Dataset Information

Association of chronic and acute inflammation of the mucosa-associated lymphoid tissue with psychiatric disorders and suicidal behavior.

ABSTRACT: Immune dysregulation due to chronic inflammation is a hypothesized risk factor underlying psychiatric disorders and suicidal behavior. Whether tonsillectomy and acute appendicitis used, respectively, as proxies for chronic and acute inflammation within the mucosa-associated lymphoid tissue (MALT) are associated with psychiatric disorders and suicidal behavior is currently unknown. A birth cohort study was conducted including 3,052,875 individuals born in Sweden between 1973 and 2003. We identified 210,686 individuals ever exposed to tonsillectomy and 86,928 individuals ever exposed to acute appendicitis, as well as 317,214 clusters of siblings discordant for tonsillectomy, and 160,079 sibling clusters discordant for acute appendicitis. Outcomes were an aggregate risk of 'any psychiatric disorder', 'any suicidal behavior', 12 individual psychiatric disorders, suicide attempts and deaths by suicide. Tonsillectomy was associated with increased odds of 'any psychiatric disorder' (adjusted odds ratio [aOR]?=?1.39; 95% confidence interval (CI)?=?1.38-1.41) and 'any suicidal behavior' (aOR?=?1.41; 95% CI?=?1.37-1.44), and most individual disorders. Acute appendicitis also increased the odds of 'any psychiatric disorder' and 'any suicidal behavior' (aOR?=?1.23; 95% CI?=?1.20-1.25, and aOR?=?1.32; 95% CI?=?1.28-1.37, respectively). Exposure to both tonsillectomy and appendicitis was associated with the highest odds of 'any psychiatric disorder' (aOR?=?1.70; 95% CI?=?1.59-1.82) and 'any suicidal behavior' (aOR?=?1.90; 95% CI?=?1.70-2.12). In sibling comparisons, the associations were attenuated but remained significant. We conclude that inflammation within the MALT, particularly when chronic, is robustly associated with a broad range of psychiatric disorders and suicidal behavior.

SUBMITTER: Isung J

PROVIDER: S-EPMC6742630 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Association of chronic and acute inflammation of the mucosa-associated lymphoid tissue with psychiatric disorders and suicidal behavior.

Isung Josef J Isomura Kayoko K Almqvist Catarina C Lichtenstein Paul P Larsson Henrik H Wester Tomas T Rück Christian C Fernández de la Cruz Lorena L Sidorchuk Anna A Mataix-Cols David D

Translational psychiatry 20190912 1

Immune dysregulation due to chronic inflammation is a hypothesized risk factor underlying psychiatric disorders and suicidal behavior. Whether tonsillectomy and acute appendicitis used, respectively, as proxies for chronic and acute inflammation within the mucosa-associated lymphoid tissue (MALT) are associated with psychiatric disorders and suicidal behavior is currently unknown. A birth cohort study was conducted including 3,052,875 individuals born in Sweden between 1973 and 2003. We identifi ...[more]

PMID: 31515504

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Project description:ImportanceMaternal immune activation (MIA) leading to altered neurodevelopment in utero is a hypothesized risk factor for psychiatric outcomes in offspring. Primary antibody immunodeficiencies (PIDs) constitute a unique natural experiment to test the MIA hypothesis of mental disorders.ObjectiveTo assess the association of maternal and paternal PIDs with psychiatric disorders and suicidal behavior in offspring.Design, setting, and participantsCohort study of 4 294 169 offspring of parents with and without PIDs living in Sweden at any time between 1973 and 2013. Data were extracted from Swedish nationwide health and administrative registers and were analyzed from May 5 to September 30, 2022. All individuals with diagnoses of PIDs identified between 1973 and 2013 from the National Patient Register were included. Offspring were included if born before 2003. Parent-offspring pairs in which both parents had a history of PIDs were excluded.ExposuresLifetime records of parental PIDs according to the International Classification of Diseases, Eighth Revision (ICD-8); International Classification of Diseases, Ninth Revision (ICD-9); and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnostic codes.Main outcomes and measuresLifetime records of 10 psychiatric disorders and suicidal behavior identified using ICD-8, ICD-9, and ICD-10 diagnostic codes, including suicide attempts and death by suicide, among offspring. Covariates included sex, birth year, parental psychopathology, suicide attempts, and autoimmune diseases. Additional analyses excluded offspring with their own PIDs and autoimmune diseases. Poisson regression models were fitted separately for mothers and fathers to estimate incidence rate ratios (IRRs) and 95% CIs for the risk of psychiatric and suicidal behavior outcomes in the offspring of PID-exposed vs PID-unexposed mothers or fathers.ResultsThe cohort included 4 294 169 offspring (2 207 651 males [51.4%]) and 3 954 937 parents (1 987 972 females [50.3%]). A total of 7270 offspring (0.17%) had parents with PIDs, and 4 286 899 offspring had parents without PIDs. In fully adjusted models, offspring of mothers with PIDs had an increased risk of any psychiatric disorder, while no such risks were observed in offspring of fathers with PIDs (IRR, 1.17; 95% CI, 1.10-1.25 vs IRR, 1.03; 95% CI, 0.94-1.14; P < .001). Likewise, an increased risk of suicidal behavior was observed among offspring of mothers with PIDs but not offspring of fathers with PIDs (IRR, 1.20; 95% CI, 1.06-1.36 vs IRR, 1.10; 95% CI, 0.91-1.34; P = .01). For the offspring of mothers with PIDs, the risk of developing any psychiatric disorder was significantly higher for those with mothers with 6 of 10 individual disorders, with IRRs ranging from 1.15 (95% CI, 1.04-1.26) for anxiety and stress-related disorders and 1.15 (95% CI, 1.03-1.30) for substance use disorders to 1.71 (95% CI, 1.37-2.14) for bipolar disorders. Offspring of mothers with both PIDs and autoimmune diseases had the highest risk for any psychiatric disorder (IRR, 1.24; 95% CI, 1.11-1.38) and suicidal behavior (IRR, 1.44; 95% CI, 1.17-1.78).Conclusions and relevanceFindings of this cohort study suggest that maternal, but not paternal, PIDs were associated with a statistically significant increased risk of psychiatric disorders and suicidal behavior in the offspring, particularly when PIDs co-occur with autoimmune diseases. These findings align with the MIA hypothesis of mental disorders, but the precise mechanisms remain to be elucidated.

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Dataset Information

Association of chronic and acute inflammation of the mucosa-associated lymphoid tissue with psychiatric disorders and suicidal behavior.

Publications

Association of chronic and acute inflammation of the mucosa-associated lymphoid tissue with psychiatric disorders and suicidal behavior.

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