Advancing paternal age and schizophrenia: the impact of delayed fatherhood.
OBJECTIVE
It is well known that advancing paternal age is associated with an increased risk of schizophrenia in offspring, but the mechanism behind this association remains unknown. This study investigates if delayed fatherhood rather than advancing paternal age per se might explain the increased risk of schizophrenia in offspring associated with advancing paternal age.


METHODS
This is a register-based study of the Swedish population looking at people born 1955-1985 who have 1 or 2 siblings (n = 2 589 502). The main analysis investigated whether the association between advancing paternal age and schizophrenia was explained by delayed fatherhood. Possible confounding factors were taken into account. Cox regression was used throughout.


RESULTS
In the main analysis the association between advancing paternal age and increased risk of schizophrenia in offspring disappeared after controlling for delayed fatherhood (hazard ratio [HR] = 0.93, 95% CI = 0.72-1.21 comparing 45+ years old fathers to those 25-29), whereas delayed fatherhood showed an association with increased risk of schizophrenia in offspring comparing 35-39 and 40-44 years old fathers to 25-29 year olds (HR = 1.37, 95% CI = 1.18-1.58; HR = 1.81, 95% CI = 1.44-2.28, respectively). The results remained when controlling for possible confounders.


CONCLUSIONS
This study suggests that the association between paternal age and schizophrenia is not due to paternal age per se, but rather to an unknown factor associated with both delayed fatherhood and schizophrenia.
Division of Public Health Epidemiology, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden mats.ek@ki.se.
Mats
M
Ek
Division of Public Health Epidemiology, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
Susanne
S
Wicks
Division of Public Health Epidemiology, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
Anna C
AC
Svensson
Division of Public Health Epidemiology, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
Selma
S
Idring
Division of Public Health Epidemiology, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
Christina
C
Dalman
D000328:Adult; D000367:Age Factors; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010331:Paternal Age; D011618:Psychotic Disorders / Q000209:etiology*; D012042:Registries; D012559:Schizophrenia / Q000209:etiology*; D013548:Sweden; D055815:Young Adult
epidemiology; parents; psychotic disorders; registries; risk factors