David’s withdrawal

• describe schizophrenia and its associated positive and negative symptoms;
• describe the causative factors and associated neurotransmitters;
• explain the pharmacological approaches to managing the symptoms;
• explain how neuroleptic drugs may produce their clinical benefits and side effects;
• outline the benefits of using haloperidol in schizophrenic patients.

Emma made an appointment for her 27-year-old brother, David, to visit his doctor and persuaded him to keep the appointment. She has been very concerned about his recent behaviour and thoughts. David claims to be able to see and talk to his mum, who died 10 years ago. Recently, he has avoided visits to his local football club and he no longer mixes with his friends. Sometimes he talks very slowly and quietly but on some occasions he is very loud and violent in speech.

David has not previously been a religious man, but recently he keeps talking about God. He appears to think that God is talking to him, asking him to perform certain tasks. David was initially very reluctant to talk to the doctor but eventually revealed that he thought his sister was trying to poison him, so he had stopped eating at home. His doctor made a diagnosis and prescribed haloperidol.

What is the likely diagnosis of David’s symptoms?

The likely diagnosis is schizophrenia. This is the most common form of psychosis.

What are the positive symptoms of schizophrenia?

The positive symptoms are symptoms such as hallucinations, which are usually auditory, and delusions. Some thought disorders and abnormal behaviours may also be placed in this category.

What are the negative symptoms of schizophrenia?

The negative symptoms are features such as social withdrawal, apathy and lack of purposeful behaviour. There is usually a reduction or flattening of emotional responses.

Patients also develop cognitive disruption so that speech and written communication is affected, that is they may use a string of words with no rational meaning. Many schizophrenic patients describe religious experiences, such as hearing the word of God, or claim particular artistic sensitivity, for example they understand the hidden meaning of poems, novels, pictures and so on.

Can both positive and negative symptoms occur together?

Positive and negative symptoms usually occur together; thus, these patients withdraw from society and cannot maintain relationships. Commonly, they have persecuted feelings, for example that somebody is following or checking up on them.

Identify the positive and negative symptoms presented in this case.

Positive: delusions, auditory hallucinations; negative: social withdrawal and neglect.

Are all David’s symptoms consistent with the profile of schizophrenia?

Yes, see answers presented above.

What other conditions could be confused with schizophrenia and should be eliminated before a final diagnosis is made?

Other conditions which may present similar symptoms include: drug-induced psychosis such as one brought on by lysergic acid diethylamide, or LSD, or amphetamine, personality disorder or affective psychosis. In older patients dementia may present with schizophrenia-like symptoms, but these patients usually have significant memory deficits, which do not occur in schizophrenia.

What is the main neurotransmitter associated with schizophrenia?

Dopamine is thought to be the main neurotransmitter associated with schizophrenia. But there is evidence of the involvement of other neurotransmitter systems, particularly glutamate, and also serotonin (5-HT) and GABA.

What are the possible causes of schizophrenia?

Schizophrenia appears to involve both genetic and environmental factors. Possible causes of schizophrenia are:

(1) an increase in the release of dopamine from the nerve terminal.

(2) the development of a hypersensitivity in dopamine receptors.

(3) problems with inactivation of dopamine at the synapse.

(4) failure of dopaminergic feedback mechanisms.

(5) development of an imbalance between the activity of the dopamine and glutamate systems.

To what category of drugs does haloperidol belong? Comment on the mechanism of action of haloperidol.

Haloperidol is an antipsychotic or neuroleptic agent. It is an antagonist at dopamine receptors, particularly of the D2 subtype. These drugs help to control the symptoms (mainly the positive symptoms) of schizophrenia by antagonizing the dopamine receptors in different brain areas, such as the frontal and temporal lobes. Antipsychotic agents, such as haloperidol, take days or weeks to achieve their therapeutic effect and may produce some motor disturbances.

Name other neuroleptic drugs you know of and comment on the problems associated with neuroleptic therapy.

Other neuroleptic agents include phenothiazines, such as chlorpromazine, promazin and thioridazine, and thioxanthines, such as flupenthixol. The non-specific blockade of dopaminergic receptors afforded by these drugs leads to development of side effects, such as endocrine dysfunction and extrapyramidal motor symptoms. The unwanted antagonism of motor tracts results in extrapyramidal side effects, such as Parkinsonism and tardive dyskinesia. The latter is associated with involuntary movements of the face, limbs and trunk. Chronic neuroleptic therapy can inhibit the release of GABA. This in turn leads to changes in mobility.

The agents used in treating schizophrenia are most successful in treating the positive symptoms; negative symptoms, such as apathy and social withdrawal, seem to be less responsive to current drug treatment.

Key Points

• Schizophrenia is the most common form of psychosis and appears to involve both genetic and environmental factors.
• The symptoms may be classified as positive and negative.
• Positive symptoms are symptoms such as hallucinations, which are usually auditory, and delusions; some thought disorders and abnormal behaviours may also be placed in this category.
• The negative symptoms are features such as social withdrawal, apathy and lack of purposeful behaviour, reduction or flattening of emotional responses and development of cognitive disruption so that speech and written communication are affected.
• Neurotransmitters associated with schizophrenia are dopamine as the main neurotransmitter, plus other neurotransmitter systems, particularly glutamate, but also serotonin (5-HT) and GABA.
• Antipsychotics are also referred to as neuroleptic drugs, such as haloperidol, phenothiazines (e.g. chlorpromazine, promazin and thioridazine) and thioxanthines (e.g. flupenthixol). All theses agents are used in treating the symptoms and are mostly successful with positive symptoms.
• Haloperidol helps to control the positive symptoms of schizophrenia by antagonising dopamine receptors (D₂ receptors) in several brain areas, but may produce motor disturbances.
• Other neuroleptic agents such as phenothiazines, which are non-selective dopamine antagonists, can cause endocrine dysfunction as well as extrapyramidal side effects.