Genomic imprinting in the development and evolution of psychotic spectrum conditions

Abstract

I review and evaluate genetic and genomic evidence salient to the hypothesis that the development and evolution of psychotic spectrum conditions have been mediated in part by alterations of imprinted genes expressed in the brain. Evidence from the genetics and genomics of schizophrenia, bipolar disorder, major depression, Prader-Willi syndrome, Klinefelter syndrome, and other neurogenetic conditions support the hypothesis that the etiologies of psychotic spectrum conditions commonly involve genetic and epigenetic imbalances in the effects of imprinted genes, with a bias towards increased relative effects from imprinted genes with maternal expression or other genes favouring maternal interests. By contrast, autistic spectrum conditions, including Kanner autism, Asperger syndrome, Rett syndrome, Turner syndrome, Angelman syndrome, and Beckwith-Wiedemann syndrome, commonly engender increased relative effects from paternally expressed imprinted genes, or reduced effects from genes favouring maternal interests. Imprinted-gene effects on the etiologies of autistic and psychotic spectrum conditions parallel the diametric effects of imprinted genes in placental and foetal development, in that psychotic spectrum conditions tend to be associated with undergrowth and relatively-slow brain development, whereas some autistic spectrum conditions involve brain and body overgrowth, especially in foetal development and early childhood. An important role for imprinted genes in the etiologies of psychotic and autistic spectrum conditions is consistent with neurodevelopmental models of these disorders, and with predictions from the conflict theory of genomic imprinting.

The consequences of polyandry for population viability, extinction risk and conservation

“…Loci of paternal origin in the offspring are predicted to draw more resources from the mother than are maternal loci, because males may not be the father of offspring produced later in the female's life. Such genomic tug-of-war has been proposed to be a causative agent of human diseases including preeclampsia and mental illness [83,84].…”

A Model for Genomic Imprinting in the Social Brain: Juveniles

“…However, no formal analysis of this idea has been undertaken. Such an analysis is necessary not only to explain GI in the juvenile and adult (post-infant) brains, but also to understand recent research linking GI to important neurological disorders within the autistic and psychotic spectra (Badcock and Crespi 2006, 2008;Crespi 2008;Crespi and Badcock 2008).We develop an evolutionary demographic model (Grafen 1985;Taylor and Frank 1996;Rousset 2004;Wild and West 2009;Gardner 2010) that extends the kinship theory of GI to social interactions in a viscous population. Our results provide a novel and unique insight into the role of imprinted genes in the social brain, and allow us to predict how mutations and epimutations of imprinted genes will affect the balance between altruism and egoism in the social brain.…”

“…However, no formal analysis of this idea has been undertaken. Such an analysis is necessary not only to explain GI in the juvenile and adult (post-infant) brains, but also to understand recent research linking GI to important neurological disorders within the autistic and psychotic spectra (Badcock andCrespi 2006, 2008;Crespi 2008;Crespi and Badcock 2008).…”

Successful Computational Prediction of Novel Imprinted Genes from Epigenomic Features

“…Thus, far, about 100 mouse imprinted genes have been identified, with many more genes predicted to be imprinted (http://igc.otago.ac.nz/home.html) (25,32). The identification of novel imprinted genes has become increasingly important with the realization that imprinting defects are associated with a variety of complex disorders, such as obesity, diabetes, and schizophrenia (8,27,39,52).…”