Bipolar disorder (BD) is characterized by mood fluctuations and is prone to misdiagnosis as major depressive disorder (MDD). Quantifying the relationship between symptom fluctuations and conversion risk is essential for early identification.

In a national prospective cohort of patients with MDD (enrolled from May 2022 to February 2025), depressive and manic symptoms were assessed using clinician-rated and self-report instruments. Two measures were calculated: the time in target range (TTR), the proportion of numbers of evaluations with scores below predefined clinical cutoffs; and Statistical Process Control (SPC) stability, evaluated with a person-specific approach defining each individual’s normal fluctuation range via their 25th–75th percentiles. The outcome was the incidence of manic or hypomanic episodes that met the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria. Cox regression models were used to evaluate the associations of the TTR and SPC with the conversion to BD.

Among the 2,367 eligible patients with MDD (mean [SD] age, 29.88 [9.79] years; 792 [33.46%] male), 69 (2.92%) converted to BD in the 52-week follow-up. During weeks 0-8, higher TTR of the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16) (cutoff set at ≤10) and the 33-item Hypomania Checklist (HCL-33) (cutoffs set at ≤7 and ≤15) were significantly associated with a lower risk of conversion between Weeks 8 and 52. Additionally, a greater SPC-evaluated stability of the HCL-33 scores was significantly associated with lower conversion risk over the same period.

While further validation in independent samples is still needed, continuous monitoring of hypomanic symptoms, especially evaluated with the HCL-33, may be of clinical significance for the early identification of conversion to BD.

To systematically identify and prioritize age- and sex-specific modifiable risk factors for incident depression, and to characterize integrated risk patterns to pinpoint high-risk populations across different life stages.

Using data from 428,078 participants in a cohort, incident depression was identified using hospital records. Cox proportional hazards models were applied to assess age- (the middle-aged, quinquagenarian and the elderly) and sex-specific (females and males) associations between modifiable risk factors and depression incidence. Population-attributable fractions (PAFs) prioritized predominant factors, and self-organizing maps (SOMs) visualized integrated risk patterns. Mendelian randomization (MR) analyses examined potential causal associations between top-ranked factors and depression risk.

During a mean follow-up of 13.11 years, 15,106 (3.53%) participants developed depression. Hazard ratios for modifiable factors were similar between sexes but varied by age. Generally, the overall PAFs decreased with age (PAF of 83.47% in the middle-aged, 82.96% in the quinquagenarian and 76.77% in the elderly). Health-related factors consistently showed the highest PAFs (33.46–38.12%) across all age subgroups and females, driven by weak grip strength (12.60–18.09%) and unhealthy body mass index (6.94–7.80%). Socioeconomic factors ranked first in males (24.55%), with unemployment contributing the most (9.27%). Lifestyle factors ranked second in younger groups and females, led by poor sleep quality and smoking. Environmental exposure and social support were the last two risk profiles across all subgroups, jointly contributing to about 12% of PAF. SOM integrated patterns predominated by less social support and low socioeconomic status increased depression risk up to 4.37-fold. Potential causal associations between the top five risk factors and depression were observed by MR analyses.

Health condition, socioeconomic status and lifestyle factors demonstrated stronger associations and greater PAFs for depression among relatively younger adults, pinpointing the importance of targeting these impactful factors from an earlier age.

Poor school achievement in comprehensive education (~ age 15) has been associated with the later risk of mental disorders, but it remains unclear whether school achievement in upper secondary education (~ age 18) is also associated with this risk. We examined whether school achievement in upper secondary education is associated with the later risk of mental disorders and whether school achievement in comprehensive education modifies these associations.

We studied all individuals born in Finland between 1980 and 2001 (N = 579 781). Individuals were followed from graduation from upper secondary education (ages 18–20) until first mental disorder diagnosis, emigration, death, or December 31, 2023. Matriculation examination grade point average (GPA) at the end of upper secondary education was the main exposure. Time to a mental disorder diagnosis was the outcome. Associations were estimated using Cox proportional hazards models, including sibling-stratified analyses and stratification across comprehensive education GPA groups.

Upper secondary GPA showed no consistent association with any mental disorder diagnosis as a broad category. Greater upper secondary GPA was generally associated with smaller risk of substance use disorders and greater risk of depression, anxiety, eating, and personality disorders. Reduction in GPA from comprehensive to upper secondary education was associated with greater risk of schizophrenia, and improvement with greater risk of bipolar disorder.

Associations between school achievement in upper secondary education and later mental disorders are disorder-specific, with higher school achievement associated with either an increased or decreased risk depending on the specific disorder.

Acute musculoskeletal pain is a common reason for emergency department (ED) care, but ED-based cohorts designed to support chronic pain prevention research remain limited. We evaluated first-year recruitment, retention, and baseline characterization in PREVENT, an ED-based observational cohort of adults with acute musculoskeletal pain.

We analyzed first-year data from PREVENT, conducted in an urban academic ED. Adults with acute neck or low back pain were screened and enrolled during the index ED visit. Feasibility outcomes included screening, eligibility, enrollment, and completion of 1-, 3-, and 6-month follow-up assessments. Baseline measures characterized pain-related cognition, psychological symptoms, function, and social needs. Social needs burden (SNB) was categorized as 0, 1, or ≥2 endorsed domains. Associations between SNB and baseline outcomes were examined using general linear models and Fisher’s exact tests.

Between January 21, 2025 and March 22, 2026, 439 individuals were screened, 81 were eligible, and 46 were enrolled. The most common reason for ineligibility was absence of a qualifying traumatic mechanism. Follow-up completion was 22.5% at 1 month, 13.2% at 3 months, and 17.9% at 6 months; 65% completed no follow-up assessments. At baseline, 58.5% endorsed at least one social need domain. Pain catastrophizing, fear of movement, low pain self-efficacy, maladaptive pain beliefs, and disability were common. Greater SNB was associated with higher pain-related distress, anxiety and depressive symptoms, and disability.

PREVENT demonstrated feasible ED-based recruitment and baseline phenotyping, while identifying retention challenges. Findings support refined follow-up procedures and risk-informed approaches to ED-initiated chronic pain prevention studies.

To identify resilience to trauma using longitudinal psychological assessments and uncover its genetic components.

This prospective cohort study included 12,946 surgical patients from the China Surgery and Anesthesia Cohort (CSAC) with assessments of depressive symptoms from pre-surgery through 1, 6, and 12 months post-surgery, using the 9-item Patient Health Questionnaire (PHQ-9). Linear mixed-effects models predicted post-surgery PHQ-9 scores; individuals with much lower observed PHQ-9 score than expected (i.e. lowest 25th percentile of residuals) were defined as resilient. We performed genome-wide association study (GWAS) analysis to identify variants associated with psychological resilience. We examined the identified variant in 2,285 patients from the China Severe Trauma Cohort (CSTC) using genotype stratification and additive models.

CSAC participants had a mean age of 52.2 years and 58.5% were female. Overall, 2,328 (18.0%) were identified as resilient and exhibited a lower prevalence of psychological symptoms. GWAS identified a lead single-nucleotide polymorphism (rs11766511, P = 3.082 × 10−8) mapped to the gene sidekick cell adhesion molecule 1 (SDK1), as a candidate locus implicating neural signaling pathways in stress response and resilience. In CSTC, genotype stratification suggested a lower symptom burden among GG genotype of rs11766511 compared with AA carriers (e.g. Beta = −0.94 [−1.76 to −0.12] for PHQ-9 score). The additive genetic model showed a directionally consistent but non-significant protective pattern of the G allele across psychological symptoms.

Longitudinal assessments of depressive symptoms offer a reliable method for measuring psychological resilience. The rs11766511 locus mapped to SDK1 may represent a candidate genetic signal for psychological resilience and warrants confirmation.

Although BMI is associated with sarcopenia, factors that modify this association are unclear. This study aimed to clarify how demographic and lifestyle factors affect the association between BMI and sarcopenia in middle-aged and older adults.

A 9-year follow-up study.

Community-based cohort in Japan.

A total of 6632 individuals aged 40–74 years participated in this study. BMI, demographic and lifestyle factors and disease history were assessed in a baseline survey conducted between 2011 and 2014. Sarcopenia was not assessed at baseline. Sarcopenia status was assessed based on the diagnostic criteria of the Asian Working Group for Sarcopenia 2019 during follow-up examinations conducted in 2021 and 2022. The OR for the presence of sarcopenia at follow-up was calculated using multivariable logistic regression analysis.

A lower BMI was associated with a higher odds of sarcopenia in both males and females (P for trend < 0·0001). Significant interactions were observed between BMI and age (P for interaction = 0·0003) and between BMI and physical activity (PA) level (P for interaction = 0·0272), in sarcopenia. Specifically, the odds of sarcopenia among underweight individuals (< 18·5 kg/m2) were significantly higher than that of their counterparts in the subgroup aged < 68 years and in the subgroup with high total PA (≥ 40·1 MET-h/d).

Low BMI is strongly associated with sarcopenia, and this relationship is modified by age and PA level. Specifically, the adverse impact of being underweight on sarcopenia was greater among middle-aged individuals and those with high PA levels.

Emerging evidence suggests that attention-deficit hyperactivity disorder (ADHD) may be associated with increased likelihood of experiencing interpersonal harm, including from intimate partners.

This study aims to test the long-term associations between ADHD traits in childhood and experiences of intimate partner violence (IPV) up to midlife (age 51 years).

Data were from the 1970 British Cohort Study, a nationally representative longitudinal study of people born during 1970. ADHD traits were assessed at age 10 years. Lifetime experience of five types of IPV was measured at age 51 years (harassment, economic abuse, physical violence, threats/coercive control, sexual violence). Regression models were used to test associations between childhood ADHD traits and midlife IPV, adjusting for gender, ethnicity and childhood social class.

Adjusted models showed that ADHD traits in childhood were associated with higher risk of experiencing any form of IPV, a greater number of different IPV experiences and all individual subtypes of IPV by age 51 years. Post-estimation showed that around one in seven men and one in four women without high ADHD traits experience some form of IPV by midlife. In people with high ADHD traits (4.40%), these estimates increase to approximately one in five men and one in three women.

Higher levels of childhood ADHD traits are associated with an increased risk of experiencing IPV by middle age. These findings highlight that ADHD may be associated with increased vulnerability to interpersonal harm in relationships. Identifying people with ADHD at greatest risk, as well as addressing the needs of people with ADHD within IPV prevention and response systems is important for reducing harm and addressing inequalities faced by people with ADHD over the life course.

Childhood maltreatment has been associated with increased risk of cognitive impairment in later life, but little is known about whether distinct joint trajectories of social isolation and depression across midlife predict this risk.

Using a prospective cohort design with documented childhood maltreatment and matched controls (N = 1196) followed from ages 0 to 11 into late midlife, we modelled joint trajectories of social isolation and depression (ages 29–47) using group-based trajectory modelling (GBTM) and examined their associations with cognitive impairment with no dementia (CIND) at age 59 through modified Poisson regression, controlling for risk factors related to neurodegenerative outcomes (i.e., hypertension, diabetes, obesity, limited physical activity, hearing impairment, smoking, excessive alcohol consumption and traumatic brain injury).

GBTM identified four groups: ‘Not isolated or depressed’ (67.7%), ‘Moderately isolated’ (11.7%), ‘Moderately depressed’ (16.5%) and ‘Chronically isolated and depressed’ (4.1%). Using the ‘Not isolated or depressed’ group as the reference category, membership in the highest-risk trajectory (‘Chronically isolated and depressed’) was associated with a 41.5% higher risk of CIND, whereas the ‘Moderately isolated’ and ‘Moderately depressed’ groups did not differ significantly from the reference group. Black non-Hispanic participants and those with documented childhood maltreatment histories had 32.8% and 21.2% higher risk of CIND, respectively, and each additional year of education was associated with a 4.9% reduction in CIND risk.

Sustained co-occurring social isolation and depression from early to mid-adulthood predicted increased risk of CIND independent of established risk factors, highlighting prolonged social and emotional difficulties as modifiable targets for late midlife cognitive health.

Research on the link between threat-related and deprivation-related adverse childhood experiences (ACEs) and the risk of gastrointestinal (GI) and liver diseases in later life remains limited. This study aims to evaluate the independent associations of threat-related and deprivation-related ACEs with the development of GI and liver disorders in middle-aged and older Chinese adults.

This prospective cohort study used data from the China Health and Retirement Longitudinal Study, which included participants aged 45 and older who had complete ACE data, two health assessments, and no pre-existing GI or liver conditions at baseline. Participants reported on five threat-related and deprivation-related ACEs before age 17. GI and liver diseases were classified based on self-reported physician diagnoses.

The outcomes of GI and liver diseases are based on self-reported physician diagnosis and broad categories. Compared with no exposures, participants with two or more threat-related ACEs exhibited a higher risk of both chronic liver disease (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.04–1.52; P = 0.016) and GI disease (HR, 1.36; 95% CI, 1.20–1.55; P < 0.001); two or more deprivation-related ACEs showed stronger associations with GI disease (HR, 1.48; 95% CI, 1.28–1.70; P < 0.001); and no significant associations with liver disease risk across all exposure levels. Additionally, depressive symptoms accounted for 10.7% (P = 0.003) of the association between threat-related ACEs and liver disease risk and accounted for 12.7% (P < 0.001) of the association between threat-related ACEs and GI disease risk. Midlife loneliness accounted for 5.3% (P = 0.001) of the association between threat-related ACEs and incident GI diseases and for 3.7% (P = 0.004) of the association between deprivation-related ACEs and incident GI diseases.

Threat-related ACEs are directly associated with an increased risk of liver and GI diseases. A modest proportion of this observed relationship is partially mediated through depressive symptoms and loneliness in middle age.

This study aimed to examine the association between protein intake and risk of sarcopenia, with a specific focus on protein sources, in middle-aged and older adults.

This was a 9-year follow-up study. Dietary protein intake was assessed by a validated FFQ with energy adjustment using the residual method. Sarcopenia was defined by using height-adjusted appendicular lean mass and grip strength. Adjusted OR for sarcopenia were calculated by multivariable logistic regression analysis.

Baseline surveys (2011–2014) for the Murakami and Uonuma cohorts assessed body size, lifestyle and medical history. Sarcopenia-related measurements were conducted in 2021–2022 in Murakami, Sekikawa, Uonuma and Minamiuonuma, Japan.

6232 individuals aged 40–74 years (mean age, 62·4 years; females, 54·8 %).

An inverse association between plant protein intake and sarcopenia was observed in males (Pfor trend = 0·018), although total and animal protein intakes were not. Animal-to-plant protein ratio was U-shaped in its association with sarcopenia; adjusted OR for the lowest and highest quintiles of the ratio compared to the middle quintile were 1·71 (95 % CI: 0·96, 3·07) and 1·97 (95 % CI: 1·10, 3·53), respectively, for males (Pfor quadratic term = 0·017), and 1·93 (95 % CI: 1·06, 3·51) and 1·65 (95 % CI: 0·90, 3·05), respectively, for females (Pfor quadratic term = 0·010).

An imbalanced intake of plant and animal proteins may increase the risk of sarcopenia, highlighting the importance of balanced protein intake.

Psychotic-like experiences (PLEs) are common in adolescence and often associated with later mental health difficulties. Although many psychosocial factors are related to PLEs, little is known about how these factors interact over time. Longitudinal network analysis allows examination of the stability of symptom associations and identification of potential intervention targets. This study investigated the structure and temporal stability of PLE networks in a large community-based adolescent cohort.

Adolescents aged 13–19 years (N = 605 with complete data across all time points) completed assessments at baseline, 12 months, and 24 months. Measures included positive and negative PLEs, cognitive biases, depression, anxiety, trauma, and interpersonal sensitivity. Networks were estimated at each time point, and permutation-based tests were used to compare network structure and overall connectivity across time. Centrality stability was assessed using bootstrapping procedures.

Network structures were stable across the 2-year period, with no significant differences in overall organization or connectivity between time points. Depression consistently showed the highest centrality, followed by anxiety and attributional bias. Positive PLEs were most strongly associated with anxiety, while negative PLEs showed their strongest associations with depression. Attributional bias remained centrally positioned and was strongly linked to trauma. All networks showed robust accuracy and high stability.

Despite considerable developmental change during adolescence, the psychosocial architecture of PLEs remained notably stable. Depression, anxiety, and attributional biases emerged as consistent key nodes, highlighting them as promising targets for prevention and early intervention in adolescents at risk for persistent PLEs.

Depression is often accompanied by multisystem comorbidities, but the time trajectories of these comorbidities remain unclear.

We aimed to define the temporal sequence of comorbidity accrual relative to depression diagnosis, and examine how this trajectory differs in recurrent depression.

A total of 32 953 individuals with depression were identified in the UK Biobank cohort, including 2402 with recurrent depression. The time between diagnosis of depression or recurrent depression and ten common comorbidities was established to determine the temporal order and rate of comorbidity diagnosis in relation to depression, based on the sequence of recorded diagnostic events. We further stratified the cohort by polygenic risk score, gender, age and history of antidepressant or antihypertensive medication use.

The study included 32 953 participants (mean age at diagnosis 52.6 years; 63.1% female). Hypertension and dorsopathies preceded depression diagnosis by a median of 2.6 years (interquartile range (IQR) −7.0 to 0.0) and 1.0 year (IQR −5.0 to 2.0), respectively. Alzheimer’s disease and obesity emerged after diagnosis at medians of 2.5 years (IQR 0.0–5.0) and 0.8 years (IQR −2.0 to 3.0). High genetic risk was associated with an earlier onset of pre-depression cardiometabolic conditions, with hypertension occurring 2.8 years before diagnosis in individuals with a high polygenic risk score compared with 2.3 years in individuals with a low polygenic risk score. Crucially, individuals with recurrent depression exhibited a profoundly different trajectory, with most comorbidities manifesting many years after the index diagnosis. Stratification by medication history indicated that antihypertensive drug use was associated with an earlier recorded diagnosis of cardiometabolic conditions, whereas antidepressant use was linked to a later diagnosis of neurodegenerative diseases.

These findings identify three critical windows for intervention and reveal a distinct, delayed comorbidity trajectory in recurrent depression. This underscores the need for long-term, integrated surveillance strategies tailored to depression subtype and treatment history.

Chronotype reflects individual variation in circadian rhythm (CR) (e.g., morningness versus eveningness). CR and chronotype have been associated with dementia pathology, and recent literature suggests that impaired sleep quality and CR disturbances may represent relevant causal factors for dementia. Current evidence is scarce and consists of just a small number of cross-sectional analyses and one longitudinal study. The aim of this study is to investigate the longitudinal association between chronotype and dementia risk in the older adult population, aged 60 years and older.

Linking data from the Lifelines Cohort Study and data from Vektis obtained by Statistics Netherlands led to a sample for analysis of n = 16,757 participants. Chronotype was measured with the Munich ChronoType Questionnaire (MCTQ) between 2011 and 2015. Chronotype was categorised into five categories: extremely early, slightly early, intermediate, slightly late, extremely late. Dementia incidence was based on having at least one dementia indicator from the Vektis dataset in the years 2018 until 2024. A discrete-time survival model was used to examine the association between chronotype and dementia. Age was specified as the underlying time scale in the discrete-time logistic survival analysis. Sex was included as a covariate. Interactions between age, sex, and educational attainment and chronotype were measured by including relevant interaction terms in the model.

The median age in the sample was 65 years old, and 54% was female. In total, 7% got dementia during a mean follow-up period of 6.6 years. Most individuals had an intermediate chronotype (56%), with about 20% of the individuals having a slightly early and late chronotype, and only about 3% having an extremely early and late chronotype. Individuals with a slightly early (HR, 1.26 [95% CI: 1.08, 1.46]) and an extremely late chronotype (HR, 1.42 [95% CI: 1.00, 2.02]) had an elevated risk of dementia. There were no significant interactions.

Having a slightly early as well as an extremely late chronotype was associated with an elevated risk of dementia.

Cohort studies of individuals with a suicide attempt are crucial for identifying risk and protective factors to prevent recurrence. The SURVIVE prospective cohort study aims to investigate the demographic and clinical profiles of individuals presenting with suicidal behaviour.

A total of 1,741 individuals (289 adolescents aged 12–17 and 1,443 adults aged 18 and older) were recruited from emergency departments at eight hospitals across five Spanish regions following a suicide attempt. Baseline data were collected using structured clinical interviews and validated self-report instruments. Sociodemographic and psychiatric variables were analysed.

Most participants were female, and approximately 20% were migrants. Religious affiliation was reported by 35.6% of adolescents and 48.4% of adults. Depression and anxiety were the most prevalent psychiatric diagnoses, while trauma-related and eating disorders were more frequent in adolescents, and substance use disorders in adults. Non-suicidal self-injury was reported by 76.6% of adolescents and 40.1% of adults. The most common method of attempt was self-poisoning in both groups. Psychotropic medication use was widespread, with both groups receiving a similar number of prescriptions.

The SURVIVE study provides a detailed characterization of suicide attempters in Spain, highlighting age-specific clinical patterns and contextual risk factors such as migration and religion. These findings underscore the need for tailored prevention strategies that consider developmental stage, psychiatric comorbidity, and social vulnerability.

Postinfectious autoimmune processes are hypothesized to be causally implicated in tic disorders, including Tourette syndrome and chronic tic disorder. However, this hypothesis remains controversial. In this nationwide cohort study, we aimed to clarify the mechanisms underlying the association between proneness to infections and tic disorders.

Using Swedish national registers, we identified 3,886,533 individuals (probands) born between 1970 and 2008 with available data on both biological parents. Probands were linked to six clusters of relatives: parents, full siblings, maternal half-siblings, paternal half-siblings, aunts/uncles, and cousins. Cox proportional hazards regression models were used to estimate the risk of tic disorders in probands exposed to infections and their relatives, compared with unexposed probands and their relatives. We also examined dose–response associations using logistic regression models.

Probands exposed to infections had an increased risk of tic disorders (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.40–1.52), as did their relatives. The observed risks increased with the degree of genetic relatedness, from HR (95% CI) of 1.15 (1.12–1.19) in cousins to 1.31 (1.25–1.37) in first-degree relatives. There was a dose–response association between the number of infections in the probands and the odds for tic disorders in the probands and their relatives. Results remained consistent after adjustment for infections in relatives, tic disorders in probands, and autoimmune diseases in probands and relatives.

Our results suggest an important role of shared genetic factors in the association between infections and tic disorders, potentially pointing to pleiotropic mechanisms.