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- Isung, Josef, et al.
(författare)
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Association of Primary Humoral Immunodeficiencies With Psychiatric Disorders and Suicidal Behavior and the Role of Autoimmune Diseases
- 2020
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Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 77:11, s. 1147-1154
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Tidskriftsartikel (refereegranskat)abstract
- Importance: The hypothesis that disrupted immune function is implicated in the pathophysiology of psychiatric disorders and suicide is gaining traction, but the underlying mechanisms are largely unknown. Primary humoral immunodeficiencies (PIDs) are rare deficiencies of the immune system-mainly dysfunction of antibody production-and are associated with adverse health problems, such as recurrent infections and autoimmune diseases.Objective: To establish whether PIDs that affect antibody function and level are associated with lifetime psychiatric disorders and suicidal behavior and whether this association is explained by the co-occurrence of autoimmune diseases.Design, Setting, and Participants: This population- and sibling-based cohort study included more than 14 million individuals living in Sweden from January 1, 1973, through December 31, 2013. Register-based data on exposure, outcomes, and covariates were collected through December 31, 2013. Individuals with a record of PID were linked to their full siblings, and a family identification number was created. Data were analyzed from May 17, 2019, to February 21, 2020.Exposures: Lifetime records of PID and autoimmune disease.Main Outcomes and Measures: Lifetime records of 12 major psychiatric disorders and suicidal behavior, including suicide attempts and death by suicide.Results: A lifetime diagnosis of PID affecting immunoglobulin levels was identified in 8378 patients (4947 women [59.0%]; median age at first diagnosis, 47.8 [interquartile range, 23.8-63.4] years). A total of 4776 clusters of full siblings discordant for PID was identified. After adjusting for comorbid autoimmune diseases, PIDs were associated with greater odds of any psychiatric disorder (adjusted odds ratio [AOR], 1.91; 95% CI, 1.81-2.01) and any suicidal behavior (AOR, 1.84; 95% CI, 1.66-2.04). The associations were also significant for all individual psychiatric disorders (range of AORs, 1.34 [95% CI, 1.17-1.54] for schizophrenia and other psychotic disorders to 2.99 [95% CI, 2.42-3.70] for autism spectrum disorders), death by suicide (AOR, 1.84; 95% CI, 1.25-2.71), and suicide attempts (AOR, 1.84; 95% CI, 1.66-2.04). In the sibling comparisons, the associations were attenuated but remained significant for aggregated outcomes (AOR for any psychiatric disorder, 1.64 [95% CI, 1.48-1.83]; AOR for any suicidal behavior, 1.37 [95% CI, 1.14-1.66]), most individual disorders (range of AORs, 1.46 [95% CI, 1.23-1.73] for substance use disorders to 2.29 [95% CI, 1.43-3.66] for autism spectrum disorders), and suicide attempts (AOR, 1.41; 95% CI, 1.17-1.71). Joint exposure for PID and autoimmune disease resulted in the highest odds for any psychiatric disorder (AOR, 2.77; 95% CI, 2.52-3.05) and any suicidal behavior (AOR, 2.75; 95% CI, 2.32-3.27). The associations with psychiatric outcomes (AORs, 2.42 [95% CI, 2.24-2.63] vs 1.65 [95% CI, 1.48-1.84]) and suicidal behavior (AORs, 2.43 [95% CI, 2.09-2.82] vs 1.40 [95% CI, 1.12-1.76]) were significantly stronger for women than for men with PID.Conclusions and Relevance: Primary humoral immunodeficiencies were robustly associated with psychopathology and suicidal behavior, particularly in women. The associations could not be fully explained by co-occurring autoimmune diseases, suggesting that antibody dysfunction may play a role, although other mechanisms are possible. Individuals with both PID and autoimmune disease had the highest risk of psychiatric disorders and suicide, suggesting an additive effect. Future studies should explore the underlying mechanisms of these associations.
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| 2. |
- Isung, Josef, et al.
(författare)
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Association of Tourette Syndrome and Chronic Tic Disorder With Cervical Spine Disorders and Related Neurological Complications
- 2021
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Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 78:10, s. 1205-1211
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Severe forms of Tourette syndrome or chronic tic disorder (TS/CTD) may involve repeated head jerking. Isolated case reports have described a spectrum of severe neck disorders in individuals with TS/CTD. However, the nature and prevalence of cervical spine disorders in TS/CTD are unknown.Objective: To establish if TS/CTD are associated with an increased risk of cervical spine disorders and related neurological complications compared with individuals from the general population.Design, Setting, and Participants: All individuals born from 1973 to 2013 and living in Sweden between 1997 and 2013 were identified. Individuals with a record of TS/CTD diagnosed in specialist settings were matched on age, sex, and county of birth with 10 unexposed individuals randomly selected from the general population. Cox proportional hazards regression models were used to estimate the risk of vascular and nonvascular cervical spine disorders among exposed individuals, compared with unexposed individuals. Models were adjusted for other known causes of cervical spine injury. Data were analyzed from March 19 to May 16, 2021.Exposures: International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses of TS/CTD in the Swedish National Patient Register.Main Outcomes and Measures: Records of cervical vascular disorders (ie, aneurysm, cerebral infarction, transitory cerebral ischemia) and cervical nonvascular disorders (ie, spondylosis, cervical disc disorders, fractures of the cervical spine, cervicalgia) and cervical surgeries. Covariates included rheumatic disorders, traffic injuries, fall- or sport-related injuries, and attention-deficit/hyperactivity disorder comorbidity.Results: A total of 6791 individuals with TS/CTD were identified (5238 [77.1%] were male; median [interquartile] age at first diagnosis, 15.6 [11.4-23.7] years) and matched to 67 910 unexposed individuals. Exposed individuals had a 39% increased risk of any cervical spine disorder (adjusted hazard ratio, 1.39; 95% CI, 1.22-1.59). Adjusted hazard ratios for cervical vascular and nonvascular disorders were 1.57 (95% CI, 1.16-2.13) and 1.38 (95% CI, 1.19-1.60), respectively. Risks were similar among men and women.Conclusions and Relevance: Individuals with severe TS/CTD are at increased risk of cervical spine disorders. These outcomes are relatively rare but may lead to persistent disability in some individuals and thus require close monitoring to facilitate early interventions.
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| 3. |
- Isung, Josef, et al.
(författare)
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Differential effects on blood and cerebrospinal fluid immune protein markers and kynurenine pathway metabolites from aerobic physical exercise in healthy subjects
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Mounting evidence shows that physical exercise modulates systemic inflammation. However, its effect on cerebrospinal fluid (CSF) immune-marker profiles in man are largely unknown. We here report a study on healthy subjects (n=27, males=12, mean age 28.7, range 22-52) allocated to either an acute exercise setting over four consecutive days, or a training intervention over 4 weeks. Paired plasma and CSF samples collected at baseline, after 7 days of exercise abstention, and the day after completion of the exercise interventions, were analyzed for protein inflammation markers using a multiplex proximity extension assay and neurotransmitters and kynurenine pathway (KP) metabolites using liquid chromatography, respectively. Routine cell counts, and albumin, immunoglobulin G and neurofilament light chain concentrations in CSF remained unchanged in both paradigms, while several inflammatory proteins became upregulated after acute exercise. However, only changes in three CSF (vascular endothelial growth factor-A, interleukin-7 and matrix metalloproteinase-10) and 12 plasma proteins reached significance levels after adjustment for multiple comparisons and exclusion of less stable proteins. Similarly, KP metabolites only changed among participants after acute exercise, while neurotransmitter levels, except for increased CSF serine, remained stable. Both in plasma and CSF changes in KP metabolites and inflammatory proteins correlated, suggesting that these processes are functionally linked. These findings suggest that acute aerobic physical exercise affects immune markers and KP metabolites systemically and in the CSF.
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| 4. |
- Zhang, Tianyang, et al.
(författare)
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Prenatal and Early Childhood Infections and Subsequent Risk of Obsessive-Compulsive Disorder and Tic Disorders : A Nationwide, Sibling-Controlled Study
- 2023
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 93:11, s. 1023-1030
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Postinfectious autoimmune processes are hypothesized to be causally related to both obsessive-compulsive disorder (OCD) and tic disorders, but current evidence is conflicting. This study examined whether prenatal maternal (and paternal, as an internal control) infections and early childhood infections in the offspring (i.e., during the first 3 years of life) were associated with a subsequent risk of OCD and Tourette syndrome or chronic tic disorder (TS/CTD).METHODS: Individuals exposed to any prenatal maternal infection (n = 16,743) and early childhood infection (n = 264,346) were identified from a population-based birth cohort consisting of 2,949,080 singletons born in Sweden between 1973 and 2003 and were followed through 2013. Cox proportional hazard regression models were used to estimate hazard ratios (HRs). Sibling analyses were performed to control for familial confounding.RESULTS: At the population level, and after adjusting for parental psychiatric history and autoimmune diseases, a significantly increased risk of OCD and TS/CTD was found in individuals exposed to prenatal maternal (but not paternal) infections (OCD: HR, 1.33; 95% CI, 1.12-1.57; TS/CTD: HR, 1.60; 95% CI, 1.23-2.09) and early childhood infections (OCD: HR, 1.19; 95% CI, 1.14-1.25; TS/CTD: HR, 1.34; 95% CI, 1.24-1.44). However, these associations were no longer significant in the sibling analyses.CONCLUSIONS: The results do not support the hypothesis that prenatal maternal or early-life infections play a direct causal role in the etiology of either OCD or TS/CTD. Instead, familial factors (e.g., genetic pleiotropy) may explain both the propensity to infections and the liability to OCD and TS/CTD.
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