Schizophrenia and twins

‘Schizophrenia makes people lonely and vulnerable’

When Corven and Michael were born in February 1984, the whole family celebrated the gift of healthy identical twin boys. Michael was born first and was the heavier baby, but at 10 kg, Corven was big enough to take care of himself, and shrugged off Michael’s thirty-minute age advantage.

The boys had an uneventful but caring childhood. Their mother, Maureen, relaxed her strict vegetarian beliefs to allow the boys chicken and white meat, but they could not be persuaded to eat broccoli or fish! Their parents smoked and drank alcohol in moderation, but nothing to get worried about. Both boys tried cigarettes as young teenagers, but did not take to them. In recent years, Corven has rediscovered cigarettes and discovered cannabis, but for most of the time their use is under control.

The boys were successful at school, with respectable B grade A-levels, and went to different Universities. Michael chose a law degree, hoping to follow his father and become a solicitor. Corven, always a fan of William Blake, chose English.

In the past year, the family have become very concerned about Corven’s behaviour. Never an early riser, Corven has taken to staying in bed for days at a time, not eating, washing or shaving. He sits in a room with the curtains drawn and the lights off. The only light is from his computer screen. He says that he has found a website, which is all about him. Its pages tell the world exactly what he is thinking, and he hears voices telling him to do things. Sometimes people stand outside in the street below talking to him. He knows there is a global conspiracy to cause a world war, and he has been chosen as the gift-bearer to stop the conflict.

His missed deadlines and erratic behaviour have alarmed the University, who tried to get Corven to see a counsellor. Appointments were made and missed; eventually Corven ran away from his hall of residence, hitch-hiking the one hundred miles back home.

Mum and Dad are frantic with worry. Always tense, the situation is now frightening, since Corven was ‘told’ that Michael and Maureen are part of the conspiracy. At one point, Corven tried to attack his mother, but she distracted him from the impulse. They all live with the fear that it could happen again, and have contacted the family doctor for urgent help. She is cautious, and has insisted that they see mental health specialists.

The specialists will eventually diagnose ‘schizophrenia’, although this is a difficult disease to diagnose because its symptoms vary so much in their nature and severity. Few schizophrenics have all of the characteristics shown by Corven, and there are many people showing some of these characteristics who do not have schizophrenia.

Schizophrenia always involves a patient experiencing perceptual difficulties, distinguishing what is real from what is not real. Delusions (false beliefs) and a sense of persecution may appear. People with schizophrenia often show perceptual disturbances, hearing voices, seeing visual hallucinations or tasting and feeling unusual sensations. These are called positive symptoms because they cause a disturbance of normal behaviour. ‘Negative symptoms’ cause the person to withdraw from normal social life.

Nature and nurture in schizophrenia

Schizophrenia affects about 1 person in 100 in most populations, although the frequency in some families is much greater than this, evidence that inherited (genetic) factors may be important.

Michael and Corven are identical twins (Monozygotic, MZ): a single sperm fertilised an egg to produce one zygote, which later split into two separate embryos. The twins have identical genomes with half of their genes coming from their mother and half from their father. Studies show that the chance of two identical twins developing schizophrenia is about 48%. This is called the ‘frequency of concordance’.

Michael and Corven received some genes from their parents that made it more likely that they will develop schizophrenia. Remarkably, studies of children born to schizophrenic parents but adopted into other families suggest that genetic factors are more important in the development of schizophrenia than the shared family environment. Schizophrenia cannot be explained by ‘bad parenting’ or ‘poverty’ although both of these factors can make an attack more severe.

Yet, the frequency of concordance of 48% can be read in a different way: there is a 52% chance that Michael will not develop schizophrenia, despite having the same genes as Corven. Genes must play a very subtle role in the development of schizophrenia, because they will only lead to schizophrenia when certain factors in the environment are also present. It is perhaps not surprising that psychologists have yet to identify with absolute certainty the genes involved in schizophrenia.

The nature-nurture debate in psychology tried to separate and compare the effects of genes (nature) from the effects of the environment (nurture). Although this model is helpful when considering differences between people in populations, it breaks down when thinking about the development of individuals.

A better model is to think of genes ‘predisposing’ a person to schizophrenia. This does not mean that schizophrenia is the inevitable outcome – far from it. Schizophrenia will develop only if certain ‘risk factors’ are also present in the person’s life.

Think of the genetic predisposition as a car speeding down a road, and the various risk factors as speed cameras lurking along the route. Activating a single speed camera might cause inconvenience, annoyance and some points on the licence, but little else. This could be like the mildly eccentric behaviour shown by those people who have ‘schizotypal’ personalities, but who do not have the full condition.

Triggering more speed cameras will have an increasingly severe effect, until the driver loses the licence to drive. This is like people who have mild or severe schizophrenia. Of course, you have to have a speeding car to trigger the speed cameras. People without the genetic predisposition will never develop schizophrenia, even if they have all of the risk factors in their lives. 

‘risk factors are like speed cameras that trap unwary drivers’

The rest of this article will explore how Corven developed schizophrenia whilst Michael did not. Psychologists understand very little about the origins of schizophrenia, and much of what follows is tentative, but it gives a vivid picture of how the genetic car drives through the speed cameras of life.

The development of schizophrenia

‘The moment when identical twins form’

Maureen’s egg was fertilised by a sperm when it was travelling down one of her Fallopian tubes towards her uterus. Twenty-four hours after fertilisation the egg arrived at the surface of the uterus. It had divided into two cells which had become separated from each other. Michael fell onto the soft surface first, two hours ahead of Corven. What a difference two hours makes.

As soon as the boys touched the surface of the uterus, they started to develop separate attachments to the mother (the placentas). These are the life-support systems for the next forty weeks, providing oxygen and nutrients, and taking away wastes like carbon dioxide and urea. Each twin formed a separate placenta: this increased their chances of developing into healthy babies, but also meant that they were in direct competition with each other for food and oxygen. There is nothing identical about the twins’ lives in the uterus.

Michael arrived first at the uterus surface, and he was able to grow a larger and more effective placenta than Corven. This gave Michael a fairly crucial advantage in what happened next.

Both twins have a gene that produces an unusually large amount of a chemical (an enzyme) that breaks down a phosphoplipid that is an essential component of nerve cells. In most people this is not a problem as long as their diet contains enough nutrients needed to build more phosopholipid. Small amounts of these nutrients can be found in nuts and vegetables, but they are mostly found in fish and meat.

For the twins, developing on the surface of Maureen’s uterus, these nutrients were in short supply. What was there was mostly grabbed by Michael’s placenta. Michael received enough nutrients to offset the damaging effects of his genes, whilst Corven did not. Michael’s nerve cells began to grow normally, whilst Corven’s did not. The first speed camera has flashed.

The twin’s genetic makeup also includes a gene that slows the growth of glia cells. Glia cells are found alongside nerve cells and help to maintain connections between nerve cells in the brain. A single nerve cell may have thousands of other nerve cells connecting with it, so glia play an important (if poorly understood) role in maintaining these connections.

‘Glia cells help nerve cells to make and maintain their connections.’

In October, five weeks into the pregnancy, Maureen developed influenza. It was not too serious, and her body responded by producing antibodies to fight the infection. The virus and the antibodies crossed the twins’ placentas and entered their bloodstreams.

Infection by the virus seems to weaken the actions of the glia still further. The virus is a second speed camera: its effects are felt more severely in Corven than Michael because of the existing deficiency in nutrients.

After five weeks of pregnancy the newly formed nerve cells travel to their position in the brain and form connections with other nerve cells. Nerve cells are made in the inner layers of the brain and travel outwards to the cortex. A protein called ‘reelin’ seems to be important in ensuring that the nerve cells travel to the right place. In some schizophrenics the level of reelin is very low, and nerve cells do not move to the right location. Nerve cells automatically set up connections with neighbouring nerve cells, although these will be affected because the nerve cells are in the wrong places.

When a baby is born each nerve cell contains countless connections (called dendrites) to other cells. During childhood and adolescence, some of these connections are removed (like pruning branches off a tree). Usually the connections that are pruned are those that are ineffective or not used very much.

‘nerve cells form lots of connections with other nerve cells’

A schizophrenic nerve cell has many connections with the ‘wrong’ cells and many connections that are needed for normal information processing are missing. Pruning may become haphazard and cut essential links, whilst allowing unwanted connections to persist.

This takes time to happen and could explain why schizophrenic experiences normally develop only in adults. It could help to explain the confusion schizophrenics experience in processing information. CAT scans of the brains of schizophrenics often show the presence of large fluid-filled spaces (ventricles) that are missing from unaffected brains. Large-scale pruning of these nerve cell connections might help to account for these ventricles.

‘The ventricles in larger in the affected twin’

Looking back, Maureen might have been able to spot the signs that all was not well with Corven. But at the time it was put down to boyish teenage behaviour. The final speed camera that triggered the schizophrenic episode will probably never be known, but pressures of work or stress of personal relationships are the most likely culprits. Cannabis may be a risk factor for some people, and schizophrenics smoke more cigarettes than other groups, although this is not considered to be a risk factor in itself.

Michael and Corven had the activities of their brains assessed using a PET scanner. Corven’s brain had significantly reduced activity in the pre-frontal and temporal lobes compared to Michael. This could explain his symptoms of schizophrenia.

‘PET scans showed differences in activity in the cortex of Michael and Corven’

The reduction in activities of the pre-frontal and temporal lobes seem to be due to an over-stimulation of nerve cells in the limbic system that communicate with the cortex using the neurotransmitter dopamine. The drug clozapine reduces the hallucinations and confusion because it reduces the activity of dopamine, preventing the cortex from being over-stimulated.

Corven is now living at home cared for by his Mum and Dad. He has good days and bad days, but the drugs at least help to stabilise the condition, and keep the daylight nightmares away. Mum and Dad agonise about ‘why’ this has happened, and whose ‘fault’ it is. But it is no-one’s fault: there are just too many speed cameras on the road of life.