Article

Influence of paternal age in schizophrenia

Pôle de psychiatrie du CHU de Créteil, groupe hospitalier Henri-Mondor-Albert-Chenevier, AP-HP, 40, rue Mesly, 94000 Créteil, France.
L Encéphale (Impact Factor: 0.7). 06/2011; 37(3):199-206. DOI: 10.1016/j.encep.2010.12.005
Source: PubMed

ABSTRACT

La schizophrénie est une pathologie complexe dont la composante génétique est largement démontrée. Malgré une fertilité réduite, le taux de prévalence reste stable et pourrait s’expliquer par l’apparition de mutations génétiques de novo. Un âge paternel avancé est la source majeure de nouvelles mutations dans l’espèce humaine et pourrait ainsi être associé à un risque accru de développer, dans la descendance, une schizophrénie. L’âge de conception allant croissant, il est possible que la population atteinte de schizophrénie augmente également dans les années à venir. L’objectif de ce travail est de faire une revue de la littérature existante sur ce facteur de risque, d’en synthétiser les résultats et de discuter les différentes interprétations avancées. Toutes les études publiées entre 2000 et 2009 ont été sélectionnées via la Bibliothèque nationale de médecine (PubMed® base de données). Après avoir contrôlé plusieurs facteurs confondants, il existe un lien significatif ente l’âge paternel et le risque de développer une schizophrénie. Plus l’âge paternel est élevé, plus le risque de développer une schizophrénie est important (11 études sur 13 retrouvent des odd-ratios ou des risques relatifs compris entre 1,84 et 4,62 en faveur d’une augmentation du risque chez les descendants de pères plus âgés au moment de la conception). Compte tenu de ce risque important, plusieurs axes de recherche peuvent être développés : l’identification de manière précise de l’âge à partir duquel le risque est augmenté ; l’identification des phénotypes ou endophénotypes associés à un âge paternel avancé ; les mécanismes qui pourraient expliquer cette augmentation du risque.

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Available from: Andrei Szoke, Jul 09, 2015
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    • "Advanced parental age (APA) has been identified as a critical factor with regard to the development of distinct psychiatric pathologies such as schizophrenia and mood disorders in humans [1] [2] [3] [4]. This phenomenon becomes apparent either at advanced maternal or paternal age [5]. "
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    ABSTRACT: Increasing paternal age is known to be associated with a great variety of psychiatric disorders such as schizophrenia or autism. Hence the factor "age" may be taken as strategic tool to analyse specific scientific hypotheses. Additionally, this finding also needs to be addressed in rather pragmatically performed breeding protocols of model organisms, since otherwise artefacts may challenge the validity of the results.Our study was performed to investigate influences of advanced age of mouse dams (30 vs. 16. weeks) on maternal- and offspring behaviour. Adult offspring of both sexes was analysed in a test battery comprising paradigms for exploration, anxiety and depressive-like behaviours. Final blood sampling was conducted for stressphysiological analysis.Interestingly, advanced age of the mothers was associated with increased nest-building quality while maternal activity was unaffected. Moreover "maternal (mice) age" (MA) affected emotionality in the offspring, which became apparent in the dark-light box and the social recognition paradigm.These findings not only emphasize MA to model a potent risk factor with regard to emotional stability, but also underscore the vast necessity to include information about breeding protocols into the methods section of any animal study.
    Full-text · Article · Apr 2015 · Physiology & Behavior
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    • "Illness risk is increased for relatives of probands, likely through rare genetic variants of large effect and common variants with small effects, which may interact with life course exposures to determine illness risk, although most cases have no family history (FH) of the disease (Svrakic et al. 2013). Another risk factor for schizophrenia is advanced paternal age (APA), demonstrated over a decade ago (Malaspina et al. 2001) and well replicated (Hubert et al. 2011). A study in the Icelandic cohort suggested that APA was related to schizophrenia risk through de novo mutations that increased in association with paternal aging (Kong et al. 2012). "

    Full-text · Dataset · Nov 2014
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    • "Illness risk is increased for relatives of probands, likely through rare genetic variants of large effect and common variants with small effects, which may interact with life course exposures to determine illness risk, although most cases have no family history (FH) of the disease (Svrakic et al. 2013). Another risk factor for schizophrenia is advanced paternal age (APA), demonstrated over a decade ago (Malaspina et al. 2001) and well replicated (Hubert et al. 2011). A study in the Icelandic cohort suggested that APA was related to schizophrenia risk through de novo mutations that increased in association with paternal aging (Kong et al. 2012). "
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    ABSTRACT: Leukocyte telomere length (LTL) is longer in association with advanced paternal age, but this association has not been examined along with family history (FH) in schizophrenia. LTL was measured by PCR and compared across cases and controls as part of a study to examine the characteristics of paternal age related schizophrenia. The 53 schizophrenia cases had similar mean LTL as 20 controls, although cases were significantly older than controls and overwhelmingly smoked cigarettes. Multivariate analyses showed that a FH of schizophrenia was associated with longer LTL in both male and female cases. Later paternal age was also related to longer LTL in male cases, but with shorter LTL in female cases. Male cases with older fathers and a FH had the longest LTL. The genetic architecture associated with a familial risk for schizophrenia may include pathways that lengthen LTL. Paternal aging conferred an additional increase in LTL lengthening in male cases, but reduced LTL in female cases. The gender difference in LTL for paternal aging is consistent with the severe illness features reported for female cases with older fathers and could implicate epigenetic alterations in the paternal X chromosomal region with advanced paternal age in association with the risk for schizophrenia.
    Full-text · Article · Jul 2014
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