Schizophrenia Genetics

Genetics Meaning

Genetics is a field of study which is concerned with the link between our genes and our traits, often in relation to health and disease. We inherit half of our genotype from the father and half from the mother. However, we're not a perfect combination of their traits.

When fertilisation occurs, several complex processes can occur that mix up the genes of our parents. Moreover, parts of our genetic material can mutate and change.

Both the traits we are born with and the ones we develop throughout our lifespan can be linked to the genes our parents passed onto us. These traits are called a phenotype, a physical expression of our genotype.

Not all of our traits can be fully accounted for by the genes we inherited. Heritability estimates take values from 0 to 1, where 1 indicates that a trait is fully attributed to our genes and 0 indicates no genetic influence. We can also talk about heritability in terms of percentages.

Is Schizophrenia Genetic?

Schizophrenia is genetic to an extent, yes. Originally, schizophrenia was thought to be due to one "schizogene". Now we know that schizophrenia is a polygenic disorder. Schizophrenia is thought to be a result of genetic factors and environmental factors.

A person can be genetically vulnerable to developing schizophrenia, and their environment can act as a trigger to the actualisation of developing the disorder.

Schizophrenia Genetics Research

Let's look at the evidence for the heritability of schizophrenia from family, twin, and adoption studies. Famous examples include Gottesman (1991), Gottesman and Shields (1996), and Tienari et al. (2004).

Family Studies of Schizophrenia: Gottesman (1991)

In his book Schizophrenia Genesis: The Origins of Madness, Gottesman (1991) pooled data from a number of early studies that reported the concordance of schizophrenia within families. This data became highly influential in supporting the biological explanation of schizophrenia.

As you can see in the table below, the concordance rates generally appear to increase as the degree of genetic relatedness between family members increases. This data strongly supports the influence of genes on the development of schizophrenia.

Table 1 - Risk of developing schizophrenia for people with various degrees of relatedness to a person with schizophrenia.

However, this data has also been highly criticised as Gottesman failed to provide citations for the papers he analysed and also, many papers at the time have been biased due to lack of an appropriate methodology or eugenics (Joseph & Leo, 2006).

Twin Study of Schizophrenia: Gottesman and Shields (1996)

Gottesman and Shields performed their own twin study to investigate the heritability of schizophrenia.

• Identical twins share 100% of the same genes, while fraternal twins only share 50%. If a trait has a strong genetic link, the concordance rates for identical twins should be higher than for fraternal twins.

The study was conducted in a London hospital, which included 57 twin pairs (24 monozygotic and 33 dizygotic twin pairs) from a large sample of psychiatric patients.

• From the twin pairs included, at least one twin had a schizophrenia diagnosis.
• A number of measures were used to assess participants including hospital notes, interviews, questionnaires, and personality and disordered thinking tests.

The researchers found that in identical twin pairs with one twin diagnosed with schizophrenia, the other twin was 54% likely to be hospitalised for either schizophrenia or a related disorder.

In fraternal twin pairs, the likelihood of the other twin being hospitalised was 18%. Overall concordance rates for developing both severe and mild schizophrenia were higher for monozygotic twin pairs, supporting the contribution of genetics to schizophrenia.

Fig. 2: Concordance rates of schizophrenia in identical twins are reported to be around 50%.

Adoption Studies of Schizophrenia: Tienari et al. (2004)

Adoption studies look at whether adopted children develop traits, which are more similar to their biological parents or the adopted parents that raised them. If the former is true then the study supports the influence of genetics, but if the latter is true, then it's likely that the trait is influenced mostly by the environment rather than biology.

Tienari et al. (2004) conducted a longitudinal study with a national Finnish sample of adoptees. The researchers wanted to compare the clinical outcomes of adopted children with and without schizophrenic mothers.

The researchers conducted an assessment of the adopted environment through interviews, and clinical observations made by psychiatrists to investigate the environment as well.

When adoptees were assessed after a median of 12 years follow-up, researchers found that the adopted family environment was a strong predictor of developing schizophrenia, but only in adoptees with a high genetic risk.

Children adopted from schizophrenic mothers were more likely to also develop the disorder, especially if their adopted environment increased this vulnerability.

List of Genes Associated with Schizophrenia

Even though schizophrenia is certainly heritable, there is no one gene that can cause schizophrenia. Current research supports the theory that schizophrenia is a polygenetic disorder, which means that it is associated with variations in multiple genes.

Historically, researchers attempted to identify a set of candidate genes implicated in schizophrenia and psychosis.

• Some examples of candidate genes that were proposed were COMT, DRD4, and AKT1, all three of which are implicated in the processes of dopamine transmission in the brain.

Benzel et al. (2007) tested the association between variations of eight genes from the ERBB and NRG gene families, as well as their interactions in schizophrenia. They found several significant associations between certain gene variations and the disorder. Strong evidence was also found for the role of gene interactions in increasing susceptibility to schizophrenia.

A later study, conducted by Ripke and colleagues (2014) scanned for gene variations associated with schizophrenia across the entire genotype. They compared genotypes of almost 37,000 schizophrenia patients to a large control group of 113,000. The researchers found schizophrenia to be associated with variations in 108 genes, supporting the polygenetic model of the disorder.

Schizophrenia Genetic Testing

Could genetic tests for schizophrenia be used to assess risk, and aid diagnosis and treatment? While researchers can perform genetic tests for the purpose of genetic studies, individual genetic tests are not available or recommended in clinical settings as their predictive power is not strong enough yet (and may never be).

This is because even a relatively high genetic risk doesn't mean that a person will develop the disorder. Vasos et al. (2017) tested whether genetic tests could predict the diagnosis of schizophrenia in a first-episode psychosis sample. It was found that the polygenic risk only accounted for 10% of the risk for developing schizophrenia, compared to being given another diagnosis or recovering.

Fig. 3: - With known genetic associations of schizophrenia, the use of genetic tests is frequently discussed.

Evaluation of the Genetics of Schizophrenia

While the advances in knowledge about the heritability and genetic underpinnings for schizophrenia have helped to destigmatise the disorder and educate people about the risks, the genetic explanation on its own doesn't fully account for people's mental health outcomes. Let's look at the debates related to the genetic explanation of schizophrenia.

Nature vs. Nurture

Although there is extensive evidence on the contribution of genetics to schizophrenia, we can't say that genetics determine whether one develops schizophrenia or not. Even in monozygotic twin pairs, where all the genetic vulnerability (and much of the environment) is shared, we don't see 100% concordance rates.

Therefore, it's important to not underestimate the importance of nurture, which can independently contribute to psychological outcomes and interact with genetic risk factors.

Reductionism vs. Holism

Looking only at the genetic contribution when explaining the development of a complex disorder such as schizophrenia, can be considered reductionistic. Without considering all the other factors such as upbringing, personality, experiences or coping styles, which can also modulate genetic expression, we can miss the full picture.

In contrast, explanations that look at disorders as more than a sum of their parts, are called holistic.