Maternal primary immunodeficiency linked to offspring’s psychiatric disorders, suicidality

Children born to mothers, not fathers, with primary antibody immunodeficiencies had greater risks for certain psychiatric disorders and for suicidal behavior, according to data published in JAMA Psychiatry.

“Primary antibody immunodeficiencies affect both sexes, creating a natural experiment that can help assess differential associations of maternal vs. paternal primary antibody immunodeficiencies for offspring outcomes,” Josef Isung, MD, PhD, of the Centre for Psychiatry Research at Karolinska Institutet in Stockholm, Sweden, and colleagues wrote. “Specifically, while both mothers and fathers share approximately 50% of their segregating genes with their offspring, only mothers share an intrauterine environment with their offspring at a crucial time in neurodevelopment. This fact offers an opportunity to partially separate the implications of genetic and environmental factors of primary antibody immunodeficiencies for the behavioral outcomes of children exposed to these parental conditions.”

Defining the cohort

Isung and colleagues included all people living in Sweden who were listed in multiple Swedish national health and administrative registers from 1973 to 2013. Among these, the researchers identified people with primary antibody immunodeficiencies (PIDs) as well as 4,294,169 offspring born in the country from 1973 to 2003. Children were followed until they were aged 10 years or older.

The researchers compared offspring psychiatric outcomes for those born to mothers with PID, father with PID and parents without PID. They excluded six parents and their children who had both maternal and paternal PID exposure.

In total, 7,270 (0.17%) offspring had one parent with PID.

Psychiatric disorders

Compared with offspring whose parents did not have PIDs, children whose mothers had PID had a greater risk for any psychiatric disorder (incidence rate ratio [IRR] = 1.17; 95% CI, 1.1-1.25). Those whose fathers had PID did not have a greater risk for any psychiatric disorder.

Specifically, children of mothers with PID were more likely to have ADHD (IRR = 1.3; 95% CI, 1.12-1.52), autism spectrum disorders (IRR = 1.49; 95% CI, 1.17-1.91), bipolar disorders (IRR = 1.71; 95% CI, 1.37-2.14) major depression and other mood disorders (IRR = 1.23; 95% CI, 1.11-1.36), anxiety and stress-related disorders (IRR = 1.15; 95% CI, 1.04-1.26) and substance use disorders (IRR = 1.15; 95% CI, 1.03-1.3) compared with children who did not have PID exposure.

Offspring of fathers with PID were more likely to have bipolar disorders compared with children whose parents did not have PID (IRR = 1.5; 95% CI, 1.06-2.11). However, there were few cases of bipolar disorder in this group, so this finding “should be interpreted cautiously,” Isung and colleagues wrote.

Suicidal behavior

Similarly, children of mothers with PID (IRR = 1.2; 95% CI, 1.06-1.36) but not fathers with PID were more likely to exhibit suicidal behavior compared with children with no parents with PID.

Overall, children born to mothers with both PIDs and an autoimmune disease had the greatest risks for any psychiatric disorder (IRR = 1.24; 95% CI, 1.11-1.38) and suicidal behaviors (IRR = 1.44; 95% CI, 1.17-1.78).

“The findings of this cohort study suggest that maternal, but not paternal, PIDs are associated with a small but statistically significant increased risk of psychiatric disorders and suicidal behavior in offspring, particularly when they co-occur with autoimmune diseases,” Isung and colleagues wrote. “While the mechanisms are likely multifactorial, the results support the maternal immune activation hypothesis as a potential contributor to altered neurodevelopment, psychiatric disorders and suicidal behavior in offspring.”