Dataset Information

Correlates of suicidal behaviors and genetic risk among United States veterans with schizophrenia or bipolar I disorder.

ABSTRACT:

Objective

Persons diagnosed with schizophrenia (SCZ) or bipolar I disorder (BPI) are at high risk for self-injurious behavior, suicidal ideation, and suicidal behaviors (SB). Characterizing associations between diagnosed mental and physical health problems, prior pharmacological treatments, and aggregate genetic factors has potential to inform risk stratification and mitigation strategies.

Methods

In this study of 3,942 SCZ and 5,414 BPI patients receiving VA care, self-reported SB and ideation were assessed using the Columbia Suicide Severity Rating Scale (C-SSRS). These cross-sectional data were integrated with electronic health records (EHR), and compared by lifetime diagnoses, treatment histories, follow-up screenings, and mortality data. Polygenic scores (PGS) for traits related to psychiatric disorders, substance use, and cognition were constructed using available genomic data, and exploratory genome-wide association studies were performed to identify and prioritize specific loci.

Results

Only 20% of veterans who self-reported SB had a corroborating ICD-9/10 code in their EHR; and among those who denied prior behaviors, more than 20% reported new-onset SB at follow-up. SB were associated with a range of psychiatric and non-psychiatric diagnoses, and with treatment with specific classes of psychotropic medications (e.g., antidepressants, antipsychotics, etc.). PGS for externalizing behaviors, smoking, suicide attempt, and major depressive disorder were also associated with attempt and ideation.

Conclusions

Among individuals with a diagnosed mental illness, a GWAS for SB did not yield any significant loci. Self-reported SB were strongly associated with clinical variables across several EHR domains. Overall, clinical and polygenic analyses point to sequelae of substance-use related behaviors and other psychiatric comorbidities as strong correlates of prior and subsequent SB. Nonetheless, past SB was frequently not documented in clinical settings, underscoring the value of regular screening based on direct, in-person assessments, especially among high-risk individuals.

SUBMITTER: Bigdeli TB

PROVIDER: S-EPMC10029042 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Correlates of suicidal behaviors and genetic risk among United States veterans with schizophrenia or bipolar I disorder.

Bigdeli Tim B TB Barr Peter B PB Rajeevan Nallakkandi N Graham David P DP Li Yuli Y Meyers Jacquelyn L JL Gorman Bryan R BR Peterson Roseann E RE Sayward Frederick F Radhakrishnan Krishnan K Natarajan Sundar S Nielsen David A DA Wilkinson Anna V AV Malhotra Anil K AK Zhao Hongyu H Brophy Mary M Shi Yunling Y O'Leary Timothy J TJ Gleason Theresa T Przygodzki Ronald R Pyarajan Saiju S Muralidhar Sumitra S Gaziano J Michael JM Huang Grant D GD Concato John J Siever Larry J LJ DeLisi Lynn E LE Kimbrel Nathan A NA Beckham Jean C JC Swann Alan C AC Kosten Thomas R TR Fanous Ayman H AH Aslan Mihaela M Harvey Philip D PD

medRxiv : the preprint server for health sciences 20230308

<h4>Objective</h4>Persons diagnosed with schizophrenia (SCZ) or bipolar I disorder (BPI) are at high risk for self-injurious behavior, suicidal ideation, and suicidal behaviors (SB). Characterizing associations between diagnosed mental and physical health problems, prior pharmacological treatments, and aggregate genetic factors has potential to inform risk stratification and mitigation strategies.<h4>Methods</h4>In this study of 3,942 SCZ and 5,414 BPI patients receiving VA care, self-reported S ...[more]

PMID: 36945597

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Project description:ImportanceUnderstanding the origins of clinical heterogeneity in bipolar disorder (BD) will inform new approaches to stratification and studies of underlying mechanisms.ObjectiveTo identify components of genetic liability that are shared between BD, schizophrenia, and major depressive disorder (MDD) and those that differentiate each disorder from the others and to examine associations between heterogeneity for key BD symptoms and each component.Design, setting, and participantsUsing data from the Bipolar Disorder Research Network in the United Kingdom, components of liability were identified by applying genomic structural equation modeling to genome-wide association studies of schizophrenia, BD, and MDD. Polygenic risk scores (PRS) representing each component were tested for association with symptoms in an independent BD data set. Adults with DSM-IV BD or schizoaffective disorder, bipolar type, were included. Data were collected from January 2000 to December 2013, and data were analyzed from June 2020 to February 2022.Main outcomes and measuresPRS representing the components of liability were tested for association with mania and depression, psychosis, and mood incongruence of psychosis in participants with BD, measured using the Bipolar Affective Disorder Dimensional Scale.ResultsOf 4429 included participants, 3012 (68.0%) were female, and the mean (SD) age was 46.2 (12.3) years. Mania and psychosis were associated with the shared liability component (mania β = 0.29; 95% CI, 0.23-0.34; P = 3.04 × 10-25; psychosis β = 0.05; 95% CI, 0.04-0.07; P = 2.33 × 10-13) and the components that differentiate each of schizophrenia (mania β = 0.08; 95% CI, 0.03-0.14; P = .002; psychosis β = 0.03; 95% CI, 0.01-0.04; P = 1.0 × 10-4) and BD (mania β = 0.14; 95% CI, 0.09-0.20; P = 1.99 × 10-7; psychosis β = 0.02; 95% CI, 0.01-0.03; P = .006) from the other disorders. The BD differentiating component was associated with mania independently of effects on psychosis (β = 0.14; 95% CI, 0.08-0.20; P = 4.32 × 10-6) but not with psychosis independently of mania. Conversely, the schizophrenia differentiating component was associated with psychosis independently of effects on mania (β = 0.01; 95% CI, 0.003-0.03; P = .02), but not with mania independently of psychosis. Mood incongruence of psychosis was associated only with the schizophrenia differentiating component (β = 0.03; 95% CI, 0.01-0.05; P = .005). Depression was associated with higher MDD differentiating component (β = 0.07; 95% CI, 0.01-0.12; P = .01) but lower BD differentiating component (β = -0.11; 95% CI, -0.17 to -0.06; P = 7.06 × 10-5).Conclusions and relevanceIn this study of BD, clinical heterogeneity reflected the burden of liability to BD and the contribution of alleles that have differentiating effects on risk for other disorders; mania, psychosis, and depression were associated with the components of genetic liability differentiating BD, MDD, and schizophrenia, respectively. Understanding the basis of this etiological heterogeneity will be critical for identifying the different pathophysiological processes underlying BD, stratifying patients, and developing precision therapeutics.

Dataset Information

Correlates of suicidal behaviors and genetic risk among United States veterans with schizophrenia or bipolar I disorder.

Objective

Methods

Results

Conclusions

Publications

Correlates of suicidal behaviors and genetic risk among United States veterans with schizophrenia or bipolar I disorder.

Similar Datasets

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