Incidence Of Major Depressive Disorder Research Articles

Association between a selective 5-HT4 receptor agonist and incidence of major depressive disorder: emulated target trial.

The serotonin 4 receptor (5-HT4R) is a promising target for the treatment of depression. Highly selective 5-HT4R agonists, such as prucalopride, have antidepressant-like and procognitive effects in preclinical models, but their clinical effects are not yet established. To determine whether prucalopride (a 5-HT4R agonist and licensed treatment for constipation) is associated with reduced incidence of depression in individuals with no past history of mental illness, compared with anti-constipation agents with no effect on the central nervous system. Using anonymised routinely collected data from a large-scale USA electronic health records network, we conducted an emulated target trial comparing depression incidence over 1 year in individuals without prior diagnoses of major mental illness, who initiated treatment with prucalopride versus two alternative anti-constipation agents that act by different mechanisms (linaclotide and lubiprostone). Cohorts were matched for 121 covariates capturing sociodemographic factors, and historical and/or concurrent comorbidities and medications. The primary outcome was a first diagnosis of major depressive disorder (ICD-10 code F32) within 1 year of the index date. Robustness of the results to changes in model and population specification was tested. Secondary outcomes included a first diagnosis of six other neuropsychiatric disorders. Treatment with prucalopride was associated with significantly lower incidence of depression in the following year compared with linaclotide (hazard ratio 0.87, 95% CI 0.76-0.99; P = 0.038; n = 8572 in each matched cohort) and lubiprostone (hazard ratio 0.79, 95% CI 0.69-0.91; P < 0.001; n = 8281). Significantly lower risks of all mood disorders and psychosis were also observed. Results were similar across robustness analyses. These findings support preclinical data and suggest a role for 5-HT4R agonists as novel agents in the prevention of major depression. These findings should stimulate randomised controlled trials to confirm if these agents can serve as a novel class of antidepressant within a clinical setting.

The Effects of Diet on the Elimination and Prevention of Mental Health Illnesses

The study investigates the relationship between diet type and mental health, focusing on the impact of nutrient deficiencies on mental health illnesses and their treatment. We gathered results from 15 participants over ten years using self-administered questionnaires and biochemical assessments. The study discovered significant correlations between diets and mental health diseases, with Western diets increasing the incidence of major depressive disorder, anxiety disorder, and ADHD. Mediterranean and high-fiber diets showed protective effects, reducing the rates of these disorders by 40% and 30%, respectively. Some participants also showed deficiencies in omega-3 PUFAs and vitamin D. Pharmacological interventions, such as omega-3 supplementation and Mediterranean diets, improve mental health outcomes. The study emphasizes the importance of dietary change in preventing and treating psychiatric disorders and emphasizes the need for clinical and population-level dietary changes.

Sleep disturbances and incident risk of major depressive disorder in a population-based cohort

Sleep disturbances are well-known symptoms of major depressive disorder (MDD). However, the prospective risk of MDD in the presence of sleep disturbances in a general population-based cohort is not well known. This study investigated associations between both polysomnography (PSG)-based or subjective sleep features and incident MDD. Participants representative of the general population who had never had MDD completed sleep questionnaires (n = 2000) and/or underwent PSG (n = 717). Over 8 years’ follow-up, participants completed psychiatric interviews enabling the diagnosis of MDD. Survival Cox models were used to analyze associations between sleep features and MDD incidence. A higher Epworth Sleepiness Scale and presence of insomnia symptoms were significantly associated with a higher incidence of MDD (hazard ratio [HR] [95 % confidence interval (CI)]: 1.062 [1.022–1.103], p = 0.002 and 1.437 [1.064–1.940], p = 0.018, respectively). Higher density of rapid eye movements in rapid eye movement (REM) sleep was associated with a higher incidence of MDD in men (HR 1.270 [95 % CI 1.064–1.516], p = 0.008). In women, higher delta power spectral density was associated with a lower MDD incidence (HR 0.674 [95 % CI 0.463–0.981], p = 0.039). This study confirmed the associations between subjective and objective sleep features and the incidence of MDD in a large community dwelling cohort.

The gut microbiota and post-traumatic major depression disorder: insights from bidirectional two-sample Mendelian randomization.

Exposure to trauma is often associated with an increased incidence of Major Depressive Disorder (MDD), yet the mechanisms underlying MDD development post-trauma remain elusive. The microbiota-gut-brain axis has been implicated in neuropsychiatric disorders, suggesting its potential role in post-traumatic MDD (PTMDD) development. Our study aimed to assess the significance of the gut microbiome-brain interaction in PTMDD. We conducted a bidirectional two-sample Mendelian Randomization (MR) analysis to investigate the causal relationship between the gut microbiota and both PTMDD and trauma exposure in MDD. Genome-wide association study (GWAS) summary datasets for PTMDD and trauma exposure in MDD, both derived from the UK Biobank. The PTMDD dataset included 24,090 individuals (13,393 cases and 10,701 controls), while the dataset for trauma exposure in MDD comprised 22,880 participants (13,393 cases and 9,487 controls). Additionally, gut microbiota data from the MiBioGen consortium included 14,306 European individuals across 18 diverse cohorts. Our research identified a significant negative association between the phylum Verrucomicrobia (odds ratio (OR) [95% confidence interval (CI)] =0.799 [0.684-0.933], P=0.005) and the risk of developing PTMDD, suggesting a protective role for Verrucomicrobia against PTMDD. Conversely, our findings indicate no causal effects of the gut microbiota on trauma exposure in MDD. However, reverse analysis revealed that both PTMDD and MDD influence certain bacterial traits, affecting 5 and 9 bacterial traits, respectively. Moreover, Verrucomicrobia (OR [95% CI] = 1.166 [1.051 - 1.294], P=0.004) was found to be positively impacted by trauma exposure in MDD. Our findings provide a cause-and-effect relationship between the gut microbiota and PTMDD, contributing to our understanding of the microbiota-gut-brain axis and its role in neuropsychiatric disorder development after trauma. This information provides an opportunity for new treatment and prevention methods which are aimed at the gut-brain interaction.

Associations between body weight change and incidence of major depressive disorder in patients with type 2 diabetes mellitus: a nationwide longitudinal follow-up cohort study of 1.1 million.

Comorbid depression substantially affects the management of glycemia and diabetes-related complications among patients with type 2 diabetes mellitus. In this study, we sought to determine the association between weight change over 4 years and depression risk among patients with type 2 diabetes mellitus. This population-based retrospective cohort study from the National Health Insurance Services of Korea included 1 111 345 patients with type 2 diabetes who were divided into groups according to body weight change over 4 years. Body weight changes were compared with the preceding 4-year period (2005-2008). Depression was defined according to the International Classification of Diseases 10th revision code for depression (F32 and F33) on one or more inpatient or outpatient claims. During a median follow-up of 7.4 years, 244 081 cases of depression were identified. We observed a U-shaped association between body weight change and depression risk with a higher risk among both groups of weight loss (hazard ratio (HR) 1.17, 95% CI 1.15-1.19 for ⩾ -10%; HR 1.07, 95% CI 1.06-1.08 for -10 to -5%) and weight gain (HR 1.06, 95% CI 1.04-1.08 for ⩾10%; HR 1.02, 95% CI 1.01-1.04 for 5-10%) compared with the stable weight group (-5 to 5%). A U-shaped association between body weight change and depression risk was observed in this large nationwide cohort study. Our study suggests that patients with type 2 diabetes and weight change, either gain or loss, could be considered a high-risk group for depression.

Influence of PCDH9 (rs9540720) and narcissistic personality traits on the incidence of major depressive disorder in Chinese first-year university students: findings from a 2-year cohort study.

Objective: The objective of this study was to explore the influence of the polymorphism of the protocadherin 9 (PCDH9) gene and the narcissistic personality trait (NPT) on the risk of major depressive disorder (MDD) in Chinese first-year university students. Methods: A 2-year cohort study was conducted among Chinese first-year university students who were enrolled in 2018 from two universities in Shandong Province, China. The snapshot technique was used to detect the genotypes of PCDH9 (rs9540720). The Chinese version of the Composite International Diagnostic Interview was used for the MDD assessment. The NPTs were measured by 11 items based on DSM-IV. Patient Health Questionnaire-9 and the Beck Anxiety Inventory were used to assess depressive and anxiety symptoms, respectively. Logistic regression modeling was carried out to examine the relationship between rs9540720, NPTs, and the incidence of MDD. Results: A total of 5,327 students participated in the baseline and follow-up studies and provided their blood samples. PCDH9 (rs9540720) (ORGG+GA = 2.33, 95% CI: 1.35-4.02) and NPTs (OR5-9 = 2.26, 95% CI: 1.40-3.64) increased the risk of MDD onset. There was no multiplicative interaction between NPTs and Rs9540720 (OR = 1.51, 95% CI: 0.30-7.63). Furthermore, there was no additive interaction between them (RERI = 2.40, 95% CI: -0.82-5.62; AP = 0.47, 95% CI: -0.04-0.97; and S = 2.37, 95% CI: 0.54-10.33). Conclusion: PCDH9 (rs9540720) and more NPTs are the risk factors for the incidence of MDD in Chinese first-year university students.

Global, regional, and national burdens of depressive disorders in adolescents and young adults aged 10–24 years from 1990 to 2019: A trend analysis based on the Global Burden of Disease Study 2019

BackgroundDepressive disorders (DD) including dysthymia and major depressive disorder (MDD) are common among adolescents and young adults. However, global trends in DD burden remain unclear. MethodsWe analysed data from the Global Burden of Disease 2019 study on incidence, prevalence, disability-adjusted life years (DALYs), and mortality due to DD from 1990 to 2019 at global, regional and national levels. ResultsGlobally, dysthymia incidence increased notably in females, older age groups, and lower-middle income countries from 1990 to 2019. In contrast, MDD incidence decreased slightly over this period except in high-income North America. Females and middle-income countries had the highest dysthymia burden while North America had the highest MDD incidence and DALYs. Oman and Malaysia experienced largest increases in dysthymia and MDD burden respectively. ConclusionDespite certain global indicators suggesting a leveling off or decrease, it's clear that depressive disorders continue to be a significant and increasing issue, particularly among women, teenagers, and young adults. Differences between regions and countries indicate that specific interventions aimed at addressing economic inequalities, improving healthcare systems, and taking cultural factors into account could make a real difference in lessening the burden of depressive disorders. More research is needed to understand what's driving these trends so that we can develop better strategies for preventing and managing these conditions.

Exploring protective factors in a high-risk subsample: the pivotal role of paternal support in preventing depression in a cohort of young adults.

Major depressive disorder (MDD) is a global concern due to its widespread prevalence and morbidity. Identifying protective factors in high-risk individuals, including those with a familial predisposition, maltreatment history, and socio-economic vulnerabilities, is crucial. We assessed a high-risk subsample within a young adult population cohort (n = 791; mean age = 31.94 [SD = 2.18]) across three waves. Using multiple regression models to analyse higher education, feeling supported, spirituality, psychotherapy access, higher socioeconomic status, involvement in activities, cohabitation, and family unity in Waves 1 and 2, and their association with MDD resilience at Wave 3. In the high-risk group, MDD incidence was 13.7% (n=24). Paternal support had a protective effect on MDD incidence (OR = 0.366; 95% CI [0.137 to 0.955], p = 0.040) and suicidal attempt risk (OR = 0.380; 95% CI [0.150 to 0.956], p = 0.038). Higher resilience scores were also protective (OR = 0.975; 95% CI [0.953 to 0.997], p = 0.030), correlating with reduced BDI (r = 0.0484; B = -0.2202; 95% CI [-0.3572 to -0.0738]; p = 0.003) and MADRS scores (r = 0.0485; B = -0.2204; 95% CI [-0.3574 to -0.0741]; p = 0.003). Our paper emphasizes reorienting the MDD approach, focusing on positive prevention strategies. It highlights fathers' crucial role in family-based interventions and promoting resilience in high-risk populations.

The long-term spatio-temporal trends in burden and attributable risk factors of major depressive disorder at global, regional and national levels during 1990-2019: a systematic analysis for GBD 2019.

Caused by multiple risk factors, heavy burden of major depressive disorder (MDD) poses serious challenges to public health worldwide over the past 30 years. Yet the burden and attributable risk factors of MDD were not systematically known. We aimed to reveal the long-term spatio-temporal trends in the burden and attributable risk factors of MDD at global, regional and national levels during 1990-2019. We obtained MDD and attributable risk factors data from Global Burden of Disease Study 2019. We used joinpoint regression model to assess the temporal trend in MDD burden, and age-period-cohort model to measure the effects of age, period and birth cohort on MDD incidence rate. We utilized population attributable fractions (PAFs) to estimate the specific proportions of MDD burden attributed to given risk factors. During 1990-2019, the global number of MDD incident cases, prevalent cases and disability-adjusted life years (DALYs) increased by 59.10%, 59.57% and 58.57%, respectively. Whereas the global age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR) and age-standardized DALYs rate (ASDR) of MDD decreased during 1990-2019. The ASIR, ASPR and ASDR in women were 1.62, 1.62 and 1.60 times as that in men in 2019, respectively. The highest age-specific incidence, prevalence and DALYs rate occurred at the age of 60-64 in women, and at the age of 75-84 in men, but the maximum increasing trends in these age-specific rates occurred at the age of 5-9. Population living during 2000-2004 had higher risk of MDD. MDD burden varied by socio-demographic index (SDI), regions and nations. In 2019, low-SDI region, Central sub-Saharan Africa and Uganda had the highest ASIR, ASPR and ASDR. The global PAFs of intimate partner violence (IPV), childhood sexual abuse (CSA) and bullying victimization (BV) were 8.43%, 5.46% and 4.86% in 2019, respectively. Over the past 30 years, the global ASIR, ASPR and ASDR of MDD had decreased trends, while the burden of MDD was still serious, and multiple disparities in MDD burden remarkably existed. Women, elderly and populations living during 2000-2004 and in low-SDI regions, had more severe burden of MDD. Children were more susceptible to MDD. Up to 18.75% of global MDD burden would be eliminated through early preventing against IPV, CSA and BV. Tailored strategies-and-measures in different regions and demographic groups based on findings in this studywould be urgently needed to eliminate the impacts of modifiable risk factors on MDD, and then mitigate the burden of MDD.

Sex difference in incidence of major depressive disorder: an analysis from the Global Burden of Disease Study 2019

BackgroundMajor depressive disorder (MDD) is a leading mental disorder causing severe impairment. This study was aimed to evaluate sex difference in global MDD incidence by year, age, and socioeconomic status, according to the Global Burden of Disease Study 2019 (GBD 2019).MethodsGlobal and national sex-specific incidence estimates of MDD, from 1990 to 2019, in different age groups, were extracted from the GBD 2019. Socioeconomic development index (SDI) as an indicator of national socioeconomic development was used. Absolute (female minus male) and relative (female to male ratio) sex difference in age-standardized incidence rates (ASRs), as well as risk ratios (RR and 95% confidence interval), were computed by year and age. Linear regression analyses were conducted to investigate socioeconomic-associated sex difference in incidence.ResultsAbsolute and relative sex difference in ASRs showed a slight declining trend during 1990 and 2019, with absolute difference decreasing from 1818.23 to 1602.58, and relative difference decreasing from 1.71 to 1.61. Worldwide, females had a higher risk of MDD than males in 1990 (RR: 1.706 (1.705–1.706)) and 2019 (RR: 1.602 (1.619–1.620)). The highest RRs were observed in the Region of the Americas. Sex difference in incidence rates increased rapidly with age for those under 20 years old. The highest RR (1.913 (1.910–1.915)) was observed in the age group of 10–14. Relative sex difference had a significant positive relationship with SDI (standardized β = 0.267, P < 0.001).ConclusionsDespite that slight improvement in sex difference in global MDD incidence has been achieved, sex difference still persists in the past decades, with females always having a higher incidence than males. Greater sex difference was found at younger ages and in more developed countries. The findings highlight the importance of making sex-specific health policy to reduce sex difference in MDD incidence.

Secular trends in the incidence of major depressive disorder and dysthymia in China from 1990 to 2019

BackgroundDepression is increasingly recognized as a worldwide serious, public health concern. A better understanding of depression is important for advancing its management and learning the difference between major depressive disorder (MDD) and dysthymia. Our aim is to conduct a concurrent analysis of the trends of both MDD and dysthymia in China.MethodsThe data on depression from 1990 to 2019 were collected from the Global Burden of Disease Study 2019 (GBD 2019). To determine the average annual percent changes (AAPC) and relative risks (RRs), joinpoint regression and the age-period-cohort models were employed, respectively.ResultsThe incidence number of MDD and dysthymia continuously increased in China from 1990 to 2019, however, the age-standardized rates (ASR) had a decreasing trend in both men and women. The results from joinpoint regression showed that a declining trend was presented in young people (< 50 years) but an increased trend in the elderly (≥ 50 years) both in men and women, during 1990–2019. Age is the most influential factor for MDD and dysthymia. Age RRs for MDD incidence had an overall increasing trend with age. Period RR in MDD presented a U-shaped pattern, while Cohort RRs presented an inverted U-shaped pattern. On the other hand, RRs in dysthymia for period and cohort effects had no statistical significance, only the age effect presented an inverted U-shaped pattern.ConclusionsThe disparities in trends observed between MDD and dysthymia during the period of 1990–2019 indicated the significance of distinguishing between these two disorders. The age, period and cohort effects all had a greater impact on MDD than on dysthymia, and age effects presented different influential patterns in these two. To alleviate the burden of depressive disorders in China, proactive measures need to be implemented, with particular attention to the elderly population.

Major depressive disorder and chronic gastritis: A bidirectional two-sample Mendelian randomization study

ObjectiveObservational studies have posited a strong correlation between chronic gastritis (CG) and major depressive disorder (MDD), but the nature of this association remains uncertain, owing to the challenges of establishing the temporal sequence. The present study sought to elucidate the elusive relationship between CG and MDD by employing a bidirectional two-sample Mendelian randomization (MR) approach. MethodsWe extracted instrumental variants for MDD and CG from published genome-wide association study data, focusing on individuals of primarily European descent. A comprehensive suite of MR estimations and sensitivity analyses was performed to ensure the robustness of the findings. Each outcome database was analyzed separately in both directions. ResultsFor MDD and CG, 221 and 5 genetic variants, respectively, were selectively extracted as instrumental variants. The results suggest that MDD is causally associated with an elevated risk of CG (IVW: 23andMe, OR = 1.33; 95% CI = 1.15–1.54; p = 1.06 × 10–4); conversely, no strong evidence was found to corroborate that CG exerts a causal effect on the incidence of MDD (IVW: OR = 1.01; 95% CI = 0.95–1.07; p = 0.68). ConclusionsThese findings provide novel insights into the causal relationship between CG and MDD, which may have implications for clinical decision-making in patients with MDD and CG.

0323 Natural Evolution of Insomnia in Major Depressive Disorders

Abstract Introduction Insomnia is a fairly common sleep disturbance affecting nearly one third of the general population. Although its predictive value for major depressive disorder (MDD) has been well documented, little is known about its role in the appearance of a first episode or in the recurrence. In this study, we examine the predictive value of insomnia symptoms in the incidence and recurrence of MDD. Methods In this longitudinal study, 2 interview waves were conducted between 2002 and 2015. The initial interviews (wave 1 [W1]) were carried out with 12,218 individuals aged ≥18 years from the general population in 8 US states. At follow-up 3 years later (wave 2 [W2]), 10,931 of the initial participants agreed to be interviewed again. Data were analyzed for the individuals who participated in both interviews (N=10,931). A diagnosis of MDD was made according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. Insomnia symptoms were defined according to DSM-5 criteria A, C, and D for insomnia disorder. Results The 12-month prevalence of MDD was 9.5% (95% CI, 9.0%-10.0%) and 12.1% (95% CI, 11.5%-12.7%) in W1 and W2, respectively. Over the course of the study, 2.6% of participants experienced recurrence of depression (95% CI, 2.3%-2.9%). After adjusting for age, gender, race, and body mass index, participant characteristics in W1 that predicted recurrent MDD in W2 included early morning awakenings (EMA) (relative risk [RR], 3.2; 95% CI, 2.3-4.4), being dissatisfied with one’s sleep (RR, 2.8; 95% CI, 2.1-3.7), nocturnal awakenings (RR, 2.4; 95% CI, 1.8-3.2), and difficulty initiating sleep (DIS) (RR, 2.0; 95% CI, 1.5-2.9). MDD incidence was predicted by DIS (RR, 3.8; 95% CI, 2.5-5.9), being dissatisfied with one’s sleep (RR, 2.1; 95% CI, 1,4-3.2), and EMA (RR, 2.0; 95% CI, 1.2-3,2) at W1. Conclusion Insomnia symptoms appear to play an important part in predicting both the development of a first depressive episode as well as the recurrence of depression. Support (if any) Data analysis study were funded by Takeda Pharmaceutical Company.

Perceived parenting styles and incidence of major depressive disorder: results from a 6985 freshmen cohort study

BackgroundEven though a fair amount of studies focus on depression among college students, the effect of perceived parenting styles on the incidence of major depressive disorder (MDD) among representative freshmen in Chinese context is scarcely studied. The aim of this study is to investigate the effect of parenting styles on MDD in Chinese freshmen.MethodsA total of 9,928 Chinese freshmen were recruited in 2018. 6985 valid questionnaires were collected at one-year follow-up. Composite International Diagnostic Interview 3.0 (CIDI-3.0) was used for the diagnosis of MDD. Egna Minnen Beträffande Uppfostran (EMBU) questionnaire and Beck Depression Inventory-II (BDI-II) were used to assess parenting styles and baseline depressive symptoms, respectively. The associations between parenting styles and MDD incidence was analyzed with logistic regression.ResultsThe incidence of MDD in freshmen was 2.23% (95%CI: 1.91-2.60%). Maternal overprotection (OR = 1.03, 95%CI: 1.01–1.05) and disharmony relationship between parents (OR = 2.35, 95% CI: 1.42–3.89) increased the risk of new-onset MDD in freshmen, respectively. Mild depressive symptoms (OR = 2.06, 95%CI: 1.06–4.02), moderate (OR = 4.64, 95%CI: 2.55–8.44) and severe depressive symptoms (OR = 7.46, 95%CI: 2.71–20.52) at baseline increased the risk of new-onset MDD.ConclusionsMaternal overprotection, disharmony relationship between parents and baseline depressive symptoms are risk factors for new-onset MDD in Chinese freshmen.

Exosomes may be the carrier of acupuncture treatment for major depressive disorder.

The incidence of major depressive disorder (MDD) is increasing all over the world. There is a great need for complementary or alternative therapies with high safety, few side effects, and precise efficacy to care for MDD. In China, acupuncture has significant laboratory data and clinical trials to demonstrate its antidepressant efficacy. However, there is no clear answer as to how it works. Exosomes are membranous vesicles that rely on cellular multivesicular bodies (MVBs) fused to the cell membrane for release into the extracellular matrix. Almost all cell types are capable of producing and releasing exosomes. As a result, exosomes contain complex RNAs and proteins from their relatives (Cells that secretes exosomes). They can cross biological barriers and participate in biological activities, such as cell migration, angiogenesis, and immune regulation. These properties have made them a popular research topic. Some experts have suggested that exosomes may serve as delivery vehicles for acupuncture to work. This presents both an opportunity and a new challenge for improving the protocols of acupuncture as a treatment for MDD. To better define the relationship between MDD, exosomes, and acupuncture, we reviewed the literature from the last few years. Inclusion criteria included randomized controlled trials and basic trials evaluating acupuncture in the treatment or prevention of MDD, the role of exosomes in the development and progression of MDD, and the role of exosomes in acupuncture. We believe that acupuncture may affect the distribution of exosomes in vivo, and exosomes may be a new carrier for acupuncture treatment of MDD in the future.

Incidence of major depressive disorder over time in patients with liver cirrhosis: A nationwide population-based study in Korea.

There is yet to be a large-scale longitudinal study on the course of depression incidence within the duration of cirrhosis. The aim of this study is to analyze the incidence of depression from before to after diagnosis of cirrhosis over time. Incidence Rate (IR) was defined as the number of newly diagnosed patients with MDD divided by the sum of observation periods by using claims database in Korea. Incidence Rate Ratio (IRR) was defined as the IR in the specific interest period divided by the IR in the control period. The control period was defied as 1 to 2 years before diagnosis of cirrhosis. The IRs before and after cirrhosis diagnosis were 3.56 and 7.54 per 100 person-year, respectively. The IRR was 2.12 (95% confidence Interval: 2.06-2.18). The IRR of developing depression mildly increased before diagnosis of cirrhosis (-360 days to -181 days, IRR 1.14, p < 0.001; -180 days to -90 days, IRR 1.24, p < 0.001; -90 days to -31 days, IRR 1.56, p < 0.001) and rapidly increased immediately after diagnosis of cirrhosis (+30 days to +89 days, IRR 2.12, 95% confidence interval: 2.06-2.18, p < 0.001). The pattern of increasing depression immediately after the diagnosis of cirrhosis was observed equally in all sexes and ages. Thus, clinicians must pay close attention to screening for depression within the first three months of liver cirrhosis diagnosis.

Sleep to Reduce Incident Depression Effectively (STRIDE): study protocol for a randomized controlled trial comparing stepped-care cognitive-behavioral therapy for insomnia versus sleep education control to prevent major depression

BackgroundPrevention of major depressive disorder (MDD) is a public health priority. Strategies targeting individuals at elevated risk for MDD may guide effective preventive care. Insomnia is a reliable precursor to depression, preceding half of all incident and relapse cases. Thus, insomnia may serve as a useful entry point for preventing MDD. Cognitive-behavioral therapy for insomnia (CBT-I) is recommended as the first-line treatment for insomnia, but widespread implementation is limited by a shortage of trained specialists. Innovative stepped-care approaches rooted in primary care can increase access to CBT-I and reduce rates of MDD.Methods/designWe propose a large-scale stepped-care clinical trial in the primary care setting that utilizes a sequential, multiple assignment, randomized trial (SMART) design to determine the effectiveness of dCBT-I alone and in combination with clinician-led CBT-I for insomnia and the prevention of MDD incidence and relapse. Specifically, our care model uses digital CBT-I (dCBT-I) as a first-line intervention to increase care access and reduce the need for specialist resources. Our proposal also adds clinician-led CBT-I for patients who do not remit with first-line intervention and need a more personalized approach from specialty care. We will evaluate negative repetitive thinking as a potential treatment mechanism by which dCBT-I and CBT-I benefit insomnia and depression outcomes.DiscussionThis project will test a highly scalable model of sleep care in a large primary care system to determine the potential for wide dissemination and implementation to address the high volume of population need for safe and effective insomnia treatment and associated prevention of depression.Trial registrationClinicalTrials.gov NCT03322774. Registered on October 26, 2017

Histamine and histamine receptors: Roles in major depressive disorder.

Although the incidence of major depressive disorder (MDD) is high and its social impact is great, we still know very little about the pathophysiology of depression. The monoamine hypothesis of depression suggests that 5-HT, NE, and DA synergistically affect mood, which is the basis of current drug therapy for depression. However, histamine as a monoamine transmitter is rarely studied. Our review is the first time to illustrate the effect of histaminergic system on depression in order to find the way for the development of new antidepressant drugs. The brain neurotransmitter histamine is involved in MDD, and the brain histaminergic system operates through four receptors. Histamine and its receptors can also regulate the immune response to improve symptoms of depression. In addition, H3R can interact with other depression-related transmitters (including 5-HT, DA, GLU, and MCH); thus, histamine may participate in the occurrence of depression through other neural circuits. Notably, in rodent studies, several H3R and H1R antagonists were found to be safe and effective in alleviating depression-like behavior. To highlight the complex functions of histamine in depression, and reveals that histamine receptors can be used as new targets for antidepressant therapy.

Gender differences of genetic etiology in the incidence of major depressive disorder among Han freshmen

Objective: To analyze the gender differences of genetic etiology in the incidence of major depression disorder among Han freshmen. Methods: A 1-year follow-up survey was carried out among 8 079 Han freshmen from Jining, Rizhao and Weifang without lifetime major depressive disorder (MDD) at baseline (April to October 2018) and 4 828 venous blood samples were also collected. After extracting DNA, Sequenom Mass Array time-of-flight mass spectrometry biochip technology was used to detect the genotypes of 17 single nucleotide polymorphisms (SNPs) MDD-related loci. Logistic regression was used for univariate analysis. Generalized multifactor dimension reduction was used to analyze gene-gene interactions. Composite International Diagnostic Interview (CIDI) 3.0 was used for MDD diagnosis. Results: The 1-year incidence of MDD among Han freshmen was 2.23% (95%CI: 1.91%-2.60%) and the gender difference of incidence between males (1.97%, 95%CI: 1.52%-2.56%) and females (2.39%, 95%CI: 1.98%-2.90%) was not statistically significant (P>0.05). AG genotype of rs768705 (nearby gene: TMEM161B) was a risk factor for MDD (OR=1.98, 95%CI: 1.24-2.83). The TC genotype of rs17727765 (nearby gene: CRYBA1) was only a risk factor for MDD in males (OR=9.61, 95%CI: 2.04-45.30). An 8-loci interaction model (PMFBP1, OLFM4, LHPP, ENOX1, TMEM161B, SPPL3, FBXL4 and L3MBTL2) could predict MDD in women with an accuracy rate of 60.05%. No effective prediction model was found for MDD in men. Conclusions: There might be gender differences in the genetic etiology of MDD. Further researches on the genetic causes of MDD in men should be explored.

Clinical and economic burden of major depressive disorder with acute suicidal ideation or behavior in a US Veterans Health Affairs database

Objective Although a high incidence of major depressive disorder (MDD) and an increased risk of suicide are observed among the veteran population, there are yet limited real-world data characterizing patients with MDD with acute suicidal ideation/behavior (MDSI) in the Veterans Health Administration (VHA) system. We assessed the clinical and economic burden, including comorbidities, treatment patterns, health care resource utilization, and health care costs, among veterans and their family members with MDSI within the VHA system. Methods This retrospective, longitudinal analysis of VHA datasets (10/1/2015–3/31/2018) evaluated the clinical and economic burden associated with MDSI and compared this population with matched MDD alone (ie, MDD diagnosis without acute suicidal ideation/behavior) and non-MDD (ie, neither MDD nor acute suicidal ideation/behavior) cohorts. Results Among 11,203 patients with MDSI, the proportions of patients who filled a prescription for ≥1 antidepressant during the 12-month pre- and 6-month post-periods were significantly higher compared with patients with MDD alone (53.7% vs 28.8%; P <0.05, and 72.3% vs 44.1%; P <0.05, respectively). During the 12-month pre-period, the MDSI cohort had the highest proportion of patients with ≥1 mental health–related inpatient visit compared with the MDD alone and non-MDD cohorts (13.2% vs 2.3% vs 1.4%, respectively; P <0.05), and the highest mental health–related costs per patient ($8,853 vs $1913 vs $1079, respectively). For the 6-month post-period, the MDSI cohort had the highest proportion of patients with ≥1 mental health–related inpatient visit compared with the MDD alone and non-MDD cohorts (60.4% vs 7.9% vs 0.8%, respectively; P <0.05), and had the highest mental health–related costs per patient ($20,334 vs $4803 vs $545, respectively). Conclusions Findings demonstrate significant clinical and economic burden for those in the VHA system diagnosed with MDSI and highlight unmet needs and opportunities for improving the care of this vulnerable group.