Schizophrenia

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Introduction

Schizophrenia is a long-term mental health problem which affects thinking, perception and affect.¹

Schizophrenia affects about 1 in 100 people. It affects men and women equally and is usually diagnosed between the ages of 15 and 35.²

The age of onset tends to be slightly earlier in men (18-25) and later in women (25-35).²

There is a higher incidence of schizophrenia in urban areas and among migrants. The incidence is also higher in lower socioeconomic classes, but this may be a consequence, rather than a cause, of schizophrenia.²

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Aetiology

The precise cause of schizophrenia is unknown, but it is believed to be a consequence of a combination of psychological, environmental, biological and genetic factors.

It is thought that people may have a susceptibility to schizophrenia and that emotional life experiences can act as a trigger for developing the illness.³

Pathophysiology

Schizophrenia is believed to develop because of physical changes to the brain and to changes in neurotransmitters.

Neurodevelopmental hypothesis

People who experienced hypoxic brain injury at birth or who were exposed to viral infections in-utero are at greater risk of developing schizophrenia.

Those with temporal lobe epilepsy or who smoke cannabis while their brain is still developing are also at higher risk. This suggests that brain development is implicated in the pathophysiology of schizophrenia.

Imaging has shown changes in the brains of people with schizophrenia, including enlarged ventricles, small amounts of grey matter loss and smaller, lighter brains.

Neurotransmitter hypothesis

An excess of dopamine and overactivity in the mesocorticolimbic system is believed to cause the positive symptoms of schizophrenia. Dopamine antagonists are therefore used to treat schizophrenia.

There is also thought to be less dopamine activity in the mesocortical tracts, causing the negative symptoms in schizophrenia. This explains why dopamine antagonists are more successful at treating positive than negative symptoms.

Psychotic symptoms are seen in people with Parkinson’s disease if they are overtreated with levodopa as this increases the amount of dopamine in the brain. Amphetamines and cocaine also increase dopamine release and lead to psychosis.

Dopamine is not the only neurotransmitter implicated in schizophrenia. There is also an increase in serotonin activity and a decrease in glutamate activity.⁶

Subtypes of schizophrenia

ICD-10 lists six types of schizophrenia:

• Paranoid schizophrenia
• Hebephrenic schizophrenia
• Catatonic schizophrenia
• Undifferentiated schizophrenia
• Residual schizophrenia
• Simple schizophrenia

Paranoid schizophrenia

Paranoid schizophrenia is the most common type and is characterised by paranoid delusions and auditory hallucinations.

Hebephrenic schizophrenia

Hebephrenic schizophrenia is usually diagnosed in adolescents and young adults. It is characterised by mood changes, unpredictable behaviour, shallow affect and fragmentary hallucinations.

The outlook is often poor as negative symptoms may develop rapidly.

Simple schizophrenia

Simple schizophrenia is similar to hebephrenic schizophrenia in that it is characterised by negative symptoms.

However, in simple schizophrenia, patients have never experienced positive symptoms.

Catatonic schizophrenia

Catatonic schizophrenia is characterised by its psychomotor features, such as posturing, rigidity and stupor.

Undifferentiated schizophrenia

Patients are designated as having undifferentiated schizophrenia when their symptoms do not fit neatly into one of the other categories of schizophrenia.

Residual schizophrenia

Residual schizophrenia is again characterised by negative symptoms. It usually occurs when the positive symptoms have ‘burnt out’.⁶

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Risk factors

Family history and genetics

Patients are more likely to develop schizophrenia if there is a family history of the illness. For example, the monozygotic twin of a person with schizophrenia has a 50% chance of developing schizophrenia, while a dizygotic twin has a 15% chance.

An adopted child still has a 12% chance of developing schizophrenia if their birth parent was a sufferer.⁴ The chance is 48% for a child where both parents are affected.⁶

There is also some increased risk with advanced paternal age, where the father was aged over 55.⁷

Pregnancy

Malnutrition and viral infections during pregnancy increase the chance of developing schizophrenia. Other complications such as pre-eclampsia and emergency caesarean section also increase the risk.⁶

Drug abuse

Using cannabis is known to increase the risk of developing schizophrenia, particularly when used as a teenager. Many other drugs can also cause psychotic symptoms, including amphetamines, cocaine and LSD.⁶

Social and environmental

Schizophrenia is more prevalent in urban areas and among lower socioeconomic classes, but this may be a consequence of living with schizophrenia, rather than being a cause.

Stressful life experiences are known to increase the risk of developing schizophrenia and this is seen particularly among first- and second-generation migrants. Those who have experienced physical or sexual abuse during childhood are also more at risk.

Ethnicity

In the United Kingdom, Afro-Caribbean men are more affected than other ethnicities.

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Clinical features

Symptoms can be divided into positive and negative. Positive symptoms tend to represent a change in behaviour or thought; while negative symptoms usually involve a decline in normal functioning.³

Positive symptoms

Positive symptoms of schizophrenia include:^4,5

• Thought echo (hearing your own thoughts out loud)*
• Thought insertion or withdrawal*
• Thought broadcasting*
• 3^rd person auditory hallucinations*
• Delusional perception *
• Passivity and somatic passivity*
• Odd behaviour
• Thought disorder
• Lack of insight

*These are also referred to as Schneider’s first-rank symptoms. For more information, see the Geeky Medics guide to exploring first-rank symptoms in a psychiatric history.

Negative symptoms

Negative symptoms of schizophrenia include:⁵

• Blunted affect
• Apathy
• Social isolation
• Poverty of speech
• Poor self-care

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Investigations

If a patient is suspected to have schizophrenia, they will be referred to the local community mental health team where a psychiatrist or specialist nurse carries out a detailed assessment.³

Investigations are used to rule out the other causes of confusion/psychotic symptoms.⁶

Laboratory investigations

Relevant laboratory investigations include:

• Baseline blood tests: including FBC, TFTs, U&Es, LFTs, CRP and a fasting glucose
• Urine culture: to rule out urinary tract infection causing delirium
• Urine drug screen: to rule out drug intoxication
• HIV testing if applicable
• Syphilis serology if applicable
• Serum lipids: before starting antipsychotics

Imaging

Relevant imaging investigations include:

• CT head: if an organic neurological cause is suspected

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Diagnosis

According to ICD-10, a diagnosis of schizophrenia requires:¹

1. A first-rank symptom or persistent delusion present for at least one month:

• Delusional perception
• Passivity
• Delusions of thought interference: thought insertion, thought withdrawal and/or thought broadcasting
• Auditory hallucinations: thought echo, third-person voices and/or running commentary

2. No other cause for psychosis such as drug intoxication or withdrawal, brain disease (including dementia/delirium/epilepsy), or extensive depressive or manic symptoms (unless it is clear that schizophrenic symptoms antedate the affective disturbance).

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Management

The management of schizophrenia may involve several multidisciplinary teams including:

• Early intervention team (initial referral after the first psychotic episode)
• Community mental health team (provide day-to-day support and treatment)
• Crisis resolution team (for patients experience an acute psychotic episode)

Care programme approach

Patients with schizophrenia will usually have a care programme approach (CPA).

There are four stages to a CPA:

• Assessing health and social needs
• Creating a care plan
• Appointing a key worker to be the first point of contact
• Reviewing treatment

Voluntary and compulsory hospital admission

Some patients with schizophrenia may require an inpatient stay. Most patients are admitted voluntarily but occasionally they may be detained under the Mental Health Act.

Antipsychotic medication

The drugs used to treat schizophrenia are D2 (dopamine) receptor antagonists. They can be divided into ‘typical’ and ‘atypical’ antipsychotics.

Typical antipsychotics

The ‘typical’ group are older and cause generalised dopamine receptor blockade. Examples include:

• Haloperidol
• Chlorpromazine
• Flupentixol decanoate (depot injection)

Side effects of typical antipsychotics are broad, and may include:

• Extrapyramidal side effects (EPSEs): parkinsonism, akathisia, dystonia, dyskinesia
• Hyperprolactinaemia: leads to sexual dysfunction, increased risk of osteoporosis, amenorrhoea in women, galactorrhoea, gynaecomastia and hypogonadism in men
• Metabolic side effects: weight gain, increased risk of developing type 2 diabetes, hyperlipidaemia, increased risk of developing metabolic syndrome
• Anticholinergic side effects: tachycardia, blurred vision, dry mouth, constipation, urinary retention
• Neurological side effects: seizures, neuroleptic malignant syndrome (potentially life-threatening)

Atypical antipsychotics

Atypical antipsychotics are more selective in their dopamine blockade and also block serotonin 5-HT2 receptors.

They are less likely to causes EPSEs and hyperprolactinaemia, but still cause the other debilitating side effects described above.

Examples of atypical antipsychotics include:

• Olanzapine
• Risperidone (depot injection)
• Clozapine
• Amisulpride
• Quetiapine

Aripiprazole is a partial dopamine agonist and so is less likely to cause EPSEs than the others.

Clozapine is often used when both typical and atypical antipsychotics have been ineffective. However, patients on clozapine require regular blood tests to check their neutrophil levels as clozapine can cause agranulocytosis, which is potentially life-threatening.⁶

Psychological treatments

Psychological therapies used include:

• Cognitive behavioural therapy (CBT)
• Family therapy

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Complications

As well as the side effects from antipsychotic medications, complications of schizophrenia may include:⁴

• Suicide: the lifetime risk of suicide is approximately 5%
• Cardiovascular disease: there is an increased risk of premature death due to cardiovascular disease, in addition, patients with schizophrenia are more likely to smoke
• Cancer: delayed diagnosis and late presentation of cancer
• Substance abuse: up to one-third of patients with schizophrenia use drugs
• Social isolation

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Key points

• Schizophrenia is a long-term mental health problem that affects thinking, perception and affect.
• Schizophrenia affects about 1 in 100 people (men and women are equally affected).
• There are six main subtypes: paranoid, hebephrenic, catatonic, undifferentiated, residual schizophrenia and simple.
• Symptoms can be divided into positive and negative. Positive symptoms tend to represent a change in behaviour or thought; while negative symptoms usually involve a decline in normal functioning.
• Patients with schizophrenia will usually be managed with a multidisciplinary care programme approach.
• Typical and atypical antipsychotics are used in the management of schizophrenia. 
• Clozapine is often used when both a typical and atypical antipsychotic have been ineffective. Regular monitoring of full blood counts is required due to the risk of agranulocytosis. 

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Editor

Dr Chris Jefferies

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References

1. World Health Organization, 2004. International statistical classification of diseases and related health problems: instruction manual (Vol. 2). World Health Organization.
2. World Health Organization. ICD-10
3. Torrey EF, Buka S, Cannon TD, Goldstein JM, Seidman LJ, Liu T, Hadley T, Rosso IM, Bearden C, Yolken RH. Paternal age as a risk factor for schizophrenia: how important is it? Schizophrenia Research. 2009 Oct;114(1-3):1-5. Available from: doi: 10.1016/j.schres.2009.06.017. Epub 2009 Aug 14.
4. National Institute for Health and Care Excellence. Psychosis and schizophrenia. Published in 2020. Available from: [LINK]

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