Imprinted brain theory
Encyclopedia
The imprinted brain theory is an evolutionary psychology
theory regarding the causes of autism spectrum
disorders and psychosis
.
s 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 Crespi in a 2008 review, the only comprehensive theory explaining observed patterns of imprinting in humans and other organisms.
, 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 delusion
s and paranoia
, while people with autism seem to be blind to the intentions of others. There are other contrasts such as ambivalence vs. single-mindedness.
Schizotypal personality disorder
is argued to be analogous to Aspberger syndrome with both being less severe forms.
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.
thickness, and low levels of growth factor
s. Autism has been associated with high or normal birth weight, faster body growth, increased brain size, increased cortical thickness, and high levels of growth factors.
Different growth rates and growth factors levels may affect cancer
risk. Schizophrenia is associated with a decreased risk of cancer while the opposite occurs for autism.
Factors such nutrition during pregnancy can affect imprinting. Schizophrenia is associated with maternal starvation during pregnancy while autism have become increasingly common in affluent societies.
Reduced imagination, literalness, and inability at deception characterize autism while enhanced imagination, delusions, and self-deception characterizes schizophrenia. Other characteristics of autism are sensory filtering, narrow focus, and repetitive behaviors while schizophrenia is characterized by reduced sensory filtering, loose associations, and creativity. Pain and smell perception seem increased in autistic children while schizophrenia is associated with reduced pain and smell perception.
Autism is associated with reduced or lacking inner speech while schizophrenia is associated with auditory hallucinations and thought insertion
s.
In schizophrenia global or top-down processing of stimuli seems less affected than local or bottom-up processing. This is also a typical pattern seen in in the processes involved in dyslexia
which is associated with schizophrenia. In contrast, autism is associated with increased local relative to global processing and hyperlexia
is almost always associated with autism.
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.
Autism is characterized by avoidance of gaze while schizophrenia is characterized by increased responsiveness to gaze. In schizophrenia there is a high rate of smoking, possibly a form of self-medication. Smoking rate seems to be low in autism.
The size of the corpus callosum
is increased in schizophrenia while it is decreased in autism. Lateralization of brain function
is decreased in schizophrenia, possibly due to slower brain development, while autism is associated with reversed lateralization compared to normal, possibly due to brain development in infancy and childhood being faster in 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 autsim. Functional imaging
shows overactivation of certain brain regions involved in social functioning while the same regions are underactivated in autism.
Schizophrenia is associated with a female pattern digit ratio
while autism is associated with a male pattern digit ratio.
Increased paternal age is 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 imprinted genes. 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 imprinted genes 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.
The Beckwith-Wiedemann syndrome
is caused by increased effects of paternally imprinted genes and have increased incidence of autism.
Areas off the human genome
linked with 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.
Data from copy number variation and single gene association studies support shared genetic mechanisms causing schizophrenia and autism.
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.
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:
A 2011 literature review by Schlomer, Del Giudice, and Ellis in Psychological Review
stated regarding the theory:
Evolutionary psychology
Evolutionary psychology is an approach in the social and natural sciences that examines psychological traits such as memory, perception, and language from a modern evolutionary perspective. It seeks to identify which human psychological traits are evolved adaptations, that is, the functional...
theory regarding the causes of autism spectrum
Autism spectrum
The term "autism spectrum" is often used to describe disorders that are currently classified as pervasive developmental disorders. Pervasive developmental disorders include autism, Asperger syndrome, Childhood disintegrative disorder, Rett syndrome and Pervasive Developmental Disorder Not Otherwise...
disorders and psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
.
The conflict theory of imprinting
Genomic imprinting is an epigenetic process by which certain geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s are expressed in a parent-of-origin-specific manner. The imprinted brain theory is a variant of the conflict theory of imprinting
The kinship theory of genomic imprinting
The kinship theory of genomic imprinting is an evolutionary account of the origin and evolution of imprinted genes. When two alleles at a diploid locus differ in their optimal gene expression level depending on their parent of origin, the theory predicts the evolutionary outcome to be imprinted...
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 Crespi in a 2008 review, the only comprehensive theory explaining observed patterns of imprinting in humans and other organisms.
The theory
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 investmentParental investment
In evolutionary biology, parental investment is any parental expenditure that benefits one offspring at a cost to parents' ability to invest in other components of fitness...
, 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
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
such as in schizophrenia spectrum disorders while an extreme genomic imprinting in favor of paternal genes is argued to cause autism spectrum
Autism spectrum
The term "autism spectrum" is often used to describe disorders that are currently classified as pervasive developmental disorders. Pervasive developmental disorders include autism, Asperger syndrome, Childhood disintegrative disorder, Rett syndrome and Pervasive Developmental Disorder Not Otherwise...
disorders. Thus, people with schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
empathize and read too much into situations and see hidden intentions everywhere, causing delusion
Delusion
A delusion is a false belief held with absolute conviction despite superior evidence. Unlike hallucinations, delusions are always pathological...
s and paranoia
Paranoia
Paranoia [] is a thought process believed to be heavily influenced by anxiety or fear, often to the point of irrationality and delusion. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concerning a perceived threat towards oneself...
, while people with autism seem to be blind to the intentions of others. There are other contrasts such as ambivalence vs. single-mindedness.
Schizotypal personality disorder
Schizotypal personality disorder
Schizotypal personality disorder, or simply schizotypal disorder, is a personality disorder that is characterized by a need for social isolation, anxiety in social situations, odd behavior and thinking, and often unconventional beliefs.-Genetic:...
is argued to be analogous to Aspberger syndrome with both being less severe forms.
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.
Supporting evidence
Empirical evidence regarding growth rates and personality are argued to support the theory. Autism is associated with overgrowth of the head and body while schizophrenia is associated with slow development and undergrowth. Schizophrenia has been associated with low birth weight, slow maturation, smaller brain size, decreased corticalCerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
thickness, and low levels of growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
s. Autism has been associated with high or normal birth weight, faster body growth, increased brain size, increased cortical thickness, and high levels of growth factors.
Different growth rates and growth factors levels may affect cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
risk. Schizophrenia is associated with a decreased risk of cancer while the opposite occurs for autism.
Factors such nutrition during pregnancy can affect imprinting. Schizophrenia is associated with maternal starvation during pregnancy while autism have become increasingly common in affluent societies.
Reduced imagination, literalness, and inability at deception characterize autism while enhanced imagination, delusions, and self-deception characterizes schizophrenia. Other characteristics of autism are sensory filtering, narrow focus, and repetitive behaviors while schizophrenia is characterized by reduced sensory filtering, loose associations, and creativity. Pain and smell perception seem increased in autistic children while schizophrenia is associated with reduced pain and smell perception.
Autism is associated with reduced or lacking inner speech while schizophrenia is associated with auditory hallucinations and thought insertion
Thought insertion
Thought insertion is the idea that another thinks through the mind of the patient. The patient may sometimes be unable to distinguish between their own thoughts and those inserted into their minds. A patient who is diagnosed with this disorder is found to be convinced of their beliefs and...
s.
In schizophrenia global or top-down processing of stimuli seems less affected than local or bottom-up processing. This is also a typical pattern seen in in the processes involved in dyslexia
Dyslexia
Dyslexia is a very broad term defining a learning disability that impairs a person's fluency or comprehension accuracy in being able to read, and which can manifest itself as a difficulty with phonological awareness, phonological decoding, orthographic coding, auditory short-term memory, or rapid...
which is associated with schizophrenia. In contrast, autism is associated with increased local relative to global processing and hyperlexia
Hyperlexia
Hyperlexia was initially identified by Silberg and Silberg , who defined it as the precocious ability to read words without prior training in learning to read typically before the age of 5. They indicated that children with hyperlexia have a significantly higher word decoding ability than their...
is almost always associated with autism.
In both mild and severe autism and severe schizophrenia the theory of mind
Theory of mind
Theory of mind is the ability to attribute mental states—beliefs, intents, desires, pretending, knowledge, etc.—to oneself and others and to understand that others have beliefs, desires and intentions that are different from one's own...
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.
Autism is characterized by avoidance of gaze while schizophrenia is characterized by increased responsiveness to gaze. In schizophrenia there is a high rate of smoking, possibly a form of self-medication. Smoking rate seems to be low in autism.
The size of the corpus callosum
Corpus callosum
The corpus callosum , also known as the colossal commissure, is a wide, flat bundle of neural fibers beneath the cortex in the eutherian brain at the longitudinal fissure. It connects the left and right cerebral hemispheres and facilitates interhemispheric communication...
is increased in schizophrenia while it is decreased in autism. Lateralization of brain function
Lateralization of brain function
A longitudinal fissure separates the human brain into two distinct cerebral hemispheres, connected by the corpus callosum. The sides resemble each other and each hemisphere's structure is generally mirrored by the other side. Yet despite the strong anatomical similarities, the functions of each...
is decreased in schizophrenia, possibly due to slower brain development, while autism is associated with reversed lateralization compared to normal, possibly due to brain development in infancy and childhood being faster in in the right hemisphere and autism being associated with increased brain growth during this period. The mirror neuron
Mirror neuron
A mirror neuron is a neuron that fires both when an animal acts and when the animal observes the same action performed by another. Thus, the neuron "mirrors" the behaviour of the other, as though the observer were itself acting. Such neurons have been directly observed in primate and other...
system, involved in the theory of mind and empathy, is developed but dysregulated in schizophrenia while it is underdeveloped in autsim. Functional imaging
Functional imaging
Functional imaging , is a method of detecting or measuring changes in metabolism, blood flow, regional chemical composition, and absorption....
shows overactivation of certain brain regions involved in social functioning while the same regions are underactivated in autism.
Schizophrenia is associated with a female pattern digit ratio
Digit ratio
The digit ratio is the ratio of the lengths of different digits or fingers typically measured from the bottom crease where the finger joins the hand to the tip of the finger. It has been suggested by some scientists that the ratio of two digits in particular, the 2nd and 4th , is affected by...
while autism is associated with a male pattern digit ratio.
Increased paternal age is strong risk factor for schizophrenia but the rate of ordinary nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
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 imprinted genes. It is associated with a high frequency of psychosis. The sister syndrome Angelman syndrome
Angelman syndrome
Angelman syndrome is a neuro-genetic disorder characterized by intellectual and developmental delay, sleep disturbance, seizures, jerky movements , frequent laughter or smiling, and usually a happy demeanor....
is caused of loss by a set of normally expressed maternally imprinted genes in the same region and is associated with a high frequency of autism.
XXX syndrome and XXY syndrome, having an extra X chromosome
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
, are associated with a high frequencies of psychosis. Turner syndrome
Turner syndrome
Turner syndrome or Ullrich-Turner syndrome encompasses several conditions in human females, of which monosomy X is most common. It is a chromosomal abnormality in which all or part of one of the sex chromosomes is absent...
, females having only one X chromosome, is associated with a high frequency of autism.
Some mutations in the MECP2
MECP2
MECP2 is a gene that provides instructions for making its protein product, MECP2, also referred to as MeCP2. MECP2 appears to be essential for the normal function of nerve cells. The protein seems to be particularly important for mature nerve cells, where it is present in high levels...
gene can cause Rett syndrome
Rett syndrome
Rett syndrome is a neurodevelopmental disorder of the grey matter of the brain that almost exclusively affects females. The clinical features include small hands and feet and a deceleration of the rate of head growth . Repetitive hand movements, such as wringing and/or repeatedly putting hands into...
with autistic symptoms. A different mutation can lead to PPM-X syndrome which includes psychosis. The MECP2 gene is involved in controlling imprinted genes.
The Beckwith-Wiedemann syndrome
Beckwith-Wiedemann syndrome
Beckwith–Wiedemann syndrome is an overgrowth disorder usually present at birth characterized by an increased risk of childhood cancer and certain congenital features. Originally, Dr...
is caused by increased effects of paternally imprinted genes and have increased incidence of autism.
Areas off the human genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
linked with 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.
Data from copy number variation and single gene association studies support shared genetic mechanisms causing schizophrenia and autism.
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.
Reception
In a book review in The British Journal of Psychiatry of a 2009 book about the theory, Carl Fredrik Johansson wrote:"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."
A 2011 literature review by Schlomer, Del Giudice, and Ellis in Psychological Review
Psychological Review
Psychological Review is a scientific journal that publishes articles on psychological theory. It was founded by Princeton psychologist James Mark Baldwin and Columbia psychologist James McKeen Cattell in 1894 as a publication vehicle for psychologists not connected with the Clark laboratory of G....
stated regarding the theory:
"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."
External links
- 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