JAMA Psychiatry最新文献

Importance: Research suggests an increase in mental disorder incidence in recent years, but this trend remains unexplained, and there is a lack of large studies based on a representative sample that investigate mental disorders over the full spectrum.

Objective: To explore sex- and age-specific incidence of any mental disorder and 19 specific disorders according to birth cohort and calendar period.

Design, setting, and participants: This was a population-based cohort study among 5 936 202 individuals aged 1 to 80 years living in Denmark at some point between January 1, 2004, and December 31, 2021. Data were derived from the Danish Civil Registration System and analyzed from February to August 2024.

Exposures: Birth cohort (8 categories from 1924 to 2011) and calendar period (six 3-year categories from 2004 to 2021).

Main outcomes and measures: Incidence rates of mental disorders from 2004 to 2021 by sex and age, according to birth cohort and calendar period, including the first years of the COVID-19 pandemic, using Danish health register data.

Results: The population comprised 2 933 857 female individuals and 3 002 345 male individuals, who were followed up for 83.8 million person-years, with median ages at start and end of follow-up of 30.2 and 46.2 years, respectively. There was an overall mental disorder incidence rate of 55.27 every 10 000 person-years. For diagnoses of any mental disorder, higher incidence rates were observed for more recent birth cohorts and calendar periods in the younger ages. Over older ages, incidence rates did not vary so greatly. An increase was observed in rates of most types of mental disorders, especially among young people, and decreases for other types (eg, substance use disorders). Prominent sex differences were also observed. For example, for schizophrenia, a large increase was seen in incidence rates for female individuals in more recent birth cohorts at younger ages, but no change for male individuals, leading to a higher peak incidence for female individuals than for male individuals in the most recent periods. For personality disorders, a large increase was observed in incidence for female individuals over time and a slight decrease for male individuals.

Conclusions and relevance: This comprehensive investigation of mental disorders incidence in Denmark indicates sex- and age-specific patterns according to birth cohorts and calendar periods. While trends may partly be explained by increases in incidence, several other factors may contribute, such as diagnostic practices, health sector capacity, and risk factors for mental disorders.

Importance: Exposure to war is associated with poor mental health outcomes. Adverse and traumatic experiences can lead to long-lasting DNA methylation changes, potentially mediating the link between adversity and mental health. To date, limited studies have investigated the impact of war on DNA methylation in children or adolescents, hampering our understanding of the biological impact of war exposure.

Objective: To identify salivary DNA methylation differences associated with war exposure in refugee children and adolescents.

Design, setting, and participants: This cohort study included Syrian refugee children and adolescents, and their primary caregiver were recruited from tented settlements in Lebanon. Data collection was carried out in 2 waves, 1 year apart, from October 2017 to January 2018 and October 2018 to January 2019. Children and their caregiver were interviewed, and children provided saliva samples for DNA extraction. Data analysis was conducted in 2022, 2023, and 2024.

Exposure: War exposure assessed by interviewing children and their caregiver using the War Events Questionnaire.

Main outcomes and measures: Salivary DNA methylation levels were assayed with the Infinium MethylationEPIC BeadChip (Illumina). Epigenetic aging acceleration was estimated using a set of preexisting epigenetic aging clocks. A literature search was conducted to identify previously reported DNA methylation correlates of childhood trauma.

Results: The study population included 1507 children and adolescents (mean [SD] age, 11.3 [2.4] years; age range, 6-19 years; 793 female [52.6%]). A total of 1449 children provided saliva samples for DNA extraction in year 1, and 872 children provided samples in year 2. Children who reported war events had a number of differentially methylated sites and regions. Enrichment analyses indicated an enrichment of gene sets associated with transmembrane transport, neurotransmission, and intracellular movement in genes that exhibited differential methylation. Sex-stratified analyses found a number of sex-specific DNA methylation differences associated with war exposure. Only 2 of 258 (0.8%) previously reported trauma-associated DNA methylation sites were associated with war exposure (B = -0.004; 95% CI, -0.005 to -0.003; Bonferroni P = .04 and B = -0.005; 95% CI, -0.006 to -0.004; Bonferroni P = .03). Any war exposure or bombardment was nominally associated with decreased epigenetic age using the Horvath multitissue clock (B = -0.39; 95% CI, -0.63 to -0.14; P = .007 and B = -0.42; 95% CI, -0.73 to -0.11; P = .002).

Conclusions and relevance: In this cohort of Syrian refugee children and adolescents, war exposure was associated with a small number of distinct differences in salivary DNA methylation.

Importance: Adolescent cannabis use has been consistently posited to contribute to the onset and progression of psychosis. However, alternative causal models may account for observed associations between cannabis use and psychosis risk, including shared vulnerability for both cannabis use and psychosis or efforts to self-medicate distress from psychosis spectrum symptomology.

Objective: To test 3 hypotheses that may explain cannabis-psychosis risk associations by modeling psychosis spectrum symptom trajectories prior to and after cannabis initiation across adolescent development (approximately 10-15 years of age).

Design, setting, and participants: This cohort study used data from 5 waves across 4 years of follow-up from the Adolescent Brain Cognitive Development (ABCD) Study. The ABCD study is an ongoing large-scale, longitudinal study of brain development and mental and physical health of children in the US launched in June 2016. Data are collected from 21 research sites. The study included data from 11 868 adolescents aged 9 to 10 years at baseline. Three participants were excluded from the present analysis owing to missing data. Data analysis was performed from September 2023 to July 2024.

Main outcomes and measures: Discontinuous growth curve modeling was used to assess trajectories of psychosis spectrum symptoms before and after cannabis initiation. Control variables considered for this investigation were age, sex, internalizing and externalizing symptoms, socioeconomic status, parental mental health, and other substance use.

Results: Among the 11 858 participants at wave 1, the mean (SD) age was 9.5 (0.5) years; 6182 (52%) participants were male. Consistent with a shared vulnerability hypothesis, adolescents who used cannabis at any point during the study period reported a greater number of psychosis spectrum symptoms (B, 0.86; 95% CI, 0.68-1.04) and more distress (B, 1.17; 95% CI, 0.96-1.39) from psychosis spectrum symptoms relative to those who never used cannabis. Additionally, consistent with a self-medication hypothesis, the number of psychosis spectrum symptoms (B, 0.16; 95% CI, 0.12-0.20) and distress (B, 0.23; 95% CI, 0.21-0.26) from psychosis spectrum symptoms increased in the time leading up to cannabis initiation. We observed mixed evidence for an increase in psychosis symptoms after cannabis initiation (ie, contributing risk hypothesis).

Conclusion and relevance: The findings underscore the importance of accounting for shared vulnerability and self-medication effects when modeling cannabis-psychosis risk associations.

Importance: Individuals with psychiatric disorders have been reported to have elevated levels of inflammatory biomarkers, and prospective evidence is limited regarding the association between inflammatory biomarkers and subsequent psychiatric disorders risk.

Objective: To assess the associations between inflammation biomarkers and subsequent psychiatric disorders risk.

Design, setting, and participants: This was a prospective cohort study including individuals from the Swedish Apolipoprotein Mortality Risk (AMORIS) cohort, with no prior psychiatric diagnoses and having a measurement of at least 1 inflammatory biomarker. Data from the UK Biobank were used for validation. Longitudinal trajectories of studied biomarkers were visualized before diagnosis of psychiatric disorders in the AMORIS cohort via a nested case-control study. In addition, genetic correlation and mendelian randomization (MR) analyses were conducted to determine the genetic overlap and causality of the studied associations using publicly available GWAS summary statistics.

Exposures: Inflammatory biomarkers, eg, leukocytes, haptoglobin, immunoglobulin G (IgG), C-reactive protein (CRP), platelets, or albumin.

Main outcomes and measures: Any psychiatric disorder or specific psychiatric disorder (ie, depression, anxiety, and stress-related disorders) was identified through the International Statistical Classification of Diseases, Eighth, Ninth, and Tenth Revision codes.

Results: Among the 585 279 individuals (mean [SD] age, 45.5 [14.9] years; 306 784 male [52.4%]) in the AMORIS cohort, individuals with a higher than median level of leukocytes (hazard ratio [HR], 1.11; 95% CI, 1.09-1.14), haptoglobin (HR, 1.13; 95% CI, 1.12-1.14), or CRP (HR, 1.02; 95% CI, 1.00-1.04) had an elevated associated risk of any psychiatric disorders. In contrast, we found an inverse association for IgG level (HR, 0.92; 95% CI, 0.89-0.94). The estimates were comparable for depression, anxiety, and stress-related disorders, specifically, and these results were largely validated in the UK Biobank (n = 485 620). Analyses of trajectories revealed that individuals with psychiatric disorders had higher levels of leukocytes and haptoglobin and a lower level of IgG than their controls up to 30 years before the diagnosis. The MR analysis suggested a possible causal relationship between leukocytes and depression.

Conclusions and relevance: In this cohort study, inflammatory biomarkers including leukocytes, haptoglobin, CRP, and IgG were associated with a subsequent risk of psychiatric disorders, and thus might be used for high-risk population identification. The possible causal link between leukocytes and depression supports the crucial role of inflammation in the development of psychiatric disorders.