Schizophrenia is called a 'divided mind' though this isn't actually the case. It's a psychiatric disorder or thoughts and perceptions as well as mood. It is characterised by symptoms that are either unusually present (positive symptoms) or normal functions may be absent (negative symptoms). It is thought to have a hereditary component, though the environment is likely to have a strong impact. It has been suggested that insults to the developing foetus may programme it to a tendency towards schizophrenia later in life. Insults could be things such as the maternal use of drugs, poor maternal nutrition, viral infection and autoimmune processes. Cannabis has been linked to the development of schizophrenia.
Positive symptoms may include believing that thoughts are not their own, hallucinations (particularly auditory), disorganised speech and delusions.
Negative symptoms include withdrawal from society- particularly a lack of speech. Patients may even be catatonic.
The current theory for schizophrenia is that dopamine hyperactivity underlies schizophrenia. Due to this thought, dopamine antagonists have been used in the treatment of schizophrenia but this usually only targets the positive symptoms. The mesolimbic pathway is indicated in these symptoms and it is thought that the high dopamine here creates the positive symptoms. Giving L-Dopa in diseases such as Parkinson's makes them display the positive symptoms. However, the negative symptoms may be a result of too little dopamine on the mesocortical pathway.
Drug treatments are classically called the Typical neuroleptics. These are largely receptor antagonists for dopamine. Chlorpromazine (a Phenothiazine) was the first drug to be used in schizophrenics and it controls the positive symptoms. Butyrophenones such as Haloperidol have also been used, as have Thioxanthines such as clopenthixol. These drugs are all pharmacologically promiscuous so have been considered 'dirty' drugs- they act on many different receptors such as histamine, dopamine, muscarinic, noradrenaline and 5-HT receptors. It can lead to many side effects such as motor problems and a dry mouth.
Atypical neuroleptics have less side effects and also act to treat the negative side effects. These are:
Selective D2 antagonists (amisulpiride)
Multi Acting Receptor Targeted Agents (clozapine)
Serotonin-Dopamine antagonists (sertindole)
and finally
D2 receptor partial agonist (aripiprazole).
The last of these is particularly important as this can help with the positive and negative symptoms. In the mesocortical pathway where there is too little dopamine, the partial agonist will provide some stimulation. In the mesolimbic pathway where there is too much dopamine activity, a partial agonist will limit the binding of dopamine and cause a less potent response, lowering the stimulation.
The side effects of the neuroleptics are anti-emesis (a very good side effect!), and they can also cause increased release of prolactin which is usually inhibited by dopamine. This causes gynaecomastia. There are also the muscarinic side effects of dry mouth, constipation and visual disturbance and adrenoreceptor side effects of postural hypotension. Sedation may be caused by histamine block.
The motor disturbances which are more common the the typical neuroleptics are acute dystonias and tardive dyskinesia. The last of these is a severely disabling motor disturbance with involuntary movements of the face and tongue moving on to the limbs and trunk. This is generally irreversible so this needs to be carefully monitored. It's better to give neuroleptics that don't have this effect such as clozapine which targets D4 which is mainly expressed in the limbic region. However, clozapine can cause myocarditis.
There is still a lot to learn about this condition and about treating it as at the moment we do not know exactly what is effected. Serotonin may be important in schizophrenia.
Generally, there must be a more complicated mechanism behind the effect as neuroleptics do not work instantly but take time; indicating the vital secondary effects.