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.

Skin autofluorescence of advanced glycation end products and mortality in affective disorders in the lifelines cohort study: A mediation analysis.

OBJECTIVE: Life expectancy in patients suffering from affective disorders is considerably diminished. We investigated whether skin autofluorescence (SAF), indicating concentration of advanced glycation end products in the skin and oxidative stress, mediates the association between affective disorders and excess mortality. METHODS: Included were 81,041 participants of the Lifelines cohort study. Presence of major depressive disorder, dysthymia, generalised anxiety disorder, panic disorder or social phobia was assessed with the Mini-International Neuropsychiatric Interview. SAF was assessed as mediator in Cox proportional hazards models for all-cause or natural-cause mortality. RESULTS: Mortality was increased in cases with major depression compared to controls (36.4 vs. 22.5 per 100,000 person years). Partial mediation by SAF of the association between affective disorders and mortality was shown (9.0-10.5%, P<.001-.002), although attenuated by cardiometabolic parameters and history of physical illness. For major depressive disorder, partial mediation by 5.5-10.3% was shown (crude model: P<.001; fully adjusted model: P=.03). LIMITATIONS: The relatively short duration of follow-up and the relatively young cohort resulted in a lack of power to detect an association between mortality and dysthymia, social phobia and two or more comorbid disorders. CONCLUSION: Evidence of partial mediation by SAF of the association between affective disorders and all-cause and natural-cause mortality was demonstrated, although attenuated by health factors. For major depression, mediation by SAF was largest and remained significant after adjustment for sociodemographic and health factors, identifying oxidative stress as possible determinant of premature death.

The impact of psychiatric and medical comorbidity on the risk of mortality: a population-based analysis.

BACKGROUND: As life expectancy increases, more people have chronic psychiatric and medical health disorders. Comorbidity may increase the risk of premature mortality, an important challenge for health service delivery. METHODS: Population-based cohort study in Ontario, Canada of all 11 246 910 residents aged ⩾16 and <105 on 1 April 2012 and alive on 31 March 2014. Secondary analyses included subjects having common medical disorders in 10 separate cohorts. Exposures were psychiatric morbidity categories identified using aggregated diagnosis groups (ADGs) from Johns Hopkins Adjusted Clinical Groups software® (v10.0); ADG 25: Persistent/Recurrent unstable conditions; e.g. acute schizophrenic episode, major depressive disorder (recurrent episode), ADG 24: Persistent/Recurrent stable conditions; e.g. depressive disorder, paranoid personality disorder, ADG 23: Time-limited/minor conditions; e.g. adjustment reaction with brief depressive reaction. The outcome was all-cause mortality (April 2014-March 2016). RESULTS: Over 2 years' follow-up, there were 188 014 deaths (1.7%). ADG 25 conferred an almost threefold excess mortality after adjustment compared to having no psychiatric morbidity [adjusted hazard ratio 2.94 (95% CI 2.91-2.98, p < 0.0001)]. Adjusted hazard ratios for ADG 24 and ADG 23 were 1.12 (95% CI 1.11-1.14, p < 0.0001) and 1.31 (95% CI 1.26-1.36, p < 0.0001). In all 10 medical disorder cohorts, ADG 25 carried significantly greater mortality risk compared to no psychiatric comorbidity. CONCLUSIONS: Psychiatric disorders, particularly those graded persistent/recurrent and unstable, were associated with excess mortality in the whole population, and in the medical disorder cohorts examined. Future research should examine whether service design accounting for psychiatric disorder comorbidity improves outcomes across the spectrum of medical disorders.

The Prevalence of Suicidal Behaviour in Fibromyalgia Patients.

OBJECTIVE: Fibromyalgia (FM) is a condition associated with chronic pain in muscles and soft tissues. Extant literature has demonstrated an association between FM, mood symptoms and suicidal behaviour. This systematic review aims to synthesize available literature assessing the prevalence of suicidality in FM populations and qualitatively review the included articles. METHODS: PsycINFO, Google Scholar and PubMed databases were systematically searched for studies published from database inception to 15 February 2020. Studies were included that assessed FM as a primary or co-primary disease condition, as well as an assessment of suicidal behaviour (suicidal ideations (SI), suicide attempts (SA) and death by suicide (SC)). The quality of the studies was assessed using the Newcastle-Ottawa Scale. RESULTS: 699 unique articles were reviewed for eligibility. Data were derived from nine studies (cross-sectional: k = 5; retrospective cohort: k = 4) that assessed suicidal behaviour in FM participants (SI: k = 5, SC: k = 3, SA: k = 3). Four studies assessing SI found elevated rates of SI among FM participants. Three studies found elevated risk for SC and three studies found increased SA in FM participants relative to the general population. In two studies, this association was no longer significant after adjusting for depression and other psychiatric comorbidities. CONCLUSION: Preliminary findings suggest that FM is associated with significantly higher risks for SI, SA and SC compared to the general population. There may be unique risk factors underlying suicidal behaviour in FM patients and the interaction between FM and other known risk factors (i.e., mental illness) require further investigation.

Dose-response relationship between physical activity and mortality in adults with noncommunicable diseases: a systematic review and meta-analysis of prospective observational studies.

BACKGROUND: This study aims to investigate the relationship between post-diagnosis physical activity and mortality in patients with selected noncommunicable diseases, including breast cancer, lung cancer, type 2 diabetes, ischemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), osteoarthritis, low back pain and major depressive disorder. METHODS: A systematic search was conducted of PubMed, Scopus and the Web of Science from their inception to August 2018. Additionally, the search was updated in August 2019. Eligibility criteria included prospective observational studies examining the relationship between at least three physical activity categories (e.g. low, moderate, high) and all-cause mortality as the primary outcome. RESULTS: In total, 28 studies were included in the meta-analysis: 12 for breast cancer, 6 for type 2 diabetes, 8 for ischemic heart disease and 2 for COPD. The linear meta-analysis revealed that each 10 metabolic equivalent task hours increase of physical activity per week was associated with a 22% lower mortality rate in breast cancer patients (Summary Hazard Ratio [HR], 0.78; 95% CI: 0.71, 0.86; I2: 90.1%), 12% in ischemic heart disease patients (HR, 0.88; 95% CI: 0.83, 0.93; I2: 86.5%), 30% in COPD patients (HR, 0.70; 95% CI: 0.45, 1.09; I2: 94%) and 4% in type 2 diabetes patients (HR, 0.96; 95% CI: 0.93, 0.99; I2: 71.8%). There was indication of a non-linear association with mortality risk reductions even for low levels of activity, as well as a flattening of the curve at higher levels of activity. The certainty of evidence was low for breast cancer, type 2 diabetes and ischemic heart disease but only very low for COPD. CONCLUSION: Higher levels of post-diagnosis physical activity are associated with lower mortality rates in breast cancer, type 2 diabetes, ischemic heart disease and COPD patients, with indication of a no-threshold and non-linear dose-response pattern.

Prevalence and Prognostic Association of a Clinical Diagnosis of Depression in Adult Congenital Heart Disease: Results of the Boston Adult Congenital Heart Disease Biobank.

Background In adults with acquired heart disease, depression is common and associated with adverse outcomes. Depression may also be important in adults with congenital heart disease (CHD). Methods and Results We conducted a cohort study of outpatients with CHD, aged ≥18 years, enrolled in a prospective biobank between 2012 and 2017. Clinical data were extracted from medical records. Survival analysis assessed the relationship between depression, defined by a history of clinical diagnosis of major depression, with all-cause mortality and a composite outcome of death or nonelective cardiovascular hospitalization. A total of 1146 patients were enrolled (age, 38.5±13.8 years; 49.6% women). Depression had been diagnosed in 219 (prevalence=19.1%), and these patients were more likely to have severely complex CHD (41.3% versus 33.7%; P=0.028), cyanosis (12.1% versus 5.7%; P=0.003), and worse functional class (≥II; 33.3% versus 20.4%; P<0.0001), and to be taking antidepressant medication at time of enrollment (68.5% versus 5.7%; P<0.0001). Depression was associated with biomarkers indicative of inflammation (hsCRP [high-sensitivity C-reactive protein], 1.71 [25th-75th percentile, 0.82-4.47] versus 1.10 [0.45-2.40]; P<0.0001) and heart failure (NT-proBNP [N-terminal pro-B-type natriuretic peptide], 190 [92-501] versus 111 [45-264]; P<0.0001). During follow-up of 605±547 days, 137 participants (12.0%) experienced the composite outcome, including 33 deaths (2.9%). Depression was associated with increased risk for both all-cause mortality (multivariable hazard ratio, 3.0; 95% CI, 1.4-6.4; P=0.005) and the composite outcome (multivariable hazard ratio, 1.6; 95% CI, 1.1-2.5; P=0.025), adjusting for age, sex, history of atrial arrhythmia, systolic ventricular function, CHD complexity, and corrected QT interval. Conclusions In adults with CHD, major depression is associated with impaired functional status, heart failure, systemic inflammation, and increased risk for adverse outcomes.

Electroconvulsive therapy, depression severity and mortality: Data from the Danish National Patient Registry.

BACKGROUND: The effects of electroconvulsive therapy are usually estimated from changes in depression scales from studies with relatively small patient samples. Larger patient samples can be achieved from epidemiological registers, which provide information on other social and clinical predictors, results and risks. AIMS: To examine whether depression severity predicts the use of electroconvulsive therapy, risk of re-hospitalization, suicidal behaviour and mortality following electroconvulsive therapy in patients with major depression. METHODS: A cohort of 92,895 patients diagnosed with single or recurrent depression between 2005 and 2016 in the Danish National Patient Registry was followed for electroconvulsive therapy and adverse outcomes. Associations between electroconvulsive therapy and outcomes were analysed using Cox regression. RESULTS: A total of 5004 (5.4%) patients were treated with electroconvulsive therapy. Depression severity was the strongest predictor of electroconvulsive therapy. Electroconvulsive therapy was used more frequently above age 70, in those better educated or married, whereas comorbid alcohol abuse or history of prior stroke at study entry were associated with lower rates. Electroconvulsive therapy was associated with lower mortality. The adjusted hazard ratio for the association between electroconvulsive therapy and suicide in patients with mild depression was 6.99 (3.30-14.43), whereas it was 1.10 (0.55-2.20) in those with severe depression and psychotic symptoms. A similar pattern was seen for emergency contacts and attempted suicide. CONCLUSIONS: Electroconvulsive therapy was associated with lower all-cause mortality and the relative risk for re-hospitalization and attempted and committed suicide was lowest in patients with the most severe depression. Electroconvulsive therapy is an important treatment, with significant public health benefits, for patients with severe depression.

Depression may not be a risk factor for mortality in stroke patients with nonsurgical treatment: A retrospective case-controlled study.

Patients with depression have more comorbidities than those without depression. The cost of depression-associated comorbidities accounts for the largest portion of the growing cost of depression treatment. Patients with depression have a higher risk of stroke with poor prognoses than those without depression; however, previous studies evaluating the relationship between depression and stroke prognosis have not accounted for surgical treatment or other risk factors. Therefore, we investigated whether depression is a risk factor for mortality in stroke patients with nonsurgical treatment after adjusting for other risk factors.We retrospectively analyzed the data of patients with major depressive disorder (MDD) and age and sex-matched controls without MDD during 1999 to 2005. We then identified patients who developed stroke in both groups and analyzed risk factors for death in these stroke patients who received nonsurgical treatments during a follow-up period from 2006 to 2012.Patients with MDD had higher Charlson Comorbidity Index Scores (CCISs) and exhibited higher frequencies of comorbidities such as diabetes mellitus, hypertension, hyperlipidemia, and coronary heart disease than controls without MDD, and most of MDD patients had very low or high socioeconomic status (SES) and lived in urban settings. Most stroke patients with MDD who received nonsurgical treatment were female, had very low or high SES, and lived in urban settings; in addition, stroke patients with MDD who received nonsurgical treatment had higher CCISs and frequencies of hyperlipidemia and coronary heart disease than those without MDD who received nonsurgical treatment. However, depression was not a risk factor for death in stroke patients with nonsurgical treatment.Hemorrhagic stroke, age, sex, and CCISs were risk factors for death in stroke patients with nonsurgical treatment, but depression did not affect the mortality rate in these patients.

Major depressive episodes and mortality in the Canadian household population.

OBJECTIVE: To explore the association between major depressive episodes (MDE) and subsequent mortality in a representative sample of the general household population, with adjustment for other determinants of mortality. METHOD: The analysis used four datasets from the Canadian Community Health Survey (CCHS); the CCHS 1.1 (conducted in 2000 and 2001), the CCHS 1.2 (conducted in 2002), the CCHS 2.1 (conducted in 2003 and 2004) and the CCHS 3.1 (conducted in 2005 and 2006). Each survey included an assessment of past-year major depressive episodes (MDEs) and was linked to mortality data from the Canadian Mortality Database for January 1, 2000 to December 31, 2011. The hazard ratio (HR) for all-cause mortality was estimated in each survey sample. Random effects, individual-level meta-analysis was used to pool estimates from the four survey data sets. Estimates were adjusted for other determinants of mortality prior to pooling in order to help quantify the independent contribution of MDE to all-cause mortality. RESULTS: The unadjusted HR was 0.77 (95% CI 0.63-0.95). A naïve interpretation of this HR suggests a protective effect of MDE, but the estimate was found to be strongly confounded by age (age adjusted HR for MDE: 1.61, 95% CI 1. 34-1.93) and by sex (sex adjusted HR for MDE: 1.15, 95% CI 0.75-1.77). The age and sex adjusted HR was: 1.70 (95% CI 1.45-2.00). No evidence of effect modification by any determinant of mortality was found, including sex. After adjustment for a set of mortality risk factors, the pooled HR was weakened, but remained statistically significant, HR = 1.29 (I-squared = < 1%, tau-squared < 0.001, 95% CI 1.10-1.51). Smoking was the strongest single confounding variable. CONCLUSIONS: MDE is associated with elevated mortality. The elevated risk is partially attributable to psychosocial, behavioral and health-related determinants. Since MDE itself may have caused changes to these variables, these estimates cannot fully quantify the independent contribution of MDE to mortality. However, these results suggest that clinical and public health efforts to counteract the effect of MDE on mortality may benefit from attention to a broad set of mortality risk factors e.g. smoking, physical activity, management of medical conditions.

Depression and cause-specific mortality in an ethnically diverse cohort from the UK: 8-year prospective study.

BACKGROUND: Depression is associated with increased mortality, however, little is known about its variation by ethnicity. METHODS: We conducted a cohort study of individuals with ICD-10 unipolar depression from secondary mental healthcare, from an ethnically diverse location in southeast London, followed for 8 years (2007-2014) linked to death certificates. Age- and sex- standardised mortality ratios (SMRs), with the population of England and Wales as a standard population were derived. Hazard ratios (HRs) for mortality were derived through multivariable regression procedures. RESULTS: Data from 20 320 individuals contributing 91 635 person-years at risk with 2366 deaths were used for analyses. SMR for all-cause mortality in depression was 2.55(95% CI 2.45-2.65), with similar trends by ethnicity. Within the cohort with unipolar depression, adjusted HR (aHRs) for all-cause mortality in ethnic minority groups relative to the White British group were 0.62(95% CI 0.53-0.74) (Black Caribbean), 0.53(95% CI 0.39-0.72) (Black African) and 0.69(95% CI 0.52-0.90) (South Asian). Male sex and alcohol/substance misuse were associated with an increased all-cause mortality risk [aHR:1.94 (95% CI 1.68-2.24) and aHR:1.18 (95% CI 1.01-1.37) respectively], whereas comorbid anxiety was associated with a decreased risk [aHR: 0.72(95% CI 0.58-0.89)]. Similar associations were noted for natural-cause mortality. Alcohol/substance misuse and male sex were associated with a near-doubling in unnatural-cause mortality risk, whereas Black Caribbean individuals with depression had a reduced unnatural-cause mortality risk, relative to White British people with depression. CONCLUSIONS: Although individuals with depression experience an increased mortality risk, marked heterogeneity exists by ethnicity. Research and practice should focus on addressing tractable causes underlying increased mortality in depression.

The Impact of (the Concept of) Treatment-Resistant Depression: An Opinion Review.

Treatment-resistant depression refers to major depressive disorder, treatment of the disorder, and failure to obtain an "acceptable" outcome. Regarding the disorder, the heterogeneous concept of major depressive disorder and the multiple definitions of treatment-resistant depression, hesitating between a categorical and a more dimensional approach, as well as the divergence between diagnostic criteria and the items in the assessment scales are a source of confusion. Classifications do not take into account the dramatic influence of patient characteristics strongly impacting outcome, although these can be the cause of so-called pseudo-resistance. Outcome is the result of spontaneous evolution, nonspecific factors (including placebo), and active treatment factors. These should be differentiated to have a reliable estimation of the impact of different treatment modalities before we can asses treatment-resistant depression or before we can ascertain the (non)efficacy of treatments for treatment-resistant depression.The impact and burden of major depressive disorder and treatment-resistant depression are immense and go far beyond their economic cost. It is often forgotten that both are not only associated with increased suicidality but also with nonsuicidal mortality and that both can even result in requests for assisted dying. The caregiver burden and associated stigma are also too often overlooked despite that it has been suggested that they do influence (treatment) outcome.

Healthcare cost, service use and mortality in major psychiatric disorders in Taiwan.

BACKGROUND: We aimed to examine the differences in the cost distributions, service use, and mortality outcomes, across major psychiatric disorders in Taiwan. METHOD: A national cohort of adult patients (n = 68,068) who had newly received a diagnosis of schizophrenia, bipolar disorder, and major depressive disorder (MDD) was identified from the National Health Insurance Research Database and followed for the subsequent three years. Variations in the 1-year and 3-year healthcare cost distributions and mortality outcomes were examined according to age group (18-64 years, ≥65 years) and diagnosis. RESULTS: Regardless of age group, individuals with schizophrenia had the highest total and psychiatric healthcare costs. Healthcare costs for psychiatric services accounted for 84.25%, 60%, and 29.62% of the 1-year total healthcare costs for younger patients with a diagnosis of schizophrenia, bipolar disorder, and MDD, respectively. Psychiatric inpatient care costs constituted a major part of the 1-year psychiatric healthcare costs, e.g., 85.86% for schizophrenia patients aged 18-64 years, while psychiatric medication costs contributed to a relatively smaller part. For those older than 65 years, costs of other specialties for comorbid physical conditions were more prominent. LIMITATIONS: The perspective of the current analysis was limited to healthcare services, and we were not able to analyse wider economic impacts. CONCLUSIONS: Psychiatric inpatient care costs contributed to a significant share of psychiatric expenditures, emphasizing the need of developing strategies to reduce rehospitalisations. For those aged 65 years or older, efforts to improve interdisciplinary service care for comorbid physical conditions may be required.

Cost-Effectiveness of a Pharmacogenetic Test to Guide Treatment for Major Depressive Disorder.

BACKGROUND: Recent clinical trials indicate that pharmacogenetic-guided treatment of major depressive disorder (MDD) results in higher treatment response rates by genetically matching patients to medications and avoiding a trial-and-error process. OBJECTIVE: To evaluate the cost-effectiveness of a pharmacogenetic test (IDGx) that has demonstrated effectiveness compared with standard of care (SOC) medication management among patients with varied MDD severity. METHODS: Data from a large prospective, randomized controlled trial of treatment-naive patients or patients with inadequately controlled MDD in general practice and psychiatric treatment settings were used to build a Markov state-transition probability model. Analyses were conducted from the societal perspective. Treatment response rates, mortality rates, direct and indirect medical costs, and utility inputs were derived from the reference study and published scientific literature. The cost of the pharmacogenetic test was $2,000. A 3% discount rate was used to discount costs and effects. Univariate one-way sensitivity analyses were performed to determine the effect of input parameters on net monetary benefit. RESULTS: For moderate to severe MDD, the model estimated a cumulative effect over 3 years of 2.07 quality-adjusted life-years (QALYs) for the pharmacogenetic-guided treatment group and 1.97 QALYs for the SOC group, including a lower probability of death from suicide (0.328% and 0.351%, respectively). Total costs over 3 years were $44,697 (IDGx) and $47,295 (SOC). This difference includes a savings of $2,918 in direct medical costs and $1,680 in indirect costs. Results were more pronounced when only severely depressed patients were evaluated. CONCLUSIONS: Pharmacogenetic testing among moderate to severe MDD patients improved QALYs and resulted in cost savings. Sensitivity analyses supported the robust nature of the current findings of the dominant IDGx test to guide treatment. DISCLOSURES: Funding for this analysis was provided by AltheaDx, which is the manufacturer of the IDgenetix test. AltheaDx personnel assisted in the study design, data collection, and review of the manuscript. Maciel and Garces are employed by AltheaDx. Groessl has received funding as a consultant from American Specialty Health.

Mortality in unipolar depression preceding and following chronic somatic diseases.

OBJECTIVE: It is largely unknown how depression prior to and following somatic diseases affects mortality. Thus, we examined how the temporal order of depression and somatic diseases affects mortality risk. METHOD: Data were from a Danish population-based cohort from 1995 to 2013, which included all residents in Denmark during the study period (N = 4 984 912). Nineteen severe chronic somatic disorders from the Charlson Comorbidity Index were assessed. The date of first diagnosis of depression and somatic diseases was identified. Multivariable Cox proportional Hazard models with time-varying covariates were constructed to assess the risk for all-cause and non-suicide deaths for individual somatic diseases. RESULTS: For all somatic diseases, prior and/or subsequent depression conferred a significantly higher mortality risk. Prior depression was significantly associated with a higher mortality risk when compared to subsequent depression for 13 of the 19 somatic diseases assessed, with the largest difference observed for moderate/severe liver disease (HR = 2.08; 95% CI = 1.79-2.44), followed by metastatic solid tumor (HR = 1.48; 95% CI = 1.39-1.58), and myocardial infarction (HR = 1.40; 95% CI = 1.34-1.49). CONCLUSION: A particularly high mortality risk was observed in the presence of prior depression for most somatic diseases. Future studies that assess the underlying mechanisms are necessary to adequately address the excessive mortality associated with comorbid depression.

Secular trends in excess mortality of late-life depression.

BACKGROUND: Late-life depression is associated with premature mortality, however, little is known whether excess mortality rates of depression have changed over time. This study aims to identify and explain secular trends in excess mortality of major depressive disorder (MDD) and subthreshold depression (SUBD). METHODS: Cohort-sequential-longitudinal study of 4084 community-dwelling older adults in the Netherlands based on data from the Longitudinal Aging Study Amsterdam (LASA). Six measurement cycles were included from 1992/93 until 2008/09, each linked to the overall 5-year mortality, covering a 16-year time span. MDD and SUBD were identified using a two-stage screening procedure with the Center for Epidemiological Studies Depression Scale and the Diagnostic Interview Schedule. Age and sex were covariates. Education, health and lifestyle factors, and use of antidepressants were included as putative explanatory factors. Generalized Estimating Equations was used to investigate the association between the interaction 'Depression × Time' and 5-year mortality, and to find explanatory factors for the trend. RESULTS: A downward trend in excess mortality of MDD was found (OR = .92, 95%-CI:.85-.99, P = .04), adjusted for age and sex, which could not be explained by education, health and lifestyle factors, nor antidepressants use. Sex differences in the trend were not found (P = .77). No trend in excess mortality of SUBD was found (OR = 1.01, 95%-CI: .97-1.04, P = .65). LIMITATIONS: The findings do not imply a similar trend for other countries. CONCLUSIONS: The results indicate a favorable development in excess mortality of community-dwelling older adults with MDD, while those with SUBD do not show a clear trend in excess mortality.

Mortality risk associated with psychological distress and major depression: A population-based cohort study.

BACKGROUND: Few studies have examined the impact of psychological distress on mortality. We aimed to estimate mortality rates of psychological distress and major depressive disorder (MDD) compared to a referent group with no MDD or psychological distress. METHODS: Our study population (N = 10 181) consisted of respondents from the Canadian Community Health Survey Cycle 1.2 linked to Ontario health administrative databases followed for up to 11 years. We used Cox proportional hazards models to assess overall, sex-specific, as well as short-term (within two years of follow-up) and long-term (follow-up ≥ two years) mortality among those with DSM-criteria MDD and psychological distress independent of MDD adjusted for socio-demographic, lifestyle and clinical factors. RESULTS: Individuals with psychological distress (n = 666) had a similar mortality rate as those with MDD (n = 428) and significantly greater adjusted hazards of death than the referent group (hazard ratio = 1.57, 95% CI = 1.14-2.15). The risk of death was greatest in the short-term among those with MDD, however, we observed a persistent 1.6-fold increased risk in both the short- and long-term among those with psychological distress compared to the referent. Women with MDD had the greatest mortality rate and died a median of 15 years earlier than women in the referent group. LIMITATIONS: Psychological distress and MDD were ascertained at baseline with small number of deaths in the early follow-up period. Survey variables were prone to self-report bias with a possibility of residual confounding. CONCLUSIONS: Focused longitudinal research and targeted management strategies for those with psychological distress and women with MDD are warranted.

The Association Between Major Depressive Disorder and Outcomes in Older Veterans Hospitalized With Pneumonia.

BACKGROUND: Major depressive disorder ("depression") has been identified as an independent risk factor for mortality for many comorbid conditions, including heart failure, cancer and stroke. Major depressive disorder has also been linked to immune suppression by generating a chronic inflammatory state. However, the association between major depression and pneumonia has not been examined. The aim of this study was to examine the association between depression and outcomes, including mortality and intensive care unit admission, in Veterans hospitalized with pneumonia. MATERIALS AND METHODS: We conducted a retrospective national study using administrative data of patients hospitalized at any Veterans Administration acute care hospital. We included patients ≥65 years old hospitalized with pneumonia from 2002-2012. Depressed patients were further analyzed based on whether they were receiving medications to treat depression. We used generalized linear mixed effect models to examine the association of depression with the outcomes of interest after controlling for potential confounders. RESULTS: Patients with depression had a significantly higher 90-day mortality (odds ratio 1.12, 95% confidence interval 1.07-1.17) compared to patients without depression. Patients with untreated depression had a significantly higher 30-day (1.11, 1.04-1.20) and 90-day (1.20, 1.13-1.28) mortality, as well as significantly higher intensive care unit admission rates (1.12, 1.03-1.21), compared to patients with treated depression. CONCLUSION: For older veterans hospitalized with pneumonia, a concurrent diagnosis of major depressive disorder, and especially untreated depression, was associated with higher mortality. This highlights that untreated major depressive disorder is an independent risk factor for mortality for patients with pneumonia.

Neuropathy and presence of emotional distress and depression in longstanding diabetes: Results from the Canadian study of longevity in type 1 diabetes.

AIM: To determine the association of neuropathy and other complications with emotional distress and depression among patients with longstanding type 1 diabetes (T1DM). METHODS: Canadians with ≥50years of T1DM completed a questionnaire including assessment of distress and depression by the Problem Areas in Diabetes Scale (PAID) and Geriatric Depression Scale (GDS), respectively. Complications were determined using the Michigan Neuropathy Screening Instrument (Questionnaire Component), fundoscopy reports, renal function tests, and self-reported peripheral-(PVD) and cardiovascular (CVD) disease. Associations were analyzed by Poisson regression. RESULTS: Among 323 participants, 137 (42.4%) had neuropathy, 113 (36.5%) nephropathy, 207 (69.5%) retinopathy, 95 (29.4%) CVD, and 31 (9.8%) PVD. The neuropathy subgroup had higher prevalence of distress (13 (9.5%) vs. 6 (3.3%), p=0.029) and depression (34 (24.9%) vs. 12 (6.5%), p<0.001). Adjusting for diabetes complications, neuropathy was associated with higher PAID (adjusted RR 1.44 (95% CI 1.14-1.82), p=0.003) and GDS scores (adjusted RR1.57 (1.18-2.11), p=0.002). Independent of potential confounders, neuropathy remained associated with higher PAID (adjusted RR 1.39 (1.10-1.76), p=0.006) and GDS scores (adjusted RR 1.37 (1.03-1.83), p=0.032). Associations with neuropathy were not fully explained by neuropathic pain. CONCLUSION: Compared to other complications, neuropathy had the greatest association with distress and depression in longstanding T1DM, independent of pain. Strategies beyond pain management are needed to improve quality of life in diabetic neuropathy.

Pharmacological treatments and risk of readmission to hospital for unipolar depression in Finland: a nationwide cohort study.

BACKGROUND: Little is known about the comparative effectiveness of long-term pharmacological treatments for severe unipolar depression. We aimed to study the effectiveness of pharmacological treatments in relapse prevention in a nationwide cohort of patients who had been admitted to hospital at least once as a result of unipolar depression. METHODS: Our nationwide cohort study investigated the risk of readmission to hospital in 1996-2012 in all patients in Finland who had been admitted to hospital at least once for unipolar depression (without a diagnosis of schizophrenia or bipolar disorder) in Finland between Jan 1, 1987, and Dec 31, 2012. We used nationwide databases to obtain data for hospital admission, mortality, and dispensed medications. Exposure and non-exposure periods for medications were established using the PRE2DUP method. The primary analysis was within-individual analysis of readmission to hospital in the total cohort, in which each individual was used as his or her own control to eliminate selection bias. Putative survival and protopathic biases were controlled in sensitivity analyses. Since 33 independent statistical comparisons were done for specific medications, the level of statistical significance was set at p<0·0015. FINDINGS: Data from 123 712 patients were included in the total cohort, with a mean follow-up time of 7·9 years (SD 5·3). Lithium use was associated with a lower risk of re-admission to hospital for mental illness than was no lithium use (hazard ratio [HR] 0·47 [95% CI 0·40-0·55]; p<0·0001), whereas the groups of antidepressants (HR 1·10 [1·06-1·13]; p<0·0001) and antipsychotics (HR 1·16 [1·12-1·20]; p<0·0001) were not associated with a reduced risk of readmission to hospital. Risk of hospital readmission was lower during lithium therapy alone (HR 0·31 [0·21-0·47]; p<0·0001) than during use of lithium with antidepressants (HR 0·50 [0·43-0·59]; p<0·0001). After lithium, clozapine (HR 0·65 [0·46-0·90]; p=0·010) and amitriptyline (HR 0·75 [0·70-0·81]; p<0·0001) were the specific agents associated with the next lowest risk of readmission. In the sensitivity analyses controlling for survival and protopathic biases, all drugs were associated with lower rates of readmission to hospital than they were in the primary analysis, showing the same rank order in comparative effectiveness. The lowest mortality was observed during antidepressant use (HR 0·56 [0·54-0·58]; p<0·0001). INTERPRETATION: Our results indicate that lithium, especially without concomitant antidepressant use, is the pharmacological treatment associated with the lowest risk of hospital readmission for mental illness in patients with severe unipolar depression, and the outcomes for this measure related to antidepressants and antipsychotics are poorer than lithium. Lithium treatment should be considered for a wider population of severely depressed patients than those currently considered, taking into account its potential risks and side-effects. FUNDING: The Finnish Ministry of Health.

Assessing the presence of shared genetic architecture between Alzheimer's disease and major depressive disorder using genome-wide association data.

Major depressive disorder (MDD) and Alzheimer's disease (AD) are both common in older age and frequently co-occur. Numerous phenotypic studies based on clinical diagnoses suggest that a history of depression increases risk of subsequent AD, although the basis of this relationship is uncertain. Both illnesses are polygenic, and shared genetic risk factors could explain some of the observed association. We used genotype data to test whether MDD and AD have an overlapping polygenic architecture in two large population-based cohorts, Generation Scotland's Scottish Family Health Study (GS:SFHS; N=19 889) and UK Biobank (N=25 118), and whether age of depression onset influences any relationship. Using two complementary techniques, we found no evidence that the disorders are influenced by common genetic variants. Using linkage disequilibrium score regression with genome-wide association study (GWAS) summary statistics from the International Genomics of Alzheimer's Project, we report no significant genetic correlation between AD and MDD (rG=-0.103, P=0.59). Polygenic risk scores (PRS) generated using summary data from International Genomics of Alzheimer's Project (IGAP) and the Psychiatric Genomics Consortium were used to assess potential pleiotropy between the disorders. PRS for MDD were nominally associated with participant-recalled AD family history in GS:SFHS, although this association did not survive multiple comparison testing. AD PRS were not associated with depression status or late-onset depression, and a survival analysis showed no association between age of depression onset and genetic risk for AD. This study found no evidence to support a common polygenic structure for AD and MDD, suggesting that the comorbidity of these disorders is not explained by common genetic variants.