Paternal age as a risk factor for schizophrenia in offspring

Schizophrenia is one of the most disabling conditions that affect human beings. There is robust evidence of an association between advancing paternal age and schizophrenia in offspring. The understanding of this association is limited, i.e. the mechanism is not known. This thesis aimed to further understand the mechanisms behind the association. The studies were conducted using Swedish register data from different sources. Different explanations were examined with possible confounders taken into account.

The first study showed that adoptive paternal age was not associated with increased risk of schizophrenia in adopted subjects. This indicates that there is no increased risk of developing schizophrenia due to the psychosocial environment of an older father.

The second study found that advancing paternal age is associated with increased risk of autism spectrum disorder in offspring. In contrast to schizophrenia this association is interacting with maternal age and advancing maternal age is associated with increased risk of autism spectrum disorder.

In the third study factors associated with both delayed fatherhood and increased risk of schizophrenia in offspring was implicated as explanation to the paternal age effect. For the second time delayed fatherhood rather than advancing paternal age per se was shown to be associated with increased risk of schizophrenia in offspring.

The fourth study found that personal characteristics could be implicated as factors explaining the association between age at fatherhood and schizophrenia.

In conclusion, this thesis provides knowledge about the association between advancing paternal age and schizophrenia. It shows that advancing paternal age is not a specific risk factor to schizophrenia even though there might be different mechanisms behind the association to autism spectrum disorder. The association between advancing paternal age and increased risk of schizophrenia in offspring is most likely due to factors that are associated with both delayed fatherhood and increased risk of schizophrenia in offspring. These factors could be related to social functioning. This has important implications regarding clinical understanding and public health advice as well as directions of future research.

List of scientific papers

I. Ek M, Wicks S, Magnusson C, Dalman C. Adoptive paternal age and risk of psychosis in adoptees: a register based cohort study. PLoS One. 2012;7(10):e47334.
https://doi.org/10.1371/journal.pone.0047334

II. Idring S, Magnusson C, Lundberg M, Ek M, Rai D, Svensson AC, Dalman C, Karlsson H, Lee BK. Parental age and the risk of autism spectrum disorders: findings from a Swedish population-based cohort. Int J Epidemiol. 2014;43(1):107-15.
https://doi.org/10.1093/ije/dyt262

III. Ek M, Wicks S, Svensson AC, Idring S, Dalman C. Advancing Paternal Age and Schizophrenia: The Impact of Delayed Fatherhood. Schizophrenia Bulletin 2014.
https://doi.org/10.1093/schbul/sbu154

IV. Ek M, Wicks S, Svensson AC, Dal H, Zammit S, Hemmingsson T, Dalman C. Personal Characteristics previously shown to be associated with Schizophrenia and their association with Teenage and Delayed Fatherhood. [Manuscript]