Genetics and Neurotransmitters in Schizophrenia

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Questions and Answers

What role do genetic factors play in the production of neurotransmitters in relation to schizophrenia?

Genetic factors can affect the production and levels of neurotransmitters and their receptor sites.

How does the DISC1 gene contribute to brain development processes relevant to schizophrenia?

The DISC1 gene controls differentiation and migration of neurons during brain development.

What findings were revealed by the 2014 GWAS study regarding schizophrenia?

The GWAS study identified 108 distinct loci, with 83 being novel in relation to schizophrenia.

Explain the significance of the dopamine receptor D2 gene in the context of schizophrenia pathology.

The dopamine receptor D2 gene is significant because it highlights the importance of dopamine neurotransmission in schizophrenia. Signup and view all the answers

In what ways can twin studies contribute to understanding heritability estimates in schizophrenia?

Twin studies can provide insights into genetic predispositions by comparing concordance rates between monozygotic and dizygotic twins. Signup and view all the answers

What environmental influences might interact with genetic factors in the development of schizophrenia?

Environmental factors may include stress, drug use, and social support systems that interact with genetic susceptibility. Signup and view all the answers

How do susceptibility genes contribute to the complexity of schizophrenia?

Susceptibility genes often have small effects and act in concert with epigenetic and environmental factors. Signup and view all the answers

What types of neurotransmission are affected by genes identified in schizophrenia research?

Genes related to both dopaminergic and glutamatergic neurotransmission are notably affected. Signup and view all the answers

What was the main outcome of Tienari's study regarding adoptees and schizophrenia?

The study found a higher probability of schizophrenia or related conditions among adoptees with biological mothers diagnosed with schizophrenia-spectrum disorder. Signup and view all the answers

How did the family-rearing environment influence the risk of schizophrenia in high-genetic-risk adoptees?

Growing up in a dysfunctional family magnified the risk of developing schizophrenia in adoptees with a biological mother diagnosed with schizophrenia. Signup and view all the answers

What significance does the study have concerning the diathesis-stress model?

The findings support the diathesis-stress model by showing that genetic predisposition interacts with environmental stressors to influence the probability of developing schizophrenia. Signup and view all the answers

What did the study reveal about the protective effect of adoptive family environments?

The research suggested that being raised in a healthy adoptive family could have a protective effect against developing schizophrenia, even for those at genetic risk. Signup and view all the answers

How were the adoptee groups selected and compared in Tienari's study?

The study involved 303 adoptees, comparing those with high-genetic risk (biological mothers with schizophrenia) to a low-genetic risk group matched on demographic variables. Signup and view all the answers

What methodology did Tienari use to observe and evaluate the family environments of the adoptees?

Tienari employed clinical procedures that included joint interviews with families and semi-structured personal interviews with family members to assess family functioning. Signup and view all the answers

What questions regarding the heritability of schizophrenia remain unanswered based on the study findings?

Key questions include how schizophrenia is transmitted, what is inherited, and which specific genes may be related to the disorder. Signup and view all the answers

In what way does Tienari's study contribute to understanding heritability estimation?

The study provides evidence of hereditary factors by demonstrating a higher rate of schizophrenia in biological descendants of affected mothers, indicating heritable risk. Signup and view all the answers

What do Twin Studies demonstrate about the heritability of schizophrenia?

Twin Studies show that there is a genetic predisposition for schizophrenia, evidenced by higher concordance rates in monozygotic (MZ) twins compared to dizygotic (DZ) twins. Signup and view all the answers

How do environmental factors contribute to the aetiology of schizophrenia?

Environmental factors interact with genetic predisposition, influencing whether individuals with a genetic tendency for schizophrenia will develop the disorder. Signup and view all the answers

What were the findings regarding the risk of schizophrenia for the children of discordant twins in MZ and DZ pairs?

In MZ pairs, children of the twin without schizophrenia had a risk of 17.4%, nearly the same as the 16.8% risk for children of the twin with schizophrenia; in DZ pairs, the risk was 17.4% for the child of the affected twin and 2.1% for the unaffected twin. Signup and view all the answers

What are the limitations of twin studies in estimating the heritability of schizophrenia?

Twin studies cannot solely account for environmental influences, and the non-100% concordance rates suggest that not all individuals with genetic susceptibility will express schizophrenia. Signup and view all the answers

What conclusion can be drawn regarding genetic transmission and schizophrenia from studies like Gottesman & Bertelson (1989)?

The studies indicate a significant genetic component in the predisposition to schizophrenia but also emphasize that genetics does not guarantee the disorder's expression. Signup and view all the answers

In the context of twin studies, how do monozygotic twins differ from dizygotic twins regarding schizophrenia research?

Monozygotic twins share 100% of their genes, making them ideal for studying genetic influences, while dizygotic twins share about 50%, allowing researchers to compare genetic predisposition across different genetic similarities. Signup and view all the answers

Why might some individuals carry schizophrenia-related genes without exhibiting the disorder?

Some individuals may have protective environmental factors or personality traits that prevent the expression of schizophrenia despite having genetic susceptibility. Signup and view all the answers

What is meant by the term 'concordance rates' in the context of schizophrenia research?

Concordance rates refer to the likelihood that both twins in a pair will exhibit the same disorder; higher rates among MZ twins suggest a stronger genetic influence. Signup and view all the answers

Study Notes

Schizophrenia Lecture 10

Core textbook reading: Kalat, J.W. (2019). Biological Psychology, 13th edition. Boston, Massachusetts: Cengage Learning. Chapter 14, Module 14.3.

Aetiology of Schizophrenia

Both genetic and environmental factors play a role in schizophrenia.
Studies show a predisposition for schizophrenia can be transmitted genetically.
Evidence for genetic transmission comes from family studies, twin studies, and adoption studies.

Twin Studies

Concordance rates in MZ twins show a predisposition for schizophrenia is inherited.
Genetic factors are not the sole determinant, as concordance rates aren't 100%.
Some individuals carry genes for schizophrenia but don't develop the disorder.
Research using Norwegian and Danish medical records supports a genetic component to high concordance rates in MZ twins (e.g., Gottesman & Bertelson, 1989; Kringlen & Kramer, 1989).
Gottesman & Bertelson (1989) posed a hypothetical question about children of discordant twins (identical or fraternal).
Data from MZ twins showed children of both twins had an almost identical risk of schizophrenia, confirming inheritability. The risk in DZ pairs was significantly lower, differing from MZ pairs, thereby disproving the sole genetic factor assumption and confirming environmental involvement.
Twin studies have been criticized for: -Twins not being representative of the general population (higher mortality rate, more birth injuries, lower birth weights). -Potential for concordance due to shared common environments or prenatal environmental issues to be misattributed to genetic factors. -Shared environments and parental treatment differences between MZ and DZ twins
Large-scale Danish twin studies (Hilker et al., 2018) reported concordance rates of 33% in identical twins and 7% in fraternal twins, but genetics heritability was estimated to be 79%. This study used the proband-wise method for counting concordant twins, which has been criticized for potential double-counting issues (Torrey et al., 2019; Torrey, 1992). The proband-wise method inflated concordance rate, thereby influencing heritability estimation.
The modeling process used for calculating genetic heritability has been criticized. The model assumes: -Twins are comparable to the general population. -MZ and DZ pairs experience environmental effects similarly. -Gene-environment interactions are minimum.

Adoption Studies

Adoption studies examine adopted children who develop schizophrenia, supporting a genetic basis.
Genetic and rearing factors can be disentangled to some extent.
A hypothesis suggests adults with schizophrenia adopted as children are more likely to have biological relatives with schizophrenia compared to adults adopted as children without schizophrenia.
Adoption studies try to exclude environmental influences.
Kety (1994), using Danish records, found that 12.5% of first-degree biological relatives of adoptees with schizophrenia also had the disorder, unlike adoptees without the disorder.
No schizophrenia was found in the biological relatives of adoptees without schizophrenia, indicating the environmental component.
- Similar results were observed by Heston (1966) and Kety (1988).
Tienari et al. (2004) conducted a Finnish adoption study, the first to examine family rearing and the interaction of genotype and environment variables, leading to higher probability of schizophrenia for children of biological mothers with schizophrenia that are also raised in dysfunctional or harsh environments.
Adoptee families were matched demographically, and their environments were blindly evaluated in their family home setting.
Clinical procedures included joint interviews of entire families and semi-structured personal interviews. Data were collected using the Oulu Family Rating Scale (OPAS) to objectively assess family functioning.
Schizophrenia was higher in children with biological risk of and rearing in dysfunctional family environments compared to children without biological risk or with dysfunctional rearing environments.

Diathesis-Stress Model

A model showing the converging of early biological susceptibility (genetic liability) with later stressors (prenatal health problems and adverse life events and family environments). The risk of schizophrenia increases over time from converging factors.

Heritability of Schizophrenia

Many questions remain unanswered: how the disorder is transmitted, what is being inherited, and the associated genes and functions.
Multiple susceptibility genes with small effects interact with epigenetic and environmental factors.
Genes like COMT (catechol-O-methyltransferase), involved in dopamine metabolism; G72, contributing to glutamatergic activity; and Neuregulin 1, involved in NMDA, GABA, and ACh receptor regulation. They contribute to schizophrenia.
Dysbindin (presynaptic glutamate function) and DISC1 (disrupted in schizophrenia 1), which affect neuron differentiation, migration, and dendritic spine production in the hippocampus, participate in schizophrenia.

GWAS Study

A genome-wide association (GWAS) study of >35,000 individuals with schizophrenia and >110,000 controls identified 108 distinct genetic loci, 83 previously unlinked to schizophrenia, and genes encoding proteins for glutamatergic neurotransmission.
Genes expressed in immune tissues were also linked to schizophrenia, supporting the immune system linkage hypothesis.
Ma et al. (2018) identified 6 crucial genes related to increased schizophrenia risk, linking 5 of them to neurodevelopment.

Summary

Many genes involved in schizophrenia have unknown transmission and expression, with small effects.
A polygenic risk score explains at least 7% of schizophrenia liability.
Some schizophrenia cases can be linked to rare copy number variants (CNVs), including duplications, deletions, and inversions. Some CNVs are linked with increased risk of developing schizophrenia, by up 20 times.

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Description

Explore the complex relationship between genetic factors and neurotransmitter production in schizophrenia. This quiz delves into the role of specific genes, such as DISC1 and dopamine receptor D2, as well as findings from twin studies and significant research studies like the 2014 GWAS. Test your knowledge on how genetic and environmental factors intertwine in the development of this mental disorder.