Incident Major Depressive Disorder Research Articles

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.

HSD99 Telemedicine and the Utilization of Outpatient Mental Health Services By Patients with Incident Major Depressive Disorder during the COVID-19 Pandemic

To examine the role of telemedicine in providing access to outpatient psychotherapy for children and young adults with incident major depressive disorder (MDD) before and during the COVID-19 pandemic, overall and by race and ethnicity. Medical claims from a large, national insurer were retrospectively analyzed to identify two cohorts of individuals aged 10-26 years old, based on incident diagnosis (“index”) date of MDD (pre-COVID: March-December 2018, COVID: March-December 2020). We tracked health care utilization, utilization by site of care, modality of care, and psychotherapy The majority of patients in the two cohorts (pre-COVID: N=7,758, COVID: N=8,517) were White (78.9% and 78.8%, respectively), followed by Hispanic (11.5% and 10.9%), Black (6.6% and 7.1%), and Asian (3.0% and 3.2%). While pre-index utilization was similar between cohorts, the COVID cohort had 919 psychotherapy visits per 1,000 patients compared to 735 for the pre-COVID cohort in the month post-index. The increase in visits is largely attributable to an increase in telemedicine visits for the COVID cohort. Similarly, psychotherapy visits increased for all racial and ethnic groups in the COVID cohort compared to the pre-COVID cohort in the month post-index: 22.3% for Whites (931 visits per 1,000 patients in COVID cohort vs. 759 in pre-COVID cohort), 45.0% for Asians (951 vs. 656), 20.5% for Blacks (792 vs. 657) and 46.5% for Hispanics (860 vs. 587). Telemedicine increased access to mental health services during the pandemic across races and ethnicities, but racial and ethnic disparities persisted. Health systems should capitalize on the telehealth infrastructure developed during the pandemic to sustain this increased access to care while continuing work to reduce disparities.

Genetic risk, muscle strength and risk of incident major depressive disorder: results from the UK Biobank.

Genetic factors and muscle strength both contribute to the risk of major depressive disorder (MDD), but whether high muscle strength can offset the risk of MDD with different genetic risk is unknown. This study aims to examine whether a higher muscle strength is associated with lower risk of MDD regardless of genetic risk among middle-aged and older adults. This cohort study obtained data from the UK Biobank, which includes 345,621 individuals aged 40-69years (mean (standard deviation): 56.7 (7.99) years) without baseline MDD. Polygenic risk score for MDD was categorised as low, intermediate or high. The mean of the right- and left-hand grip strength values was used in the analysis and was divided into three categories. 9,753 individuals developed MDD within 2,752,461 person-years of follow-up. The multivariable adjusted hazard ratios (HRs) (95% confidence intervals (CIs)) of MDD across increased grip strength categories were 1.00, 0.72 (0.68-0.75) and 0.56 (0.53-0.59) (P for trend <0.0001). The HRs (95% CIs) of incident MDD across the genetic risk categories were 1.00, 1.11 (1.05-1.17) and 1.20 (1.13-1.28) (P for trend <0.0001); 4.07% of individuals with a high genetic risk and low grip strength developed MDD, and 1.72% of individuals with a low genetic risk and high grip strength developed MDD, with an HR (95% CI) of 0.44 (0.39-0.50). Both muscle strength and genetic risk were significantly associated with incident MDD. A higher muscle strength was associated with a lower MDD risk among individuals with a high genetic risk. Improving muscle strength should be encouraged for all individuals, including individuals with high genetic risk for MDD.

Genetic susceptibility and lifestyle modify the association of long-term air pollution exposure on major depressive disorder: a prospective study in UK Biobank

BackgroundEvidence linking air pollution to major depressive disorder (MDD) remains sparse and results are heterogeneous. In addition, the evidence about the interaction and joint associations of genetic risk and lifestyle with air pollution on incident MDD risk remains unclear. We aimed to examine the association of various air pollutants with the risk of incident MDD and assessed whether genetic susceptibility and lifestyle influence the associations.MethodsThis population-based prospective cohort study analyzed data collected between March 2006 and October 2010 from 354,897 participants aged 37 to 73 years from the UK Biobank. Annual average concentrations of PM2.5, PM10, NO2, and NOx were estimated using a Land Use Regression model. A lifestyle score was determined based on a combination of smoking, alcohol drinking, physical activity, television viewing time, sleep duration, and diet. A polygenic risk score (PRS) was defined using 17 MDD-associated genetic loci.ResultsDuring a median follow-up of 9.7 years (3,427,084 person-years), 14,710 incident MDD events were ascertained. PM2.5 (HR: 1.16, 95% CI: 1.07–1.26; per 5 μg/m3) and NOx (HR: 1.02, 95% CI: 1.01–1.05; per 20 μg/m3) were associated with increased risk of MDD. There was a significant interaction between the genetic susceptibility and air pollution for MDD (P-interaction < 0.05). Compared with participants with low genetic risk and low air pollution, those with high genetic risk and high PM2.5 exposure had the highest risk of incident MDD (PM2.5: HR: 1.34, 95% CI: 1.23–1.46). We also observed an interaction between PM2.5 exposure and unhealthy lifestyle (P-interaction < 0.05). Participants with the least healthy lifestyle and high air pollution exposures had the highest MDD risk when compared to those with the most healthy lifestyle and low air pollution (PM2.5: HR: 2.22, 95% CI: 1.92–2.58; PM10: HR: 2.09, 95% CI: 1.78–2.45; NO2: HR: 2.11, 95% CI: 1.82–2.46; NOx: HR: 2.28, 95% CI: 1.97–2.64).ConclusionsLong-term exposure to air pollution is associated with MDD risk. Identifying individuals with high genetic risk and developing healthy lifestyle for reducing the harm of air pollution to public mental health.

Subclinical Hypothyroidism and Incident Depression in Adolescents and Young Adults: Results from a Nationwide Representative Prospective Study.

Background: Although the relationship between subclinical hypothyroidism and major depressive disorder (MDD) has been studied in adults in cross-sectional and prospective population-based studies, this has not yet been done in adolescents. However, since thyroid function and MDD risk are subjected to maturational processes and ramifications of illness duration over the life span, these findings may not readily transfer to adolescents. Methods: The relationship between subclinical hypothyroidism and MDD was studied in a representative subsample of the nationwide KIGGS ("The German Health Interview and Examination Survey for Children and Adolescents") survey. A total of 4118 adolescents were examined over a median period of 6 years, and data were analyzed by a logistic regression approach accounting for important covariates related to thyroid function and/or MDD risk. The same approach was chosen to investigate the relationship between quartiles of thyrotropin (TSH) and free thyroxine (fT4) levels and incident MDD in euthyroid participants to broaden the focus on the relationship between thyroid hormone levels and MDD in a dose-response manner. Results: During the observation period, 121 cases of MDD were reported. There was no association between subclinical hypothyroidism and MDD when comparing 111 adolescents with subclinical hypothyroidism with 4007 euthyroid adolescents, representative of ∼106,000 and 3,610,000 adolescents from the general pediatric population, respectively. This also applied when studying the relationship between quartiles of TSH and fT4 levels and MDD in euthyroid participants. All results were confirmed by sensitivity analyses accounting for thyroid autoimmunity. Conclusions: Consistent with findings in adults, there is no association between subclinical hypothyroidism or quartiles of TSH and fT4 levels in the normal range and MDD in adolescents, despite potential age-related differences regarding thyroid function and MDD risk.

0669 The Role Of Hypersomnolence In Depression: Results From A Longitudinal Study Of The American General Population

Abstract Introduction Insomnia symptoms have often been pointed out as an important factor for the relapse and/or the maintenance of depression. However, the contribution of hypersomnolence in depression is less studied and the conclusions are unclear. Our aim is to examine the association between hypersomnolence and depression in the US general population. Methods This longitudinal study was carried out in eight states in the U.S. A total of 12,218 subjects were interviewed by phone during the first wave (W1) and 10,931 at the second wave (W2) three years apart. The analyses included only the subjects who participated in the 2 waves (N=10,931). Hypersomnolence symptoms and Major Depressive Disorder (MDD) were assessed according to DSM-5 criteria. Results At W1, 27.2% (95% CI 26.4%-28.0%) of the sample had at least one hypersomnolence symptoms listed in the DSM5 occurring at least 3 days per week. This prevalence at W2 was 26.4% (95% CI 25.6%-27.2%). The incidence of DSM5 hypersomnolence symptoms was 20.5% which represents a yearly incidence of 5.8%. For MDD, the prevalence was 5.1% (95% CI 4.7%-5.5%) and 4.2% (95% CI 3.8%-4.6%) in W1 and W2, respectively. At W1, 54.2% of participants with a MDD also had hypersomnolence. At W2, 50.7% of MDD subjects also reported hypersomnolence. After adjusting for age, gender and medical conditions, persistent hypersomnolence (i.e., reported at both interviews) predicted incident MDD (i.e., absent at the first interview but present at the follow-up) with a relative risk of 2.0 (95% CI 1.5-2.8). Similarly, persistent hypersomnolence predicted persistent MDD with a relative risk of 3.8 (95% CI 2.5-5.8). After adjusting for the presence of insomnia, persistent hypersomnolence remained a strong predictor for persistent MDD (RR: 2.4) but not for incident MDD. Conclusion Hypersomnolence, especially when it is persistent, is an important contributing factor for persistent MDD. While the presence of insomnia mitigates the predictive value of hypersomnolence in incident MDD, it had little effect on the association between persistent hypersomnolence and persistent MDD. Support (If Any)

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.

Clinical and societal burden of incident major depressive disorder: A population-wide cohort study in Stockholm.

ObjectiveMajor depressive disorder (MDD) is a highly prevalent condition and a significant contributor to global disability. The vast majority of MDD is handled by primary care, but most real‐life studies on MDD only include data from secondary care. The aim of this study was therefore to estimate the total clinical and societal burden of incident MDD including data from all healthcare levels in a large well‐defined western European healthcare region.MethodsPopulation‐wide observational study included healthcare data from Region Stockholm, Sweden's largest region with approximately 2.4 million inhabitants. All patients in Region Stockholm having their first unipolar MDD episode between January 1, 2012, and December 31, 2018, were included. The sample also included matched study population controls. Outcomes were psychiatric and non‐psychiatric comorbid conditions, antidepressant therapy use, healthcare resource utilization, work loss, and all‐cause mortality.ResultsIn the study period, 137,822 patients in Region Stockholm were diagnosed with their first unipolar MDD episode. Compared with matched controls, MDD patients had a higher burden of non‐psychiatric and psychiatric comorbid conditions, 3.2 times higher outpatient healthcare resource utilization and 8.6 times more work loss. MDD was also associated with a doubled all‐cause mortality compared with matched controls (HR: 2.2 [95% CI: 2.0–2.4]).ConclusionsThe high mortality, morbidity, healthcare resource utilization, and work loss found in this study confirms that MDD is associated with individual suffering and low functioning leading to substantial costs for patients and society. These findings should motivate additional efforts in improving outcomes for MDD patients.

Community-Level Social Support Infrastructure and Adult Onset of Major Depressive Disorder in a South Asian Postconflict Setting

Individual-level social support protects against major depressive disorder (MDD) among adults exposed to trauma. Little is known about the consequences of community-level interventions in the general population. To determine the potential consequences of neighborhood social infrastructure on incident MDD in a high-risk general population. This longitudinal, multilevel study estimated associations between a neighborhood-level program in a case-control design and subsequent individual outcomes across 10 years (2006-2015) in a cohort of young adults. Exogenously placed social programs simulate natural experiment conditions in a high-poverty population experiencing armed conflict (1998-2006). The western Chitwan valley in Nepal has a general population at high risk of MDD, with neighborhoods exposed to interventions to improve social support. From a random sample (response rate 93%) selected to represent the general population in 2016, participants aged 25 to 34 years in 2006 were studied. These individuals resided within 149 neighborhoods that varied in their availability of active social support programs. The analyses were conducted between October 2020 and November 2021. The Small Farmers Development Program (SFDP) uses shared, joint liability financial credit among neighbors to build social capital and cohesion within neighborhoods. Onset of DSM-IV MDD after the conflict, assessed by the Nepal-specific, clinically validated World Mental Health Composite International Diagnostic Interview with a life history calendar. The hypothesis tested was that exposure to SFDP reduced adult onset of MDD. Of the 1917 survey participants, 886 (46.2%) were women, and 856 (44.7%) were of Brahmin or Chhetri ethnicity. Of the 149 neighborhoods, 21 had an active SFDP group, and 156 of 1917 (8.1%) participants experienced MDD between 2006 and 2015. Discrete-time hazard models showed participants living in neighborhoods with an SFDP experienced incident MDD at nearly half the rate as others (odds ratio = 0.55; 95% CI, 0.30-1.02; P = .06). A multivariate, multilevel matching analysis showed the incidence of MDD among adults living in neighborhoods with an SFDP was 19 of 256 (7.4%), compared with 33 of 256 (12.9%) in the matched sample with no SFDP (z = 2.05; P = .04). Living in a neighborhood with community-level social support infrastructure was associated with reduced subsequent rates of adult-onset MDD, even in this high-risk population. Investments in such infrastructure may reduce population-level MDD, supporting clinical focus on potentially unpreventable cases.

Mortality and Suicide Related to Major Depressive Disorder Before and After Type 2 Diabetes Mellitus.

Objective: This study investigated differences in suicide and all-cause mortality from ICD-9-CM comorbid major depressive disorder (MDD) and type 2 diabetes mellitus (T2DM) depending on which was diagnosed first.Methods: A longitudinal administrative claims database including 2 million samples and national death registry data from 2000 through 2015 in Taiwan were used. Patients with newly diagnosed T2DM were identified and further classified into 3 groups: (1) MDD before T2DM, (2) T2DM without any diagnosis of MDD (from which matched controls were selected), and (3) MDD after T2DM, based on the sequential occurrence dates between incident T2DM and MDD. Multivariable Cox proportional hazard models were analyzed.Results: Both the MDD before T2DM and MDD after T2DM groups had significantly higher risks of all-cause mortality (adjusted hazard ratio [AHR] = 1.21; 95% CI, 1.08-1.35 and AHR = 1.55; 95% CI, 1.45-1.66, respectively) and committed suicide (AHR = 5.05; 95% CI, 2.46-10.37and AHR = 14.32; 95% CI, 7.44-27.55, respectively) than their matched controls, while the MDD before T2DM and MDD after T2DM groups exhibited differences in mortality (significant; P < .0001) and death by suicide (nonsignificant).Conclusions: The study findings indicated suicide and mortality rates were higher in both the MDD before and MDD after T2DM groups when compared with matched controls. Public health initiatives are needed to survey and treat comorbid MDD with T2DM. Furthermore, additional studies are needed to clarify the underlying pathophysiology of the association between MDD and T2DM to find better suicide prevention strategies among those high-risk patients who have comorbid T2DM and MDD.

Trajectories of somatic drug utilization patterns in Major Depressive Disorder: A Study protocol for a Danish nationwide register study using Latent Class Analysis

Background: Major Depressive disorder (MDD) is a heterogeneous, multi-etiological disorder that is associated with chronic medical conditions and a high somatic treatment burden. A better understanding of the somatic diseases and treatment burden in MDD can be provided through a mapping of the somatic drug utilization patterns over time. The objective of this study is therefore to characterize the somatic drug profiles and their transitions over time (i.e. trajectories) among MDD patients. Methods: This descriptive study will be a nationwide register-based study including all Danish patients with an incident MDD diagnosis between 2011 and 2015. Using Latent Class Analysis, we will identify homogenous MDD patient subgroups according to somatic drug utilization (i.e. drug profiles). The development in somatic drug profiles will be depicted in four different time intervals from three years prior to the MDD diagnosis to three years after the diagnosis. Patients will be assigned to the latent class (drug profile) to which they have the highest probability of belonging using modal assignment. The treatment trajectories will be performed by cross tabulating these assignments. Discussion: Profiles and trajectories of somatic drug use will provide a new perspective on patterns of somatic drug burden in MDD patients. Moreover, identifying homogenous subgroups of MDD patients regarding somatic drug use can contribute to a deeper understanding of MDD etiology. In the future, this knowledge could help optimizing MDD treatment by studying if different antidepressants will show different efficacy and safety depending on the profiles and trajectories of somatic diseases.

Incident Major Depressive Disorder Predicted by Three Measures of Insulin Resistance: A Dutch Cohort Study.

Major depressive disorder is the leading cause of disability worldwide. Yet, there remain significant challenges in predicting new cases of major depression and devising strategies to prevent the disorder. An important first step in this process is identifying risk factors for the incidence of major depression. There is accumulating biological evidence linking insulin resistance, another highly prevalent condition, and depressive disorders. The objectives of this study were to examine whether three surrogate measures of insulin resistance (high triglyceride-HDL [high-density lipoprotein] ratio; prediabetes, as indicated by fasting plasma glucose level; and high central adiposity, as measured by waist circumference) at the time of study enrollment were associated with an increased rate of incident major depressive disorder over a 9-year follow-up period and to assess whether the new onset of these surrogate measures during the first 2 years after study enrollment was predictive of incident major depressive disorder during the subsequent follow-up period. The Netherlands Study of Depression and Anxiety (NESDA) is a multisite longitudinal study of the course and consequences of depressive and anxiety disorders in adults. The study population comprised 601 NESDA participants (18-65 years old) without a lifetime history of depression or anxiety disorders. The study's outcome was incident major depressive disorder, defined using DSM-IV criteria. Exposure measures included triglyceride-HDL ratio, fasting plasma glucose level, and waist circumference. Fourteen percent of the sample developed major depressive disorder during follow-up. Cox proportional hazards models indicated that higher triglyceride-HDL ratio was positively associated with an increased risk for incident major depression (hazard ratio=1.89, 95% CI=1.15, 3.11), as were higher fasting plasma glucose levels (hazard ratio=1.37, 95% CI=1.05, 1.77) and higher waist circumference (hazard ratio=1.11 95% CI=1.01, 1.21). The development of prediabetes in the 2-year period after study enrollment was positively associated with incident major depressive disorder (hazard ratio=2.66, 95% CI=1.13, 6.27). The development of high triglyceride-HDL ratio and high central adiposity (cut-point ≥100 cm) in the same period was not associated with incident major depression. Three surrogate measures of insulin resistance positively predicted incident major depressive disorder in a 9-year follow-up period among adults with no history of depression or anxiety disorder. In addition, the development of prediabetes between enrollment and the 2-year study visit was positively associated with incident major depressive disorder. These findings may have utility for evaluating the risk for the development of major depression among patients with insulin resistance or metabolic pathology.

Association of Primary and Behavioral Health Integrated Care Upon Pediatric Mental Disorder Treatment.

The objective of this study was to examine whether linkage with mental health (MH) treatment differed across 3 different integrated care arrangements (ICAs), following incident attention deficit hyperactive disorder (ADHD) and major depressive disorder (MDD) diagnoses given by primary care providers (PCPs) in the pediatric setting. Using claims linking with multiple public data sources, we examined the treatment initiation among children receiving an incident diagnosis of ADHD or MDD from PCPs working in practices with various ICAs. ICAs were categorized as PCP practiced alone (non-co-located), PCP practiced with specialist outside the practice but co-located at the practice site (co-located), and employed specialists who were co-located (co-located and co-affiliated). A total of 4203 incident ADHD and 298 incident MDD cases diagnosed by PCPs were identified, of which 3123 (74%) with ADHD and 200 (67%) with MDD received treatment within 90 days since the diagnosis. Children diagnosed with ADHD by co-located and co-affiliated PCPs were twice as likely to receive treatment as those diagnosed by non-co-located PCPs (odds ratio [OR]=1.93; 95% confidence interval [CI], 1.24-2.78). Of those treated, children diagnosed by co-located and co-affiliated PCPs were 2 times more likely to receive guideline recommended psychotherapy (OR=2.15; 95% CI, 1.35-3.44). These patients were also more likely to be treated at the diagnosing site versus elsewhere. Similar beneficial effects were not observed in those first diagnosed by co-located but non-affiliated PCPs. Service co-location between co-affiliated PCPs and MH specialists was associated with significant higher ADHD treatment rate and the receipt of guideline-recommended psychotherapy.

Increased risk of major depressive disorder in sleep apnea patients in Taiwan

The association between sleep apnea (SA) and depression had been reported in a few previous studies. However, whether SA increases the risk of major depressive disorder (MDD) has not been studied comprehensively in a large-scale study. We performed this population-based cohort study to assess the association between SA and MDD. We identified adult patients having SA from the Taiwan National Health Insurance Research Database and excluded those having MDD before SA diagnosis. Thirty control subjects were randomly selected to match to each SA patient by age and sex. Totally, 10,259 SA patients were matched to 102,590 control subjects. The incidence rate and cumulative incidence of MDD were significantly higher in SA patients than in the control subjects (both p < 0.0001). Multivariable Cox regression analysis showed that SA remained an independent risk factor for incident MDD after adjusting for age, sex, residency, income level, and comorbidities (hazard ratio = 2.9 [95% CI 2.8–3.1], p < 0.0001). In summary, SA patients have an increased risk to develop MDD. Physicians caring for SA patients must pay attention to their psychosocial health status.

Prediction of Major Depressive Disorder Following Beta-Blocker Therapy in Patients with Cardiovascular Diseases.

Incident depression has been reported to be associated with poor prognosis in patients with cardiovascular disease (CVD), which might be associated with beta-blocker therapy. Because early detection and intervention can alleviate the severity of depression, we aimed to develop a machine learning (ML) model predicting the onset of major depressive disorder (MDD). A model based on L1 regularized logistic regression was trained against the South Korean nationwide administrative claims database to identify risk factors for the incident MDD after beta-blocker therapy in patients with CVD. We identified 50,397 patients initiating beta-blockers for CVD, with 774 patients developing MDD within 365 days after initiating beta-blocker therapy. An area under the receiver operating characteristic curve (AUC) of 0.74 was achieved. A history of non-selective beta-blockers and factors related to anxiety disorder, sleeping problems, and other chronic diseases were the most strong predictors. AUCs of 0.62–0.71 were achieved in the external validation conducted on six independent electronic health records and claims databases in the USA and South Korea. In conclusion, an ML model that identifies patients at high-risk for incident MDD was developed. Application of ML to identify susceptible patients for adverse events of treatment may serve as an important approach for personalized medicine.

1164 Prospective Associations Between Sleep Duration, Variability and Timing and Diseases from an Electronic Health Record Biobank in 24,065 Individuals

Abstract Introduction Implementation of electronic health records (EHR) across healthcare systems linking clinical to survey data has enabled systematic assessments of longitudinal relationships between sleep traits and diseases classified by PheWAS codes where ICD-9/10 codes are collapsed to categories based on clinical similarity. In the Partners Biobank, a hospital-based virtual cohort from Mass General Brigham in greater Boston, MA, we aimed to assess associations between sleep traits and incident diseases. Methods Self-reported weekday/weekend bed and wake times from a survey at consent were used to derive sleep traits. Incident diseases were defined as two incident PheWAS codes on separate dates ≥1y after consent. Cox proportional hazards models compared short (&amp;lt;7h) and long (≥9h) sleep duration, with 7-8h (referent group), adjusted for age, gender, race/ethnicity, and employment status, then further adjusted for BMI. Similarly, sleep midpoint (midpoint between weekend wake/bed times), sleep debt (difference in weekend/weekday sleep duration), and social jetlag (difference in weekend/weekday sleep midpoint) were assessed. Results The analytical sample consisted of 24,065 adults (mean sleep duration =8.12h) seeking regular care with sleep data. Participants had a total of 7,513,649 ICD codes of which incident 323,946 ICD codes mapped to 137,137 PheWAS codes. Over a median follow-up of 2.73 years (interquartile range: 1.82-3.98), participants sleeping &amp;lt;7h had a significantly higher risk of incident Acute pain [hazard ratio(95% confidence interval)=1.46(1.2-1.78)], Tobacco use disorder [1.42(1.18-1.71)], Sciatica [1.72(1.3-2.27)], and Edema [1.69(1.25-2.28)]. Each additional hour of later sleep midpoint and increased sleep debt and social jetlag associated with higher risk of incident Major depressive disorder [midpoint:1.30(1.14-1.49); debt:1.23(1.09-1.38); jetlag:1.54(1.27-1.84)]. Associations retained significance upon further adjustment for BMI, except for Edema, and no other associations were observed at the Bonferroni threshold (P=0.0125). Conclusion Our findings in a large hospital-based virtual cohort support unique inter-relationships between sleep duration/timing on somatic, behavioral, and mental health outcomes. Support H.S.D. and R.S. are supported by NIDDK grant R01DK107859. B.C. is supported by K01-HL135405-01. S.R. and R.S. are partially supported by R35 NHLBI HL 135816.

A temporal relationship between nonmedical opioid Use and major depression in the U.S.: A Prospective study from the National Epidemiological Survey on Alcohol and Related Conditions

BackgroundGiven the existing strong cross-sectional relationship between nonmedical opioid use (NMOU) and major depressive disorder (MDD), this study focused on the temporal relationship between NMOU and major depression. MethodsData sources were derived from Wave 1 and Wave 2 of the National Epidemiological Survey on Alcohol and Related Conditions. Logistic regression was applied to predicted NMOU at the follow-up survey based on baseline MDD diagnosis and symptoms of MDD among the sample without lifetime NMOU at baseline (N=32,982). In parallel, we examined the relationship between past year NMOU at baseline and new onset of MDD diagnosis (N=28,649) and between past year NMOU at baseline and new onset of symptoms of MDD (N=23,214) among people without major depression diagnosis or symptoms at baseline. ResultsMDD diagnosis (aOR=1.68, 95% CI=1.43, 1.98) and symptoms of major depression (aOR=1.25, 95% CI=1.14, 1.38) at baseline were associated with higher odds of incident NMOU. The baseline NMOU was associated with lower odds incident MDD diagnosis (aOR=0.79, 95%CI=0.66, 0.94) in the adjusted model. However, the baseline NMOU was associated with higher odds of new onset of major depressive symptoms at wave 2 in the sample without baseline symptoms of MDD (aOR=1.42, 95%CI=1.23, 1.63). ConclusionSymptoms of MDD and MDD diagnosis increased the new onset of NMOU, while NMOU only increased the risks of new onset of symptoms of MDD.

Physical frailty and the risk of major depressive disorder: The Irish Longitudinal Study on Ageing

Although frailty is a well-established risk factor for adverse health outcomes in later life, little is known about the role of physical frailty on the development of incident major depressive disorder (MDD). The purpose of this study was to determine whether frailty is an important and independent predictor of incident major depressive disorder (MDD) in elderly people without probable depression at baseline. Of the 3671 older individuals from the population-based Irish Longitudinal Study on Ageing, we classified participants as non-frail (0), pre-frail (1–2), and frail (3–5) at baseline according to the five criteria of the physical frailty phenotype. The World Health Organization Composite International Diagnostic Interview Short-Form was used to assess whether respondents fulfilled the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria for MDD over a 4-year follow-up. After adjusting for demographic factors, living arrangements, health behaviors, common chronic diseases including hypertension, diabetes, cancer, lung disease, heart problems, and stroke, those classified as pre-frail (HR = 1.40, 95%CI = 1.14–1.73) and frail (HR = 2.20, 95%CI = 1.23–3.92) presented a higher risk to develop incident MDD over the 4-year follow-up compared to non-frail participants. Shrinking and exhaustion, as physical frailty components, were individually predictive of onset of MDD. The present study supports a significant role of physical frailty as a predictor of incident MDD in older adults. It is necessary to identify groups with a high vulnerability for MDD according to easily identifiable frailty criteria, and to delay or prevent at least in part, some of the negative health outcomes related to this disorder.

Major Depressive Disorder Among HIV Infected Youth in Uganda: Incidence, Persistence and Their Predictors.

Incidence and persistence of major depressive disorder (MDD) in children and adolescents with HIV (CA-HIV) in Uganda is described. 1339 CA-HIV attending care were enrolled and followed up for 12months. MDD was assessed using the DSM-5 referenced Child and Adolescent Symptom Inventory-5 (CASI-5), with a prevalence for MDD at baseline of 5% (95% CI 3.3-7.3). Kaplan-Meir method was used to estimate incidence of MDD and Cox models were fitted to investigate predictors of incident MDD. Cumulative incidence of MDD over 12months was 7.6 per 100 person-years 95% CI (6.2-9.4) and a rate of persistent MDD of 10/105 (9.5% CI 3.9-15.1). Significant independent predictors of incident MDD were: highest educational level of CA-HIV (protective), increasing depressive scores and decreasing CD4 Nadir. These finding have implications for what should constitute components of a mental health integration model in HIV youth services and for the future development of individualised mental health care.

Subthreshold depression may exist on a spectrum with major depressive disorder: Evidence from gray matter volume and morphological brain network

BackgroundSubthreshold depression (StD) is a prevalent condition that may increase the risk of incident major depressive disorder (MDD). However, the relationship between StD and MDD remains unclear. MethodsA total of 153 adult subjects, including 53 drug-naive MDD, 50 StD and 50 healthy control (HC) subjects, underwent a T1-weighted magnetic resonance imaging scan, and the gray matter volume (GMV) alterations among the three groups were quantitatively analyzed using voxel-based morphometry (VBM). Then, to capture the whole-brain connectivity characteristics, we constructed morphological brain networks (MBN) based on the similarity among brain regions of individual VBM images and compared the network connection strengths among the three groups. ResultsThe StD and MDD subjects had similar patterns of GMV reductions in the orbitofrontal cortex and left temporal gyrus, although the magnitude of the reductions was smaller in StD subjects. Moreover, a total of 21 morphological connections were significantly different among the three groups. For the majority of the different connections (15/21), the connection strength of the StD group took an intermediate position between that of the MDD and HC groups. LimitationsThere is still a lack of a consistent definition of StD, and the age range of the subjects in this study was wide. Meanwhile the mechanisms and biological significance of the MBN remains to be clarified. ConclusionsThese results may support the hypothesis that depression is better expressed as a spectrum and that StD exists on a spectrum with MDD.