Recurrent Major Depression Research Articles

Micronutrients and Major Depression: A Mendelian Randomisation Study.

Various vitamins and minerals have been implicated in the aetiology of depression. To estimate the effects of micronutrient exposures on major depressive disorder (MDD) and recurrent depression (rMDD) using Mendelian randomisation (MR), a method using genetic data to estimate causal effects given certain assumptions. We undertook a comprehensive bidirectional MR study of multiple micronutrient exposures on MDD and rMDD. Summary statistics were obtained from the Psychiatric Genomics Consortium (PGC) genome-wide association studies (GWASs) of MDD (cases = 116,209; controls = 314,566) and rMDD (cases = 17,451; controls = 62,482). None of the micronutrients with available genetic instruments were strongly associated with MDD or rMDD using traditional MR methods. However, using methods to increase analytical power by accounting for genetically correlated variants (e.g., cIVW) highlighted five micronutrients with possible causal effects. Point estimates for rMDD were the largest magnitude, with three micronutrients suggestive of a protective effect: serum iron (ORcIVW 0.90 per SD increase; 95% CI 0.85-0.95; p = 0.0003); erythrocyte copper (ORcIVW 0.97; 95% CI 0.95-0.99; p = 0.0004); and 25(OH) vitamin D (ORcIVW 0.81; 0.66-0.99; p = 0.04). Apparent adverse effects of increased selenium on the risk of MDD (ORcIVW 1.03; 95% CI 1.02-1.05; p = 0.0003) and rMDD (ORcIVW 1.08; 95% CI 1.00-1.08; p = 0.06), and serum magnesium on rMDD (ORcIVW 1.21; 1.01-1.44; p = 0.04); were less consistent between methods and may be driven by pleiotropy. Our results suggest weak evidence for a protective effect of iron, copper and 25(OH)D on major depressive outcomes, with mixed evidence for selenium and magnesium. There was no evidence to support a causal effect of any other micronutrients on MDD or rMDD, although genetic instruments were lacking, with insufficient power to detect small but important effects. Future micronutrient supplementation trials should ensure ample statistical power given modest causal effect estimates and consider potential risks of supplementation, as some micronutrient effect estimates suggested potential harm in excess.

Major depression recurrence is associated with differences in obesity-related traits in women, but not in men.

Obesity-related cardiometabolic comorbidity is common in major depressive disorder (MDD). However, sex differences and MDD recurrence may modify the MDD-obesity-link. Sex-specific associations of MDD recurrence (single [MDDS] or recurrent episodes [MDDR]) and obesity-related traits were analyzed in 4.100 adults (51.6% women) from a cross-sectional population-based cohort in Germany (SHIP-Trend-0). DSM-IV-based lifetime MDD diagnoses and MDD recurrence status were obtained through diagnostic interviews. Obesity-related outcomes included anthropometrics (weight, body mass index, waist- and hip-circumference, waist-to-hip ratio, waist-to-height ratio), bioelectrical impedance analysis of body fat mass and fat-free mass, and subcutaneous (SAT) and visceral adipose tissue (VAT) from abdominal magnetic resonance imaging. Sex-stratified linear regression models predicting obesity-related traits from MDD recurrence status were adjusted for age, education, and current depressive symptoms. 790 participants (19.3%) fulfilled lifetime MDD criteria (23.8% women vs. 14.5% men, p<0.001). In women, MDDS was inversely associated with anthropometric indicators of general and central obesity, while MDDR was positively associated with all obesity-related traits, except waist-to-hip ratio and fat-free mass. In women, MDDR versus MDDS was associated with higher levels of obesity across all outcomes except fat-free mass. In men, MDD was positively associated with SAT regardless of MDD recurrence. Additionally, lifetime MDD was positively associated with VAT in men. Results remained significant in sensitivity analyses after exclusion of participants with current use of antidepressants. The MDD-obesity association is modified by MDD recurrence and sex independent of current depressive symptoms. Accounting for sex and MDD recurrence may identify individuals with MDD at increased cardiometabolic risk.

Amelioration of suicidal ideation in routine care psychotherapy: Preliminary findings from a large multicenter assessment

BackgroundSuicidal ideation represents a major concern in clinical practice. Yet, little is known about the effects of routine psychotherapy on the amelioration of suicidal ideation. Therefore, the aim of the current study is to assess mental disorder-specific changes of suicidal ideation in a large sample of adult outpatients undergoing routine-care cognitive-behavioural therapy in Germany. MethodsA total of N = 4549 adult outpatients, 64.2% female; age: M(SD) = 36.83 (14.03), range: 18–89 years of age, who completed cognitive-behavioral therapy at one of 26 outpatient clinics in Germany were included in the current study. Amelioration of suicidal ideation was assessed using the Suicide Item (Item 9) of the Beck-Depression Inventory. ResultsSuicidal ideation was reported by 36.7% of the patients pretreatment and by 17.6% posttreatment. Effect sizes were small to moderate (d = 0.25 -0.51) and 4.4% reported an increase in suicidal ideation. Residual suicidal ideation at the posttreatment assessment was more likely in patients diagnosed with recurrent Major Depression, Dystymia, and Borderline Personality Disorder, and older patients. LimitationThe study relies on a naturalistic sample, no waitlist or control conditions were involved. ConclusionAcross primary diagnoses, a significant proportion of patients experience an amelioration of suicidal ideation over the course of routine-care psychotherapy. Still, a substantial proportion of patients report no change or an increase in suicidal ideation during treatment. Thus, continuous monitoring of suicidal ideation appears to be imperative throughout the psychotherapeutic process.

A Computing System for Complex Cases of Major Recurrent Depression Based on Latent Semantic Analysis: Relationship between Life Themes and Symptoms

The paper presents a computing procedure with the goal of suggesting applicable solutions to improve complex cases of major recurrent depression. The focus is on identifying the patients’ illness patterns and on finding solutions for alleviating problematic symptoms. The illness patterns synthesize the outcomes of the relationship between the patients’ life themes and symptoms. The testing of the effectiveness of illness improvement solutions was conducted by evaluating and comparing the Beck scores of patients after each psychotherapy session. In addition to latent semantic analysis used to identify semantic relationships between life themes and symptoms, the research also employed the correlation method to find life themes/symptoms that are experienced undistortedly and associations between life themes that amplify latent symptoms. The computing system was applied to eleven patients with severe forms of depression and their progress was monitored for six months. The results obtained following the application of the computing system demonstrated its ability to describe personalized illness patterns and to significantly improve, through its suggestions, the illness of all patients. These findings recommend the use of the computing system in severe cases of major recurrent depression.

Family-based preventive intervention for children of parents with severe mental illness: A randomized clinical trial.

Children of parents with a severe mental illness have an increased risk of developing a lifetime mental illness. We aimed to compare the effects of a preventive family-based intervention, VIA Family, with treatment as usual (TAU) on these children's global functioning. Between 2017 and 2021, we conducted a pragmatic, rater-blinded, two-arm parallel-group superiority trial in Denmark. Families with at least one child aged 6-12years and at least one biological parent with schizophrenia spectrum disorder, bipolar disorder, or recurrent major or moderate depression were included. We randomly allocated 95 families with their 113 children to VIA Family or TAU (ratio 1:1). VIA Family was individually tailored and based on case management. The intervention included options for psychoeducation, parental support, and treatment for emerging child psychiatric symptoms. Blinded raters assessed children and their families at baseline and after 18months. The primary outcome was the difference in change between groups at end-of-treatment in daily global functioning measured with the Children's Global Assessment Scale. Secondary outcomes were emotional and behavioral problems and days absent from school. We analyzed data blinded to allocation. At post-intervention, differences in mean change from baseline between VIA Family and TAU were non-significant (CGAS: -1.20, 95% CI=-6.61; 4.21, p=0.66), as were the differences on the secondary and exploratory outcomes. Contrary to our hypothesis, we did not find a superior effect of VIA Family compared with TAU. The short follow-up period and large sample heterogeneity might explain the null findings. Therefore, a possible long-term, preventive treatment effect has yet to be explored.

Factors Associated with Transition to Serious Mental Illness.

There is increasing interest in early intervention and detection strategies for youth at-risk of developing a serious mental illness (SMI). Little is known about early factors that may be related to the later development of a SMI; thus, the aim of this study was to determine what clinical factors might relate to the development of in this study psychosis, bipolar disorder and severe or recurrent major depression in at-risk youth. The sample consisted of 162 youth aged 12-26 years at different stages of risk. Thirty-one participants developed a SMI during the study. Those who made a transition were compared on a range of baseline clinical and functional measures with those who did not make the transition. A Cox regression model was used to assess the association between measures and later development of a SMI. Female sex, attenuated psychotic symptoms as assessed with the Scale of Psychosis-Risk Symptoms (SOPS) and ratings on the K-10 Distress Scale, were found to be significantly associated with the later transition to mental illness. Females were 2.77 times more likely to transition compared to males. For the SOPS and K-10 scales, there is a 14% increase in the transition rate relative to a one-scale increase in SOPS and a 7% increase in the transition rate relative to a one-point increase in the K-10. Results from these longitudinal data provide further insight into the specific clinical measures that may be pertinent in early detection of mental illnesses.

Distinct effects of first-episode and recurrent major depressive disorder on brain changes related to suicidal ideation: Evidence from the REST-meta-MDD Project

BackgroundSignificant differences in clinical manifestations between first-episode and recurrent major depression disorder (FE-MDD/R-MDD) have been demonstrated in previous studies, including the degree of suicide attempt. However, the potential brain mechanism underlying the effect of depressive episode frequency on suicidal ideation (SI) remains unclear. MethodsIn this study, 102 patients with FE-MDD (SI/non-SI: N = 70/32) and 71 matched normal controls (NCs), as well as 75 patients with R-MDD (SI/non-SI: N = 37/38) and 49 matched NCs were screened from the Chinese REST-meta-MDD consortium. T1-weighted and resting-state fMRI images were used to calculate gray matter volume (GMV) and fractional amplitude of low-frequency fluctuations (fALFF), respectively. ResultsGroup comparisons revealed that FE-MDD showed changes only in GMV, while R-MDD showed changes in both GMV and fALFF compared to NCs. SI-specific GMV decreases were observed in the right cerebellum, superior marginal gyrus, and left middle temporal gyrus in FE-MDD patients, while SI-specific fALFF decreases in bilateral superior frontal gyrus and increases in bilateral cerebellum and left parahippocampal gyrus were obserevd in R-MDD patients. Moreover, a negative correlation was found between GMV value in right cerebellum and HAMD score. ConclusionsThese findings suggest that first-episode and recurrent MDD show different effects on brain structure and function in patients with SI, providing a potential explanation for the distinct clinical manifestations of MDD patients from a brain mechanisms perspective.

Ketamine modulates disrupted in schizophrenia-1/glycogen synthase kinase-3β interaction.

Disrupted in schizophrenia-1 (DISC1) is a scaffolding protein whose mutated form has been linked to schizophrenia, bipolar affective disorders, and recurrent major depression. DISC1 regulates multiple signaling pathways involved in neurite outgrowth and cortical development and binds directly to glycogen synthase kinase-3β (GSK-3β). Since ketamine activates GSK-3β, we examined the impact of ketamine on DISC1 and GSK-3β expression. Postnatal day 7 rat pups were treated with ketamine with and without the non-specific GSK-3β antagonist, lithium. Cleaved-caspase-3, GSK-3β and DISC1 levels were measured by immunoblots and DISC1 co-localization in neurons by immunofluorescence. Binding of DISC1 to GSK-3β was determined by co-immunoprecipitation. Neurite outgrowth was determined by measuring dendrite and axon length in primary neuronal cell cultures treated with ketamine and lithium. Ketamine decreased DISC1 in a dose and time-dependent manner. This corresponded to decreases in phosphorylated GSK-3β, which implicates increased GSK-3β activity. Lithium significantly attenuated ketamine-induced decrease in DISC1 levels. Ketamine decreased co-immunoprecipitation of DISC1 with GSK-3β and axonal length. These findings confirmed that acute administration of ketamine decreases in DISC1 levels and axonal growth. Lithium reversed this effect. This interaction provides a link between DISC1 and ketamine-induced neurodegeneration.

Distinct resting-state effective connectivity of large-scale networks in first-episode and recurrent major depression disorder: evidence from the REST-meta-MDD consortium.

Previous studies have shown disrupted effective connectivity in the large-scale brain networks of individuals with major depressive disorder (MDD). However, it is unclear whether these changes differ between first-episode drug-naive MDD (FEDN-MDD) and recurrent MDD (R-MDD). This study utilized resting-state fMRI data from 17 sites in the Chinese REST-meta-MDD project, consisting of 839 patients with MDD and 788 normal controls (NCs). All data was preprocessed using a standardized protocol. Then, we performed a granger causality analysis to calculate the effectivity connectivity (EC) within and between brain networks for each participant, and compared the differences between the groups. Our findings revealed that R-MDD exhibited increased EC in the fronto-parietal network (FPN) and decreased EC in the cerebellum network, while FEDN-MDD demonstrated increased EC from the sensorimotor network (SMN) to the FPN compared with the NCs. Importantly, the two MDD subgroups displayed significant differences in EC within the FPN and between the SMN and visual network. Moreover, the EC from the cingulo-opercular network to the SMN showed a significant negative correlation with the Hamilton Rating Scale for Depression (HAMD) score in the FEDN-MDD group. These findings suggest that first-episode and recurrent MDD have distinct effects on the effective connectivity in large-scale brain networks, which could be potential neural mechanisms underlying their different clinical manifestations.

Plasma Brain-Derived Neurotrophic Factor Levels in First-Episode and Recurrent Major Depression and before and after Bright Light Therapy in Treatment-Resistant Depression.

Brain-derived neurotrophic factor (BDNF) is implicated in the etiology and treatment response in major depressive disorder (MDD). However, peripheral BDNF concentrations have not been compared across different MDD stages. Bright light therapy (BLT) offers some potential in treatment-resistant depression (TRD), but its effects on BDNF levels are unknown. This study included a cross-sectional analysis of plasma BDNF concentration in females with TRD, unmedicated MDD patients, and healthy controls (HC), and measurements of longitudinal BLT effects on plasma BDNF levels in TRD patients. The present study included 55 drug-naïve, first-episode patients, 25 drug-free recurrent-episode MDD patients, 71 HC participants, and 54 TRD patients. Patients were rated by Hamilton Depression Rating Scale (HAMD)-17 and the Montgomery-Åsberg Depression Rating Scale (MADRS). Patients with TRD received BLT during 4 weeks. The total HAMD-17 and MADRS scores decreased following BLT. All patient groups had lower plasma BDNF than HC, but BDNF levels did not differ between first- and recurrent-episode BDNF patients and TRD patients before or after BLT. However, responders and remitters to BLT had higher post-treatment plasma BDNF concentrations than patients who did not achieve response or remission. The changes in plasma BDNF levels may be candidates for biomarkers of treatment response to BLT in TRD patients.

The long-term effects of ABM on symptom severity in patients with recurrent depression: A randomized sham-controlled trial

BackgroundThe present study reports on long-term outcomes of ABM over one year in self-reported and clinician-rated depression symptoms, anxiety symptoms, and relapse rates. MethodsWe conducted a double-blind randomized sham-controlled trial in 301 participants with recurrent major depression disorder between January 2015 and October 2016 (#NCT02658682). Participants were allocated to ABM or sham condition twice daily for 14 consecutive days. Long-term effects of ABM were assessed by BDI-II, HDRS and BAI at one-, six-, and 12-months follow-up. Relapse rates at 12-months follow-up were also assessed. ResultsThere was no long-term effect of ABM (as compared to sham) on clinician-rated depression symptoms, on anxiety symptoms, nor in relapse rates. By 12 months follow-up, there was a small effect on self-reported depression favoring ABM over sham. LimitationsThe lack of an assessment-only condition hinders comparison to natural trajectories of depression symptoms. ConclusionsThe overall long-term effect of ABM was limited, and currently there is no convincing evidence for implementing this as a viable treatment option in clinical populations. We speculate if the sham condition should be replaced by another control condition when investigating the clinical utility of ABM.

Reactivity toward daily events: Intraindividual variability and change in recurrent depression – A measurement burst study

In Major Depressive Disorder, first evidence shows heightened mood-reactivity toward daily events. Related longitudinal studies in remitted patients with recurrent major depression are lacking. Long-term changes in such short-term within-person associations can be analysed via measurement burst designs. Two bursts, separated by approximately 4.4 years, consisted of a baseline session and an Ambulatory Assessment (burst-1: 3 days, burst-2: 5 days). Via smartphone, 54 initially remitted patients with recurrent major depression indicated their negative and positive affect, rumination, self-acceptance, and the occurrence of negative and positive daily events ten times and collected saliva cortisol samples five times per day. In bursts with higher depression levels, patients showed blunted negative affect- and cortisol-reactivity and stronger decreases in positive affect and self-acceptance toward negative daily events, as well as stronger increases in self-acceptance following positive daily events. However, patients with higher depression levels demonstrated stronger ruminative stress-reactivity within bursts. Furthermore, patients with higher depression levels showed an increase of affective stress-reactivity over bursts, such that negative affect more strongly increased and positive affect more strongly decreased following negative daily events over bursts. Following positive daily events, patients with higher depression levels showed stronger decreases in negative affect within bursts and a decrease of self-acceptance-reactivity over bursts. To conclude, measurement burst designs enable to examine intraindividual variability and change of micro-level processes, and possible moderators thereof, potentially providing prognostic information for the course of recurrent major depression.

Cardiorespiratory fitness and cardiovascular risk among in-patients with depression compared to healthy controls.

Compared to the general population, individuals with depression have an increased risk for cardiovascular diseases. Nevertheless, little is known so far whether cardiorespiratory fitness (CRF) moderates this relationship. Therefore, we examined whether common physiological cardiovascular risk factors differ between patients with depression and healthy (non-depressed) controls, whether patients and controls differ in CRF, and whether higher CRF is associated with a lower cardiovascular risk in both patients and healthy controls. Additionally, we examined whether within the patient sample, cardiovascular risk factors differ between patients with mild, moderate and severe depression, and whether the relationship between symptom severity and cardiovascular risk is moderated by patients' CRF levels. Data from a multi-centric, two-arm randomized controlled trial (RCT) was analyzed, including 210 patients (F32, single episode: n = 72, F33, recurrent major depression: n = 135, F31-II, bipolar type II: n = 3) and 125 healthy controls. Waist circumference, body mass index, body fat, blood pressure, cholesterol levels, triglycerides, and blood glucose were considered as cardiovascular risk markers. CRF was assessed with a submaximal ergometer test. Differences between groups were examined via χ2-tests and (multivariate) analyses of covariance. Compared to healthy controls, patients with depression had a higher cardiovascular risk as evident from about half of the examined indicators. In the total sample, participants with good CRF had more favourable scores across nearly all risk markers than counterparts with poor CRF. For most variables, no interaction occurred between group and fitness, indicating that in patients and controls, similar differences existed between participants with poor and good CRF. Few differences in risk markers were found between patients with mild, moderate and severe depression, and no interaction occurred between depression severity and CRF. Patients with depression and healthy controls differ in several cardiovascular risk markers, putting patients at increased risk for CVDs. In contrast, people with good CRF show more favourable cardiovascular risk scores, a relationship which was observed in both healthy controls and patients with depression. Physical health of psychiatric patients should receive the clinical attention that it deserves. Lifestyle interventions targeting healthy diet and/or physical activity are recommended as a physically active and healthy lifestyle contributes equally to patients' mental well-being and cardiovascular health.

Trait and state effects of different modes of thinking on salivary cortisol in daily life in patients with recurrent major depression and healthy individuals

Habitual modes of thinking such as repetitive negative thinking (RNT), but also momentary cognitive processes such as mindwandering could be vulnerability factors for the course of Major Depressive Disorder (MDD). On the physiological level, cortisol represents an important biological stress marker of the hypothalamic-pituitary-adrenal (HPA) axis. Being a dynamic and non-invasive measure, salivary cortisol can be assessed in daily life via Ambulatory Assessment (AA). So far, consensus exists on a dysregulation of the HPA axis in MDD. However, findings are ambiguous and AA-studies examining both trait and state level effects of cognitive processes on cortisol release in daily life in patients with recurrent major depression (rMDD) and healthy controls (HCs) are lacking. A sample of 119 (nrMDD=57, nHCs=62) participants underwent a baseline session, including self-rated questionnaires (RNT, mindfulness) followed by a 5-day AA, where participants indicated the occurrence of mindwandering and levels of mentalshift problems ten times per day via smartphone, and collected saliva cortisol samples five times per day. Via multilevel models, we found habitual RNT, but not mindfulness, to predict higher cortisol levels, with the effects being stronger in rMDD patients. State mindwandering and mentalshift problems predicted increased cortisol 20 min later across groups. State cognitions did not mediate the effects of habitual RNT on cortisol release. Our results suggest independent mechanisms of action for trait and state cognitions on cortisol activity in daily life and indicate a greater physiological vulnerability toward trait RNT and the tendency to experience mentalshift problems in patients with recurrent major depression.

Association Between Depression and Physical Conditions Requiring Hospitalization

Depression is associated with an increased risk of physical illness, but the most common causes of hospitalization among people with depression are unclear. To examine the association of depression with an array of physical conditions requiring hospital treatment. In this outcomewide prospective multicohort study, primary analysis was based on data from the UK Biobank, a population-based study in the United Kingdom. Analyses were repeated in an independent data set of 2 cohorts in Finland, a population-based study and an occupational cohort. Data analysis was conducted between April and September 2022. Self-reported depression, recurrent severe major depression, recurrent moderate major depression, and a single major depressive episode. A total of 77 common health conditions ascertained from linkage data to national hospital and mortality registries. The analytical sample of UK Biobank participants consisted of 130 652 individuals (71 565 women [54.8%]; 59 087 men [45.2%]; mean [SD] age at baseline, 63.3 [7.8] years). The pooled data from the Finnish replication cohorts included 109 781 participants (82 921 women [78.6%]; 26 860 men [21.4%]; mean [SD] age, 42 [10.8] years). In the main analysis, severe/moderately severe depression was associated with the incidence of 29 nonoverlapping conditions requiring hospital treatment during a 5-year follow-up. Twenty-five of these associations remained after adjustment for confounders and multiple testing (adjusted hazard ratio [HR] range, 1.52-23.03) and were confirmed in the analysis of the Finnish cohorts. These included sleep disorders (HR, 5.97; 95% CI, 3.27-10.89), diabetes (HR, 5.15; 95% CI, 2.52-10.50), ischemic heart disease (HR, 1.76; 95% CI, 1.36-2.29), chronic obstructive bronchitis (HR, 4.11; 95% CI, 2.56-6.60), bacterial infections (HR, 2.52; 95% CI, 1.99-3.19), back pain (HR, 3.99; 95% CI, 2.96-5.38), and osteoarthritis (HR, 1.80; 95% CI, 1.46-2.20). The highest cumulative incidence was observed for endocrine and related internal organ diseases (245 per 1000 persons with depression; risk difference relative to unaffected individuals: 9.8%), musculoskeletal diseases (91 per 1000 persons; risk difference, 3.7%), and diseases of the circulatory system and blood (86 per 1000 persons; risk difference, 3.9%). The cumulative incidence was lower for hospital-treated mental, behavioral, and neurological disorders (20 in 1000 persons; risk difference, 1.7%). Depression was also associated with disease progression in people with prevalent heart disease or diabetes, and for 12 conditions, there was evidence of a bidirectional relationship. In this study, the most common causes of hospitalization in people with depression were endocrine, musculoskeletal, and vascular diseases, not psychiatric disorders. These findings suggest that depression should be considered as a target for the prevention of physical and mental disease.

The fNIRS evaluation of frontal and temporal lobe cortical activation in Chinese first-episode medication-naïve and recurrent depression during a verbal fluency task.

Functional near-infrared spectroscopy (fNIRS) identifies neurophysiological differences between psychiatric disorders by assessing cortical hemodynamic function. Few trials have studied differences in brain functional activity between first-episode medication-naïve depression patients (FMD) and recurrent major depression (RMD). We aimed to determine the differences between FMD and RMD in oxygenated hemoglobin concentration ([oxy-Hb]), and to investigate the correlation between frontotemporal cortex activation and clinical symptoms. We recruited 40 patients with FMD, 53 with RMD, and 38 healthy controls (HCs) from May 2021 to April 2022. Symptom severity was assessed with the 24-item Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A). A 52-channel fNIRS measured changes in [oxy-Hb] during VFT performance. Both patient groups performed poorly during the VFT task compared with HC (FDR p < 0.05), but there was no significant difference between the two patient groups. Analysis of variance showed that mean [oxy-Hb] activation was lower in both the frontal and temporal lobes in the MDD group compared with HCs (FDR p < 0.05). Additionally, patients with RMD had a significantly lower hemodynamic response in the right dorsolateral prefrontal cortex (DLPFC) and dorsal frontal pole cortex (DFPC) than patients with FMD (FDR p < 0.05). No significant correlation was found between changes in mean [oxy-Hb] and either medical history or clinical symptoms (FDR p < 0.05). The presence of different neurofunctional activity in some of the same brain regions in FMD and RMD patients implied a link between the level of complexity activation in frontal regions and the stage of MDD. Cognitive impairment may already be present at the beginning of an MDD episode. www.chictr.org.cn, identifier ChiCTR2100043432.

Decomposing Working Memory in Recurrent Major Depression: Impaired Encoding and Limited Maintenance Immune-to-Encoding Constraint.

It is generally believed that working memory (WM) is dysfunctional in depression. However, whether this impaired performance originates from impaired encoding, maintenance or both stages is still unclear. Here, we aimed to decompose the abnormal characteristics of encoding and maintenance in patients with recurrent major depressive disorder (MDD). Thirty patients and thirty-nine healthy controls completed a spatial working memory task where the encoding time and the retention time could vary under different load levels. Encoding performance was assessed by comparing accuracies between short and long encoding times, and maintenance performance was assessed by comparing accuracies between short and long retention times. The results show a lower performance in depression than the controls. However, while the decreased accuracy by long retention (vs. short retention) was increased by a short encoding time in the control group, the retention performance of the depression group did not further suffer from the short encoding time. The generally impaired encoding, together with limited maintenance of immunity against the constrained encoding time, suggests a common bias for fixed internal processing over external processing in recurrent MDD. The paradigm provided in this study can be a convenient and efficient clinical test for assessing the WM encoding and maintenance function.

Depression in healthcare workers: Results from the nationwide AMADEUS survey

BackgroundThere is now a wealth of evidence showing that work is a major determinant of physical and mental health. Recent studies have suggested increased rates of depression in healthcare workers (HCWs) in the context of the Covid-19 pandemic, with direct impact on care quality and productivity. AimTo determine the rate of clinical depression in a national sample of HCWs in France during the post-Covid-19 area and to identify related factors (professional, individual and health-related risk behaviors) using a structural equation modeling analysis. MethodA survey comprising a number of standardized scales was sent to public and private national healthcare facilities through the mail or disseminated through emails from professional associations and social networks. Results10,325 participants were recruited; 3122 (30.2%, 95% confidence interval [29.4–31.1]) met likely diagnostic criteria for clinical depression. Professional factors had the largest total effect (β = 0.57) (burn-out: β = 0.74, sustained bullying at the workplace β = 0.48 and decision-making latitude β = −0.47), followed by individual factors (β = 0.30) (the main individual factor was recurrent major depression, path coefficient = 0.67).Professional factors had both a direct (path coefficient = 0.38) and indirect (through health risk behaviors, path coefficient = 0.19) effect on depression. Individual factors had a direct (path coefficient 0.21) and indirect (through health risk behaviors (path coefficient = 0.09) effect on depression. Health risk behaviors had a direct effect on depression (path coefficient = 0.31). InterpretationThese results provide potential explanations for the likely causes of poor psychological health among HCWs. We propose several potential interventions related to professional factors and health risk behaviors. Our results suggest that improving organizational issues, reducing exposure to potentially morally injurious events, promoting brief naps at work and provision of evidence-based prevention approaches have been reported to be helpful in supporting the mental health of hospital staff (not only relaxation or stress management but training in leadership aspects, increasing the knowledge and practice of giving efficient performance feedback, reducing conflicting demands and peer support programs such as Trauma Risk Management. Our data suggest that developing caregivers reported experience and outcome measures (CREMs/CROMs) would be helpful to monitor work environment and its effect on depression in healthcare workers.

Association of interleukin-8 and risk of incident and recurrent depression in long-term breast cancer survivors

BackgroundIn cancer patients, an interleukin (IL)-8 gene variant that leads to higher production of IL-8, is associated with lower risk of depressive symptoms. In non-cancer adults, higher levels of IL-8 correlate with lower severity of depressive symptoms, decreased risk of suicide, and improved treatment response in females, but not males. This study evaluates the prospective association between circulating levels IL-8 and incident and recurrent major depressive disorder in breast cancer survivors. MethodsIn this single site, prospective cohort study with protocol modification extending follow-up from 24- to 32 months, recruitment occurred between September 2013 and January 2018, and follow-up was completed February 2021. Participants were identified from a Kaiser Permanente of Southern California health plan-based sample of 219 breast cancer survivors, who were two or more years since diagnosis of early stage breast cancer (TNM 0-II), aged 55 to 85 years, with no major depression or health events in last year. Circulating levels of IL-8 were obtained at enrollment. Primary outcome was time to incident or recurrent major depressive disorder as diagnosed by interview and DSM-5 criteria. ResultsAmong 219 participants (mean age, 70 years; 100% female; 16 [7.3%] Asian, 42 [19.2%] Black, 161 [73.5%] White), 84% completed 24 months follow-up. After protocol modification, 59% completed 32 months follow-up. Median follow-up was 28.5 months.The primary endpoint occurred in 27 participants (12.4%, 5.7 events /100 person years; 95% CI 2.7 – 8.8). Higher IL-8 was associated with lower risk of incident and recurrent depression (hazard ratio, HR, 0.52, 95% CI 0.26 – 1.05). Among those with levels of IL-8 in the highest quartile, the primary endpoint occurred in 2 participants (3.6%; 1.6 events/100 person years; 95% CI 1.3 – 1.9), as compared to 25 participants in the pooled lower quartiles (15.2%; 7.2 events/100 persons years; 95%CI 7.0 – 7.4; rate difference, 5.6 per 100 person years, 95%CI 5.2 – 5.9; HR, 0.21, 95%CI 0.05 – 90, multivariable adjusted HR, 0.20, 95%CI 0.05 - 0.88). ConclusionsAmong breast cancer survivors, higher IL-8 at enrollment was associated with a decreased risk of incident and recurrent major depression. These findings provide insights into mechanisms of depression risk and development of novel therapies for depression prevention, and suggest that testing for IL-8 may have prognostic value in identifying resilience or risk of depression.

Major depression favors the expansion of Th17-like cells and decrease the proportion of CD39+Treg cell subsets in response to myelin antigen in multiple sclerosis patients.

Mood disorders have been associated with risk of clinical relapses in multiple sclerosis (MS), a demyelinating disease mediated by myelin-specific T cells. We aimed to investigate the impact of major depressive disorder (MDD) and cytokine profile of T-cells in relapsing remitting MS patients. For our study, plasma and PBMC were obtained from 60 MS patients (30 with lifetime MDD) in remission phase. The PBMC cultures were stimulated with anti-CD3/anti-CD28 beads or myelin basic protein (MBP), and effector and regulatory T cell phenotypes were determined by flow cytometry. The cytokine levels, both in the plasma or in the supernatants collected from PBMC cultures, were quantified by Luminex. In some experiments, the effect of serotonin (5-HT) was investigated. Here, higher Th17-related cytokine levels in response to anti-CD3/anti-CD28 and MBP were quantified in the plasma and PBMC cultures of the MS/MDD group in comparison with MS patients. Further, elevated frequency of CD4+ and CD8+ T cells capable of producing IL-17, IL-22 and GM-CSF was observed in depressed patients. Interestingly, the percentage of myelin-specific IFN-γ+IL-17+ and IFN-γ+GM-CSF+ CD4+ T cells directly correlated with neurological disabilities. In contrast, the occurrence of MDD reduced the proportion of MBP-specific CD39+Tregs subsets. Notably, the severity of both neurological disorder and depressive symptoms inversely correlated with these Tregs. Finally, the addition of 5-HT downregulated the release of Th17-related cytokines in response to anti-CD3/anti-CD28 and myelin antigen. In summary, our findings suggested that recurrent major depression, by favoring imbalances of effector Th17 and Treg cell subsets, contributes to MS severity.