Depression Cohort Research Articles

Association between childhood trauma and medication adherence among patients with major depressive disorder: the moderating role of resilience

BackgroundSuboptimal medication adherence is a major reason for failure in the management of major depressive disorder (MDD), childhood trauma might be an essential risk factor of suboptimal medication adherence. This study aimed to comprehensively explore the associations between different types of childhood trauma and medication adherence among patients with MDD, and to test whether resilience has moderating effects on the foregoing associations.MethodsParticipants were from the Depression Cohort in China (ChiCTR registry number 1900022145), 282 MDD patients with completed both baseline and 12-weeks follow-up investigations were included in this study. The diagnosis of MDD was assessed by trained psychiatrists using the Mini-International Neuropsychiatric Interview (M.I.N.I.). Childhood trauma was evaluated using the Childhood Trauma Questionnaire-28 item Short Form (CTQ-SF), and resilience was evaluated using the Connor-Davidson Resilience Scale (CD-RISC). Demographic characteristics, depression symptoms, anxiety symptoms, suicidal ideation, suicidal attempt, insomnia symptoms, and painful somatic symptoms were also investigated. Participants were divided into groups of optimal and suboptimal adherence based on their Medication Adherence Rating Scale scores. Logistic regression and stratified analyses were performed.ResultsA total of 234 participants (83%) reported suboptimal medication adherence. After adjusting for covariates, CTQ total scores (AOR = 1.03, 95%CI = 1.01–1.06), CTQ measures of sexual abuse (AOR = 1.17, 95%CI = 1.01–1.37), and CTQ measures of physical neglect (AOR = 1.12, 95%CI = 1.02–1.23) were all associated with an increased likelihood of suboptimal adherence. There were significant moderating effects of resilience on the associations of childhood trauma (P = 0.039) and physical neglect (P = 0.034) with medication adherence. The stratification analyses showed that CTQ total scores and CTQ measures of physical neglect were independently associated with an increased risk of suboptimal adherence among patients with MDD with low-resilience or moderate-resilience, while not significantly associated with suboptimal adherence in those with high-resilience.ConclusionChildhood trauma was a significant risk factor of suboptimal adherence among patients with MDD, and resilience moderated the foregoing association. Obtaining a history of childhood trauma and assessing resilience may help identify patients with suboptimal adherence when providing MDD pharmacotherapy. Psychiatrists may consider enhancing resilience to cope with the adverse effects of childhood trauma on medication adherence.

The relationship between cortisol awakening response and trait resilience in two patient cohorts and one population-based cohort

Objectives We examined (1) the proportion of cortisol awakening non-responders, (2) the association between cortisol awakening response (CAR) and trait resilience, and (3) the association between CAR increase and trait resilience in two patient cohorts (depression and myocardial infarction [CVD]) and one population-based cohort. Methods Eight hundred and eighty study participants delivered CAR scores (response and increase) based on three self-collected saliva samples and a trait resilience score. Descriptive data of CAR non-responders were reported and calculated. Associations between CAR response/increase and trait resilience, sociodemographic and compliance variables were evaluated using multiple logistic and multiple linear regression analyses stratified by cohort. Results The proportion of CAR non-responders was high in all cohorts (57% depression cohort, 53.4% CVD cohort, 51.6% control cohort). In the depression cohort age was associated with CAR response and increase. In the CVD cohort salivary collection on a weekday was associated with CAR response and awakening time with CAR increase. In the control cohort age was associated with CAR response and sex with CAR increase. Conclusions We observed many CAR non-responders and significant associations between CAR response and CAR increase with single sociodemographic and compliance variables. We did not find significant relationships between CAR response or increase and trait resilience.

Impact of cognitive-affective and somatic symptoms in subthreshold depression transition in adults: Evidence from Depression Cohort in China (DCC)

BackgroundSymptoms of subthreshold depression may differentially affect the illness transition. We examined the impact of cognitive-affective and somatic symptoms on different subthreshold depression transitions as well as risk factors influencing the aforementioned symptoms changes. MethodsAdults with subthreshold depression in the Depression Cohort in China were enrolled. Data collection was conducted at baseline, 6 and 12 months from 2019 to 2020. Cognitive-affective and somatic symptoms were assessed using the Patient Health Questionnaire-9. A total of 993 participants completed 12-month follow-up and were divided into persistent, intermittent and remission groups according to change in depressive symptoms. The longitudinal change of cognitive-affective and somatic symptoms in the three groups, as well as risk factors was analyzed using the generalized linear mixed-model. ResultsThere were 24.07 %, 34.04 % and 41.89 % of participants proceeding into persistent, intermittent and remission subthreshold depression groups, respectively. Cognitive-affective symptoms were the core symptoms for predicting the deterioration in persistent subthreshold depression (t = 2.48, P = 0.013), whereas somatic symptoms improved over time (t = −2.82, P = 0.005). Anxiety symptoms were the primary risk factors for worsening cognitive-affective symptoms (P < 0.001), following by insomnia symptoms, age, marital status, resilience and social functions. Somatic symptoms were affected by insomnia symptoms, anxiety symptoms and Body Mass Index successively. LimitationsMajor Depressive Episode was not explored in follow-up. ConclusionCognitive-affective symptoms in subthreshold depression are at greater risk of illness deterioration. Future studies should endeavor to identify specific risk factors in different symptoms to forestall the transition from subthreshold to Major Depressive Disorder.

Effects of Pharmacokinetic Gene Variation on Therapeutic Drug Levels and Antidepressant Treatment Response.

Introduction Pharmacogenetic testing is proposed to minimize adverse effects when considered in combination with pharmacological knowledge of the drug. As yet, limited studies in clinical settings have investigated the predictive value of pharmacokinetic (pk) gene variation on therapeutic drug levels as a probable mechanism of adverse effects, nor considered the combined effect of pk gene variation and drug level on antidepressant treatment response. Methods Two depression cohorts were investigated for the relationship between pk gene variation and antidepressant serum concentrations of amitriptyline, venlafaxine, mirtazapine and quetiapine, as well as treatment response. For the analysis, 519 patients (49% females; 46.6±14.1 years) were included. Results Serum concentration of amitriptyline was associated with CYP2D6 (higher concentrations in poor metabolizers compared to normal metabolizers), of venlafaxine with CYP2C19 (higher concentrations in intermediate metabolizers compared to rapid/ultrarapid metabolizers) and CYP2D6 (lower metabolite-to-parent ratio in poor compared to intermediate and normal metabolizers, and intermediate compared to normal and ultrarapid metabolizers). Pk gene variation did not affect treatment response. Discussion The present data support previous recommendations to reduce starting doses of amitriptyline and to guide dose-adjustments via therapeutic drug monitoring in CYP2D6 poor metabolizers. In addition, we propose including CYP2C19 in routine testing in venlafaxine-treated patients to improve therapy by raising awareness of the risk of low serum concentrations in CYP2C19 rapid/ultrarapid metabolizers. In summary, pk gene variation can predict serum concentrations, and thus the combination of pharmacogenetic testing and therapeutic drug monitoring is a useful tool in a personalized therapy approach for depression.

Comparing emotional working memory in adolescents and young adults with and without depressive symptoms: developmental and psychopathological differences

Depressive symptoms are associated with working memory impairments. Yet, comparative studies examining working memory across the developmental spectrum in depressed and non depressed cohorts are lacking. This study examined emotional working memory in 74 adolescents (mean age = 14; 21 with depressive symptoms) and 92 adults (mean age = 22; 36 with depressive symptoms). Participants completed two versions of an emotional face n-back task, and either paid attention to the valence of the emotion or the gender. Both tasks were completed at low load (0-back) and high load (2-back). In the high load condition, healthy adolescents showed a bias towards positive faces, both speeding up reaction times (RTs) when emotion was task relevant but slowing RTs when they were task irrelevant. This interaction was neither significant in adolescents with depressive symptoms nor in young adults. Depressive symptoms did not influence RTs in low load. The results indicate that adolescents with depressive symptoms might lack the bias towards positive affective material at high load WM task present in healthy adolescents.

Screening Depressive Symptoms and Incident Major Depressive Disorder Among Chinese Community Residents Using a Mobile App-Based Integrated Mental Health Care Model: Cohort Study.

BackgroundDepression is associated with significant morbidity and human capital costs globally. Early screening for depressive symptoms and timely depressive disorder case identification and intervention may improve health outcomes and cost-effectiveness among affected individuals. China’s public and academic communities have reached a consensus on the need to improve access to early screening, diagnosis, and treatment of depression.ObjectiveThis study aims to estimate the screening prevalence and associated factors of subthreshold depressive symptoms among Chinese residents enrolled in the cohort study using a mobile app–based integrated mental health care model and investigate the 12-month incidence rate and related factors of major depressive disorder (MDD) among those with subthreshold depressive symptoms.MethodsData were drawn from the Depression Cohort in China (DCC) study. A total of 4243 community residents aged 18 to 64 years living in Nanshan district, Shenzhen city, in Guangdong province, China, were encouraged to participate in the DCC study when visiting the participating primary health care centers, and 4066 (95.83%) residents who met the DCC study criteria were screened for subthreshold depressive symptoms using the Patient Health Questionnaire-9 at baseline. Of the 4066 screened residents, 3168 (77.91%) with subthreshold depressive symptoms were referred to hospitals to receive a psychiatric diagnosis of MDD within 12 months. Sleep duration, anxiety symptoms, well-being, insomnia symptoms, and resilience were also investigated. The diagnosis of MDD was provided by trained psychiatrists using the Mini-International Neuropsychiatric Interview. Univariate and multivariate logistic regression models were performed to explore the potential factors related to subthreshold depressive symptoms at baseline, and Cox proportional hazards models were performed to explore the potential factors related to incident MDD.ResultsAnxiety symptoms (adjusted odds ratio [AOR] 1.63, 95% CI 1.42-1.87) and insomnia symptoms (AOR 1.13, 95% CI 1.05-1.22) were associated with an increased risk of subthreshold depressive symptoms, whereas well-being (AOR 0.93, 95% CI 0.87-0.99) was negatively associated with depressive symptoms. During the follow-up period, the 12-month incidence rate of MDD among participants with subthreshold depressive symptoms was 5.97% (189/3168). After incorporating all significant variables from the univariate analyses, the multivariate Cox proportional hazards model reported that a history of comorbidities (adjusted hazard ratio [AHR] 1.49, 95% CI 1.04-2.14) and anxiety symptoms (AHR 1.13, 95% CI 1.09-1.17) were independently associated with an increased risk of incident MDD. The 5-item World Health Organization Well-Being Index was associated with a decreased risk of incident MDD (AHR 0.90, 95% CI 0.86-0.94).ConclusionsElevated anxiety symptoms and unfavorable general well-being were significantly associated with subthreshold depressive symptoms and incident MDD among Chinese residents in Shenzhen. Early screening for subthreshold depressive symptoms and related factors may be helpful for identifying populations at high risk of incident MDD.

A longitudinal study of perinatal depression and the risk role of cognitive fusion and perceived stress on postpartum depression.

To explore fluctuations in perinatal depression based on physiological, psychological and interpersonal dimensions to analyse risk factors across three time points: in the third trimester and at weeks 1 and 6 postpartum. Pregnant women experience depression at multiple time points and require screening. Studies have shown protective and negative factors related to postpartum depression. Cognitive fusion refers to an individual's emotions and behaviours that are regulated and influenced by that individual's own cognitive overregulation, especially when facing stress. This is an important psychological factor related to depression, but little is known about it in pregnant women. A longitudinal study was conducted from June 2019-July 2020, and the findings are reported following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Pregnant women (n=207) were recruited, and a questionnaire survey was performed at 32-34weeks of pregnancy and at weeks 1 and 6 postpartum. Repeated-measures analysis of variance was performed to analyse the changes in depression over time. Regression analysis and linear mixed modelling were used to identify risk factors. Pearson's correlation analysis was performed to analyse the relationships between variables. Of the pregnant women, 36.70% experienced antenatal depression and prolonged depression with the onset of postpartum depression (12.21%). Some depressive moods disappeared spontaneously after delivery (47.37%). Perceived stress was the highest risk predictor of postpartum depression (β=0.332), followed by cognitive fusion (β=0.178), which remained stable over time and might have been positively related to having a vulnerable personality (0.2<r<0.4). Social support plays a positive role in lowering postpartum depression (β=-0.027). Changes in depression were influenced by multiple factors with stability and predictability across time. Psychological dimensions, such as perceived stress and cognitive fusion, are risk factors for developing postpartum depression and antenatal depression. Pregnant women can be divided into depressive cohorts according to screening at different time points to provide targeted interventions.

Differential Prognostic Value of Revascularization for Coronary Stenosis With Intermediate FFR by Coronary FlowReserve.

The authors sought to evaluate comparative prognosis between deferred versus performed percutaneous coronary intervention (PCI) according to coronary flow reserve (CFR) values of patients with intermediate fractional flow reserve (FFR). For coronary stenosis with intermediate FFR, the prognostic value of PCI remains controversial. The prognostic impact of PCI may be different according to CFR in patients with intermediate FFR. From the ILIAS Registry (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry, N=2,322), 400 patients (412 vessels) with intermediate FFR (0.75-0.80) were selected. Patients were stratified into preserved CFR (>2.0, n=253) and depressed CFR (≤2.0, n=147) cohorts. Per-vessel clinical outcomes during 5 years of follow-up were compared between deferred versus performed PCI groups in both cohorts. The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization. Among the study population, PCI was deferred for 210 patients (219 vessels, 53.2%) (deferred group) and performed for 190 patients (193 vessels, 46.8%) (performed group). The risk of TVF was comparable between the deferred and performed groups (12.8% vs 14.2%; adjusted HR: 1.403; 95%CI: 0.584-3.369; P=0.448). When stratified by CFR, PCI was performed in 39.1% (100/261 vessels) of the preserved CFR cohort and 61.9% (93/151 vessels) of the depressed CFR cohort. Within the preserved CFR cohort, the risk of TVF did not differ significantly between the deferred and performed groups (11.0% vs 13.9%; adjusted HR: 0.770; 95%CI: 0.262-2.266; P=0.635). However, in the depressed CFR cohort, the deferred group had a significantly higher risk of TVF than the performed group (17.2% vs 14.2%; adjusted HR: 4.932; 95%CI: 1.312-18.53; P=0.018). A significant interaction was observed between CFR and the treatment decision (interaction P =0.049). Results were consistent after inverse probability weighting adjustment. In patients with intermediate FFR of 0.75 to 0.80, the prognostic value of PCI differed according to CFR, with a significant interaction. PCI was associated with a lower risk of TVF compared with the deferral strategy when CFR was depressed (≤2.0), but there was no difference when CFR was preserved (>2.0). CFR could be used as an additional risk stratification tool to determine treatment strategies in patients with intermediate FFR. (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry [ILIAS Registry]; NCT04485234).

Pharmacogenetic testing among patients with depression in a US managed care population.

Actionable drug–gene pairs relevant to depression treatment include CYP2D6 and CYP2C19 with specific antidepressants. While clinical use of pharmacogenetic testing is growing, little is known about pharmacogenetic testing for depression treatment in managed care. We determined the incidence of single‐gene CYP2D6 and CYP2C19 testing following a new depression episode among US managed care patients, and described characteristics and antidepressant use of patients receiving tests. We used paid medical and pharmacy claims for patients from commercial health plans in the US. For adult patients with a new depression episode from January 1, 2013 to June 30, 2018, we identified covered claims for single‐gene CYP2D6 and CYP2C19 pharmacogenetic tests and antidepressant fills. Fewer than 1% (n = 1795) of the depressed cohort (n = 438,534) received a single‐gene CYP2D6 or CYP2C19 test through their insurance within 365 days of their earliest depression episode. The percentage of patients who received a test nearly tripled from 0.2% in 2013 to 0.5% in 2014 before plateauing at 0.4% from 2014 to 2017. Among the patients who received a single‐gene CYP2D6 or CYP2C19 test and filled an antidepressant within 365 days of their depression diagnosis, up to 30% may have had their initial antidepressant informed by the test result. Our findings describe the use of antidepressants before and after pharmacogenetic testing, which is clinically relevant as pharmacogenomic testing becomes more common in clinical practice. Our study also emphasizes the need for procedure and billing codes that capture multiple‐gene panel tests to be more widely implemented in administrative databases.

P256. ABCB1 Gene Variants and Antidepressant Response and Tolerability: A Systematic Review and Meta-Analysis Including Results From the CAN-BIND-1 Cohort

The p-glycoprotein efflux pump, encoded by the ABCB1 gene, has been shown to alter concentrations of various antidepressants in the brain. In this study, we investigated the association between selected ABCB1 single nucleotide polymorphisms (SNPs) and antidepressant treatment outcomes, including new and unpublished data from the Canadian Biomarker and Integration Network for Depression (CAN-BIND-1) cohort.

Mood and Behaviors of Adolescents With Depression in a Longitudinal Study Before and During the COVID-19 Pandemic.

ObjectiveTo investigate whether, compared to pre-pandemic levels, depressive and anxiety symptoms in adolescents with depression increased during the pandemic.MethodWe used data from National Institute of Mental Health Characterization and Treatment of Depression (NIMH CAT-D) cohort, a longitudinal case-control study that started pre-pandemic. Most of the participants are from the states of Maryland and Virginia in the United States. We compared depressive symptoms (1,820 measurements; 519 measurements pre-pandemic and 1,302 during the pandemic) and anxiety symptoms (1,800 measurements; 508 measurements pre-pandemic and 1,292 ratings during the pandemic) of 166 adolescents (109 girls, 96 adolescents with depression) before and during the pandemic. Data were collected during yearly clinical visits, interim 4-month follow-up visits, inpatient stays, and weekly outpatient sessions, with additional data collection during the pandemic. Pre-pandemic, healthy volunteers (HVs) had a median of 1 depressive and anxiety rating (range, 1-3), and adolescents with depression had a median of 2 ratings (anxiety rating range, 1-25; depressive rating range, 1-26). During the pandemic, HVs had a median of 8 anxiety ratings and 9 depressive ratings (range, 1-13), and adolescents with depression had a median of 7 anxiety and depressive ratings (range, 1-29). We also analyzed adolescent- and parent-reported behaviors in the CoRonavIruS Health Impact Survey (CRISIS), totaling 920 self-reported measures for 164 adolescents (112 girls, 92 adolescents with depression). HVs had a median of 7 surveys (range, 1-8), and adolescents with depression had a median of 5 surveys (range, 1-8).ResultsPre-pandemic, adolescents with depression had a mean depressive score of 11.16 (95% CI = 10.10, 12.22) and HVs had a mean depressive score of 1.76 (95% CI = 0.40, 3.13), a difference of 9.40 points (95% CI = 7.78, 11.01). During the pandemic, this difference decreased by 22.6% (2.05 points, 95% CI = 0.71, 3.40, p = .003) due to 0.89 points decrease in severity of scores in adolescents with depression (95% CI = 0.08, 1.70, p = .032) and 1.16 points increase in HVs’ depressive symptoms (95% CI = 0.10, 2.23, p = .032). Compared to their pre-pandemic levels, adolescents with depression reported overall lower anxiety symptoms during the pandemic. Parent-on-child reports also were consistent with these results.ConclusionContrary to our hypothesis, we found that both depressive and anxiety symptoms were lower for adolescents with depression during the pandemic compared to before. In contrast, the depression scores for the HVs were higher during the pandemic relative to their pre-pandemic ratings; these scores remained much lower than those of adolescents with depression.Clinical trial registration informationCharacterization and Treatment of Adolescent Depression; https://clinicaltrials.gov/; NCT03388606.

Logistic regression models for patient-level prediction based on massive observational data: Do we need all data?

ObjectiveProvide guidance on sample size considerations for developing predictive models by empirically establishing the adequate sample size, which balances the competing objectives of improving model performance and reducing model complexity as well as computational requirements. Materials and MethodsWe empirically assess the effect of sample size on prediction performance and model complexity by generating learning curves for 81 prediction problems (23 outcomes predicted in a depression cohort, 58 outcomes predicted in a hypertension cohort) in three large observational health databases, requiring training of 17,248 prediction models. The adequate sample size was defined as the sample size for which the performance of a model equalled the maximum model performance minus a small threshold value. ResultsThe adequate sample size achieves a median reduction of the number of observations of 9.5%, 37.3%, 58.5%, and 78.5% for the thresholds of 0.001, 0.005, 0.01, and 0.02, respectively. The median reduction of the number of predictors in the models was 8.6%, 32.2%, 48.2%, and 68.3% for the thresholds of 0.001, 0.005, 0.01, and 0.02, respectively. DiscussionBased on our results a conservative, yet significant, reduction in sample size and model complexity can be estimated for future prediction work. Though, if a researcher is willing to generate a learning curve a much larger reduction of the model complexity may be possible as suggested by a large outcome-dependent variability. ConclusionOur results suggest that in most cases only a fraction of the available data was sufficient to produce a model close to the performance of one developed on the full data set, but with a substantially reduced model complexity.

Depression, diabetes and immigration status: a retrospective cohort study using the Canadian Longitudinal Study on Aging.

Background:A bidirectional association between depression and diabetes exists, but has not been evaluated in the context of immigrant status. Given that social determinants of health differ between immigrants and nonimmigrants, we evaluated the association between diabetes and depression incidence, depression and diabetes incidence, and whether immigrant status modified this association, among immigrants and nonimmigrants in Canada.Methods:We employed a retrospective cohort design using data from the Canadian Longitudinal Study on Aging Comprehensive cohort (baseline [2012–2015] and 3-year follow-up [2015–2018]). We defined participants as having diabetes if they self-reported it or if their glycated hemoglobin A1c level was 7% or more; we defined participants as having depression if their Center for Epidemiological Studies Depression score was 10 or higher or if they were currently undergoing depression treatment. We excluded those with baseline depression (Cohort 1) and baseline diabetes (Cohort 2) to evaluate the associations between diabetes and depression incidence, and between depression and diabetes incidence, respectively. We constructed logistic regression models with interaction by immigrant status.Results:Cohort 1 (n = 20 723; mean age 62.7 yr, standard deviation [SD] 10.1 yr; 47.6% female) included 3766 (18.2%) immigrants. Among immigrants, 16.4% had diabetes, compared with 15.6% among nonimmigrants. Diabetes was associated with an increased risk of depression in nonimmigrants (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.08–1.49), but not in immigrants (adjusted OR 1.12, 95% CI 0.80–1.56). Younger age, female sex, weight change, poor sleep quality and pain increased depression risk. Cohort 2 (n = 22 054; mean age 62.1 yr, SD 10.1 yr; 52.2% female) included 3913 (17.7%) immigrants. Depression was associated with an increased risk of diabetes in both nonimmigrants (adjusted OR 1.39, 95% CI 1.16–1.68) and immigrants (adjusted OR 1.60, 95% CI 1.08–2.37). Younger age, male sex, waist circumference, weight change, hypertension and heart disease increased diabetes risk.Interpretation:We found an overall bidirectional association between diabetes and depression that was not significantly modified by immigrant status. Screening for diabetes for people with depression and screening for depression for those with diabetes should be considered.

Reward Deficiency Syndrome (RDS) Surprisingly Is Evolutionary and Found Everywhere: Is It "Blowin' in the Wind"?

Reward Deficiency Syndrome (RDS) encompasses many mental health disorders, including a wide range of addictions and compulsive and impulsive behaviors. Described as an octopus of behavioral dysfunction, RDS refers to abnormal behavior caused by a breakdown of the cascade of reward in neurotransmission due to genetic and epigenetic influences. The resultant reward neurotransmission deficiencies interfere with the pleasure derived from satisfying powerful human physiological drives. Epigenetic repair may be possible with precision gene-guided therapy using formulations of KB220, a nutraceutical that has demonstrated pro-dopamine regulatory function in animal and human neuroimaging and clinical trials. Recently, large GWAS studies have revealed a significant dopaminergic gene risk polymorphic allele overlap between depressed and schizophrenic cohorts. A large volume of literature has also identified ADHD, PTSD, and spectrum disorders as having the known neurogenetic and psychological underpinnings of RDS. The hypothesis is that the true phenotype is RDS, and behavioral disorders are endophenotypes. Is it logical to wonder if RDS exists everywhere? Although complex, “the answer is blowin’ in the wind,” and rather than intangible, RDS may be foundational in species evolution and survival, with an array of many neurotransmitters and polymorphic loci influencing behavioral functionality.

A Cross-sectional Study of the Patterns and Impact of Socio-demographic Factors in Anxious and Depressed Alcohol Dependent Patients

Introduction: Socio-demographic factors may play a pivotal role in anxious and depressed alcohol dependent patients. Identifying the patterns and impact of these factors may be important in the successful management of Alcohol Use Disorders (AUDs). Aim: To assess the patterns and impact of socio-demographic factors in anxious and depressed alcohol dependent patients. Materials and Methods: This cross-sectional study was conducted at Rama Medical College Hospital and Research Center Hapur, Uttar Pradesh, India, from August 2018 to January 2020. Patients with history of substance dependence, gross brain damage, severe medical complications, or evidence of drinking during the hospital stay were excluded. Severity of Alcohol Dependence Questionnaire (SADQ) was used to rate the extent of alcohol dependence and Hamilton Depression Rating Scale (HAM-D or HDRS) to rate depression. Sociodemographic data was recorded in each patient which included age, gender, background, education level, employment status, occupation, marital status, and family type. The severity of anxiety symptoms was measured on Hamilton Anxiety Rating Scale (HAM-A). Independent t-tests, Chi-square tests, oneway Analysis of Variance (ANOVA) and Pearson’s correlation analysis were used for statistical analysis. A p-value &lt;0.05 was considered statistically significant. Results: The total of 90 alcohol dependent patients with mean age of 37.6±9.3 years and mean HDRS score was 8.5±4.3. The overall prevalence of depression cohort was. Out of these 30 (33.3%) had mild and 6 (6.7%) had moderate depression, respectively. The mean Hamilton anxiety scale score was 18.6±5.2. Patients who had a lower Socio-economic Status (SES) (p-value= 0.049 and 0.004), were martially separated (p-value&lt;0.001 and 0.027), living in a nuclear family (p-value=0.005 and &lt;0.001) and were unemployed (p-value&lt;0.001 and p-value&lt;0.001) had significantly higher depression and anxiety scores, respectively. Conclusion: In anxious and depressed alcohol dependent patients, lower SES, martial separation, living as a single family and unemployment significantly influenced depression and anxiety

Major depressive disorder, when under treatment, may not affect functional outcomes in patients with tibial plateau fractures

BackgroundThe purpose of this study is to determine if treated psychological depression is associated with poorer functional outcomes in patients who sustain tibial plateau fractures. MethodsPatients with a tibia plateau fracture were prospectively followed. Functional status was assessed using the Short Musculoskeletal Function Assessment (SMFA) at baseline (pre-injury), 3 months, 6 months, and 1 year post injury. Clinical outcomes were recorded at each follow up visit and radiographic outcomes were obtained from follow up radiographs. Records were reviewed to identify patients who were being treated for major depressive disorder (MDD). SMFA scores and clinical outcomes were compared between the depression and no depression cohorts. Results420 patients were treated for a tibial plateau fracture and the mean age was 50.83 ± 15.60 years. Forty-two (10%) patients with 42 fractures were being treated for MDD at the time of their fracture. Patients with MDD were older (p = 0.05) and were more likely female (p < 0.01). At baseline, the clinical depression cohort had worse Total SMFA scores compared to the non-depressed cohort (5.90 ± 14.41 vs. 2.69 ± 8.35, p < 0.01). There were no differences in total SMFA score or any SMFA subscores at 3, 6, and 12 months. The incidence of wound complications, reoperations, and radiographic outcomes also did not differ between the cohorts. ConclusionDespite patients with MDD reporting higher SMFA (poorer) scores at baseline, MDD was not associated with worse injuries, diminished clinical or poorer functional outcomes following tibial plateau fractures.

Multimodal neuroimaging biomarkers of Alzheimer’s disease in older adults with depression: Preliminary findings from a pilot cohort

AbstractBackgroundSubclinical depressive symptoms in older adults have been linked to AD pathology and cognitive decline. However, it’s unclear how these findings translate to the spectrum of clinically significant late life depressive symptoms. To explore this, we examined cross‐sectional associations between depressive symptoms and neuroimaging biomarkers of AD (ATN) in a pilot cohort of older adults with moderate‐to‐severe depressive symptoms and compared these participants to non‐depressed older adults.MethodSeventeen community‐dwelling clinically‐normal (CN) older adults meeting DSM5 criteria for major depression (73.4±4.7 y.o., 58.8% female) underwent MRI, amyloid‐(C11‐PiB)‐PET, and tau‐(F18‐FTP)‐PET and completed a clinical battery including the 30‐item Geriatric Depression Scale (GDS) and Preclinical Alzheimer’s Cognitive Composite (PACC). A comparison group of non‐depressed older adults (no history of depression, GDS≤5; 73.0±5.5 y.o., 63.2% female) derived from existing observational studies at our site with similar clinical‐neuroimaging batteries were matched using nearest neighbor propensity score to depressed participants by age, sex, and APOE‐ε4 carrier status in a 4:1 ratio (Table 1). We examined cortical amyloid and regional tau and atrophy in a priori regions of interest (ROI) previously implicated in AD and mood (medial temporal lobe, amygdala, frontal cortex). We utilized t‐tests to explore group differences and linear regressions adjusted for age to investigate associations between depressive symptoms and ATN biomarkers.ResultIn the depressed group, depressive symptoms were significantly associated with elevated FTP in all ROI and with lower hippocampal volume, but not with cortical PiB (Table 2, Fig. 1). There were no significant group differences compared to non‐depressed controls in cortical PiB, regional FTP, or volume measures; however, participants with depression had worse cognitive performance on the PACC than non‐depressed participants (t=‐2.04, p=0.050).ConclusionPreliminary findings in this pilot sample suggest that moderate‐to‐severe depressive symptoms in older adults may be more closely associated cross‐sectionally with tau and hippocampal volume than cortical amyloid. Future work in a larger depressed cohort and with longitudinal follow‐up is needed to characterize risk in older adults with depression and consider opportunities for AD prevention.

The Australian Genetics of Depression Study: New Risk Loci and Dissecting Heterogeneity Between Subtypes

BackgroundMajor depressive disorder (MDD) is a common and highly heterogeneous psychiatric disorder, but little is known about the genetic characterization of this heterogeneity. Understanding the genetic etiology of MDD can be challenging because large sample sizes are needed for gene discovery—often achieved with a trade-off in the depth of phenotyping. MethodsThe Australian Genetics of Depression Study is the largest stand-alone depression cohort with both genetic data and in-depth phenotyping and comprises a total of 15,792 participants of European ancestry, 92% of whom met diagnostic criteria for MDD. We leveraged the unique nature of this cohort to conduct a meta-analysis with the largest publicly available depression genome-wide association study to date and subsequently used polygenic scores to investigate genetic heterogeneity across various clinical subtypes of MDD. ResultsWe increased the number of known genome-wide significant variants associated with depression from 103 to 126 and found evidence of association of novel genes implicated in neuronal development. We found that a polygenic score for depression explained 5.7% of variance in MDD liability in our sample. Finally, we found strong support for genetic heterogeneity in depression with differential associations of multiple psychiatric and comorbid traits with age of onset, longitudinal course, and various subtypes of MDD. ConclusionsUntil now, this degree of detailed phenotyping in such a large sample of MDD cases has not been possible. Along with the discovery of novel loci, we provide support for differential pathways to illness models that recognize the overlap with other common psychiatric disorders as well as pathophysiological differences.

Hyperdynamic Left Ventricular Ejection Fraction in ICU Patients With Sepsis.

To evaluate the cause and prognosis of hyperdynamic left ventricular ejection fraction in critically ill patients with sepsis. Retrospective, single-center cohort study. University Hospital ICU, Birmingham, United Kingdom. ICU patients who received a transthoracic echocardiogram within 7 days of sepsis between April 2016 and December 2019. None. The 90-day mortality rates of normal (55-70%), depressed (< 55%), and hyperdynamic left ventricular ejection fraction (> 70%) were compared. Multivariate logistic regression analysis was performed to determine the association of left ventricular ejection fraction phenotypes with mortality and the association of clinical variables with left ventricular ejection fraction phenotypes. One thousand fourteen patients met inclusion criteria and were 62 years old (interquartile range, 47-72), with mostly respiratory infections (n = 557; 54.9%). Ninety-day mortality was 32.1% (n = 325). Patients with hyperdynamic left ventricular ejection fraction had a higher mortality than depressed and normal left ventricular ejection fraction cohorts (58.9% [n = 103] vs 34.0% [n = 55] vs 24.7% [n = 167]; p < 0.0001, respectively). After multivariate logistic regression, hyperdynamic left ventricular ejection fraction was independently associated with mortality (odds ratio, 3.90 [2.09-7.40]), whereas depressed left ventricular ejection fraction did not (odds ratio, 0.62 [0.28-1.37]). Systemic vascular resistance was inversely associated with hyperdynamic left ventricular ejection fraction (odds ratio, 0.79 [0.58-0.95]), and age, frailty, and ischemic heart disease were associated with depressed left ventricular ejection fraction. Hyperdynamic left ventricular ejection fraction was associated with mortality in septic ICU patients and may reflect unmitigated vasoplegia from sepsis. Depressed left ventricular ejection fraction was not associated with mortality but was associated with cardiovascular disease.

Chronotype changes with age; seven-year follow-up from the Netherlands study of depression and anxiety cohort

BackgroundChronotype reflects an individual's optimal daily timing of sleep, activity, and cognitive performance. Previous, cross-sectional, studies have suggested an age effect on chronotype with later chronotypes in adolescents and earlier chronotypes in children and elderly. Additionally, later chronotypes have been associated with more depressive symptoms. Few studies have been able to study longitudinal associations between chronotype and age, while adjusting for depressive symptoms. MethodsChronotype was assessed twice with the Munich Chronotype Questionnaire 7 years apart in the Netherlands Study of Depression and Anxiety (T1: N = 1842, mean age (SD): 42.63 years (12.66)) and T2: N = 1829, mean age (SD) 50.67 (13.11)). The longitudinal association between change in age and change in chronotype was tested using a generalized estimated equation analysis adjusted for covariates (including level of depressive symptoms). Using age-bins of 5 years (age at T2), change in chronotype between T1 and T2 was analyzed with Linear Mixed Models. ResultsWe found a change towards an earlier chronotype with higher age (B (95% CI): -0.011 (-0.014–0.008), p < 0.001). For the age-bins, the difference in chronotype was significant for the 25–29 years age-bin. LimitationsThe sample did not include individuals younger than 19 years or older than 68 years. ConclusionsIn the whole sample chronotype changed towards becoming more morning-type over a period of 7 years, but this change was only significant for those aged 25–29 years. The study was performed in a large naturalistic cohort study with a wide age-range, including patients with a diagnosis of depressive and anxiety disorder and healthy controls.