- 1 -PreamblePreamble

§If madness is as old as humankind is, we might be tempted to assume that schizophrenia, one of today’s best known, most common, and most recognised forms of madness, has been present since the dawn of civilization. (Gottesman... 91. P.1).Surprisingly to the contrary, it has been argued that to search the centuries for schizophrenia is a valueless task, because schizophrenia is of recent origin. (Howell.91.p.10).Supporting this Torrey cited in Howell asserts, “There are no descriptions of schizophrenia, as we know it, before the early 19th century when Halsen in England and Pinel in France gave clear descriptions” (93.p.10).At this juncture, it is pertinent to note as Cromwell, informs, “the term “schizophrenic psychosis” by way of Eugene Bleuler’s writings” is enveloped with all the elements of our language, embedded in our consciousness with all the cultural influences that reflect the times. (93.p3.)

-What then is schizophrenia-?

By way of explanations this paper will attempt to bring to light the above question through explanation of the reasoning behind twin studies in the genetic versus environmental contributions to abnormal behaviour ;focussing on research in the often misunderstood and misrepresented malady of the modern human condition; that being schizophrenia.

§ ▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬This paper will give clear explanation of the rationale of twin studies

in schizophrenia.

It will demonstrate central issues, being why twin studies are

relevant and not so relevant to the contributions twin studies make

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in the determinations of the genetic and environmental make up of

abnormal behaviour in schizophrenia.

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This is to be achieved through facilitating examples of the

conundrums linked and associated with twin study investigations of

schizophrenia, and, how genetic and environmental contributions

impact positively and not so positively in the pursuit of scientific

understanding of schizophrenia per se.

Defining facets of this paper will be frame worked by the above, and

described by two main elements.

First, how one defines schizophrenia vis a vis diagnostics, and

secondly but not insignificant to the previous element; so scribed’

and most integral to the whole concept as presented above ,the

effects upon a person(s) experiencing living day to day, year by year

with schizophrenia, particularly with respect to women and

schizophrenia. †

The aetiology of major mental disorders involves a complex

interplay of nature and nurture.

Ridley.M.2007 cited in Roberts .S.S .et al p.97 argues, “Simplistic

nature nurture arguments are no longer tenable; especially, when

nurture is limited to the post uterine environments”.

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Schizophrenia is for so many afflicted a chronic relapsing and remitting condition that “affects approximately 1% of the world’s populations”. (The Neurophysiology of Schizophrenia. 2003), (Mowry, Nancarrow.2001),(Gottesman and Shields.82.p.113),and(Portin and Alanen.97.p1)

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Interestingly it is also been demonstrated that schizophrenia occurs,

“across all socio-economic groups with recent evidence of an urban/

rural gradient reported”.

(Mortensen PB, Pedersen, CB, Westergard T. et al, cited in, Mowry and Nancarrow .2001)

Mowry and Nancarrow reiterate, “while causes for schizophrenia

remain unknown, evidence from family, twin and adoption studies

clearly demonstrate that it aggregates in families”(2001).

Further to this, Mowry and Nancarrow assert this clustering can be

largely, “attributable to genetic rather than cultural and

environmental factors”. (2001).

With respect to familiality these same authors argue that twin

studies have shown that this familiality is predominantly genetic (vs.

cultural/environmental) factors. (Mowry and Nancarrow.2001).

With respect to genetics and twin studies into schizophrenia:

Tsuang, Gilbertson, and Faraone 91, and Risch 90; cited in Mowry

and Nancarrow 2001; highlight that concept by stating. “The

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prevalence of schizophrenia in offspring is approximately 8%; (there

is a high 50% or more monozygotic concordance rate), suggesting

the involvement of multiple genes”. (2001)

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Contra to this hypothesis it is significant to note Portin and Alanens

perspective on genetic versus environment causality.

Basing there findings on the Finland twin studies, they assert,

“simple genetic hypothesis are not valid where schizophrenia is

concerned”. (1997.p.1). Accordingly; Portin and Alanens conflicting

evidence as to the proportion of the genetic component apparent

in the Scandinavian studies; in particular Danish and Finland twin

studies into schizophrenia, highlights yet another conundrum.

Most notably,and in relation to the Finland study where researcher

Pekka Tienare reported a 0% concordance rate in identical twins,

in respect to schizophrenia. These studies were, as Gottesman and

Shields poignantly point out, were carried out on one or both, and

male twins only. (82.p102); and what is most noteworthy; “half the

starting sample of 3.000 pairs were lost by age 16 by death

(ordinary and war related), in one or both pairs”. (Gottesman and

Shields.82.p102).

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Intervening literature and contradictory opinions on the causal factors in schizophrenia has significance; at this point of the argument; and, it is of interest to note, that some people will argue that family environment, rather than families’ genes accounts in relation to the twin concordance and discordance findings in relation to schizophrenia.

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Gottesman and Shields contend in relation to the genetic/ environmental conundrum argues.

To disprove the genetic hypothesis it would be necessary to show samples known to differ genetically such as MZ and DZ co-twins of schizophrenics(100% vs.50% gene overlap) do not differ in their rates of schizophrenia when exposed to the same environments”.(82.p101).

Gottesman and Shields further this by highlighting

The nature of shared environments for parent-offspring pairs is quite different from that shared by two siblings, yet the risk of schizophrenia is the same ,as is the degree of genetic relatedness”(82.p.101).

Gottesman and Shields analysis of older and more recent twin

studies in schizophrenia highlights the significance of meshing;

maintaining and comparing studies; the statistical processes used;

and analysing comparative summaries of concordance and

discordance in schizophrenic twin studies, so as one can proffer a

balanced viewpoint in respect to the genetic vis a vis environmental

elements.

Gottesman and Shields report;

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The rates reported in the older studies are simple pairwise ones; they are less satisfactory than proband rates for comparison with the risks reported for other relatives and for the general population. (82.p102)

† Note: (See appendix for tables 6.1, and table 6.2 concordance rates in older and newer schizophrenic twin series).

With respect to concordance rates and diagnostic measures, Gottesman and Shields, also express concerns in having concordance rates too broad or too narrow in orientation to the diagnosis of schizophrenia. (82.p111)

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These authors state in fact that:

Extremes eroded the MZ: DZ contrasts: sample size unmercifully: too broad raised both the MZ and DZ rates to dilute an indicator of “biological specificity”, the ratio of the rates. (Gottessman and Shields .82.p.111.).

† Note See appendix (Refer to table 6.3 “possible reasons for the magnitude of MZ concordance rates, for confounding element summary).

Newer twin studies of schizophrenia have addressed such

confounding elements as so described above, through processes of:

using proband rates method; also, through using “more thorough

sample investigation; or, longer follow up times since the first

published results”. (ibid).

This therefore, resulting in; “No bizarre findings of MZ rates of 0%, a

result incompatible with either genetical or environmental

arguments” (Gottesman and Shields .82.p.112).

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Regarding diagnostic issues in these twin studies, these were

addressed; as well as confirmed using a diagnostic criterion cut off

that was similar as possible to the consensus diagnosis formed in

Gottessman’s Maudsley twin study. (Gotesman and

Shields.82p.112).

♠

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In relation to discordant monozygotic twins, a further conundrum is

apparent.

Gottesman and Bertelsen .89;cited in Portin and Alanen, found “no

difference between the prevalence of schizophrenia in the children

of the sick twin (16.8%), and the offspring of the twin who remained

healthy”. (97.p .2).

However comparative studies (using pairwise methodologies),

reported a completely contradictory result to this end “the sample

17.9% of the children of the sick twin were ill, compared to only

4.4% of the offspring of the healthy twin”. (Klinglen and Kramer

cited in Portin and Alanen .97.p2).

As noted by Portin and Alanen in relation to this “the difference did

not reach the level of statistical significance ;however these

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contradicting findings again indicate the problems encountered in

genetic studies of schizophrenia”(97.p.2).

Just reiterating ,and, as noted on page one of this paper ,multiple

authors postulate that the lifetime prevalence of schizophrenia in

the adult population ,regardless of race or country is about 1%,(and

furthermore), in the siblings of patients it is 8-10%,and in children of

patients it is 12-15%.(Gottesman .93.cited,in Portin & Alanen

97.p.1.)

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Page 8 of 15It can therefore be assumed, that such insufficiencies of the strength of genetic evidence, must lead to the assumption “that environmental factors also play a role in the aetiology of schizophrenia” .(Portin and Alanen 97.p.1).

♠

The methodological conundrum of genetically grounded evidence also exists in relation to gender and twin studies of schizophrenia; especially so in relation to older studies: these were as ,Gottesman and Shields argue, “unbalanced in this regard”. (82.112).

In relation to gender differences, a similar conundrum of methodology exists; Gottesman and Shields argue; in relation to concordance.

Female twin pairs tend to be concordant more often than male twin pairs, and that of two of the recent studies, those with the lowest rate of concordance only sampled male twin pairs. (Gottesman and Shields .82.p.113).

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Authors Gottesman and Shields believe that a complete evaluation

of this source of variation is onerous because its source of variation

has been closely linked “with other problems of sampling such as

chronicity of illness. (82.p114).

These authors stated preferred reason in relation to the older

studies in relation to concordance and chronicity as follows.

…Higher MZ concordance rates in the earlier studies is those samples ,unlike the recent ones ,were heavily weighted with chronic unremitting cases of schizophrenia; such cases are much more likely than others to have schizophrenic partners

(Gottesman, and Shields. 82. P.114).

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† Note (see appendix for table 6.4 sex sampling and concordance).

The concordance rates as so described and processed in table 6.4

sex sampling and concordance, show there is:

No sex differences in concordance for schizophrenia and no difference in the representation by sex …the higher concordance in females is accounted for entirely by the use of samples with biases –(interestingly)- through the loss of certain cases. (Gottesman and Shields .82.p.114).

Furthermore evidence to the fact that with opposite –sex twins,

when studied, are no less concordant than same –sex fraternal twin

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pairs further reinforces the aforementioned explanations.

(Gottesman and Shields .82.114.).

Furthermore as noted historically, gender differences in

schizophrenia have been confirmed by such empirical data as

mentioned above, this being so since the turn the 20th century.

However also of note is that the study of schizophrenia has

remained largely “gender blind”. (Jarboe .98.p.4).

Clearly, there is a great deal of work to be achieved in the area of

studying women suffering from schizophrenia.

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The complexity of the research approaches necessary to explore the

area of gender differences in schizophrenia is immense, and may

explain the aforementioned conundrums as highlighted in this paper

as so found in research methodologies; therefore highlighting some

of the obstacles to the systematic study of gender differences and

specifically women suffering from schizophrenia .

It can again be postulated, from everything mentioned prior, that

such “insufficiencies” of the strength of genetic evidence, must lead

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to the assumption “that environmental factors also play a role in the

aetiology of schizophrenia”. (Portin and Alanen 97.p.1).

This paper will now address the relevance that twin studies have; in

their contributions to women presenting with a diagnostic condition

of schizophrenia.

That being ,the realm of the environmental elements inherent to the

aetiology of schizophrenia twin studies, and its association with

epidemiological elements of; gender –based research, and

consequences for the person; that being a woman so diagnosed with

schizophrenia.

Although gender-based research into schizophrenia has been lacking, Jarboe argues,Much of the credit for encouraging examination of this issue belongs -

Page 11 of 15to epidemiologists who have described significant differences in the age of onset, course and outcome of schizophrenia found between men and women with schizophrenia. (98.p.5)

† Note (see appendix namely Table one: Gender differences in Schizophrenia.).

With respect to table one; Gender differences in Schizophrenia, Jarboe states, “these findings suggest a better outcome for women with schizophrenia “(98.p.6)-(in comparison to male health outcomes).

However as Milburn and D’Ercole 91 cited in Jarboe illustrate ,

..There is evidence to suggest that women who fail to make a good recovery have outcomes worse than men in the same situation. Homelessness, poverty and victimization have a greater subjective impact on a psychotic woman’s quality of life than a man’s. (98.p.6).

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Additionally relevant to the above facets Walter and Kenward

cited in Jarboe, concur as well that relating to women who are

chronically unwell with schizophrenia, they are at a very

heightened risk of, “domestic conflicts or abusive behaviours

from family members and thus increases the risk of

homelessness. (Jarboe .98.p6.).

By way of extrapolations into the above issues the above

might help clarify why researchers have met with difficulties

as noted in twin studies research, a major obstacle in

statistical methodologies as these authors believe: the

chronicity of illness contribution and concordance rates per se

as “unbalanced in this regard’ (Gottesman and

Shields.82.p113). Created by Anne Percy

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Hence: this conundrum, is noted as being specific ,and,

“peculiar” to female twin studies, as so presented, within this

paper.

A further conundrum of the complexities inherent in schizophrenia:

and perhaps closely tied in with diagnostics per se; in relation to

twin studies and the environmental /genetic components per se,

has been in the pursuit of the scientific understanding of this

disease.

This being from the standpoint of Neuro developmental theories.

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Neurodevelopment theories extracted partly from studies of twins

in Schizophrenia attempt to build on epidemiological gender

differences, however as noted by Jarboe, “these theories do not

explain the excess of female patients presenting with their first

episode of schizophrenia in their late 20s and 30s”. (98.p.8.).

The above poses an important question relating to the efficacy of

twin study research, particularly regarding the more “classic”

studies of the early 20th century, and women’s experiences of

schizophrenia from that time onward, in relation to the developing

field euro-developmental and its’ linkages to schizophrenia.

With resect to longitudinal designs and diagnostic methodology as

has been mentioned previously by Gottesman and Shields ,the

newer twin studies of schizophrenia are attempting to address such

confounding elements as onset and course of schizophrenia, by

having longer follow -up times since the first published results, and

more thorough sample investigation”(82.p.111.) Created by Anne

Percy

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Nasralla, 93, cited in Jarboe .98, argues that “Neurodevelopment in

women with schizophrenia may be under genetic control whereas;

neurodevelopment in men with schizophrenia appears to be

mediated by adverse environmental factors” (98.p.7.).

Further more and in relation to the above statements, Nasrallah and

Wilcox cited in Jarboe report,

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Males are more prone to neurological brain insult as a result of obstetrical complications, they have been reported to have a greater incidence of structural brain pathologies than women. (Jarboe.98.p.7.).

Twin studies have illustrated that foetal hypoxia and low birth

weight have been correlated, with an early onset of schizophrenia.

(Jarboe..89.p.7).

Further to this, some research has demonstrated that “females are

at decreased risk of neuro-developmental disorders when compared

to men” (Jarboe.89.p7.)

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