Wednesday, April 8, 2009

Schizophrenia and Autism as Diametrically Opposed Disorders Determined by a Genetic Tug of War

Autism and Schizophrenia are intensely studied disorders, and many hypothesis exist theorizing environmental and genetic causes. Bernard Crespi and Christopher Badcock recently developed a theory that could not only provide insight into what causes these two disorders but also could connect the two in an illuminating way. The basis of their theory is made of two parts.
1) That Autism and Schizophrenia are diametrically related disorders.
2) That a tug of war between maternal and paternal genes can lead to the expression of either disorder in their offspring.

This is a deeply controversial explanation both because it is a large overriding explanation of such a huge range of mental conditions and also because gender assumptions underlie the genetic part of the theory.

Autism and Schizophrenia as Diametrically Opposed

“The core of this hypothesis is that psychosis and autism represent two extremes on a cognitive
spectrum with normality at its center (Crespi, 2008).”

Autism is characterized by impairments in social interaction. Generally this is characterized by some combination of deficits in language and communication, and repetitive and restricted behaviors and interests. Autistic behavior tends to be more self-oriented or selfish than normal behavior. Often autistic individuals are mechanistic focused as opposed to mentalistic, Meaning they are concerned with their physical environment as opposed to social interaction. Brain size and head size is generally larger with a notable increase in cortical thickness. The hippocampus is larger which may be related to the cause of the enhanced visual-spatial, mathematic and mechanistic aspects of some autistic cognition. The amygdala is highly activated when humans gaze upon one another, and when they perceive emotion given off from the eyes and surrounding face. It is especially sensitive to fear. Autistic individuals tend to have larger amygdalas as well as lower levels of oxytocin.

Schizophrenic behavior is grouped into either positive or negative symp
toms. Positive symptoms are hyper-sensitivity or awareness to the outside world, for example the development of hallucinations or delusions. Negative symptoms are loss of will, flat affect and psychomotor retardation. Whole brain size is smaller in schizophrenia with reductions in grey matter, white matter and lower cortical thickness. The hippocampus is smaller in size and altered in shape which could contribute to symptoms like paranoia and delusions because it is responsible for updating and creating one’s social and spatial worldviews and coordinates its communication with the amygdala. The amygdala is smaller and seemingly underdeveloped, possibly leading to their notable over-responsiveness to gaze and misunderstanding of gaze ie paranoia.

Badcock and Crespi concluded that the characteristic symptoms of autism and schizophrenia are opposite, where autism is generally more inward, schizophrenia tends to be an exaggerated concern with the outside world resulting in paranoia.

The Case for Imprinting and Maternal and Paternal Genes Are Involved

Some genes are expressed when inherited from one parent but not when inherited from the other. “This is achieved through a process called imprinting, in which genes in the sperm and egg are marked for expression or silencing in a later embryo and child (Badcock, Crespi, Battle of the Sexes May Set the Brain, 2008).”
Imprinted genes have the most far-reaching effects on growth and development, and imprinting is “also common among genes that drive brain development (Badcock, Crespi Battle of the Sexes May Set the Brain, 2008),”

Asperger viewed autism as an extreme variant of male intelligence. This idea stemmed from the view that autistics had difficulty empathizing, and socializing as well as a high capacity for order and systematizing rules governing objects. This was also consistent with the higher number of male autistics as well as increased empathy, emotional and language development in girls.

In schizophrenia Crespi and Badcock viewed negative symptoms as less influenced by the paternal brain and relatively unaffected by the maternal brain. Positive symptoms, on the other hand, are more a consequence of the maternal brain as they are hyper-mentalistic outputs to the limbic system, creating fear or paranoia.

Prader-Willi and Angelman Syndromes As Evidence

These two syndromes provide a great piece of evidence for Crespi and Badcock’s theory, because they result from opposite disruptions on a strand of imprinted genes on chromosome 15. Scientists know that Prader-Willi syndrome is from an increase in maternal gene expression, while Angelman syndrome occurs when there is an imbalance towards less maternal gene expression. Prader-Willi is characterized by low birth weight and a high incidence of psychosis in adulthood. Angelman is characterized by autistic-like behavior: non-reciprocal social behavior, poor eye contact, and repetitive behaviors.

Crespi and Badcock concluded that the correlation between psychosis in Prader-Willi syndrome and autistic behavior in Angelman syndrome supports a diametric relation between imprinted genes and a connection between maternal and paternal gene expression.

Beckwith-Wiedemann and Silver-Russell Syndrome as More Evidence

Crespi and Badcock thought that these syndromes would act almost as sister syndromes to
Prader-Willi and Angelman. The data is a little less clear. A gene called IGF2, which controls growth is normally only expressed from one’s father. Paternal gene expression bias creates Beckwith-Wiedemann syndrome. Normally the child’s birth weight is more than 50% above normal, and has a greatly elevated risk of autism. Maternal gene expression causes Silver-Russell syndrome shows lower weight and higher incidence of psychosis. I should note that I found less definitive data on these two syndromes.


Crespi and Badcock concluded that based on the research about autism and schizophrenia one can see their diametrically opposed features. In each comparison between the above syndromes, Crespi and Badcock noted that there was a connection between autism and paternal gene expression as well as psychosis and maternal gene expression. Ultimately they supported their hypothesis based on these relationships. Their theory opens up a new way to examine autism and schizophrenia, and although Crespi and Badcock have compelling evidence there is still much research to be done to either confirm or contradict their findings. It is another valuable part of the quest to better understand the origins of these two disorders.


1. Badcock, C. &. Crespi, B.(2008, August 28). Battle of the Sexes May Set the Brain. Nature , 454, pp. 1054-1055.
2. Badcock, C. (2008). Nature or Nurture? Genes or Society? Autism or Psychosis? A New Theory Resolves Some Long-Standing Contradictions in Explaining Mental Illness. Sociology Research News , 5 (3), 2-4.
3. Carey, B. (2008, November 11). In a Novel Theory of Mental Disorders, Parents' Genes Are in Competition. New York Times .
4. Crespi, B. &. Badcock, C. (2008). Psychosis and Autism as Diametrical Disorders of the Social Brain. Behavioral and Brain Sciences , 31, 241-320.


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