Specific Depressive Symptoms Research Articles

Network models of late life depression symptoms and cognitive impairments across time

Objectives Prevalence of late life depression symptoms is estimated to be up to 29%. For older adults, depression symptoms can constitute both a risk and outcome for cognitive impairment. Understanding how specific depression symptoms and cognitive impairment domains interact over time in older adults is key for prevention, early identification, and treatment. Method Using cross-sectional psychometric network models, this study aimed to explore interactions between late-life depression symptoms and cognitive impairment domains across different time points using data from waves 7–9 of the English Longitudinal Study of Ageing (ELSA). Results Across 3544 participants, ≥65 years of age, with no diagnosed dementia-related disorders, the depression symptom everything was an effort showed high expected influence across all time points. Across two time points, object naming and verbal fluency also showed high expected influence. Self-reported memory demonstrated high bridge centrality connecting depression symptom and cognitive impairment domains. Network centralities differed significantly across time points. Conclusion For older adults, fatigue appears a key depression symptom. Cognitive impairment domains become more influential over time, and perceived memory loss links cognitive impairment to depression symptoms. Practical implications are discussed in relation to targeting depression symptoms and cognitive impairment domains.

Inverse association of oxidative balance score with depression and specific depressive symptoms among cancer population: Insights from the NHANES (2005-2020).

The rising prevalence of depression among cancer patients is alarming. This study examines the relationship between the Oxidative Balance Score (OBS)-a composite measure of dietary and lifestyle factors-and depression, including specific depressive symptoms in this population. Data were analyzed from 3,280 adult cancer patients collected in NHANES from 2005-2020. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), where a score of 10 or above indicated depression. Symptoms experienced frequently were classified as specific depressive symptoms. Weighted logistic regression models were utilized to explore the correlation between OBS and depression, along with distinctive depressive symptoms. There was a negative correlation between OBS and depression. The highest quartile of OBS (OR 0.313, 95% CI: 0.161-0.609), along with dietary OBS (OR 0.429, 95% CI: 0.234-0.786) and the third quartile of lifestyle OBS (OR 0.404, 95% CI: 0.226-0.722), was associated with reduced depression risk. OBS was correlated with lower risks of all four somatic depressive symptoms and one cognitive symptom. Dietary OBS was associated with fewer risks of three somatic symptoms and one cognitive symptom. Lifestyle OBS showed a negative correlation with two somatic symptoms. Stratified analyses indicated that the inverse relationship between OBS and depression risk was consistent across subgroups, including females and individuals under 65. a nonlinear association was observed between OBS (p = 0.024), dietary OBS (p<0.001), lifestyle OBS (p = 0.021), and depression. OBS is inversely related to depression and specific depressive symptoms in cancer patients. Encouraging a diet and lifestyle rich in antioxidants may help reduce the risk of depression in this group.

A network analysis of rumination on loneliness and the relationship with depression

Previous literature has suggested a significant association between loneliness and depression. Importantly, research has shown that rumination can modulate the loneliness–depression relationship. However, most studies only treated loneliness, rumination or depression as unitary constructs. Considering the heterogeneity of the three concepts, we examined the relationship between specific loneliness, rumination items and depressive symptoms using the network analysis approach. In a large community adult sample (N = 900), we constructed the loneliness–depression and loneliness–rumination–depression network using a cross-sectional design. The results suggested that loneliness has no robust association with depressive symptoms. Instead, a connection between a specific ruminative thought (‘think about how alone you are’) and a specific loneliness item (‘how often do you feel alone’) is essential in maintaining the loneliness–rumination–depression network (partial r = 0.307). Our findings indicate that ruminating on the feeling of loneliness is the key underlying factor modulating the loneliness–depression relationship. Interventions for depression should focus on ameliorating ruminative thoughts, especially on loneliness feelings.

Differential relations between depressive symptoms and everyday function in older adults using multiple modes of functional assessment

AbstractBackgroundThe impact of depressive symptoms on everyday function in older adults remains poorly understood. Depression may decrease motivation, impair cognition, and/or bias self‐reports of functional ability. The present study examined relations between depressive symptoms and everyday function as measured by self‐report, informant‐report, and an objective performance‐based measure which evaluates functional/cognitive capacity but requires only minimal motivation.Method88 community dwelling older adults with normal cognition or mild cognitive impairment completed the Geriatric Depression Scale (GDS‐15), tests of cognitive abilities, and the performance‐based Naturalistic Action Test (NAT), which requires preparation of a breakfast and lunch using real objects presented on a table. Video recordings of the NAT were scored for completion time and errors. Participants and their study partners also completed the Instrumental Activities of Daily Living – Compensation (IADL‐C) Questionnaire, which evaluates the ability to perform a range of everyday tasks in daily life. A Spearman correlation matrix was used to assess associations among measures.ResultGDS‐15 scores were significantly associated with both questionnaires (participant IADL‐C: r = .369, p &lt; .001; informant IADL‐C: r = .265, p = .022) but did not correlate with NAT scores. Global cognitive composite scores were negatively correlated with self‐reported IADL‐C scores (r = ‐.320, p = .003) and NAT scores (completion time: r = ‐.376, p &lt; .001; errors: r = ‐.349, p &lt; .001), but did not correlate with informant‐reported IADL‐C scores. Ancillary analyses showed the two questionnaire measures were significantly correlated (self‐report x informant‐report IADL‐C, r = .362, p = .002) but did not correlate significantly with NAT scores, and the GDS‐15 did not correlate with the cognitive composite.ConclusionAmong community dwelling older adults, depressive symptoms were associated with participant‐reported and informant‐reported everyday function, but not with performance‐based tasks or cognitive abilities. The pattern of correlates suggests that depressive symptoms may affect function in everyday contexts by decreasing motivation to engage in daily activities without altering cognitive capacity to perform everyday tasks. Future research should investigate relations among specific depressive symptoms, such as apathy, and multiple measures of everyday function.

Association of grip strength, sleep duration, and comorbidities with depressive symptoms in middle-aged and older patients with chronic lung diseases: a cross-sectional network analysis based on CHARLS data.

Depressive symptoms are prevalent among patients with chronic lung diseases (CLDs) and adversely impact their quality of life. This study aims to explore the association of grip strength (GS), sleep duration, and comorbidities with depressive symptoms in patients with CLDs, with an in-depth analysis of the underlying mechanisms. Based on data from the China Health and Retirement Longitudinal Study (CHARLS), this study included participants aged 45 and above with diagnosed CLDs. Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10). Binary logistic regression, subgroup analysis, and network analysis were conducted to examine the intricate relationships between GS, sleep duration, comorbidities, and specific depressive symptoms. Among the 1,427 participants, 39.8% exhibited depressive symptoms. Adjusted analyses revealed that GS (OR = 0.964, p < 0.001) and sleep duration (OR = 0.808, p < 0.001) were negatively associated with depressive symptoms, whereas the number of comorbid chronic diseases (OR = 1.189, p < 0.001) showed a significant positive correlation with depressive symptoms. Subgroup analyses demonstrated variations in these relationships across different demographic characteristics and lifestyle factors. Network analysis pinpointed "depressed" as the core symptom, with "annoyed," "exhausted," and "lonely" as secondary core symptoms. The robust associations between specific factors and depressive symptoms (GS with "annoyed," sleep and comorbid chronic diseases with "depressed") suggested potential targets for interventions. This study underscores the complex interplay of GS, sleep duration, and comorbidities with depressive symptoms in patients with CLDs. These findings offer new perspectives for improving the mental health of this vulnerable population.

Revealing the potential causality of suicidal ideation and psychopathic symptoms among survivors 10 years after the Wenchuan earthquake using network analysis.

Little is known about the interactions and causal inference between psychopathic symptoms and suicidal ideation (SI) among earthquake survivors. Using a 10-year large cohort of Chinese adolescents exposed to the Wenchuan earthquake, this study aimed to structure networks of suicidal ideation and some specific symptoms of posttraumatic symptoms and depression among survivors of the Wenchuan earthquake to clarify the interactions and causality between these symptoms. A total of 684 survivors who completed surveys at 6 months and 10 years postearthquake and had one or above psychopathic symptoms were included in the analyses. Sociodemographic, posttraumatic stress symptoms, depressive symptoms, and suicidal ideation were measured at 6 months and/or 10 years postearthquake. Network analyses were performed based on R Version 4.1.3. The Gaussian graphical model network revealed that "depressed mood" had the highest expected influence value. In addition, the directed acyclic graph network revealed that anhedonia could affect "depressed mood," which further leads to "suicidal ideation." The pathway of "anhedonia → depressed mood → suicidal ideation" was a crucial psychopathic mechanism of suicidal ideation. It informs that intervening in anhedonia and depressed mood among earthquake-exposed survivors is necessary to potentially decrease the risk of future suicidal ideation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Socioeconomic and Demographic Modifiers of Depression's Impact on Emergency Room Utilization: A Stratified Analysis

Socioeconomic and Demographic Modifiers of Depression's Impact on Emergency Room Utilization: A Stratified Analysis

Association between neutrophil-to-lymphocyte ratio and specific depressive symptoms: an analysis of a population-based cross-sectional survey

BackgroundThe exact mechanisms underlying depression are not well understood. Chronic, low-grade inflammation is believed to play an important role in its development. The present study investigates the potential association between depressive symptoms and the neutrophil-to-lymphocyte ratio (NLR).MethodsSeven data cycles of the National Health and Nutrition Examination Survey were extracted. Multivariable logistic regression and a generalized additive model were employed to determine the association.ResultsThirty thousand eight hundred ninety-six subjects were analyzed. The results indicated that anhedonia and fatigue were significantly associated with NLR. Additionally, the generalized additive model results indicated a non-linear relationship between anhedonia, sleep disturbance and NLR. Subgroup analyses demonstrated that the correlation between anhedonia and NLR was significant in the above-60-year-old group (OR: 1.63, 95% CI: 1.14–2.33) and the male group (OR: 1.50, 95% CI: 1.07–2.10). Sleep disturbance was associated with NLR in the female group (OR: 1.36, 95% CI: 1.04–1.77). Fatigue was associated with NLR (OR: 1.30, 95% CI: 1.02–1.67) in the female group, as was the case in the non-Hispanic White group (OR: 1.32, 95% CI: 1.02–1.70).ConclusionsThere were associations between NLR and specific symptoms, and these associations varied across demographic subgroups. There was a non-linear association between anhedonia, sleep disturbance and NLR. These findings could potentially contribute to the advancement of precision medicine within the field of mental health.

Dissecting the association between long COVID and depressive symptoms in a nationally representative population from France

Depressive symptoms may overlap with those of long COVID. This cross-sectional study aims to compare the prevalence of depressive symptoms among individuals infected with SARS-CoV-2 with versus without long COVID and to explore specific associations with each of the nine core symptoms of major depression. Data regarding age, gender, SARS-CoV-2 infections, current symptoms, their date of onset, impact on daily functioning, and consideration of alternative diagnoses were collected through phone interviews between September and December 2022 in a nationally representative sample of adults aged ≥18. Data on chronic health conditions and depressive symptoms (PHQ-9) were collected online in infected participants with or without long COVID, according to the WHO definition of the post-COVID-19 condition. Among 1247 participants (mean age (SD): 48.3 (14.3) years, 53.3% of women), 12.8% had long COVID and 87.2% experienced SARS-CoV-2 infection at least 3months prior to the survey without long COVID. Participant with long COVID were four-fold more likely to have a PHQ-9 score≥10 than those without (44.0% versus 11.1%). Three symptoms out of nine were independently associated with long COVID: little interest or pleasure (aOR [95% CI]: 2.01 [1.03-3.92]), feeling tired or having little energy (1.92 [1.10-3.33]), and poor attention/concentration (2.02 [1.03-3.96]). Clinicians should screen patients with long COVID for major depression but associations with specific depressive symptoms suggest some clinical overlap. Future studies should consider the course of each depressive symptom separately and focus on those less prone to overlap with symptoms of long COVID.

Specific depressive symptoms, body mass index and diabetes in middle-aged and older Chinese adults: Analysis of data from the China Health and Retirement Longitudinal Study (CHARLS)

This study examined the association between specific depressive symptoms and incident diabetes, and whether overweight or obesity mediates this relationship among middle-aged and older adults in China. In a nationally representative prospective cohort study of 11,893 middle-aged and older Chinese adults without baseline diabetes, we used Cox models to assess the association between depressive symptoms and diabetes. The quantile g-computation (qgcomp) model evaluated the contribution of 10 specific depressive symptoms to diabetes risk, and a two-stage regression method explored the mediation effect of overweight or obesity. Over a median follow-up of 7.1years, 1,314 cases of diabetes were identified. Elevated depressive symptoms were associated with increased diabetes risk (HR 1.23; 95% CI 1.09-1.38). Eight out of 10 depressive symptoms were significantly associated to diabetes, with loneliness (weight=18%; HR 1.23; 95% CI 1.10-1.39), restless sleep (weight=17%; HR 1.16; 95% CI 1.04-1.29), and bother (weight=15%; HR 1.19; 95% CI 1.07-1.33) being the primary contributors. Mediation analysis showed that overweight and obesity reduced the depression-diabetes risk association by 8.21% and 12.61%, respectively. Diagnosis of diabetes was self-reported. Eight out of ten specific depressive symptoms were associated to diabetes, overweight and obesity may partially mitigate the effect of depressive symptoms on diabetes among middle-aged and older adults in China. Our results highlight the importance of tailoring diabetes prevention and management strategies according to specific depressive symptoms among middle-aged and older adults in China.

Changes in tripartite dimensions of anxiety and depression in emerging adults before and during COVID-19

Objective Using the tripartite model of anxiety and depression, we examined general distress (common to anxiety/depression), anxious arousal (uniquely anxiety), and anhedonic depression (uniquely depressive) symptoms before and during the pandemic in emerging adults, who may experience higher levels of distress as a result of the COVID-19 pandemic relative to others. Participants Emerging adults (n = 89, 53% White) ages 18-24, participated in four data waves (Baseline: Fall 2017-Fall 2018; January 2020; July 2020; January 2021). Methods We estimated covariance pattern models with various patterns of residual correlation, (selecting the best-fitting structure) and patterns of change (i.e., stable, linear, and quadratic). Results Scores in all tripartite dimensions were elevated at baseline; anxious arousal remained elevated, while depression-specific symptoms decreased over time. Conclusions Findings contribute to a fine-grained approach to understanding emotional distress relating to the COVID-19 pandemic, proving potentially useful in conceptualizing the mental health of emerging adults in relation to disruptive life events.

Early change in specific depression symptoms and later outcome in internet-delivered psychotherapy for depression: A cohort study and cross-lagged network analysis

Symptom reduction occurring early in depression treatment is associated with favourable post-treatment outcome, but it is not known how early reduction in specific depression symptoms affect treatment outcome. We aimed to determine the impact of symptom-specific change from pre-treatment to week four during internet-delivered CBT (ICBT) on overall and symptom-specific depression severity at post-treatment. We hypothesized that change in mood and emotional involvement would be most strongly associated with later overall depression severity. 1300 participants with Major Depressive Disorder were followed over 12weeks of ICBT using the self-report Montgomery-Åsberg Depression Rating Scale gauging nine symptoms. Linear models, informed by causal inference and cross-lagged network analysis methods, were used to estimate associations between early symptom-specific change and post-treatment depression severity, controlling for register-based and self-reported pre-treatment confounders. Early reduction in all symptoms was associated with lower overall and symptom-specific depression severity post-ICBT. Seven symptoms showed similar associations between early change and overall depression severity post-treatment: mood (standardized beta [β]=0.44), feelings of unease (β=0.39), ability to concentrate (β=0.46), initiative (β=0.43), emotional involvement (β=0.42), pessimism (β=0.44), and zest for life (β=0.42). Change in sleep (β=0.27) and appetite (β=0.27) had weaker associations with overall depression severity at post-treatment and were the only symptoms showing the hypothesized difference compared with mood and emotional involvement. The impact of early symptom-specific reduction on post-treatment depression severity in ICBT for MDD may be similar across most symptoms, but less for the sleep and appetite symptoms, although causal interpretations rests on several assumptions.

Reinforcement learning processes as forecasters of depression remission

Aspects of reinforcement learning have been associated with specific depression symptoms and may inform the course of depressive illness. We applied support vector machines to investigate whether blood‑oxygen-level dependent (BOLD) responses linked with neural prediction error (nPE) and neural expected value (nEV) from a probabilistic learning task could forecast depression remission. We investigated whether predictions were moderated by treatment use or symptoms. Participants included 55 individuals (n=39 female) with a depression diagnosis at baseline; 36 of these individuals completed standard cognitive behavioral therapy and 19 were followed during naturalistic course of illness. All participants were assessed for depression diagnosis at a follow-up visit. Both nPE and nEV classifiers forecasted remission significantly better than null classifiers. The nEV classifier performed significantly better than the nPE classifier. We found no main or interaction effects of treatment status on nPE or nEV accuracy. We found a significant interaction between nPE-forecasted remission status and anhedonia, but not for negative affect or anxious arousal, when controlling for nEV-forecasted remission status. Our sample size, while comparable to that of other studies, limits options for maximizing and evaluating model performance. We addressed this with two standard methods for optimizing model performance (90:10 train and test scheme and bootstrapped sampling). Results support nEV and nPE as relevant biobehavioral signals for understanding depression outcome independent of treatment status, with nEV being stronger than nPE as a predictor of remission. Reinforcement learning variables may be useful components of an individualized medicine framework for depression healthcare.

A network approach to emotion regulation and symptom activation in depression and anxiety.

Emotions can be regulated through several regulatory strategies that are involved in the development of psychopathological symptoms. Despite the well-established association between psychopathology and emotion dysregulation, little is known about the relationship between individual symptoms of depression and anxiety and emotion regulation strategies (ERS), as well as between ERS themselves. We conducted a cross-sectional study and examined the interactions between six ERS (reappraisal, engagement, rumination, suppression, arousal control, and distraction) and assessed their distinctive association with the activation of specific symptoms of depression and anxiety in a community sample of 376 adults (80.4% female; Mage = 32.70; SDage = 11.80). The Regulation Emotion Systems Survey (RESS) was used to measure ERS. The Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) were used to assess psychological symptoms. An exploratory graph analysis was performed to examine the structural properties of the network of interactions between these behaviors. Additionally, to test the association of ERS with the activation of the depression symptoms network, an expected symptoms activity (ESA) was conducted. Six communities were found that correspond to the six ERS. Rumination and suppression have a significant association with symptom activation (particularly low self-esteem), whereas reappraisal reduces symptomatic activation. The effect of arousal control, engagement, and distraction appears to depend on the remaining ERS rather than having much influence on their own. This study provides insight into how ERS interact with each other and with individual symptoms of depression and anxiety. Understanding the effects of these interactions on symptom activation and comorbidity can improve our understanding of psychopathology.

Temporal Associations Between Specific Depressive Symptoms and Physical Inactivity in Middle Aged and Older Adults

Temporal Associations Between Specific Depressive Symptoms and Physical Inactivity in Middle Aged and Older Adults

Genetic factors and symptom dimensions associated with antidepressant treatment outcomes: clues for new potential therapeutic targets?

Treatment response and resistance in major depressive disorder (MDD) show a significant genetic component, but previous studies had limited power also due to MDD heterogeneity. This literature review focuses on the genetic factors associated with treatment outcomes in MDD, exploring their overlap with those associated with clinically relevant symptom dimensions. We searched PubMed for: (1) genome-wide association studies (GWASs) or whole exome sequencing studies (WESs) that investigated efficacy outcomes in MDD; (2) studies examining the association between MDD treatment outcomes and specific depressive symptom dimensions; and (3) GWASs of the identified symptom dimensions. We identified 13 GWASs and one WES of treatment outcomes in MDD, reporting several significant loci, genes, and gene sets involved in gene expression, immune system regulation, synaptic transmission and plasticity, neurogenesis and differentiation. Nine symptom dimensions were associated with poor treatment outcomes and studied by previous GWASs (anxiety, neuroticism, anhedonia, cognitive functioning, melancholia, suicide attempt, psychosis, sleep, sociability). Four genes were associated with both treatment outcomes and these symptom dimensions: CGREF1 (anxiety); MCHR1 (neuroticism); FTO and NRXN3 (sleep). Other overlapping signals were found when considering genes suggestively associated with treatment outcomes. Genetic studies of treatment outcomes showed convergence at the level of biological processes, despite no replication at gene or variant level. The genetic signals overlapping with symptom dimensions of interest may point to shared biological mechanisms and potential targets for new treatments tailored to the individual patient's clinical profile.

Network analysis of depressive symptoms and C-reactive protein levels in major depressive disorder

C-reactive protein (CRP) levels have been implicated in the severity and symptomatology of major depressive disorder (MDD). The aim of this study was to explore the structure of depressive symptoms in patients with MDD according to different groups of CRP levels using network analysis. The study included 864 individuals (mean age=54.05, 67.48% male) diagnosed with MDD from the 2015-2020 National Health and Nutrition Examination Survey (NHANES). Analyses examined how depressive symptoms and CRP level were related to each other, and how the network structure of depressive symptoms differed across groups with different CRP levels. A direct positive correlation was observed between CRP levels and specific depressive symptoms (e.g., appetite change, energy loss, and feelings of worthlessness). Moreover, there was a stronger correlation between depressive symptoms in the medium CRP and high CRP groups compared to the low CRP group. Furthermore, it was observed that there were notable structural differences between the high-CRP and moderate-CRP groups. The study is based on cross-sectional data, which precludes the drawing of causal conclusions. Furthermore, it does not take into account confounding factors such as body mass index (BMI) and lifestyle. The findings underscore the pivotal role of CRP as a marker of the severity of depressive symptoms. Routine CRP level testing and anti-inflammatory therapies may be beneficial for depressed patients with elevated CRP levels in clinical practice.

Effects of electroacupuncture on cognitive symptoms in major depressive disorder: a pilot study and randomized controlled trial.

To investigate the impact of electroacupuncture on cognitive function, quality of life (QoL), and depression severity in patients with major depressive disorder (MDD). This double-blinded randomized controlled trial included 60 participants aged 18-55 with cognitive symptoms related to MDD at Thammasat University Hospital. Participants were divided into two groups: the electroacupuncture group combined with standard pharmacological treatment (EG; n=30) and the control group receiving standard pharmacological treatment with placebo acupuncture (CG; n=30). The study assessed 1) executive functions using the Trail making test- B and Stroop Color and Word Test, 2) delayed recall, and 3) subjective cognitive complaint and Quality of life (QoL) using WHODAS 2.0. Depressive symptoms were measured using the Thai version of the Patient Health Questionnaire (PHQ-9). Baseline and post-intervention assessments were conducted over 10 weeks. Mann-Whitney U test analyzed treatment effects by comparing median differences between groups. Both groups exhibited similar demographics and cognitive traits. Cognitive improvement was observed in both groups at the endpoint. Intention-to-treat analysis revealed significantly higher median scores for subjective cognitive complaints in the EG compared to the CG (EG: Median = 5.5, CG: Median = 0.0, p=0.049). No serious side effects were identified from either electroacupuncture or placebo acupuncture. Electroacupuncture improved subjective complaints in MDD patients with cognitive symptoms, but did not show effects on specific cognitive functions, QoL, or depressive symptoms. This study provides initial evidence supporting the potential of electroacupuncture in MDD patients with cognitive symptoms, suggesting opportunities for further research. NCT06239740, February 2, 2024, ClinicalTrials.gov.

Association of both depressive symptoms scores and specific depressive symptoms with all-cause and cardiovascular disease mortality

BackgroundThe presence of depression related to an increased risk of all-cause and cardiovascular disease (CVD) mortality has been reported. However, studies conducted on certain specific depressive symptoms are scarce. Our purpose was to assess the effect of both depressive symptoms scores and certain specific depressive symptoms on all-cause and CVD mortality.MethodsIn the present cohort study, all participants, aged 18 years or older, were enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2014. Depressive symptoms score was assessed using the validated 9-item Patient Health Questionnaire Depression Scale (PHQ-9), which ranges from 0 to 27, with a PHQ-9 score ≥ 10 diagnosed as depression. The outcome events were all-cause and CVD mortality, which were followed up from 2005 to 2014. The associations of both depressive symptoms score and certain specific depressive symptoms with all-cause and CVD mortality were examined by weighted multivariable proportional hazards models.ResultsA total of 26,028 participants aged ≥ 18 years were included in the statistical analysis, including 12,813 (49.2%) males and 13,215 (50.8%) females, with a mean (SD) age of 47.34 (18.86) years. During the 9.32 (3.20) years of mean (SD) follow-up, 3261 deaths were recorded, of which 826 were cardiovascular deaths. All-cause mortality was 16.87/1000 person-years in subjects with depression. In terms of CVD mortality, these figures were 4.53/1000 person-years. In the full model (model 3), elevated depressive symptoms scores were independently associated with an increased risk of all-cause mortality (Highest depression symptom score group: adjusted hazard ratio, 1.63; 95% CI 1.44–1.85) and CVD mortality (Highest depression symptom score group: adjusted hazard ratio, 1.73; 95% CI 1.34–2.24). All 9 specific depressive symptoms that make up the PHQ-9 were related to an increased risk of all-cause mortality. However, only 3 symptoms, including trouble sleeping or sleeping too much, poor appetite or overeating, and suicidal ideation, were no significantly associated with an increased risk of CVD mortality.ConclusionsThe elevated depressive symptoms scores were strongly associated with an increased risk of all-cause and CVD mortality in US adults. Furthermore, all 9 specific depressive symptoms were associated with high all-cause mortality. However, trouble sleeping or sleeping too much, poor appetite or overeating, and suicidal ideation might not increase the risk of CVD mortality.

Aticaprant, a kappa opioid receptor antagonist, and the recovered 'interest and pleasure' in the concept of major depressive disorder.

Lack of positive mood and anhedonia probably are the most specific depressive symptoms. Anhedonia is a multifaceted concept: the clinical language describes anticipatory/consummatory anhedonia and sensory/social anhedonia while the cognitive neuroscience language describes readiness for reward, energy expenditure to attain reward, updating reward presence and value. Mounting evidence supports the potential of kappa-opioid receptor (KOR) antagonists as novel pharmacotherapies for major depressive disorder : aticaprant is a potent, selective, short-acting KOR antagonist. The fast-fail approach evaluated the impact of aticaprant on the brain circuitry hypothesized to mediate anhedonia and significantly increased fMRI activation in the ventral striatal activation during reward anticipation as compared to placebo; the aticaprant induced changes in the self-reported psychological measures of anhedonia were rather inconsistent. The recently reported results of a phase 2a randomized, double-blind, placebo-controlled trial investigating the efficacy and safety of aticaprant, co-administered to an oral SSRI/SNRI antidepressant in depressed patients who had an inadequate response to 1 or 2 antidepressants. The improvement from baseline favoured the co-administration of aticaprant over the co-administration of placebo at all time points (during 6 weeks), and this was confirmed by higher response rates with aticaprant. A mid-split of patients with higher or lower than median anhedonia also showed that the patients with higher baseline anhedonia had the largest decrease on the MADRS. Tolerability and safety were reassuring. These promising results of the co-administration of aticaprant to an SSRI/SNRI in depressed patients with prominent anhedonia support he further investigation of aticaprant in larger trials.