Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.
Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.
These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.
Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.
The study was published in the November issue of JAMA Psychiatry.
Registry study
Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.
They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.
The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.
Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.
While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.
The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.
Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.
The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
Strong link to autism
Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.
In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).
About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.
In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.
The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)
It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.
Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.
Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.
The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.