A chronic brain disorder that causes a loss of touch with reality, experienced by around 1% of the population. While the symptoms are already debilitating, the poor understanding and heavy stigma associated with it make schizophrenia even more difficult to live with.

Causes

Symptoms

Treatment

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Causes

The causes of schizophrenia are still not fully understood, but we have evidence based theories strongly supported by years of research.

The Dopamine Hypothesis

On a molecular level, schizophrenia is thought to be caused by excessive activity of the neurotransmitter dopamine in the brain.

The dopamine hypothesis stating this possible link was first proposed in the 1960s when it was discovered that amphetamine — which increases dopamine levels — induced psychosis in healthy patients and reserpine — which depletes dopamine levels — reduced psychosis in patients.

This is a simplified explanation. There are also other neurotransmitters thought to be involved, either to a lesser degree or secondarily to dopamine, such as serotonin, acetylcholine, and glutamate. The dopamine hypothesis is the foundation of the development of antipsychotics.

This is the molecular explanation. The risk factors for actually developing the disease are thought to be a combination of genetic and environmental.

Genetic Factors

Genetic factors, inherited in your DNA, mean that your genetic code puts you at risk.

Twin studies have shown that if your identical twin has schizophrenia your risk of developing it is 40-50%. This is in comparison to 1% normally, 2% if a relative has it, and 10% if a parent or sibling has it. This proves that while genetics are definitely important, they cannot be the sole determining factor, because if they were, identical twins with completely identical DNA would have 100% chance, not 50%.

Environmental Factors

Environmental factors, meaning everything that is not your DNA, are thought to have an impact also. Stressors that have been linked to schizophrenia include social isolation and childhood abuse or trauma.

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Symptoms

There are two types of symptoms of schizophrenia: Positive and negative.

Positive Symptoms are an excess of or “adding on” to normal function and behavior. They include:
-psychosis
-paranoid or grandiose delusions
-auditory and visual hallucinations
-disorganized thought, speech and behavior.

Negative symptoms are a reduction of or “taking away” from normal function and behavior. They include:
-flat affect or blank facial expression
-monotone voice
-lack of eye contact
-lack of gesturing
-social withdrawal
-avolition (lack of motivation)
-alogia (difficulty speaking)

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Treatment

There are two classes of antipsychotics: First generation or “typical” drugs, and second generation or “atypical” drugs.

First generation antipsychotics (FGAs)

First introduced in 1950 after the discovery of chlorpromazine as an antipsychotic.

Mechanism:
These drugs work primarily by blocking the D2 dopamine receptors.

Side effects:
Significant risk of causing EPS or extrapyramidal symptoms, movement disorders including
-dystonia
-akathisia
-parkinsonism
-tardive dyskinesia.

Second generation antipsychotics (SGAs)

First introduced in 1958 after the discovery of clozapine, an antipsychotic that showed much lower risk of EPS.

Mechanism:
These drugs are more selective in their dopamine pathways, which is thought to result in the significantly low risk of EPS. They also act on serotonin and glutamate receptors. While helpful in treating symptoms, the blocking of serotonin receptors is thought to cause the metabolic side effects associated with atypical drugs.

Side effects:
Metabolic side effects including:
-weight gain
-diabetes
-increase in blood pressure
-increase in blood sugar.

While these side effects are distressing to patients, and can potentially lead to cardiovascular issues, they are thought to be more tolerable than EPS. Today, second generation drugs are being prescribed more and more frequently while first generation prescriptions are decreasing.

Clozapine

FGAs and SGAs have very different mechanisms and side effects. However, when compared to each other, studies have not yet proven a significant difference in their ability to treat the actual symptoms of schizophrenia. The exception to this is clozapine. Clozapine has been found to be significantly more effective at reducing both positive and negative symptoms than all other antipsychotics.

However, clozapine puts patients at risk for agranulocytosis, a white blood cell deficiency that can lead to severe infection and death. The risk of this side effect and others — such as myocarditis, seizures, and arrhythmia — makes clozapine a drug that is reserved for treatment-resistant forms of schizophrenia only. (cases where the patient has been treated by at least two different drugs and they have not worked.)

The exact mechanism of clozapine is not fully understood. It acts on a wide variety of receptors in the brain, which is thought to account for the range of severe side effects. It is also known to act more weakly on the D2 dopamine receptor — dissociate from the receptor quickly — and have a high affinity for the 5-HT2A serotonin receptor, and these are thought to account for clozapine’s unusually high effectiveness.

Clozapine is of interest as a subject of research. Better understanding its mechanisms and properties is a possible step to developing antipsychotics that are both as effective and as safe as possible.

Therapy

While drugs are used to manage psychotic symptoms, therapy is used to help manage stress, cope with challenges, and prevent relapse.

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