Abstract
BackgroundMaternal immune responses and brain-reactive antibodies have been proposed as possible causal mechanisms for schizophrenia and some child psychiatric disorders. According to this hypothesis maternal antibodies may cross the placenta and interact with the developing CNS of the fetus causing future neurodevelopmental disorders. Therefore, we investigated if children of mothers with cancer might be at higher risk of developing psychiatric disorders, with particular focus on small-cell lung cancer, which is known to induce production of antibodies binding to CNS elements.MethodsNationwide population-based registers were linked, including the Danish Psychiatric Central Register and The Danish Cancer Registry. Data were analyzed as a cohort study using survival analysis techniques. Incidence rate ratios (IRRs) and accompanying 95% confidence intervals (CIs) were used as measures of relative risk.ResultsIn general, parental cancer was not associated with schizophrenia in the offspring (IRR, 0.98; 95% CI, 0.95-1.01). Furthermore, we found no temporal associations with maternal cancer in general; neither around the pregnancy period. However, maternal small-cell lung cancer increased the risk of early-onset schizophrenia and maternal small-cell lung cancer diagnosed within 20 years after childbirth increased the risk of schizophrenia. Parental cancer was not associated with child psychiatric disorders (IRR, 1.01; 95% CI, 0.98-1.05) except for the smoking related cancers. There was a significantly increased risk of child psychiatric disorders in offspring of both mothers (IRR, 1.35; 95% CI, 1.16-1.58) and fathers (IRR, 1.47; 95% CI, 1.30-1.66) with lung cancer of all types.ConclusionsIn general, parental cancer did not increase the risk of schizophrenia nor of child psychiatric disorders. However, maternal small-cell lung cancer increased the risk of schizophrenia in subgroups; and lung cancer in general increased the risk of child psychiatric disorders, which could be due to risk factors associated with parental smoking.
Highlights
Psychiatric disorders have complex, multifactorial, and to a large extent unknown etiologies, but immunological hypotheses have become increasingly prominent
The overall risk of schizophrenia in children of parents with cancer was close to unity (IRR, 0.98; 95% confidence intervals (CIs), 0.95-1.01), compared to children of parents with no cancer diagnosis during our study period
A total of 929 cases of schizophrenia had a parent with lung cancer, corresponding to an Incidence rate ratios (IRRs) of 1.06 for children of mothers with lung cancer, and an IRR of 1.06 for children of fathers with lung cancer
Summary
Psychiatric disorders have complex, multifactorial, and to a large extent unknown etiologies, but immunological hypotheses have become increasingly prominent. Several other autoantibodies with brain-reactive potential are associated with small-cell lung cancer [18]; and some autoantibodies in mothers with small-cell lung cancer might be able to react with the nervous system of the fetus, predisposing for future psychiatric disorders in the offspring [6,7,15]. Maternal immune responses and brain-reactive antibodies have been proposed as possible causal mechanisms for schizophrenia and some child psychiatric disorders According to this hypothesis maternal antibodies may cross the placenta and interact with the developing CNS of the fetus causing future neurodevelopmental disorders. Maternal small-cell lung cancer increased the risk of schizophrenia in subgroups; and lung cancer in general increased the risk of child psychiatric disorders, which could be due to risk factors associated with parental smoking
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