Genetic Explanation of Schizophrenia

The role of genes

stock-photo-microscopic-view-of-chromosome-x-216321241The human genome comprises around 23000 genes, each gene carrying specific instructions about how to build a unique person! With regard to brain development, genes code for the construction of neurotransmitters, receptors and enzymes and therefore genetic variation may be responsible for some of the neurochemical irregularities described elsewhere in this chapter.

Schizophrenia as a heritable condition

This explanation focuses on genetic inheritance, suggesting that schizophrenia is a heritable condition that passes from one generation to the next. Although specific genes have not been shown to directly cause schizophrenia, a numerous chromosomes appear to be implicated including 22, 1, 18, 15, 14, 13, 12, 11, 10, 8, 6, 5, 3. In addition, many specific regions on these chromosomes have also been identified. Some of the strongest evidence suggests the importance of chromosomes 13 and 6.

Variations in numerous individual genes are thought to increase the risk of an individual developing schizophrenia, including genes that regulate neurochemicals such as dopamine and serotonin. In 2014, Jessica Wright indicated that as many as 700 genes have been linked to schizophrenia and by now this figure is likely to be in the thousands.

Gene mutations and deletions

Gene mutations can be passed down from parents to their offspring (known as germline mutations) or they happen spontaneously, (known as acquired mutations). In the latter case, these changes may result from an environmental factor or an error during cell division, such as a deletion or duplication of a strand of DNA. Larger deletions are also possible; for example Di George Syndrome is caused by the deletion of around 30-40 neighboring genes located in a specific region of chromosome 22 known as 22q11.21. This syndrome is particularly pertinent here because as many as 25% of people with this condition go onto develop schizophrenia.

The COMT gene

The link with between schizophrenia and Di George may be due to the deletion of a specific gene called COMT. This gene provides instructions for the creation of catechol-O-methyltransferase; an enzyme which breaks down neurotransmitters such as dopamine, in brain regions such as the prefrontal cortex. Deletion of the COMT gene would mean that dopamine levels are poorly regulated resulting in schizophrenic symptoms.

The DISC 1 gene

People with an abnormality to the gene Disrupted-in-Schizophrenia 1 or DISC1 are 1.4 times more likely to develop schizophrenia than people without this abnormality. This gene codes for the creation of GABA which is important in the regulation of neurotransmitters such as glutamate and dopamine in regions such as the limbic system, (see p 000).

starsStretch and challenge

Epigenetics and DNA methylation

Ezra Susser and colleagues (1992) reported the results of a sickening ‘natural experiment’ in the Netherlands which demonstrates the role of epigenetic factors in schizophrenia. In 1944, the Nazis blocked the distribution of food to the Dutch people and 22000 of them died of starvation, in what became called the Dutch Hunger Winter. Susser reports that women, who became pregnant during the famine, whilst consuming as little as 580 calories a day, went on to have low birth weight babies. Whilst this may be unsurprising, what is more interesting is that these babies were twice as likely to develop schizophrenia when they grew up as babies conceived in happier times.

Can you think of any other factors which may also have affected the unborn babies, increasing their risk of future mental disorders?


MZ/DZ twin studies

schiz.riskOne strength of the genetic explanation of schizophrenia is that it is supported by Irving Gottesman and James Shields’ (1966) seminal research on mono- and dizygotic twin pairs.

They found a concordance rate of  42% for MZ twins and only 9% for DZs. When other psychiatric diagnoses were taken into account for the co-twin, the rate went up to 79% for MZ and 45% for DZs. Perhaps the most compellingly finding was that the chance of being ‘psychologically normal’ was just 21% for the co-twins of MZs and 55% for the DZs.

This shows that while schizophrenia is not entirely a genetic disorder, the fact that the concordance rate is greater for MZs than DZs, shows that biology certainly play a significant part.

Competing argument: Caution should be exercised care when interpreting results from MZ/DZ twin studies; MZ do not only share more DNA than DZ; they are also likely to be treated more similarly due to more similar appearance and the fact that they are always the same sex, (DZs, can be different sexes). This reduces the validity of the conclusion that the greater amount of shared DNA is responsible for their similar pathology.

Protective environmental factors

One weakness of the argument that schizophrenia is genetic is the fact that the concordance rate is far from 100% for MZ twins.

Pederson and Mortenson’s research neatly demonstrates that the longer a person has been exposed to city life and the denser the population in that city, the greater their risk of developing schizophrenia.

This suggests that rural dwelling may to help protect a person from developing a disorder to which they are genetically predisposed.

Research evidence on DISC1 and COMT

A strength of the suggestion that schizophrenia may be linked to DISC1 and COMT is that it is supported by a wealth of research evidence.

In a review of 14 studies, Tarik Dahoun and colleagues (2017) concluded that DISC1 is associated with presynaptic dopamine dysregulation. While Michael Egan and colleagues (2001) propose a link between decreased dopamine activity in the prefrontal cortex and the ‘Val’ allele of the COMT gene. They state that inheriting two copies of the Val polymorphism increases risk of schizophrenia by 50%.

This shows how genetic variations underpin neurochemical differences which can predispose a person towards schizophrenia.

Application: Genetic counselling

A strength of the increased understanding of the genetics of schizophrenia is that it has been used to inform genetic counselling.

When a family member receives a diagnosis of schizophrenia, the family may want more information about whether the condition is heritable. ‘Recurrence risk’ can be calculated and the counsellor will then help the family to interpret this information.

This service can provide support during difficult times, help to allay fears while also helping people to make rational choices about family planning.

EXTRA: Issues and debates

One relevant debate here is clearly that of nature and nurture.

Pekka Tienari’s 21 year longitudinal adoption study  support the ‘diathesis-stress model’ , suggesting that adoptees of schizophrenic biological mothers were more sensitive to family dysfunction in the adoptive home than those from low risk matched backgrounds.

This supports an interactionist approach to explaining schizophrenia.

Practice Questions

  1. Describe one biological explanation of schizophrenia other than the function of neurochemicals (5)
  2. Compare one biological and one non-biological explanation of schizophrenia (4)
  3. Elizabeth has been diagnosed with schizophrenia. Discuss whether her sister Zara should be concerned about her own wellbeing (8)
  4. Assess the role of nature and nurture in the development of schizophrenia (20)