gene, where art thou?
now 80 years since scientisits first claimed schizophrenia was genetic.
Yet, no such gene has been identified. Some private genetic research
firms are now abandoning their search for a schizophrenia blood
test, and a senior psychologist says the quest for the schizophrenia
gene has been biggest failure in medical history. Is it? Adam
schizophrenia rooted in our DNA? Pick up a medical textbook or ask
a psychiatrist. Both will tell you it is. Almost without exception.
psychiatric research it is accepted wisdom that schizophrenia is
approximately 50% genetic, with DNA abnormalities "predisposing"
a person to schizophrenia. Robin Murray, professor of psychiatry
at London's Institute
of Psychiatry, states no "sensible person" questions schizophrenia's
strong genetic underpinnings.
factors - including trauma, abuse, neglect, stress, cannabis use
and maternal viruses during pregnancy - contribute the other 50%
of causes, it is widely cited.
dissenting researchers argue psychiatry has consistently "hyped"
the genetic basis for schizophrenia. Some argue there is no solid
evidence at all for a genetic cause. "The
scientific literature and the press repeatedly convey the misleading
impression that schizophrenia is proven to be a genetic disorder,"
says psychiatrist Joanna Moncrieff, a senior lecturer in social
and community psychiatry at University College of London.
for the role of genes in the aetiology of schizophrenia has their
roots in German eugenics of the late 1920s. But ironically, 80 years
on, the one undisputed fact is that no schizophrenia gene has been
was confirmed in April when an American Journal of Psychiatry April
study reported that
the genes most widely assumed to play a causal role in schizophrenia
are, in fact, unlikely to play a role.
examined 14 schizophrenia "candidate genes" identified
from 25 years of molecular genetics. It was an unprecedented study
as it analysed the genetic material of 1,870 patients diagnosed
with schizophrenia or schizoaffective disorder, and 2002 control
patients. It was the "most comprehensive" study of its
kind, according to an editorial in the journal.
critics, this non-finding was no surprise. "The reason that
this study did not find evidence for a gene is that there are no
such genes," asserted American clinical psychologist Dr Jay
Joseph and author of The Missing Gene: Psychiatry, Heredity, and
the Fruitless Search for Genes. "For 25 years
psychiatry has been looking for a schizophrenia gene. They keep
Even the study's lead researcher Professor Pablo Gejman, director
of the Centre For Psychiatric Genetics at Northwestern University
in Illinois, admitted the results were not "as expected".
He admitted: "The genetics of
schizophrenia has remained illusive at a molecular level."
claims for a genetic basis to schizophrenia first really gathered
force in the sixties. The records of same-gene identical twins -
from Finland to America - were examined to find the ratio of one
"schizophrenic" twin having a "schizophrenic"
researchers Irving Gottesman and James Shield summarised these twin
studies in their 1972 book, The Genetics of Schizophrenia. They
claimed that if one twin had schizophrenia, his/her co-twin had
an almost 50 per cent
(48%) chance of also being schizophrenic. Contemporary researchers
regularly cite the work of Gottesman and Shields. Their 50 per cent
genetic statistic has stuck for more than three decades.
there have been rigorous critiques of Gottesman and Shields' work.
In her book, Schizophrenia, a Scientific Delusion, Mary Boyle, emeritus
professor of clinical psychology at the University of East London,
numerous methodological flaws in their study, including that they
were unblind and the results were "massaged". Moreover,
Gottesman and Shields had not, in fact, measured schizophrenia,
but "schizophrenic spectrum". They had
judged identical twins to be "concordant" with schizophrenia,
even if neither were diagnosed with schizophrenia. For example,
one twin had "affective disorder", the other "schizoactive
schizophrenic spectrum disorder was invented to render the results
positive," claims Moncrieff.
the fundamental flaw of almost all twin studies - including many
of those now being conducted as part of the Institute of Psychiatry's
Maudsley Schizophrenia Twin Study programme - is that a shared environment
could as feasibly account for identical twins both being diagnosed
a bid to exclude the influence of "nurture", geneticists
studied adoptees. In the mid-seventies US Harvard professor Seymour
Kety and colleagues devised a methodology which, they hoped, would
eliminate environment as a variable.
book, the Transmission of Schizophrenia, suggested 9% of blood-relations
of adoptee schizophrenics had a schizophrenic diagnosis, compared
with two per cent of the relatives of non-schizophrenic adoptees.
This original and subsequent Kety adoption studies are, arguably,
the most cited research in support of a genetic theory of schizophrenia.
Again, critics, such as Boyle, Joseph and Open University biologist
Steven Rose, have highlighted what they argue are gross methodological
flaws. Not only was the schizophrenia spectrum again used, Kety
invented another diagnosis called "latent schizophrenia".
This was for "potential schizophrenics".
American psychiatrist Peter Breggin has described his reaction when
he read Kety's original study. He was "shocked" to find
there was actually no increase in schizophrenia among close biological
relatives, such as mothers, fathers, full brothers and sisters.
"Thus the studies actually tended to disprove the genetic origin
of the presumed illness," he wrote.
geneticists are adamant there is sufficient twin, family and adoption
study evidence to support a strong genetic schizophrenia link. Nick
Craddock, professor of psychiatry at Cardiff University insists
there is "lots of data" to support the 50% statistic.
"We are sure that genetics is
involved," he asserts. Some geneticists argue schizophrenia
has an 80 per cent genetic basis.
genetic argument has been bolstered by reports that blood tests
for schizophrenia are in the pipeline. For example, one company,
Suregene, based in Louisville in America, issued a press release
announcing that by this year it expected to have "perfected"
a blood test to detect schizophrenia.
Suregene's chief executive Mike Brennan has confirmed to psychminded.co.uk
that the firm has dropped such plans. Instead, it is turning its
attention to finding a genetic root to "paranoia", not
schizophrenia. Mr Brennan said: "We've gone away from referring
to the genetic test as a schizophrenia test, and started referring
to it as a test for psychosis," he
said. Moreover, the test is for "research purposes" only.
another genetics firm, the UK-based and drug firm-backed Curidium,
announced in a press release in July last year that it was producing
a "blood diagnostic test", called PsychINDx, for schizophrenia/bipolar
patients. But Curidium has confirmed that PsychINDx is not a schizophrenia
test, but one to assess which drug would be suitable for a particular
hoping to crack a genetic schizophrenia code are now examining variants
of millions of genes, a strategy known as genome-wide association.
Yet, even the geneticists accept the clock is ticking. It's crunch
we don't get a [genetic] answer in two to three years and nothing
striking comes up then any genetic effect is so tiny it's not worth
finding," declares Professor Murray.
time too, say some.Richard
Bentall, professor of clinical psychology at the University of Bangor
argues that with schizophrenia being an invalid, fuzzy medical diagnosis,
the project was always doomed. "Geneticists have been
continuously confident they would find a gene for schizophrenia.
There's probably been no big a failure in the history of medicine."
the genetic consensus has determined how clinicians treat the one
in 100 people diagnosed with schizophrenia. Anti-psychotic drugs
are the first-line treatment for those with this diagnosis. These
presumed, in some way, to effect the underlying gene-determined
physiology of schizophrenia. This assumption is often why any non-drug
form of treatment is ridiculed, even demonised. One NHS psychologist,
Rufus May from
Bradford, was earlier this year dubbed "dangerous" for
advocating a non-drug approach. Some doctors advocated he be disciplined.
such as Bentall argue there is sound evidence demonstrating that
schizophrenia "symptoms", such as voice-hearing, delusions
and thought disorders, are related to trauma, such as abuse. But
they point out that an estimated 99 per cent of all psychiatric
research into the causes of
schizophrenia is slanted towards genetics or bio-physiology.
upon millions of pounds have been spent on psychiatric genetics,"
says Prof Bentall. "Yet, it's been a complete damp squid."
Coleman was sexually abused when a child. In adulthood he heard
abusive voices, was diagnosed with schizophrenia and was in and
out of mental health services for 13 years. He now helps run Working
To Recovery, a training organisation for services working with
people diagnosed with psychosis. It is based in the Isle of Lewis,
Scotland. Coleman is currently advising a World Health Organisation
mental health project in Jerusalem. He says:
is becoming increasing obvious that the main reason [for schizophrenia]
is not biology, but things that happened in a person's life.
instance, people's voices are clearly asssociated with life
experiences - such as here in Palestine with the war between the
Palestinian and Israelis. Research clearly shows there is a link
people can talk through these causes. What happened in someone's
life is central to that person's recovery. This would not happen
if schizophrenia was a biological condition.
stress is genetic then some people may have a vulnerability. But
this is not a vulnerability to schizophrenia.
looked at my family's past. I can see no genetic link. Apart from
my grand-father getting dementia there's nothing. So where did the
gene come from?
time to understand mental health problems as not being about a person's
genes, but about society. It is something society has to deal with"
* An edited
version of this article first appeared in Mental
Health Today magazine
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