatment under similar circumstances. • Patients who responded well to treatment were less likely to have a negative attitude towards renewed ECT. • Patients with prior experience of ECT were less likely to have a negative attitude towards renewed ECT. • Patients with a negative attitude towards renewed ECT were less likely to undergo ECT throughout the follow-up period. [ABSTRACT FROM AUTHOR]

Recent research has explored the linkage between major depressive disorder (MDD) and inflammation, especially via altered peripheral blood immune markers. However, the relationship between several novel leukocyte-derived ratios (LDR) and psychological stress in MDD remains uncertain. This study aimed to explore the relationship between LDR, clinical characteristics, recent life events, and childhood maltreatment in MDD patients. A cross-sectional case-control study was conducted involving 59 healthy controls (HC) and 50 unmedicated MDD patients. Subjects underwent psychological assessments and peripheral blood measurements. LDR assessed in this study included neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), white blood cell-to-mean platelet volume ratio (WMR), systemic immune inflammation index (SII), multiplication of neutrophil and monocyte counts (MNM), and systemic inflammation response index (SIRI). MDD patients displayed significant alterations in WMR, PLR, and MNM compared to HC, as well as correlations between several LDR and various clinical features (duration of untreated psychosis and dNLR, the nine-item Patient Health Questionnaire and PLR, the 7-item Generalized Anxiety Disorder Questionnaire and SIRI (NLR and dNLR). There was a significant difference in the comparison of WMR in first-episode patients than in recurrent patients. Analyses further revealed an association between Life Event Scale total scores and NLR (dNLR). No correlation was found between Childhood Trauma Questionnaire total (or subscale) scores and LDR. Additionally, WMR and dNLR presented potential predictive value for distinguishing between MDD and HC. The study concludes that MDD and some clinical features are associated with alterations in some peripheral blood LDR. These findings emphasize the potential role of peripheral blood LDR in the pathogenesis and clinical heterogeneity of MDD. [ABSTRACT FROM AUTHOR]

Suicide attempts are one of the most serious comorbidities in patients with major depressive disorder (MDD), and the prevalence of suicide attempts is higher in younger people compared to older people, with significant gender differences. This study aimed to investigate the relationship between suicide attempts, clinical symptoms, thyroid hormones, and metabolic parameters in young first-episode and drug-naïve (FEND) MDD patients of different genders. A total of 1289 FEND MDD patients were recruited. Depression, anxiety, and psychotic symptoms were assessed using the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and the Positive and Negative Syndrome Scale (PANSS) positive subscale, respectively. Thyroid hormones and glucolipid metabolism indicators were also tested. Network analysis was employed to delineate the interplay between thyroid dysfunction, clinical symptoms, and metabolic disorders. Among young FEND MDD patients, the rate of suicide attempts was 17.4% in males and 19.8% in females, showing no significant gender difference in the incidence of suicide attempts (χ2 = 1.06, p = 0.303). In the network model, PANSS positive subscale (Expected Influence = 0.578) and HAMD scores (Expected Influence = 0.576) were identified as the individual symptoms that most affected male patients, whereas TSH (Thyroid-Stimulating Hormone) (Expected Influence = 0.972) and PANSS positive subscale (Expected Influence = 0.937) were identified as the individual symptoms that most affected female patients. In addition, we found that TSH (Expected Influence = 0.438) was a pivotal node connecting metabolic disturbances and clinical symptoms. Our findings emphasize the important role of psychotic symptoms in young MDD patients with suicide attempts. Moreover, our results highlight the pivotal role of serum TSH levels in the pathophysiology of young female MDD patients with suicide attempts. [ABSTRACT FROM AUTHOR]

Depression is a growing public health concern, and exercise is an adjunctive treatment modality to improve depression, but the optimal form of exercise and the optimal dose are still unclear. This systematic review examined the efficacy of four major types of exercise (aerobic, resistance, mixed, and mind-body) on depression, as well as the dose-response relationship between total and specific exercise and depressive symptoms. We included randomized controlled trials that included participants aged 18 years or older with a diagnosis of major depressive disorder or a depressive symptom score above a threshold as determined by a validated screening measure, implemented one or more exercise therapy groups, and assessed depressive symptoms at baseline and follow-up. Forty-six studies (3164 patients) were included in the meta-analysis. Aerobic (standardised mean difference (SMD) = -0.93; 95% CI: -1.25 to -0.62) and mind-body exercise (SMD) = -0.81; 95% CI: -1.19 to -0.42) improved depressive symptoms better compared to controls, followed by mixed (SMD = -0.77; 95% CI: -1.20 to -0.34) and resistance exercise (SMD = -0.76; 95% CI: -1.24 to -0.28). This dose-response meta-analysis showed a U-shaped curve between exercise dose and depressive symptoms. The minimum effective dose was estimated to be 320 metabolic equivalent (METs) -min per week and the optimal response was 860 METs-min per week. These findings lead us to advocate that clinicians carefully select the appropriate dose of exercise based on the patient's individual characteristics and needs, in conjunction with psychological care interventions. • Aerobic, resistance, mixed and mind-body exercise interventions have significant and comparable benefits in improving clinical depressive symptoms in patients with MDD. • There was a U-shaped dose-response relationship between overall exercise volume and depression level, with the maximum significant response occurring at 860 METs-min, and a minimal clinically meaningful difference (MCID) in depression improvement with 477 METs-min of exercise per week. [ABSTRACT FROM AUTHOR]

Major Depressive Disorder (MDD) is frequently associated with social dysfunction and impaired decision-making, but its impact on social decisions remains unclear. Thus, we conducted a series of meta-analyses to examine the effects of MDD on key social decision phenomena, including trust, altruistic punishment, and cooperation. We searched Web of Science, PubMed, PsycINFO, and Embase up to December 2023, using Hedges' g to compare social decision-making between MDD patients and healthy controls (HCs). Meta-analytic results showed that MDD patients exhibited a significant reduction in trust (Hedges' g = −0.347, p < 0.001), no significant difference in altruistic punishment (Hedges' g = 0.232, p = 0.149), and an increase in cooperative behaviors (Hedges' g = 0.361, p = 0.002) compared to HCs. The moderation analysis revealed that age (p = 0.039) and region (p = 0.007) significantly moderated altruistic punishment, with older MDD patients and those from Asian and European regions having larger MDD-HC contrast than others. Regarding cooperation, moderation analysis indicated that age (p = 0.028), years of education (p = 0.054), and treatment coverage (p = 0.042) were significant moderators, indicating larger MDD-HC contrast in older, less-educated and better-treated people. These findings suggest MDD has different impacts on different social decisions, highlighting the need for fine-tuned therapeutic interventions that address these differences. The data also underscores the importance of considering demographic and treatment-related variables in managing MDD, which could inform personalized treatment strategies and improve social functionality and patient outcomes. [ABSTRACT FROM AUTHOR]

Non-invasive neurostimulation, including bright light therapy (BLT), repetitive transcranial magnetic (rTMS) and transcranial direct current stimulation (tDCS), has been shown to alleviate depressive symptoms in major depressive disorder (MDD). However, the efficacy of these interventions in addressing sleep disturbances in MDD patients remains a subject of debate. We aimed to conduct a meta-analysis of available randomized controlled trials (RCTs) to assess the effectiveness of non-invasive neurostimulation in improving sleep disturbances and depressive symptoms in MDD patients. Systematic searches for relevant RCTs were conducted in the databases PubMed, Cochrane Library, Web of Science, EMBASE, Wanfang and China National Knowledge Infrastructure up to January 2024. Data on outcomes comparable across the studies were meta-analyzed using Review Manager 5.3 and Stata 14. The pooled results were reported as standardized mean differences (SMD) with their respective 95% confidence intervals (CI). Our analysis encompassed 15 RCTs involving 1348 patients. Compared to sham or no stimulation, non-invasive neurostimulation significantly improved sleep quality (SMD -0.74, 95%CI -1.15 to −0.33, p = 0.0004) and sleep efficiency (SMD 0.35, 95%CI 0.10 to 0.60, p = 0.006). It also significantly reduced severity of depressive symptoms (SMD -0.62, 95%CI -0.90 to −0.35, p < 0.00001). Subgroup analysis further demonstrated that patients experiencing sleep improvements due to neurostimulation showed a marked decrease in depressive symptoms compared to the control group (SMD = −0.90, 95% CI [-1.26, −0.54], p < 0.0001). Current evidence from RCTs suggests that neurostimulation can enhance sleep quality and efficiency in individuals with MDD, which in turn may be associated with mitigation of depressive symptoms. CRD42023423844. [ABSTRACT FROM AUTHOR]

In clinical practice, accurately identifying self-injurious behavior among adolescents with major depressive disorder (MDD) is crucial for individualized treatment. This study aimed to examine the differences in prefrontal cortex activation using the functional near-infrared spectroscopy (fNIRS) during the verbal fluency task (VFT) assessment of adolescents with MDD and self-harm (SH) compared with those without SH. A total of 60 eligible patients were included for final analysis, with the SH group containing 36 participants, and the Non-SH group containing 24 participants. We found that right middle frontal gyrus (rMFG) was more activated in the SH group than that in the Non-SH group during the VFT assessments (z = −3.591, p = 0.004, FDR correction). The z-scores of beta values of rMFG exhibited a good discriminatory power with the area under the curve (AUC) in distinguishing the two groups (AUC = 0.775, p < 0.001). These findings reveal that the fNIRS-VFT paradigm may be a useful tool for discovering neurobiological differences among adolescents with MDD. • The first study using fNIRS to explore PFC activation among adolescents with depression and self-injurious behavior. • Enhanced activation in right MFG is associated with self-injurious behavior in adolescents with depression. • The fNIRS-VFT paradigm may be a useful tool for discovering neurobiological differences among adolescents with MDD. [ABSTRACT FROM AUTHOR]

Transcranial alternating current stimulation (tACS) is an emerging non-invasive neuromodulation treatment for major depressive disorder (MDD), but its mechanism remains unclear. Therefore, we evaluated the effects of tACS on event-related potentials (ERP) based on a randomized controlled study. All patients were divided into two groups to receive either 20 sessions 77.5Hz-tACS or 20 sessions of sham stimulation during 4 weeks. The Hamilton Depression Rating Scale for Depression −17 item (HAMD-17) and ERP during face-word Stroop task were recorded before and after the treatment (the fourth weekend). Our findings indicate a significant alleviation of depressive symptoms after tACS. For the behavioral performance, sham group showed a significant decrease in reaction time to the sad incongruent condition and an increase in accuracy to the happy condition. The active group showed an increase in accuracy to the incongruent condition. ERP analysis revealed that tACS significantly shortened the latency of P2 to incongruent condition, decreased the amplitude and prolonged the latency of N2 to negative condition. These ERP alterations suggest a potential rectification of negative bias and enhancement of cognitive functioning in patients with MDD, offering insights into the antidepressant mechanisms of tACS. • Transcranial alternating current stimulation (tACS) has antidepressant effect. • tACS modifies behavioral performance and ERP in patients with MDD. • tACS might improve cognitive functioning in patients with MDD. [ABSTRACT FROM AUTHOR]

Over 300 million individuals worldwide suffer from major depressive disorder (MDD). Individuals with MDD are less physically active than healthy people which results in lower cardiorespiratory fitness (CRF) and less favorable perceived fitness compared with healthy controls. Additionally, individuals with MDD may show autonomic system dysfunction. The purpose of the present study was to evaluate the CRF, perceived fitness and autonomic function in in-patients with MDD of different severity compared with healthy controls. We used data from 212 in-patients (age: 40.7 ± 12.6 y, 53% female) with MDD and from 141 healthy controls (age: 36.7 ± 12.7 y, 58% female). We assessed CRF with the Åstrand-Rhyming test, self-reported perceived fitness and autonomic function by heart rate variability (HRV). In specific, we used resting heart rate, time- and frequency-based parameters for HRV. In-patients completed the Beck Depression Inventory-II (BDI-II) to self-assess the subjectively rated severity of depression. Based on these scores, participants were grouped into mild, moderate and severe MDD. The main finding was an inverse association between depression severity and CRF as well as perceived fitness compared with healthy controls. Resting heart rate was elevated with increasing depression severity. The time-based but not the frequency-based autonomic function parameters showed an inverse association with depression severity. The pattern of results suggests that among in-patients with major depressive disorder, those with particularly high self-assessed severity scores show a lower CRF, less favorable perceived fitness and partial autonomic dysfunction compared to healthy controls. To counteract these conditions, physical activity interventions may be effective. [ABSTRACT FROM AUTHOR]

Suicide is a serious global issue, with major depressive disorder (MDD) being a significant risk factor for suicidal thoughts and behaviors. There is an urgent need to determine whether event-related potential components (ERPs) could be used as an indicator to assess suicidal risk. From 2020 to 2023, 258 participants in total were recruited into the study. All participants were divided into four groups: MDD patients at high (n = 66), moderate (n = 66), and low risk (n = 56) of suicide, and healthy controls (HCs)(n = 70). Each participant provided socio-demographic information and underwent evaluations using clinical psychological scales such as 7-item Generalized Anxiety Disorder (GAD-7), Health Questionnaire-9 items (PHQ-9), and Nurses' Global Assessment of Suicide Risk (NGASR). The auditory brainstem response test and ERP examination were performed for all subjects. Our study found that the amplitude of P2–P3 and N2–P3 was significantly reduced in MDD patients at moderate and high risk of suicide, and these were negatively correlated with NGASR total score (all P < 0.05). Point B latency was positively correlated with NGASR total score (P < 0.05). Patients with MDD patients at low risk for suicide had a lower A-B amplitude compared to HCs (P < 0.05). No differences were found in MMN or P50 components between the four groups (all P > 0.05). MDD patients at higher risk of suicide exhibited severe impairment of cognitive function. ERP indices, such as the amplitude of P2–P3 and N2–P3, could be associated with the risk of suicide in MDD patients. • Compared to HCs, MDD patients at moderate and high risk for suicide had a lower P2–P3b amplitude and NGASR total score. • Compared to HCs, MDD patients at moderate and high risk for suicide had a lower N2–P3 amplitude and NGASR total score. • Compared to HCs, MDD patients at low risk for suicide had a lower A-B amplitude. • Point B latency was positively correlated with NGASR total score. [ABSTRACT FROM AUTHOR]

One in five people will likely suffer from major depressive disorder (MDD) during their life. Thirty percent of those with MDD will experience Treatment Resistant Depression (TRD), which is characterized by a failure to respond to two adequately administered trials of antidepressants. Esketamine is a rapidly acting intranasal antidepressant. Present-day Esketamine research has limited data in real-world populations. This study aimed to assess Esketamine treatment in a real-world community-based population. This naturalistic retrospective study included 94 individuals age 18 and above diagnosed with TRD, treated with Esketamine in an outpatient setting. The treatment was given in a single clinic, from January 2021 to January 2023, following approval of the Institutional Internal Review Board. The treatment included an acute phase (biweekly treatment, continuing 4–8 weeks), followed by a maintenance phase (once a week to once a month, for 6–12 months). Dosing ranged from 28 mg to 84 mg. Demographic and clinical data were retrospectively gathered. Depressive symptoms were assessed using the Quick Inventory of Depressive Symptomatology, at baseline and during each treatment phase. All patients completed the acute phase. About 60% completed the maintenance phase. Linear improvement of depressive symptoms was revealed in both phases. A sub-analysis of patients with comorbid personality disorder revealed a similar improvement pattern in the acute phase with milder improvement during the maintenance phase, compared to the other patients. This study supports the use of Esketamine for TRD, including patients with comorbid personality disorder and previous electroconvulsive therapy. [ABSTRACT FROM AUTHOR]

Sleep disturbance is one of the most frequent somatic symptoms in major depressive disorder (MDD), but the neural mechanisms behind it are not well understood. Sleep efficiency (SE) is a good indicator of early awakening and difficulty falling asleep in MDD patients. Our study aimed to investigate the relationship between sleep efficiency and brain function in MDD patients. We recruited 131 MDD patients from the Fourth People's Hospital in Hefei, and 71 well-matched healthy controls who were enrolled from the community. All subjects underwent resting-state functional MRI. Brain function was measured using the fractional amplitude of low-frequency fluctuation (fALFF), sleep efficiency was objectively measured by polysomnography (PSG), and clinical scales were used to evaluate depressive symptoms and sleep status. Multivariate regression analysis was performed to assess the relationship between the amplitude of the low frequency fluctuation fraction and sleep efficiency. Three brain regions with relevance to sleep efficiency in MDD patients were found: inferior occipital gyrus (Number of voxels = 25, peak MNI coordinate x/y/z = −42/-81/-6, Peak intensity = 4.3148), middle occipital gyrus (Number of voxels = 55, peak MNI coordinate x/y/z = −30/-78/18, Peak intensity = 5.111), and postcentral gyrus (Number of voxels = 26, peak MNI coordinate x/y/z = −27/-33/60, Peak intensity = 4.1263). But there was no significant relationship between fALFF and SE in the healthy controls. The reduced sleep efficiency in MDD may be related to their lower neural activity in the inferior occipital gyrus, middle occipital gyrus, and postcentral gyrus. The findings may provide a potential neuroimaging basis for the clinical intervention in patients with major depressive disorder with sleep disturbances. [ABSTRACT FROM AUTHOR]

Previous studies have documented negative associations between somatic symptoms and remission of major depressive disorder (MDD). However, the correlations of specific somatic symptoms with remission remain uncertain. We aimed to explore the associations between specific somatic symptoms and remission focusing on sex differences among patients with MDD. We used data from patients with MDD in the Depression Cohort in China. At baseline, total somatic symptoms were evaluated using the 28-item Somatic Symptoms Inventory and were categorized into pain, autonomic, energy, and central nervous system (CNS) symptoms. To measure remission of MDD, depressive symptoms were evaluated using the Patient Health Questionnaire-9 after 3 months of treatment. We ultimately included 634 patients. Compared with quartile 1 of total somatic symptom scores, the full-adjusted ORs (95% CIs) for remission from quartile 2 to quartile 4 were 0.52 (0.30, 0.90), 0.44 (0.23, 0.83), and 0.36 (0.17, 0.75), respectively (P -value for trend = 0.005). The restricted cubic spline showed no non-linear associations between total somatic symptoms with remission (P -value for non-linear = 0.238). Pain, autonomic, and CNS symptoms showed similar results. Sex-stratified analysis showed that total somatic symptoms, pain symptoms, and autonomic symptoms were negatively correlated with remission in females, whereas CNS symptoms were negatively associated with remission in males. Our findings indicate that specific somatic symptoms exert differential effects on remission of MDD. Therapeutic interventions that target pain, autonomic, and CNS symptoms may increase the probability of remission. Furthermore, interventions for somatic symptoms should be tailored by sex, and females deserve more attention. [ABSTRACT FROM AUTHOR]

The relationship between suicide attempts and lipid profiles in patients with major depressive disorder (MDD) remains uncertain. The purpose of this study was to investigate sex differences in the relationship between suicide attempts and plasma lipid profiles in a large sample of first-episode and drug naive (FEDN) MDD patients. We recruited 1718 FEDN MDD patients and gathered demographic, clinical, and blood lipid data. The Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale and the Positive and Negative Syndrome Scale were used to assess the symptoms of patients. There was no significant difference in the prevalence of suicide attempts between male and female MDD patients. The suicide attempt group had higher levels of depression, anxiety, psychotic symptoms, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), but lower levels of high-density lipoprotein cholesterol (HDL-C) levels than the non-suicide attempt group. Binary logistic regression showed that TC levels were significantly correlated with suicidal attempts in both male and female patients. Correlation analysis revealed that the levels of TC, HDL-C and LDL-C were significantly associated with the number of suicide attempts in both male and female patients. Further multiple linear regression revealed that TC levels were significantly associated with the number of suicide attempts in male patients only. Lipid biomarkers, particularly high TC levels, are associated with suicide attempts in both male and female MDD patients. However, there is gender difference in association between lipid biomarkers, especially TC levels, and the number of suicide attempts in MDD patients. • There was no gender difference in the prevalence of suicide attempts in MDD patients. • Suicide attempters had higher depression severity, anxiety, and psychotic symptoms. • 3.Suicidal attempters showed higher TC, LDL-C, but lower HDL-C levels. • TC levels were significantly associated with suicide attempts in both male and female patients. • Only male patients' s TC levels associated with the number of suicide attempts. [ABSTRACT FROM AUTHOR]

Cariprazine has been approved by the Food and Drug Administration for treating bipolar depression and as an adjunctive treatment for Major Depressive Disorder (MDD). However, it remains unclear about its pharmacological efficacy in treating MDD. Therefore, a meta-analysis was conducted to investigate the adjunctive use of cariprazine in MDD. Electronic databases were searched for eligible studies evaluating the efficacy and safety of cariprazine in patients with MDD up to November 15, 2023. The changes in Montgomery-Asberg Depression Rating Scale (MADRS) score and incidence of adverse events (AEs), which represents of efficacy and tolerability, are considered as the main outcomes. A total of 3066 patients with MDD included in all across 5 RCTs. With regard to MADRS score, cariprazine group showed better results than control group (SMD = −0.12, 95% CI -0.19 to −0.04, P = 0.002, 5 RCTs, n = 3066). Cariprazine, meanwhile, improved the MADRS response (RR = 1.19, 95% CI 1.08 to 1.31, P = 0.0004, 5 RCTs, n = 3066). For safety outcomes, statistical difference was observed in AEs (RR = 1.26, 95% CI 1.18 to 1.35, P < 0.00001, 5 RCTs, n = 3077). The suicide ideation and SAEs showed no statistical difference between two groups. Cariprazine demonstrated antidepressant effect as an augmentation therapy in treating MDD. Meanwhile, the tolerability of it was acceptable as an adjunctive treatment. However, studies with larger sample sizes are still needed to explore the optimal dosage. • Cariprazine had significant efficacy when used as an adjunctive therapy to patients with major depressive disorder. • AEs with cariprazine as ADT adjunct are acceptable, unlikely to harm mental or physical health significantly. • By employing Trial Sequential Analysis (TSA), we confirmed the reliability of the antidepressant effect of cariprazine. [ABSTRACT FROM AUTHOR]

The brain of major depressive disorder (MDD) is associated with altered functional connectivity (FC) compared to that of healthy individuals when processing positive and negative visual stimuli. Building upon alterations in brain connectivity, some researchers have employed electroencephalography (EEG) to study FC in MDD, aiming to enhance both diagnosis and treatment; however, the results have been inconsistent and the studies involving FC during emotional recognition are limited. This study aims to 1) investigate the effects of MDD on EEG patterns during visual emotional processing, 2) explore the therapeutic effects of antidepressant treatment on brain FC within the first week, and assess whether these effects can be predictive of treatment outcomes four weeks later, and 3) study baseline FC parameter biomarkers that can be used to predict treatment responsiveness in MDD patients. This clinical observational study recruited 38 healthy controls (HC) and 48 MDD patients. Patients underwent an EEG exam while looking at validated images of happy and sad faces at week 0 and 1. MDD patients were categorized into treatment responders and non-responders after 4 weeks of treatment. We conducted the FC analysis (node strength (NS), global efficiency (GE), and cluster coefficient (CC)) on HC and MDD patients using graph theoretical analysis. Multivariable linear regression was used to evaluate the influence of MDD on FC compared to HC, while controlling for confounding variables including age, gender, and academic degrees. At week 0 and week 1, MDD patients revealed to have significant reductions in FC parameters (NS, GE and CC) compared to HC. When comparing MDD patients at week 1 post-antidepressant treatment and pre-treatment, no significant differences in FC changes were observed. Multivariable regression revealed a significant negative effect on FC of MDD. Compared to the treatment non-responsive group, the responsive group revealed a significantly higher FC in delta band frequency at baseline. MDD patient group showed impaired FC during visual emotion-processing and we observed baseline FC parameters to be associated with treatment response at week 4. While signs of FC changes were observed in the brain after a week of treatment, it is possible that one week may still be insufficient to demonstrate significant alterations in the brain. Our results suggest the potential utilization of EEG-based FC as an indicative measure for predicting treatment response and monitoring treatment progress in MDD patients. [ABSTRACT FROM AUTHOR]

The adipokines secreted by adipocytes might play an important role through crossing the blood brain barrier to the brain, which could mediate the common physiological pathway between depression and obesity. CTRP4, a member of the CTRP family, is highly expressed in human adipose tissue and brain tissue. this study aimed to measure serum C1q/TNF-related protein 4 (CTRP4) levels in depressive patients to explore the association between CTRP4 levels and depression. depressive patients (n = 138), healthy controls (n = 100) were enrolled from September 2020 to December 2021. The level of serum CTRP4 was measured by enzymes linked to immunosorbent assay (ELISA). Other biochemical indicators were measured by Advia 2400 automatic biochemistry analyzer. Depressive symptoms of patients were assessed using the Hamilton Depression Scale-24 item (HAMD-24). this study found that serum CTRP4 levels in the MDD group were lower than that of the health control (P < 0.001). Serum CTRP4 levels were negatively correlated with HAMD-24 scores (r = −0.368; P = 0.001). The serum CTRP4 levels were negatively correlated with Total Cholesterol (TC), Triglyceride (TG) and Low-Density Lipoprotein Cholesterol (LDL-C), but were positively associated with high density lipid-cholesterol (HDL-C) (r = −0.267, r = −0.255, r = −0.312 and r = 0.280; P = 0.017, P = 0.023, P = 0.005 and P = 0.012). The ROC curve of CTRP4 showed that the Area Under Curve (AUC) was 0.856, P < 0.001. the serum CTRP4 levels in MDD patients were lower than that in health control, which might mediate the physiological progress of MDD patients. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) has consistently proven to be a multifactorial and highly comorbid disease. Despite recent depression-related research demonstrating causalities between MDD-related factors and a small number of variables, including brain structural changes, a high-statistical power analysis of the various factors is yet to be conducted. We retrospectively analyzed data from 155 participants (84 healthy controls and 71 patients with MDD). We used magnetic resonance imaging and diffusion tensor imaging data, scales assessing childhood trauma, depression severity, cognitive dysfunction, impulsivity, and suicidal ideation. To simultaneously evaluate the causalities between multivariable, we implemented two types of MDD-specified structural equation models (SEM), the behavioral and neurobehavioral models. Behavioral SEM showed significant results in the MDD group: Comparative Fit Index [CFI] = 1.000, Root Mean Square Error of Approximation [RMSEA]) = 0.000), with a strong correlation in the scales for childhood trauma, depression severity, suicidal ideation, impulsivity, and cognitive dysfunction. Based on behavioral SEM, we established neurobehavioral models showing the best-fit in MDD, especially including the right cingulate cortex, central to the posterior corpus callosum, right putamen, pallidum, whole brainstem, and ventral diencephalon, including the thalamus (CFI >0.96, RMSEA <0.05). Our MDD-specific model revealed that the limbic-associated regions are strongly connected with childhood trauma rather than depression severity, and that they independently affect suicidal ideation and cognitive dysfunction. Furthermore, cognitive dysfunction could affect impulsivity. [ABSTRACT FROM AUTHOR]

Response to antidepressants is related to hippocampal neurogenesis integrity, a process mediated by neurotrophins, such as Brain Derived Neurotrophic Factor (BDNF). In turn, pro-inflammatory state appears to reduce neurogenesis, and has been associated with refractory depressive states. We propose to analyze the human neural progenitor cells derived from the olfactory epithelium (HNPCs-OE) as an indicator of neurogenesis in humans. Therefore, we compared the number and content of HNPCs-OE in depressed patients taking antidepressants, according to response to treatment. Twenty depressed patients were followed during eight weeks after antidepressant treatment was prescribed. At the end evaluation they were divided in two groups according to Hamilton depression rating scale (HDRS) scores: responders and non-responders. We compared the number and components of HNPCs-OE between groups and observed an elevation of interleukine-8 in those patients who do not achieve response to treatment, BDNF levels were no related to antidepressant response. • Human neuronal progenitor cells derived from the olfactory epithelium were studied in depressed patients. • The cells number was higher in younger than older depressed patients. • The cells number was associated to depression scores after antidepressant treatment. • Increased interleukine-8 was observed in patients who did not achieve response to antidepressant. [ABSTRACT FROM AUTHOR]

The study investigates morphometric changes using surface-based measures and logistic regression in Major depressive-disorder (MDD) and Manic-disorder patients as compared to controls. MDD (n = 21) and manic (n = 20) subjects were recruited from psychiatric clinics, along with 19 healthy-controls from local population, after structured and semi-structured clinical interview (DSM-IV, brief Psychotic-Rating Scale (BPRS), Young Mania Rating Scale (YMRS), Hamilton depression rating scale (HDRS), cognitive function by postgraduate Institute Battery of Brain Dysfunction (PGIBBD)). Using 3D T1-weighted images, gray matter (GM) cortical thickness and GM-based morphometric signatures (using logistic regression) were compared among MDD, manic disorder and controls using analysis of covariance (ANCOVA). No significant difference was found between the MDD and manic disorder patients. When compared to controls, cortical thinning was observed in bilateral rostral middle frontal gyrus and parsopercularis, right lateral occipital cortex, right lingual gyrus in MDD; and bilateral rostral middle frontal and superior frontal gyrus, right middle temporal gyrus, left supramarginal and left precentral gyrus in Manic disorders. Logistic regression analysis exhibited GM cortical thinning in the bilateral parsopercularis, right lateral occipital cortex and lingual gyrus in MDD; and bilateral rostral middle, superior frontal gyri, right middle temporal gyrus in Manic with a sensitivity and specificity of 85.7 % and 94.7 % and 90.0 % and 94.7 %, respectively in comparison with controls. Both groups exhibited GM loss in bilateral rostral middle frontal gyrus brain regions compared to controls. Multivariate analysis revealed common changes in GM in MDD and manic disorders associated with mood temperament, but differences when compared to controls. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a heterogeneous mental disorder, and accompanying anxiety symptoms, known as anxious depression (AD), are the most common subtype. However, the pathophysiology of AD may be distinct in depressed patients without anxiety (NAD) and remains unknown. This study aimed to investigate the relationship between functional connectivity and peripheral transcriptional profiles in patients with AD and NAD. Functional imaging data were collected to identify differences in functional networks among patients with AD (n = 66), patients with NAD (n = 115), and healthy controls (HC, n = 200). The peripheral transcriptional data were clustered as co-expression modules, and their associations with AD, AND, and HC were analyzed. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses of the genes in the significant module were performed. Correlation analysis was performed to identify functional network-associated gene co-expression modules. A network was identified which consisted of 23 nodes and 28 edges that were significantly different among three sample groups. The regions of the network were located in temporal and occipital lobe. Two gene co-expression modules were shown to be associated with NAD, and one of which was correlated with the disrupted network in the AD group. The biological function of this module was enriched in immune regulation pathways. The results suggested that immune-related mechanisms were associated with functional networks in AD. • The anxious depression is the most common subtype of depresison, and the pathophysiology of anxious depression may be distinct in non-anxious depression. • An FC network consisting of 23 nodes and 28 edges, mainly located in temporal and occipital regions, was associated with anxious depresion. • Peripheral transcriptional profiles showed that immune-related pathway might play important roles in MDD. • The immune-related biological processes were associated with disrupted functional connectivity in a widely distributed connectome centralized in paralimbic regions and the occipital lobe in patients with anxious depression. [ABSTRACT FROM AUTHOR]

Anger is among the core symptoms in male-specific inventories of depression and has consistently been linked with suicidal ideation. In this study, we assessed whether this link may be mediated via other prominent symptoms of depression in men, namely risk-taking and alcohol misuse. We used self-reported data from 322 men responding to a 3-wave survey over 6 months. Regression with mediation analysis was employed to test whether anger at baseline predicted suicidal ideation six months later through the mediating effects of risk-taking or alcohol misuse at 3 months. We found a statistically significant indirect effect (indicating a mediation effect) of anger at baseline on suicidality at 6-months follow-up through risk taking at 3-months follow-up (effect = 0.007, SE = 0.003, 99% Confidence interval = 0.0002 to 0.0161). Anger at baseline was not significantly associated with alcohol misuse at 3-months follow-up (β =.062, t = 0.919, p =.358), thus nullifying alcohol misuse as a possible mediator between anger and suicidal ideation. In conclusion, the results of this study suggest that risk-taking, but not alcohol misuse, may be a mediator between anger and suicidal ideation in the context of male depression. If these results are replicated, assessing anger and risk-taking may inform monitoring of suicidality. Also, anger and risk-taking may be promising targets for treatment aimed at reducing the risk of suicide. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder with remarkable inter-subject variability in clinical manifestations. Neuroimaging changes of the cerebellum have been recently proposed as a way to characterize MDD-related brain disruptions and might further explain various clinical symptoms. However, the cerebellar contributions to MDD clinical heterogeneity remain largely unknown. The analyzed data consisted of 251 MDD patients and 235 matching healthy controls (HC). The inter-subject variability of functional connectomes (IVFC) was estimated via Pearson's correlation analysis between each pair of the cerebellar and cerebral regions based on resting-state functional magnetic resonance imaging (rs-fMRI). A partial least squares (PLS) regression analysis was performed to determine the potential dimension linking the IVFC to clinical symptom measures. The results indicated that similar spatial distribution patterns of the cerebellar IVFC were observed between MDD and HC, but the MDD group exhibited abnormal IVFC alterations in the bilateral Cerebelum_4_5, bilateral Cerebelum_6, Vermis_1_2 and Vermis_8. The PLS model revealed that the IVFC pattern in the left Cerebelum_6 was significantly associated with three HAMD-17 items including the work and activities, psychomotor retardation, and depressed mood. These findings provided new evidence for the cerebellar changes in MDD. Specifically, we found that the altered inter-subject variability measurements correlated with clinical manifestations of this illness. Elucidating this variability could prove helpful for the evaluation of MDD heterogeneity as well as for understanding its pathophysiological mechanism. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) remains a significant global health concern, with limited and slow efficacy of existing antidepressants. Electroconvulsive therapy (ECT) has superior and immediate efficacy for MDD, but its action mechanism remains elusive. Therefore, the elucidation of the action mechanism of ECT is expected to lead to the development of novel antidepressants with superior and immediate efficacy. Recent studies suggest a potential role of hippocampal astrocyte in MDD and ECT. Hence, we investigated antidepressant effect of electroconvulsive stimulation (ECS), an animal model of ECT, -related genes in hippocampal astrocyte with a mouse model of MDD, in which corticosterone (CORT)-induced depression-like behaviors were recovered by ECS. In this model, both of CORT-induced depression-like behaviors and the reduction of hippocampal astrocyte were recovered by ECS. Following it, astrocytes were isolated from the hippocampus of this model and RNA-seq was performed with these isolated astrocytes. Interestingly, gene expression patterns altered by CORT were reversed by ECS. Additionally, cell proliferation-related signaling pathways were inhibited by CORT and recovered by ECS. Finally, serum and glucocorticoid kinase-1 (SGK1), a multi-functional protein kinase, was identified as a candidate gene reciprocally regulated by CORT and ECS in hippocampal astrocyte. Our findings suggest a potential role of SGK1 in the antidepressant effect of ECS via the regulation of the proliferation of astrocyte and provide new insights into the involvement of hippocampal astrocyte in MDD and ECT. Targeting SGK1 may offer a novel approach to the development of new antidepressants which can replicate superior and immediate efficacy of ECT. [ABSTRACT FROM AUTHOR]

Many aspects of the impact of childhood trauma remain unknown, such as the age at which individuals are most vulnerable to trauma, whether traumatic experiences have more severe and lasting effects when experienced early in life, and whether early life trauma causes psychiatric conditions such as anxiety and major depressive disorder (MDD) that persist over time or evolve into other disorders. Thus, this study aimed to investigate the impact of traumatic experiences in childhood on susceptibility to mood disorders in adulthood, particularly MDD. Animal models were used to address these questions, and different stressor protocols at various stages of the offspring's life were used. Three-hit starting with injections of Poly: IC was performed on the 9th day of gestation and then considered the first stressor. After birth, the animals were exposed to the maternal deprivation (MD) protocol, which separated the pups from the mother 3 h a day during the first ten days of life. From the 60th day of life, the animals were divided to receive the chronic mild stress (CMS) protocol over 21 days. The stressors can induce anxiety-like behaviors, such as increased locomotor activity through a maternal immune activation protocol using Poly: IC and demonstrating depressive-like behaviors through the MD and CMS protocols. It also showed changes in brain structures for pro-inflammatory parameters, IL-1β and TNF-α, and alterations in anti-inflammatory parameters, IL-4 and IL-10, at different ages of life. The study also found that regulating pro- and anti-inflammatory cytokines is necessary for appropriate neuronal behavior, and stress responses can be both friendly and enemy, with costs and benefits balanced to provide the best-fit result. In conclusion, phenotypic characteristics of animals' life history are shaped by signals transmitted directly or indirectly to developing animals, known as "predictive adaptive responses." [ABSTRACT FROM AUTHOR]

There is a tremendous need for brief, valid, and free assessments of anxiety in child mental healthcare. The goal of this study was to determine the psychometric properties of two such measures, the GAD-7 and PROMIS-Anxiety-4a, in 1000 children, adolescents, and young adults (8-20 years-old) with depression and/or suicidality. The GAD-7, the PROMIS-Anxiety-4a, and other validated assessments of anxiety, physical functioning, and psychiatric diagnoses were completed. Confirmatory factor analyses showed an acceptable fit for a single factor in both measures via all indices but the RMSEA. They demonstrated measurement invariance across pre-adolescents (8-12 years-old) and adolescents and emerging adults (13-20 years-old), though scalar invariance was not observed for the GAD-7. Both measures showed strong convergent validity, GAD-7: r = 0.68; PROMIS-Anxiety-4a: r = 0.75, divergent validity with a measure of physical function, GAD-7: r = -0.24; PROMIS-Anxiety-4a: r = -0.28, good internal consistency, ω = 0.89 for both, and high test-retest reliability, GAD-7: r = 0.69; PROMIS-Anxiety-4a: r = 0.71. Both measures also showed acceptable sensitivity and specificity in detecting the presence of any anxiety disorder, GAD-7 cut-off score of 10: AUC = 0.75; PROMIS-Anxiety-4a cutoff score of 12: AUC = 0.79. The GAD-7 correlated similarly with the Screen for Child Anxiety Related Disorders total score and generalized anxiety subscale, and also showed similar diagnostic sensitivity and specificity when used to detect the presence of any anxiety disorder vs. generalized anxiety disorder specifically. Results suggest that both of these brief, publicly available instruments are valid and reliable assessments of anxiety among youth in treatment for depression and/or suicidality. • Explored psychometrics of GAD-7 & PROMIS-Anxiety-4a among depressed/suicidal youth. • Both showed acceptable single factor fit. • Both showed strong convergent and divergent validity. • Both showed acceptable diagnostic utility in screening for anxiety disorders. • GAD-7 is valid in assessing anxiety broadly and generalized anxiety specifically. [ABSTRACT FROM AUTHOR]

Pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α are elevated in response to psychosocial stress; however, less is known about other inflammatory markers. We explored response to the Trier Social Stress Test (TSST) of 16 cytokines and growth factors in patients with major depressive disorder (MDD, n = 12) vs. healthy volunteers (HV, n = 16). Outcomes were baseline and post-stress levels estimated by area under the curve (AUC i) and peak change over 3 timepoints. We also explored correlations between biomarkers and clinical characteristics. Baseline concentrations were higher in MDD for platelet-derived growth factor (PDGF)-AB/BB (p = 0.037, d = 0.70), granulocyte-macrophage colony-stimulating factor (GM-CSF, p = 0.033, d = 0.52), and IL-8 (p = 0.046, d = 0.74). After TSST, AUC i was higher in MDD for GM-CSF (p = 0.003, d = 1.21), IL-5 (p = 0.014, d = 1.62), and IL-27 (p = 0.041, d = 0.74). In MDD, depression severity correlated positively with soluble CD40L (sCD40L) for AUC i (Spearman's ρ = 0.76, p = 0.004) and with baseline vascular endothelial growth factor A (VEGFA, r = 0.85, p < 0.001), but negatively with baseline monokine induced by gamma interferon (MIG, aka CXCL9; r = −0.77, p = 0.003). Effect sizes were robust in this exploratory study, although interpretation of the results must be cautious, given small sample size and multiple comparisons. Differential study of stress-induced biomarkers may have important ramifications for MDD treatment. • Exploration of 16 inflammatory markers in relation to the Trier social stress test • Levels differentiated MDD from healthy controls at baseline and after acute stress • MDD baseline levels were higher in GM-CSF, IL-8, and PDGF-AB/BB • MDD post-stress had higher GM-CSF, IL-5, and IL-27 • Depression severity correlated with baseline VEGF & MIG and predicted sCD40L response [ABSTRACT FROM AUTHOR]

Mood disorders significantly impact global health, with MDD ranking as the second leading cause of disability in the United States and BD ranking 18th. Despite their prevalence and impact, the relationship between premorbid intelligence and the subsequent development of BD and MDD remains inconclusive. This study investigates the potential of premorbid Intelligence Quotient (IQ) and school failure frequency as risk factors for Bipolar Disorder (BD) and Major Depressive Disorder (MDD) in a birth cohort setting. We analyze data from the Pelotas population-based birth cohort study, comprising 3580 participants aged 22, who had no prior mood disorder diagnoses. Utilizing regression models and accounting for potential confounders, we assess the impact of IQ and school failure, measured at age 18, on the emergence of BD and MDD diagnoses at age 22, using individuals without mood disorders as comparators. Results reveal that lower IQ (below 70) at 18 is associated with an increased risk of BD (Adjusted Odds Ratio [AOR] 1.75, 95%CI: 1.00–3.09, p < 0.05), while higher IQ (above 120) is linked to MDD (AOR 2.16, 95%CI: 1.24–3.75, p < 0.001). Moreover, an elevated number of school failures is associated with increased BD risk (AOR 1.23, 95%CI: 1.11–1.41, p < 0.001), particularly for BD type 1 (AOR 1.36, 95% CI: 1.17–1.58, p < 0.001). These findings offer insights into the distinct premorbid intellectual characteristics of BD and MDD and contribute to a deeper understanding of their developmental trajectories, potentially informing the development of risk assessment tools for mood disorders. • At 18, high intellectual functioning doubles the risk of Major Depressive Disorder (MDD) within 4 years. • At 18, low/borderline intellectual functioning increases Bipolar Disorder (BD) risk 1.75x in 4 years. • BD linked to more school failures compared to those without mood disorders. • Absence of school dropout is a protective factor for Bipolar I Disorder. [ABSTRACT FROM AUTHOR]