JAMA Psychiatry最新文献

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.

Importance: Research suggests that low-grade, nonresolving inflammation may predate adult mental and physical illness. However, evidence to date is largely cross-sectional or focuses on single disorder outcomes.

Objectives: To examine trajectories of inflammation as measured by C-reactive protein (CRP) levels in a large sample of children and adolescents, and to explore associations between different identified trajectories and mental and related cardiometabolic health outcomes in early adulthood.

Design, setting, and participants: In a longitudinal cohort study using data from the large UK-based Avon Longitudinal Study of Parents and Children (ALSPAC), latent class growth analysis (LCGA) was used to explore different trajectories of inflammation, with logistic regression exploring association with mental and physical health outcomes. Participants with measurable CRP data and associated mental and cardiometabolic health outcomes recorded were included in the analysis. Data analysis was performed from May 1, 2023, to March 30, 2024.

Exposures: Inflammation was assessed via CRP levels at ages 9, 15, and 17 years. LCGA was used to identify different trajectories of inflammation.

Main outcomes and measures: Outcomes assessed at age 24 years included psychotic disorders, depressive disorders, anxiety disorders, hypomania, and, as a measure of insulin resistance, Homeostasis Model Assessment (HOMA2) score.

Results: A total of 6556 participants (3303 [50.4%] female) were included. Three classes of inflammation were identified: persistently low CRP levels (reference class, n = 6109); persistently raised CRP levels, peaking at age 9 years (early peak, n = 197); and persistently raised CRP levels, peaking at age 17 years (late peak, n = 250). Participants in the early peak group were associated with a higher risk of psychotic disorder (odds ratio [OR], 4.60; 95% CI, 1.81-11.70; P = .008), a higher risk of severe depression (OR, 4.37; 95% CI, 1.64-11.63; P = .02), and higher HOMA2 scores (β = 0.05; 95% CI, 0.01-0.62, P = .04) compared with participants with persistently low CRP. The late peak group was not associated with any outcomes at age 24 years.

Conclusions and relevance: Low-grade systemic inflammation peaking in midchildhood was associated with specific mental and cardiometabolic disorders in young adulthood. These findings suggest that low-grade persistent inflammation in early life may be an important shared common factor for mental-physical comorbidity and so could be relevant to future efforts of patient stratification and risk profiling.

Importance: Advancing precision psychiatry, where treatments are based on an individual's biology rather than solely their clinical presentation, requires attention to several key attributes for any candidate biomarker. These include test-retest reliability, sensitivity to relevant neurophysiology, cost-effectiveness, and scalability. Unfortunately, these issues have not been systematically addressed by biomarker development efforts that use common neuroimaging tools like magnetic resonance imaging (MRI) and electroencephalography (EEG). Here, the critical barriers that neuroimaging methods will need to overcome to achieve clinical relevance in the near to intermediate term are examined.

Observations: Reliability is often overlooked, which together with sensitivity to key aspects of neurophysiology and replicated predictive utility, favors EEG-based methods. The principal barrier for EEG has been the lack of large-scale data collection among multisite psychiatric consortia. By contrast, despite its high reliability, structural MRI has not demonstrated clinical utility in psychiatry, which may be due to its limited sensitivity to psychiatry-relevant neurophysiology. Given the prevalence of structural MRIs, establishment of a compelling clinical use case remains its principal barrier. By contrast, low reliability and difficulty in standardizing collection are the principal barriers for functional MRI, along with the need for demonstration that its superior spatial resolution over EEG and ability to directly image subcortical regions in fact provide unique clinical value. Often missing, moreover, is consideration of how these various scientific issues can be balanced against practical economic realities of psychiatric health care delivery today, for which embedding economic modeling into biomarker development efforts may help direct research efforts.

Conclusions and relevance: EEG seems most ripe for near- to intermediate-term clinical impact, especially considering its scalability and cost-effectiveness. Recent efforts to broaden its collection, as well as development of low-cost turnkey systems, suggest a promising pathway by which neuroimaging can impact clinical care. Continued MRI research focused on its key barriers may hold promise for longer-horizon utility.