Disclosures: Isung reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
June 16, 2020
2 min read

Primary humoral immunodeficiencies linked to psychiatric disorders, suicidal behavior

Disclosures: Isung reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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Primary humoral immunodeficiencies appeared significantly associated with psychiatric disorders and suicidal behavior, according to study results published in JAMA Psychiatry.

Josef Isung

“Because primary immunodeficiencies (PIDs) are rare disorders, this kind of study is only possible in countries that have large nationwide health records like Sweden,” Josef Isung, MD, PhD, of the department of clinical neuroscience at Karolinska Institutet, told Healio Psychiatry. “This is the first study to examine this research question using nationwide data focusing on a broad range of mental disorders and suicide at the same time. The study is also unique in that it examined the contribution of autoimmune diseases to the associations.”

Prior studies suggested the etiological importance of immune disruption in psychiatric disorders via multiple mechanisms, including postinfectious priming of microglia, altered neurodevelopment or microbial dysbiosis; however, research is sparse regarding the neuropsychiatric consequences of the underproduction of homeostatic antibodies. PIDs may provide a “model to disentangle the effects of humoral immunodeficiency and autoimmune diseases on psychiatric disorders,” according to Isung and colleagues.

In the current population- and sibling-based cohort study, the researchers sought to determine whether PIDs that impact antibody level and function were linked to lifetime psychiatric disorders and suicidal behavior, as well as whether the co-occurrence of autoimmune diseases explained this association. They included more than 14 million individuals who lived in Sweden from 1973 through 2013 and collected register-based data on exposure, outcomes and covariates through 2013. They linked those with a record of PID to their full siblings and created a family identification number. Lifetime records of autoimmune disease and PID served as the exposures, and main outcomes and measures were lifetime records of 12 major psychiatric disorder and suicidal behavior, including death by suicide and suicide attempts.

The researchers identified a lifetime diagnosis of PID affecting immunoglobulin levels among 8,378 patients, of whom 59% were women and for whom the median age at first diagnosis was 47.8 years. They also identified 4,776 clusters of full siblings discordant for PID.

Results showed an association between PIDs and increased risk for any psychiatric disorder (adjusted OR [aOR] = 1.91; 95% CI, 1.81-2.01) and any suicidal behavior (aOR = 1.84; 95% CI, 1.66-2.04) after adjusting for comorbid autoimmune diseases. Isung and colleagues also noted significant associations for all individual psychiatric disorders, death by suicide and suicide attempts. The associations were attenuated but remained significant in the sibling comparisons for aggregated outcomes, most individual disorders and suicide attempts. Joint exposure for autoimmune disease and PID was associated with the highest risk 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). Women with PID exhibited significantly stronger associations with psychiatric outcomes and suicidal behaviors compared with men with PID.

“For this patient group, our results would motivate an increased overall awareness not only of the known medical consequences and risks for having primary immunodeficiencies — such as increased susceptibility of serious and recurrent infections, as well as autoimmune diseases — but also the associated psychiatric burden that seems overall robustly associated with PID,” Isung told Healio Psychiatry.