Genetic theories underlie many of the biological theories, since it is often assumed that only those people with a genetic vulnerability will manifest the neuropathological condition that causes schizophrenia, or succumb to the virus, or the malnutrition, that causes the neuropathology that in turn causes schizophrenia. Indeed, a genetic factor is necessary to give credibility to any biological explanation of the cause, because one of the few uncontested features of schizophrenia is that schizophrenia tends to run in families. Without a plausible genetic argument the phenomenon of family propensity for schizophrenia might be better explained by environmental causes.
The idea that a single dominant genetic component might be solely responsible—that there could be a ‘schizophrenia gene’—has to be discounted by other observable phenomena. Breggin argues that when geneticists go in search of a dominant gene as the cause for a disease such as Huntington’s chorea, the quest makes sense because there is prior knowledge from the set pattern of family inheritance that a dominant gene is responsible,[41] but this is clearly not the case with schizophrenia. Although there is a family association with schizophrenia, there is no set pattern of inheritance.
However, some genetic researchers have not been deterred from embarking on the quest for the ‘schizophrenia gene’ and occasionally announcing success. In 1988 it was announced that Chromosome 5 was the site of the schizophrenia gene: ‘For the first time, scientists have obtained evidence that a specific chromosome mutation contains a gene predisposing its bearers to schizophrenia and closely related mental disorders’. The announcement had been made in the 10 November 1988 issue of Nature and a refutation came so swiftly it was published in the same edition of the same journal.
More recently the search for the schizophrenia gene has concentrated on Irish families, and in 1995 a team of scientists from the United States "headed by Scott Diehl of the National Institute of Health found a specific region of Chromosome 6 that appears to contain a gene for the disorder. ‘If our finding holds up, it means that, contrary to what a lot of researchers have thought, there is at least one major gene that predisposes a person to schizophrenia,’ said Diehl."[42]
The equivocal statement, ‘If our finding holds up,’ was a definite warning that Diehl himself was uncertain about the claims he was making for Chromosome 6. Ten days later the reason for this uncertainty was revealed. It seems that Diehl had published the results of work he had been engaged in as a junior research scientist at the Medical College of Virginia under the direction of Dr Kenneth Kendler. But Diehl had moved on to another research facility in 1993. A simmering dispute had continued between Diehl and Kendler between 1993 and 1995 over whether Diehl had any rights to the research he had undertaken while working for Kendler. Diehl’s 1995 announcement of having discovered the schizophrenia gene turned out to be a pre-emptive strike to claim ownership of the intellectual property. But it seems that Diehl had only completed 10 per cent of the gene mapping work envisioned in Kendler’s research scheme and Diehl’s article only described preliminary findings. At stake were millions of dollars of research funding to complete the project.[43]
Many genetic researchers are not convinced that Kendler and Diehl are even on the right track in pursuing Chromosome 6. Some researchers have targeted Chromosome 22 as being the most likely site for the schizophrenia gene.[44] Most genetic research, however, now assumes that there is no single schizophrenia gene and that a variety of separate genetic factors are involved.[45]
The basis for the genetic theory is a well-observed family association with schizophrenia.[46] Psychiatric textbooks often misleadingly present this association as concordance rates indicating established genetic risk factors for schizophrenia.
Genetic Risk for Schizophrenia
Source: Norman L. Keltner, ‘Schizophrenia and Other Psychoses’, in Norman L. Keltner, Lee Hilyard Schwecke and Carol E. Bostrom, eds., Psychiatric Nursing, Mosby, St Louis, 1995, p. 368.
These concordance rates, however, can also support arguments for an environmental cause. In cases, for instance, where one or both parents have schizophrenia it can be argued that it is not the transmission of genes that passes the condition on to offspring but rather the parental role model. Similarly, if one child develops schizophrenia due to an environmental cause in family life, then it is likely other children in the family will also be affected in the same way.[47]
This exploitation of concordance research by advocates of an environmental cause has prompted genetic researchers to explore the concordance rates of siblings who have been reared separately. The adoption studies that are most frequently cited, however, are quite old, dating back to the 1960s and 1970s. Of these the most important was published in 1975 by a team led by Seymour Kety.[48]
The Kety study was sponsored by the National Institute for Mental Health in the United States and involved locating Danish schizophrenics who had been adopted as children, before their schizophrenia had become apparent. Denmark was chosen because of the efficiency of the official system of record-keeping. The second step in the investigation required locating and psychiatrically assessing the biological relatives of the adopted schizophrenics to see if there was a higher incidence of schizophrenia amongst them than there was amongst the relatives of a control group of non-schizophrenic adoptees. The findings showed that schizophrenia and ‘schizophrenia spectrum’ disorders were more prevalent amongst the relatives of the schizophrenic adoptees, and this was taken to be positive evidence of a genetic link for schizophrenia.[49]
However, this study has been severely criticised. Claims have been made that there was a double sleight-of-hand involved in the presentation of the results.[50] It has been pointed out that the Kety study could not find any increase in schizophrenia amongst the close relatives of the adopted schizophrenics—mothers, fathers, sisters and brothers—and that the only significant increase they found was amongst paternal half-siblings. Furthermore, this increased incidence amongst paternal half-siblings was all contained within one large family.
On top of this, the distantly related association with schizophrenia was largely due to the inclusion of ‘schizophrenia spectrum’ disorders in the comparative study. The Kety study used the second edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-II) to define the relevant range of disorders, and this edition of the manual included a category, which has since been dropped, called ‘latent schizophrenia’. This was a supposed tendency towards schizophrenia without a history of psychosis. It was similar to the Soviet concept of ‘sluggish schizophrenia’, and almost anybody could be fitted into it. Fourteen of a total of eighteen half-siblings diagnosed with schizophrenia spectrum disorders only had this latent form.
Breggin argues that the four cases of full-blown schizophrenia within the one family could be best explained by an environmental cause, perhaps sexual abuse. He dismisses the cases of latent schizophrenia as irrelevancies.
Adoption studies have also been severely criticised because of concerns that adoption practices may have been influenced by eugenics policies in the countries where the most influential adoption studies were carried out. Jay Joseph has analysed the development of eugenics policies, and their translation into laws sanctioning sterilisation of mentally ill people, in Denmark, Finland and Oregon.[51] He argues that a number of adoption studies undertaken in Denmark in the 1960s and 1970s, others undertaken in Finland in the 1970s and 1980s, and another in Oregon in the 1960s all used schizophrenic adoptees who were placed for adoption at a time when eugenics legislation was in force.
Jay’s argument is that adoption agencies would have been influenced by eugenics policies in regard to the type of families children were placed into. If a child who was given up for adoption had a natural mother who had schizophrenia, or if there was any known mental illness in the family of the mother or father, the child would most likely have been placed in a family of lower socio/economic status. This in turn would have increased the likelihood that these children would have been reared in a more stressful environment, and they would therefore have been more likely to develop schizophrenia.
The most persuasive evidence for a genetic link comes from the study of concordance rates in twins. The twin method is widely used to determine whether a particular trait has any connection with genetic inheritance. The method involves comparing the concordance rates of monozygotic (MZ) twins (one egg, identical) with concordance rates of dizygotic (DZ) twins (two egg, fraternal). In schizophrenia studies these comparisons are confined to twins where both members have been reared together. The object is to determine whether the 100 per cent genetic concordance of monozygotic twins, compared to the 50 per cent genetic concordance of dizygotic twins, reflects in similarly divergent concordance rates for schizophrenia. The results are quite impressive.
When the results are pooled of 14 twin studies conducted between 1928 and 1998 the pooled concordance rates for monozygotic twins is 44 per cent compared to 9 per cent for dizygotic twins.[52] At first glance this offers convincing evidence for a genetic factor in schizophrenia. However, critics of the studies point to two major problems with this approach. The first is that the studies themselves all have methodological problems. The most serious of these methodological problems are the familiar ones concerning diagnostic criteria and subjective methods of diagnosis for schizophrenia. It is pointed out that all of these studies were undertaken by researchers who set out to confirm the genetic hypothesis and that in most cases non-blinded diagnostic procedures were used. Given the subjective nature of schizophrenia diagnosis, this gives rise to concerns that diagnoses might have been inflated for one group and deflated for the other.
The other major problem concerns the possibility that concordance rates might have been confounded by environmental factors. Analysis of the studies has shown that, although there is no sex-link to the genetic hypothesis for schizophrenia, the twin studies show a distinct pattern of sex-linked concordance: ‘female MZ pairs were more concordant than male MZ pairs; female DZs were more concordant than male DZs; DZ same-sex twins were more concordant than opposite-sexed DZs; and DZ twins were more concordant than ordinary siblings, despite sharing the same genetic relationship’.[53]
These results suggest that something other than genes is responsible for the concordance patterns. It is suggested that the most likely explanation is that family environments tend to compress the identities of twins so that they experience a phenomena called ‘ego-fusion’. This occurs as a result of families endeavouring to treat them equally, which often means duplication of clothing and experience. The more similar the twins are, whether MZs or same sex, the more duplicated their experience tends to be. The result is that if one twin experiences madness the other will have a propensity to follow, depending on their history of duplicated experience: ‘It is therefore concluded that there is no reason to accept that the twin method measures anything other than the environmental differences distinguishing identical and fraternal twins’.[54]
It is not only the gene sceptics who warn about excessive optimism pervading the genetic quest. Some of the leading researchers in the field also find it necessary to keep the issue in perspective:
"The search for genes of major effect in schizophrenia, however, is premised not so much on hard evidence that they exist, as on the absence of evidence that they do not . . . Recent work suggests that such genes of major effect exist in other common disorders, but linkage studies in schizophrenia must still be regarded as acts of faith."[55]
Next: Theories of an Environmental/Experiential Cause
[41] Breggin, op.cit., p. 122.
[42] Mark Bowden, ‘Study finds evidence for gene that may help cause schizophrenia,, p. 501.
[43] Mark Bowden, ‘Top human geneticists argue over ownership of schizophrenia research’, p. 511.
[44] K. C. Murphy et al., ‘The molecular genetics of schizophrenia’, pp. 147–57.
[45] Peter McGuffin et al., ‘Genetic basis of schizophrenia’, pp. 678–83.
[46] S. L. Varma, et al., ‘Psychiatric morbidity in the first-degree relatives of schizophrenic patients’, pp. 7–11.
[47] P. J. Tienari and L. C. Wynne, ‘Adoption studies of schizophrenia’, pp. 233–37.
[48] S. S. Kety et al., ‘Mental illness in the biologic and adoptive families of adoptive individuals who have become schizophrenic: a preliminary report based on psychiatric interviews’, pp. 147–65.
[49] Donald W. Black et al., ‘Schizophrenia, Schizophreniform Disorder, and Delusional (Paranoid) Disorders’, p. 379.
[50] Breggin, op.cit., pp. 118–121.
[51] Jay Joseph, ‘The Genetic Theory of Schizophrenia: A Critical Overview’, pp. 119– 45.
[52] Ibid., p. 123.
[53] Ibid., p. 126.
[54] Ibid., pp. 126, 136–137.
[55] Michael Owen and Peter McGuffin, ‘The molecular genetics of schizophrenia: blind alleys, acts of faith, and difficult science’, pp. 664–6.