JAMA Psychiatry最新文献

Importance: Schizophrenia and bipolar disorder are highly heritable psychiatric disorders with strong genetic and phenotypic overlap. Twin and molecular methods can be leveraged to predict the shared genetic liability to these disorders.

Objective: To investigate whether twin concordance for psychosis depends on the level of polygenic risk score (PRS) for psychosis and zygosity and compare PRS from cases and controls from several large samples and estimate the twin heritability of psychosis.

Design, setting, and participants: In this case-control study, psychosis PRS were generated from a genome-wide association study (GWAS) combining schizophrenia and bipolar disorder into a single psychosis phenotype and compared between cases and controls from the Schizophrenia and Bipolar Twin Study in Sweden (STAR) project. Further tests were conducted to ascertain if twin concordance for psychosis depended on the mean PRS for psychosis. Structural equation modeling was used to estimate heritability. This study constituted an analysis of existing clinical and population datasets with genotype and/or twin data. Included were twins from the STAR cohort and from the Swedish Twin Registry. Data were collected during the 2006 to 2013 period and analyzed from March 2023 to June 2024.

Exposures: PRS for psychosis based on the most recent GWAS of combined schizophrenia/bipolar disorder.

Main outcomes and measures: Psychosis case status was assessed by clinical interviews and/or Swedish National Register data.

Results: The final cohort comprised 87 pairs of twins with 1 or both affected and 59 unaffected pairs from the STAR project (for a total of 292 twins) as well as 443 pairs with 1 or both affected and 20 913 unaffected pairs from the Swedish Twin Registry. Among the 292 twins (mean [SD] birth year, 1960 [10.8] years; 158 female [54.1%]; 134 male [45.9%]), 134 were monozygotic twins, and 158 were dyzygotic twins. PRS for psychosis was higher in cases than in controls and associated with twin concordance for psychosis (1-SD increase in PRS, odds ratio [OR], 2.12; 95% CI, 1.23-3.87 on case status in monozygotic twins and OR, 2.74; 95% CI, 1.56-5.30 in dizygotic twins). The association between PRS for psychosis and concordance was not modified by zygosity. The twin heritability was estimated at 0.73 (95% CI, 0.30-1.00), which overlapped with the estimate in the full Swedish Twin Registry (0.69; 95% CI, 0.43-0.85).

Conclusions and relevance: In this case-control study, using the natural experiment of twins, results suggest that twins with greater inherited liability for psychosis were more likely to have an affected co-twin. Results from twin and molecular designs largely aligned. Even as illness vulnerability is not solely genetic, PRS carried predictive power for psychosis even in a modest sample size.

Importance: Mental illnesses are a leading cause of disability globally, and functional disability is often in part caused by cognitive impairments across psychiatric disorders. However, studies have consistently reported seemingly opposite findings regarding the association between cognition and psychiatric symptoms.

Objective: To determine if the association between general cognition and mental health symptoms diverges at different symptom severities in children.

Design, setting, and participants: A total of 5175 children with complete data at 2 time points assessed 2 years apart (aged 9 to 11 years at the first assessment) from the ongoing Adolescent Brain and Cognitive Development (ABCD) study were evaluated for a general cognition factor and mental health symptoms from September 2016 to August 2020 at 21 sites across the US. Polynomial and generalized additive models afforded derivation of continuous associations between cognition and psychiatric symptoms across different ranges of symptom severity. Data were analyzed from December 2022 to April 2024.

Main outcomes and measures: Aggregate cognitive test scores (general cognition) were primarily evaluated in relation to total and subscale-specific symptoms reported from the Child Behavioral Checklist.

Results: The sample included 5175 children (2713 male [52.4%] and 2462 female [47.6%]; mean [SD] age, 10.9 [1.18] years). Previously reported mixed findings regarding the association between general cognition and symptoms may consist of several underlying, opposed associations that depend on the class and severity of symptoms. Linear models recovered differing associations between general cognition and mental health symptoms, depending on the range of symptom severities queried. Nonlinear models confirm that internalizing symptoms were significantly positively associated with cognition at low symptom burdens higher cognition = more symptoms) and significantly negatively associated with cognition at high symptom burdens.

Conclusions and relevance: The association between mental health symptoms and general cognition in this study was nonlinear. Internalizing symptoms were both positively and negatively associated with general cognition at a significant level, depending on the range of symptom severities queried in the analysis sample. These results appear to reconcile mixed findings in prior studies, which implicitly assume that symptom severity tracks linearly with cognitive ability across the entire spectrum of mental health. As the association between cognition and symptoms may be opposite in low vs high symptom severity samples, these results reveal the necessity of clinical enrichment in studies of cognitive impairment.

Importance: According to the World Health Organization, more than 700 000 individuals worldwide die by suicide each year. Medical conditions likely increase the risk of suicide.

Objective: To (1) provide age- and sex-specific pairwise estimates of the risk of suicide across a comprehensive range of medical conditions, (2) investigate whether there is a dose-response-like relationship at play (ie, the higher the disability burden due to medical morbidity, the higher the risk of suicide), and (3) determine if the risk of suicide with medical conditions is particularly pronounced among those who had mental disorder preceding the medical conditions.

Design, setting, and participants: This cohort study was an observational study of population-based data for all individuals living in Denmark at some point between 2000 and 2020. The data analysis took place from September 2023 to May 2024.

Exposures: Thirty-one specific medical conditions as well as prior mental disorder.

Main outcomes and measures: The main outcome was suicide. Associations between the 31 specific medical conditions, nested within 9 categories, and suicide were examined via Poisson regression, yielding incidence rate ratios (IRRs). Subsequent analyses included an interaction term to assess whether a previous hospital-treated mental disorder modified the associations. Finally, the association between the disability burden of medical conditions and suicide was examined for those with and without prior mental disorder, respectively.

Results: A total of 6 635 857 individuals (3 337 613 females and 3 298 244 males) were included in the analyses of the associations between medical conditions and suicide. Except for endocrine disorders, all categories of medical conditions were associated with a statistically significant increased risk of suicide (which was most pronounced for gastrointestinal conditions [IRR, 1.7; 95% CI,1.5-1.8], cancer [IRR, 1.5; 95% CI, 1.4-1.6], and hematological conditions [IRR, 1.5; 95% CI, 1.3-1.6]). Interaction between mental disorder and individual medical conditions did not seem to play a major role for suicide risk. For those without but not for those with mental disorder, there was a dose-response-like relationship between the disability burden of medical conditions and suicide.

Conclusions and relevance: Medical conditions are generally associated with increased risk of suicide in a dose-response-like manner. Individuals with hospital-treated mental disorder appear to be at such elevated risk of suicide that additional disability associated with medical conditions has little impact in this regard.