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Many mental illnesses, including autism, paranoia, and depression, may be underpinned by a conflict between genes inherited from father and mother. It is known that male mammals “turn off” many genes in their spermatozoa, the active work of which is beneficial to the mother, but disadvantageous to the embryo, while females turn off genes in their eggs with the opposite effect. A number of facts indicate that a shift in the balance of gene activity to the "fatherly" side can lead to autism, to the "mother" side - to paranoia, depression and psychosis.
Nature magazine published a short essay by British sociologist Christopher Badcock and Canadian biologist Bernard Crespi in which the authors made a bold attempt to provide a unified explanation for a wide range of mental disorders, including autism, paranoia, depression, schizophrenia and various types of psychosis ... It has long been known that these diseases are largely hereditary, but the patterns of their inheritance do not always fit into standard genetic models. Badcock and Crespi suggested that the reasons for these abnormalities lie not so much in the genes themselves that the child receives from the father and mother, but in the balance of activity (expression) of these genes.
In mammals, including humans, the so-called genomic imprinting is widespread. The essence of the phenomenon is that some genes in the germ cells of parents are “labeled” in a special way (for example, by methylation of cytosine bases). The “tagged” gene in the offspring simply does not work. Some genes are turned off in sperm cells, others in eggs. As a result, the offspring inherits some of the traits only from the mother (if the corresponding genes are disabled in the sperm), some - only from the father (if the gene is disabled in the egg). In the germ cells of the offspring, old labels can be removed and replaced with new ones. As a result, grandchildren may show signs of a grandfather or grandmother that were not expressed in their parents. Imprinting is an example of the so-called "epigenetic", or supragenetic, heredity, that is,
It is assumed that genomic imprinting has evolved due to conflicts of interest between the sexes. In mammals, a somewhat antagonistic relationship develops between a female and her young during intrauterine development. Simply put, the embryo tries to suck out more juices from the mother, and the mother tries to maintain strength and health in order to be able to give birth to other children in the future. The male in this conflict is generally on the side of the calf. It is still unknown from whom the female will give birth to other children, but this one will give birth to her own. Therefore, males turn off in their sperm those genes that protect the mother from the excessive claims of the embryo, and mothers, on the contrary, turn off those genes in their eggs that can enhance these claims. Indeed,
For example, the human embryo receives from both the father and mother one copy of the IGF2 gene, which encodes a protein that promotes rapid growth. Normally, the paternal copy of this gene is active, and the maternal copy is disabled. In this case, as in many others, genomic imprinting works in strict accordance with the theory. The mother, by turning off the IGF2 gene in her eggs, tries to slow down the growth of the baby and thereby make her life easier during pregnancy, childbirth and breastfeeding. The father, supplying the child with an active copy of the gene, on the contrary, is trying to accelerate the growth of the embryo, contrary to the “selfish” interests of the mother.
Thus, the maternal and paternal genes in the fetus are playing a tug-of-war game. As a result of this game, a certain balance is established in the course of evolution, which ensures the normal development of the embryo (for example, turning off a gene by one of the parents can be balanced by an increase in the activity of its working copy as a result of mutations and selection, etc.). Disruption of this balance is fraught with unpleasant consequences. So, if both copies of the IGF2 gene turn out to be active in a human embryo (that is, there is a shift in the balance of gene activity towards the "paternal" side), the child will suffer from the so-called Beckwith -Wiedemann syndrome, which is characterized by a sharply increased weight of the child at birth and overgrowth of some organs. Children,
It is believed that several hundred of the approximately 20,000 human genes undergo genomic imprinting, although this has been precisely established for only 63 genes. Most of them have a serious impact on the growth and development of the child. Especially often genes are imprinted, on which the work of the placenta, the organ responsible for the embryo's withdrawal of resources from the mother's body, depends. In addition, a number of genes associated with brain development are imprinted. This means that genetic tug-of-war can, in principle, affect behavior, thinking, and personality traits.
The authors of the essay mention the ideas of the leading evolutionary theorist of the 20th century, William Donald Hamilton, the author of the concept of the "selfish gene." This concept has gained worldwide fame thanks to the work of Richard Dawkins (see: R. Dawkins. The Selfish Gene). It was Hamilton who first suggested that the most important driving force of evolution could be a conflict between genes, including between genes of the same organism. Hamilton also assumed that internal genetic conflict could have psychological consequences. He noted that people can be divided into two groups: "people-people" and "things-people", that is, people with thinking oriented towards other people, and people with thinking oriented towards things. He attributed himself to the second group and believed that although such a mental structure is fraught with asociality, it was he who allowed him to achieve success in science. According to the authors of the essays, Hamilton suffered from a mild form of autism.
The authors believe that a pronounced tendency towards "thing" thinking is nothing more than autism. Autistic children at an early age are distinguished by self-isolation and extreme selfishness and give a lot of trouble to their caregivers (first of all, of course, mothers). This led the authors to believe that some cases of autism may be due to a paternal shift in the balance of gene activity associated with brain development. This assumption was later factually confirmed. It turned out that people with Beckwith-Wiedemann syndrome have a dramatically increased risk of developing autism. In addition, many autistic individuals have been found to have increased IGF2 gene activity. These data indicate that there may indeed be some connection between autism and genomic imprinting.
If a shift in the balance of gene activity to the "paternal" side leads to autism, then its shift to the "maternal" side, in theory, should give some opposite effect. What mental state can be considered the opposite of autism? According to the authors, the true "antipode" of autism is paranoia, as well as a number of other mental disorders with similar symptoms. For example, autistic people usually do not notice or pay attention to the fact that someone is watching them; paranoid, on the contrary, are painfully sensitive to such things, they often imagine that they are being watched, spied on, spied on. Autists are not capable of coordinated actions in a group, they are not able to understand the reasons, motives and mechanisms of collective activity. Paranoid, on the other hand, are painfully focused on such actions - real or imagined, they are characterized by delusional ideas of a conspiracy nature, in any event they tend to see the intrigues of some secret groups. In general, autists are characterized by a weak development of the so-called "theory of mind" (they cannot understand the motives, thoughts and desires of other people), while paranoid people, on the contrary, have a "theory of mind" in a certain sense hypertrophied. That is why paranoid people see an intelligent design, someone's conscious intervention or secret meaning in almost everything that surrounds them (this is due to their numerous religious, magical and mystical illusions). Many other symptoms of autism and paranoia, according to the authors, are also diametrical opposites. In general, autists are characterized by a weak development of the so-called "theory of mind" (they cannot understand the motives, thoughts and desires of other people), while paranoid people, on the contrary, have a "theory of mind" in a certain sense hypertrophied. That is why paranoids see an intelligent design, someone's conscious intervention or secret meaning in almost everything that surrounds them (this is due to their numerous religious, magical and mystical illusions).
The authors suggest that the symptoms of autism in general stem from an underdeveloped "theory of mind" (they call this state "hypentalism"), while paranoia and a wide range of psychotic deviations are characterized by the opposite state - "hypermentalism."
According to the authors, small deviations in the balance of genomic imprinting in the “maternal” side should lead not only to a slowdown in the growth of children, which makes them “cheaper” to bear and feed, but also to such changes in behavior and thinking that make it easier for mothers to take care of them. ... Such children should be more sensitive, less demanding, they should have a stronger developed ability to feel the mental state of loved ones and subtly respond to it. A strong shift in the balance to the "maternal" side leads to psychosis. On the contrary, a slight shift in the balance towards the “fatherly” side should change the behavior of children towards greater exactingness, selfishness, and concentration “on things”. A strong "paternal" bias leads to severe "hypentalism" and autism.
The researchers cite a number of facts in support of their hypothesis. So, geneticists have found on the 15th human chromosome a region containing several genes that undergo imprinting. Children whose balance of the activity of these genes is shifted to the "paternal" side suffer from Angelman syndrome. Such children at an early age are hyperactive and constantly require attention to themselves. Among them, the percentage of autistic people is very high. Children whose balance is shifted to the "maternal" side suffer from Prader-Willi syndrome. They are distinguished by drowsiness, exceptional calmness and undemanding at an early age; later, most of them begin to suffer from various psychoses and depression.
According to the authors, there are two main factors on which the ratio of hypo- and hypermentalist tendencies in human thinking depends. The first factor, as we already know, is the activity of genes undergoing parental imprinting. The second factor is gender. For men, in general, hypomenalism and "orientation towards things" are more characteristic, for women - hypermentalism and "orientation towards people".
Incidentally, a strong positive correlation has recently been shown between the concentration of the male sex hormone testosterone in the blood of the embryo during fetal development and the propensity of the child to autism. In other words, the authors believe that the thinking of men normally tilts slightly towards autism, and women - towards paranoia. This is consistent with the fact that autism is more common in men than in women. The authors also note that their theory helps explain another fact that has so far remained unexplained: although women are less likely to have autism than men, their disease is usually more severe. In contrast, schizophrenia and depression tend to be more severe in men than in women.
Perhaps, the authors believe, mental illness develops more often, but proceeds in a milder form, when the direction of action of two factors - gender and imprinting balance - coincide, as in men in the case of autism or in women with depression. When a failure of genomic imprinting directs a person's mental development in the direction opposite to that to which he is predisposed due to his gender, the disease develops less often, but proceeds in a more severe form, as in women with autism and men suffering from psychosis.
To test the hypothesis, it is necessary to study in detail all human genes undergoing parental imprinting and to identify the function of these genes. This work is now progressing very successfully, and research methods are rapidly improving. If an interesting and bold hypothesis about the common nature of a wide range of mental illnesses is confirmed, it will even be possible to think about the development of universal methods of their treatment and prevention. Indeed, in pharmacological adjustment of gene activity nothing is impossible - technically it is much easier than changing the nucleotide sequence of a gene in all cells of the body.
Nature magazine published a short essay by British sociologist Christopher Badcock and Canadian biologist Bernard Crespi in which the authors made a bold attempt to provide a unified explanation for a wide range of mental disorders, including autism, paranoia, depression, schizophrenia and various types of psychosis ... It has long been known that these diseases are largely hereditary, but the patterns of their inheritance do not always fit into standard genetic models. Badcock and Crespi suggested that the reasons for these abnormalities lie not so much in the genes themselves that the child receives from the father and mother, but in the balance of activity (expression) of these genes.
In mammals, including humans, the so-called genomic imprinting is widespread. The essence of the phenomenon is that some genes in the germ cells of parents are “labeled” in a special way (for example, by methylation of cytosine bases). The “tagged” gene in the offspring simply does not work. Some genes are turned off in sperm cells, others in eggs. As a result, the offspring inherits some of the traits only from the mother (if the corresponding genes are disabled in the sperm), some - only from the father (if the gene is disabled in the egg). In the germ cells of the offspring, old labels can be removed and replaced with new ones. As a result, grandchildren may show signs of a grandfather or grandmother that were not expressed in their parents. Imprinting is an example of the so-called "epigenetic", or supragenetic, heredity, that is,
It is assumed that genomic imprinting has evolved due to conflicts of interest between the sexes. In mammals, a somewhat antagonistic relationship develops between a female and her young during intrauterine development. Simply put, the embryo tries to suck out more juices from the mother, and the mother tries to maintain strength and health in order to be able to give birth to other children in the future. The male in this conflict is generally on the side of the calf. It is still unknown from whom the female will give birth to other children, but this one will give birth to her own. Therefore, males turn off in their sperm those genes that protect the mother from the excessive claims of the embryo, and mothers, on the contrary, turn off those genes in their eggs that can enhance these claims. Indeed,
For example, the human embryo receives from both the father and mother one copy of the IGF2 gene, which encodes a protein that promotes rapid growth. Normally, the paternal copy of this gene is active, and the maternal copy is disabled. In this case, as in many others, genomic imprinting works in strict accordance with the theory. The mother, by turning off the IGF2 gene in her eggs, tries to slow down the growth of the baby and thereby make her life easier during pregnancy, childbirth and breastfeeding. The father, supplying the child with an active copy of the gene, on the contrary, is trying to accelerate the growth of the embryo, contrary to the “selfish” interests of the mother.
Thus, the maternal and paternal genes in the fetus are playing a tug-of-war game. As a result of this game, a certain balance is established in the course of evolution, which ensures the normal development of the embryo (for example, turning off a gene by one of the parents can be balanced by an increase in the activity of its working copy as a result of mutations and selection, etc.). Disruption of this balance is fraught with unpleasant consequences. So, if both copies of the IGF2 gene turn out to be active in a human embryo (that is, there is a shift in the balance of gene activity towards the "paternal" side), the child will suffer from the so-called Beckwith -Wiedemann syndrome, which is characterized by a sharply increased weight of the child at birth and overgrowth of some organs. Children,
It is believed that several hundred of the approximately 20,000 human genes undergo genomic imprinting, although this has been precisely established for only 63 genes. Most of them have a serious impact on the growth and development of the child. Especially often genes are imprinted, on which the work of the placenta, the organ responsible for the embryo's withdrawal of resources from the mother's body, depends. In addition, a number of genes associated with brain development are imprinted. This means that genetic tug-of-war can, in principle, affect behavior, thinking, and personality traits.
The authors of the essay mention the ideas of the leading evolutionary theorist of the 20th century, William Donald Hamilton, the author of the concept of the "selfish gene." This concept has gained worldwide fame thanks to the work of Richard Dawkins (see: R. Dawkins. The Selfish Gene). It was Hamilton who first suggested that the most important driving force of evolution could be a conflict between genes, including between genes of the same organism. Hamilton also assumed that internal genetic conflict could have psychological consequences. He noted that people can be divided into two groups: "people-people" and "things-people", that is, people with thinking oriented towards other people, and people with thinking oriented towards things. He attributed himself to the second group and believed that although such a mental structure is fraught with asociality, it was he who allowed him to achieve success in science. According to the authors of the essays, Hamilton suffered from a mild form of autism.
The authors believe that a pronounced tendency towards "thing" thinking is nothing more than autism. Autistic children at an early age are distinguished by self-isolation and extreme selfishness and give a lot of trouble to their caregivers (first of all, of course, mothers). This led the authors to believe that some cases of autism may be due to a paternal shift in the balance of gene activity associated with brain development. This assumption was later factually confirmed. It turned out that people with Beckwith-Wiedemann syndrome have a dramatically increased risk of developing autism. In addition, many autistic individuals have been found to have increased IGF2 gene activity. These data indicate that there may indeed be some connection between autism and genomic imprinting.
If a shift in the balance of gene activity to the "paternal" side leads to autism, then its shift to the "maternal" side, in theory, should give some opposite effect. What mental state can be considered the opposite of autism? According to the authors, the true "antipode" of autism is paranoia, as well as a number of other mental disorders with similar symptoms. For example, autistic people usually do not notice or pay attention to the fact that someone is watching them; paranoid, on the contrary, are painfully sensitive to such things, they often imagine that they are being watched, spied on, spied on. Autists are not capable of coordinated actions in a group, they are not able to understand the reasons, motives and mechanisms of collective activity. Paranoid, on the other hand, are painfully focused on such actions - real or imagined, they are characterized by delusional ideas of a conspiracy nature, in any event they tend to see the intrigues of some secret groups. In general, autists are characterized by a weak development of the so-called "theory of mind" (they cannot understand the motives, thoughts and desires of other people), while paranoid people, on the contrary, have a "theory of mind" in a certain sense hypertrophied. That is why paranoid people see an intelligent design, someone's conscious intervention or secret meaning in almost everything that surrounds them (this is due to their numerous religious, magical and mystical illusions). Many other symptoms of autism and paranoia, according to the authors, are also diametrical opposites. In general, autists are characterized by a weak development of the so-called "theory of mind" (they cannot understand the motives, thoughts and desires of other people), while paranoid people, on the contrary, have a "theory of mind" in a certain sense hypertrophied. That is why paranoids see an intelligent design, someone's conscious intervention or secret meaning in almost everything that surrounds them (this is due to their numerous religious, magical and mystical illusions).
The authors suggest that the symptoms of autism in general stem from an underdeveloped "theory of mind" (they call this state "hypentalism"), while paranoia and a wide range of psychotic deviations are characterized by the opposite state - "hypermentalism."
According to the authors, small deviations in the balance of genomic imprinting in the “maternal” side should lead not only to a slowdown in the growth of children, which makes them “cheaper” to bear and feed, but also to such changes in behavior and thinking that make it easier for mothers to take care of them. ... Such children should be more sensitive, less demanding, they should have a stronger developed ability to feel the mental state of loved ones and subtly respond to it. A strong shift in the balance to the "maternal" side leads to psychosis. On the contrary, a slight shift in the balance towards the “fatherly” side should change the behavior of children towards greater exactingness, selfishness, and concentration “on things”. A strong "paternal" bias leads to severe "hypentalism" and autism.
The researchers cite a number of facts in support of their hypothesis. So, geneticists have found on the 15th human chromosome a region containing several genes that undergo imprinting. Children whose balance of the activity of these genes is shifted to the "paternal" side suffer from Angelman syndrome. Such children at an early age are hyperactive and constantly require attention to themselves. Among them, the percentage of autistic people is very high. Children whose balance is shifted to the "maternal" side suffer from Prader-Willi syndrome. They are distinguished by drowsiness, exceptional calmness and undemanding at an early age; later, most of them begin to suffer from various psychoses and depression.
According to the authors, there are two main factors on which the ratio of hypo- and hypermentalist tendencies in human thinking depends. The first factor, as we already know, is the activity of genes undergoing parental imprinting. The second factor is gender. For men, in general, hypomenalism and "orientation towards things" are more characteristic, for women - hypermentalism and "orientation towards people".
Incidentally, a strong positive correlation has recently been shown between the concentration of the male sex hormone testosterone in the blood of the embryo during fetal development and the propensity of the child to autism. In other words, the authors believe that the thinking of men normally tilts slightly towards autism, and women - towards paranoia. This is consistent with the fact that autism is more common in men than in women. The authors also note that their theory helps explain another fact that has so far remained unexplained: although women are less likely to have autism than men, their disease is usually more severe. In contrast, schizophrenia and depression tend to be more severe in men than in women.
Perhaps, the authors believe, mental illness develops more often, but proceeds in a milder form, when the direction of action of two factors - gender and imprinting balance - coincide, as in men in the case of autism or in women with depression. When a failure of genomic imprinting directs a person's mental development in the direction opposite to that to which he is predisposed due to his gender, the disease develops less often, but proceeds in a more severe form, as in women with autism and men suffering from psychosis.
To test the hypothesis, it is necessary to study in detail all human genes undergoing parental imprinting and to identify the function of these genes. This work is now progressing very successfully, and research methods are rapidly improving. If an interesting and bold hypothesis about the common nature of a wide range of mental illnesses is confirmed, it will even be possible to think about the development of universal methods of their treatment and prevention. Indeed, in pharmacological adjustment of gene activity nothing is impossible - technically it is much easier than changing the nucleotide sequence of a gene in all cells of the body.
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