Biological Explanations and Drug Therapy for Schizophrenia

Schizophrenia is a serious mental disorder affecting perception and thought, with positive symptoms (added experiences such as hallucinations and delusions) and negative symptoms (losses such as speech poverty and avolition). Biological explanations argue that its origins lie in genes and brain chemistry.

The starting evidence is that schizophrenia clusters in families. The more genes two people share, the more likely they are to share the disorder. This does not prove genetics on its own, because families also share environments, but it is what any genetic explanation must account for.

Relationship to a person with schizophrenia	Genes shared	Approximate risk of also developing it
Identical (MZ) twin	100%	~48%
Non-identical (DZ) twin	50%	~17%
Sibling	50%	~9%
General population (no affected relative)	—	~1%

Risk rises with genetic closeness. The lifetime risk for the general population is about 1%, but for the identical twin of a person with schizophrenia it rises to roughly 48%.

Concordance rate is the probability that, if one twin has schizophrenia, the other has it too. Gottesman's large family study produced the figures used across AQA answers: about 48% for identical (MZ) twins, about 17% for non-identical (DZ) twins, and about 1% for the general population. MZ twins share 100% of their genes and DZ twins share 50%, so the much higher MZ figure points to a genetic influence.

Crucially, schizophrenia is polygenic: no single "schizophrenia gene" exists. Instead, many different genes each add a small amount of risk, and only a combination raises risk substantially. Ripke et al. carried out a genome-wide study and identified over 100 genetic loci associated with the disorder.

It is also aetiologically heterogeneous — different combinations of genes can lead to schizophrenia in different people, so no one genetic profile is shared by all patients.

Because MZ concordance is about 48% and not 100%, genes cannot be the whole story. If schizophrenia were purely genetic, identical twins would show 100% concordance. Environment must also contribute, which is why genes are described as a vulnerability.

Neural correlates are patterns of brain structure or activity associated with symptoms. The most important neural correlate for schizophrenia involves the neurotransmitter dopamine, and the explanation built around it is the dopamine hypothesis.

The hypothesis has two versions you must distinguish:

Version	Dopamine level	Brain region	Symptoms linked
Original	Excess (hyperdopaminergia)	Subcortical (e.g. mesolimbic pathway)	Positive (hallucinations, delusions)
Revised (addition)	Low (hypodopaminergia)	Prefrontal cortex	Negative and cognitive

The original hypothesis proposed hyperdopaminergia — an excess of dopamine activity, caused by too much dopamine or too many D2 receptors, in subcortical areas such as the mesolimbic pathway. This overactivity was linked to positive symptoms such as hallucinations.

The revised hypothesis kept subcortical hyperdopaminergia but added that low dopamine (hypodopaminergia) in the prefrontal cortex is linked to negative and cognitive symptoms. This explains why some symptoms involve too much dopamine and others too little, depending on the brain region.

The original version explains positive symptoms through excess subcortical dopamine; the revised version adds low prefrontal dopamine to explain negative and cognitive symptoms.

Several lines of evidence connect dopamine to schizophrenia. None proves cause on its own, but together they build the case.

• Amphetamines increase dopamine activity, and in large doses can induce psychosis-like symptoms (hallucinations, delusions) in people without schizophrenia, and worsen symptoms in those who have it.
• Antipsychotic drugs reduce dopamine activity and reduce the intensity of symptoms — the reverse pattern.
• L-dopa, used to treat Parkinson's disease, raises dopamine and can produce schizophrenia-like symptoms as a side effect.

Dopamine is not the only neural correlate. Brain-scanning studies have found enlarged ventricles (the fluid-filled cavities of the brain) in some patients, associated particularly with negative symptoms and a loss of surrounding brain tissue.

The drug evidence is a two-way street: substances that raise dopamine trigger symptoms, and substances that lower it relieve them. This is the strongest circumstantial support for the dopamine hypothesis.

A key limitation, examined later, is that this evidence is correlational — abnormal dopamine activity is associated with schizophrenia, but the studies cannot establish that it is the cause.

Antipsychotic drugs are the main biological treatment. They follow directly from the dopamine hypothesis: if excess dopamine activity produces symptoms, reducing dopamine should relieve them.

Typical (first-generation) antipsychotics, such as chlorpromazine, are dopamine antagonists. They block D2 receptors in the synapse, so dopamine cannot bind and dopamine activity falls. This mainly reduces positive symptoms such as hallucinations and delusions. Chlorpromazine also has a strong sedative effect and is often used to calm anxious or agitated patients.

The trade-off is the side effects caused by blocking dopamine throughout the brain:

• Extrapyramidal side effects — movement problems, most seriously tardive dyskinesia (involuntary movements of the face, such as lip-smacking and blinking), which can be irreversible.
• Neuroleptic malignant syndrome — a rare but potentially fatal reaction involving high temperature and rigidity.

Typical antipsychotics work by blocking D2 dopamine receptors, reducing dopamine activity and mainly easing positive symptoms. Because the blockade is not selective, they commonly cause movement (extrapyramidal) side effects.

Atypical (second-generation) antipsychotics were developed to treat a wider range of symptoms with fewer side effects. Examples are clozapine and risperidone.

Unlike typical drugs, they act on dopamine receptors and serotonin receptors (and others). By occupying dopamine receptors only temporarily and also acting on serotonin, they aim to treat positive symptoms and some negative and cognitive symptoms, while producing fewer movement side effects.

Feature	Typical (e.g. chlorpromazine)	Atypical (e.g. clozapine, risperidone)
Generation	First	Second
Main receptor action	Blocks D2 (dopamine)	Dopamine and serotonin
Symptoms targeted	Mainly positive	Positive + some negative/cognitive
Movement side effects	More common	Fewer

Clozapine carries a serious risk of agranulocytosis — a dangerous drop in white blood cells — so patients need regular blood monitoring. Because of this risk it is usually reserved for cases where other drugs have failed.

Atypical antipsychotics act on dopamine and serotonin receptors, target positive and some negative symptoms, and cause fewer movement side effects. Clozapine is effective but risks agranulocytosis, so it requires blood monitoring.

Genetics is supported by twin and adoption studies. MZ concordance (~48%) far exceeds DZ (~17%), and Tienari's adoption study found children of schizophrenic mothers had a raised risk of the disorder even when adopted into other families, pointing to a genetic rather than purely environmental cause. However, MZ concordance is well below 100%, so genes are a vulnerability, not a certainty. Twin studies are also confounded because MZ twins usually share more similar environments than DZ twins, so shared experience may inflate the concordance.

The dopamine hypothesis has strong drug-based support — antipsychotics that lower dopamine reduce symptoms, while amphetamines that raise it worsen them. But the picture is more complex than dopamine alone: glutamate is also implicated, and newer drugs act on serotonin. The evidence is largely correlational, so it is unclear whether abnormal dopamine causes schizophrenia or results from it.

Drug therapy is effective and practical. Thornley et al. reviewed data and found chlorpromazine more effective than a placebo at reducing symptoms; drugs are cheap and allow patients to live in the community rather than in hospital. But antipsychotics treat symptoms, not the cause, cause serious side effects, and raise the ethical concern of a "chemical straitjacket" used to sedate patients. Some effectiveness data may be biased by selective publication and by studies funded by drug companies.

Biological explanations may be reductionist. Reducing schizophrenia to genes and dopamine can ignore psychological and social factors such as family dysfunction and life stress. The interactionist diathesis-stress model — a biological vulnerability triggered by environmental stress — offers a fuller account and fits the sub-100% concordance data.

1. Quoting MZ concordance as 100%

Identical twins do not show 100% concordance for schizophrenia. Gottesman's figure is about 48%. Writing 100% both misstates the data and destroys the key evaluation point that environment must also matter.

2. Saying schizophrenia is caused by a single gene

Schizophrenia is polygenic: many genes each contribute a small amount of risk, and Ripke et al. found over 100 associated loci. Referring to "the schizophrenia gene" loses credit.

3. Confusing typical and atypical antipsychotics

Point of confusion	Typical	Atypical
Receptors	D2 dopamine only	Dopamine and serotonin
Symptoms	Mainly positive	Positive + some negative
Side effects	More movement effects	Fewer movement effects

Mixing these up (for example, saying typical drugs act on serotonin) is a frequent error.

4. Treating the dopamine correlation as proven cause

The evidence linking dopamine to schizophrenia is correlational. Do not write that "high dopamine causes schizophrenia" as an established fact — it is unclear whether abnormal dopamine is a cause or a consequence, and glutamate is also involved.

5. Getting the direction of the revised hypothesis backwards

The revised hypothesis pairs high subcortical dopamine (positive symptoms) with low prefrontal dopamine (negative and cognitive symptoms). Swapping the regions or the levels reverses the explanation.