Does Schizophrenia have a genetic basis?

Gottesman & Shields (1966) twin study

Aims: The main aim of this study was to see if whether schizophrenia had a genetic basis. Using a twin study methodology, Gottesman and Shields planned to test different twin pairs to investigate the concordance rates of schizophrenia in twins. They also wanted to replicate other studies that had indicated a genetic basis to the disorder, to find if their findings would be similar (to test for reliability). Procedure Researchers looked at patient records from a short-stay psychiatric hospital with a large outpatients department. The records covered a sixteen year history from 1948 to 1964. Over that time, 392 patients were seen who said that they had a twin of the same sex, and of those 68 had a diagnoses of schizophrenia or a related psychosis although six patients were discounted either because their twin counterparts were overseas or it was unclear whether they were monozygotic (MZ) or dizygotic (DZ) twins. This left 62 patients: and 5 twin pairs were both on the register, leaving 57 study pairs. The other 52 patients twin counterparts were tracked down to participate in the study. Monozygotic Female Male Total 11 13 24 Dizygotic 16 17 33 Total 27 30 57 Of the 62 patients in the participant sample, exactly half were male, and half were female. Their ages ranged from 19 to 64 with the average patient age being 32. Zygocity was determined using three methods: fingerprint testing, blood testing and resemblance assessments (this was done before DNA testing was around).

Multiple data collection methods were used, involving both primary and secondary resources. These included: . . . . . hospital notes case histories based on self-report questionnaires and interviews with the twins and their parents tape-recorded 30 minute samples of verbal behaviour from semi-structured interviews personality testing testing to measure disordered thinking, conducted both on the twin sets and their respective parents.

The researchers wanted to look at concordance rates. If the one twin had been diagnosed with schizophrenia, they wanted to know how often their counterpart twin
Patricia George / Ardingly College / IB Psychology / BLOA / Genetics & Schizophrenia

would also be diagnosed with schizophrenia, or a related psychosis. The patient who had been admitted to the psychiatric hospital initially first coming to attention was called the proband. The data was analysed between each proband and their twin, with twin pairs being categorised in four ways.

Findings
The tables below display the main results from Gottesman and Shields study. The four categories were: Category1 both the proband and co-twin had been hospitalized and diagnosed with schizophrenia Category2 both had hospitalisation, but the co-twin had been given another diagnosis related to schizophrenia Category 3 the co-twin had some psychiatric abnormality, but nothing related to schizophrenia Category 4 proband had schizophrenia, but the co-twin was diagnosed as clinically normal Monozygotic Category Number % 1 10 43 1&2 13 54 1, 2 & 3 19 79 4 5 21
Total 24 100

Dizygotic Number % 2 9 6 18 15 45 18 55
33 100

Categories 1, 2 & 3 Males Females Concordance Rates Severe Schizophrenic Mild Schizophrenic

MZ 66% 91% MZ 75% 17%

DZ 29% 62% DZ 62% 0%

Note: severe means having longer than two years hospitalisation, mild means less than two years

In summary, the results showed: . . . . There was a significant difference found between MZ and DZ twins in all measures MZ twins were always more similar in diagnosis than DZ twins in each case where the co-twin had some diagnosis Similarity was greater between female twins compared to male twins (for both MZ and DZ twins) Concordance rates were higher for both MZ and DZ twins for severe schizophrenia compared to mild schizophrenia

Conclusions
Patricia George / Ardingly College / IB Psychology / BLOA / Genetics & Schizophrenia

 The findings suggested that the closer the genetic relationship between two people, the greater the likelihood that if one of them is diagnosed with schizophrenia , the cotwin is also going to develop schizophrenia or a related psychotic disorder. The study also suggested that this relationship was more prevalent among females than males. However, as twins in the monozygotic twin pairs did not have 100% concordance rates, the implication is that schizophrenia is not caused entirely by genes. Instead, the results led Gottesman and Shields to believe that genetic factors do predispose someone to schizophrenia, by lowering their threshold for coping with stress, but environmental triggers may also be needed to actually start the development of the disorder. They said the diathesis-stress model best fit this explanation, taking on board a biological and environmental explanation. Gottesman and Shields also looked at 11 other studies, and concluded that their results did support each other, although they thought there were some methodological issues, such as with the sampling techniques. This is how they concluded their results were reliable, and that there is a genetic element to schizophrenia. Evaluation: Strengths The results are supported and backed up by other studies which have produced similar findings, such as Inouye (1961) who found a 74% concordance rate of twins with a progressive chronic schizophrenia disorder, and a 39% concordance rate for mild schizophrenia One of the findings of their analysis of the other studies was that the sampling techniques were questionable, but a strength of Gottesman and Shields study is that the sampling was carefully controlled using multiple measures to make sure that twins were correctly allocated either MZ or DZ twin status, and a lot of data was gathered using multiple research methods to check the diagnoses were correct Evaluation: Weaknesses It would have been useful to know more about what related psychosis meant when describing the schizophrenia scale to take into account the related disorders, as they failed to make this clear Gottesman and Shields suggested that there are different types of schizophrenia and some might be caused by life events (so environmental stimuli), such as being a prisoner of war, and it was hard to distinguish between such types in the results of the study

Patricia George / Ardingly College / IB Psychology / BLOA / Genetics & Schizophrenia

 Gottesman & Shields (1991) went on to investigate the influence of genes on schizophrenia by combining the results of 40 investigations spanning over 60 years. MZ DZ These results cannot be interpreted as meaning that schizophrenia is 48% genetic. This is because MZ twins are brought up in largely the same environment as well as sharing all of their genes. It is the difference between MZ twins and DZ twins, and the comparison of this with the baseline rate in the population (1%) that demonstrates how heavily the condition is influenced by genetic factors So what we can say is: A monozygotic co-twin of an individual with schizophrenia has a 48 times greater chance of developing schizophrenia than a random member of the population, whilst a dizygotic co-twin of an individual with schizophrenia has a 17 times greater chance of developing schizophrenia than a random member of the population. This difference demonstrates that there is a strong genetic component to schizophrenia, but that environmental factors are also important. Concordance rate for schizophrenia (%) 48 17

Adoption study of schizophrenia

Heston, L. L. (1966) Psychiatric Disorders in Foster Home Reared Children of Schizophrenic Mothers. The British Journal of Psychiatry, Volume 112, pages 819-825
Abstract: source: http://bjp.rcpsych.org/content/112/489/819.abstract This report compares the psycho-social adjustment of 47 adults born to schizophrenic mothers with 50 control adults, where all subjects had been separated from their natural mothers from the first few days of life. The comparison is based on a review of school, police, veterans, and hospital, among several other records, plus a personal interview and MMPI which were administered to 72 subjects. An I.Q. and social class determination were also available. Three psychiatrists independently rated the subjects. The results were: (1) Schizophrenic and sociopathic personality disorders were found in those persons born to schizophrenic persons in an excess exceeding chance expectation at the 0.05 level of probability. Five of 47 persons born to schizophrenic mothers were schizophrenic. No cases of schizophrenia were found in 50 control subjects. (2) Several other comparisons, such as persons given other psychiatric diagnoses,
Patricia George / Ardingly College / IB Psychology / BLOA / Genetics & Schizophrenia

 felons, and persons discharged from the Armed Forces for psychiatric or behavioural reasons, demonstrated a significant excess of psycho-social disability in about one-half of the persons born to schizophrenic mothers. (3) The remaining one-half of the persons born to schizophrenic mothers were notably successful adults. They possessed artistic talents and demonstrated imaginative adaptations to life which were uncommon in the control group. The logic behind adoption studies: if offspring are separated from their biological parents, then any above-chance behavioural or psychological similarities to the biological parents must be largely due to genetic factors.

Summary of Heston (1966) adoption study:

Heston looked for relationships between schizophrenia incidence in mothers and in their biological children who had been brought up in foster homes Incidence rates for adoptees with no family history of schizophrenia were at the baseline level for the general population roughly 1% Incidence rates for adoptees with a family history of schizophrenia was 10% So having a family history of schizophrenia increases your risk of developing schizophrenia 10-fold, even if you are brought up away from your biological family This suggests that there is a strong genetic input to schizophrenia.

Patricia George / Ardingly College / IB Psychology / BLOA / Genetics & Schizophrenia