Biological explanations and Treatment for Schizophrenia

What are the 3 explanations for schizophrenia?

• Biological explanation

• Psychological explanation

• Cognitive explanation

What is a candidate gene?

Genes which are believed to be related to a particular trait such as disease or physical attribute (COMT and SERT genes for OCD eg)

What occurs if a person inherits multiple candidate genes?

• They are likely to develop specific disorders because each gene equates to a genetic vulnerability for different symptoms

What is dopamine?

It is a neurotransmitter that is released in the brain responsible for allowing you to feel pleasure, satisfaction and motivation

What is concordance rate?

A term used to describe the rate of probability that 2 people with shared genes will develop the same disease

Polygenic

Attribute determined by multiple genes rather than 1

Heritability

The extent to which a condition or trait has been passed on generationally through families via genes (genetic inheritance)

What study was carried out on extensive generational research comparing diagnoses of schizophrenia and who carried it out?

• The Human Genome project

• Gottesman (1991)

What was the procedure of the Human Genome project?

Diagnoses of schizophrenia were researched and compared across different relatives in a large sample of families.

• The percentage genes shared, relation to the individual with schizophrenia and risk of developing schizophrenia were measured

What was the main finding and 2 other findings in comparison of schizophrenia research?

Main finding:

It was found that there is a strong relationship between degree of genetic similarity and the likelihood of sharing schizophrenia

Other findings:

• Schizophrenia basis is not entirely genetic; not 100% concordance rate for twins, differences must be a result of experiences

• Significant difference in sz diagnosis across different types of twins: in fraternal twins (17%) and identical twins (48%), compared to 1% risk in general population

What are the 2 biological explanations for schizophrenia?

• Candidate genes (genetic explanation)

• Dopamine hypothesis

How do candidate genes explain schizophrenia?(include polygenetics)

• Individual candidate genes are expected to be responsible for the inherited vulnerability of developing schizophrenia (eg dysbindin, proline dehydrogenase)

• Schizophrenia is polygenic, meaning that it is a combination of the effect of multiple genes and with each inherited gene there is an increased risk of different symptoms to be presented OR differing severity of schizophrenia (hence the sub types of Schizophrenia).

  
  

What is one other study which investigates the genetic basis of schizophrenia?

Study by Sekar et al (2016):

• The genomes of 65,000 people and 700 post mortem brains were analysed and found that the strongest known genetic risk for schizophrenia comes from the gene known as C4.

• Researchers found that increased expression of the C4A variant drives excessive synaptic pruning during postnatal brain development

2 strengths of candidate genes as an explanation of schizophrenia

Genetic explanations are supported by highly scientific, objective, and reliable research methods, such as modern genome-wide association studies (GWAS) and large-scale meta-analyses.

• For example, Gottesman (1991) demonstrated a clear, quantifiable correlation between genetic similarity and risk of developing schizophrenia (e.g., a 48% concordance rate for identical twins compared to 1% in the general population), giving the explanation strong empirical validity.

Practical applications to drug therapies due to specifically pointed out genes

Limitation of candidate genes as an explanation

• Genetics is only a partial explanation of schizophrenia, not a complete explanation because if schizophrenia were purely biological, then concordance rates for MZ twins would be 100%, which no research has ever found

Who first suggested the dopamine hypothesis?

Van Rossum (1966)

What is a cause of schizophrenia according to the dopamine hypothesis?

The dopamine hypothesis states that an overstimulation of dopamine receptors may be a contributory factor to a person’s vulnerability to schizophrenia

Hyperdopaminergia

This refers to higher than usual levels of dopamine in the subcortex of the brain.

What type of symptoms are linked with hyperdopaminergia?

Positive symptoms of schizophrenia

What could cause hyperdopaminergia?

When there is higher number of dopamine receptors causing over-activity of dopamine then leading to sensory hallucinations

Hypodopaminergia

This refers to lower than usual levels of dopamine in the pre frontal cortex

What type of symptoms are linked with hypodopaminergia?

Negative symptoms

What could cause hypodopaminergia?

When less dopamine being transmitted across synapses

List 2 neural correlates causing negative symptoms in schizophrenia (name each negative symptom caused)

• Hypoactivity in the ventral striatum: Causes avolition (loss of motivation/ reward anticipation)

• Hypodopaminergia in the Dorsolateral Prefrontal Cortex : Causes alogia/speech poverty

List 2 neural correlates causing positive symptoms in schizophrenia (name each positive symptom caused)

• Hyperdopaminergia in Broca’s area: Causes auditory hallucinations

• Hypersensitivity of dopamine D2 receptors in the mesolimbic pathway : Causes Delusions/paranoia

Study investigating neural correlates of schizophrenia

• Study by Juckel et al (2006)

• Researchers used fMRI scans to measure brain activity in individuals with schizophrenia (unmedicated) while they performed task in anticipation of a monetary reward

• Found significantly lower levels of activity in the ventral striatum of individuals with schizophrenia compared to healthy controls.

Strength the biological explanation as a whole

• Use empirical supporting evidence. Brain imaging techniques such as PET and fMRI provides objective evidence for neural correlates of schizophrenia (eg study by Juckel et al (2006)

Weaknesses of the biological explanation (2)

• Reductionist- does not consider the psychological and cognitive explanations for schizophrenia (universal theory of how schizo is caused cannot be made)

• There is a correlation-causation issue which reduces the internal validity of the biological explanation.

  • It is unclear whether reduced activity in the ventral striatum causes avolition, or if suffering from severe schizophrenic symptoms causes the brain region's activity to drop.

  • Alternatively, a third variable, such as long-term antipsychotic medication, may be causing the altered brain activity, meaning the biological explanation cannot definitively prove the root cause of the disorder. (limits face validity)

    
    

What is the biological treatment for schizophrenia?

Drug therapy

In what form is drug therapy usually taken?

Usually taken in the form of tablets or syrup.

In extreme cases where the individual is unlikely to take their medication, it can be administered via injection every 1-2 weeks

How was schizophrenia treated in the pre 20th century?

Typically treated through confinement, involving removing the patient from society through keeping the patient at home, living in mental institutions,  or even permanently restrained or sedated. 

How was schizophrenia treated in the early 20th century?

Through newly developed treatments such as:

• Electroconvulsive Therapy, where electric currents are used to induce seizures

• Frontal lobotomy, where connections in the brain’s pre frontal cortex were severed

What are the 2 categories of drug therapy?

• Typical antipsychotics

• Atypical antipsychotics

What are typical antipsychotics?

First generation antipsychotics used to manage schizophrenia developed in the 1950’s

How do typical antipsychotics work?

• Typical antipsychotics act as dopamine antagonists

• Typical antipsychotics block dopamine D2 receptors on the postsynaptic membrane without activating them

• By blocking these receptor sites, dopamine transmission across the synapse is reduced, normalising neurotransmission in hyperactive pathways and reducing positive symptoms.

What is a common typical antipsychotic and its dosage?

• Chlorpromazine

• Daily doses usually range between 400mg and 800mg starting low and increasing when necessary

What secondary effect does chlorpromazine have and what is the use of this effect?

• It acts as an antagonist on histamine receptors producing a strong sedative effect

• This means that it is administered to calm patients when they are first admitted to hospital or during acute psychotic episodes with high anxiety

What is a limitation of typical antipsychotics?

• They block dopamine indiscriminately throughout the brain, frequently causing extrapyramidal side effects

List 3 extrapyramidal side effects caused by typical side effects

• Tardive dyskinesia:  Involuntary repetitive movements of the face, tongue, and jaw.

• Parkinsonian symptoms: Tremors, muscle stiffness, and slow movement.

• Neuroleptic Malignant Syndrome (NMS): A rare, potentially fatal condition caused by blocking dopamine in the hypothalamus, leading to high fever, delirium, and fluctuating blood pressure.

What are atypical antipsychotics?

They are second generation antipsychotics used to manage schizophrenia developed in the 1970’s onwards

Why were atypical antipsychotics designed?

They were designed to maintain or improve therapeutic effectiveness on positive symptoms while addressing negative symptoms (e.g., avolition, speech poverty) and reducing severe extrapyramidal side effects.

How do atypical antipsychotics work?

They work by targeting multiple neurotransmitter systems rather than dopamine alone

How do typical antipsychotics target dopamine D2 receptors?

• Dopamine D2 receptors: They temporarily/transiently bind to D2 receptors and then rapidly dissociate, allowing normal bursts of dopamine transmission. This transient action significantly reduces extrapyramidal side effects

Which other receptors do atypical antipsychotics target and how?

• Serotonin (5-HT2A) and glutamate receptors

•  They block serotonin 5-HT2A receptors and modulate glutamate activity, which helps elevate mood, reduce cognitive impairment, and alleviate negative symptoms.

What are 2 examples of typical antipsychotics?

• Risperidone (1990’s)

• Clozapine (1970’s)

Which receptors do clozapine bind to?

• Dopamine D2 receptors

• Serotonin (5-HT2A)

• Glutamate

What are the clinical benefits of clozapine?

•  Highly effective at reducing negative symptoms, depression, and anxiety, and improving cognitive functioning.

• It is routinely used when patients fail to respond to other drugs (treatment-resistant schizophrenia) and for patients at high risk of suicide (30% to 50% of people with schizophrenia attempt suicide).

What are the risks of clozapine?

• Carries a risk of agranulocytosis: a potentially fatal blood condition caused by a severe drop in white blood cell count

• Patients taking clozapine must undergo mandatory regular blood testing

What receptors do Risperidone bind to?

• Binds strongly to dopamine D2 receptors -

• Serotonin 5-HT2A receptors.

What are the clinical benefits of clozapine ?

• Designed to match the effectiveness of Clozapine without the risk of agranulocytosis

• Because it binds more strongly to D2 and serotonin receptors than Clozapine, it is effective in much smaller doses (typically 4 mg to 8 mg daily) and produces fewer side effects.

Research on effectiveness of drug therapy

Strengths of drug therapy

Weaknesses of drug therapy