Saner Views Of Schizophrenia

SANER VIEWS OF SCHIZOPHRENIA

A briefing document prepared for the Royal Society and Association of British Science Writers by Wendy Barnaby

December 1995

Summary Schizophrenia is an illness which affects about 1% of the
population but which costs the country as much as cancer or heart
disease to treat.

The four speakers related something of the history of schizophrenia,
and outlined the way in which attitudes to sufferers and their
families have changed. The illness is now recognised to be a
disorder of the brain, and scans show which areas are affected. Some
of these are involved in the processing of language. Current
thinking treats these abnormalities as existing before the onset of
symptoms, which usually happens during the 20s.

Although schizophrenia is pretty equally spread geographically and
throughout social classes, African Caribbean migrants to the UK are
more at risk than other people. The reasons for this are not known.

The causes of the illness are not yet understood. Three of the
speakers (Professors Murray, Lewis and Harrison) think that they are
to be found in both genetic and environmental factors. Dr Crow
argues that the disorder is purely genetic in origin.

SANER VIEWS OF SCHIZOPHRENIA

Sanity, madness and the family revisited

Robin Murray, Professor of Psychological Medicine in the Institute
of Psychiatry, introduced the briefing by saying that just because
schizophrenia is a psychotic condition, there is no need to have
crazy ideas about its causes.

The essential positive symptoms of schizophrenia are auditory
hallucinations and bizarre ideas. Sufferers find that the privacy of
their own thoughts disappears; they hear voices in the brain and may
believe they are the target of remarks made by, for example,
television commentators or strangers in the street. The voices can
be extremely distressing and patients can kill themselves to escape
them.

Society has tried to cope with schizophrenics in different ways. The
number of people in mental hospitals in the UK grew from the 1860s
to 150 000 in the 1950s when anti-psychotic drugs were introduced,
and has since dropped to about 50 000. Community care has been
relatively successful in small towns where families and
psychiatrists can keep tabs on patients, but in large cities such as
London this is impossible and there are frequently no beds to admit
patients to when they become psychotic. Here the system has largely
broken down. Anti-psychotic drugs do enable sufferers to live in the
community, providing they take their medication; but these drugs
have unpleasant side-effects. A raft of new drugs will be introduced
over the next couple of years, and they ought to have fewer
side-effects so more patients ought to take their medication. There
is also some evidence that cognitive/behavioural treatment can be
useful in modifying some symptoms of psychosis.

The medical view of the condition itself has also changed. In the
late 1950s, R.D. Laing published The Divided Self and later, with
Esterson, Sanity, Madness and the Family. With these books he
founded the anti-psychiatry movement, arguing that schizophrenia was
not a medical disorder but a coping mechanism adopted by sensitive
people to weather pathological family interactions. This view put
the blame for the condition squarely on other family members, many
of whom suffered tremendously as a result. In fact, it is now
recognised that the condition is caused by a brain dysfunction, and
imaging of the brain has begun to show what is going wrong.

There have been two main theories that have tried to explain
auditory hallucinations. One says they result from a disorder of
inner speech (the sort of speech we hear in our heads when we recite
poetry silently to ourselves). Another says it is an abnormality in
that part of the brain which interprets external speech so that
memories of speech are inserted into consciousness.

When people use inner speech they activate part of the brain in the
left frontal lobe known as Broca's area. This can be seen on PET
(positron emission tomography) scans which map regional blood flows
in the brain. It has recently been shown that when patients are
hearing voices, Broca's area is active. This suggests that the
hallucinations are a misinterpretation of inner speech. We now also
know (see The Lancet of 2 September 1995, McGuire et al) that the
same area of the brain is activated when normal subjects repeat to
themselves in their minds the sorts of sentences typical of
hallucinations (eg "You are stupid.") If the same subjects imagine
an alien voice saying the same sentences (to mimic schizophrenics
hearing alien voices), their brains show activation in a region of
the temporal lobe which monitors internal speech and differentiates
between it and external speech. Schizophrenics, on the other hand,
when asked to imagine alien voices repeating hallucinatory messages,
do not activate this monitoring area of the brain. This suggests
that the brain of a person with schizophrenia fools him or her into
thinking that an internal message is coming from the outside.

Thus functional brain imaging is beginning to show the abnormal
physiology underlying the symptoms of schizophrenia. It does not
however explain the causes of the condition. There is general
agreement that genetic factors are important here: the chances that
any person will develop the illness are partly determined by how
closely he or she is related to someone with it. In the general
population, the risk is less than 1%; but for an identical twin of a
patient the risk rises to nearly 50%, and for a child of two
schizophrenic parents the risk is 46%. So far, no genes which may
predispose people to schizophrenia have been identified, although
there is an enormous amount of research into this.

Even for an identical twin, however, there is still a 50% chance of
escaping the illness; and most interpret this to mean that there
must be an environmental effect as well. Many studies suggest that
patients are twice as likely as normal to have had pre or perinatal
complications. Although there is an association there, there is no
agreement about whether obstetric complications might damage the
brain or whether pre-existing damage due to genetic abnormality or
prenatal viral infections might cause the complications (as well as
the schizophrenia).

Further reading:

Jones P.B., Rodgers B., Murray R.M. and Marmot M.: Child
developmental risk factors or adult schizophrenia in the British
1946 birth cohort. The Lancet, 1994. 344, 1398-1402.

Murray R.M.: Neurodevelopmental Schizophrenia: The Rediscovery of
Dementia Praecox. British Journal of Psychiatry, 1994. 165, 6-12.

McGuire P., Silbersweig D., Wright I., David A., Murray R.M.,
Frackowiak R. and Frith C.: Abnormal monitoring of inner speech: a
physiological basis for auditory hallucinations. The Lancet, 1995.
346, 596-600.

McGrath J., Castle D. and Murray R. M.: How can we judge whether or
not prenatal exposure to influenza causes schizophrenia? In Neural
Development and Schizophrenia, Eds S.A. Mednick and J.M. Hollister.
Plenum Press, New York, 1995.

Is the brain abnormal in schizophrenia?

Shon Lewis, Professor of Psychiatry at the University of Manchester,
recalled that the father of schizophrenia, Emil Kraepelin, wrote the
definitive description of the symptoms of the disorder 100 years
ago. As well as identifying the positive symptoms, such as delusions
and hallucinations, he described the more subtle negative symptoms
(loss of will power, loss of spontaneity and poor self-care) which
are better predictors of the long-term outcome of schizophrenia. His
thinking has influenced current approaches to researching the causes
of the illness. It is Kraepelin's idea that the condition might be a
congenital disorder involving brain abnormalities which show
themselves in early adult life, that has regained popularity during
the last 10 years.

Schizophrenia affects nearly 1 in 100 people and about 2 people in
10 000 develop it in any one year. In general there is little
geographical or social class skew, although African Caribbean
migrants to the UK are particularly at risk. The outcome of the
disorder, which usually comes on in early adult life, is variable.
At one extreme, 1 in 6 patients will recover from the first episode
and will never relapse; at the other, about 10% will never recover
from their first episode and will be disabled by the chronic effects
of it. Most people lie between these extremes, suffering acute bouts
and being more or less disabled between them by the negative
symptoms, which never really disappear. Men and women are equally
susceptible but men tend to have an earlier onset and a poorer
outcome.

It may be that the gap of 20 or 30 years from birth before the onset
of symptoms is not as real as had been supposed. Both Robin Murray
and Tim Crow have analysed large data sets on development and have
discovered that there are subtle abnormalities in people who go on
to develop schizophrenia. About 30% of them have been reported as
being clumsy and withdrawn. There is also an excess of winter births
and an increase in those whose relatives are sufferers.

Since the mid 1970s, CT scans (which produce computer-generated
images of tissue density) have enabled researchers to picture the
structure of the brain. Patients with schizophrenia often show a
small increase in the size of the fluid spaces in the brain called
the lateral ventricles. This was at first thought to be evidence of
a degenerative brain disorder, and researchers expected that if they
followed up the patients years later their findings would be
magnified. In the event, however, they were not: the earlier changes
were no worse, several years on. This caused rethinking and the
adoption of the hypothesis that the condition might be
neurodevelopmental, that is, that the brain changes were there
before the onset of the illness. Researchers now think that the
condition is a disorder of the brain which has devastating effects
on the mind.

With the advent of MRI (magnetic resonance imaging, which provides
detailed anatomical pictures of the brain), the field has moved on.
MRI can distinguish between the grey matter, consisting of cells in
the cerebral cortex, and the white matter which is the nerve fibres
that link them up. The latest studies show a subtle but definite
(5-10%) reduction in the volume of the cerebral cortex in people
with schizophrenia. This is changing the focus of the hunt for the
seat of the disorder from a single place in the brain to several or
many areas of the cortex, and to the idea that the problem could be
malfunctions in the way they communicate with each other.

The brain changes are minor and probably predate the illness.
Functional brain imaging shows that negative symptoms seem to be
correlated with reductions in metabolism in the front of the brain,
particularly on the left side, whereas positive symptoms are
correlated with abnormalities in Broca's area, again on the left
side of the brain in most people.

While talking about the science of schizophrenia, we should not
forget that it costs as much as cancer or heart disease to treat. In
1995 it will have cost the UK #2 600 million.

Schizophrenia as an error in the evolution of language

Dr Tim Crow of Oxford University began by saying that he would take
the view that environmental factors are irrelevant to schizophrenia.
It is an intrinsic condition which raises profound issues about the
nature of human development. It is a blind alley in the evolution of
language.

The epidemiology of the disease forces on us two major constraints
about its origins. On the question of incidence, the best evidence
is a World Health Organisation study, which examined the disease in
10 very different countries including India, Japan, Denmark, the UK
and North America, and concluded that "schizophrenic illnesses are
ubiquitous, appear with similar incidence in different cultures and
have clinical features that are more remarkable by their similarity
across cultures than by their difference". This suggests that the
disease is independent of the environment. The second constraint is
the age of onset. The condition is unusual before the age of 15. It
peaks in the early 20s and 30s, and falls off slowly in the fourth
and fifth decades of life. Again, it seems as though psychosis (of
which schizophrenia is the most defined sub-entity) differs from
other conditions because it strikes at the healthiest and most
reproductive phase of life. This presents a problem, because the
illness is associated with a biological disadvantage. People who
develop schizophrenia are less likely than the general population to
have children. Therefore if it is genetic, one must ask why the
genes are not selected out of the population. Onset is earlier in
males than in females; so considering all these facts, we need an
evolutionary explanation for the disease which shows what advantage
it confers which balances out the obvious disadvantages.

The problem is related to the rapid increase of brain volume in man
over the most recent couple of millions of years of evolution, from
Homo erectus to Homo sapiens. Darwin suggested that it could be
explained by the beginnings of the use of language. The clue to the
mechanism was apparent even before Darwin in the work of Paul Broca,
who suggested that language was localised on the left side of the
brain. Language is the function in the human brain that is most
lateralised, ie located on one side or the other (but even so, about
8-10% of people have it in the right hemisphere).

There is evidence of structural changes in the brain in
schizophrenia: an increase in the size of fluid-filled cavities and
a reduction in cortical mass. A third finding, which may be the key
to the other two and the key to the origin of schizophrenia, is that
anatomical asymmetries do not develop normally. Schizophrenics'
brains are more symmetrical than normal. The National Child
Development Study (NCDS) included 98% of births in one week in March
1959, and followed them up at ages 7, 11, 16 and 23 years. From this
cohort (n = nearly 17 000), those who developed schizophrenia were
investigated. It was discovered that they had shown some indications
of failure of language development: at 7, they mispronounced words,
and their reading ability was impaired. At 11, they were asked to
tick squares with their right and left hands. The individuals who
later became schizophrenic differed from the others on this test:
they failed to show the trend towards right-handedness that implies
the left hemisphere dominance for speech that is shown in the normal
population. In other words, they showed evidence of a failure to
develop hemispheric specialisation. Handedness is a
genetically-determined trait, and Marian Annett at the University of
Leicester has proposed that it depends on a single gene which she
calls the right-shift factor. A single dose of this gene biases the
left hemisphere to be dominant and produces right-handedness; a
double dose produces even more right-handedness. The theory explains
the transmission of handedness in families, but is controversial in
its contention that it relates to aspects of intellectual ability:
that extremes of handedness are associated with cognitive
impairments. There is some support for this theory in the NCDS
study. Verbal scores show that there is a sex difference (females do
better than males) and that there is quite a strong relationship
between degree of handedness and verbal ability. It is
disadvantageous either to be extremely right-handed or equally
skilled in using the right or left hand. This mid-point of
lateralisation is termed the point of hemispheric indecision, and
the pre-schizophrenic children are closer to it than the general
population.

Researchers are trying to find the gene for handedness - if it
exists - on the X and Y chromosomes, as there is an a priori case
that it is associated with them.

Schizophrenia is, as the other speakers have said, something to do
with brain growth and development. The evidence suggests that the
brain evolved by increasing hemispheric specialisation, and that
this gives a clue to the mechanism of the evolution of language,
which differentiates our species from others. The asymmetry which is
associated with schizophrenia is a genetic problem which is
intrinsic to the diversity of Homo sapiens.

Further reading:

Annett M.: Left, right, hand and brain. London: Lawrence Erlbaum,
1985.

Corabllis M.C.: The lop-sided ape: evolution of the generative mind.
Oxford University Press, 1991.

Corballis M.C., Lee K., McManus I.C. and Crow T.J.: Is the
handedness gene on the sex chromosomes? 1994 (unpublished).

Crow T.J.: Sexual selection, Macheavellian intelligence and the
origins of psychosis. Lancet 1993, 342: 594-598.

Crow T.J.: A Darwinian approach to the origins of psychosis. British
Journal of Psychiatry, 1995, 167: 12-25.

Is there an increased risk of schizophrenia and related psychoses in
African Caribbean migrants in the United Kingdom?

Glynn Harrison, Professor of Community Mental Health at the
University of Nottingham, recalled that it was in the 1930s that an
increase of schizophrenia was first recorded amongst migrants - in
that case, Norwegian migrants to Canada. This kind of work began in
the UK in the 1960s and 70s, and various studies have shown that
African Caribbean migrants have consistently had higher rates of
mental disorders than have migrants from Ireland, Europe or Asia. At
first it was assumed that the results must have reflected faulty
methodology; and in the 80s the politics of the issue clouded the
science. It was suspected that western-trained doctors might be
mis-diagnosing behaviour more normal in another culture. There was
also a suspicion that the high rates of compulsory admissions of
African Caribbeans might be disguised racism on the part of (mainly)
white psychiatrists. These suspicions reflected the then fashionable
ideas of the anti-psychiatry movement, which regarded psychiatry as
an agent of the state that controlled behaviour politically
unacceptable to the establishment. And of course psychiatry was
misused in exactly this way in the Soviet Union. The elements of
madness, race and coercion made a seductive mix for many television
programmes.

At the end of the 1980s, however, more reliable studies appeared.
Nottingham was the UK field centre for the WHO study mentioned by Dr
Crow; and Professor Harrison's group applied the principles of that
study to research in which they identified every new case of
schizophrenia in a defined area. Its findings - that African
Caribbean migrants are 6 to 10 times more likely to suffer from
schizophrenia than other migrants to the UK - have since been
replicated by other groups. In Holland, migrants from the Dutch
Caribbean have been found to have a higher incidence of the disorder
than migrants from other areas, eg Morocco. A more recent, larger
study in Nottingham has found at least a five-fold increased risk.

How can these results be explained? There is as yet no answer; but
several theories have been examined. One is the ethnic vulnerability
idea: that black people intrinsically have a higher risk of
developing psychotic illnesses. There is, however, no evidence in
the epidemiological data available that supports this idea. Studies
in Africa and the Caribbean show that schizophrenia rates are the
same as for other parts of the world. Another idea is that people
who are vulnerable to schizophrenia tend to be less
socially-integrated than others; so could they be the ones who
migrate? In fact the evidence is that African Caribbean migrants to
the UK are better adapted than the people they left behind. To
explain the increased second-generation risk, it would have to be
hypothesised that parents, both of whom were at an increased risk,
had children whose risk was then further increased. But preliminary
data shows that siblings run a higher familial risk than parents.
This suggests that siblings may have been exposed to some factor
which predisposes them to the illness: in other words, an
environmental cause may be to blame.

If the risk factor is environmental, what could it be? Some people
have suggested cannabis, but this is not convincing. The stress of
being subjected to racism has also been suggested; but other groups
who suffer equally (eg south Asians) are at lower risk. Perhaps it
is high exposure to other risk factors. African Caribbean babies
having lower birth weight paradoxically have a higher chance of
survival. It may be that this predisposes to schizophrenia later on.
Or could mothers from the Caribbean have an idiosyncratic immune
response to certain viruses they have not been previously exposed
to?

All this is speculation. We know that the increase is nothing to do
with being black and cannot be accounted for by mis-diagnosis. There
is however undoubtedly a higher risk for first- and
second-generation African Caribbean migrants. Studying the
relationship between moving people and the risk of disorders has
benefited other diseases - multiple sclerosis, hypertension, certain
forms of cancer - and will hopefully lead to more understanding of
schizophrenia too.