M28 - MATERNAL AGE AT BIRTH IS ASSOCIATED WITH OFFSPRING LEUKOCYTE TELOMERE LENGTH IN FAMILIES WITH BIPOLAR DISORDER

Abstract

Background There is already a number of reports correlating the effect of parents’ ages with the risk of schizophrenia, but studies looking for an association between parental age and Bipolar Disorder (BD) are scarce and with inconsistent findings. BD has recently been related to a process of accelerated aging, with studies showing association with Leukocyte Telomere Length (LTL) in this population. However, little is known regarding the inheritance of telomere length, with some studies estimating the heritability between 36–86%. About the effect of a parent' age determining LTL, just a few studies have noted longer telomere lengths among offspring of older mothers, and none have shown an interaction or association with a psychiatric disorder. The present investigation assessed the impact of maternal and paternal age at birth as a determinant for the offspring's LTL with and without BD diagnosis within families with several members affected by this disease. Methods Telomere length (T) was estimated in a sample of 144 individuals, including 60 BD patients from 18 Brazilian families, which was measured in relation to the single copy gene (S) – β-globin gene (HBB) – using a singleplex real time PCR, providing a ratio of number of copies of T by S (T/S). The analysis were obtained by a linear mixed model (LMM). Results We found a positive association between maternal age at childbirth and offspring early life telomere length (β=0.012; p=0.015), whereas there was no association of paternal age on offspring telomere length (β=0.008; p=0.232). The LMM analysis also showed a significant positive relationship on interaction between bipolarity and maternal age demonstrates a strong influence on telomere length (β=0.022; p=0.024). The same analysis showed no association on interaction between bipolarity and paternal age (β=0.009; p=0.223). Discussion An association between maternal age and offspring LTL and the interaction with BD was observed. It could be speculated that an influence of oxidative stress during first pregnancy, changes in mitochondrial DNA or even other parent-specific imprinting mechanism, such as DNA methylation, relevant to the neurodevelopment of the brain. To our knowledge, this is the first study evaluating association of maternal age and telomere length in the offspring of families with several members affected by BD. Additional studies are needed to confirm these preliminary findings.