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.

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

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

We’ve also produced a video demonstration of how a patient with schizophrenia may present.

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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 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 of 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.

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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. The chance of developing schizophrenia is approximately 40% for a child where both parents are affected.⁴

There is thought to be a strong genetic link. 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.⁵ An adopted child still has a 12% chance of developing schizophrenia if their birth parent was a sufferer.

There is also some increased risk with advanced paternal age, where the father was aged over 55.

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.

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

The subtypes of schizophrenia that featured in ICD-10 were removed in the updated ICD-11 and replaced with a symptom specifier.

Symptom specifier

The symptom specifier records information about the presence or absence of symptoms, their time course, and response to treatment.

It includes the following categories: positive, negative, depressive, manic, psychomotor, and cognitive deficits. Cognitive deficits are included due to their prognostic role in patients’ psychosocial and functional recovery.

Symptoms are assessed from zero (absent) to four (severe). The specifier must be re-assessed throughout the disease’s course.

Positive symptoms

Positive symptoms tend to represent a change in behaviour or thought. In contrast, negative symptoms usually involve a decline in normal functioning.

Examples of positive symptoms of schizophrenia include:

• Thought echo (hearing your own thoughts out loud)*
• Thought insertion or withdrawal*
• Thought broadcasting*
• Third person auditory hallucinations*
• Delusional perception *
• Passivity and somatic passivity*
• Grossly disorganised behaviour that impedes goal-directed activity
• Lack of insight
• Formal thought disorder (e.g. neologisms)

*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

Examples of negative symptoms of schizophrenia include:

• Blunted affect
• Apathy / avolition
• Social isolation
• Poverty of speech (alogia)
• Poor self-care

Depressive mood symptoms

Examples of depressive mood symptoms of schizophrenia include:

• Feelings of sadness
• Feelings of emptiness
• Inability to feel pleasure in activities (anhedonia)

Manic mood symptoms

Examples of manic mood symptoms of schizophrenia include:

• Euphoria
• Expansiveness
• The subjective experience of increased energy

Psychomotor disturbance symptoms

Examples of psychomotor disturbance symptoms of schizophrenia include:

• Catatonic restlessness
• Posturing
• Stupor
• Mutism

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Investigations

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

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

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-11, a diagnosis of schizophrenia requires:

At least two symptoms to be present most of the time for at least one month, including positive, negative, depressive, manic, psychomotor, and cognitive symptoms,

AND of the two symptoms, one core symptom needs to be present:

1. Persistent delusions
2. Persistent hallucinations
3. Disorganised thinking
4. Experiences of influence, passivity or control (i.e. the experience that one’s feelings, impulses, actions or thoughts are not generated by oneself)

AND the symptoms are not a manifestation of another medical condition and are not due to the effects of a substance or medication on the central nervous system, including withdrawal effects.

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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 experiencing 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, and 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 ‘first generation’ (typical) and ‘second generation’ (atypical) antipsychotics.

First-generation antipsychotics

The ‘typical’ group are older and thought to primarily exert their effects by blocking dopamine-2 receptors. 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

Atypical antipsychotics

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

They are less likely to cause EPSEs and usually cause less hyperprolactinaemia, but they 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 indicated when two anti-psychotics, including an atypical antipsychotic, 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.

Psychological treatments

Psychological therapies used include:

• Cognitive behavioural therapy (CBT)
• Family therapy

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Complications

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

• Cardiovascular disease: there is an increased risk of premature death due to cardiovascular disease; in addition, patients with schizophrenia are more likely to smoke
• Suicide: the lifetime risk of suicide is about 5%
• Cancer: delayed diagnosis and late presentation of cancer
• Substance abuse: up to 1/3 of patients with schizophrenia use substances
• Social isolation

Overall, the life expectancy of patients with schizophrenia is reduced by approximately 15 -25 years.⁶

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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).
• The core symptoms of schizophrenia include persistent delusions, persistent hallucinations, disorganized thinking and experiences of influence, passivity or control (i.e., the experience that one’s feelings, impulses, actions or thoughts are not generated by oneself)
• 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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Reviewer

Dr Emily Jackson

Psychiatry registrar

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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-11
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.
4. McDonald C, Murphy KC. The new genetics of schizophrenia.Psychiatr Clin North Am.2003;26(1):41–63.
5. Fischer M. Psychoses in the offspring of schizophrenic monozygotic twins and their normal co-twins.Br J Psychiatry. 1971;118:43–52.
6. Wildgust HJ, Hodgson R, Beary M. The paradox of premature mortality in schizophrenia: new research questions. J Psychopharmacol. 2010 Nov;24(4 Suppl):9-15.

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