Depression exhibits significant heterogeneity in its genetic underpinnings. The role of genetic components in the development of depression and its comorbidities remains insufficiently explored.

First, depression risk loci from a large-scale genome-wide meta-analysis were annotated to Gene Ontology (GO) terms by functional enrichment. GO-based polygenic risk scores (GO-PRS) were then calculated for individuals in the UK Biobank. Principal component analysis (PCA) was applied for dimensionality reduction, followed by cluster analysis to identify genetic subtypes of depression. Multistate models were applied to assess the impact of genetic patterns on the trajectory from healthy status to incident depression, and depression to 26 subsequent diseases, as well as the associations between environmental factors and disease trajectories across genetic subtypes.

Participants were categorized into three genetic subtypes: immune-dominant, neuro-dominant, and comprehensive-risk. Significant differences in risk of depression and subsequent diseases, and susceptibility to environmental factors were observed across subtypes. Comprehensive-risk subtype showed higher risks of depression compared to immune-dominant (HR: 1.10, 95% CI: 1.05–1.15) and neuro-dominant subtype (HR: 1.12, 95% CI: 1.08–1.16). Comprehensive-risk subtype exhibited higher risks of transition from depression to subsequent diseases, such as anemia compared to immune-dominant subtype, and diseases of the digestive system compared to neuro-dominant subtype. Environmental factors were more strongly associated with the transition from depression to subsequent diseases in immune-dominant and comprehensive-risk subtypes, including cardiovascular, respiratory, and metabolic diseases.

Our findings highlight the genetic heterogeneity of depression and comorbidities, and shed light on how genetic components modulate responses to environmental factors.

Childhood irritability and harsh parenting are associated with youth suicide attempts. Parents’ harsh reactions have been associated with children’s irritable behavior. While studies have shown individual associations of irritability and parenting behaviors with suicide risk, few have considered these factors jointly. We aimed to identify profiles of children based on irritability and parenting during childhood and examine their associations with youth suicide attempt.

Participants (N = 1626) were from the Québec Longitudinal Study of Child Development. Mothers reported on childhood irritability, harsh parenting, and positive parenting between ages 3.5 and 8; youth self-reported suicide attempt between ages 13 and 23.

We identified four profiles based on the joint development of irritability and parenting during childhood: (1) low irritability, low harsh parenting, and high positive parenting (30.3%); (2) moderate irritability, moderate harsh parenting, and high positive parenting (28.4%); (3) moderate irritability, moderate harsh parenting, and low positive parenting (26.6%); and (4) high irritability, high harsh parenting, and low positive parenting (14.8%). In logistic regression analyses, only children in the high irritability, high harsh parenting, and low positive parenting profile had higher odds of attempting suicide (OR = 2.51; 95% CI = 1.55–4.09) compared to those in the low irritability, low harsh parenting, and high positive parenting profile. This association remained significant (OR = 1.80; 95% CI = 1.03–3.15) in models adjusting for covariates.

Children with chronically high irritability were also those experiencing the harshest parenting and the least positive parenting, as well as those most at risk of suicide attempt. Targeting both child and parental behavior may maximize suicide prevention efforts among children with high irritability.

The months following psychiatric hospitalization are associated with heightened suicide risk among adolescents. Better characterizing predictors of trajectories of suicidal ideation (SI) post-discharge is critical.

We examined trajectories of SI over 18 months post-discharge and emotional processing variables (recognition, reactivity, and regulation) as predictors using a multi-method approach. Participants were 180 adolescents recruited from a pediatric psychiatric inpatient unit, assessed during hospitalization and 3, 6, 12, and 18-months post-discharge. At each time-point, participants reported on SI; at baseline, they completed measures of emotion dysregulation, reactivity, and a behavioral task measuring facial emotion recognition.

A three-group model best fits the data (Chronic SI, Declining SI, and Subthreshold SI groups). The Chronic SI group, compared to the Declining SI group, had greater difficulty identifying children’s sad facial expressions. The Declining SI group compared to the Subthreshold SI group reported greater overall emotion dysregulation and difficulties engaging in goal-directed behavior. No other emotional processing variable was significantly associated with specific SI trajectories.

The findings suggest that difficulties in properly identifying peer emotions may be predictive of resolution of severe SI post-discharge. Furthermore, the results suggest that emotion regulation may be an important target for discharge planning.

Little is known about the diagnostic trajectories following a first psychiatric diagnosis in childhood or adolescence. Such knowledge could aid clinicians in treatment, risk prediction, and psychoeducation. This study presents a comprehensive nationwide overview of diagnostic trajectories in children and adolescents after their first diagnosis in child and adolescent psychiatric hospitals.

Patients aged 0 to 17 years who received their first psychiatric diagnosis between January 1996 and December 2011 were identified through the Danish National Patient Registries. Shifts at the International Classification of Diseases (ICD-10) two-cipher level (F00-F99), grouped into 19 categories, were identified. Subsequent diagnoses during 10 years of follow-up until December 2021 were identified and analyzed using state sequence analysis and Cox proportional hazard regression models.

A total of 77,464 children and adolescents (32,733 [42.26%] girls) were identified with a first-time psychiatric diagnosis. Among these, 46.7% of girls and 37.6% of boys had at least one diagnostic shift after 10 years of follow-up. High entropy and low diagnostic stability were found in first-time diagnoses often presenting in adolescence, such as affective disorders, psychotic illness, and personality disorders, while lower entropy and high diagnostic stability were found in neurodevelopmental disorders and eating disorders. For most categories, girls had higher mean entropy measures than boys (P < 0.05).

Diagnostic shifts are common in child and adolescent psychiatric services, particularly when the first contact occurs in adolescence. Adequate focus on psychoeducation about emerging diagnostic shifts, and on timely detection, particularly in girls, and particularly in adolescence, is warranted.

The association between negative wealth shocks and depression among middle-aged and older individuals remains unclear. Our study aimed to assess the association between negative wealth shocks and depression and its trajectories, and to explore cross-national differences in these associations

Our sample included 21 999 participants, of which 9519 were from the Health and Retirement Study (2012–2020), 4936 from the English Longitudinal Study of Ageing (2012–2020), 2520 from the China Health and Retirement Longitudinal Study (2011–2020), and 5024 from the Mexican Health and Aging Study (2012–2021). We used latent class trajectory models to identify depressive trajectories, alongside mixed-model logistic regression and multinomial logistic regression to evaluate associations.

In the USA (OR 1.73, 95% CI 1.40–2.16), England (OR 1.71, 95% CI 1.09–2.70), and China (OR 1.38, 95% CI 1.09–1.75), negative wealth shocks were associated with subsequent depressive symptoms, but not in Mexico (OR 1.06, 95% CI 0.86–1.29). Additionally, negative wealth shocks were associated with several depressive trajectories in the USA and China. This association occurred only in increasing–decreasing trajectory in England, while no significant association was found across any trajectory in Mexico.

Negative wealth shocks were associated with subsequent depressive symptoms, with significant associations observed in some specific depressive trajectories. These associations exhibited cross-national differences, underscoring the importance of considering country-specific contexts when addressing the mental health impacts of wealth shocks.

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.

Emotional problems, especially anxiety, have become increasingly common in recent generations. Few population-based studies have examined trajectories of emotional problems from early childhood to late adolescence or investigated differences in psychiatric and functional outcomes.

Using the Avon Longitudinal Study of Parents and Children (ALSPAC, n = 8286, 50.4% male), we modeled latent class growth trajectories of emotional problems, using the parent-reported Strength and Difficulties Questionnaire emotional scale (SDQ-E) on seven occasions (4–17 years). Psychiatric outcomes in young adulthood (21–25 years) were major depressive disorder (MDD), generalized anxiety disorder (GAD), and self-harm. Functional outcomes were exam attainment, educational/occupational status, and social relationship quality.

We identified four classes of emotional problems: low (67.0%), decreasing (18.4%), increasing (8.9%), and persistent (5.7%) problems. Compared to those in the low class, individuals with decreasing emotional problems were not at elevated risk of any poor adult outcome. Individuals in the increasing and persistent classes had a greater risk of adult MDD (RR: 1.59 95% CI 1.13–2.26 and RR: 2.25 95% CI 1.49–3.41) and self-harm (RR: 2.37 95% CI 1.91–2.94 and RR: 1.87 95% CI 1.41–2.48), and of impairment in functional domains. Childhood sleep difficulties, irritability, conduct and neurodevelopmental problems, and family adversity were associated with a persistent course of emotional problems.

Childhood emotional problems were common, but those whose symptoms improved over time were not at increased risk for adverse adult outcomes. In contrast, individuals with persistent or adolescent-increasing emotional problems had a higher risk of mental ill-health and social impairment in young adulthood which was especially pronounced for those with persistent emotional problems.

Patients with remitted psychosis wish to reduce antipsychotic doses yet facing increased risks of relapse. Examining dose-tapering processes may provide insights to re-evaluate the risk-to-benefit balance. We aimed to depict and subgroup tapering trajectories, and explore factors associated with different dose-reduction patterns.

A 2-year open-label randomized prospective comparative trial from August 2017 to September 2022 in Taiwan. Patients with a history of schizophrenia-related psychotic disorders under stable medications and symptoms were eligible, randomizing a proportion to conduct guided dose reduction. We depicted the trajectories of individual patients and named subgroups based on dose-tapering patterns. Predictors of baseline characteristics for designated subgroups were examined by logistic regression analysis; changes in outcomes were compared by paired t-test.

Fifty-one patients undergoing guided dose reduction, 18 (35.3%) reduced 4 steps consecutively (sequential reducers, SR), 14 (27.5%) reduced 1 to 3 steps (modest reducers, MR), 3 (5.9%) re-escalated to previous level (alert reducers, AR), 7 (13.7%) returned to baseline level (baseline returners, BR), 6 (11.7%) relapsed (failed reducers, FR) and 3 (5.9%) withdrew without relapse (early exits, EE). Patients with a history of relapse assumed a conservative dose-tapering pace; only the SR subgroup exhibited significant improvements in functioning and quality of life while failing to identify variables for predicting who would become SR or FR.

Guided dose reduction comprises dynamic processes with differences between individual trajectories. The proposed naming of dose-tapering patterns/subgroups provides a framework depicting patients undergoing dose-tapering. Longer-term observation and more flexible tapering approaches are anticipated to reveal favorable outcomes.

Nonsuicidal self-injury (NSSI) is prevalent in adolescent clinical samples. There is evidence that NSSI can be treated effectively but data on individual treatment outcomes is limited. The goal of this study was to examine response, remission, exacerbation, and relapse rates over one and two years, respectively, among a clinical sample of adolescents with NSSI. Furthermore, we aimed to identify clinically relevant predictors of NSSI trajectories.

The sample consists of n = 203 adolescents (12–17 y., 94% female) from a specialized outpatient clinic for risk-taking and self-harming behavior with NSSI on at least five days in the six months before first assessment. Assessments were completed at baseline and one (FU1) and two (FU2) years later using structured clinical interviews and self-report questionnaires.

At FU1, 75% reported a reduction in NSSI frequency by at least 50% (treatment response); among those, one third (25% of the entire sample) achieved a remission (0 NSSI); an exacerbation (⩾50% more NSSI) was observed in 11% of patients. Of those in remission, 41% relapsed one year later. Predictors of non-response or non-remission were inpatient treatment and depressive symptoms. Adolescents with lower NSSI frequency at baseline had a higher risk of exacerbation. Due to limited sample size at FU2 no prediction model for relapse was established.

While most adolescents presenting with NSSI achieved significant improvement, more attention should be paid to the rather low rates of full remission. Prediction and early detection of individuals who deteriorate during or relapse after treatment is critical.