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Neuropsychopharmacology REVIEWS (2015) 40, 129140& 2015 American College of Neuropsychopharmacology. All rights reserved 0893-133X/15
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Mechanisms of Non-Genetic Inheritance and Psychiatric Disorders
Miklos Toth*,1
1Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA
Inheritance is typically associated with the Mendelian transmission of information from parents to offspring by alleles (DNA sequence). However, empirical data clearly suggest that traits can be acquired from ancestors by mechanisms that do not involve genetic alleles, referred to as non-genetic inheritance. Information that is non-genetically transmitted across generations includes parental experience and exposure to certain environments, but also parental mutations and polymorphisms, because they can change the parental intrinsic environment. Non-genetic inheritance is not limited to the first generation of the progeny, but can involve the grandchildren and even further generations. Non-genetic inheritance has been observed for multiple traits including overall development, cardiovascular risk and metabolic symptoms, but this review will focus on the inheritance of behavioral abnormalities pertinent to psychiatric disorders. Multigenerational non-genetic inheritance is often interpreted as the transmission of epigenetic marks, such as DNA methylation and chromatin modifications, via the gametes (transgenerational epigenetic inheritance). However, information can be carried across generations by a large number of bioactive substances, including hormones, cytokines, and even microorganisms, without the involvement of the gametes. We reason that this broader definition of non-genetic inheritance is more appropriate, especially in the context of psychiatric disorders, because of the well-recognized role of parental and early life environmental factors in later life psychopathology. Here we discuss the various forms of non-genetic inheritance in humans and animals, as well as rodent models of psychiatric conditions to illustrate possible mechanisms.
Neuropsychopharmacology Reviews (2015) 40, 129140; doi:http://dx.doi.org/10.1038/npp.2014.127
Web End =10.1038/npp.2014.127 ; published online 25 June 2014
INTRODUCTION
The traditional view that Mendelian inheritance can fully explain heritability is no longer satisfactory (Bonduriansky, 2012). Several lines of evidence indicate the existence of multiple mechanisms that underlie the acquisition and transmission of traits across generations (Figure 1). Non-genetic inheritance could partly explain missing heritability, the discrepancy between the high heritability of complex disorders, and the small number of identified risk genes associated with those disorders (Manolio et al, 2009; Slatkin, 2009). In principle, non-genetic inheritance comprises all parentoffspring mechanisms of inheritance, except...