Imprinted brain theory
||This article may lend undue weight to certain ideas, incidents, or controversies. (April 2014)|
The conflict theory of imprinting
Genomic imprinting is an epigenetic process by which certain genes are expressed in a parent-of-origin-specific manner. The imprinted brain theory is a variant of the conflict theory of imprinting which argues that in diploid organisms, such as humans, the maternal and paternal set of genes may have antagonistic reproductive interests since the mother and father may have antagonistic interests regarding the development of the child. The conflict theory of imprinting is supported by an extensive amount of empirical evidence and is, according to Bernard Crespi in a 2008 review, the only comprehensive theory explaining observed patterns of imprinting in humans and other organisms.
The imprinted brain theory argues that since it is uncertain if a woman's other and future children have and will have the same father, as well as the father generally having lower parental investment, it may be in the father's reproductive interest for his child to maximize usage of the mother's resources while it may be in the mother's interest to limit this in order to have resources for her other and future children.
Thus, a genomic imprinting with slight maternal bias would be associated with factors such as decreased growth, more tractable behavior, and an empathizing and less self-centered personality causing less demands on the mother. The opposite would occur for a slight paternal bias.
However, an extreme genomic imprinting in favor of maternal genes is argued to cause psychosis such as in schizophrenia spectrum disorders while an extreme genomic imprinting in favor of paternal genes is argued to cause autism spectrum disorders. Thus, people with schizophrenia empathize and read too much into situations and see hidden intentions everywhere, causing delusions and paranoia, while people with autism seem to be blind to the intentions of others. This could be confirmed by a recent neuroimaging study.
The theory is compatible with various genetic or environmental factors increasing the risk for schizophrenia and autism since many factors, genetic or environmental, are known to affect genomic imprinting. In the view many different factors may change overall imprinting balance and cause similar disorders.
For empirical evidence regarding growth rates, personality and other characteristics that are argued to support the theory, see below. A direct comparison of autism and schizophrenia risks in relation to birth weight within the same population also supports these claims.
Factors such as nutrition during pregnancy can affect imprinting. Schizophrenia is associated with maternal starvation during pregnancy while autism has become increasingly common in affluent societies.
The imprinted brain theory regarding autism spectrum disorders is somewhat similar although not identical with the extreme male brain theory of autism. According to the imprinted brain theory there could be a mismatch and more severe problems when extreme genomic imprinting occurs in the opposite sex, which would explain why female autism (and male psychosis) is often particularly severe, which is a problem for the "extreme male brain" theory which predicts the opposite.
In both mild and severe autism and severe schizophrenia the theory of mind is impaired. This may occur by different mechanisms, such as by the presence of delusions in schizophrenia. However, there is evidence that people with schizotypal personality have an enhanced theory of mind and increased emphatic ability. Lateralization of brain function is decreased in schizophrenia, possibly due to slower brain development. Autism is associated with reversed lateralization compared to normal, possibly due to brain development in infancy and childhood being faster in the right hemisphere and autism being associated with increased brain growth during this period. The mirror neuron system, involved in the theory of mind and empathy, is developed but dysregulated in schizophrenia while it is underdeveloped in autism. Functional imaging shows overactivation of certain brain regions involved in social functioning in schizophrenia while the same regions are underactivated in autism.
Increased paternal age is a strong risk factor for schizophrenia but the rate of ordinary nucleotide mutations appears to be too slow to explain this. However, imprinting is affected by a higher rate of mutation and may thus explain the age effect.
Many imprinted genes are expressed mainly or entirely in the brain suggesting that differences in imprinting have important effects on the brain.
Prader–Willi syndrome is a genetic disorder caused by loss of a set of normally expressed paternally genes, which are imprinted in the mother. It is associated with a high frequency of psychosis. The sister syndrome Angelman syndrome is caused of loss by a set of normally expressed maternally genes, which are imprinted in the father, in the same region and is associated with a high frequency of autism.
XXX syndrome and XXY syndrome, having an extra X chromosome, are associated with a high frequencies of psychosis. Turner syndrome, females having only one X chromosome, is associated with a high frequency of autism.
Some mutations in the MECP2 gene can cause Rett syndrome with autistic symptoms. A different mutation can lead to PPM-X syndrome which includes psychosis. The MECP2 gene is involved in controlling imprinted genes.
Areas off the human genome linked with imprinted genes, psychosis, and parent-of-origin effects each occupy only a very small part of the human genome and overlap of these areas would not be expected if they were unrelated. However, many of the areas overlap.
"In terms of the plausibility of the theory, it is appealing in its symmetry, offering some compelling examples of how the disorders complement each other in their symptomatology. Testable hypotheses are offered but most remain untested. More significantly, far too little is known about the relationship between genes and the aetiology of these disorders, and the understanding of the struggle for expression between parental genes is at a very early stage."
Stearns et al. commented on new genetic evidence supporting the theory in 2010 in an article in the Proceedings of the National Academy of Sciences of the United States of America:
"Here Crespi, Stead, and Elliot extend such analysis of autism and schizophrenia to the impacts of copy number variants (deletions and duplications), further single-gene associations, growth signaling pathways, and brain growth (16). They make a plausible case that the risk of autism is increased by disruption of maternal interests and the uninhibited expression of paternal interests, and that the risk of schizophrenia is increased by the disruption of paternal interests and the uninhibited expression of maternal interests. This is an unconventional but creative approach to serious mental diseases. If it is correct, it will be one of the least expected and most surprising connections in the history of human evolutionary biology."
"Recently, Crespi and Badcock (2008a; Badcock, 2009) argued that genomic imprinting can help explain the evolution of the human brain and the origin of some important psychological disorders. They reviewed a large body of evidence linking imprinted genes to the etiology of autism and psychosis, and proposed that autistic-spectrum conditions are associated with a "paternally biased" pattern of brain development (i.e., over-expression of paternal genes and/or under-expression of maternal genes), while psychotic-spectrum syndromes would be associated to a "maternally biased" development. Although Crespi and Badcock’s model is still speculative in several respects, and has been met with criticism by some researchers (e.g., Dickins, Dickins, & Dickins, 2008; Keller, 2008; Thakkar, Matthews, & Park, 2008; but see also Crespi & Badcock, 2008b; Crespi, Stead, & Elliot, 2009), it does hold considerable promise for an integrated evolutionary theory of psychopathology, and may be useful to understand normal variation in personality as well (see Del Giudice, Angeleri, Brizio & Elena, 2010). A better understanding of the genetic and epigenetic basis of autism and psychosis may also permit the development of improved methods for the early diagnosis and treatment of these conditions."
- In a Novel Theory of Mental Disorders, Parents’ Genes Are in Competition - NYT article
- The Imprinted Brain - Blog about the theory by one of the creators
- Bernard Crespi (2008). "Genomic imprinting in the development and evolution of psychotic spectrum conditions". Biological Reviews. 83: 441–93. PMID 18783362. doi:10.1111/j.1469-185X.2008.00050.x.
- Christopher Badcock; Bernard Crespi (2008). "Battle of the sexes may set the brain". Nature. 454 (7208): 1054–1055. PMID 18756240. doi:10.1038/4541054a.
- Benedict Carey (2008): In a Novel Theory of Mental Disorders, Parents’ Genes Are in Competition, The New York Times.
- Angela Ciaramidaro (2015). "Schizophrenia and Autism as Contrasting Minds: Neural Evidence for the Hypo-Hyper-Intentionality Hypothesis (Free)". Schizophrenia Bulletin. 41 (1): 171–179. doi:10.1093/schbul/sbu124.
Consistent with these studies, it has been hypothesized that ASD and SCZ thus may be located at the extreme ends of a cognitive architecture ranging from a mechanistic hypo-intentional (to treat person as objects) to a mentalistic hyper-intentional (to treat objects as persons) mode of cognition, respectively.
- Bernard Crespi, Christopher Badcock (2008). "Psychosis and autism as diametrical disorders of the social brain" (PDF). Behavioral and Brain Sciences. 31 (3): 241–261; discussion 261–320. PMID 18578904. doi:10.1017/S0140525X08004214.
- Sean G. Byars; et al. (2014). "Opposite risk patterns for autism and schizophrenia are associated with normal variation in birth size: Phenotypic support for hypothesized diametric gene-dosage effects" (PDF). Proceedings of the Royal Society B: Biological Sciences. 281 (1794): 20140604. PMC . PMID 25232142. doi:10.1098/rspb.2014.0604.
- Badcock, C. (2011). "The imprinted brain: How genes set the balance between autism and psychosis". Epigenomics. 3 (3): 345–359. PMID 22122342. doi:10.2217/epi.11.19.
- Bernard Crespi (2011). "Autism and cancer risk". Autism Research. 4 (4): 302–310. PMID 21823244. doi:10.1002/aur.208.
- Jones, Rebecca (2012). "Brief Report: Female-To-Male Transsexual People and Autistic Traits". Journal of Autism and Developmental Disorders. 44 (301): 301–306. doi:10.1007/s10803-011-1227-8.
- Rajkumar, Ravi (2014). "Gender Identity Disorder and Schizophrenia: Neurodevelopmental Disorders with Common Causal Mechanisms?". Schizophrenia Research and Treatment. 2014: 1–8. doi:10.1155/2014/463757.
- Crespi, B.; Stead, P.; Elliot, M. (2009). "Colloquium Paper: Comparative genomics of autism and schizophrenia". Proceedings of the National Academy of Sciences. 107: 1736–41. PMC . PMID 19955444. doi:10.1073/pnas.0906080106.
- Stearns, S. C.; Nesse, R. M.; Govindaraju, D. R.; Ellison, P. T. (2010). "Colloquium Paper: Evolutionary perspectives on health and medicine". Proceedings of the National Academy of Sciences. 107: 1691–1695. doi:10.1073/pnas.0914475107.
- Johansson, C. F. (2010). "The Imprinted Brain: How Genes Set the Balance between Autism and Psychosis". The British Journal of Psychiatry. 196 (4): 334–335. doi:10.1192/bjp.bp.109.071084.
- Schlomer, G. L.; Del Giudice, M.; Ellis, B. J. (2011). "Parent–offspring conflict theory: An evolutionary framework for understanding conflict within human families". Psychological Review. 118 (3): 496–521. PMID 21604906. doi:10.1037/a0024043.