The clinical course of major depressive disorder (MDD) is heterogeneous, and early-onset MDD often has a more severe and complex clinical course. Our goal was to determine whether polygenic scores (PGSs) for psychiatric disorders are associated with treatment trajectories in early-onset MDD treated in secondary care.

Data were drawn from the iPSYCH2015 sample, which includes all individuals born in Denmark between 1981 and 2008 who were treated in secondary care for depression between 1995 and 2015. We selected unrelated individuals of European ancestry with an MDD diagnosis between ages 10–25 (N = 10577). Seven-year trajectories of hospital contacts for depression were modeled using Latent Class Growth Analysis. Associations between PGS for MDD, bipolar disorder, schizophrenia, ADHD, and anorexia and trajectories of MDD contacts were modeled using multinomial logistic regressions.

We identified four trajectory patterns: brief contact (65%), prolonged initial contact (20%), later re-entry (8%), and persistent contact (7%). Relative to the brief contact trajectory, higher PGS for ADHD was associated with a decreased odds of membership in the prolonged initial contact (odds ratio = 1.06, 95% confidence interval = 1.01–1.11) and persistent contact (1.12, 1.03–1.21) trajectories, while PGS-AN was associated with increased odds of membership in the persistent contact trajectory (1.12, 1.03–1.21).

We found significant associations between polygenic liabilities for psychiatric disorders and treatment trajectories in patients with secondary-treated early-onset MDD. These findings help elucidate the relationship between a patient's genetics and their clinical course; however, the effect sizes are small and therefore unlikely to have predictive value in clinical settings.

General medical conditions (GMCs) often co-occur with mental and substance use disorders (MSDs).

To explore the contribution of GMCs to the burden of disease in people with MSDs, and investigate how this varied by age.

A population-based cohort of 6 988 507 persons living in Denmark during 2000–2015 followed for up to 16 years. Danish health registers were used to identify people with MSDs and GMCs. For each MSD, years lived with disability and health loss proportion (HeLP) were estimated for comorbid MSDs and GMCs, using a multiplicative model for disability weights.

Those with any MSD lost the equivalent of 43% of healthy life (HeLP = 0.43, 95% CI 0.40–0.44) after including information on GMCs, which was an increase from 25% before including GMCs (HeLP = 0.25, 95% CI 0.23–0.27). Schizophrenia was associated with the highest burden of disease (HeLP = 0.77, 95% CI 0.68–0.85). However, within each disorder, the relative contribution of MSDs and GMCs varied. For example, in those diagnosed with schizophrenia, MSDs and GMCs accounted for 86% and 14% of the total health loss; in contrast, in those with anxiety disorders, the same proportions were 59% and 41%. In general, HeLP increased with age, and was mainly associated with increasing rates of pulmonary, musculoskeletal and circulatory diseases.

In those with mental disorders, the relative contribution of comorbid GMCs to the non-fatal burden of disease increases with age. GMCs contribute substantially to the non-fatal burden of disease in those with MSDs.

Major depressive disorder (MDD) is characterised by a recurrent course and high comorbidity rates. A lifespan perspective may therefore provide important information regarding health outcomes. The aim of the present study is to examine mental disorders that preceded 12-month MDD diagnosis and the impact of these disorders on depression outcomes.

Data came from 29 cross-sectional community epidemiological surveys of adults in 27 countries (n = 80 190). The Composite International Diagnostic Interview (CIDI) was used to assess 12-month MDD and lifetime DSM-IV disorders with onset prior to the respondent's age at interview. Disorders were grouped into depressive distress disorders, non-depressive distress disorders, fear disorders and externalising disorders. Depression outcomes included 12-month suicidality, days out of role and impairment in role functioning.

Among respondents with 12-month MDD, 94.9% (s.e. = 0.4) had at least one prior disorder (including previous MDD), and 64.6% (s.e. = 0.9) had at least one prior, non-MDD disorder. Previous non-depressive distress, fear and externalising disorders, but not depressive distress disorders, predicted higher impairment (OR = 1.4–1.6) and suicidality (OR = 1.5–2.5), after adjustment for sociodemographic variables. Further adjustment for MDD characteristics weakened, but did not eliminate, these associations. Associations were largely driven by current comorbidities, but both remitted and current externalising disorders predicted suicidality among respondents with 12-month MDD.

These results illustrate the importance of careful psychiatric history taking regarding current anxiety disorders and lifetime externalising disorders in individuals with MDD.

The most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries.

Face-to-face interviews with community samples totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents.

3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2–4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness.

ADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population sample from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them.

Comorbidity with general medical conditions is common in individuals with eating disorders. Many previous studies do not evaluate types of eating disorder.

To provide relative and absolute risks of bidirectional associations between (a) anorexia nervosa, bulimia nervosa and eating disorders not otherwise specified and (b) 12 general medical conditions.

We included all people born in Denmark between 1977 and 2010. We collected information on eating disorders and considered the risk of subsequent medical conditions, using Cox proportional hazards regression. Absolute risks were calculated using competing risks survival analyses. We also considered risks for prior medical conditions and subsequent eating disorders.

An increased risk was seen for almost all disorder pairs (69 of 70). Hazard ratios for those with a prior eating disorder receiving a subsequent diagnosis of a medical condition ranged from 0.94 (95% CI 0.57−1.55) to 2.05 (95% CI 1.86−2.27). For those with a prior medical condition, hazard ratios for later eating disorders ranged from 1.35 (95% CI 1.26–1.45) to 1.98 (95% CI 1.71–2.28). Absolute risks for most later disorders were increased for persons with prior disorders, compared with reference groups.

This is the largest and most detailed examination of eating disorder–medical condition comorbidity. The findings indicate that medical condition comorbidity is increased among those with eating disorders and vice versa. Although there was some variation in comorbidity observed across eating disorder types, magnitudes of relative risks did not differ greatly.

Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner.

In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16.

Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline.

These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.

This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.

We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.

Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.

These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.

Previous work has identified associations between psychotic experiences (PEs) and general medical conditions (GMCs), but their temporal direction remains unclear as does the extent to which they are independent of comorbid mental disorders.

In total, 28 002 adults in 16 countries from the WHO World Mental Health (WMH) Surveys were assessed for PEs, GMCs and 21 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders. Discrete-time survival analyses were used to estimate the associations between PEs and GMCs with various adjustments.

After adjustment for comorbid mental disorders, temporally prior PEs were significantly associated with subsequent onset of 8/12 GMCs (arthritis, back or neck pain, frequent or severe headache, other chronic pain, heart disease, high blood pressure, diabetes and peptic ulcer) with odds ratios (ORs) ranging from 1.3 [95% confidence interval (CI) 1.1–1.5] to 1.9 (95% CI 1.4–2.4). In contrast, only three GMCs (frequent or severe headache, other chronic pain and asthma) were significantly associated with subsequent onset of PEs after adjustment for comorbid GMCs and mental disorders, with ORs ranging from 1.5 (95% CI 1.2–1.9) to 1.7 (95% CI 1.2–2.4).

PEs were associated with the subsequent onset of a wide range of GMCs, independent of comorbid mental disorders. There were also associations between some medical conditions (particularly those involving chronic pain) and subsequent PEs. Although these findings will need to be confirmed in prospective studies, clinicians should be aware that psychotic symptoms may be risk markers for a wide range of adverse health outcomes. Whether PEs are causal risk factors will require further research.

There is growing interest in linking vitamin D deficiency with autism spectrum disorders (ASDs). The association between vitamin D deficiency during gestation, a critical period in neurodevelopment, and ASD is not well understood.

To determine the association between gestational vitamin D status and ASD.

Based on a birth cohort (n=4334), we examined the association between 25-hydroxyvitamin D (25OHD), assessed from both maternal mid-gestation sera and neonatal sera, and ASD (defined by clinical records; n=68 cases).

Individuals in the 25OHD-deficient group at mid-gestation had more than twofold increased risk of ASD (odds ratio (OR)=2.42, 95% confidence interval (CI) 1.09 to 5.07, P=0.03) compared with the sufficient group. The findings persisted in analyses including children of European ethnicity only.

Mid-gestational vitamin D deficiency was associated with an increased risk of ASD. Because gestational vitamin D deficiency is readily preventable with safe, inexpensive and readily available supplementation, this risk factor warrants closer scrutiny.

Traumatic events are associated with increased risk of psychotic experiences, but it is unclear whether this association is explained by mental disorders prior to psychotic experience onset.

To investigate the associations between traumatic events and subsequent psychotic experience onset after adjusting for post-traumatic stress disorder and other mental disorders.

We assessed 29 traumatic event types and psychotic experiences from the World Mental Health surveys and examined the associations of traumatic events with subsequent psychotic experience onset with and without adjustments for mental disorders.

Respondents with any traumatic events had three times the odds of other respondents of subsequently developing psychotic experiences (OR=3.1, 95% CI 2.7–3.7), with variability in strength of association across traumatic event types. These associations persisted after adjustment for mental disorders.

Exposure to traumatic events predicts subsequent onset of psychotic experiences even after adjusting for comorbid mental disorders.