GENETIC THEORIES OF SCHIZOPHRENIA
TERMINOLOGY
MONOZYGOTIC (MZ) TWINS: Identical twins originate from a single fertilised egg (zygote) that splits into two embryos. MZ twins share 100% of their genetic material, making them valuable in studies exploring the genetic basis of traits or disorders, as any differences between them are primarily due to environmental factors.
ALLELE: An allele is a variant form of a gene. Different alleles can result in other traits, such as eye colour or blood type. In the context of genetic disorders, specific alleles may carry a risk for conditions like schizophrenia.
DIZYGOTIC (DZ) TWINS: Also known as fraternal twins, DZ twins develop from two separate eggs fertilised by two different sperm. Similar to regular siblings, DZ twins share about 50% of their genetic material. Comparing the concordance rates of a trait in MZ and DZ twins helps researchers understand the genetic versus environmental contribution to that trait.
CONCORDANCE RATE: This is the probability that both individuals in a pair (such as twins or family members) will display a particular trait or disorder if one of them does. In genetic research, a higher concordance rate in MZ twins than DZ twins suggests a stronger genetic influence on the trait or disorder.
FAMILY STUDY: This study examines the prevalence of a specific trait or disorder within a family. It helps determine whether close relatives of individuals with a condition like schizophrenia have a higher risk of developing the same condition, indicating a possible genetic component.
PEDIGREE: A pedigree is a diagram that shows the occurrence and appearance of a particular trait within a family over multiple generations. It is used to track the inheritance patterns of genetic conditions. It can help identify whether a disorder is likely monogenic (caused by a single gene) or polygenic (influenced by multiple genes).
MONOGENIC: Refers to traits or disorders caused by a mutation in a single gene. Monogenic disorders often follow simple inheritance patterns, such as dominant or recessive. Examples include Huntington's disease and cystic fibrosis. Schizophrenia is not considered monogenic, as it does not result from a mutation in just one gene.
POLYGENIC: Refers to traits or disorders influenced by multiple genes, each contributing a small effect. Schizophrenia is considered polygenic, involving many genetic variations spread across the genome, along with environmental influences.
META-ANALYSIS: A statistical method that combines the results of multiple independent studies on a particular topic to provide a more comprehensive understanding. In genetic research, a meta-analysis can pool data from various studies to better estimate the genetic risk factors associated with disorders like schizophrenia.
GENETIC THEORY INTRODUCTION
Schizophrenia is a debilitating mental illness that causes significant distress to sufferers and their families. Over the years, researchers have made considerable efforts to identify its underlying causes in the hope of developing effective treatments and preventative measures.
One prominent explanation is the genetic theory, which posits that schizophrenia has a strong hereditary component.
METHODS OF GENETIC RESEARCH
To gain deeper insights into the heritability and risk factors of schizophrenia, researchers utilise a variety of methods, including:
PEDIGREE ANALYSIS: Examining family trees to trace the inheritance patterns of schizophrenia across generations.
FAMILY STUDIES: Investigating the prevalence of schizophrenia among relatives, particularly first-degree relatives such as parents and siblings.
TWIN STUDIES: Comparing concordance rates between monozygotic (identical) and dizygotic (fraternal) twins to differentiate between genetic and environmental influences.
ADOPTION STUDIES: Studying individuals adopted at birth to separate the effects of genetic predisposition from the environment in which they were raised.
GENOME-WIDE ASSOCIATION STUDIES (GWAS): Analysing the entire genome to identify specific genetic variants associated with schizophrenia.
EPIGENETIC RESEARCH: Exploring how environmental factors can modify gene expression without altering the DNA sequence.
These diverse approaches provide a comprehensive understanding of how genetic and environmental factors interact to contribute to the development of schizophrenia.
REFERENCES
Gottesman, I. I., & Shields, J. (1972). Schizophrenia and Genetics: A Twin Study Vantage Point. New York: Academic Press.
Gottesman, I. I., & Shields, J. (1976). A critical review of recent adoption, twin, and family studies of schizophrenia: Behavioral genetics perspectives. Schizophrenia Bulletin, 2(3), 360-401. doi:10.1093/schbul/2.3.360
Additional data from aggregated studies are cited in Gottesman and Shields' reviews.
The studies referenced used earlier editions of the DSM (DSM-III) and ICD (ICD-8 or ICD-9), consistent with the diagnostic standards of their time.
The data spans decades, focusing on European populations.
Concordance rates are not definitive, reflecting both genetic and environmental influences on schizophrenia.
CONCORDANCE RATES AND GENETIC RELATEDNESS IN SCHIZOPHRENIA
A common way to study genetic influences is by investigating the frequency of schizophrenia among family members. This approach evaluates whether the correlation coefficient for schizophrenia increases with genetic relatedness. For example, monozygotic (MZ) twins share 100% of their genes, while dizygotic (DZ) twins share 50%, and so on.
Concordance rates measure the probability that two individuals with shared genetics (e.g., twins or relatives) will develop the same trait, such as schizophrenia. These rates fall under intraclass correlations, focusing on similarity within a defined group (e.g., family members or twins).
In genetic research, concordance rates are crucial for understanding the heritability of conditions like schizophrenia. For instance:
If both twins share a diagnosis, they are concordant.
If only one twin has the diagnosis, they are discordant.
REFERENCES
Gottesman, I. I., & Shields, J. (1972). Schizophrenia and Genetics: A Twin Study Vantage Point. New York: Academic Press.
Gottesman, I. I., & Shields, J. (1976). A critical review of recent adoption, twin, and family studies of schizophrenia: Behavioral genetics perspectives. Schizophrenia Bulletin, 2(3), 360-401. doi:10.1093/schbul/2.3.360
Additional data from aggregated studies are cited in Gottesman and Shields' reviews.
The studies referenced used earlier editions of the DSM (DSM-III) and ICD (ICD-8 or ICD-9), consistent with the diagnostic standards of their time.
The data spans decades, focusing on European populations.
Concordance rates are not definitive, reflecting both genetic and environmental influences on schizophrenia.
RELATIONSHIP BETWEEN GENETIC RELATEDNESS AND SCHIZOPHRENIA
Gottesman and Shields (1991) examined schizophrenia concordance rates across different degrees of genetic relatedness using data collected in European countries between 1920 and 1987. The findings showed that the likelihood of developing schizophrenia diminishes as genetic relatedness decreases:
Monozygotic (MZ) twins had the highest concordance rate: 48%.
Dizygotic (DZ) twins showed a significantly lower concordance rate: 17%.
First-degree relatives (e.g., siblings, parents, children): 9-13%.
Second-degree relatives (e.g., half-siblings, aunts/uncles, nieces/nephews): 2-6%.
Third-degree relatives (e.g., cousins): around 2%.
The general population 1%,
Supporters of the genetic model argue that these findings demonstrate a clear pattern: the closer the genetic relationship, the higher the risk of developing schizophrenia. Particularly noteworthy is the 31% difference between the concordance rates of MZ and DZ twins, which is often seen as evidence of a genetic influence, as MZ twins are genetically identical.
Additionally, studies indicate that children with both parents diagnosed with schizophrenia, who inherit two sets of faulty genes, are at significantly higher risk of developing psychosis, further suggesting a substantial genetic contribution to the disorder.
Concordance rates and correlation coefficients both highlight the role of genetic relatedness in the development of schizophrenia. However, they are not absolute, demonstrating the importance of environmental factors alongside genetic predisposition.
ANALYSIS OF FAMILY STUDIES RESEARCH IN SCHIZOPHRENIA
Overall, there are many problems with using family and twin studies, including Gottesman, 2010.
RETROSPECTIVE NATURE OF STUDIES
Family and twin studies on schizophrenia often rely on retrospective data, meaning they examine past cases and are limited in terms of their ability to re-assess participants based on modern criteria. This becomes problematic because psychiatric diagnoses, including schizophrenia, have evolved significantly over time. The diagnostic criteria outlined in earlier versions of diagnostic manuals like the DSM (Diagnostic and Statistical Manual of Mental Disorders) and ICD (International Classification of Diseases) were not as comprehensive or as well-defined as those in current editions. This means that individuals diagnosed with schizophrenia in the early 20th century may have been diagnosed with a set of symptoms that no longer meet the modern standards for the disorder. The inability to check these old diagnoses against current definitions questions the reliability of findings. This compromises the internal validity of retrospective studies, meaning the conclusions we draw from these findings might not reflect what we would see if those studies were replicated with current diagnostic practices. Furthermore, because the data cannot be revisited or re-examined, the credibility of such results is diminished, leaving room for uncertainty about their accuracy.
INFLUENCE OF ENVIRONMENTAL FACTORS ON MZ VS DZ TWIN CONCORDANCE
One common assumption in twin studies is that higher concordance rates in monozygotic (MZ) twins, as compared to dizygotic (DZ) twins, point to a genetic influence. However, this interpretation oversimplifies the relationship between genetics and the environment. While MZ twins are genetically identical, this genetic similarity is only one factor contributing to their concordance. MZ twins are often treated more similarly than DZ twins due to their identical appearance and gender, which can lead to shared experiences that may not be purely genetic but environmental. For example, MZ twins are likely to be dressed alike, placed in the same classes, and encouraged to pursue similar interests, all because of their physical similarities. This can create an artificial environment that increases their likelihood of having similar outcomes, including developing schizophrenia. In contrast, DZ twins, who are not identical and may have different physical characteristics and gender, are less likely to be treated identically. This can lead to more significant environmental variation, which may account for the lower concordance rates observed in DZ twins. Furthermore, many twin studies fail to adequately control gender, which can affect the way others treat both MZ and DZ twins. Therefore, the assumption that genetic factors alone account for the higher concordance in MZ twins is problematic, as the environment may significantly shape these outcomes.
DIFFICULTY ESTABLISHING CAUSE AND EFFECT
The challenge of establishing a clear cause-and-effect relationship is central to interpreting the findings of family and twin studies on schizophrenia. While these studies suggest that genetics may play a role in the development of the disorder, they do not definitively prove that genetics are the primary cause.
MZ and DZ twins share significant environmental influences, such as growing up in the same household, having similar socioeconomic backgrounds, and experiencing similar familial or cultural contexts. These shared environmental factors could contribute substantially to the similarities in their concordance rates, blurring the line between genetic and environmental influences. In particular, it is difficult to rule out the possibility that individuals genetically predisposed to schizophrenia might also be more likely to experience environmental stressors that increase their risk of developing the disorder, such as family conflict or trauma. Therefore, the difficulty in isolating genetic influences from environmental ones complicates efforts to determine the specific role that genetics plays in the development of schizophrenia.
CHILDREN OF SCHIZOPHRENIC PARENTS
Especially relevant to this nature-nurture argument is Gottesman’s assumption that the 27-39% concordance rate for children with two schizophrenic parents is genetic. However, this finding becomes more complex when we consider research by Tienari, which shows that children of parents with schizophrenia are often adopted away, primarily due to the severe impact the parent’s condition can have on the child’s emotional and cognitive development. Living with a schizophrenic parent must be incredibly stressful and confusing for a child, as schizophrenia often results in significantly impaired cognition, language, and emotional regulation. Furthermore, delusions and hallucinations experienced by the parent can be frightening and challenging for a child to understand. It is, therefore, logical to propose that a child of a schizophrenic parent may struggle to have rational conversations or seek emotional support when the disorder is active. This creates a chaotic and unpredictable environment that can significantly impact the child’s mental health.
The interaction between genetic predisposition and such an environment makes it nearly impossible to disentangle the two factors when considering the causes of schizophrenia. The mental illness of a parent may not only contribute to the development of mental health issues in their children. Still, it could also exacerbate genetic vulnerability, creating a situation where genetic and environmental influences are inseparable.
DZ TWINS VERSUS SIBLINGS
A closer inspection of some of the other concordance rates also suggests nurture is causal rather than nature—for instance, the concordance rates of dizygotic (DZ) twins and normal siblings. Dizygotic twins are no more similar genetically than regular siblings, yet they have a much higher concordance rate (roughly 17% compared to 9%). If schizophrenia was purely genetic, then the incidence of schizophrenia in DZ twins and normal siblings should be identical as they both only share 50% of their DNA.
DZ twins’ higher concordance rate could be interpreted as environmental and/or psychological because DZ twins live in the same zeitgeist and are more likely to assess their social and emotional world from the same level of maturity. For example, parents arguing may be perceived negatively by an older sibling and remain unnoticed by a younger sibling. Still, DZ twins may conclude similar disturbed observations about their parent’s relationship simply because they are the same age. Moreover, family dynamics/hierarchies continually change (e.g., things like family economics, job satisfaction, being the oldest, youngest, family stresses/illness) and thus may be interpreted differently by siblings of differing ages.
SEPARATED MZ TWIN RESEARCH
Separated twin studies offer a unique approach to untangling the influence of nature and nurture. If both twins are concordant for schizophrenia despite being raised in different environments, it suggests that genetic factors may be at play. For example, Gottesman and Shields (1982) found that the concordance rate for schizophrenia in 12 pairs of monozygotic (MZ) twins reared apart was 58% (7 out of 12 pairs), even though these twins had been raised in different environments. This rate is even higher than the concordance rate observed in MZ twins raised together, which implies that genetic factors could play a significant role in the disorder’s development.
A03 RESEARCH ANALYSIS ON SEPARATED MZ TWINS
However, several criticisms and limitations exist when evaluating these separated twin studies. First, very few separated twin pairs have been studied, as it is incredibly challenging to find such twins. This makes generalisability a potential issue, as the small sample size (12 pairs) limits the ability to draw broad conclusions. With such a limited number of cases, inferential statistics and probability calculations may not be reliable.
Another issue is the reason for the separation. It’s essential to question whether the events leading up to the separation were traumatic, and if so, how this could have impacted the twins’ mental health. Furthermore, the trauma they experienced after the separation—such as the emotional strain of being raised apart—could also be a contributing factor to the development of schizophrenia.
Lastly, and perhaps most crucially, the validity of twin studies has been questioned. In his book The Gene Illusion (2003), clinical psychologist Jay Joseph challenges the validity of genetic theories in psychiatry and psychology, particularly those based on twin and adoption studies. Joseph argues that many of the separated MZ twins studied were not wholly separated; they lived near each other or had contact in various forms, such as letters or occasional visits. This ongoing contact between the twins could lead to shared environmental influences, complicating the interpretation of genetic effects. If the twins were regularly exposed to similar environmental factors, it would be difficult to isolate the genetic component of schizophrenia.
Joseph’s work critiques the methodological foundations of genetic research in mental health and argues that environmental factors, rather than genetics, may have a more significant role in the development of disorders such as schizophrenia, criminal behaviour, and IQ. While The Gene Illusion has faced some criticism, particularly concerning its conclusions, it remains influential among those who argue that environmental influences are overwhelmingly responsible for mental disorders.
The Gene Illusion is a 2003 book by clinical psychologist Jay Joseph, in which the author challenges the evidence underlying genetic theories in psychiatry and psychology. Focusing primarily on twin and adoption studies, he attempts to debunk the methodologies used to establish genetic contributions to schizophrenia, criminal behaviour, and IQ. In the nature and nurture debate on the causes of mental disorders, Joseph's criticisms of genetic research in psychiatry have found their place among those who argue that the environment is overwhelmingly the cause of these disorders. Some of the conclusions of The Gene Illusion have been criticised in book reviews.
RESEARCH ON THE FIVE REMAINING NON-CONCORDANT TWINS.
Gottesman and Shields (1982) researched the remaining five non-concordant twins from their study, where five out of the 12 MZ twins did not develop schizophrenia despite their MZ twin sibling being diagnosed with the disorder. The researchers hypothesised that if any of these five non-concordant twins had a child who developed schizophrenia, this could help resolve the nature-nurture debate. Specifically, if a child of a non-concordant twin developed schizophrenia, it could not be attributed to environmental factors, such as growing up with a schizophrenic parent, since these non-concordant twins were not affected by the disorder. Therefore, any development of schizophrenia in the child would have to be genetic and inherited from the mother’s side, i.e., the non-schizophrenic twin’s identical twin sibling (the other MZ twin).
The results of this longitudinal study showed that 9% of children born to non-concordant twins developed schizophrenia. Given that the general risk for developing schizophrenia is around 1%, this finding seems to support the idea of a genetic basis for the disorder.
A03 RESEARCH ANALYSIS ON NON-CONCORDANT TWINS
While the statistic seems promising, it is essential to consider the study's small sample size. With only five non-concordant twins, the number of children born to them was likely limited. For example, if each non-concordant twin had four children, this would result in 20 children. Nine per cent of 20 children have schizophrenia. This small number of cases is insufficient to provide a statistically significant result. Therefore, although the study suggests a potential genetic link, the numbers are too small to draw robust conclusions, and the findings lack the statistical power to support the genetic argument for schizophrenia conclusively.
ADOPTION STUDIES RESEARCH
The most effective way to separate the effects of genes from the environment is to study adopted children who later develop schizophrenia and compare them with their biological and adoptive parents. Adoption studies provide a unique design that helps disentangle genetic influences from environmental factors.
TIENARI’S FINNISH ADOPTION STUDY
Tienari began his Finnish adoption study in 1969. He followed 112 adopted children who had been separated from their biological mothers and diagnosed with paranoid schizophrenia. These children had been separated from their mothers anytime from infancy to four years of age. A matched control group consisted of 135 adopted children who did not have biological mothers with schizophrenia or any diagnosed mental illness.
Procedure: The schizophrenic adoptees (experimental group) were between 5-7 years old at the start of the study, while the control group had been adopted earlier. Tienari tracked these adoptees over time to examine the development of schizophrenia.
Findings: 7% of the adoptees in the experimental group developed schizophrenia, compared to only 1.5% of the control group.
Conclusion: The higher concordance rate for schizophrenia in the experimental group (children with schizophrenic biological mothers) supports the role of genetic factors in the development of schizophrenia.
A03 RESEARCH ANALYSIS ADOPTION STUDIES
Adoption studies have been one of the most promising methods for understanding schizophrenia, revealing that adopted offspring of mothers with schizophrenia have a 7% chance of developing the disorder despite being raised in adoptive homes. In comparison, the rate of children adopted from non-schizophrenic mothers is 1.5%. Many psychologists believe that adoption studies show a clear genetic link, suggesting that genetics play a significant role in the risk of schizophrenia.
Additionally, Tienari’s study was a prospective longitudinal, natural experiment, which avoids many of the problems associated with retrospective, correlational studies used in family and twin research (e.g., poor participant memory and the inability to establish cause-and-effect relationships).
Kety (1976, 19994) and Heston (1976) conducted similar studies, which showed similar results. This adds validity to Tienari’s findings.
ISSUES WITH INTERNAL VALIDITY
However, internal validity issues exist, specifically regarding individual participant differences. Tienari claimed to have matched his experimental and control groups. The schizophrenic adoptees were removed from their mothers before the age of four, although the exact timing of this is unclear. These children were then adopted between the ages of 5 and 7 years. It is unclear where they spent the intervening year, whether in an institution or a potentially disruptive environment.
It is also not known whether the schizophrenic adoptees experienced deprivation, privation, or abuse during their first four years of life. It seems likely that children of schizophrenic mothers were adopted because of family problems, which could have contributed to early trauma. In contrast, the control group did not experience such late adoptions or disruptions in early infancy, which means that critical extraneous variables, such as early environmental factors, were not controlled. Studies on children who suffered neglect in their early years (e.g., Rutter, Hodges, and Tizard) show that such experiences can lead to long-lasting problems with language, relationships, and emotional regulation. Early disruptions in care and family discord could have significant implications for a child’s mental health.
Given these issues, can we conclusively state that the results of Tienari’s study are purely due to genetics? Interestingly, Tienari also observed that adoptees were more likely to develop schizophrenia if their new families were disturbed. This finding supports the idea that schizophrenia is a disorder with both biological and psychological causes, aligning with the diathesis-stress model (which posits that both genetic vulnerability and environmental stressors contribute to the development of the disorder).
ETHICS FOR TIENARI
Tienari has faced ethical criticism for his study, mainly because the children he studied were probably taken from their biological mothers without informed consent. If the mothers were schizophrenic, they would likely have been unable to consent to their child being adopted, as they may have been considered mentally incapacitated during the active phases of their illness. Some researchers argue that Tienari was wrong to study these children if he benefited from a potentially immoral decision, considering the mother’s inability to give consent due to their mental illness.
KETY’S DANISH-AMERICAN ADOPTION STUDY
Seymour Kety's study (1968) similarly investigated the genetic basis of schizophrenia using adoption as a tool to separate genetic and environmental influences. Kety worked with the Danish Adoption Register, identifying 34 schizophrenic adoptees (index cases) and 33 controls, matched for factors such as age, gender, age at adoption, and adoptive family social class.
Procedure: Kety examined 150 biological relatives and 156 adoptive relatives of the participants, tracking them through Danish family and health records. A panel of Danish psychiatrists conducted blind diagnoses of family members, grouping them into categories for schizophrenia spectrum disorders.
Findings: 8.7% of the biological relatives of schizophrenic adoptees were diagnosed with schizophrenia spectrum disorders, compared to only 1.9% of the biological relatives of controls. The adoptive relatives of schizophrenic adoptees did not show a significant increase in schizophrenia spectrum disorders compared to the control group.
Conclusion: Kety concluded that schizophrenia has a significant genetic component, as the biological relatives of schizophrenic adoptees were much more likely to develop schizophrenia than their adoptive relatives.
EVALUATION OF KETY'S DANISH-AMERICAN ADOPTION STUDY
STRENGTHS
Natural Experiment: Adoption studies naturally separate genetic and environmental influences, providing a strong basis for evaluating heritability.
Rigorous Matching: Kety matched controls to index cases based on age, gender, age at adoption, and adoptive family social class, reducing confounding variables.
Blind Diagnoses: Using psychiatrists unaware of participants’ group memberships reduced diagnostic bias.
Replicability: The study was replicated multiple times (1975, 1978, 1994), consistently supporting the genetic hypothesis for schizophrenia.
LIMITATIONS
Broad Diagnoses: The inclusion of “schizophrenia spectrum disorders” may have inflated findings by including less severe or unrelated conditions like "inadequate personality."
Diagnostic Variability: Changes in diagnostic criteria over time mean participants may not meet current DSM-5 standards for schizophrenia, limiting the validity of conclusions.
Environmental Factors: The study did not account for the potential influence of contact between adoptees, biological families, or shared prenatal environments.
Criticisms of Bias: Critics like Jay Joseph argue that methodological adjustments may have been made to favour a genetic explanation, such as redefining schizophrenia as a "spectrum" to bolster findings
EVALUATION OF FAMILY TWIN AND ADOPTION STUDIES
Research into the genetics of schizophrenia, including meta-analyses, twin studies, and adoption studies, is limited by significant validity issues due to outdated and inconsistent diagnostic criteria. Early studies often used broad definitions of schizophrenia, encompassing conditions that no longer meet the stricter criteria introduced with DSM-III (1980) and refined in later editions like DSM-5.
Many of these studies, including those analysed by Gottesman, relied on diagnoses that included subtypes and symptoms no longer recognised, such as “paranoid schizophrenia” or milder psychotic disorders. This likely inflated concordance rates in twin studies and genetic transmission findings in adoption studies. For example, Tienari’s adoption study and Kety’s Danish-American adoption study were conducted over periods when diagnostic criteria varied, complicating the interpretation of their results.
In summary, while early studies suggest a genetic component to schizophrenia, their reliance on outdated classifications means the findings may overestimate heritability. Modern research must carefully contextualise these results within current diagnostic standards to provide a more accurate understanding of schizophrenia’s genetic basis.
GENETIC RESEARCH IN SCHIZOPHRENIA
The idea that schizophrenia might be linked to genetics has long intrigued researchers. Early studies sought to identify a single gene or a few genes responsible for the disorder, known as the MONOGENETIC THEORY. However, extensive research has ruled this out. Behavioural genetics expert Robert Plomin highlights that, unlike conditions such as Huntington's disease, schizophrenia does not have a single identifiable genetic cause. Instead, it arises from a complex interplay of genetic and environmental factors.
Modern genetic research reveals that schizophrenia is a polygenic disorder, meaning many genes influence it, each contributing a small effect. Advanced technologies, such as genome-wide association studies (GWAS), have helped identify genetic variations linked to schizophrenia, deepening our understanding of its biological underpinnings.
Although family and twin studies were pivotal in establishing the heritability of schizophrenia, they have largely fallen out of favour. These methods lack the precision of newer techniques, such as GWAS, which provide detailed insights into specific genetic contributions rather than broad heritability estimates.
GENES ASSOCIATED WITH SCHIZOPHRENIA
Numerous genes have been linked to schizophrenia, with most affecting brain development, communication between neurons, and the immune system. Below are some of the most important discoveries:
C4 GENE (COMPLEMENT COMPONENT 4)
What it does: C4 plays a role in the immune system and synaptic pruning, where unnecessary connections between neurons are removed during adolescence.
How it relates to schizophrenia: Overactive C4 leads to excessive pruning, which may disrupt neural connectivity and contribute to cognitive and behavioural symptoms.
DISC1 (DISRUPTED IN SCHIZOPHRENIA 1)
What it does: DISC1 is involved in brain development and maintaining neuron structure.
How it relates to schizophrenia: Variants in DISC1 can impair brain development, potentially leading to the disorganised thinking seen in schizophrenia.
CACNA1C
What it does: This gene regulates calcium channels, critical for neuron signalling.
How it relates to schizophrenia: Mutations in CACNA1C disrupt communication between neurons, affecting cognition and mood regulation.
GRIN2A
What it does: GRIN2A is associated with NMDA receptor activity, which is essential for memory and learning.
How it relates to schizophrenia: Variants in GRIN2A can reduce NMDA receptor function, potentially contributing to hallucinations and cognitive deficits.
HOW GENES ARE IDENTIFIED
GENOME-WIDE ASSOCIATION STUDIES (GWAS)
GWAS analyses the entire genome of individuals with and without schizophrenia to identify genetic differences. This method has pinpointed over 270 genetic loci associated with the disorder, including C4, DISC1, and CACNA1C.
LINKAGE STUDIES
Linkage studies, used in earlier genetic research, tracked family genetic markers. While helpful in establishing heritability, they lacked the precision to identify specific genes.
CANDIDATE GENE STUDIES
These studies focused on genes with known roles in brain function. DISC1, for example, was identified due to its involvement in neural development and its disruption in families with a history of schizophrenia.
CRITICISMS OF GENETIC RESEARCH IN SCHIZOPHRENIA
LACK OF CAUSAL PATHWAYS
While GENOME-WIDE ASSOCIATION STUDIES (GWAS) have identified genetic variants associated with schizophrenia, they do not explain how these variations lead to specific symptoms like hallucinations or delusions.
LIMITATIONS OF GWAS FINDINGS: GWAS identifies statistical associations, not the biological mechanisms or pathways by which genes contribute to symptoms.
EXAMPLE: The C4 GENE, linked to synaptic pruning, helps explain some biological processes in schizophrenia. However, researchers do not fully understand how this leads to specific symptoms like paranoia or auditory hallucinations.
CHALLENGE: Many genetic variants interact with multiple other genes and environmental factors, making it difficult to pinpoint exact causal pathways.
IMPLICATIONS FOR RESEARCH: Understanding the biological pathways that connect genes to schizophrenia symptoms is essential for developing targeted treatments, but we are far from achieving this goal.
DIAGNOSTIC OVERLAP
Many genes associated with schizophrenia are also linked to other mental illnesses, making it challenging to develop disorder-specific treatments or understand schizophrenia as a distinct condition.
EXAMPLES OF SHARED GENES:
CACNA1C: Associated with schizophrenia, bipolar disorder, and depression.
GRIN2A: Implicated in schizophrenia, autism spectrum disorder, and epilepsy.
IMPLICATIONS FOR DIAGNOSIS:
These overlaps suggest that mental illnesses may not be entirely distinct but could exist on a shared spectrum of neurodevelopmental and psychiatric disorders.
Treatments targeting specific genes may inadvertently benefit multiple disorders, complicating efforts to develop schizophrenia-specific interventions.
LIMITED CLINICAL APPLICATION
Despite advances in genetic research, translating findings into clinical practice has proven difficult.
POLYGENIC RISK SCORES (PRS):
PRS estimate an individual’s genetic vulnerability to schizophrenia by summing the effects of numerous risk alleles.
LIMITATIONS OF PRS:
PRS explain only 25-30% of schizophrenia risk, leaving a significant role for environmental factors.
PRS are not accurate enough to predict who will develop schizophrenia.
High PRS does not guarantee the disorder, and low PRS does not rule it out.
TREATMENT CHALLENGES:
The identified genetic variants have not led to significant breakthroughs in personalised medicine for schizophrenia.
Current treatments, such as antipsychotics, focus on managing symptoms rather than targeting genetic causes.
ENVIRONMENTAL FACTORS AND THE DIATHESIS-STRESS MODEL
Genetic predisposition alone does not cause schizophrenia. Environmental factors interact with genetic vulnerabilities in what is often referred to as the DIATHESIS-STRESS MODEL.
EPIGENETICS:
WHAT IT MEANS: Epigenetics refers to changes in gene expression caused by environmental influences rather than changes to the DNA sequence itself.
EXAMPLES:
TRAUMA: Childhood abuse or neglect can cause epigenetic changes that activate or suppress certain genes, increasing vulnerability to schizophrenia.
STRESS: Chronic stress during sensitive periods, such as adolescence, can trigger epigenetic modifications that impact brain function.
TRAUMA:
EXAMPLES: Childhood abuse, neglect, or bullying are strongly linked to schizophrenia. These experiences may alter brain development, especially in stress-regulation areas like the hippocampus.
SUBSTANCE USE:
CANNABIS AND GENETICS: Cannabis use during adolescence increases schizophrenia risk, particularly in individuals with specific genetic vulnerabilities, such as those related to the AKT1 GENE, which affects dopamine signalling.
SOCIAL ENVIRONMENT:
URBAN UPBRINGING: Growing up in urban areas increases schizophrenia risk by up to 2.4 times, possibly due to chronic stressors like social isolation and economic hardship.
MIGRATION: Migrants, especially those from ethnic minority groups, show higher rates of schizophrenia, likely due to social marginalisation and discrimination.
EVALUATION OF BIOLOGICAL THEORIES:
DETERMINISM
Biological theories of schizophrenia are deterministic, suggesting that individuals have no control over developing or overcoming the disorder. This determinism has both positive and negative implications:
Positive Implications:
Biological explanations reduce blame on individuals and their families, attributing schizophrenia to genetic and neurochemical factors rather than personal or parental fault. This can help alleviate stigma, as it frames schizophrenia as a medical condition rather than a moral or behavioural failing. Additionally, this perspective may encourage greater societal empathy and access to medical treatment.However, the genetic basis of schizophrenia could raise concerns about stigma in other areas. For instance, individuals with schizophrenia or a family history of the disorder may face social or reproductive discrimination due to fears of passing on the condition to offspring.
Negative Implications:
The deterministic outlook may lead to fatalism, where individuals and families feel powerless to improve their situation. This could result in over-reliance on medication while neglecting lifestyle changes or psychological interventions that could alleviate symptoms. The belief that schizophrenia is predestined may also contribute to despair or reluctance to seek non-biological treatments.
PHYSIOLOGICAL REDUCTIONISM AND NATURE VS NURTURE
Biological theories are reductionist, as they attempt to explain a complex disorder solely in terms of genetics, neurotransmitters, and brain structure. While reductionism can provide valuable insights into the biological mechanisms underlying schizophrenia, it overlooks the interplay of psychological and environmental factors. For example, parenting styles, stress, and life experiences can all contribute to the disorder's onset or progression.
Limitations of Reductionism:
Biological explanations cannot fully account for schizophrenia. For instance, the 48% concordance rate among monozygotic twins highlights that even identical genetic material does not guarantee the development of schizophrenia. This indicates that other factors, such as psychological stress or family dynamics (e.g., expressed emotion), also play a significant role. Ignoring these influences risks oversimplifying the disorder and neglecting holistic approaches to treatment and prevention.Nature and Nurture Integration:
Current understanding acknowledges that schizophrenia arises from an interaction of biological and environmental factors. The Diathesis-Stress Model provides a more comprehensive explanation, suggesting that individuals with a genetic predisposition may only develop schizophrenia when exposed to environmental triggers such as abuse, bullying, or family discord.
AETIOLOGICAL HETEROGENEITY AND THE DIATHESIS-STRESS MODEL
Schizophrenia is now understood as an aetiologically heterogeneous disorder, meaning it has multiple potential causes and no single defining feature. The inclusion of "spectrum" in its name by DSM-5 reflects this complexity, recognising that schizophrenia results from a combination of biological vulnerabilities and environmental pressures.
Biological Factors:
Genetic predispositions, birth complications, exposure to viruses, and brain abnormalities (e.g., overactivity of dopamine D2 receptors in areas like Broca's region) are significant contributors. These factors may explain the cognitive and linguistic impairments associated with schizophrenia, as well as the distinction between positive and negative symptoms.Environmental Factors:
External stressors such as trauma, family conflict, or socioeconomic pressures may act as triggers that interact with these biological vulnerabilities. This interplay supports the idea that schizophrenia is neither purely nature nor nurture but rather an interaction between the two.
CONCLUSION
Genetic research has provided valuable insights into schizophrenia, but significant challenges remain. The lack of causal pathways, overlapping genetic risks, and limited clinical applications highlight the complexity of understanding and treating the disorder. Moreover, focusing solely on genetic risks ignores the crucial role of environmental factors. The DIATHESIS-STRESS MODEL, which integrates genetic predispositions and environmental influences, offers a more comprehensive framework for understanding schizophrenia. Future research must continue to explore these interactions to develop effective prevention and treatment strategies.
