Age paternel avancé et risque augmenté de bipolarité
Auteur : Dr Hantouche
Bipo / Cyclo > Bipolarité adulte > Spectre bipolaire : dépistage
Selon une étude du centre de recherches Karolinska Institut de Stockholm parue le 2 septembre 2008, un enfant dont le père est âgé de plus de 30 ans à sa conception aurait davantage de risques d’être atteint d’un trouble bipolaire par rapport à un autre ayant un géniteur de 20 ans lors de sa conception. Ce risque grimperait jusqu’à 37% supplémentaires en cas de paternité après 55 ans selon l’institut suédois.
La chercheuse Emma Frans a indiqué que l’explication serait génétique : "A la différence des femmes, la division des cellules sexuelles chez les hommes se poursuit tout au long de la vie, ce qui accroît le risque de changements génétiques avec les années".
L’étude a été menée sur 14 000 Suédois (hommes et femmes) bipolaires.
A côté de cette explication (dégradation de la qualité génétique du sperme), on peut aussi s’interroger sur le tempérament hyperthymique ou la présence d’un trouble bipolaire chez les hommes acceptant de devenir pères à lʼâge de 55 ans ou plus.
Alors j’ai écrit au Dr Emma FRANS, premier auteur de cette étude et voilà sa réponse :
"Dear Dr Hantouche,
Thank you for the interest in our research,
We also considered family history of psychosis as a potential confounder and controlled for it (model 3). We could then see that the odds ratios were slightly decreased. However, when only adjusting for psychotic fathers (most commonly bipolar fathers) the odds ratios was actually increased (data not shown in the article). Even though we only can look at inpatients this trend shows that a bipolar father is probably not a confounder but rather leads to and underestimation of the results.
We do not have data on personality of the fathers which we consider to be a limitation. Advancing paternal age has earlier been linked to autism and schizophrenia and as far as I know, the only study where the personality issue has been addressed was conducted by Reichenberg et al (Molecular Psychiatry, 2008). Here they showed that the link between autism and advancing paternal age could not be explained by autistic personality traits of the fathers. However, we can not be sure that the same is true for bipolar disorder and bipolar-like personality traits and therefore we acknowledge this limitation in the article.
The hypothesis that has been most recognized explaining the link between paternal age and various disorders such as some cancers, several genetic disorders and recently psychiatric disorders suggests that the quality of sperm decreases with age, leading to genetic and epigenetic alterations that causes these disorders. This might also be the mechanism behind our finding since bipolar is greatly influenced by genes. This is, however, only a hypothesis and other factors might explain the association. We plan to look further into this in future studies and see if we can detect genetic alterations in individuals with psychiatric disorders and old fathers"
Advancing paternal age and bipolar disorder. Arch Gen Psychiatry. 2008 Sep;65(9):1034-40
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO
Box 281, SE-171 77 Stockholm, Sweden
CONTEXT: Advancing paternal age has been reported as a risk factor for neurodevelopmental disorders. OBJECTIVES: To determine whether advanced paternal age is associated with an increased risk of BPD in the offspring and to assess if there was any difference in risk when analyzing patients with early-onset BPD separately. DESIGN: A nationwide nested case-control study based on Swedish registers was performed. Risk for BPD in the offspring of older fathers was estimated using conditional logistic regression analysis controlling for potential confounding of parity, maternal age, socioeconomic status, and parental family history of psychotic disorders. SETTING: Identification of 7,328,100 individuals and their biological parents by linking the nationwide Multigeneration Register and the Hospital Discharge Register. PARTICIPANTS: A total of 13,428 patients with a BPD diagnosis on at least 2 separate hospital admissions was identified. Five healthy control subjects matched for sex and year of birth were randomized to each case. Main Outcome Measure Bipolar disorder based on ICD codes at discharge from hospital treatment. RESULTS: An association between paternal age and risk for BPD in the offspring of older men was noted. The risk increased with advancing paternal age. After controlling for parity, maternal age, socioeconomic status, and family history of psychotic disorders, the offspring of men 55 years and older were 1.37 (95% confidence interval [CI], 1.02-1.84) times more likely to be diagnosed as having BPD than the offspring of men aged 20 to 24 years. The maternal age effect was less pronounced. For early-onset (<20 years) cases, the effect of paternal age was much stronger (odds
ratio, 2.63; 95% CI, 1.19-5.81), whereas no statistically significant maternal age effect was found. CONCLUSIONS: Advanced paternal age is a risk factor for BPD in the offspring. The results are consistent with the hypothesis that advancing paternal age increases the risk for de novo mutations in susceptibility genes for neurodevelopmental disorders.